ISSN 1305–3124 PERINATAL PERINATAL JOURNAL JOURNAL PERINATAL Volume 24 | Issue 2 | August 2016 JOURNAL A L J O www.perinataljournal.com A T U N R I N R A E L P Contents Volume 24 | Issue 2 | August 2016
P L E R A I N N R A U T A L J O Original Article The cesarean rates and indications between 2010 and 2014 in the Obstetrics 61 Department of Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital Gökçe Naz Küçükbafl, Özlem Moralo¤lu, fiule Özel, Salim Erkaya, Yasemin Taflc›, Rahime Bedir F›nd›k Comparison of first trimester uterine artery Doppler parameters in hyperemesis 66 gravidarum with normal pregnancy ‹smail B›y›k, Gökhan Ocako¤lu, Emin Üstünyurt, Fatih Y›lmaz, Fatih Keskin An obstetric emergency case: vulvovaginal hematoma – our four-year results 72 Özlem Yörük, Ayflegül Öksüzo¤lu, Elif Gül Yapar Eyi, Burcu K›sa Karakaya, Necati Hançerlio¤lu Evaluation of the measurement of ACTH, fibronectin, pentraxin 3 levels and 77 cervical length in pregnant women under threatened preterm delivery Filiz Aktenk, Burcu Artunç Ülkümen, Yeflim Güvenç, Halil Gürsoy Pala, Arzu Oran Hepatitis B seropositivity of pregnant women and the review of Turkish literature 83 Rabia Zehra Bakar, Banu Dane Posterior fossa anomalies: related anomalies and the methods of 89 pregnancy termination Emine Ayd›n, Mert Turgal, Sema Can, Özgür Özyüncü 96 Modified transabdominal cervico-isthmic cerclage: analysis of 16 cases Ebru Çelik Kavak, Salih Burçin Kavak, Yakup Baykufl, Hüsnü Çelik Results of fetal anomaly screening performed at 11–14 weeks 100 of gestation at a tertiary center Tu¤ba K›nay, Metin Kaplan, Mehmet Metin Altay, fiafak Özdemirci, Sinan Karadeniz, Ahmet Okyar Erol
Case Report Intrafetal laser therapy in acardiac twin pregnancy: a case report 106 Resul Ar›soy, Oya Pekin, Kaan Pakay, Emre Erdo¤du, Oya Demirci, Murat Muhçu Volume
Clinical Guidelines Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of 110
Turkish Perinatology Society 24
Cihat fien, Murat Yayla, Olufl Api, Elif Gül Yapar Eyi, Burcu Artunç Ülkümen; | Issue Diabetes and Pregnancy Study Group of Turkish Perinatology Society 2
| August 2016 The Official Publication of Perinatal Medicine Foundation Turkish Perinatology Society Turkish Society of Ultrasound in Obstetrics and Gynecology
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Volume 24 | Issue 2 | August 2016
Editor-in-Chief Advisory Board Cihat fien, Abdallah Adra, Beirut, Lebanon Narendra Malhotra, Agra, India Istanbul University, Arif Akflit, Eskiflehir, Turkey Giampaolo Mandruzzato, Trieste, Italy Saadet Arsan, Ankara, Turkey Alexandra Matias, Porto, Portugal Istanbul, Turkey Abdel-Latif Ashmaig, Khartoum, Sudan Ratko Matijevic, Zagreb, Croatia Alev At›fl-Ayd›n, Istanbul, Turkey Israel Meizner, Tel Aviv, Israel Editors Manuel Carrapato, Porto, Portugal Mohammed Momtaz, Cairo, Egypt Julene Carvalho, London, UK Murat Yayla Giovanni Monni, Cagliari, Italy Rabih Chaoui, Berlin, Germany Kypros Nicolaides, London, UK Ac›badem International Frank Chervenak, New York, NY, USA Lütfü Öndero¤lu, Ankara, Turkey Hospital, Istanbul, Turkey Bülent Çakmak, Tokat, Turkey Soner R. Öner, Izmir, Turkey Filiz Çayan, Mersin, Turkey Okan Özkaya, Isparta, Turkey Olufl Api Ebru Çelik, Malatya, Turkey Alexander Papitashvilli, Tbilisi, Georgia Vincenzo D’Addario, Bari, Italy ‹brahim Polat, Istanbul, Turkey Yeditepe University, Nur Daniflmend, Istanbul, Turkey Ritsuko Pooh, Osaka, Japan Istanbul, Turkey Cansun Demir, Adana, Turkey Ruben Quintero, Tampa, FL, USA Jan Deprest, Leuven, Belgium Nebojsa Radunovic, Belgrade, Serbia Ebru Dikensoy, ‹stanbul, Turkey Guiseppe Rizzo, Rome, Italy Gian Carlo DiRenzo, Perugia, Italy Stephen Robson, Newcastle, UK Tony Duan, Shanghai, PRC Roberto Romero, Detroid, MI, USA Joachim Dudenhausen, Berlin, Germany Levent Salt›k, Istanbul, Turkey Alaa Ebrashy, Cairo, Egypt Haluk Sayman, Istanbul, Turkey Elif Gül Yapar Eyi, Ankara, Turkey Mekin Sezik, Isparta, Turkey Ali Gedikbafl›, Istanbul, Turkey Ulrich Gembruch, Bonn, Germany Jiri Sonek, Dayton, OH, USA Anne Greenough, London, UK Yunus Söylet, Istanbul, Turkey Gökhan Göynümer, Istanbul, Turkey Milan Stanojevic, Zagreb, Croatia Arif Güngören, Hatay, Turkey Florin Stomatian, Cluj, Romania Melih A. Güven, Istanbul, Turkey Turgay fiener, Eskiflehir, Turkey Joseph Haddad, Paris, France Alper Tanr›verdi, Ayd›n, Turkey Davor Jurkovic, London, UK Ebru Tar›m, Adana, Turkey Oliver Kagan, Tübingen, Germany Neslihan Tekin, Eskiflehir, Turkey Burçin Kavak, Elaz›¤, Turkey Ilan Timor-Tritsch, New York, NY, USA ‹schiro Kawabata, Osaka, Japan Seyfettn Uluda¤, Istanbul, Turkey Selahattin Kumru, Düzce, Turkey Liliana Voto, Buenos Aires, Argentina Mertihan Kurdo¤lu, Ankara, Turkey Miroslaw Wielgos, Warsaw, Poland As›m Kurjak, Zagreb, Croatia Simcha Yagel, Tel Aviv, Israel Nilgün Kültürsay, Izmir, Turkey Ahmet Yal›nkaya, Diyarbak›r, Turkey Malcome Levene, Leeds, UK Ivica Zalud, Honolulu, HI, USA Names are in alphabetical order.
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Volume 24 | Issue 2 | August 2016 iii T A L J O A U N R I N R A E L P Contents
P L E R A Volume 24, Issue 2, August 2016 I N N R A U T A L J O www.perinataljournal.com
Original Article The cesarean rates and indications between 2010 and 2014 in the Obstetrics Department of Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital 61 Dr. Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Araflt›rma Hastanesi Do¤um Ünitesi’nde 2010–2014 sezaryen oranlar› ve endikasyonlar› Gökçe Naz Küçükbafl, Özlem Moralo¤lu, fiule Özel, Salim Erkaya, Yasemin Taflc›, Rahime Bedir F›nd›k Comparison of first trimester uterine artery Doppler parameters in hyperemesis gravidarum with normal pregnancy 66 Hiperemezis gravidarumlu olgular›n ilk trimester uterin arter Doppler parametrelerinin normal gebelerle karfl›laflt›r›lmas› ‹smail B›y›k, Gökhan Ocako¤lu, Emin Üstünyurt, Fatih Y›lmaz, Fatih Keskin An obstetric emergency case: vulvovaginal hematoma – our four-year results 72 Obstetrik bir acil durum: Vulvovajinal hematom – Dört y›ll›k sonuçlar›m›z Özlem Yörük, Ayflegül Öksüzo¤lu, Elif Gül Yapar Eyi, Burcu K›sa Karakaya, Necati Hançerlio¤lu Evaluation of the measurement of ACTH, fibronectin, pentraxin 3 levels and cervical length in pregnant women under threatened preterm delivery 77 Erken do¤um tehdidi olan gebelerde ACTH, fibronektin, pentraksin 3 düzeyleri ve servikal uzunluk ölçümlerinin de¤erlendirilmesi Filiz Aktenk, Burcu Artunç Ülkümen, Yeflim Güvenç, Halil Gürsoy Pala, Arzu Oran Hepatitis B seropositivity of pregnant women and the review of Turkish literature 83 Gebelerde hepatit B seropozitifli¤i ve Türk literatürüne bir bak›fl Rabia Zehra Bakar, Banu Dane Posterior fossa anomalies: related anomalies and the methods of pregnancy termination 89 Posterior fossa anomalileri: ‹liflkili anomaliler ve gebeliklerin sonlanma flekilleri Emine Ayd›n, Mert Turgal, Sema Can, Özgür Özyüncü Modified transabdominal cervico-isthmic cerclage: analysis of 16 cases 96 Servikal yetmezlikte modifiye transabdominal serviko-istmik serklaj: 16 olgunun analizi Ebru Çelik Kavak, Salih Burçin Kavak, Yakup Baykufl, Hüsnü Çelik Results of fetal anomaly screening performed at 11–14 weeks of gestation at a tertiary center 100 Üçüncü basamak bir merkezde 11–14. gestasyonel haftada yap›lan fetal anomali taramas› sonuçlar› Tu¤ba K›nay, Metin Kaplan, Mehmet Metin Altay, fiafak Özdemirci, Sinan Karadeniz, Ahmet Okyar Erol
Case Report Intrafetal laser therapy in acardiac twin pregnancy: a case report 106 Akardiyak ikiz gebelikte intrafetal lazer tedavisi: Olgu sunumu Resul Ar›soy, Oya Pekin, Kaan Pakay, Emre Erdo¤du, Oya Demirci, Murat Muhçu
Clinical Guidelines Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society 110 Gebelikte diyabet: Tan› ve tedavi. Türk Perinatoloji Derne¤i Uygulama Rehberi Cihat fien, Murat Yayla, Olufl Api, Elif Gül Yapar Eyi, Burcu Artunç Ülkümen; Diabetes and Pregnancy Study Group of Turkish Perinatology Society
iv Perinatal Journal A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatal Journal 2016;24(2):61–65 I N N R A U T A L J O
The cesarean rates and indications between 2010 and 2014 in the Obstetrics Department of Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital
Gökçe Naz Küçükbafl, Özlem Moralo¤lu, fiule Özel, Salim Erkaya, Yasemin Taflc›, Rahime Bedir F›nd›k Department of Obstetrics, Ankara Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital, Ankara, Turkey
Abstract Özet: Dr. Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Araflt›rma Hastanesi Do¤um Ünitesi’nde 2010–2014 sezaryen oranlar› ve endikasyonlar› Objective: World Health Organization (WHO) declared cesarean Amaç: Dünya Sa¤l›k Örgütü (DSÖ) maternal ve fetal mortaliteyi section rate decreasing maternal and fetal mortality as 10–15%. The azaltan sezaryen ameliyat oran›n› %10–15 olarak aç›klam›flt›r. Se- cesarean rates gradually increase and the ministries of health try to zaryen oranlar› giderek artmakta ve sa¤l›k bakanl›klar›, politikalarla get under control these rates by various policies. The cesarean rate bu oranlar› kontrol alt›nda tutmaya çal›flmaktad›r. 1988’den 2010’a increased from 5% to 45% in Turkey from 1988 to 2010. Turkish kadar Türkiye'de sezaryen oran› %5’ten %45’e yükselmifltir. T.C. Ministry of Health and Turkish Society of Obstetrics and Sa¤l›k Bakanl›¤› ile Türk Jinekoloji ve Obstetrik Derne¤i (TJOD), Gynecology (TJOD) have aimed to decrease cesarean rate to 35% sezaryen oran›n› 2013’te %35’e düflürmeyi amaçlam›fllard›r. Bu ça- in 2013. This study aims to investigate and evaluate cesarean rates l›flma, üçüncü basamak kad›n sa¤l›¤› ve do¤um hastanesi olan Anka- and the most common cesarean indications of 2010–2014 in Ankara ra Dr. Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Araflt›rma (ZTB) Dr. Zekai Tahir Burak Maternal Health Training and Research Hastanesi’nde, 2010–2014 sezaryen oranlar› ile en s›k sezaryen en- (ZTB) Hospital which is a tertiary maternity and obstetrics hospital. dikasyonlar›n›n araflt›r›lmas› ve incelenmesini amaçlamaktad›r. Methods: The archive records of the patients who delivered in the Yöntem: ZTB Hastanesi’nde 2010–2014 y›llar› aras›nda do¤um obstetrics department of ZTB Hospital between 2010 and 2014 ünitesinde do¤um yapan hastalar›n arfliv kay›tlar›, sezaryen say›s›- were investigated to determine the number of cesarean section and n›n saptanmas› ve sezaryen endikasyonlar›n›n belirlenmesi ama- cesarean indications. c›yla tarand›. Results: Between 2010 and 2014, 64,154 deliveries occurred in ZTB Bulgular: 2010–2014 y›llar› aras›nda ZTB Hastanesi’nde 64.154 Hospital. Of them, 23,200 were cesarean section. Mean cesarean rate do¤um gerçekleflmifltir. Bunlar›n 23.200’ü sezaryen ile do¤umdur. of five years was found as 36.2 ±3.96%. When cesarean indications Befl y›l›n ortalama sezaryen oran› %36.2±3.96 olarak hesaplan- were evaluated, the most common 10 reasons of cesarean section maktad›r. Sezaryen endikasyonlar› incelendi¤inde, sezaryen ameli- were found as previous single or multiple cesarean section (50.9%), yat›n›n en s›k 10 sebebinin s›ras›yla önceden geçirilmifl bir veya cephalopelvic disproportion (16.5%), fetal distress (12.1%), breech birden çok sezaryen ameliyat› (%50.9), bafl-pelvis uyumsuzlu¤u presentation (7.7%), non-progressive labor (3.2%), macrosomic baby (%16.5), fetal distres (%12.1), makat prezentasyon (%7.7), ilerle- (≥4000 g for the fetus of diabetic pregnant women, and ≥4500 g for meyen eylem (%3.2), makrozomik bebek (diyabetik gebe fetüsü other pregnant women), malpresentation (face, foot, deflection pres- için ≥4000 g, di¤er gebelerde ≥4500 g; %2.0), malprezentasyon entation etc.; except breech presentation, 1.6%), and cord prolapsus (yüz, ayak, defleksiyon prezentasyon vb.; makat prezentasyon ha- (0.8%). The greatest portion of cesarean section indications is the riç, %1.6) ve kordon prolapsusu (%0.8) oldu¤u görülmektedir. Se- previous cesarean section, which is 50.9%. zaryen ameliyat endikasyonlar›n›n en büyük k›sm›n›, %50.9 oran- Conclusion: We found that the mean cesarean rate (36.2%) for la, önceden geçirilmifl sezaryen ameliyat› oluflturmaktad›r. 2010–2014 in the obstetrics department of our hospital was close to Sonuç: Hastanemiz do¤um ünitesi 2010–2014 sezaryen oranlar› or- the rate (35%) aimed by TJOD and the Ministry of Health in 2013. talamas›n›n (%36.2), 2013’te TJOD ve Sa¤l›k Bakanl›¤› taraf›nca In order to decrease cesarean rates in Turkey to the level (15%) planlanan hedefe (%35) yak›n oldu¤u görülmektedir. Türkiye’de se- determined by WHO, further studies, the implementation of obstet- zaryen oran›n› DSÖ taraf›ndan belirlenen hedefe (%15) düflürmek ric guideline recommendations through the joint works of the için, ek çal›flmalar›n yap›lmas›, obstetrik rehber önerilerinin bakan- Ministry and the society in Turkey and additional briefing of preg- l›k ve dernek ortak çal›flmalar› ile Türkiye’de uygulanmas› ve Türk nant women and Turkish obstetricians are required. obstetrisyenleriyle gebelerin ileri bilgilendirilmesi gerekmektedir. Keywords: Cesarean, indication, rate, vaginal delivery. Anahtar sözcükler: Sezaryen, endikasyon, oran, vajinal do¤um.
Correspondence: Gökçe Naz Küçükbafl, MD. Ankara Zekai Tahir Burak Kad›n Sa¤l›¤› Available online at: E¤itim ve Araflt›rma Hastanesi, Do¤um Ünitesi, Ankara, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242001 doi:10.2399/prn.16.0242001 Received: March 21, 2016; Accepted: May 9, 2016 QR (Quick Response) Code: Please cite this article as: Küçükbafl GN, Moralo¤lu Ö, Özel fi, Erkaya S, Taflc› Y, Bedir F›nd›k R. The cesarean rates and indications between 2010 and 2014 in the Obstetrics Department of Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital. Perinatal Journal 2016;24(2):61–65. ©2016 Perinatal Medicine Foundation Küçükbafl GN et al.
Introduction It is known that cesarean section is a method developed to help the babies of deceased mothers to survive, to bury deceased mother and baby separately in accor- dance with religious beliefs or to help mothers to sur- vive through an alternative method which are conclud- ed that the babies cannot be delivered vaginally.[1] Today, cesarean sections are carried out with many medical indications such as placenta previa, ablatio pla- centae, cord prolapsus etc. On the other hand, it is also known that cesarean section is performed on maternal demand. This caused normal delivery rate to decrease globally. World Health Organization (WHO) asserts that Fig. 1. Vaginal delivery and cesarean rates in years between 2010 the cesarean rate which will decrease maternal and fetal and 2014 at Ankara Dr. Zekai Tahir Burak Maternal Health mortality has been 10–15% since 1985 and that there Training and Research Hospital. is no evidence showing that cesarean rates above 15% decrease maternal or newborn mortality.[2] It is seen in the last three decades that the cesarean rates in Turkey Results change by years but tend to increase. The cesarean rate It was found in the archive investigation that 64,154 which was 5% in 1988 was over 45% in 2010.[3] With deliveries occurred at our hospital between 2010 and the joint project of Turkish Society of Obstetrics and 2014. Of them, 23,200 were cesarean section. It is seen Gynecology (TJOD) initiated in 2011, it was aimed to that cesarean rates change by years (Fig. 1). Mean decrease cesarean rate in 2013 to 35% in Turkey.[4] cesarean rate of 5 years was calculated as 36.2±3.96% While it is obvious that the improvement in this field (Table 1). can be achieved by cooperation with all healthcare organizations, reference central obstetric training and When cesarean indications were evaluated, the research hospitals, which offer public service and some most common 10 reasons of cesarean section were also providing healthcare to high risk patient group, found as previous single or multiple cesarean section have the highest responsibility. The purpose of this (50.9%), cephalopelvic disproportion (CPD, 16.5%), study is to investigate cesarean rates at Ankara Dr. fetal distress (12.1%), breech presentation (7.7%), Zekai Tahir Burak Maternal Health Training and non-progressive labor (3.2%), macrosomic baby ≥ Research Hospital between 2010 and 2014 and to ( 4000 g for the fetus of diabetic pregnant women, and ≥ determine basic cesarean indications. 4500 g for other pregnant women), malpresentation (face, foot, deflection presentation etc.; except breech Methods The archive records of the patients who were hospital- Table 1. Cesarean rates in years between 2010 and 2014 and mean ce- ized at the obstetrics service and delivered between sarean rate for these years at Ankara Dr. Zekai Tahir Burak Ma- ternal Health Training and Research Hospital. 01.01.2010 and 31.12.2014 at Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital were Years Delivery Cesarean Normal delivery % reviewed in order to determine the number of cesare- number number number an cases and cesarean indications. The arithmetic mean 2010 13,091 5349 7742 40.8 and standard deviation of numerical data were calculat- 2011 13,111 4632 8479 35.3 ed. The data were presented as definitive tables and 2012 12,461 4486 7975 36.0 graphs. The patients transferred to High Risk 2013 12,387 5142 7245 41.5 Pregnancy Service for delivery due to additional mor- 2014 13,104 3591 9513 27.4 bidity during labor were excluded from the study. Total 64,154 23,200 40,954 Mean 36.2%
62 Perinatal Journal The cesarean rates and indications between 2010 and 2014 in Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital
presentation, 1.6%), and cord prolapsus (0.8%) (Table Table 2. The most common cesarean indications in years between 2). The greatest portion of cesarean section indications 2010 and 2014 at Ankara Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital. is the previous cesarean section, which is 50.9%.
Indications Number %
Discussion Second cesarean section 8755 37.8 Mean cesarean rate at our hospital is 36.2±3.96% Head-pelvis disproportion 3831 16.5 Fetal distress 3199 13.8 between 2010 and 2014. This mean is lower than 45% Third cesarean section 2630 11.3 which is the mean cesarean rate of Turkey for the last Breech presentation 1779 7.7 5 years and it can be said that it is close to 35% which Non-progressive labor 737 3.2 is the level aimed by the Ministry of Health and Macrosomic baby 468 2.0 TJOD. When analyzed, it is seen that there is a Fourth cesarean section 430 1.8 decrease in cesarean rates as a general tendency, but Malpresentation 367 1.6 Cord prolapsus 171 0.8 this decrease has no regular pattern in the last 5 years (Fig. 1). While the highest cesarean rate in the 5 years is 41.5%, the lowest rate is 27.4% (Table 1). nant women.[9] It can be said that a drop in the cesare- The greatest portion of cesarean section indications an rates is seen with the help of classes, especially the is the previous cesarean section, which is 50.9%. childbirth class, given by Pregnancy School which Therefore, while cesarean section is decided in multi- started to offer service in our hospital in the beginning parous patients with primigravid or normal delivery of 2014. Because the lowest cesarean rate of our hospi- history, reviewing cesarean indications for a second tal was seen in 2014 with the rate of 27.4% and it was time will be useful to decrease cesarean rates in the below 35% which was the level aimed by TJOD and very beginning. If vaginal delivery after cesarean is the Ministry of Health. offered and supported with all risks and advantages to According to our study, the most common indica- patients who have cesarean section history (by paying tion in the patients without any previous cesarean sec- attention to maternal and neonatal health conditions), tion is CPD. It is also one of the major indications for the rate of cesarean due to previous cesarean section [10] primary cesarean section in the USA. In a workshop may be decreased. In the study of Costa et al., cesarean carried out by American College of Obstetricians and rates in Portugal between 2005 and 2011 were com- Gynecology (ACOG) and National Institute of Child pared and it was stated that the decrease seen depends [5] Health and Human Development (NICHD) in 2012, on this policy. it was asserted that there is an increase in cesarean rates Cesarean rate on maternal demand in the USA is due to not waiting enough by obstetricians when estab- between 1 to 7%.[6,7] It was seen in China, which is one lishing the diagnosis of cephalopelvic disproportion.[10] of the countries with highest cesarean rates where Considering the fetomaternal well-being, informing cesarean rate was declared as 58% in 2010, that cesare- obstetricians to give necessary time may cause a signif- an indication on maternal demand was increasing icant decrease in cesarean rates. [8] cesarean rate significantly. Cesarean rate of Turkey The pregnant women in labor are monitored con- being lower than of China can be explained with the tinuously by fetal tococardiography in our hospital. fact that maternal demand is not a cesarean indication There are studies reporting that the cesarean rates of in public hospitals. The results of the studies reporting pregnant women under continuous monitorization are cesarean indications in China show similarity with the significantly higher than those not under continuous results of our study when maternal demand is over- monitorization.[11,12] Delivering fetuses by cesarean sec- looked.[8] tion who are not really under stress but established In a Cochrane review entitled “Non-clinical fetal distress diagnosis due to false positivity for fetal [13] Interventions for Reducing Unnecessary Caesarean distress increases cesarean rates. Section” in 2011, it was shown that cesarean rates were It is known that increased cesarean rates lead to decreased by the childbirth classes provided to preg- increase in fetal mortality and admission rates to new-
Volume 24 | Issue 2 | August 2016 63 Küçükbafl GN et al.
born unit.[14] However, there are also studies which the criteria recommendations of the guidelines such as found that ending pregnancies with breech presentation ACOG etc. when planning cesarean section upon the by planned cesarean section decreases neonatal mortali- diagnosis of non-progressive labor. [15,16] ty and morbidity. It was reported in a meta-analysis In our hospital, we consider that fetuses of diabetic published in 2016 that ending pregnancies with breech mothers estimated to have fetal weight as 4000 g and presentation by vaginally is more risky than cesarean the fetuses of other mothers as 4500 g and above are section but this risk is not high and that it can be made macrosomic fetuses, and we recommend cesarean such a decision for an individual delivery method customized pregnant women to prevent possible vaginal labor [17] for patient. In our hospital, pregnant women with complications (shoulder dystocia etc.). ACOG bul- breech presentation during delivery are informed about letins recommend to establish macrosomic fetus diag- perinatal-neonatal mortality and morbidity risks of vagi- nosis when the fetuses of diabetic mothers are 4500 g nal delivery and that such risks are lower in cesarean sec- and the fetuses of other mothers are 5000 g and above, tion. Under the patient consent, it is preferred to deliv- and to plan cesarean section in such cases.[21] Therefore, er these pregnancies by cesarean section. Therefore, we cesarean rate due to macrosomic fetus diagnosis may distinguished breech presentation from malpresentation be higher in our hospital than other institutions fol- in our study and found that it was alone 7.7% of cesare- lowing ACOG recommendations. an indications. The recommendations of ACOG guide- Other recommendations of international guidelines lines also support to recommend cesarean section to to decrease cesarean rates are to try external cephalic pregnant women upon informing.[18] In our study, version in breech presentations after 36 weeks of ges- breech presentation is among the first 10 reasons affect- tation, provide continuous support during labor, use ing cesarean rates. partogram at intervals during labor follow-up, and Among the cesarean indications found in our study, conduct fetal blood sampling before planning cesarean non-progressive labor is the sixth common indication. section when abnormal cardiotocography is In a study performed in the USA, it was seen that the observed.[9,22] elevated rates in elective labor inductions applied dur- The cesarean rate in 2008 is 38% and it was report- ing “at term premature (37 weeks – 38 weeks and 6 ed in the study performed by Barbadoro et al. in Italy, days) pregnancy” increase the rates of non-progressive which has the highest cesarean rate in the European labor and cause increased cesarean rates secondari- [13,19] Union, that cesarean rate is higher in southern regions ly. Diagnosis criteria for non-progressive labor [23] and in women above 35-year-old. Starting from during the first phase of delivery were determined in these data, determining the groups in Turkey with the Consensus of Safe Prevention of the Primary high cesarean rates and ensuring to take special precau- Cesarean Delivery held by ACOG in 2014. tions for such groups may help to decrease cesarean Accordingly, cesarean section should be planned by rates to the optimal levels. establishing non-progressive labor diagnosis in patients with amniotomy or membrane rupture, 6 cm dilatation, having 4-hour sufficient uterine activity or Conclusion without any progress in cervical dilatation despite at We found that the mean cesarean rate (36.2%) for least 6-hour oxytocin induction when insufficient uter- 2010–2014 in the obstetrics department of our hospital [20] ine activity was found. However, it was shown in the was close to the rate (35%) aimed by TJOD and the research conducted by National Sentinel Caesarean Ministry of Health in 2013. In order to decrease Section Audit (NSCSA) that 17% of non-progressive cesarean rates in Turkey to the level (15%) determined labor diagnosis was established to the pregnant women by WHO, further studies, the implementation of [13] whose cervical dilatation was not reached to 4 cm yet. obstetric guideline recommendations through the joint In the light of the data obtained from here, cesarean works of the Ministry and the society in Turkey and rates can be reduced by determining gestational age in additional briefing of pregnant women and Turkish labor induction carefully, considering that cesarean obstetricians are required. section risk increases if elective induction is performed during at term premature period, and lastly, following Conflicts of Interest: No conflicts declared.
64 Perinatal Journal The cesarean rates and indications between 2010 and 2014 in Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital
References 12. Alfrevic Z, Devane D, Gyte GM. Continuous cardiotocogra- phy (CTG) as a form of electronic fetal monitoring (EFM) 1. U.S. National Library of Medicine (NLM): A brief history: for fetal assessment during labour. Cochrane Database Syst Part 1. [Internet] Bethesda (MD): NLM; [updated 2013 Jul Rev 2013;(5):CD006066. 26; cited 2015 Jul 26]. Available from: https://www.nlm. nih.gov/exhibition/cesarean/part1.html/ 13. National Collaborating Centre for Women’s and Children’s 2. World Health Organization (WHO): WHO statement on cae- Health. Caesarean section. London: RCOG Press; 2004. serean rates. [Internet] WHO HRP; [updated 2015 Apr; cited 14. Villar J, Valladares E, Wojdyla D, Zavetela N, Carroli G, 2015 Jul 26]. Available from: http://www.who.int/reproductive- Velazco A, et al.; WHO 2005 Global Survey on Maternal and health/publications/maternal_perinatal_health/cs-statement/ Perinatal Health Research Group. Caesarean delivery rates en/ and pregnancy outcomes: the 2005 WHO global survey on 3. Sa¤l›kta Gündem: Türk Jinekoloji ve Obstetrik Derne¤i maternal and perinatal health in Latin America. Lancet 2006; sezaryen aç›klamas›. [Internet] Sa¤l›kta Gündem; [updated 367(9525):1819–29. 2012 June 27; cited 2015 Jul 26]. Available from: http:// 15. Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Seigal www.sagliktagundem.com/haber/tjod_sezaryen_aciklamasi.htm/ S, Willian AR. Planned caeserean section versus planned 4. Türk Jinekoloji ve Obstetrik Derne¤i (TJOD): Sa¤l›k vaginal birth for breech presentation at term: a randomised Bakanl›¤› - TJOD sezaryen oranlar›n› azaltma ortak eylem multicentre trial. Lancet 2000;356(9239):1275–83. plan›. [Internet] TJOD; [updated 2013; cited 2015 Jul 20]. Available from: http://www.tjod.org/saglik-bakanligi-tjod- 16. Bergenhenegouwen LA, Meertens LJ, Schaaf J, Nijhuis JG, sezaryen-oranlarini-azaltma-ortak-eylem-plani/ Mol BW, Kok M, et al. Vaginal delivery versus caeserean sec- 5. Costa A, Policiano C, Clode N, Graça LM. Indications for tion in preterm breech delivery: a systematic review. Eur J caeserean deliveries during a 7-year period in a tertiary hos- Obstet Gynecol Reprod Biol 2014;172:1–6. pital. Acta Med Port 2013;26:649–54. 17. Berhan Y, Haileamlak A. The risks of planned vaginal breech 6. Gossman GL, Joesch JM, Tanfer K. Trends in maternal delivery versus planned caesarean section for term breech request cesarean delivery from 1991 to 2004. Obstet Gynecol birth: a meta-analysis including observational studies. BJOG 2006;108:1506–16. 2016;123:49–57. 7. Menacker F, Declercq E, Macdorman MF. Ceserean deliv- 18. ACOG Committee on Obstetric Practice. ACOG Committee ery: background, trends and epidemiology. Semin Perinatol Opinion No. 340. Mode of term singleton breech delivery. 2006;30:235–41. Obstet Gynecol 2006;108:235–7. 8. Liu Y, Li G, Chen Y, Wang X, Ruan Y, Liying Z, et al. A 19. Murthy K, Grobman WA, Lee TA, Holl JL. Trends in induc- descriptive analysis of the indications for caeserean section in tion of labor at early-term gestation. Am J Obstet Gynecol mainland China. BMC Pregnancy Childbirth 2014;14:410–1. 2011;204:435–6. 9. Khunpradit S, Tavender E, Lumbiganon P, Laopaiboon M, Wasiak J, Gruen RL. Non-clinical interventions for reduc- 20. American College of Obstetricians and Gynecologists; Society ing unnecessary caesarean section. Cochrane Database Syst for Maternal-Fetal Medicine. Obstetric care consensus no. 1: Rev 2011;(6):CD005528. safe prevention of the primary cesarean delivery. Obstet 10. Spong CY, Berghella V, Wenstrom KD, Mercer BM, Saade Gynecol 2014;123:693–711. GR. Preventing the first cesarean delivery: summary of a 21. Chatfield J. ACOG issues guidelines on fetal macrosomia. joint Eunice Kennedy Shriver National Institute of Child American College of Obstetricians and Gynecologists. Am Health and Human Development, Society for Maternal- Fam Physician 2001;64:169–70. Fetal Medicine, and American College of Obstetricians and 22. Richard F, De Brouwere V. Non-clinical interventions for Gynecologists Workshop. Obstet Gynecol 2012;120:1181– 93. reducing unnecessary caesarean section: RHL commentary (last revised: 1 September 2012). The WHO Reproductive 11. Rossignol M, Chaillet N, Boughrassa F, Moutquin JM. Health Library. Geneva: World Health Organization; 2012. Interrelations between four antepartum obstetric interven- tions and cesarean delivery in women at low risk: a systemat- 23. Barbadoro P, Chiatti C, D’Errico MM, DiStanislao F, ic review and modeling of the cascade of interventions. Birth Prospero E. Caeserean delivery in South Italy: women without 2014;41:70–8. choice. A crosssectional survey. PLoS One 2012;7:e43906.
Volume 24 | Issue 2 | August 2016 65 A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatal Journal 2016;24(2):66–71 I N N R A U T A L J O
Comparison of first trimester uterine artery Doppler parameters in hyperemesis gravidarum with normal pregnancy
‹smail B›y›k1, Gökhan Ocako¤lu2, Emin Üstünyurt3, Fatih Y›lmaz4, Fatih Keskin5 1Obstetrics and Gynecology Clinic, Karacabey State Hospital, Bursa, Turkey 2Department of Biostatistics, Faculty of Medicine, Uluda¤ University, Bursa, Turkey 3Obstetrics and Gynecology Clinic, fievket Y›lmaz Training and Research Hospital, Bursa, Turkey 4Department of Obstetrics and Gynecology, Faculty of Medicine, Uluda¤ University, Bursa, Turkey 5Obstetrics and Gynecology Clinic, Mustafakemalpafla State Hospital, Bursa, Turkey
Abstract Özet: Hiperemezis gravidarumlu olgular›n ilk trimester uterin arter Doppler parametrelerinin normal gebelerle karfl›laflt›r›lmas› Objective: The purpose of this study was to compare the first trimester Amaç: Bu çal›flman›n amac› hiperemezis gravidarum (HG), gebe- uterine artery Doppler measurements between hyperemesis gravidarum li¤in bulant› ve kusmas› (NVP) ve kontrol gruplar› aras›ndaki ilk (HG), nausea and vomiting of pregnancy (NVP) and control groups. trimester uterin arter Doppler ölçümlerini karfl›laflt›rmakt›r. Methods: In a case-control study, the ratio of bilateral uterine Yöntem: Olgu kontrol çal›flmas›nda 6 ve 14 gebelik haftas›ndaki artery pulsatility index (PI), resistive index (RI) and systole/dias- HG’li, NVP’li ve normal gebelerde transabdominal yolla bilateral tole (S/D) were measured transabdominally in 6th to 14th week of uterin arter Doppler pulsatilite indeksi (PI), rezistif indeks (RI), sis- gestation of women with hyperemesis gravidarum, nausea and tol/diastol oranlar› (S/D) ölçüldü. vomiting of pregnancy and normal pregnancy. Bulgular: K›rk dokuz HG’li, 51 NVP’li ve 50 normal gebe olmak Results: A total of 150 cases, consisting of 49 with HG, 51 NVP and üzere toplam 150 gebe de¤erlendirildi. Sa¤ ve sol uterin arter 50 normal pregnant women were evaluated. Right and left uterine Doppler PI, RI, S/D de¤erleri gruplar aras›nda benzer bulundu artery PI, RI, S/D values were found similar between groups (p>0.05). (p>0.05). Conclusion: No significant difference was found between HG, Sonuç: Bu çal›flmada HG, NVP ve kontrol gruplar› aras›nda ilk NVP and control groups in terms of first trimester uterine artery trimester uterin arter Doppler parametreleri aç›s›ndan fark bulun- Doppler parameters in this study. Prospective studies with a large mad›. Bulgular›m›z› destekleyen genifl serili prospektif çal›flmalara number of cases are required to support our findings. ihtiyaç vard›r. Keywords: Hyperemesis gravidarum, HG, uterine artery Doppler, Anahtar sözcükler: Hiperemezis gravidarum, HG, uterin arter first trimester. Doppler ölçümü, ilk trimester.
Introduction expected. The incidence of hyperemesis gravidarum (HG), [2] Nausea and vomiting of pregnancy (NVP) causes mild a more serious condition, is reported as 0.3 to 3.6%. nausea and affects 70–85% of pregnant women.[1] Pregnant In HG, ketone bodies increase in maternal blood. women with NVP usually feel better after the first Increased ketone bodies may cause metabolic acidosis. trimester and a negative perinatal effect is not usually To provide acid-base regulation in circulation, ventila-
Correspondence: ‹smail B›y›k, MD. Karacabey Devlet Hastanesi Kad›n Hastal›klar› ve Available online at: Do¤um Klini¤i, Bursa, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242002 doi:10.2399/prn.16.0242002 Received: March 20, 2016; Accepted: May 24, 2016 QR (Quick Response) Code: Please cite this article as: B›y›k ‹, Ocako¤lu G, Üstünyurt E, Y›lmaz F, Keskin F. Comparison of first trimester uterine artery Doppler parameters in hyperemesis gravidarum with normal pregnancy. Perinatal Journal 2016;24(2):66–71. ©2016 Perinatal Medicine Foundation Comparison of first trimester uterine artery Doppler parameters in hyperemesis gravidarum with normal pregnancy
tion rate increases. Respiratory alkalosis develops with with vomiting, dry mucous membranes, decreased skin increased ventilation rate. Severe respiratory alkalosis turgor and hypotension findings were considered as the and hypocapnia may cause uterine artery vasospasm, sufficient findings for hospitalization. The pregnant reduced placental perfusion, fetal hypoxia and meta- women with nausea which was not severe as much as bolic acidosis. In such case, uterine artery vascular HG, lasting for the whole day and not associated with resistance may increase. Therefore, uterine artery ketonuria and loss of weight were established with the Doppler parameters can be increased. Increased uter- diagnosis of NVP. The cases in the control group were ine artery vascular resistance may cause placental insuf- chosen among those with healthy singleton pregnancy ficiency related pregnancy complications. without full-day nausea. Some studies report that nausea and vomiting in Those with multiple pregnancies, with a history of pregnancy may be related to unwanted results associat- hypogastric artery ligation or systemic disease with ed with placental insufficiency[3] while others suggest the vascular involvement, and smokers were not included opposite.[4] Some studies carried out to predict pregnan- in the study. Those with pyelonephritis or thyrotoxico- cy complications in the first trimester with uterine artery sis were also not included in the study as these condi- Doppler are reported.[5] However, there are a limited tions can mimic HG. number of studies where the first trimester artery The demographic data of the cases such as age, gravi- Doppler measurements have been evaluated in HG. da, parity, abortion, and number of living children were recorded. Body analyses such as height, weight, and body The purpose of this study was to investigate the mass index (BMI) were recorded. The values of alanine relationship between the first trimester uterine artery amino transferase (ALT), aspartate amino transferase Doppler measurements used in the prediction of pla- (AST), urea, blood urea nitrogen (BUN), creatinine, cental deficiency in HG, NVP and control groups. ketonuria, hemoglobin, and thyroid stimulating hor- mone (TSH) were recorded as laboratory parameters. Methods The gestational week (GA) was recorded in days accord- This case-control study was carried out in Karacabey ing to the crown-rump length (CRL) measurement. State Hospital between January 2014 and September We used a 3.5 MHz curvilinear transabdominal 2015. The Non-Invasive Human Research Ethics transducer for the ultrasound investigation. We first Committee of fievket Y›lmaz Training and Research obtained a midsagittal section of the uterus and cervical Hospital approved the study. Informed consent was canal and then moved the transducer laterally until we obtained from all cases participated in the study. could visualize the paracervical vessels. Color flow Three groups of pregnant women in first trimester Doppler was used for the session. We visualized the uter- from 6 to 14 weeks of gestation were included into the ine arteries as aliasing vessels along the cervix. Pulsed wave Doppler with the sampling gate set at 2 mm was study. First and second groups consisted of women with used to obtain flow velocity waveforms. These wave- HG and nausea and vomiting of pregnancy (NVP), forms were obtained from the point on the ascending respectively. The third one was considered as the con- branch of the uterine artery that was closest to the inter- trol group and consisted of healthy pregnant women nal os. We used the smallest angle of insonation (< 30°) without any complaints. The diagnosis of HG was based to obtain the highest systolic and end-diastolic velocities. on the clinical decision as the nausea, protracted vomit- We measured the PI (pulsatility index), RI (resistive ing and inability to tolerate food intake accompanied by index) and S/D (systole/diastole ratio) when three similar obvious dehydration severe enough to justify hospital- consecutive waveforms were obtained. The presence of a ization with at least 1(+) ketonuria on dipstick urine notch in the uterine artery was also investigated. Color analysis. NVP was diagnosed when nausea and vomiting flow Doppler and pulsed Doppler durations were kept was less severe with no history of weight loss and any under a minute for safety during the measurements. sign of dehydration, no ketonuria or ketonemia or any other metabolic disorders. The number of cases in the Statistical analysis three groups was 49, 51 and 50, respectively. Continuous variables were expressed as mean ± standard In the diagnosis of HG, nausea and vomiting, loss of deviation or median (minimum–maximum) while cate- weight, ketonuria, electrolyte abnormalities associated gorical variables were presented as frequency with the
Volume 24 | Issue 2 | August 2016 67 B›y›k ‹ et al.
Table 1. Demographic and laboratory data of the cases.
Total (n=150) HG (n=49) NVP (n=51) Control (n=50) p
Age (years) 26.83±5.72 25.76±5.52 27.08±5.48 27.62±6.10 0.251 G 2 (0–6) 2 (0–6) 2 (1–6) 2 (1–6) 0.460 P 1 (0–5) 0 (0–5) 0 (0–3) 1 (0–3) 0.185 A 0 (0–3) 0 (0–2) 0 (0–3) 0 (0–3) 0.522 Y 0.50 (0–4) 0 (0–4) 0 (0–3) 1 (0–3) 0.177 GA (days) 63.50 (41–95) 61 (42–95) 63 (41–91) 64 (41–92) 0.711 Body weight 64.16±13.26 61.28±12.25 66.32±14.67 64.77±12.43 0.153 Height 1.60±0.06 1.59±0.07 1.60±0.06 1.60±0.05 0.654 BMI 25.09±5.32 23.62 (1.62–40.30) 24.60 (18–45) 24.30 (17.30–35.80) 0.362 ALT (IU/L) 12 (6–78) 11 (6–78) 12 (6–58) 13 (6–58) 0.968 AST (IU/L) 16 (7–50) 16 (11–50) 16 (7–34) 16 (10–30) 0.684 Urea (mg/dL) 18.49±5.39 20.65±5.17 18.54±5.05 16.27±5.13 <0.001 Creatinine (mg/dL) 0.62±0.10 0.61±0.06 0.61±0.07 0.63±0.02 0.638 Hemoglobin (g/dL) 12.50 (9–15.40) 12.60 (10.80–15.40) 12.20 (9–14.40) 12.60 (10.20–14.50) 0.314
ALT: alanine amino transferase, AST: aspartate amino transferase, GA: gestational age, BMI: body mass index, HG: hyperemesis gravidarum, NVP: nausea and vomiting of pregnancy related percentage. The Kruskal-Wallis or ANOVA test body weight 64 kg. There was no significant difference was used for between group comparisons whether the between the groups in terms of age, gravida, parity, abor- variables followed a normal distribution or not. The tion, number of living children, height, body weight, and Bonferroni test was used for multiple comparisons after BMI (p>0.05). There was also no significant difference in the ANOVA test. Two group comparisons were per- terms of thyroid stimulating hormone (TSH), ALT, formed using the Mann-Whitney U test. The Pearson AST, creatinine, and hemoglobin levels (p>0.05). Urea chi-square test was used for between group comparisons levels were higher in the HG group than the control of categorical variables. Statistical analyses were per- group (p<0.001). No significant difference was present for formed using SPSS v.21 (SPSS Inc., Chicago, IL, USA) urea levels with the other group comparisons (p>0.05). α and the level of significance was set at =0.05. The mean ketonuria level was 2.02±1.25 (range: 1 to 4) positive in the HG group. The ketonuria level Results was 1 positive in 26 (53.10%) cases, 2 positive in 7 A total of 150 cases consisting of 49 HG cases, 51 NVP (14.3%) cases, 3 positive in 5 (10.20%) cases and 4 pos- cases and 50 normal pregnancies were evaluated. The itive in 11 (22.40%) cases in our HG group. demographic data of the cases are presented at Table 1. Uterine artery Doppler parameters of the cases are The mean age was 26.83 years, and the mean gestational presented in Table 2. No significant difference was age 63 days. The mean BMI was 25 kg/m2 and the mean found between the groups in terms of PI, RI, and S/D
Table 2. Sonographic findings of cases.
Total (n=150) HG (n=49) NVP (n=51) Control (n=50) p
Right UtA PI 2.04±0.55 1.94±0.52 2.14±0.57 2.04±0.55 0.167 Right UtA RI 0.81 (0.16–0.92) 0.80 (0.16–0.91) 0.83 (0.43–0.92) 0.81 (0.49–0.91) 0.053 Right UtA S/D 5.62±2.23 5.24±2.03 6.19±2.51 5.40±2.04 0.072 Left UtA PI 2.16±0.58 2.16±0.54 2.22±0.65 2.08±0.56 0.485 Left UtA RI 0.83 (0.46–0.91) 0.82 (0.55–0.91) 0.83 (0.46–0.91) 0.83 (0.55–0.90) 0.681 Left UtA S/D 5.91±2.24 5.85±0.12 6.18±2.48 5.69±2.12 0.535
HG: hyperemesis gravidarum, NVP: nausea and vomiting of pregnancy, PI: pulsatility index, RI: resistive index, S/D: systole/diastole, UtA: uterine artery
68 Perinatal Journal Comparison of first trimester uterine artery Doppler parameters in hyperemesis gravidarum with normal pregnancy
values (p>0.05). A notch was present in 81 (54.40%) and that HG is associated with adverse pregnancy outcomes. absent in 68 (45.60%) cases. The notch information of Some studies have reported that limitation in weight one case was not recorded. No difference was found gain due to HG in pregnancy increased the risk of SGA between the groups in terms of the notch incidence (small-for-gestational age) and preterm birth.[3,12,13] More (p>0.05). There was no significant change in the right recently, Bolin et al. reported with a large population uterine artery Doppler parameters but the left uterine study in Sweden that pregnancies with HG had a slight- artery PI, RI, and S/D values decreased as maternal ly increased risk of preeclampsia, and especially preterm weight and BMI values increased (p=0.015, p=0.033, preeclampsia compared with pregnancies without HG. p=0.021 and p=0.017, p=0.044, and p=0.016, respective- They also found that pregnancies with HG were associ- ly). There was no change in the left uterine artery ated with an almost 50% increased risk of placental Doppler parameters but the right uterine artery RI value abruption and a slightly increased risk of an SGA birth decreased as the ketonuria increased (p=0.037). No sig- compared to the other group. The early onset nificant relationship was found between notch positivity preeclampsia risk was also increased in the women with and the ketonuria level (p>0.05). No significant relation- HG. The authors believed that early onset preeclampsia ship was found between the ketonuria level and the in particular may be related to inadequate spiral artery TSH, ALT, and AST values (p>0.05). The urea value remodelling and HG may be related to placental defi- increased as the ketonuria level increased (<0.001). ciency. They recommended a study to be conducted to evaluate HG cases with uterine artery Doppler.[14] Discussion Roseboom et al. concluded that adverse pregnancy out- comes were more prevalent among women who had suf- Ketone bodies are water-soluble molecules that are pro- fered from HG. This group more often delivered pre- duced by the liver from fatty acids during periods of low maturely and more often had a baby that was small for food intake (fasting) or carbohydrate restriction for cells [15] gestational age. Vikanes et al. reported that HG was of the body to use as energy instead of glucose. The associated with a decreased risk for delivering a child three endogenous ketone bodies are acetone, acetoacetic with a 1-minute Apgar score <7, but no difference was acid, and beta-hydroxybutyric acid. When ketone bodies observed in 5-minute score.[16] increase in maternal blood, ventilation rate increases to provide acid-base balance. Severe respiratory alkalosis Several studies aiming to predict pregnancy compli- cations such as preeclampsia, low birth weight, and and hypocapnia may cause uterine artery vasospasm, preterm birth in the first trimester have been conducted reduced placental perfusion, fetal hypoxia and metabolic [6] in recent years. These studies have focused on the pre- acidosis. In such case, uterine artery vascular resistance diction of placental deficiency with uterine artery may increase. Therefore, uterine artery PI, RI and S/D Doppler measurements and biochemical markers. Some values may elevate. studies report that high uterine artery Doppler PI values Nausea and vomiting are common problems in preg- reflect placental deficiency.[17] Many studies have tried to nancy. NVP usually improves after the first trimester of predict pregnancy complications related to abnormal pregnancy and is usually not associated with adverse placentation (preeclampsia, IUGR, low birth weight, pregnancy outcomes. However, the reports on the out- etc.) with first trimester uterine artery Doppler evalua- comes of pregnancy with HG, the most severe form of tions. Poon et al. reported that mean arterial pressure nausea and vomiting, are conflicting. NVP generally and the lowest 11–14 week uterine artery PI values recovers after the first trimester and it is usually not asso- increased and pregnancy-associated plasma protein A ciated with adverse pregnancy outcomes. On the other (PAPP-A) decreased in preeclampsia compared to the hand, gestational outcomes in HG are controversial. In controls. The risk of delivering an SGA fetus was found this study, we investigated the relationship between the to be high in pregnant women with high first trimester first trimester uterine artery Doppler measurements PI values in some studies.[18,19] There are many studies on used in the prediction of placental deficiency in HG, detecting pregnancy complications with first trimester NVP and control groups. uterine artery Doppler but only a few studies aiming to Some studies suggest that HG does not cause predict placental deficiency with first trimester uterine adverse pregnancy outcomes.[7–11] Other studies suggest artery Doppler in cases with HG.
Volume 24 | Issue 2 | August 2016 69 B›y›k ‹ et al.
First trimester PAPP-A levels have been found to 3. Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. Outcomes be low in pregnancies complicated with preeclampsia, of pregnancies complicated by hyperemesis gravidarum. [20–22] Obstet Gynecol 2006;107:285–92. SGA and preterm birth in some studies. Derbent et al. found higher PAPP-A levels in their HG cases than 4. Furneaux EC, Langley-Evans AJ, Langley-Evans SC. [23] Nausea and vomiting of pregnancy: endocrine basis and con- the control group. tribution to pregnancy outcome. Obstet Gynecol Surv 2001; We compared the uterine artery parameters of the 56:775–82. HG, NVP and control groups in this study. No signif- 5. Khong SL, Kane SC, Brennecke SP, da Silva Costa F. First- icant difference was found between the three groups in trimester uterine artery Doppler analysis in the prediction of terms of first trimester uterine artery Doppler PI, RI, later pregnancy complications. Dis Markers 2015;2015:679730. and S/D values. The lack of a difference in the PI value 6. Nageotte MP. Intrapartum fetal surveillance. In: Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR, Greene MF, that reflects placental deficiency supports the findings [23] editors. Creasy & Resnik’s maternal-fetal medicine: principles of Derbent et al. The PAPP-A value is found to be and practice. 7th ed. Philadelphia: Elsevier Saunders; 2014. p. low in placental deficiency situations. However, 491–5. Derbent et al. found the PAPP-A value to be high in 7. Weigel RM, Weigel MM. Nausea and vomiting of early the HG group.[23] The lack of a difference in PI values pregnancy and pregnancy outcome. A meta-analytical between the three groups indicates that the placental review. Br J Obstet Gynaecol 1989;96:1312–8. deficiency risk in HG may not be high. There are also 8. Tan PC, Jacob R, Quek KF, Omar SZ. Pregnancy outcome other studies that support our opinion.[8–10] However, it in hyperemesis gravidarum and the effect of laboratory clini- cal indicators of hyperemesis severity. J Obstet Gynaecol Res is possible that no difference was found because the 2007;33:457–64. uterine artery Doppler was performed in the early first 9. Tsang IS, Katz VL, Wells SD. Maternal and fetal outcomes trimester (an average of nine weeks) in this study. It in hyperemesis gravidarum. Int J Gynaecol Obstet 1996;55: would have been possible for us to answer the question 231–5. of whether abnormal Doppler findings appear later on 10. Hallak M, Tsalamandris K, Dombrowski MP, Isada NB, or not at all in HG cases if we knew the pregnancy out- Pryde PG, Evans MI. Hyperemesis gravidarum. Effects on comes. However, the limited number of cases and the fetal outcome. J Reprod Med 1996;41:871–4. fact that the pregnancy outcomes were not known are 11. Czeizel AE, Puhó E. Association between severe nausea and the limitations of our study. We therefore believe that vomiting in pregnancy and lower rate of preterm births. studies with large series evaluating first and second Paediatr Perinat Epidemiol 2004;18:253–9. trimester uterine artery Doppler in HG cases with the 12. Bailit JL. Hyperemesis gravidarum: epidemiologic findings from a large cohort. Am J Obstet Gynecol 2005;193:811–4. pregnancy outcomes may be useful. 13. Veenendaal MV, van Abeelen AF, Painter RC, van der Post JA, RoseboomTJ. Consequences of hyperemesis gravidarum for Conclusion offspring: a systematic review and meta-analysis. BJOG 2011; 118:1302–13. In conclusion, we found no significant difference 14. Bolin M, Åkerud H, Cnattingius S, Stephansson O, Wikström between HG, nausea and vomiting of pregnancy and AK. Hyperemesis gravidarum and risks of placental dysfunc- control groups in terms of uterine artery Doppler tion disorders: a population-based cohort study. BJOG 2013; parameters in this study. Prospective studies with a 120:541–7. large number of cases where the birth data were regis- 15. RoseboomTJ, Ravelli AC, van der Post JA, Painter RC. tered are required to support our findings. Maternal characteristics largely explain poor pregnancy out- come after hyperemesis gravidarum. Eur J Obstet Gynecol Conflicts of Interest: No conflicts declared. Reprod Biol 2011;156:56–9. 16. Vikanes ÅV, Støer NC, Magnus P, Grjibovski AM. Hyperemesis gravidarum and pregnancy outcomes in the Norwegian Mother References and Child Cohort – a cohort study. BMC Pregnancy Childbirth 1. American College of Obstetrics and Gynecology. ACOG 2013;13:169. Practice Bulletin #52: nausea and vomiting of pregnancy. 17. Olofsson P, Laurini RN, Marsál K. A high uterine artery pul- Obstet Gynecol 2004;103:803–14. satility index reflects a defective development of placental bed 2. Einarson TR, Piwko C, Koren G. Prevalence of nausea and spiral arteries in pregnancies complicated by hypertension and vomiting of pregnancy in the USA: a meta analysis. J Popul fetal growth retardation. Eur J Obstet Gynecol Reprod Biol Ther Clin Pharmacol 2013;20:e163–70. 1993;49:161–8.
70 Perinatal Journal Comparison of first trimester uterine artery Doppler parameters in hyperemesis gravidarum with normal pregnancy
18. Melchiorre K, Leslie K, Prefumo F, Bhide A, Thilaganathan 21. Spencer K, Cowans NJ, Avgidou K, Molina F, Nicolaides KH. B. First-trimester uterine artery Doppler indices in the pre- First-trimester biochemical markers of aneuploidy and the pre- diction of small-for-gestational age pregnancy and intrauter- diction of small-for-gestational age fetuses. Ultrasound Obstet ine growth restriction. Ultrasound Obstet Gynecol 2009;33: Gynecol 2008;31:15–9. 524–9. 22. Spencer K, Cowans NJ, Molina F, Kagan KO, Nicolaides 19. Papageorghiou AT, Yu CK, Nicolaides KH. The role of KH. First-trimester ultrasound and biochemical markers of uterine artery Doppler in predicting adverse pregnancy out- aneuploidy and the prediction of preterm or early preterm come. Best Pract Res Clin Obstet Gynaecol 2004;18:383– delivery. Ultrasound Obstet Gynecol 2008;31:147–52. 96. 23. Derbent AU, Yanik FF, Simavli S, Atasoy L, Urün E, Kuflçu 20. Spencer K, Cowans NJ, Nicolaides KH. Low levels of mater- UE, et al. First trimester maternal serum PAPP-A and free nal serum PAPP-A in the first trimester and the risk of pre- β-HCG levels in hyperemesis gravidarum. Prenat Diagn eclampsia. Prenat Diagn 2008;28:7–10. 2011;31:450–3.
Volume 24 | Issue 2 | August 2016 71 A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatal Journal 2016;24(2):72–76 I N N R A U T A L J O
An obstetric emergency case: vulvovaginal hematoma – our four-year results
Özlem Yörük, Ayflegül Öksüzo¤lu, Elif Gül Yapar Eyi, Burcu K›sa Karakaya, Necati Hançerlio¤lu Zekai Tahir Burak Maternal Health Training and Research Hospital, Ankara, Turkey
Abstract: Özet: Obstetrik bir acil durum: Vulvovajinal hematom – Dört y›ll›k sonuçlar›m›z Objective: Vulvovaginal hematomas after vaginal delivery are rare Amaç: Vajinal do¤um sonras› vulvovajinal hematomlar az rastla- but among the life-threatening complications. Though hematomas nan ancak yaflam› tehdit edebilen komplikasyonlardand›r. Hema- are related with episiotomy or operative delivery, those may occur tomlar s›kl›kla epizyotomi ya da operatif do¤um ile iliflkilendirilir- in the absence of incision or laceration due to pseudoaneurysm or se de insizyon ya da laserasyon olmaks›z›n da psödoanevrizma, traumatic arteriovenous fistula. travmatik arteriovenöz fistüle ba¤l› olarak da görülebilir. Methods: Demographic and obstetric data, symptom and exami- Yöntem: Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Araflt›rma nation findings, hematologic and biochemical parameters and Hastanesi’nde 2010–2013 y›llar› aras›nda vulvovajinal hematom ne- findings of 52 vaginal deliveries without vaginal hematoma were deni ile müdahale edilen 52 olgunun demografik, obstetrik verileri, compared in 52 cases who were intervened due to vulvovaginal semptom ve muayene bulgular›, hematolojik ve biokimyasal para- hematoma between 2010 and 2013 at Zekai Tahir Burak Maternal metreleri, vajinal hematom geliflmemifl 52 vajinal do¤uma ait bulgu- Health Training and Research Hospital. Cost analyses were calcu- lar ile karfl›laflt›r›ld›. Do¤um salonu çal›flma dönemleri, personel ile lated by reviewing delivery room work periods, compliance with uyum ve vardiyalar ile iliflkileri gözden geçirilerek maliyet analizleri personnel and relationship with shifts. ç›kar›ld›. Results: In a total of 31,163 vaginal deliveries, incidence of vulvo- Bulgular: Toplam 31.163 vajinal do¤umda, hepsi infralevator vaginal hematoma was found to be 0.16% with 52 cases that were all olan 52 olgu ile, vulvovajinal hematom insidans› %0.16 olarak bu- infralevator. Moreover, all patients with vulvovaginal hematoma lundu. Vulvovajinal hematomlu bütün hastalar›n farmakolojik in- had pharmacological induction, 37 of the women were delivered düksiyon ald›¤›, 37’sinin do¤umunun epizyotomi ile gerçekleflti¤i, with episiotomy and 13 women (23%) had compliance problem hastalar›n %23’ünde eylem ve do¤um s›ras›nda personel ile uyum with personnel during labor and delivery. The initial symptoms of sorununun dosya kay›tlar›nda yer ald›¤› belirlendi. Hematom ge- the developing hematoma were pain in vulva and perineal region. liflen hastalar›n ilk bulgular›n›n vulvada ve perinede a¤r› oldu¤u ve Hematoma was detected in 31 patients (59.6%) within the first 6 31 hastada (%59.6) do¤umdan sonra ilk 6 saat içinde hematomun hours after delivery. Transfusion was needed in 37 patients (71.2%) tespit edildi¤i görüldü. 37 hastada (%71.2) transfüzyon gerekti¤i and 35 of them (96.2%) were applied two and more erythrocyte sus- ve bu hastalar›n 35’ine (%96.2) iki ve üzeri eritrosit süspansiyon pension transfusion. It was understood from the medical records transfüzyonu uyguland›¤› görüldü. Dosya bilgilerinin de¤erlendir- that it was tried to determine bleeding focus by opening hematoma mesinden, olgular›n hepsinde genel anestezi alt›nda, hematom ala- area in all cases during general anesthesia, and laparotomy was per- n›n›n aç›larak kanama oda¤›n›n belirlenmeye çal›fl›ld›¤›, bir hasta- formed afterwards in one patient. Hospital cost and duration of hos- da laparotomiye geçildi¤i anlafl›ld›. Maliyet ve hastanede kal›fl sü- pitalization were found to be increased significantly. resinin anlaml› olarak artt›¤› belirlendi. Conclusion: Early diagnosis of vulvovaginal hematoma is estab- Sonuç: Vulvovajinal hematomun erken tan›s›, do¤umda dikkatli lished by meticulous check of birth canal during delivery and by a do¤um kanal› kontrolü yan›nda do¤um sonras› vulvar ve perineal meticulous examination again immediately in vulvar and perineal a¤r› yak›nmalar›nda hemen ve tekrar dikkatli muayene ile konur. pain complains after delivery. Labor induction should be practiced in Do¤um eylemi indüksiyonu, mutlak endikasyonlarda uygulanma- absolute indications. l›d›r. Keywords: Obstetric emergency, vulvovaginal hematoma. Anahtar sözcükler: Obstetrik acil, vulvovajinal hematom.
Correspondence: Özlem Yörük, MD. Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Available online at: Araflt›rma Hastanesi, Ankara, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242003 doi:10.2399/prn.16.0242003 Received: March 17, 2016; Accepted: May 30, 2016 QR (Quick Response) Code: Please cite this article as: Yörük Ö, Öksüzo¤lu A, Yapar Eyi EG, K›sa Karakaya B, Hançerlio¤lu N. An obstetric emergency case: vulvovaginal hematoma – our four-year results. Perinatal Journal 2016;24(2):72–76. ©2016 Perinatal Medicine Foundation An obstetric emergency case: vulvovaginal hematoma – our four-year results
Introduction The difference between the hemoglobin value meas- ured during the first admission of patients with Puerperal vulvovaginal hematomas are obstetric emer- hematoma and the hemoglobin value found when gencies that may threaten life with an incidence between [1,2] hematoma was detected was recorded. Cost per patient 1/300 and 1/1500. There is an increased vascularity in was calculated with the developing complications, the the uterus, vagina and vulva of pregnant woman. amount of blood transfusion performed and total hos- Therefore, traumas that will occur during delivery may pitalization period. easily lead to hematoma development. The risk factors for the development of postpartum vulvovaginal The statistical evaluation of the data obtained was hematomas are nulliparity, episiotomy practices, vacu- done with SPSS for Windows 11.5 (SPSS Inc., um forceps practices, breech deliveries, births above Chicago, IL, USA). T test was used for the compar- 4000 g, preeclampsia, prolonged second stage of labor, isons of independent samples in two-category cases distinctive vulvar varicose veins, and coagulopathies.[3–5] with normal distribution for variables determined by Postpartum vulvovaginal hematomas may be seen due to measurement and one-way variance analysis and pseudoaneurysm and traumatic arteriovenous fistule Bonferroni test in cases with more than two categories, without any incision or laceration.[6] It is also referred in Mann-Whitney U test was used in two-category cases the literature as a cause of severe morbidity/mortality for variables without normal distribution and Kruskall- [7] Wallis one-way variance analysis for cases with more associated with maternal deaths and near misses. than two categories, chi-square test was used for the comparison of qualitative variables, and Pearson and Methods Spearman rank correlation analyses were used to deter- A retrospective, cross-section case-controlled study mine correlation between the variables determined by was planned between 2010 and 2013 and by reviewing measurement. As the descriptive value, frequency and the records of 52 postpartum vulvovaginal hematoma percentage were used for categorical data, arithmetical cases, 52 vaginal delivery cases chosen randomly from mean±standard deviation for the variables determined the computer system within the same period were by measurement, and median (minimum–maximum) compared. The study approval was obtained from value was used for those without normal distribution. Ethics Committee 7 of Zekai Tahir Burak Maternal Statistical significance level was considered as 0.05. Health Training and Research Hospital for this study. Demographic data of patients were evaluated. The Results duration of first stage of labor was considered from a Incidence of vulvovaginal hematoma was found to be cervical dilatation of 4 cm and/or an effacement of 70 0.16% in a total of 31,163 vaginal deliveries with 52 percent to complete cervical dilatation; while the dura- cases between 2010 and 2013. Table 1 provides age, tion from complete cervical dilatation to the expulsion gravidity, parity, length of stage I stage II of the labor, of the fetus was considered as stage II. The presence of presence of episiotomy, neonatal birthweight and dura- episiotomy, forceps and vacuum practices, compliance tion of hospitalization in both groups. There was neither problem of pregnant woman with personnel during vacuum nor forceps delivery. Notes showing that these delivery were extracted from data. Each patient having patients had compliance problem with personnel during cooperation and compliance problem during delivery labor was detected in the files of 12 patients (23%) who at our hospital is visited by a psychologist and it is developed hematoma. noted to patient file. Newborn weight was recorded. Since delivery service at our hospital is offered for 24 When both groups were evaluated in terms of the hours, 365 days uninterruptedly as eight-hour shifts, delivery day and shift periods, it was seen that 38 the hours for deliveries were evaluated in three groups patients (73.1%) in the group developed hematoma which were 08:00–16:00, 16:00–00:00 and and 41 patients (78.8%) in the control group had their 00:00–08:00. Also it was recorded if deliveries were deliveries during weekdays and there was no statistical carried out during weekdays or weekends. The first significance (p=0.6) between the groups. finding of hematoma, the duration from the delivery When shift periods were compared, it was seen that up to the first detection and mean size were recorded. 21 (40.4%) patients in the group with hematoma deliv-
Volume 24 | Issue 2 | August 2016 73 Yörük Ö et al.
ered during the shift period 08:00–16:00, 12 (23.1%) 24 hours, tampon into the vagina and Foley catheter .[9] patients delivered during the shift period 16:00–00:00, In our study, drainage was applied to 52 hematoma and 19 (36.5%) patients delivered during the shift peri- cases during general anesthesia to find bleeding focus. od 00:00–08:00. In the control group, it was seen that 17 Drain was not placed in any patient. (32.7%) patients delivered during the shift period It was seen that 48 (92%) patients in the group 08:00–16:00, 14 (26.9%) patients delivered during the developing hematoma were evaluated due to pain and shift period 16:00–00:00, and 21 (40.4%) patients deliv- bleeding in vulva and perineum, hematoma was found in ered during the shift period 00:00–08:00 When the shift 31 (59.6%) patients within first 6 hours after delivery and periods in which deliveries were carried out were com- that mean hematoma size was about 65mm (between 40 pared, it was found that there was no statistical differ- and 150 mm). It was understood that hemoglobin ence between the two groups (p=0.7). decrease was 2.8±1.5g/dl during diagnosis, transfusion While the most significant finding in the clinical was needed in 37 (71.2%) patients and erythrocyte sus- diagnosis of hematomas varies depending on the local- pension transfusion was applied to 35 (96.2%) of these ization, mass, perianal pain and the rectal pressure are patients for two and more times, and coagulopathy was the main signs and symptoms that can be detected detected in two patients right after the delivery. In all of within the first 24 hours.[2] In our study, we found that the cases, hematoma area was opened during general hematomas were detected mostly due to pain in the anesthesia to find bleeding focus and hemostasis was vulvar and perianal area within 6 hours. established. It was found that laparotomy was performed in a patient by considering the pre-diagnosis of suprale- If hematomas are large, hemodynamics can be vator hematoma. spoiled as much as requiring blood product transfu- sion. In our study, we understood that mean hemoglo- It was seen that infection developed during puerper- bin decrease was 2.8 g/dl and transfusion was required al period in 6 (11.5%) patients and 39 (75%) patients in 37 (71.2%) patients. took antibiotics. It was found that cost per patient in those with hematoma was 1,167 TL according to the In the treatment of vulvovaginal hematomas, con- prices provided in the Communique of Social Security ventional approach is recommended with ice bags, Institution. methods that will provide pressure and analgesia for hematomas smaller than 5cm and not growing;[8] how- ever, surgical procedure should be considered for Discussion hematomas expanding or larger than 5 cm. If possible, Puerperal vulvovaginal hematomas are serious obstetric incision should be made within the vagina, and bleed- complications that may be life threatening. External gen- ing focuses should be repaired with eight-shaped ital region is fed by a vascular structure rich with inter- absorbable sutures. It may be required to place drain nal and external pudental arteries. Damages occurring in into hematoma space which will stay there at least for this vascular network may easily lead to hematoma for-
Table 1. Demographic and clinical data of the patients.
Hemotoma exists No hematoma p n=52 n=52
Age* 25.48±5.04 24.36±4.65 0.4 Gravida† 1 (1–4) 1 (1–5) 0.2 Parity† 0 (0–2) 0 (0–4) 0.3 Stage I (min.)* 427.50±196.47 283.88±189.87 0.001 Stage II (min.)* 22.23±2.58 19.46±1.88 0.4 Presence of episiotomy n (%) 37 (71.15%) 40 (76.92%) 0.2 Birth weight (g)* 3396.78±392.14 3281.15±376.15 0.9 Hospitalization period (day)† 3 (1–17) 1 (1–3) 0.000
*Mean±standard deviation, †Median (minimum–maximum)
74 Perinatal Journal An obstetric emergency case: vulvovaginal hematoma – our four-year results
mation.[10] Rarely, hematomas developing without any If possible, incision should be made within the vagi- obstetric trauma were also reported.[11] Puerperal na, and bleeding focuses should be repaired with eight hematomas can be seen in vulvar, vaginal, paravaginal shaped absorbable sutures. It may be required to insert and retroperitoneal localizations. Hemorrhagic shock a drain into hematoma space which will stay there at and infection may develop in cases where the diagnosis least for 24 hours. Insertion of a tamponade into the and appropriate treatment for puerperal vulvovaginal vagina and urinary dwelling Foley catheter may also be [10] hematomas are delayed and may even lead to maternal necessary. While surgery is performed usually under death.[12] general anesthesia in hematomas, regional or local anesthesia may also be applied. In our study, drainage When the risk factors were analyzed in terms of was applied to 52 hematoma cases under general anes- hematoma development, no significant difference was thesia in an attempt to find the bleeding vessel. It was found between two groups in terms of gravida, parity, not needed to place drain in any patient. Laparotomy stage II of labor, newborn birth weight and presence of may be required there is a suspicion of retroperitoneal episiotomy. However, we found by comparing two expansion of vulvovaginal hematomas. In our study, groups that stage I of labor was significantly longer in only one patient had laparotomy due to the suspicion the group developing hematoma (p=0.001). of retroperitoneal expansion. We could not find a significant difference between Infection developed during puerperal period in 6 two groups when we analyzed the day and shift periods (11.5%) patients and 39 (75%) of the patients were when hematoma developed. This result indicates that administewreed antibiotics. Cost per patient was found personal factors are more effective in the development as 1,167 TL in patients with vulvovaginal hematoma. of vulvovaginal hematoma than the attention and prac- This cost equivalents to two times of the cost of a tices of healthcare professionals. delivery without any complication. While the most significant finding in the clinical diagnosis of hematomas varies depending on the local- Conclusion ization, there are mass, pain and the feeling of rectal pressure, and it can be detected within the first 24 As postpartum vulvovaginal hematomas may result with hours.[2] In our study, we found that hematomas were serious morbidity and also mortality even rarely, hemo- detected mostly within 6 hours due to pain. dynamic findings and pain complaints in perineal and vulvar region of all cases should be carefully monitored If hematomas are large, baceuse of the detoriation for 24 hours; when hematoma is detected, applying early of hemodynamics, blood and blood product transfu- active surgical drainage by considering the hemodynam- sion may be required. In our study, we found that mean ics will decrease morbidity and hospital costs. hemoglobin decrease was 2.8 g/dl and transfusion was required in 37 (71.2%) patients. Conflicts of Interest: No conflicts declared. Patients requiring five or more units of blood or ery- throcyte transfusion are defined as near-miss cases.[7] As References 13 (25%) patients had more than 5 units of blood prod- 1. Zahn CM, Yeomans ER. Postpartum hemorrhage: placenta uct transfusion in our study, it should not be ignored accreta, uterine inversion, and puerperal hematomas. Clin that there are patients with high morbidity of vulvovagi- Obstet Gynecol 1990;33:422–31. nal hematomas. 2. Villella J, Garry D, Levine G, Glanz S, Figueroa R, Maulik D. Postpartum angiographic embolization for vulvovaginal In the treatment of vulvovaginal hematomas, conven- hematoma: a report of two cases. J Reprod Med 2001;46:65– tional approach is recommended with ice bags, tampon- 7. ade methods (such as Bakri balloon, Sengstaken- 3. Saleem Z, Rydhström H. Vaginal hematoma during parturi- Blakemore tube) that will provide pressure and analgesia tion:a population-based study. Acta Obstet Gynecol Scand for hematomas smaller than 5 cm and not growing in 2004;83:560–2. patients with stable hemodynamics;[8,13,14] but surgical pro- 4. Gilstrap LC, Cunningham FG, Van Dorsten JP. Operative obstetrics. 2nd ed. New York, NY: Mc Graw-Hill Co.; 2002. cedure should be considered for hematomas expanding Chapter 12, Genital tract lacerations and pueperal or larger than 5 cm. hematomas. p. 223–39.
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5. Joy SD, Huddleston JF, McCarthy R. Explosion of a vulvar 10. Anderson JR, Genadry R. Anatomy and embryology. hematoma during spontaneous vaginal delivery. A case In: Berek JS, editor. Novak’s gynecology. 13th ed. report. J Reprod Med 2001;46:856–8. Philadelphia, PA: Lippincott Williams &Wilkins; 2002. p. 6. Nagayama C, Gibo M, Nitta H, Uezato T, Hirakawa M, 69–121. Masamoto H, et al. Rupture of pseudoaneurysm after vagi- 11. Nelson EL, Parker AN, Dudley DJ. Spontaneous vulvar nal delivery successfully treated by selective arterial hematoma during pregnancy: a case report. J Reprod Med embolization. Arch Gynecol Obstet 2011;283:37–40. 2012;57:74–6 . 7. Pattinson R, Say L, Souza JP, Broek Nv, Rooney C; WHO 12. Lee NK, Kim S, Lee JW, Sol YL, Kim CW, Hyun Sung K, et Working Group on Maternal Mortality and Morbidity al. Postpartum hemorrhage: clinical and radiologic aspects. Eur Classifications. WHO maternal death and near-miss classifi- J Radiol 2010;74:50–9. cations. Bull World Health Organ 2009;87:734. 13. Tattersall M, Braithwaite W. Balloon tamponade for vaginal 8. You WB, Zahn CM. Postpartum hemorrhage: abnormally lacerations causing severe postpartum haemorrhage. BJOG adherent placenta, uterine inversion, and puerperal hematomas. 2007;114:647–8. Clin Obstet Gynecol 2006;49:184–97. 14. Saccardi C, Patrelli TS, Di Gangi S, D'Antona D, Battista 9. Zahn CM, Hankins GD, Yeomans ER. Vulvovaginal Nardelli G. Bakri balloon in vaginal-perineal hematomas com- hematomas complicating delivery. Rationale for drainage of plicating vaginal delivery: a new therapeutic approach. J Low the hematoma cavity. J Reprod Med 1996;41:569–74. Genit Trac Dis 2013;17:125–8.
76 Perinatal Journal A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatal Journal 2016;24(2):77–82 I N N R A U T A L J O
Evaluation of the measurement of ACTH, fibronectin, pentraxin 3 levels and cervical length in pregnant women under threatened preterm delivery
Filiz Aktenk1, Burcu Artunç Ülkümen2, Yeflim Güvenç3, Halil Gürsoy Pala2, Arzu Oran3 1Gynecology and Obstetrics Clinic, Cizre State Hospital, Mardin, Turkey 2Department of Obstetrics and Gynecology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey 3Department of Biochemistry, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
Abstract Özet: Erken do¤um tehdidi olan gebelerde ACTH, fibronektin, pentraksin 3 düzeyleri ve servikal uzunluk ölçümlerinin de¤erlendirilmesi Objective: We aimed to compare ACTH, fibronectin and pentrax- Amaç: Erken do¤um tehdidi olan gebelerde ACTH, fibronektin, in 3 levels and cervical lengths in pregnant women under the risk of pentraksin 3 düzeyleri ve servikal uzunlu¤u, komplike olmayan nor- threatened preterm delivery with the levels in non-complicated nor- mal gebelerdeki düzeyleri ile karfl›laflt›rarak bu belirteçlerin erken mal pregnant women, to determine the significance of these mark- do¤um tehdidi üzerindeki önemini belirlemek ve risk faktörü olarak ers on the threatened preterm delivery and to establish new markers kullan›labilecek yeni belirteçler oluflturabilmek amaçlanm›flt›r. which can be used as risk factors. Yöntem: Çal›flmaya Celal Bayar Üniversitesi T›p Fakültesi Kad›n Methods: Thirty healthy pregnant women and 30 pregnant women Hastal›klar› ve Do¤um Anabilim Dal›’na baflvuran 18–40 yafl ara- established the diagnosis of the threatened preterm delivery who s›, 24–34 hafta aras›nda sa¤l›kl› 30 gebe ve erken do¤um tehdidi ta- were between 18 and 40 years old and at 24–34 weeks of gestation n›s› alm›fl 30 gebe dahil edildi. Gebelerin yafl, e¤itim düzeyi, and admitted to the Department of Obstetrics and Gynecology, boy/kilo ölçümleri, gebelik say›s›, paritesi, sigara kullanma al›flkan- Faculty of Medicine, Celal Bayar University were included in the l›¤›, sistemik hastal›k varl›¤›, önceki gebelik öyküleri sorguland›. study. Age, educational level, height/weight measurements, number Çal›flmaya kat›lan tüm gebelerde transvajinal sonografi ile servikal of pregnancy, parity, smoking habit, presence of systemic disease uzunluk ölçümü yap›ld›. Venöz kan örnekleri al›nd›ktan sonra and previous pregnancy histories were reviewed. Cervical length of ACTH, fibronektin ve pentraksin 3 düzeyleri çal›fl›ld›. Sonuçlar all pregnant women participated in the study were measured by her iki grupta SPSS-20 program›nda istatistiksel olarak karfl›laflt›- transvaginal sonography. After venous blood samples were collected, r›ld›. ACTH, fibronectin and pentraxin 3 levels were studied. The results Bulgular: Çal›flmam›zda preterm eylem s›kl›¤› %27.1 olarak sap- were compared statistically in both groups via SPSS-20. tand›. Preterm eylem gerçekleflen gebelerin çal›flma grubuna oran- Results: In our study, the preterm delivery incidence was 27.1%. The lar›n›n ise %53.3 oldu¤u görüldü. Çal›flmaya al›nan gebelerde ça- rate of pregnant women, who had preterm delivery, to the study group l›flma ve kontrol gruplar› verileri karfl›laflt›r›ld›¤›nda sosyodemog- was 53.3%. When the data of study and control groups were com- rafik özellikler yönü ile anlaml› farkl›l›k izlenmedi (p>0.05). Çal›fl- pared, no significant difference was found in terms of sociodemograph- ma grubunda yer alan gebelerde ortalama serviks uzunlu¤u 17.56 ic characteristics (p>0.05). While mean cervical length in the study mm iken kontrol grubunda ortalama de¤er 44.74 mm saptand› ve group was 17.56 mm, it was found as 44.74 mm in the control group, aradaki fark istatistiksel olarak anlaml› bulundu (p<0.001). Çal›flma and the difference was considered as statistically significant (p<0.001). ve kontrol grubu verilerinde karfl›laflt›r›lan ACTH ve fibronektin ACTH and fibronectin levels were compared in the data of study and düzeyleri aras›nda istatistiksel olarak anlaml› farkl›l›k izlenmedi control groups and the difference was not found to be statistically sig- (p>0.05). Pentraksin 3 düzeyleri karfl›laflt›r›ld›¤›nda çal›flma gru- nificant (p>0.05). While mean pentraxin 3 level in the study group was bunda ortalama de¤er 35.83 pg/mL iken, kontrol grubunda 20.26 35.83 pg/mL, it was found as 20.26 pg/mL in the control group, and pg/mL saptand› ve aradaki fark istatistiksel olarak anlaml› bulundu the difference was considered as statistically significant (p<0.001). (p<0.001). Conclusion: We believe that pentraxin 3 as a new acute phase reac- Sonuç: Yeni bir akut faz reaktan› olan pentraksin 3’ün erken do¤um tant can be used as a marker to establish the diagnosis of threatened tehdidi tan›s› koymada veya tan›y› desteklemede kullan›labilecek bir preterm delivery or to support the diagnosis. belirteç olabilece¤i düflüncesindeyiz. Keywords: ACTH, cervical length measurement, fibronectin, pen- Anahtar sözcükler: Erken do¤um tehdidi, servikal uzunluk ölçü- traxin 3, threatened preterm delivery. mü, ACTH, fibronektin, pentraksin 3.
Correspondence: Burcu Artunç Ülkümen, MD. Celal Bayar Üniversitesi T›p Fakültesi Kad›n Available online at: Hastal›klar› ve Do¤um Anabilim Dal›, Manisa, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242004 doi:10.2399/prn.16.0242004 Received: March 18, 2016; Accepted: June 6, 2016 QR (Quick Response) Code: Please cite this article as: Aktenk F, Artunç Ülkümen B, Güvenç Y, Gürsoy Pala H, Oran A. Evaluation of the measurement of ACTH, fibronectin, pentraxin 3 levels and cervical length in pregnant women under threatened preterm delivery. Perinatal Journal 2016;24(2):77–82. ©2016 Perinatal Medicine Foundation Aktenk F et al.
Introduction tion, it is released from liver, endothelium cells, athero- [6] Preterm delivery is the condition of frequent and active sclerotic lesions, macrophage and neutrophiles. uterine contraction causing cervical effacement and Detection of the increase in this inflammation marker may have a role to determine inflammation and preterm dilatation during 20–37 weeks of gestation. Threatened [7,8] preterm delivery is the condition of regular uterine con- delivery that may develop due to inflammation. traction beginning before 37 weeks of gestation and Fibronectin is a dimeric glycoprotein with the molec- causing no change in the cervix. Preterm delivery is a ular weight of 440,000 Dalton. It has a role in the adhe- serious obstetric problem today with the high perinatal sion of cell-cell and cell-substrate, adherence of fibrino- mortality and morbidity rates caused by preterm deliv- gen or collagen to macrophage and fibrin clot retraction ery it cause.[1] Despite the efforts to prevent preterm of fibroblasts, and it regulates cell movements. It also delivery, desired results cannot be always achieved due helps the continuation of microvascular integrity, con- to the difficulties to understand the underlying patho- trol of vascular permeability, hemostasis and wound physiology, insufficient diagnosis methods.[2] Therefore, healing.[9,10] Plasma fibronectin level during pregnancy the most effective solution to find is to identify risky increases for 20% at third trimester and stays at this level pregnant women under risk in the appropriate time and for postpartum 6 weeks. Renal and hypertensive diseases, to decrease risk factors for such pregnant women who diabetes mellitus, surgical operation during pregnancy are candidate for preterm delivery. and blood transfusion, coagulation disorders, premature Adrenocorticotrophic hormone (ACTH) is a hor- rupture of membrane and chorioamnionitis may cause [11,12] mone in polypeptide structure with straight chain con- changes in plasma fibronectin level. It is considered taining 39 aminoacid. Other substances secreted by that preterm delivery can be identified with the detection hypothalamus such as arginine vasoporessine (AVP) also of this factor, with increasing mechanical or inflammato- stimulate ACTH release more weakly and probably this ry post-trauma release. In a study carried out, it was effect also depends on the presence of corticotrophin found that incidence rate of preterm delivery is 70% in [12] releasing hormone (CRH). ACTH increase in the circu- case that fibronectin level increases. lation causes glucocorticoid secretion from adrenal cor- In this study, we aimed to compare ACTH, tex (cortisol in human). In response to the maternal or fibronectin and PTX3 levels and cervical lengths in fetal stress, the activation of hypothalamic-hypophyseal- pregnant women under the risk of threatened preterm adrenal axis is responsible for 30% of preterm delivery. delivery with the levels in non-complicated normal preg- Physical or psychological stress of mother and placenta nant women, to determine the significance of these dysfunctions increases uteroplacental CRH secretion. markers on the threatened preterm delivery and to CRH increases ACTH secretion from hypophysis. As a establish new markers which can be used as risk factors. result, cortisol secretion in fetal and maternal adrenals increases.[3] This causes prostaglandin production. With Methods direct uterotonic effect, prostaglandines activates myometrium by increasing oxytocin receptors in Our study was a randomized prospective study conduct- myometrium and the formation of gap junction.[4] It may ed on a total of 60 pregnant women, including 30 preg- lead to myometrial contractions and cervical changes. It nant women (study group) between 24 and 34 weeks of is also considered that myometrium activation, namely gestation who were established the diagnosis of threat- delivery, is activated with the increased release of CRH, ened preterm delivery at the Gynecology and Obstetrics as if a placental clock is programmed, and with the Department of Hafsa Sultan Hospital, Celal Bayar increased release of ACTH from fetal pituitary gland University and 30 pregnant women (control group) and therefore the production of placental estrogenic admitted for routine follow-up to the Pregnancy Clinic components.[5] of Gynecology and Obstetrics Department during the Preterm delivery is responsible for 40% of the rea- same weeks of gestation between December 2013 and sons of infection and inflammation although it has a January 2015. multifactorial etiology. Pentraxin 3 (PTX3) is a new Pelvic examination was applied first to the patients acute phase marker similar to C-reactive protein in who admitted to our hospital with the complaints such terms of structure and function. As a result of inflamma- as the feelings of contraction, stiffening and pelvic pres-
78 Perinatal Journal Evaluation of the measurement of ACTH, fibronectin, pentraxin 3 levels and cervical length in pregnant women
sure in the abdomen, increased vaginal discharge and Fibronectin levels were measured with ELISA method cramps similar to those during menstruation. With by using the commercial kit (Affymetrix, eBioscience, USG, fetal biometry and amniotic fluid amount were Vienna, Austria). The kit sensitivity was 0.1 ng/mL, intra- measured. The presence of active and regular uterine assay CV was 5.3% and inter-assay CV was 6.7%. contractions was sought with external tocodynamome- Pentraxin 3 levels were measured with ELISA ter. Gestational age identification was done by confirm- method by using the commercial kit (R&D Systems, ing with the first trimester ultrasonography according to Minneapolis, MN, USA). The kit sensitivity was 0.025 last menstrual period and with the ultrasonography in ng/mL, intra-assay CV was 3.93% and inter-assay CV those with unknown last menstrual period. was 5.06%. While the bladder was empty on lithotomy position For the study, the approval of Ethics Board of in 60 pregnant women included in the study, sagittal Hafsa Sultan Hospital, Celal Bayar University, the image of the cervix was obtained with 5 mHz and 120 pregnant women to be included in the study were degree convex-angle vaginal probe in a sterile way by informed about the study and consent forms were applying lubricant gel and placing condom to the signed by the patients. probe and by avoiding to make any pressure to the cervix. Cervical measurements were done in a cross- The data obtained from the study were entered into section, where also internal os, external os, cervical the database created in SPSS (Statistical Package for canal and endocervical mucosa could be displayed, by Social Sciences; SPSS Inc., Chicago, IL, USA) and the enlarging the image as covering 3/4 of the screen. Also, statistical analyses of the data were done in the same soft- in cases where the length between internal os and ware. Mean, standard deviation, median, minimum and external os was not on a single line, they were meas- maximum values of constant variables and their sub- ured as linear sections and total cervical length was groups, and frequency numbers and percentages of class obtained by summing up them. Any funneling in inter- variables were presented. “Independent samples t-test” nal os, which is 5 mm and above, was recorded. method was used in the comparison of independent vari- ables consistent with normal distribution while “Mann- When establishing preterm delivery diagnosis, the Whitney U” test was used for the comparison of inde- presence of regular and active (45–50 mmHg) uterus pendent group inconsistent with normal distribution. contractions which were 4 times per 20 min. or 6 times Class variables were presented as frequency and percent- per 60 min. as well as the presence of any of the cervical ages in cross tables and their distributions were com- changes during ≥2 cm cervical opening or observation pared with “chi-square” test methods. In all tests, 1st were considered as the criteria. The patients having type error margin alpha was considered as 0.05 and they effacement or opening without any uterine contradic- were tested in two way; the difference between the tion were considered to have cervical failure and exclud- groups was considered to be statistically significant when ed from the study. The pregnancies with ≥4 cm cervical p value was lower than 0.05. opening, ≥80% effacement, had previous premature rupture of membrane, severe preeclampsia-eclampsia, ablatio placentae, placenta previa, chorioamnionitis, Results IUGR, dead fetus, fetal anomaly incompatible with life, These four parameters were compared in the data of and multiple pregnancy were excluded from the study. the study group consisting of pregnant women diag- The heights and weights of pregnant women who nosed with the threatened preterm delivery and fol- were included in our study were measured in the lowed-up by hospitalizing and the control group con- beginning of their pregnancies and at the week they sisting of pregnant women admitted to our were included in the study. Gynecology and Obstetrics Clinic for routine check The venous bloods collected from the pregnant and gestational follow-up; the mean cervical length was women in the study and control groups between 08:00 measured as 17.56±7.90 mm in the study group and as and 10:00 a.m. following the nocturnal fasting were 44.74±3.23 mm in the control group, and the differ- centrifuged at 4000 rpm for 15 min. at +4°C. The ence was found statistically significant (p<0.001). serums were separated into Eppendorf tubes and were In terms of fibronectin levels, the mean value was kept at deep freeze at -80 °C until analysis time. 116.18±58.36 mg/L in the study group and 99.74±47.47
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mg/L in the control group, but the difference was not considered as statistically significant (p>0.05). Similarly, mean ACTH level was found to be 26.49±14.48 pg/mL in the study group and 28.41±15.26 pg/mL in the con- trol group, but the difference was not considered as sta- tistically significant (p>0.05). When mean PTX3 levels, as the new acute phase reactant, were compared in both groups, it was found as 35.83±2.17 pg/mL in the study group and as 20.26±1.72 in the control group, and the difference was considered as statistically significant (p<0.001) (Fig. 1). In our study, we found preterm delivery incidence as 27.1%. The rate of pregnant women, who had preterm delivery, to the study group was 50%. Pregnant women in the study group who were diag- Fig. 1. Pentraxin 3 (PTX3) levels in pregnant women with the threa- nosed with the threatened preterm delivery were sepa- tened preterm delivery (TPD). rated into two groups according to the incidence of preterm delivery. According to this, Group I included Although it is known that the activation of hypothal- pregnant women who were diagnosed with the threat- amic-hypophyseal-adrenal axis is responsible for 30% of ened preterm delivery and had the preterm delivery preterm delivery in response to the maternal or fetal afterwards and Group II included pregnant women who stress, ACTH levels of study and control groups were diagnosed with the threatened preterm delivery but delivered at term. Cervical length, fibronectin, checked between 08:00 and 10:00 a.m. showed no statis- ACTH and PTX3 measurements of Group I and Group tically significant difference (p>0.05). It was thought that II were compared and it was found that there was statis- this result was obtained due to time differences in col- tically significant difference in cervical length and PTX3 lecting serum samples, problems for maintaining cold levels compared to the control group (p>0.001) while chain that may occur during the transfer of samples to there was no statistically significant difference between the laboratory, seasonal changes, maternal response to Group I and Group II (p>0.05). psychological stress, and the difference in cortisol response of maternal and fetal adrenals. In order to obtain significant results, it is required to improve study Discussion conditions, and to carry out a study with more popula- With the improvement of newborn care opportunities tion by using serum samples taken simultaneously from and significant improvement in the prognosis of babies more pregnant women chosen from a group with partic- with low birth weight, nursling, neonatal and postnatal ular demographic and physical characteristics. mortality rates decreased about by half in the last two decades. However, the mortality rates did not decrease In terms of the distribution among etiological fac- in preterm (<37 weeks) deliveries and newborns with tors, it is seen that 80% of the preterm deliveries are low birth weight (LWB <2500 g).[13] caused by spontaneous preterm delivery and preterm premature rupture of membrane (PPROM), and 20% Preterm delivery and low birth weight are the most of them are caused by maternal and fetal problems.[15] significant factors affecting perinatal mortality and morbidity in the modern obstetrics, and their improve- The recent studies support the role of infection in ment will enhance the general health of the society. As the etiology of preterm delivery. The role of subclini- preterm delivery depends on many reasons, its actual cal infection in placental membranes, chorioamnionitis mechanism is still unknown despite many studies. occurring before and after chorioamniotic membranes Therefore, protection, early diagnosis and treatment of are opened and histological infection gain importance preterm delivery have been significant problems in in the etiology.[1,13,15] Microorganisms were isolated for perinatal medicine.[14] 2–4 times more in the placental membranes of preg-
80 Perinatal Journal Evaluation of the measurement of ACTH, fibronectin, pentraxin 3 levels and cervical length in pregnant women
nant women who had preterm delivery compared to reasons of this result were considered that many types the pregnant women who delivered at term.[13] of fibronectin in different forms suppress especially Identifying and treating maternal infection has an apoptosis in embryogenesis, it is known that it affects increasing importance in order to decrease preterm hemopoietic precursor cell maturation and differentia- deliveries and avoid neonatal outcomes of prematurity. tion, it controls signal transfer between the cells and it Infection markers such as C-reactive protein, alkaline has low sensitivity and specificity to inflammatory phosphatase, beta-2 microglobulin, alpha-2 macroglobu- process occurring in the threatened preterm delivery lin, serum leucocyte count and shift to left in the formu- depending on the fact its main production site is hepa- [19] la are used to investigate maternal infection and inflam- tocytes although it is produced in many cells. matory. In previous studies, oxidative stress markers were In our study for these findings, we compared investigated within amniotic fluid for the prediction of fibronectin and PTX3 levels as an acute phase reactant preterm delivery; however, no significant result was [20] in pregnant women with and without the threatened found. It was reported that maternal serum d-dimer preterm delivery and cervical length measurement, levels might be useful in the prediction of preterm [21] which is proven for its validity and significance in many delivery. PTX3 values which are inflammatory mark- studies, as another parameter in patients with the ers are normally quite low in the plasma. However, it threatened preterm delivery. increases very quickly in inflammatory diseases, degen- erative diseases and autoimmune disorders. This Despite the frequent use of cervical length measure- increase is directly proportional to the weight of ment in the diagnosis of threatened preterm delivery, no patient. In our study, we found increase in PTX3 lev- standardization, technique, indications and examination ranges have been determined for the measurements. els of pregnant women diagnosed with the threatened According to the recommendation of American College preterm delivery compared to the control group. of Radiology, cervix and lower uterine segment should While the mean value was 35.83 pg/mL in the study be displayed in each second trimester obstetric ultra- group, it was 20.26 pg/mL in the control group. Also sonography. Specifically, the presence of short cervix when PTX3 levels of the pregnant women in the study (<30 mm) or funneling should be investigated.[16] Iams et group who had preterm delivery were compared with al. investigated 2915 low-risk singleton pregnancies the pregnant women in the control group, the mean between 24 and 28 weeks to determine deliveries before PTX3 level in the pregnant women who had preterm 35 weeks of gestation and found the sensitivity as 23% delivery was found as 37.75 pg/mL and the difference and the specificity as 93% when the threshold value of among them were considered as statistically significant cervical length measurement was taken as 20 mm, the (p<0.001). Absence of premature rupture of membrane sensitivity as 54% and the specificity as 92% when the in the pregnant women included in the study group threshold value was taken as 25 mm and the sensitivity rules out the suspicion that the increase in PTX3 lev- as 25% and the specificity as 95% when the threshold els may occur as a result of inflammatory reaction was taken as 30 mm. In the same study, they reported developing due to a possible chorioamnionitis. that preterm delivery before 35 weeks of gestation increased 6 and 9 times, respectively, when the cervical Conclusion [17] length measurement was below 26 mm. It is known The high PTX3 levels were statistically significant in that cervical length measured between 18 and 22 weeks pregnant women who were diagnosed with the threat- of gestation in asymptomatic patients is important in the [18] ened preterm delivery and whose diagnoses were sup- prediction of preterm delivery. ported with the shortening cervical lengths. Accordingly, There was no statistically significant difference we believe that pentraxin 3 as a new acute phase reactant between the fibronectin levels of the pregnant women can be used as a marker to establish the diagnosis of diagnosed with the threatened preterm delivery (mean threatened preterm delivery or to support the diagnosis. value was 28.08 mg/L) and the fibronectin levels of the Therefore, further studies at larger scales are required. pregnant women without the threatened preterm delivery (mean value was 29.02 mg/L) (p>0.05). The Conflicts of Interest: No conflicts declared.
Volume 24 | Issue 2 | August 2016 81 Aktenk F et al.
References 12. O’Brien WF. Predicting preeklampsia. Obstet Gynecol 1990; 75:445–52. 1. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap III LC, Wenstrom KD. Williams obstetrics. 22nd 13. Creasy RK, Iams JD. Preterm labor and delivery. Creasy RK, ed. New York, NY: McGraw-Hill Co; 2005. Chapter 36, Resnik R. In: Maternal-fetal medicine. 4th ed. Philedelphia, Preterm birth. p. 855–80. PA: WB Saunders Company; 1999. p. 498– 531. 2. Mc Donald HM, O’loghlin JA, Jolley P, Vigneswaran R, 14. Miniño AM, Arias E, Kochanek KD, Murphy SL, Smith BL. McDonald PJ. Prenatal microbiological risk factors associat- Deaths: Final data for 2000. Natl Vital Stat Rep ed preterm birth. Br J Obstet Gynaecol 1992:99:190–6. 2001;50:1–119. 3. fiener T. Preterm eylem ve do¤um. In: Kiflniflçi H, Gökflin E, 15. Creasy RK, Merkatz IR. Preventation of preterm birth: clin- Durukan T, Üstay K, Ayhan A, Gürkan T, Öndero¤lu L, ical opinion. Obstet Gynecol 1990;76(1 Suppl):2S–4S. editors. Temel kad›n hastal›klar› ve do¤um bilgisi. Ankara: Günefl Kitabevi; 1996. p. 1465–80. 16. Mantovani A, Garlanda C, Bottazzi B, Peri G, Doni A, Martinez de la Torre Y, et al. The long pentraxin PTX3 in 4. Hein M, Petersen AC, Helmig RB, Uldbjerg N, Reinholdt J. vascular pathology. Vascul Pharmacol 2006;45:326–30. Immunoglobulin levels and phagocytes in the cervical mucus plug at term of pregnancy. Acta Obstet Gynecol Scand 17. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, 2005;84:734–42. Das A, et al. The length of the cervix and the risk of sponta- 5. Lockwood CJ, Senyei AE, Dische MR, Casal D, Shah KD, neous preterm delivery. The National Institute of Child Thung SN, et al. Fetal fibronectin in cervical and vaginal Health and Human Development Maternal-Fetal Medicine secretions as a predictor of preterm delivery. N Engl J Med Units Network. N Engl J Med 1996;334:5675–72. 1991;325:669–74. 18. Ar›soy R, Erdo¤du E, Tu¤rul S, Mirza T, F›nd›k F, Mihmanl› 6. Salio M, Chimenti S, De Angelis N, Molla F, Maina V, M, et al. Düflük riskli asemptomatik gebeliklerde erken do¤um Nebuloni M, et al. Cardioprotective function of the long tahmininde gebeli¤in 18-22. haftalar›nda servikal uzunluk pentraxin PTX3 in acute myocardial infarction. Circulation ölçümü. Perinatoloji Dergisi 2013;21(Suppl):25. 2008;117:1055–64. 19. Foix-L’Helias L, Ancel PY, Blondel B. Risk factors for pre- 7. Mantovani A, Garlanda C, Bottazzi B, Peri G, Doni A, maturity in France and comparsons between spontaneous Martinez de la Torre Y, et al. The long pentraxin PTX3 in vascular pathology. Vascul Pharmacol 2006;45:326–30. prematurity and induced labor: results from The National Perinatal Survey 1995. [Article in French] J Gynecol Obstet 8. Mantovani A, Garlanda C, Bottazzi B. Pentraxin 3, a non- Biol Reprod (Paris) 2000;29:55–65. redundant soluble pattern recognition receptor involved in innate immunity. Vaccine 2003;21 Suppl 2:S43–7. 20. Çelik E, Karaer A, Y›lmaz E, Türkçüo¤lu I, Çelik Ö, 9. Mosesson MW, Amrani DL. The structure and biological fiiflmflek Y, et al. Investigation of the relationship between activites of plasma fibronectin. Blood 1980;56:145–58. levels of oxidative stress markers in the second trimester amniotic fluid with preeclampsia and preterm delivery. 10. Mosher DF. Physiology of fibronectin. Annu Rev Med 1984;35:561–75. Perinatal Journal 2012;20:140–5. 11. Stubbs TM, Lazarchick J, Horger EO 3rd. Plazma fibronectin 21. Yaz›c›o¤lu F, Oran R, Özsoy B, Aygün M, Özyurt ON, levels in preeklampsia: a possible biochemical marker for vas- Demirbafl R, et al. The role of uterine artery doppler and culer endhotelial damage. Am J Obstet Gynecol 1984;150: maternal serum d-dimer levels in prediction of preterm 885–7. labor. Perinatal Journal 2007;15:99–107.
82 Perinatal Journal A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatal Journal 2016;24(2):83–88 I N N R A U T A L J O
Hepatitis B seropositivity of pregnant women and the review of Turkish literature
Rabia Zehra Bakar1, Banu Dane2 1Gynecology and Obstetrics Clinic, Istanbul Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey 2Department of Gynecology and Obstetrics, Faculty of Medicine, Bezmialem Foundation University, Istanbul, Turkey
Abstract Özet: Gebelerde hepatit B seropozitifli¤i ve Türk literatürüne bir bak›fl Objective: The aim of the study was to show the progress of hep- Amaç: Türkiye’de yaflayan gebelerde son 20 y›l içindeki hepatit B atitis B seropositivity rates of pregnant women in Turkey for the seropozitiflik oranlar›n›n bölgeler ve y›llara göre seyrinin gösteril- last two decades by regions and years and to evaluate the current mesi, yap›lan çal›flmalar ›fl›¤›nda güncel durumun de¤erlendirilme- condition in consideration of the studies published. si amaçlanm›flt›r. Methods: The studies investigating hepatitis B seropositivity of Yöntem: Türkiye’de yaflayan gebelerde hepatit B seropozitifli¤i- pregnant women in Turkey were analyzed by reviewing the data- nin araflt›r›ld›¤› çal›flmalar veri tabanlar› ve literatür taramalar› ya- bases and the literature. On this topic, 64 studies performed p›larak incelendi. Bu konuda 1975–2016 y›llar› aras›nda yap›lm›fl between 1975 and 2016 were found. The studies published within 64 çal›flma tespit edildi. Son 20 y›l içindeki (1996–2016) çal›flmalar the last 2 decades (1996–2016) were arranged by their publication yay›nland›¤› y›la göre düzenlendi. Ek olarak klini¤imizde 2012– years. Additionally, the data of the women delivered in our clinic 2015 y›llar› aras›nda do¤um yapan kad›nlar›n verileri retrospektif between 2012 and 2015 were reviewed retrospectively and the olarak incelenerek ulafl›lan HBsAg seropozitiflik oran› sonucu be- result of HBsAg seropositivity rate was determined. lirtildi. Results: It was seen that the rate of HBsAg seropositivity in the stud- Bulgular: Türkiye’de HBsAg seropozitiflik oran›n›n yay›nlanan ies published in Turkey was between 1.2 and 19.2%. Considering the çal›flmalarda %1.2–19.2 aras›nda oldu¤u görüldü. Son 20 y›lda ya- studies performed within the last two decades, the highest rate was p›lan çal›flmalar incelendi¤inde en yüksek oran›n %9.3 oldu¤u, 9.3%, and no HBsAg seropositivity higher than 6% was found in the yurt genelinde uygulanan afl›lama program›n›n da etkisiyle son 7 studies performed in the last 7 years with the contribution of vaccine y›lda yap›lan çal›flmalarda %6’n›n üzerinde bir HBsAg seropozitif- program carried out throughout the country. In the study we performed li¤ine rastlanmad›¤› görüldü. Klini¤imizde yapt›¤›m›z çal›flmada in our clinic, we found the rate 2.16% in 4037 pregnant women. ise bu oran 4037 gebede %2.16 olarak bulundu. Conclusion: In Turkey, it is fought against the perinatal conta- Sonuç: Türkiye’de antenatal HBsAg taramas›, yenido¤anlara rutin gion of hepatitis B virus by antenatal HBsAg screening, routine hepatit B virüsü afl›s› ve HBsAg pozitif annelerden do¤an bebekle- hepatitis B virus vaccine of newborns and passive and active immu- re uygulanan pasif ve aktif immunizasyon uygulamalar›yla hepatit nization practices applied on newborns of the mothers who are B virüsünün perinatal bulafl› ile mücadele edilmektedir. Bunlara ek positive for HBsAg. In addition, high risk groups are vaccinated olarak yüksek riskli gruplara da hepatit B afl›s› yap›lmakta ve tüm against hepatitis B and with all these methods, it is expected to bu yöntemlerle gelecek y›llarda hepatit B oranlar›n›n ülkemizde decrease the rate of hepatitis B in future years in Turkey. daha da düflmesi beklenmektedir. Keywords: Hepatitis B, pregnancy, seropositivity, Turkey. Anahtar sözcükler: Hepatit B, seropozitivite, gebelik, Türkiye.
Introduction 240 millions of individuals have been exposed to the The infection of hepatitis B virus is still considered as chronic hepatitis B infection worldwide. The incidence one of the leading public health problems in the world. of hepatitis B varies according to the geographical According to the recent data of WHO, there are about regions and they are classified as high, medium and low
Correspondence: Rabia Zehra Bakar, MD. Istanbul Kanuni Sultan Süleyman E¤itim Available online at: ve Araflt›rma Hastanesi Kad›n Hastal›klar› ve Do¤um Klini¤i, Istanbul, Turkey. www.perinataljournal.com/20160242005 e-mail: [email protected] doi:10.2399/prn.16.0242005 QR (Quick Response) Code: Received: February 13, 2016; Accepted: June 6, 2016 Please cite this article as: Bakar RZ, Dane B. Hepatitis B seropositivity of pregnant women and the review of Turkish literature. Perinatal Journal 2016;24(2):83–88. ©2016 Perinatal Medicine Foundation Bakar RZ, Dane B
endemic regions. According to this classification, found by analyzing the studies found in the databases. Turkey is among the medium endemic regions. Except the theses published in Turkey, the theses found Hepatitis B virus seropositivity is evaluated with hep- during the database investigation were reviewed in atitis B surface antigen (HBsAg) and HBsAg seropositiv- terms of the literature. On this topic, 64 studies per- ity rate is 5% in women in the world which varies formed between 1975 and 2016 were found. The stud- between 0.6 and 20% according to the endemic regions.[1] ies performed within the last 2 decades (1996–2016) were arranged by their publication years (Table 1). Hepatitis B virus (HBV) is transmitted by body flu- ids such as infectious blood, saliva and vaginal fluid/semen or percutaneous or mucosal contact. On the Table 1. The studies carried out on HBsAg seropositivity of pregnant other hand, perinatal contagion is blamed particularly in women in Turkey within the last 20 years. the high endemic regions. Infection contagion from First author Year Region Number HBsAg HBsAg positive mother to baby can occur during positivity (%) intrauterine, intrapartum or postpartum period. While contagion during intrauterine period is rare, it is more Çepni[9] 1996 Istanbul 4078 4.4 Kuru[10] 1996 Istanbul 5366 4.2 frequent during intrapartum or postpartum period when Kadanal›[11] 1997 Erzurum 282 6.3 baby may contact with infected maternal fluids. Kaleli[12] 1997 Denizli 312 7.7 It was found that hepatitis B e antigen (HBeAg) and Ak›n[13] 1997 Bursa 310 5.5 [14] serum HBV DNA levels of mother are effective in the Gül 1998 Van 98 4.08 Biri[15] 2001 Ankara 451 7 contagion of the infection from HBV carrier mother to Aslan[16] 2001 fianl›urfa 450 4.6 [2] the baby during perinatal period. It was reported in a Yücel[17] 2001 Ankara 644 3.2 study that the risk of contagion from mothers negative Sa¤söz[18] 2002 K›r›kkale 157 4.9 for HBeAg was 10–40% and that the risk increases to Karaca[19] 2003 Istanbul 460 4.7 [20] 70–90% in positive women.[3] When it is transmitted Yegane Tosun 2003 Izmir 760 4.2 Harma[21] 2003 fianl›urfa 136 7.3 from mothers positive for HBeAg, it is considered that Y›lmazer[22] 2004 Afyon 244 2.9 the rate of the disease being chronic in the infected baby Tekay[23] 2006 fianl›urfa 2335 5.1 also increases.[4] Thanks to the active and passive immu- Madenda¤[24] 2007 Ankara 90351 2.1 nization applied together with the birth, the risk of con- Çakmak[25] 2008 Ni¤de 4831 1.2 [26] tagion to babies born from mothers positive for S›rmatel 2008 Gaziantep 397 9.3 Uyar[27] 2009 Samsun 2654 2.1 HBsAg/HBeAg is decreased. In Turkey, all newborns At›lgan[28] 2009 Rize 1130 2.56 have been vaccinated routinely for hepatitis B since Dündar[29] 2009 Istanbul 3503 2.2 1998. Kölgelier[30] 2009 Ad›yaman 660 4.7 Api[31] 2009 Istanbul 228 3.9 As the perinatal contagion of hepatitis B is still Alt›nbafl[32] 2010 Ankara 4700 2.8 important today, we aimed in this study to explain the Köksald› Motor[33] 2010 Hatay 5410 1.5 seropositivity of hepatitis B virus of pregnant women in Akdemir[34] 2010 Ankara 1422 1.2 the light of the studies carried out in Turkey and to Karl›da¤[35] 2011 Elaz›¤ 5120 1.9 [36] show the progress of HBsAg seropositivity rate by Coflkun 2011 Istanbul 795 3.7 Araz[37] 2011 Gaziantep 11840 2.1 regions and years. Gönen[38] 2011 Düzce 1028 3.3 Varol[39] 2011 Edirne 1526 3 Deveci[40] 2011 Mardin 1570 2.9 Methods Çopur Çiçek[41] 2012 fianl›urfa 56275 3.5 The studies on HBV seropositivity in pregnant women Kölgelier[3] 2012 Ad›yaman 9420 4.7 were screened in the databases of ULAKBIM Medical Çakmak[42] 2012 Kocaeli 3756 2.2 [43] Database (Turkish Medical Index), TürkMedline and Y›ld›z 2012 Diyarbak›r 2900 2.66 Özlü[44] 2013 Bolu 653 1.8 Turkish Citation Index. The studies were researched by Bal›k[45] 2013 Rize 5894 5.7 using the keywords “hepatit B” (hepatitis B), “HBsAg”, Koruk[46] 2013 fianl›urfa 261 3.2 “gebe enfeksiyon” (infection in pregnant women), “gebe Do¤an[47] 2014 Istanbul 2011 1.2 hepatit B” (hepatitis B in pregnant women), and “gebe Özcan Da¤[48] 2015 K›r›kkale 8442 3.47 Ayn›o¤lu[49] 2015 Zonguldak 1084 4 HBsAg” (HBsAg in pregnant women). Other studies were
84 Perinatal Journal Hepatitis B seropositivity of pregnant women and the review of Turkish literature
Additionally, the data of the women delivered in our comes. In a study, it was reported that preterm labor clinic between 2012 and 2015 were reviewed retrospec- rate is higher in pregnant women positive for HBsAg tively and the result of HBsAg seropositivity rate was than the pregnant women in the control group and that determined in our study. the rates of gestational diabetes, preterm labor and low birth weight are higher in carrier women positive for [6] Results HBsAg than the carrier women negative for HBsAg. In another study, it is claimed that HBsAg seropositiv- There are more than 60 studies, investigating HBsAg ity is associated with antepartum hemorrhage and low seropositivity of pregnant women in Turkey, performed APGAR scores.[7] in different years and in the same and different cities. There are more than 60 studies, investigating While these studies show that HBsAg seropositivity HBsAg seropositivity of pregnant women in Turkey, varies between 1.2 and 19.2% in Turkey, no higher pos- performed in different years and in the same and differ- itivity was found in other studies after the study report- ent cities. While these studies show that HBsAg ing the rate as 19.2%. It is seen that the highest rate seropositivity is between 1.2 and 19.2% in Turkey, the reported by the studies performed within the last two study of Turhano¤lu et al. in 1987 which was conducted decades is 9.3% (Table 1). It is seen that the rate is less on pregnant women in Diyarbak›r found the rate than 6% in the studies performed in the last 7 years with 19.2%[8] and no such positivity has been seen in all other the contribution of vaccine program carried out studies published afterwards.[8] When we evaluate the throughout the country. studies performed in the last two decades (Table 1),[9–49] In our study that we investigated the rate of HBsAg we see that the highest rate is 9.3%.[26] It is seen that seropositivity of pregnant women, we found this rate as HBsAg seropositivity rate is lower in the studies per- 2.16% in 4037 pregnant women. In the study, we retro- formed with high number of pregnant women than spectively analyzed the data of pregnant women who those with less number of pregnant women. In the first delivered at our clinic between 2012 and 2015 and found three studies with the highest pregnant woman popula- that 8.22% of the pregnant women were of foreign tion, the rates of HBsAg seropositivity were 2.1% nationality, the mean age was 28.64 (±5.77), mean week (90,351 pregnant women),[24] 3.5% (56,275 pregnant of gestation was 38.57 (±2.72), gravida was 2.51 (±1.44) women)[41] and 2.1% (11,840 pregnant women).[37] It is and parity was 1.20 (±1.16). remarkable in this regard that the numbers of pregnant women in studies with the rate above 7% are 397, 312 and 136.[26,12,21] The variety among the rates of HBsAg Discussion positivity in the studies shown in Table 1 may have Hepatitis B virus is an infectious agent which progress many reasons. While some of these studies were carried with mortality and may cause chronic liver diseases, cir- out in reference centers such as university and training rhosis and hepatocellular carcinoma. HBV is transmitted and research hospitals, some of them were performed in essentially by infected blood and body fluids as well as rural areas and maternal-pediatric health centers.[38,13] In percutaneous or mucosal contact. On the other hand, this regard, it should be remembered that the studies perinatal contagion is blamed particularly for the inci- carried out in the clinics which are reference centers dence of hepatitis B in the high endemic regions. The cannot reflect the entire society. The rates also vary by presence of this infection is important in terms of obstet- regions and years. In recent years, HBsAg seropositivity rics as it is considered that HBV infection has adverse rates tend to decrease in pregnant women as in the gen- effects on gestational outcomes. Infection contagion from eral population. With the help of country-wide vaccina- carrier mother to baby can occur during intrauterine, tion program which has been conducted since 1998, no intrapartum or postpartum period. It is thought that the HBsAg seropositivity over 6% has been found in the reasons such as skin scars, mucosal penetration, swallow- studies carried out in the last 7 years. ing maternal blood and fetomaternal bleeding due to pla- In the studies investigating perinatal contagion, [5] cental injury have a role in the intrapartum contagion. cord blood of babies of HBsAg seropositive mothers There are many studies in the literature investigat- was checked and while a study found 45% HBsAg ing the effects of HBV infection on gestational out- seropositivity in cord blood,[50] another study found no
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HBsAg seropositivity in the cord blood.[40] Kuru et al.[51] within last 20 years, we see that the rate is slightly conducted screenings on the children as well as hus- above 4% in Istanbul for the first 10 years while it bands of HBsAg seropositive cases and they found anti- decreases to the level below 4% in the last 10 years. Hbs rate over 20%. In the same study, there was no Although the rate reported in the study of Do¤an et al. statistically significant difference between seropositive published in 2014 decreases to 1.2%,[47] the reasons for and seronegative cases in terms of age, number of the slight increase in our study are considered to be the pregnancy, socioeconomical status, intravenous injec- increased migration to Istanbul from other cities and tion, and applying blood and blood products. the Middle East, and our clinic being one of the refer- We found the rate of HBsAg seropositivity of preg- ence centers. nant women in our clinic 2.16% in 4037 pregnant When we look at the distribution among the rea- women. In this study, we retrospectively analyzed the sons, we see that there is a clear decrease in HBsAg data of pregnant women who delivered at our clinic seropositivity of pregnant women in Marmara, between 2012 and 2015, and investigated HBsAg results Mediterranean/Aegean and Eastern Anatolia regions checked with ELISA method in the peripheral blood while the rates fluctuate in Central and Southeastern samples collected routinely from the pregnant women at Anatolia regions. On the other hand, the rate in Black antenatal period. Of the pregnant women, 8.22% were Sea region increased from 2.2% to 5.1% in the last 10 foreign. Of those included in the study, mean age was years (Fig. 1). This result shows that further studies are 28.64 (±5.77), mean week of gestation was 38.57 (±2.72), required to investigate the reasons for the increase in gravida was 2.51 (±1.44) and parity was 1.20 (±1.16). We Black Sea region. found that the HBsAg seropositivity rate in our clinic was consistent with the rates found in similar studies conducted in Istanbul in recent years. Conclusion When we look at the Table 1 which shows the As perinatal contagion maintains its importance in the progress of HBsAg seropositivity in different cities endemic regions, it is necessary to investigate HBV of
Fig. 1. Distribution of HBsAg seropositivity of pregnant women within the last 20 years by regions and years.
86 Perinatal Journal Hepatitis B seropositivity of pregnant women and the review of Turkish literature
pregnant women in these regions and to take protec- 12. Kaleli B, Kaleli ‹, Aktan E, Özen N, Akflit F. HBsAg in preg- tive precautions against this infection. In Turkey, it is nants and in the cord blood of their infants. [Article in Turkish] Perinatoloji Dergisi 1997;5:42–4. fought against the perinatal contagion of HBV by ante- 13. Ak›n N, Dilek S, Bilgel N. Screening for hepatitis B virus natal HBsAg screening, routine HBV vaccine of new- (HBV) seropositivity among pregnant women in the mater- borns and passive and active immunization practices nal child health and family planning (MCHFP) center in applied on newborns of the mothers who are positive Bursa (Turkey). [Article in Turkish] Aile Hekimli¤i Dergisi for HBsAg. In addition, high risk groups are vaccinat- 1997;1:86–9. ed against HPV and with all these methods, it is 14. Gül A, Türkdo¤an MK, Zetero¤lu S. The prevalance of hep- atitis B and hepatitis C in a group of pregnant women. expected to decrease the rate of hepatitis B in future [Article in Turkish] Perinatoloji Dergisi 1998;6:67–9. years in Turkey. 15. Biri A, Kilic G, Bozdayi G, Tezcan S. Prevalence of hepatitis B, hepatitis C and human immunodeficiency viruses during Conflicts of Interest: No conflicts declared. pregnancy. Turkiye Klinikleri Journal of Case Reports 2001; 19:100–3. References 16. Aslan G, Ulukanl›gil M, Seyrek A. Seroprevalance of HBsAg, anti-HBs and anti-HCV in fianl›urfa. [Article in Turkish] 1. Lee CY, Huang LM, Chang MH, Hsu CY, Wu SJ, Sung JL, Viral Hepatitis Journal 2001;7:408–11. et al. The protective efficacy of recombinant hepatitis B vac- 17. Yücel A, Bozday› G, Turgut I. Serological profile of hepatitits cine in newborn infants of hepatitis B e antigen-positive- B, hepatitis C and human immunodeficiency viruses among hepatitis B surface antigen carrier mothers. Pediatr Infect pregnant women. [Article in Turkish] Gazi Medical Journal Dis J 1991;10:299–303. 2001;12:103–5. 2. Dwivedi M, Misra SP, Misra V, Pandey A, Pant S, Singh R, 18. Sa¤söz N, Apan T. The rates of tetanus, hepatitis B and Rubella et al. Seroprevalence of hepatitis B infection during pregnan- seropositivity in pregnants. [Article in Turkish] Turkiye cy and risk of perinatal transmission. Indian J Gastroenterol Klinikleri Journal of Gynecology and Obstetrics 2002;12:52–5. 2011;30:66–71. 19. Karaca Ç, Karaca N, Usta T, Demir K, Kaymako¤lu S, Befl›fl›k 3. Kölgelier S, Demir LS, Demir NA, Ozcimen S, Tabak S. F, et al. The frequencies of hepatitis B, C, D virus infection in Seropositivity of HBsAg and anti-HCV in pregnant women the pregnant population and the rate of perinatal transmission in Ad›yaman. [Article in Turkish] Viral Hepatitis Journal of hepatitis C virus. [Article in Turkish] Akademik 2012;18:98–101. Gastroenteroloji Dergisi 2003;2:122–4. 4. Behrman RE, Kliegman RM, Jenson HB. Nelson textbook 20. Yegane Tosun S, Erensoy S, Özacar T, Yücebilgin S, Bilgiç of pediatrics. 17th ed. Philadelphia: WB Saunders; 2004. p. A. The investigation and follow-up of pregnant women and 1327–9. their children for hepatitis virus infections. [Article in 5. Comella LT, Cunnigham MD, Eyal FG. Infection diseases. Turkish] Türk Mikrobiyol Cemiyeti Dergisi 2003;33:153–9. Norwalk, CT: Appleton and Lange; 1992. p. 348–9. 21. Harma M, Harma M, Kafal› H, Güngen N, Demir N. 6. Sirilert S, Traisrisilp K, Sirivatanapa P, Tongsong T. Hepatitis B carrier status of pregnant women and vertical Pregnancy outcomes among chronic carriers of hepatitis B transmission to the newborn. [Article in Turkish] Perinatoloji Dergisi 2003;11:29–32. virus. Int J Gynaecol Obstet 2014;126:106–10. 22. Y›lmazer M, Alt›ndifl M, Çevrio¤lu S, Fenkçi V, Aktepe O, 7. Tse KY, Ho LF, Lao T. The impact of maternal HBsAg car- S›rthan E. Toxoplasma, Cytomegalovirus, Rubella, Hepatitis rier status on pregnancy outcomes: a case-control study. J B and Hepatitis C seropositivity rates in pregnant women who Hepatol 2005;43:771–5. live in Afyon region. [Article in Turkish] Kocatepe T›p Dergisi 8. Turhano¤lu M, Ar›kan E. HBsAg and antibody incidence in 2004;5:49–53. different groups in the Southeast Turkey. [Article in 23. Tekay F, Özbek E. Short communication: hepatitis B, hepatitis Turkish] Dicle Üniversitesi T›p Fakültesi Dergisi 1987;4: C and human immunodeficiency virus seropositivities in 28–31. women admitted to Sanliurfa Gynecology and Obstetrics 9. Çepni ‹, Bese T, Çetinkaya M, Gezer A, Alt›nok T, Aksu F. Hospital. [Article in Turkish] Mikrobiyol Bult 2006;40:369–73. Prevalence of hepatitis B surface antigen in pregnant women 24. Madenda¤ Y, Çöl Madenda¤ ‹, Çelen fi, Ünlü S, Dan›flman attending to obstetrics and gynecology department. [Article N. Seroprevalence of hepatitis B, hepatitis C and HIV at in Turkish] Viral Hepatitis Journal 1996;2:80–3. whole obstetric and gynecologic patients who applied our 10. Kuru U, Turan O, Kuru N, Saglam Z, Ceylan Y, Nurluoglu hospital. [Article in Turkish] Turkiye Klinikleri Journal of M, Agacfidan A. Prevalence of hepatitis B virus infection in Gynecology and Obstetrics 2007;17:442–6. pregnant Turkish women and their families. Eur Clinical 25. Cakmak B, Yoruk P, Elmas B. Ni¤de bölgesinde do¤um yapan Microbiol Infect Dis 1996;15:248–51. kad›nlarda hepatit B seropozitiflik oran›, risk faktörleri ve 11. Kadanal› A, Çelebi S, Aydos SK, Kadanal› S, Ayy›ld›z A. yenido¤an sonuçlar›. 6. Ulusal Jinekoloji Obstetrik Kongresi, Perinatal transmission of hepatit B virus in Erzurum. [Article 14 May›s 2008, Antalya. Türk Jinekoloji ve Obstetrik Derne¤i in Turkish] Atatürk Üniversitesi T›p Dergisi 1997;29:450–2. Dergisi Kongre Özel Say›s› 2008;5:115–6.
Volume 24 | Issue 2 | August 2016 87 Bakar RZ, Dane B
26. Sirmatel F, Bozkurt AI, Karsligil T, Cakmak A, Geyikli I. region. Journal of Turkish Society of Obstetrics and Hepatitis B in pregnant women and results of follow up of Gynecology 2011;8:93–9. immunized children whose mothers are hepatitis B surfage 40. Deveci Ö, Yula E, Özer TT, Tekin A, Kurkut B, Durmaz S. antigen positive. [Article in Turkish] Bak›rköy T›p Dergisi Investigation of intrauterine transmission of hepatitis B virus to (BTDMJB) 2008;4:31–3. children from HBsAg-positive pregnant women. J Microbiol 27. Uyar Y, Cabar C, Balci A. Seroprevalence of hepatitis B virus Infect Dis 2011;1:14–6. among pregnant women in northern Turkey. Hepat Mon 41. Cicek AC, Duygu F, Inakci IH. Hepatitis B and hepatitis C 2009;9:146–9. seropositivities in women admitted to gynecology and obstet- 28. Atilgan R, Kavak SB, Celik A. The ratio of hepatitis B and rics hospital in fianl›urfa city: a 3-year evaluation. [Article in hepatitis C seropositivity in pregnants. [Article in Turkish] Turkish] Viral Hepatitis Journal 2012;18:15–8. Turkiye Klinikleri Journal of Gynecology and Obstetrics 42. Çakmak B, Karatafl A. Sero-positivity ratios of hepatitis B 2009;19:34–7. and C in pregnant women living in Kocaeli region. [Article 29. Dündar Ö, Çelik S, Tütüncü L, Ergür AR, Atay V, Müngen in Turkish] Selçuk T›p Dergisi 2012;28:80–2. E. The prevalence of hepatitis B, hepatitis C, HIV, toxoplas- 43. Y›ld›z B, Bucaktepe PGE, Y›ld›z ‹, Kara ‹H. The ratio of mosis and rubella among pregmant women delivered in our HBsAg and antiHCV seropozitivity in pregnant and other clinic between 2000 and 2005. [Article in Turkish] Zeynep patients admitted to department of obstetrics and gynecolo- Kamil T›p Bülteni 2009;40:1–9. gy and their relationships with the other risk factors. [Article 30. Kölgelier S, Güler D, Demiraslan H. The prevalence of in Turkish] Konuralp T›p Dergisi 2012;4(3):27–34. HBsAg and anti-HCV in pregnant women in Ad›yaman. 44. Ozlu T, Tas T, Mengeloglu FZ, Kocoglu E, Donmez ME. [Article in Turkish] Dicle T›p Dergisi 2009;36:191–4. Frequency of HBsAg, anti-HCV and anti-HIV in pregnant 31. Api O, Bektas M, Akil A, Api M, Batirel A, Bayer F, et al. women and/or patients with gynecologic diseases in tertiary Hepatitis B Virus seroprevalence in the pregnant population hospital. [Article in Turkish] J Clin Exp Invest 2013;4:166–70. admitting to an Education and Research Hospital in 45. Bal›k G, Üstüner I, Ka¤›tç› M, Ural ÜM, Tekin YB, fientürk Istanbul. TJOD Dergisi 2009;6:103–10. fi, et al. HBsAg, AntiHBs and Anti-HCV seroprevalance in 32. Altinbas S, Erdogan M, Danisman N. The seroprevalences pregnant women living in Rize region. [Article in Turkish] of HBsAg and anti-HCV in pregnant women in Ankara. Dicle T›p Dergisi 2013;40:254–7. Arch Gynecol Obstet 2010;281:371. 46. Koruk ‹, Koruk ST, Demir C, fieyhano¤lu AS, Kara B. 33. Köksald› Motor V, Evirgen Ö, Aksakal M, ‹nci M, Önlen Y. HbsAg seropositivity and other related factors among preg- Seropositivity of Hepatitis B and Hepatitis C in women who nant women in crowded living conditions in a health district were admitted to Hatay Maternity and Children’s Hospital. where seasonal farmworkers live in fianl›urfa. [Article in [Article in Turkish] Viral Hepatitis Journal 2010;16:53–6. Turkish] Turk J Public Health 2013;11:149–59. 47. Dogan K, Guraslan H, Ozel G, Aydan Z, Yasar L. 34. Akdemir N, Bilir C, Akarsu S, Gürsoy AY. Hepatitis B and Seroprevalence rates of toxoplasma gondii, rubella, Hepatitis C seroprevalence follow up and awareness rates of cytomegalovirus, syphilis, and hepatitis B, seroprevalences rate pregnant; Ankara-Kecioren Region. [Article in Turkish] in the pregnant population in Istanbul. [Article in Turkish] Ortado¤u T›p Dergisi 2010;1:22–5. Türkiye Parazitoloji Dergisi 2014;38:228–33. 35. Karl›da¤ GE. HBsAg seroprevalence in pregnant women 48. Özcan Da¤ Z, Gül S, Ifl›k Y, Tulmaç ÖB, fiimflek Y. Hepatitis admitted to a hospital in centrum Elazig. [Article in Turkish] B and hepatitis C seropositivity rates in pregnants who live in F›rat Üniversitesi Sa¤l›k Bilimleri T›p Dergisi 2011;25:111–3. K›r›kkale region. [Article in Turkish] Bozok T›p Dergisi 36. Coflkun E‹, Dinçgez B, Koyucu RG, Ayanoglu YT, Ender 2015;5(3):1–4. Yumru A. The incidence of HBsAg, anti-HBs and anti-HCV 49. Ayn›o¤lu A, Ayn›o¤lu Ö, Akar T, Ayd›n M, Altunok ES. in pregnant women. Perinatal Journal 2011;19:71–5. HBsAg, anti-HBs and anti-HCV seropositivity rates among 37. Araz NC, Dikensoy E. Seroprevalence of hepatitis B among pregnant women attending a University Hospital in Zonguldak. pregnant women in Southern Turkey. J Pak Med Assos 2011; Viral Hepatitis Journal 2015;21:31–4. 61:176–7. 50. Olgun N, Dirik E, Kavukçu S, fiaflmaz E, Bahar H, Güner S, 38. Gönen ‹. The frequency of HBV and HCV in pregnant Okuyan M. ‹zmir yöresinde HBV’nin perinatal geçifl s›kl›¤›. women in rural areas. [Article in Turkish] Viral Hepatitis ‹nfeksiyon Dergisi 1991;5:117–20. Journal 2011;17:66–8. 51. Kuru Ü, Turan Ö, Ceylan Y, Nurluo¤lu M, Önür C, A¤açfi- 39. Varol FG, Say›n NC, Soysüren S. Seroprevalance of toxo- dan A, Biçici D ve ark. Incidence of HBsAg positivity in plasma gondii antibodies in antenatal population of Trakya pregnancy. [Article in Turkish] Klimik Dergisi 1992;5:83–6.
88 Perinatal Journal A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatal Journal 2016;24(2):89–95 I N N R A U T A L J O
Posterior fossa anomalies: related anomalies and the methods of pregnancy termination
Emine Ayd›n1, Mert Turgal2, Sema Can1, Özgür Özyüncü1 1Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey 2Gynecology and Obstetrics Clinic, Dr. Sami Ulus Training and Research Hospital, Ankara, Turkey
Abstract Özet: Posterior fossa anomalileri: ‹liflkili anomaliler ve gebeliklerin sonlanma flekilleri Objective: Posterior fossa anomalies are the group of heteroge- Amaç: Posterior fossa anomalileri göreceli olarak s›k ama halen neous malformations which are relatively common but still net olarak anlafl›lamam›fl heterojen bir malformasyonlar grubudur. unclear. In this study, we aimed to evaluate the presence of con- Bu çal›flmada posterior fossa anomalisi tan›s› alm›fl fetüslerde efllik current anomaly in fetuses diagnosed with posterior fossa anom- eden anomali varl›¤› ve gebeliklerin sonlanma flekillerinin de¤er- aly, and the methods of pregnancy termination. lendirilmesi amaçlanm›flt›r. Methods: A total of 56 cases matching the criteria and established Yöntem: Ultrasonografi veya mümkün oldu¤unda fetal manyetik with the posterior fossa anomaly during prenatal period were rezonans görüntüleme (MRG) yap›larak prenatal dönemde poste- determined by ultrasonography or fetal magnetic resonance imag- rior fossa anomalisi tan›s› alm›fl, kriterlere uyan 56 olgu belirlendi. ing (MRI) where possible. Medical histories, presence of concur- Gebeliklerin medikal öyküleri, efllik eden anomalilerin varl›¤›, rent anomalies, confirmation of diagnoses postnatally, results of postnatal olarak tan›lar›n do¤rulan›p do¤rulanmad›¤›, fetal MRG fetal MRI if any, results of cases which were terminated and had varsa sonuçlar›, terminasyon uygulanan olgulardan otopsisi olanla- autopsy, and genetic evaluations were recorded. The anomalies r›n sonuçlar›, genetik de¤erlendirmeler kaydedildi. Terminasyon (posterior fossa anomaly and additional concurrent anomalies) uygulanan olgular›n otopsi sonucunda tespit edilen anomaliler found in the autopsy in cases, which were terminated, were com- (posterior fossa anomalisi ve efllik eden ek anomaliler), prenatal ta- pared with the anomalies detected during prenatal diagnosis. n› an›nda tespit edilen anomaliler karfl›laflt›r›ld›. Results: Of 56 cases with posterior fossa anomaly detected by pre- Bulgular: Prenatal ultrasonografi ile tespit edilen toplam 56 pos- natal ultrasonography, 29 cases had Dandy-Walker malformation terior fossa anomalisi olgusundan, 29’u Dandy-Walker malfor- (51.7%), 19 cases had mega cisterna magna (33.9%), and 8 cases had masyonu (%51.7), 19’u mega sisterna magna (%33. 9), 8’i vermis hypogenesis/hypoplasia (14.2%). Termination option was preferred hipogenezisi/hipoplazisi (%14.2) idi. On bir hasta terminasyon se- by 11 patients. Mean diagnosis week of patients who had termination çene¤ini kullanm›flt›. Terminasyon seçene¤ini kullanan hastalar›n was 22.0±4.36 weeks of gestation, mean diagnosis week of patients ortalama tan› haftas› 22.0±4.36 gestasyonel hafta iken, do¤umla who delivered was 31.0±4.73 weeks. Twenty-one (37.5%) patients sonuçlanan olgular›n ortalama tan› haftas› 31.0±4.73 idi. Yirmi bir refused karyotype analysis. The results of karyotype analysis of 31 (%37.5) hasta karyotip analizini kabul etmemiflti. Otuz bir (%55.3) (55.3%) patients were normal. 46XY,ins(12;2) was found in one hastan›n karyotip analizi normal saptanm›flt›. Bir fetüste 46XY, fetus, L1 cell adhesion molecule (L1CAM) gene mutation was found ins(12;2), bir fetüste L1 cell adhesion molecule (L1CAM) gen mutas- in one fetus, and trisomy 18 was found in one fetus. yonu, bir fetüste trizomi 18 saptanm›flt›. Conclusion: In cases with posterior fossa anomaly, karyotype analy- Sonuç: Posterior fossa anomalisi olgular›nda karyotip analizi ve sis and the presence of additional concurrent anomaly are the ele- efllik eden ek anomali varl›¤› hastan›n takibinde bulunmas› gere- ments that should be included in the patient follow-up. Fetal MRI, ken unsurlard›r. Fetal MRG günümüzde dikkat çekmeye baflla- beginning to draw attention today, is a method useful in posterior yan, posterior fossa de¤erlendirmesinde faydal› olan bir yöntem- fossa evaluation. dir. Keywords: Anomalie, Dandy-Walker syndrom, fossa, posterior. Anahtar sözcükler: Anomali, Dandy-Walker sendromu, fossa, posterior.
Correspondence: Emine Ayd›n, MD. Hacettepe Üniversitesi T›p Fakültesi, Kad›n Hast. ve Available online at: Do¤um Anabilim Dal›, Ankara, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242006 doi:10.2399/prn.16.0242006 Received: April 12, 2016; Accepted: June 16, 2016 QR (Quick Response) Code: Please cite this article as: Ayd›n E, Turgal M, Can S, Özyüncü Ö. Posterior fossa anomalies: related anomalies and the methods of pregnancy termination. Perinatal Journal 2016;24(2):89–95. ©2016 Perinatal Medicine Foundation Ayd›n E et al.
Introduction diagnosis about the prognosis. The aim of this study is Posterior fossa anomalies (PFA) are the group of het- to determine the incidence rate of intracranial and erogeneous malformations which are relatively com- extracranial anomalies in fetuses with PFA diagnosis mon but still unclear. Dandy-Walker malformation and to evaluate the methods of termination in preg- (DWM), vermian hypogenesis/hypoplasia (VH) and nancies diagnosed. mega cisterna magna (MSM) are seen in 1/5000 live birth.[1] Routine posterior fossa evaluation including Methods cerebellum, vermis and cisterna magna has a significant The study was carried out at Perinatology Department, importance as there are more than one hundred syn- Faculty of Medicine, Hacettepe University. The data- dromes covering this area.[2] This area can be evaluated base was screened between 2004 and 2014. The cases with ultrasonography or fetal magnetic resonance established with PFA diagnosis during prenatal period imaging (MRI) where possible. Fetal MRI is a technol- were reached. Fifty-six cases matching the criteria were ogy capable of imaging soft tissues in more details and determined. When determining these cases, axial, coro- it helps to distinguish DWM, VH and MSM which [3,4] nal and sagittal cross-sections of 2D ultrasonography have different prognosis compared to each other. Also, the findings such as fourth ventricle imaging, the were used transabdominally. Transvaginal imaging was presence of vermis and the presence of primary fissure required only in 3 patients due to imaging quality. can be evaluated more clearly by transvaginal ultra- As diagnosis criteria, the measurements and defini- sonographic evaluation today.[5,6] In posterior fossa tions standardized by Robinson et al. were used.[12] evaluation, in which the experience of evaluator is sig- MSM was considered as cisterna magna being higher nificant as well as the technology used in imaging, (a) than 10 mm (Fig. 1). Presence of small vermis togeth- tentorium, (b) axis, size and morphology of vermis, and er with normal foliation was evaluated as VH. DWM (c) the presence of space-occupying lesions or cyst diagnostic criteria were determined as (a) vermian age- (Blake’s pouch cyst etc.) should be evaluate.[7] nesia/hypogenesis, (b) cystic dilatation of 4th ventricle, While intracranial and extracranial anomaly risk and (c) increase of tentorium together with the exten- [13] increases in fetuses with posterior fossa anomaly, the sion of posterior fossa (Fig. 2). Ventriculomegaly most common anomalies are congenital cardiac anom- (cases where lateral ventricle measurement is 10 mm alies (32%), extremity anomalies (28%), and renal and and above at the level of choroid plexus glomus in axial facial anomalies.[8] In these infants, delays in neurolog- plane and in the plane where ventricle's anterior horns, ical development are common and this rate was report- cavum septum pellucidum and choroid plexus can be ed between 20 and 80% in many studies.[9–11] While the seen) was associated with cerebrospinal fluid flow prognosis is so variable, it causes trouble to physicians change and it was not considered as additional anom- to inform the families of fetuses established prenatal aly.[14] Patient data were obtained from medical records
Fig. 1. A case with mega cisterna magna. Fig. 2. A case with Dandy-Walker malformation.
90 Perinatal Journal Posterior fossa anomalies: related anomalies and the methods of pregnancy termination
and by contacting to the patients via their registered found in the case having 46XY, ins(12;2), and bilateral phones (delivery, stillbirth, intrauterine fetal miss, ter- clubfoot, hypoplastic left heart, VSD and single umbili- mination). Medical histories, presence of concurrent cal artery was found in the case having trisomy 18. Also, anomalies, confirmation of diagnoses postnatally, the other cases with normal karyotype had additional results of fetal MRI if any, results of cases which were cranial and extracranial anomalies (Tables 2–4). terminated and had autopsy, and genetic evaluations Although dilatation in lateral ventricles was found in 23 were recorded. The anomalies (PFA and additional (41%) patients (cases where lateral ventricle measure- concurrent anomalies) found in the autopsy in cases, ment is 10 mm and above at the level of choroid plexus which were terminated, were compared with the glomus in axial plane and in the plane where ventricle’s anomalies detected during prenatal diagnosis. For this anterior horns, cavum septum pellucidum and choroid study, approval no GO 16/161 was obtained from the plexus can be seen), this was not considered as an addi- Non-Invasive Procedures Ethics Committee of tional anomaly due to the reason stated above. Hacettepe University. Definitive statistical analysis was Six of the terminated fetuses were performed done by SPSS 17.0 (Statistical Package for Windows, autopsy and the families of other fetuses refused an version 17.0; SPSS Inc., Chicago, IL, USA). autopsy. DWM was found in five fetuses which were performed autopsy. No pathology was found in the Results pathological examination of cases which preferred ter- Of 56 PFA cases detected by prenatal ultrasonography, mination and of the placentas in pregnancies which 29 (51.7%) cases had DWM, 19 (33.9%) cases had were delivered without preferring gestational termina- MSM, and 8 (14.2%) cases had VH (Table 1). All cases tion. Fetal MR was applied in two cases since their were referred to us from other centers. Mean age of the ultrasonographic evaluation was unclear, and DWM patients was 27.72±5.45, mean gravida was 2.12±1.37 was confirmed in both cases. and mean parity was 1.0±0.9. Termination option was preferred by 11 patients. Mean diagnosis week of Discussion patients who had termination was 22.0±4.36 weeks of gestation, mean diagnosis week of patients who deliv- As emphasized in the literature, first and main criterion ered was 31.0±4.73 weeks. Twenty-one (37.5%) of the DWM is the extension of posterior fossa associat- ed with the upward localization of cerebellar tentori- patients refused karyotype analysis. The results of [15] karyotype analysis of 31 (55.3%) patients were normal. um. This location change is essentially based on the 46XY,ins(12;2) was found in one fetus, L1 cell adhe- underlying pathology. As the normal position of tento- sion molecule (L1CAM) gene mutation was found in rium corresponds to the symmetry of the insertion of one fetus, trisomy 18 was found in one fetus, and one occiput nuchal muscles, it is determined according to fetus was thalassemia carrier. nuchal muscles. Even though these muscles are distin- guished well with hypointense appearances in T2- Only the thalassemia carrier among the fetuses weighed MRI, they cannot be used as reference point found to have karyotype anomaly was isolated, and oth- since they cannot be distinguished from soft tissues in ers had additional anomaly. Hydrocephalia was found in the ultrasonography. While fetal MRI is not an easily the case having L1CAM gene mutation, nasal bone accessible imaging method due to technical reasons in hypoplasia and right ventricle with double outflow were our center, fetal MRI was applied to two cases since clear imaging could not be obtained in the diagnosis. Increase Table 1. The distribution of cerebellar malformation diagnosis groups. in tentorium occurring due to the extension of posterior fossa becomes significant in the diagnosis of these cases Diagnosis group Incidence (%) and the necessity of defining nuchal muscles is eliminat- N=56 ed. Upward and too wide localization of tentorium caus- Dandy-Walker malformation (DWM) 29 (51.7%) es the necessity of MRI and determining nuchal muscles Mega cisterna magna (MSM) 19 (33.9%) to clarify the diagnosis. In this way, differential diagno- Vermis hypoplasia (VH) 8 (14.2%) sis of false positive cases, of which vermis develops nor- Total 56 (100%) mally, can be contributed.[14]
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Table 2. Distribution of cases with DWM diagnosis.
Case Diagnosis week Additional anomaly Karyotype Autopsy result Gestational no (Gestational week) analysis outcome
1 24 VSD, great artery transposition Normal DWM, VSD, great artery transposition Medical termination 2 22 N/a N/a N/a Medical termination 3 19 Corpus callosum agenesis N/a N/a Medical termination 4 26 Microcephaly, single umbilical artery N/a N/a Labor at term 5 33 N/a N/a N/a Labor at term 6 18 N/a N/a N/a Medical termination 7 18 Macrocephaly, micrognathia, retrognathia, N/a DWM, macrocephaly, micrognathia, Medical termination low ear, flattened nasal root, retrognathia, low ear, flattened six fingers in all extremities, nasal root, six fingers in renomegaly, bladder hypoplasia, all extremities, renomegaly, pancreatic cyst bladder hypoplasia, pancreatic cyst 8 31 N/a N/a N/a Labor at term 9 32 N/a N/a N/a Labor at term 10 21 N/a N/a N/a No follow-up 11 20 N/a N/a N/a Medical termination 12 26 N/a N/a N/a No follow-up 13 31 Bilateral clubfoot, hypoplastic left Trisomy 18 Bilateral clubfoot, hypoplastic left Labor at term heart, VSD, single umbilical artery heart, VSD, single umbilical artery 14 34 N/a N/a N/a No follow-up 15 17 N/a N/a DWM, dilatation at 4th ventricle Medical termination 16 19 N/a N/a N/a No follow-up 17 30 N/a N/a N/a Medical termination 18 24 Corpus callosum agenesis, L1CAM gene DWM, corpus callosum agenesis, Medical termination lung segmentation anomaly mutation lung segmentation anomaly 19 27 N/a N/a N/a No follow-up 20 N/a N/a N/a Labor at term 21 21. Nasal bone hypoplasia, right 46XY ins(12;2) Nasal bone hypoplasia, right Medical termination ventricle with double outflow ventricle with double outflow 22 35 N/a N/a N/a Labor at term 23 35 N/a N/a N/a Labor at term 24 19 N/a N/a N/a No follow-up 25 17 N/a N/a N/a No follow-up 26 13 N/a N/a N/a Intrauterine ex 27 20 N/a N/a N/a No follow-up 28 33 N/a N/a N/a Labor at term 29 18 N/a N/a N/a No follow-up
DWM: Dandy-Walker malformation, N/a: not available, VSD: ventricular septal defect
In addition, in some studies which used 3D imaging first trimester and early second trimester, it is not sup- methods were used ultrasonographically, the angles ported to establish PFA diagnosis (agenesis, dysgene- between brainstem-vermis and brainstem-tentorium sis, hypoplasia) including vermis before 18 weeks of gestation as cerebellar vermis development still contin- were evaluated in such cases and it was shown that they [18] [16,17] ues. In our series, mean week of diagnosis was 22 can be helpful in the diagnosis. weeks of gestation. Although vermis anatomy is not Although superior localization of cerebellar tento- understood clearly before 18 weeks of gestation, since rium is a finding which can be detected at the end of this malformation exists as of the third month of preg-
92 Perinatal Journal Posterior fossa anomalies: related anomalies and the methods of pregnancy termination
Table 3. Distribution of cases with mega cisterna magna.
Case Diagnosis week Additional anomaly Karyotype Autopsy result Gestational no (Gestational week) analysis outcome
1 26 ASD, small cardiothoracic diameter N/a N/a No follow-up 2 32 N/a N/a N/a No follow-up 3 39 VSD, cyst in umbilical cord N/a N/a No follow-up 4 32 N/a N/a N/a No follow-up 5 22 Left renal ureteropelvic junction stricture N/a N/a No follow-up (renal pelvis AP diameter= 9.4 mm) 6 25 N/a N/a N/a No follow-up 7 21 Diaphragmatic hernia N/a N/a No follow-up 8 25 Flexion contractor in both hands, ASD, VSD, N/a N/a Intrauterine ex multicystic dysplasia in both kidneys 9 23 Corpus callosum agenesis Normal N/a Labor at term 10 20 N/a Normal N/a Labor at term 11 36 N/a N/a N/a Labor at term 12 33 N/a Normal N/a Labor at term 13 35 N/a N/a N/a Labor at term 14 33 N/a N/a N/a Labor at term 15 23 N/a N/a N/a Labor at term 16 27 N/a N/a N/a Labor at term 17 30 N/a N/a N/a Labor at term 18 34 N/a N/a N/a Labor at term 19 32 Corpus callosum agenesis N/a N/a Labor at term
AP: anteroposterior, ASD: atrial septal defect, N/a: not available, VSD: ventricular septal defect nancy, the diagnosis can be established before this increase, these cystic masses should be considered rather week if increase of tentorium can be defined clearly.[14] than DWM.[14] In our series, there was no fetus with BPC Blake’s pouch cyst (BPC) or arachnoid cysts which or arachnoid cyst. In the typical ultrasonographic imag- may create mass effect in tentorium can cause false pos- ing of these fetuses, a small and thin continuing mem- itivity.[19] These cysts do not affect entire tentorium but brane is seen in the caudal part of inferior vermis in the only the area in the distal of tentorium. With this focal prenatal and postnatal MRI imaging, and fourth ventri-
Table 4. The distribution of cases with vermian hypogenesis/hypoplasia.
Case Diagnosis week Additional anomaly Karyotype Autopsy result Gestational no (Gestational week) analysis outcome
1 22 N/a N/a N/a No follow-up 2 28 N/a N/a N/a No follow-up 3 29 Corpus callosum agenesis N/a N/a No follow-up 4 25 N/a N/a N/a No follow-up 5 20 N/a N/a N/a Medical termination 6 20 N/a N/a N/a Medical termination 7 37 Cleft palate-lip, VSD N/a N/a Labor at term 8 35 N/a N/a N/a Labor at term
N/a: not available, VSD: ventricular septal defect
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cle is dilated. This membrane is the remnant of the pos- Conclusion teroinferior part of the membraneous piece of primitive Consequently, in cases with PFA, karyotype analysis [20] fourth ventricle. BPC should be remembered with the and the presence of additional concurrent anomaly are [20] dilatation of fourth ventricle instead of DWM. the elements that should be included in the patient fol- Apart from them, as also highlighted in the litera- low-up. Fetal MRI, beginning to draw attention today, ture, complete agenesis of vermis is seen in few patients; is an imaging method useful in identifying concurrent superior part of vermis is normal in most of them, and cranial anomalies by anatomic evaluation of vermis, only inferior part is seen as thin.[14] The current theory lobulation and fissuration, and it cannot be applied in explaining the relationship between cystic malformation all centers yet due to the technical reasons. and varying levels of vermian hypoplasia states that it is a developmental defect involving the membraneous part Conflicts of Interest: No conflicts declared. of rhombencephalon.[12] While it is difficult to make a distinction between malformed and normal vermis in References the early phases of development, it is also difficult to 1. Parisi MA, Dobyns WB. Human malformations of the mid- evaluate lobulation and fissuration when decreased vol- brain and hindbrain: review and proposed classification ume is detected. Pathological specimens obtained also scheme. Mol Genet Metab 2003;80:36–53. support that hypoplasia disappears partially together 2. De Catte L, De Keersmaeker B, Claus F. Prenatal neurolog- with dysplasia and this is revealed with developmental ic anomalies: sonographic diagnosis and treatment. Paediatr Drugs 2012;14:143–55. disorganization.[15] In our series, we did prenatal evalua- 3. Adamsbaum C, Moutard ML, André C, Merzoug V, Ferey tion on all DWM and VH cases by the examination for S, Quéré MP, et al. MRI of the fetal posterior fossa. Pediatr the presence of two fissures and three lobs. Radiol 2005;35:124–40. The importance of the presence of concurrent cra- 4. Limperopoulos C, du Plessis AJ. Disorders of cerebellar growth and development. Curr Opin Pediatr 2006;18:621–7. nial anomaly was highlighted in various series and the 5. Goldstein I, Makhoul IR, Tamir A, Rajamim BS, Nisman D. absence of cranial anomaly draws attention in cases who Ultrasonographic nomograms of the fetal fourth ventricle: [10] maintain their lives normally. In our series, there were additional tool for detecting abnormalities of the posterior cranial anomalies found in cases with normal karyotype. fossa. J Ultrasound Med 2002;21:849–56. While DWM can be seen together with normal 6. Zalel Y, Seidman DS, Brand N, Lipitz S, Achiron R. The development of the fetal vermis: an in-utero sonographic karyotype, the most common concurrent chromosomal evaluation. Ultrasound Obstet Gynecol 2002;19:136–9. anomalies are associated with 3rd, 9th, 13th and 18th 7. Garel C, Moutard ML. Main congenital cerebral anomalies: [21] chromosomes. In some series, 6th chromosome how prenatal imaging aids counseling. Fetal Diagn Ther anomaly is the most common anomaly.[14] We also had 2014;35:229–39. fetuses found to have chromosomal anomaly in our 8. Ecker JL, Shipp TD, Bromley B, Benacerraf B. The sono- series, and trisomy 18 was one of them. Without check- graphic diagnosis of Dandy-Walker and Dandy-Walker variant: associated findings and outcomes. Prenat Diagn ing the presence of chromosomal anomaly, all fetuses 2000;20:328–32. should be screened in terms of cranial and extracranial 9. Bolduc ME, Limperopoulos C. Neurodevelopmental out- anomalies (congenital cardiac anomalies, eye anomalies, comes in children with cerebellar malformations: a systemat- developmental defects, and dysmorphosis). High-reso- ic review. Dev Med Child Neurol 2009;51:256–67. lution screening methods are significant particularly in 10. Klein O, Pierre-Kahn A, Boddaert N, Parisot D, Brunelle F. [22] Dandy-Walker malformation: prenatal diagnosis and prog- cases where cardiac anomaly accompanies DWM. In nosis. Childs Nerv Syst 2003;19:484–9. our series, cases found to have trisomy 18 (hypoplastic 11. Gerszten PC, Albright AL. Relationship between cerebellar left heart) and 46XY, ins(12;2) (right ventricle with dou- appearance and function in children with Dandy-Walker ble outflow) also had cardiac anomaly, and fetuses which syndrome. Pediatr Neurosurg 1995;23:86–92. were normal for chromosome also had cardiac anomaly 12. Robinson AJ, Blaser S, Toi A, Chitayat D, Halliday W, (great artery transposition in one fetus and VSD in one Pantazi S, et al. The fetal cerebellar vermis: assessment for abnormal development by ultrasonography and magnetic fetus). In addition, facial deformities, cleft palate-lip and resonance imaging. Ultrasound Q 2007;23:211–23. lower-upper extremity deformities were reported 13. Dandy WE. Internal hydrocephalus. An experimental, clini- [14] among the concurrent anomalies similar to our series. cal and pathological study. Am J Dis Child 1914;8:406–82.
94 Perinatal Journal Posterior fossa anomalies: related anomalies and the methods of pregnancy termination
14. Guibaud L, Larroque A, Ville D, Sanlaville D, Till M, 18. Bromley B, Nadel AS, Pauker S, Estroff JA, Benacerraf BR. Gaucherand P, et al. Prenatal diagnosis of 'isolated' Dandy- Closure of the cerebellar vermis: evaluation with second Walker malformation: imaging findings and prenatal coun- trimester US. Radiology 1994;193:761–3. selling. Prenat Diagn 2012;32:185–93. 19. Garel C. Posterior fossa malformations: main features and 15. Guibaud L, des Portes V. Plea for an anatomical approach to limits in prenatal diagnosis. Pediatr Radiol 2010;40:1038–45. abnormalities of the posterior fossa in prenatal diagnosis. 20. Robinson AJ, Goldstein R. The cisterna magna septa: vestig- Ultrasound Obstet Gynecol 2006;27:477–81. ial remnants of Blake’s pouch and a potential new marker for 16. Contro E, Volpe P, De Musso F, Muto B, Ghi T, De normal development of the rhombencephalon. J Ultrasound Robertis V, et al. Open fourth ventricle prior to 20 weeks’ Med 2007;26:83–95. gestation: a benign finding? Ultrasound Obstet Gynecol 21. Imataka G, Yamanouchi H, Arisaka O. Dandy-Walker syn- 2014;43:154–8. drome and chromosomal abnormalities. Congenit Anom 17. Ghi T, Contro E, De Musso F, Farina A, Conturso R, (Kyoto) 2007;47:113–8. Bonasoni P, et al. Normal morphometry of fetal posterior 22. Lin RJ, Cherry AM, Chen KC, Lyons M, Hoyme HE, fossa at midtrimester: brainstem-tentorium angle and brain- Hudgins L. Terminal deletion of 6p results in a recognizable stem-vermis angle. Prenat Diagn 2012;32:440–3. phenotype. Am J Med Genet A 2005;136:162–8.
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P L E R A Perinatal Journal 2016;24(2):96–99 I N N R A U T A L J O
Modified transabdominal cervico-isthmic cerclage: analysis of 16 cases
Ebru Çelik Kavak1, Salih Burçin Kavak1, Yakup Baykufl2, Hüsnü Çelik3 1Department of Obstetrics and Gynecology, Faculty of Medicine, F›rat University, Elaz›¤, Turkey 2Department of Obstetrics and Gynecology, Faculty of Medicine, Kafkas University, Kars, Turkey 3Department of Obstetrics and Gynecology, Faculty of Medicine, Baflkent University, Adana, Turkey
Abstract Özet: Servikal yetmezlikte modifiye transabdominal serviko-istmik serklaj: 16 olgunun analizi Objective: The aim of the study is to evaluate 16 cases retrospec- Amaç: Çal›flman›n amac› modifiye transabdominal serviko-istmik tively who underwent modified transabdominal cervico-isthmic serklaj uygulanan 16 olgunun retrospektif olarak de¤erlendirilme- cerclage. sidir. Methods: The cases that had unsuccessful vaginal cerclage history Yöntem: Baflar›s›z vajinal serklaj öyküsü bulunan ve abdominal and underwent abdominal cervico-isthmic cerclage were analyzed serviko-istmik serklaj uygulanan olgular retrospektif olarak analiz retrospectively. Sociodemographic characteristics of the cases, edildi. Olgular›n sosyodemografik özellikleri, operasyon esnas›nda problems encountered during and after the operation and gestation- ve sonras›nda karfl›lafl›lan sorunlar ile gebelik sonuçlar› hasta dos- al outcomes were recorded by investigating patient files. Descriptive yalar› incelenerek kay›t alt›na al›nd›. Verilerin istatistiksel analizi methods were used for the statistical analysis of the data. için tan›mlay›c› metodlar kullan›ld›. Results: None of the cases developed intraoperative complication. Bulgular: Olgular›n hiçbirinde intraoperatif komplikasyon gelifl- Mean week of gestation and mean week of delivery for the operation medi. Operasyonun uyguland›¤› ortalama gebelik haftas› 14±4 were found as 14±4 and 34.4±6 days, respectively. Gestation reached gün, ortalama do¤um haftas› 34.4±6 gün olarak tespit edildi. to 34 weeks and above in 81.25% of the cases. Premature rupture of %81.25 olguda gebelik 34 hafta ve üzerine ulaflt›. ‹ki olguda erken membrane developed in two cases and these pregnancies were termi- membran rüptürü geliflti ve bu gebelikler anterior histerotomi ile nated with anterior hysterectomy. The rate of complication at early sonland›r›ld›. ‹fllem sonras› erken dönemde komplikasyon geliflme period after the operation was found as 12.5%. Preterm labor oran› %12.5 olarak tespit edildi. Bir olguda operasyondan 12 haf- occurred in one case after 12 weeks (at 29 weeks of gestation) follow- ta sonra (29. gebelik haftas›nda), preterm eylem ortaya ç›kt›, toko- ing the operation; there was no response to the tocolytic treatment, litik tedaviye yan›t al›namad› ve sezaryen ile do¤um yapt›r›ld›. therefore cesarean section was performed. All patients had cesarean Tüm hastalara sezaryen ile do¤um yapt›r›ld› ve ifllem sonunda eve section and the rate of live birth after the operation was 87.5%. canl› bebek götürme oran› %87.5 olarak tespit edildi. Conclusion: Modified transabdominal cervico-isthmic cerclage prac- Sonuç: Modifiye transabdominal serviko-istmik serklaj uygula- tice is considered as an initiative to get successful perinatal outcomes mas›, vajinal giriflim için uygun olmayan olgularda, baflar›l› peri- in cases which are inappropriate for vaginal approach. natal sonuçlar al›nabilecek bir giriflim olarak görünmektedir. Keywords: Live birth, modified transabdominal cervico-isthmic Anahtar sözcükler: Gebelik, modifiye transabdominal serviko- cerclage, pregnancy. istmik serklaj, canl› do¤um.
Introduction membranes and the removal of fetus not reached to “Cervical insufficiency” or “early cervical dilatation” is a maturity to live yet following the painless dilatation of significant reason for gestational losses at the second cervix at second trimester or early third trimester of the trimester. It is a condition resulting with the rupture of pregnancy.[1] While its incidence is not known clearly, it
Correspondence: Salih Burçin Kavak, MD. F›rat Üniversitesi T›p Fakültesi, Kad›n Available online at: Hastal›klar› ve Do¤um Anabilim Dal›, Elaz›¤, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242007 doi:10.2399/prn.16.0242007 Received: April 23, 2016; Accepted: June 17, 2016 QR (Quick Response) Code: This study was presented as a poster at the 15th National Perinatology Congress (October 11-15, 2015, Mu¤la, Turkey). Please cite this article as: Çelik Kavak E, Kavak SB, Baykufl Y, Çelik H. Modified transab- dominal cervico-isthmic cerclage: analysis of 16 cases. Perinatal Journal 2016;24(2):96–99. ©2016 Perinatal Medicine Foundation Modified transabdominal cervico-isthmic cerclage
is observed in 0.1–1% of all pregnancies and in 8% of of Medicine of F›rat University between 2003 and women who have a history of two or more losses of 2014, required abdominal cervical cerclage and under- pregnancy.[2] Its diagnosis is usually established with went modified transabdominal cervico-isthmic cer- anamnesis and clinical examination. While hysterogra- clage, were evaluated retrospectively. The ages, num- phy, cervical dilatators or catheter balloons can be used ber of pregnancy and weeks of gestation of the patients for pre-pregnancy diagnostic purposes, the only diag- were recorded. nostic method during pregnancy is transvaginal ultra- All patients were applied partially modified version sonography. of abdominal cervico-isthmic cerclage, defined by The success of non-surgical methods such as bed Benson and Durfee.[6] In brief, the operation was rest, pesser practice and pharmacological agents pre- applied under general anesthesia and the abdomen was ferred for the treatment of cervical insufficiency has not reached with transverse incision. After reaching been revealed clearly, and the treatment method for cer- abdomen, anterior peritoneum in the cervico-isthmic vical insufficiency with proven activity today is to apply area was dissected and without dissecting uterine ves- closing suture called cerclage to the cervix through sels laterally, 5 mm Mersilene tape was passed through [3] transvaginal or abdominal way. myometrium in the cervico-isthmic area and fastened Transvaginal cerclage has been used since it was rec- up in the front. All patients were administered 1 g cefa- ommended in 1950s by Shirodkar from India and zolin prophylaxis before the procedure and bed rest McDonald from Australia, and its success rate is high.[4,5] and hydration treatment were applied after the proce- As transvaginal cerclage cannot be applied to those hav- dure. The complications developed during and after ing cervical insufficiency history and congenital short the procedure were found from the operation notes. cervix and those surgically amputated cervix, placing cer- Definitive methods were used for statistical analysis. clage to cervico-isthmic region transabdominally, which is known as transabdominal cervico-isthmic cerclage, Results was recommended by Benson and Durfee in 1965.[6] This procedure was made more popular by Novy, and by The demographic characteristics and the operation extending its indications, it was recommended to apply it findings and results of the patients who underwent mod- to previous failed cerclage procedures in particular and ified transabdominal cervico-isthmic cerclage are shown to wide conizations causing tissue loss in the cervix and in the Table 1. Emergency cerclage was not applied to to the cases with cervicovaginal fistula developing after any patient. Presence or absence of congenital cervical miscarriage.[7] With this method, fetal survival rate vary- hypoplasia was not detected in any patient and it was ing between 82 and 95% was reported.[8,9] found that all patients had the history of unsuccessful vaginal cerclage. Only one case had a living child. No In our study, we present the retrospective analysis of the patients who underwent modified transabdominal major complication was found in any patient during cervico-isthmic cerclage procedure in our clinic. abdominal cerclage procedure; also, no complication developed during cesarean section operations in the same patients. Mean week of gestation and mean week Methods of delivery for the operation were found as 14±4 and The results of 16 patients, who admitted to the 34.4±6 days, respectively. Gestation reached to 34 weeks Gynecology and Obstetrics Department of the Faculty and above in 81.25% of the cases. Premature rupture of
Table 1. Demographic characteristics and operation findings and results of the cases.
Number of cases 16 Age (year) 27.6±5 Mean number of pregnancy 3.4±2 Mean week of gestation during the operation 14±4 Mean week of gestation during the delivery 34.4±6 Perinatal outcome Premature preterm labor and delivery in one case
Volume 24 | Issue 2 | August 2016 97 Çelik Kavak E et al.
membrane developed in two cases. These pregnancies ed similar live birth rates.[13] We applied cerclage during were terminated with anterior hysterotomy due to the postconceptional period to all our patients because the development of premature membrane rupture and patients were referred to our hospital during their post- anhydramnios after 4 days following the operation (17 conceptional period and mean cerclage week was 14±4. weeks and 3 days) in one case and after 4 weeks follow- Compared to vaginal cerclage, abdominal cerclage ing the operation (20 weeks and 4 days). Preterm labor has superiorities such as placing suture to an upper loca- occurred in one case after 12 weeks (at 29 weeks of ges- tion at the level of internal os, decrease in the risk of tation) following the operation; there was no response to suture migration, absence of any foreign body which will the tocolytic treatment, therefore cesarean section was cause infection in the vagina, and prevention of cervical performed. All patients had cesarean section and the rate insufficiency by the suture left in its position for the fur- of live birth after the operation was 87.5%. ther pregnancies.[14] The most significant disadvantage of this method is that the laparotomy is required twice dur- Discussion ing the pregnancy. In our two patients, pregnancy was In the diagnosis of cervical insufficiency, obstetric histo- terminated by performing anterior histerotomy due to ry has still been the most significant detail and classical- the development of premature rupture of membrane ly, patients have the history of repeating second and anhydramnios. trimester pregnancy loss. Due to the non-availability of The major intraoperative complication seen in the standardization in the diagnostic methods, the rate of patients who underwent abdominal cerclage is the performing cerclage operation varies between 1/180 and development of bleeding as a result of traumatized adja- 1/1800 per delivery.[10] When the studies performed are cent vessels and this complication can be decreased by analyzed, it is seen that excessive dilatation of the cervix applying the surgical intervention during the precon- [15] during pregnancy termination, and traumatizing cervix ceptional period where vessels are thinner. The com- with obstetric lacerations and operations such as coniza- plications defined in case series or case reports are fetal tion and loop electrosurgery excision procedure (LEEP) death, intrauterine growth retardation, suture migra- are the most significant reasons of the cervical insuffi- tion, infection, premature labor, premature rupture of [16,17] ciency. membranes, uterine rupture and rectovaginal fistule. The treatment of cervical insufficiency is surgical In our series, two patients had premature labor due to and it includes the reinforce of weak cervix with a kind the premature rupture of membrane and anhydramnios of purse string suture. While applying cervical suture after the procedure and one patient had premature labor after first trimester in a planned way is called prophylac- due to inevitable labor at 29 weeks of gestation. Since it tic (primary) cerclage, applying it after monitoring cer- was not required to lateralize uterine walls due to the vical changes is called therapeutic (secondary) cerclage modified technique applied during the procedure, no and applying it after advanced effacement-dilatation and major bleeding occurred associated with the trauma of the formation of prolapsed membranes is called emer- these vessels. Another superiority of modified transab- gency (tertiary) cerclage.[11] We applied primary cerclage dominal cervico-isthmic cerclage procedure is the to all our patients. absence of migration risk as the suture passes through the tissue. Abdominal cerclage can be before or during preg- nancy.[12] It provides a better field of vision during pre- In our study, we administered no medication such as α conceptional period and it also has less risks such as 17- hydroxyprogesterone routinely to the patients who bleeding. It is not preferred to apply cerclage after the underwent cerclage during the pregnancy. Tocolysis first trimester because it becomes difficult to reach isth- was applied only in one patient after labor started, but it mus due to growing corpus and the manipulations to be was an unsuccessful attempt. Therefore, the success done on the uterus may cause gestational complications. offered in the study only depends on the surgical Even though there is no randomized studies comparing method. the success of preconceptional and postconceptional All viable pregnancies were ended with cesarean sec- applications, in a meta-analysis reviewing abdominal tion. Uterus incisions were carried out over the cerclage cerclage cases published between 1990 and 2013 report- suture. As all our patients were planning pregnancy
98 Perinatal Journal Modified transabdominal cervico-isthmic cerclage
again, the suture was not removed during the cesarean 7. Novy MJ. Transabdominal cervicoisthmic cerclage for the section. It is recommended in other studies to keep the management of repetitive abortion and premature delivery. suture in its location when patients plan pregnancy again Am J Obstet Gynecol 1982;143:44–54. and even when they are not sure if they want pregnan- 8. Fick AL, Caughey AB, Parer JT. Transabdominal cerclage: can we predict who fails? J Matern Fetal Neonatal Med cy.[18] We could not reach the information on the obstet- 2007;20:63–7. ric histories of our patients in their further lives. 9. Anthony GS, Walker R G, Cameron AD, Price J L, Walker JJ, Calder AA. Transabdominal cervico-isthmic cerclage in Conclusion the management of cervical incompetence. Eur J Obstet Gynecol Reprod Biol 1997;72:127–30. Our study is retrospective and it has no separate con- 10. Harger JH. Comparison of success and morbidity in cervical trol group. This is the limitation of our study. On the cerclage procedures. Obstet Gynecol 1980;56:543–8. other hand, in cases candidate for the abdominal cer- 11. Rust OA, Roberts WE. Does cerclage prevent preterm clage, planning a prospective randomized controlled birth? Obstet Gynecol Clin North Am 2005;32:441–56. study is not ethical. Our study shows that high fetal 12. Burger NB, Einarsson JI, Brölmann HA, Vree FE, McElrath survival rate can be achieved together with low compli- TF, Huirne JA. Preconceptional laparoscopic abdominal cation rate thanks to the modified transabdominal cer- cerclage: a multicenter cohort study. Am J Obstet Gynecol vico-isthmic cerclage. 2012;207:273.e1–12. 13. Tulandi T, Alghanaim N, Hakeem G, Tan X. Pre and post- Conflicts of Interest: No conflicts declared. conceptional abdominal cerclage by laparoscopy or laparoto- my. J Minim Invasive Gynecol 2014;21:987–93. References 14. Herron MA, Parer JT. Transabdominal cerclage for fetal wastage due to cervical incompetence. Obstet Gynecol 1988; 1. Simcox R, Shennan A. Cervical cerclage: a review. Int J Surg 71:865–8. 2007;5:205–9. 15. Norwitz ER, Lee DM, Goldstein DP. Transabdominal cer- 2. Scarantino SE, Reilly JG, Moretti ML, Pillari VT. vico-isthmic cerclage: placing the stitch before conception. Laparoscopic removal of a transabdominal cervical cerclage. Journal of Gynecologic Techniques 1997;3:53. Am J Obstet Gynecol 2000;182:1086–8. 16. Debbs RH, DeLa Vega GA, Pearson S, Sehdev H, Marchiano 3. Newcomer J. Pessaries for the treatment of incompetent D, Ludmir J. Transabdominal cerclage after comprehensive cervix and premature delivery. Obstet Gynecol Surv 2000;55: evaluation of women with previous unsuccessful transvaginal 443–8. cerclage. Am J Obstet Gynecol 2007;197:317.e1–4. 4. Shirodkar VN. A new method of operative treatment for 17. Foster TL, Moore ES, Sumners JE. Operative complications habitual abortions in the second trimester of pregnancy. and fetal morbidity encountered in 300 prophylactic transab- Antiseptic 1955;52:299–300. dominal cervical cerclage procedures by one obstetric sur- 5. McDonald IA. Suture of the cervix for inevitable miscar- geon. J Obstet Gynaecol 2011;31:713–7. riage. J Obstet Gynaecol Br Emp 1957;64:346–50. 18. Gibb DM, Salaria DA. Transabdominal cervicoisthmic cer- 6. Benson RC, Durfee RB. Transabdominal cervico uterine clage in the management of recurrent second trimester mis- cerclage during pregnancy for the treatment of cervical carriage and preterm delivery. Br J Obstet Gynaecol 1995; incompetency. Obstet Gynecol 1965;25:145–55. 102:802–6.
Volume 24 | Issue 2 | August 2016 99 A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatal Journal 2016;24(2):100–105 I N N R A U T A L J O
Results of fetal anomaly screening performed at 11–14 weeks of gestation at a tertiary center
Tu¤ba K›nay, Metin Kaplan, Mehmet Metin Altay, fiafak Özdemirci, Sinan Karadeniz, Ahmet Okyar Erol 1Department of Obstetrics and Gynecology, Etlik Zübeyde Han›m Gynecology Training and Research Hospital, Ankara, Turkey
Abstract Özet: Üçüncü basamak bir merkezde 11–14. gestasyonel haftada yap›lan fetal anomali taramas› sonuçlar› Objective: The aim of the study is to determine and analyze the Amaç: Çal›flman›n amac› 11–14. gebelik haftas›nda fetal anomali incidence of congenital structural anomalies which can be identi- taramas› ile saptanabilen konjenital yap›sal anomalilerin insidans›- fied by fetal anomaly screening at 11–14 weeks of gestation. n› belirlemek ve analizini yapmakt›r. Methods: The patients (except those with cardiac anomalies) found Yöntem: Retrospektif kohort çal›flmas› olarak tasarlanan çal›flma- to have fetal anomaly during nuchal translucency (NT) measure- ya 2014–2016 y›llar› aras›nda üçüncü basamak bir merkezde yap›- ment performed at 11–14 weeks of gestation in the ultrasonograph- lan ultrasonografik incelemede 11–14. gebelik haftalar›nda ense ic examination at a tertiary center between 2014 and 2016 were saydaml›¤› (NT) ölçümü s›ras›nda fetal anomali saptanan hastalar included in the study designed as a retrospective cohort study. The (kardiyak anomaliler hariç) dahil edildi. Olgular›n demografik demographic characteristics, ultrasonographic findings and gesta- özellikleri, ultrasonografi bulgular› ve gebelik sonuçlar› t›bbi ka- tional outcomes were obtained from medical records. y›tlardan elde edildi. Results: Congenital structural anomaly (except cardiac anomaly) Bulgular: Anomali taramas› yap›lan 12.352 gebenin 57’sinde was identified in 57 (0.46%) out of 12,352 pregnant women who (%0.46) konjenital yap›sal anomali (kardiyak anomali hariç) tespit underwent anomaly screening. In the study group, the most com- edildi. Çal›flma grubunda en s›k nöral tüp defekti (%53.4) ve daha mon anomaly was neural tube defect (53.4%) followed by anterior sonra s›ras›yla bat›n ön duvar› defektleri (%15.5), kistik higroma abdominal wall defects (15.5%), cystic hygroma (12.1%), hydrops (%12.1) hidrops fetalis (%6.9), üriner sistem anomalisi (%6.9) ve fetalis (6.9%), urinary system anomaly (6.9%) and twin reversed ikizde ters arteryel kanlanma (twin reversed arterial perfusion, arterial perfusion (TRAP) syndrome (3.4). NT was measured over TRAP) sendromu (%3.4) izlendi. Kistik higroma ve hidrops feta- 95th percentile in all cystic hygroma and hydrops fetalis cases and in lis olgular›n›n hepsinde, bat›n ön duvar› defektlerinin %77.8’inde 77.8% of anterior abdominal wall defects. NT 95 persentilin üzerinde ölçüldü. Conclusion: With fetal anomaly screening performed together with Sonuç: ‹lk trimester NT ölçümü ile birlikte yap›lan fetal anoma- first trimester NT measurement, neural tube defect in particular and li taramas› ile baflta nöral tüp defekti olmak üzere ço¤u anomali most of the anomalies can be detected in early weeks of gestation. erken gebelik haftalar›nda saptanabilir. Keywords: First trimester, nuchal translucency, fetal anomaly. Anahtar sözcükler: Birinci trimester, ense saydaml›¤›, fetal anomali.
Introduction ments in the resolution of ultrasound devices and com- Although the screening of congenital structural anom- mon use of first trimester screening tests have enabled to alies is performed by ultrasonographic examination diagnose particular major anomalies at the first trimester between 18 and 23 weeks of gestation,[1,2] the improve- during nuchal translucency (NT) measurement.[3] In the
Correspondence: Tu¤ba K›nay, MD. Etlik Zübeyde Han›m Kad›n Hast. E¤. ve Arfl. Available online at: Hastanesi, Kad›n Hastal›klar› ve Do¤um Klini¤i, Ankara, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242010 doi:10.2399/prn.16.0242010 Received: June 18, 2016; Accepted: July 20, 2016 QR (Quick Response) Code: Please cite this article as: K›nay T, Kaplan M, Altay MM, Özdemirci fi, Karadeniz S, Erol AO. Results of fetal anomaly screening performed at 11–14 weeks of gestation at a tertiary center. Perinatal Journal 2016;24(2):100–105. ©2016 Perinatal Medicine Foundation Results of fetal anomaly screening performed at 11–14 weeks of gestation at a tertiary center
beginning, first trimester ultrasonographic examinations viability, fetus number and fetal anatomy were obtained. were only used to determine gestational age, to detect Cranium, cerebral structures, orbita, facial profile, nasal fetal heartbeat and to identify chorionicity in twin preg- bone, spinal column, lungs, diaphragm, kidneys, bladder, nancies.[3] However, 49–68% of fetal anomalies can be lower and upper extremities (long bones, hands and detected by first trimester ultrasonographic examination feet), anterior body wall and cord insertion were the today.[4–7] anatomic structures evaluated during fetal anomaly Fetal structural anomalies are seen approximately in screening. NT values of all fetuses, except those found to 3–5% of all pregnancies.[8] Since most of the fetal organs have anencephaly, measured according to the standards [9] determined by Fetal Medicine Foundation (FMF) were develop in the first 12 weeks, ultrasonographic exami- [10] nation performed between 11 and 14 weeks of gestation recorded. If not associated with cystic hygroma, isolat- ed NT increase was not considered as fetal anomaly. enables to establish early diagnosis of most of the fetal [4–7] Ultrasonographic findings were confirmed with abor- anomalies. Early diagnosis may help to take early deci- tion, termination or postnatal macroscopic examination sions on the management of patient, and to carry out of fetus in all cases except those not maintained their ges- early karyotyping for the diagnosis of chromosomal tational follow-up in the study hospital. anomalies which may cause anomaly and spontaneous abortions. The aim of this study was to determine fetal The statistical analysis was done by using SPSS 17 anomaly incidence except cardiac anomaly which can be (IBM Corp., Armonk, NY, USA). The continuous vari- detected between 11 and 14 weeks of gestation, and to ables were presented as mean ± standard deviation or analyze these anomalies. median (minimum–maximum) according to the con- formity to normal distribution, and categorical variables were presented as number and percentage. Methods In this retrospective cohort study, the medical records Results of pregnant women who admitted to Etlik Zübeyde Congenital anomaly was found in 57 of 12,352 cases who Han›m Gynecology Training and Research Hospital underwent fetal anomaly screening during NT measure- for first trimester screening tests at 11–14 weeks of ment at 11–14 weeks of gestation. Fetal anomaly inci- gestation between April 2014 and April 2016 were dence found during first trimester screening test was reviewed. The demographic characteristics, ultra- 0.46%. sonography reports and gestational outcomes of the cases were obtained from the computer record system The demographic characteristics and ultrasono- graphic findings of the cases included in the study are of the hospital. The patients who were found to have given in Table 1. The distribution of fetal anomalies fetal anomaly during NT measurement when undergo- found is shown in Fig. 1. The most common fetal ing first trimester screening test were included in the anomaly found in first trimester except cardiac anom- study. Women having molar pregnancy and ectopic alies was neural tube defect (53.4%). The second com- pregnancy, measured to have crown-rump length (CRL) <45 mm or >84 mm and detected to have fetal cardiac anomaly were exclude from the study. The Table 1. Demographic characteristics and ultrasonographic findings study was approved by Training Planning Council of of the cases found to have first trimester fetal anomaly. the hospital and informed consent was received from all patients to use medical records in scientific studies. Characteristics Ultrasonographic examination was primarily carried Age (year) 25.9±5.9 out with transabdominal probe (2–5 MHz, Hi Vision Gravida 2.2±1.3 Parity 1 (0–3) Preirus, Hitachi Medical Corporation, Tokyo, Japan). In Abortion 0 (0–2) cases where all fetal anatomic structures could not be Gestational age (day) 87.9±5.5 evaluated in a clear way transabdominally, 6–9 MHz CRL, mm 59.5±11.5 probe was used and transvaginal ultrasonography was NT, mm 3.1 (0.7–19) performed. With the CRL measurement among ultra- The data was presented as mean ± standard devition or median (minimum–maxi- sonography reports, information on gestational age, fetal mum). CRL: crown-rump length; NT: nuchal translucency
Volume 24 | Issue 2 | August 2016 101 K›nay T et al.
mon anomaly was anterior abdominal wall defect (15.5%). Ultrasonographic views of some fetal anom- alies are shown in Fig. 2. The detailed description of fetal anomalies, gesta- tional outcomes and the relationship with NT measured above 95th percentile are given in Table 2. 66.7% (n=38) of pregnancies resulted with termination, 10.5% (n=6) of them resulted with delivery and 5.3% (n=3) of them resulted with abortion. It was found that ten preg- nant women (17.5%) did not undergo their follow-up and treatment at study hospital. The most common anomaly among neural tube defects was anencephaly (24.1%). Among anterior abdominal wall defects, omphalocele was the most common anomaly diagnosed Fig. 1. Distribution of fetal anomalies. (8.6%). 5.2% of the cases had wide anterior wall defect. In these cases, liver, stomach and intestine were out of case). In all twin pregnancies, it was found during anom- abdomen and they also had ectopia cordis. aly screening that one of the fetuses was dead. The living Four cases had spontaneous multiple pregnancy (twin fetuses had megacystis, anencephaly and hydrops fetalis. pregnancy in three cases and triple pregnancy in one Megacystis case resulted with delivery and hydrops fetal-
a b
c d
Fig. 2. Fetal anomaly examples found at first trimester. (a) Encephalocele, (b) omphalocele, (c) semilobar holoprosencephaly and (d) megacystis.
102 Perinatal Journal Results of fetal anomaly screening performed at 11–14 weeks of gestation at a tertiary center
is cases resulted with termination; the case found to have and in 77.8% of anterior abdominal wall defects. In uri- anencephaly did not maintain the treatment in the study nary system anomalies and neural tube defects, this rate hospital. One case with triple pregnancy had twin was 25% and 9.6%, respectively (Table 2). reversed arterial perfusion (TRAP) syndrome. In six cases, the pregnancy resulted with delivery. In Discussion five of them, it was found that the family did not accept termination. The sixth was a triple pregnancy case. In the present study, in conformity with the literature, While two fetuses which were intrauterine ex had the fetal anomaly incidence found in first trimester TRAP syndrome, third fetus did not have any anomaly ultrasonographic examination was 0.46%. Syngelaki et and resulted with delivery at 40 weeks of gestation. Two al. also reported a similar fetal anomaly incidence [11] of 3 cases with neural tube defect resulted with delivery (0.47%) at 11–13 weeks of gestation. However, their had spina bifida and the delivery was carried out with study also included cardiac anomalies unlike our study. cesarean at 37 weeks of gestation. In three cases diag- Today, with the ultrasonographic examination per- nosed with anencephaly, the labor initiated at 33 weeks formed at 11–14 weeks of gestation, many fetal anom- of gestation and the case with previous cesarean history alies can be detected during first trimester. 53% of cen- delivered 1800 g live baby with cesarean section. In tral nervous system anomalies, 75% of gastrointestinal megacystis case with twin sibling, severe dilatation was system and abdominal wall anomalies, 25% of major uri- detected on fetal left renal pelvis and ureter when the nary anomalies, 69% of major skeletal anomalies, 99% term is reached and when labor started at 38 weeks of of hydrops fetalis, and 49% of major structural anom- gestation, the delivery was carried out with cesarean sec- alies in total can be diagnosed during first trimester.[4] In tion due to fetal macrosomy. It was found that another our study, we found that neural tube defects were the pregnancy with cystic hygroma was resulted with live most common anomaly diagnosed during first trimester. birth at 38 weeks of gestation. Among them, cranial anomalies including anencephaly, Nuchal translucency was measured over 95th per- holoprosencephaly, iniencephaly and encephalocele centile in all cystic hygroma and hydrops fetalis cases were the most common ones (25/31). In the series of
Table 2. Fetal anomalies except cardiac anomaly found at first trimester, gestational outcomes and their relationship with NT >95th percentile.
Anomaly N (%) NT >95th Gestational outcomes persentil / N (%) Termination Delivery Abortion Lost to follow-up
Neural tube defect 31 (53.4%) 3/31 (9.6%) 24/31(77.4%) 3/31 (9.6%) - 4/31 (13.0%) Holoprosencephaly 4 (6.9%) 1/4 (25.0%) 4/4 (100%) - - - Anencephaly 14 (24.1%) -/14 (-) 12/14 (85.8%) 1/14 (7.1%) - 1/14 (7.1%) Spina bifida 6 (10.3%) 0/6 (0.0%) 3/6 (50.0%) 2/6 (33.3%) - 1/6 (16.7%) Iniencephaly 3 (5.2%) 1/3 (33.3%) 3/3 (100%) - - - Encephalocele 4 (6.9%) 1/4 (25.0%) 2/4 (50.0%) - - 2/4 (50.0%) Anterior abdominal wall defect 9 (15.5%) 7/9 (77.8%) 6/9 (66.7%) 1/9 (11.1%) 2/9 (22.2%) Omphalocele 3 (5.2%) 2/3 (66.7%) 1/3 (33.3%) - 1/3 (33.3%) 1/3 (33.3%) Omphalocele containing liver 2 (3.4%) 2/2 (100%) 2/2 (100%) - - - Gastroschisis 1 (1.7%) 0/1 (0.0%) 1/1 (100%) - - - Wide anterior wall defect 3 (5.2%) 3/3 (100%) 2/3 (66.7%) - - 1/3 (33.3%) Cystic hygroma 7 (12.1%) 7/7 (100%) 3/7 (42.9%) 1/7 (14.3%) 1/7 (14.3%) 2/7 (28.5%) Hydrops fetalis 4 (6.9%) 4/4 (100%) 4/4 (100%) - - - Urinary system anomaly 4 (6.9%) 1/4 (25.0%) 1/4 (25.0%) 1/4 (25.0%) 1/4 (25.0%) 1/4 (25.0%) Megacystis 3 (5.2%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) - Hydronephrosis 1 (1.7%) 0/1 (0.0%) - - - 1/1 (100%) TRAP 2 (3.4%) 2/2 (100%) - 1/2 (50.0%) - 1/2 (50.0%)
TRAP: Twin reversed arterial perfusion
Volume 24 | Issue 2 | August 2016 103 K›nay T et al.
Dane et al., 10 of 17 patients found to have first the anomalies which can be detected at first trimester trimester fetal anomaly had cranial anomaly.[12] Akdeniz easily, they can be temporary findings in fetuses without et al.[13] reported that the most common anomaly in chromosomal anomaly.[17,18] It was shown that 92.5% of patients who underwent pregnancy termination due to omphaloceles including only intestine at 11–13 weeks of fetal anomaly at 11–24 weeks of gestation was central gestation recover at 20 weeks of gestation.[17] Megacystis nervous system anomaly (23/57). In another series, the with bladder length smaller than 15 mm has 90% chance most common fetal anomaly at 11–13 weeks of gestation to recover in fetuses with normal karyotype.[18] was anterior abdominal wall defect. Omphalocele was The retrospective design of the study presented is found in 60 of 165 fetal anomaly cases and gastroschisis the main limitation although it has a wide population. [11] was found in 19 of them. Since some of the patients found to have fetal anomaly Nuchal translucency measurement is a part of first did not maintain their follow-up and treatment at the trimester screening test. On the other hand, increased study hospital, full information on the gestational out- NT measurement may be the indication of not only fetal comes of all patients is not available. Also, being unable trisomies but also major structural anomalies. While the to evaluate cases together with karyotype analysis results relationship between NT increase and cardiac anomalies is another limitation. It is not known how much of the [14] are shown clearly, also other structural anomalies structural malformations found are associated with increase NT. In the series we present, cardiac anomalies chromosomal anomalies. were excluded from the study. When cystic hygroma and hydrops fetalis cases were also excluded, the NT was found >95th percentile in the most common anterior Conclusion abdominal wall defects (77.8%). In another series pub- With the ultrasonographic examination performed lished in 2011, NT was found >95th percentile in the during NT measurement at first trimester, it is possi- most common megacystis (69%) and lethal skeletal dys- ble to diagnosis a significant number of fetal anomalies. plasias (50%). In the study performed, when malformations are Although most of the major structural anomalies can excluded, it was found that the neural tube defects are be diagnosed with first trimester fetal anomaly screen- the fetal anomalies which can be diagnosed most com- ing, second trimester screening test is required monly at 11–14 weeks of gestation. doubtlessly. Withlov et al. reported that the rate of fetal anomaly detection rate which was 59% at early pregnan- Conflicts of Interest: No conflicts declared. cy increased to 81% with second trimester anomaly screening.[15] This rate was similar to the major congen- References ital anomaly rate (79.4%) found with second trimester 1. Stefos T, Plachouras N, Sotiriadis A, Papadimitriou D, ultrasonography in the study of Pekin et al.[16] Second Almoussa N, Navrozoglou I, et al. Routine obstetrical ultra- trimester fetal anomaly screening should be performed sound at 18-22 weeks: our experience on 7,236 fetuses. J due to the development of some structural anomalies at Matern Fetal Med 1999;8:64–9. the late periods of pregnancy or non-evaluation of 2. Goldberg JD. Routine screening for fetal anomalies: expec- tations. Obstet Gynecol Clin North Am 2004;31:35–50. anatomic structures at first trimester. In the series of 3. Donnelly JC, Malone FD. Early fetal anatomical sonogra- 44,859 cases of Syngelaki et al., 100% of acrania, allobar phy. Best Pract Res Clin Obstet Gynaecol 2012;26:561–73. holoprosencephaly, omphalocele, gastroschisis, mega- 4. Grande M, Arigita M, Borobio V, Jimenez JM, Fernandez S, cystis and body stalk anomalies could be diagnosed at Borrell A. First-trimester detection of structural abnormali- 11–13 weeks of gestation, none of corpus callosum age- ties and the role of aneuploidy markers. Ultrasound Obstet nesis, semilobar holoprosencephaly, cerebellar or vermi- Gynecol 2012;39:157–63. an hypoplasia, echogenic lung lesions, intestinal 5. Souka AP, Pilalis A, Kavalakis I, Antsaklis P, Papantoniou N, obstruction, duplex kidney, severe hydronephrosis and Mesogitis S, et al. Screening for major structural abnormalities [11] at the 11- to 14-week ultrasound scan. Am J Obstet Gynecol talipes could be diagnosed at first trimester. On the 2006;194:393–6. other hand, there are also anomalies which can be 6. Economides DL, Braithwaite JM. First trimester ultrasono- detected at first trimester but recover as weeks of gesta- graphic diagnosis of structural abnormalities in a low risk tion progress. While omphalocele and megacystis are population. Br J Obstet Gynaecol 1998;105:53–7.
104 Perinatal Journal Results of fetal anomaly screening performed at 11–14 weeks of gestation at a tertiary center
7. Ebrashy A, El Kateb A, Momtaz M, El Sheikhah A, 14. von Kaisenberg C, Chaoui R, Häusler M, Kagan KO, Aboulghar MM, Ibrahim M, et al. 13–14-week fetal anatomy Kozlowski P, Merz E, et al. Quality requirements for the scan: a 5-year prospective study. Ultrasound Obstet Gynecol early fetal ultrasound assessment at 11–13+6 weeks of gesta- 2010;35:292–96. tion (DEGUM Levels II and III). Ultraschall Med 2016;37: 8. Garne E, Dolk H, Loane M, Boyd PA; EUROCAT. EURO- 297–302. CAT website data on prenatal detection rates of congenital anomalies. J Med Screen 2010;17:97–8. 15. Whitlow BJ, Chatzipapas IK, Lazanakis ML, Kadir RA, Economides DL. The value of sonography in early pregnan- 9. Sadler TW. Third month to birth: the fetus and placenta. In: cy for the detection of fetal abnormalities in an unselected Sadler TW, editor. Langman’s medical embryology. 9th ed. Philadelphia: Lippincott Williams &Wilkins: 2004; p. population. Br J Obstet Gynaecol 1999;106:929–36. 117–48. 16. Pekin AT, Kerimo¤lu ÖS, Y›lmaz SA, Bakbak BBG, Çelik 10. Nicolaides KH, Azar G, Byrne D, Mansur C, Marks K. Fetal Ç. Detailed second trimester ultrasound examination in low nuchal translucency: ultrasound screening for chromosomal risk pregnancies: a tertiary 110 center experience. [Article in defects in first trimester of pregnancy. BMJ 1992;304:867–69. Turkish] Jinekoloji-Obstetrik ve Neonatoloji T›p Dergisi 11. Syngelaki A, Chelemen T, Dagklis T, Allan L, Nicolaides 2015;12:1–5. KH. Challenges in the diagnosis of fetal non-chromosomal 17. Kagan KO, Staboulidou I, Syngelaki A, Cruz J, Nicolaides KH. abnormalities at 11-13 weeks. Prenat Diagn 2011;31:90–102. The 11–13-week scan: diagnosis and outcome of holoprosen- 12. Dane B, Dane C, Sivri D, Kiray M, Cetin A, Yayla M. cephaly, exomphalos and megacystis. Ultrasound Obstet Ultrasound screening for fetal major abnormalities at 11–14 Gynecol 2010;36:10–4. weeks. Acta Obstet Gynecol Scand 2007;86:666–70. 13. Akdeniz N, Kale A, Erdemo¤lu M, Yal›nkaya A, Yayla M. 18. Liao AW, Sebire NJ, Geerts L, Cicero S, Nicolaides KH. Retrospective analysis of the 126 cases terminated in preg- Megacystis at 10–14 weeks of gestation: chromosomal defects nancy by the ethical committee decision. Perinatal Journal and outcome according to bladder length. Ultrasound Obstet 2005;13:80–5. Gynecol 2003;21:338–41.
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P L E R A Perinatal Journal 2016;24(2):106–109 I N N R A U T A L J O
Intrafetal laser therapy in acardiac twin pregnancy: a case report
Resul Ar›soy1, Oya Pekin1, Kaan Pakay1, Emre Erdo¤du1, Oya Demirci1, Murat Muhçu2 1Perinatology Clinic, Ministry of Health Zeynep Kamil Maternity and Pediatrics Training and Research Hospital, Istanbul, Turkey 2Perinatology Clinic, Haydarpafla Training Hospital, Gulhane Military Medical Academy, Istanbul, Turkey
Abstract Özet: Akardiyak ikiz gebelikte intrafetal lazer tedavisi: Olgu sunumu Objective: In this study, we aimed to present the case of acardiac Amaç: Bu makalede intrafetal lazer tedavisi ile baflar› ile tedavi twin pregnancy (twin reversed arterial perfusion sequence, TRAP) edilmifl akardiyak ikiz gebelik (ikizde ters arteryel kanlanma sekan- successfully treated with intrafetal laser therapy. s›, TRAP) olgusunun sunumu amaçlanm›flt›r. Case: Monochorionic diamniotic twin pregnancy, a fetus without Olgu: On dördüncü haftada klini¤imize baflvuran gebenin ultraso- heart (acardiac fetus) and a second fetus with normal appearance (pump nografi (USG) muayenesinde plasenta anteriyorda, monokoryonik fetus) were observed in the anterior placenta during USG examination diamniyotik ikiz gebelik, kalbi olmayan bir fetüs (akardiyak fetüs) of the pregnant women who admitted to our clinic at her 14 weeks of ve normal görünümde ikinci fetüs (pompa fetüs) tespit edildi. gestation. Retrograde blood flow was monitored via Doppler USG and Doppler USG ile retrograd kan ak›m› izlendi ve TRAP tan›s› ko- she was established with the diagnosis of TRAP. At her 15 weeks of nuldu. Gebeli¤in 15. haftas›nda elektif olarak intrafetal lazer uygu- gestation, abdominal aortic and iliac vein lines were coagulated elec- lamas› ile abdominal aorta ve ilyak damar hatt› koagüle edildi ve tively by intrafetal laser procedure, and it was found that acardiac fetus akardiyak fetüsün avasküler oldu¤u izlendi ve iflleme son verildi. was avascular, so the procedure was ended. In gestational follow-up vis- Gebeli¤in takiplerinde akardiyak fetüsün büyümedi¤i ve regrese its, it was seen that acardiac fetus did not grow and regressed. Pump oldu¤u izlendi. Pompa fetüs geliflimi ve Doppler bulgular› normal fetus development and Doppler findings had a normal progress. On seyretti. Gebeli¤in 37 hafta 3. gününde Apgar 8–9 olan 2800 g be- the 37 weeks and 3 days of gestation, 2800 g live newborn with 8–9 bek canl› olarak do¤urtuldu. On ayl›k olan bebe¤in geliflimi nor- Apgar score was delivered. The development of ten-month-old new- mal olup, bir komplikasyon izlenmedi. born was normal and no complication was observed. Sonuç: Bizim olgumuz da akardiyak ikiz gebeliklerde 12–16 gebe- Conclusion: Our case supports the fact that elective intrafetal laser lik haftalar› aras›nda elektif intrafetal lazer uygulamas›n›n gebelik procedure improves gestational outcomes between 12 and 16 weeks sonuçlar›n› gelifltirdi¤ini desteklemektedir. of gestation in acardiac twin pregnancies. Keywords: Acardiac twin, intrafetal laser, management. Anahtar sözcükler: Akardiyak ikiz, intrafetal lazer, yönetim.
Introduction together with a pump fetus feeding other one through arterial anastomoses in the placenta.[1] While the mortal- Acardiac twin pregnancy (twin reversed arterial perfu- ity is 100% for acardiac fetus, the pump fetus is under sion sequence, TRAP) is defined as the presence of a the risk of cardiac failure, preterm labor and associated fetus without a heart or with a non-functional heart complications, and the mortality has been reported as found in 2.6% of monochorionic twin pregnancy 55%.[2]
Correspondence: Resul Ar›soy, MD. S.B. Zeynep Kamil Kad›n ve Çocuk Hastal›klar› E¤itim Available online at: ve Araflt›rma Hastanesi, Perinatoloji Klini¤i, Istanbul, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242008 doi:10.2399/prn.16.0242008 Received: June 9, 2016; Accepted: July 6, 2016 QR (Quick Response) Code: Please cite this article as: Ar›soy R, Pekin O, Pakay K, Erdo¤du E, Demirci O, Muhçu M. Intrafetal laser therapy in acardiac twin pregnancy: a case report. Perinatal Journal 2016;24(2):106–109. ©2016 Perinatal Medicine Foundation Intrafetal laser therapy in acardiac twin pregnancy
Various fetoscopic and intrafetal techniques were (Fig. 2). Then, the procedure was ended when it was used to prevent the pump fetus loss and possible com- found that acardiac fetus was avascular. Heartbeat of plications in TRAP cases. With this case report, we the pump fetus was monitored. In the follow-up a week aimed to present acardiac twin pregnancy case which later, no vascularity was seen in the acardiac fetus and underwent intrafetal laser practice. it was found that there was no change in the dimen- sions. Heartbeat of the pump fetus was monitored and Case Report fetal Doppler findings were found normal. Since kary- otype analysis could not be performed on the amnio- Twenty-two-year-old case with gravida 1, parity 0 centesis (AC) material, the AC procedure was carried referred to our clinic with the diagnosis of monochori- out on the week 18 and karyotype analysis was normal. onic twin pregnancy at her 14 weeks of gestation. In Acardiac fetus regressed in gestational follow-ups. her ultrasonographic examination, monochorionic Pump fetus development and Doppler findings had a diamniotic twin pregnancy, a fetus without heart (40 normal progress. On 37 weeks and 3 days of gestation, mm, acardiac fetus) and a second fetus (pump fetus) cesarean section was performed with the diagnoses of with 80 mm crown-rump length were observed in the oligohydramnios and fetal distress. The 2800 g infant anterior placenta (Fig. 1). Retrograde blood flow was with 8–9 Apgar score was delivered alive. The develop- monitored via Doppler USG and she was established ment is normal and no complication has been observed with the diagnosis of TRAP. Ductus venosus flow of in the baby which is currently 10-month-old. the pump fetus was normal. The family was informed about acardiac twin pregnancy and prognosis. Elective intrafetal laser therapy was recommended for the acar- Discussion diac fetus. The family accepted the therapy one week TRAP sequence is seen in 1% of the monochorionic later at 15 weeks of gestation and informed consent of pregnancies. Although the pathogenesis of TRAP the family was obtained. sequence has still been unknown, reverse blood flow Through ultrasonography, intrafetal laser therapy from pump fetus to acardiac fetus via artery-artery was carried out by using 18 G 15 cm needle. The pelvis anastomosis is considered as an unchanging character- was entered under the fetal umbilical cord of the acar- istics.[1,3] Ruiz-Cordero et al.[4] investigated 13 TRAP diac fetus by needle, and intra-abdominal aorta and cases in their study and reported that the interruption iliac vein line were reached by passing through 400 nm in early placental and embryonic vascular development fiber needle. The veins on this line were coagulated by is the main mechanism of abnormal hemodynamic using neodymium yttrium aluminum garnet (Nd:YAG) early tissue hypoxia and the atrophy of the organs laser source (Dornier MedTech, Munich, Germany) accordingly. They highlighted that single umbilical
Acardiac fetus
a Acardiac fetusb Pump fetus
Fig. 1. Acardiac fetus (a), acardiac and pump fetuses (b).
Volume 24 | Issue 2 | August 2016 107 Ar›soy R et al.
artery, umbilical arterial thrombosis and calcification flow in acardiac fetus in 46% (11/24) of the cases. One and abnormal cord insertion (velamentous cord inser- of 11 pregnancies was terminated and invasive proce- tion) have a key role in the development of TRAP. dure was performed in 10 pregnant women (intrafetal Although most of TRAP cases are diagnosed in the laser therapy in 6 cases, RFA in 1 case and laser cord late first and second trimesters, the prognosis is poor. coagulation in 3 cases). They reported that 9 (90%) The reverse arterial flow between acardiac fetus and pregnancies resulted in live birth. In the studies related pump fetus causes high output cardiac failure, with RFA use on TRAP cases, survival rate of pump [3,11] intrauterine fetal death and polyhydramnios, all lead- fetus was reported as 71–85%. Similarly, in cases ing to preterm labor. The perfusion of acardiac fetus applied intrafetal laser therapy, the survival rate of was stopped by various techniques to decrease high pump fetus was reported as approximately 80%.[12,13] mortality rate and the complications. Fetoscopic cord Berg et al.[16] reported in their study that the survival ligation,[5] cord coagulation by laser,[6] alcohol injec- rate of pump fetus was similar in RFA and intrafetal tion,[7] monopolar or bipolar cord coagulation[8,9] and laser practices, however; preterm premature rupture of fetoscopic laser coagulation of placental anastomoses[10] membrane (PPROM) developed in 42.9% of the preg- were used to stop the flow of the acardiac fetus. nancies underwent RFA (<34 weeks) but PPROM was Intrafetal radiofrequency ablation (RFA)[3,11] and not observed in cases underwent intrafetal laser thera- intrafetal laser ablation[12,13] are used widely as minimal py. Cabassa et al.[11] reported that PPROM developed invasive techniques. Recently, it has been reported that in 57% (4/7) of the cases underwent RFA. Also, in the high intensity focused ultrasound was successfully used study of Lee et al.[3] carried out on 98 TRAP cases, they [14] on TRAP cases as the non-invasive technique. reported that PPROM developed in 17% (17/98) of Lewi et al.[15] planned the procedure between 16 and the cases after RFA therapy and four (4.1%) cases were 18 weeks of gestation in TRAP cases diagnosed at the lost due to PPROM and premature preterm labor dur- first trimester and they reported the presence of spon- ing neonatal period. However, Sugibayashi et al.[17] taneous loss in pump fetus in 33% (8/24) of the cases reported that PPROM developed (<34 weeks) in 2.9% followed up to this week, stopped spontaneous flow in (1/35) of the cases and premature preterm labor (<34 acardiac fetus in 21% (5/24) of the cases and persistent weeks) in 8.6% (3/35) of the cases after multi-stage
18 G needle: Nd YAG laser
a b
Fig. 2. Intrafetal laser practice on acardiac twin (a) and Doppler USG image (b).
108 Perinatal Journal Intrafetal laser therapy in acardiac twin pregnancy
RFA therapy of TRAP cases and they associated the 5. Quintero RA, Reich H, Puder KS, Bardicef M, Evans MI, low frequency of PPROM with the short duration of Cotton DB, et al. Brief report: umbilical-cord ligation of an the procedure. acardiac twin by fetoscopy at 19 weeks of gestation. N Engl J Med 1994;330:469–71. Although there is no consensus on the best method 6. Ville Y, Hyett JA, Vandenbussche FP, Nicolaides KH. and time, Lewi et al. reported in their study that 33% Endoscopic laser coagulation of umbilical cord vessels in twin of the siblings of acardiac twin fetuses are lost sponta- reversed arterial perfusion sequence. Ultrasound Obstet neously before 16 weeks and they highlighted the Gynecol 1994;4:396–8. necessity of performing prophylactic procedure until 7. Sepulveda W, Bower S, Hassan J, Fisk NM. Ablation of acar- 16 weeks.[15] Also, Pagani et al.[12] showed in their study diac twin by alcohol injection into the intra-abdominal umbil- that poor gestational outcomes were significantly low ical artery. Obstet Gynecol 1995;86:680–1. by intrafetal laser ablation procedure before 16 weeks 8. Rodeck C, Deans A, Jauniaux E. Thermocoagulation for the and they recommended performing elective intrafetal early treatment of pregnancy with an acardiac twin. N Engl J Med 1998;339:1293–4. laser therapy between 13 and 15 weeks of gestation. [13] 9. Tan TYT, Sepulveda W. Acardiac twin: a systematic review of Chaveeva et al. investigated the cases who underwent minimally invasive treatment modalities. Ultrasound Obstet intrafetal laser procedure between 12 and 27 weeks of Gynecol 2003;22:409–19. gestation, and they could not find any correlation 10. Hecher K, Lewi L, Grataco’s E, Huber A, Ville Y, Deprest J. between therapy week and survival rate; however, they Twin reversed arterial perfusion: fetoscopic laser coagulation found that there was an inverse correlation between of placental anastomoses or the umbilical cord. Ultrasound therapy week and delivery week and they reported that Obstet Gynecol 2006;28:688–91. the elective procedure between 12 and 14 weeks of ges- 11. Cabassa P, Fichera A, Prefumo F, Taddei F, Gandolfi S, tation might develop survival rate. Maroldi R, et al. The use of radiofrequency in the treatment of twin reversed arterial perfusion sequence: a case series and review of the literature. Eur J Obstet Gynecol Reprod Biol Conclusion 2013;166:127–32. In conclusion, we stopped the bleeding of acardiac 12. Pagani G, D'Antonio F, Khalil A, Papageorghiou A, Bhide A, fetus by intrafetal laser electively at 15 weeks of gesta- Thilaganathan B. Intrafetal laser treatment for twin reversed tion in our case. We found no complication in the ges- arterial perfusion sequence: cohort study and meta-analysis. Ultrasound Obstet Gynecol 2013;42:6–14. tational follow-ups. Our case supports the fact that 13. Chaveeva P, Poon LC, Sotiriadis A, Kosinski P, Nicolaides elective intrafetal laser therapy between 12 and 16 KH. Optimal method and timing of intrauterine intervention weeks of gestation improves gestational outcomes. in twin reversed arterial perfusion sequence: case study and meta-analysis. Fetal Diagn Ther 2014;35:267–79. Conflicts of Interest: No conflicts declared. 14. Okai T, Ichizuka K, Hasegawa J, Matsuoka R, Nakamura M, Shimodaira K, et al. First successful case of non-invasive in- References utero treatment of twin reversed arterial perfusion sequence by 1. van Gemert MJ, van den Wijngaard JP, Vandenbussche FP. high-intensity focused ultrasound. Ultrasound Obstet Gynecol Twin reversed arterial perfusion sequence is more common 2013;42:112–4. than generally accepted. Birth Defects Res A Clin Mol Teratol 15. Lewi L, Valencia C, Gonzalez E, Deprest J, Nicolaides KH. 2015;103:641–3. The outcome of twin reversed arterial perfusion sequence diag- 2. Moore TR, Gale S, Benirschke K. Perinatal outcome of forty- nosed in the first trimester. Am J Obstet Gynecol 2010;203: nine pregnancies complicated by acardiac twinning. Am J 213.e1–4. Obstet Gynecol 1990;163:907–12. 16. Berg C, Holst D, Mallmann MR, Gottschalk I, Gembruch U, 3. Lee H, Bebbington M, Crombleholme TM; North American Geipel A. Early vs late intervention in twin reversed arterial Fetal Therapy Network. The North American Fetal Therapy Network Registry data on outcomes of radiofrequency ablation perfusion sequence. Ultrasound Obstet Gynecol 2014;43:60– for twin-reversed arterial perfusion sequence. Fetal Diagn 4. Ther 2013;33:224–9. 17. Sugibayashi R, Ozawa K, Sumie M, Wada S, Ito Y, Sago H. 4. Ruiz-Cordero R, Birusingh RJ, Pelaez L, Azouz M, Rodriguez Forty cases of twin reversed arterial perfusion sequence treated MM. Twin reversed arterial perfusion sequence (TRAPS): an with radio frequency ablation using the multistep coagulation illustrative series of 13 cases. Fetal Pediatr Pathol 2016;35:63– method: a single-center experience. Prenat Diagn 2016;36:437– 80. 43.
Volume 24 | Issue 2 | August 2016 109 A L J O A T U N R I N R A E L P Clinical Guidelines
P L E R A Perinatal Journal 2016;24(2):110–127 I N N R A U T A L J O
Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
Cihat fien1, Murat Yayla2, Olufl Api3, Elif Gül Yapar Eyi4, Burcu Artunç Ülkümen5; Diabetes and Pregnancy Study Group of Turkish Perinatology Society 1Department of Perinatology, Cerrahpafla Medical School, Istanbul University, Istanbul, Turkey 2Gynecology and Obstetrics Clinic, Ac›badem International Hospital, Istanbul, Turkey 3Department of Perinatology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey 4Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital, Ankara, Turkey 5Department of Obstetrics and Gynecology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
Abstract Özet: Gebelikte diyabet: Tan› ve tedavi. Türk Perinatoloji Derne¤i Uygulama Rehberi While the routine approach for the diagnosis of gestational diabetes Gebelik diyabetinin tan›nmas›nda 50 g glukoz tarama testi ve pozi- is 50-g glucose tolerance test and 100-g OGTT in cases of a posi- tif tarama olgular›nda 100 g OGTT ile tan›n›n sa¤lanmas› uygulan- tive screen, a new approach was brought to agenda after it was found makta olan bir yaklafl›m iken, Hyperglycemia and Adverse Pregnancy in the study of Hyperglycemia and Adverse Pregnancy Outcome Outcome (HAPO) çal›flmas› sonucu kan flekeri düzeyleri ile gebelik (HAPO) study that there is a linear relationship between blood glu- sonuçlar› aras›nda do¤rusal iliflki oldu¤u, bunun da her de¤er art›fl› cose levels and gestational outcomes, and this was found to be close- ile yak›n iliflkili bulundu¤unun saptanmas›ndan sonra, yeni bir yak- ly associated with each value increase. It was shown that the lafl›m gündeme gelmifltir. Giderek klinik uygulamada yer bulan 75 g approach of establishing diagnosis based on a single value at once OGTT ile tek seferde ve tek de¤ere dayal› tan› konulmas› yaklafl›- with 75-g OGTT which is recently common in clinical practice m›, gebe popülasyonunun %18’ine tan› koydurmakla beraber, son- helps 18% of pregnant population to get diagnosed, and the diet and ras›nda yap›lan diyet ve egzersiz uygulamas›n›n, gebelik sonuçlar›n› exercise following the diagnosis improved gestational outcomes and iyilefltirdi¤i ve hatta gebelik diyabeti tan›s› almayan obez olgularda affected gestational outcomes even in obese cases without gestation- bile gebelik sonuçlar›n› olumlu etkiledi¤i ortaya konulmufltur. Ge- al diabetes. Pregestational obesity having effect on gestational out- belik öncesi obezitenin gebelik sonuçlar› üzerine, gebelik diyabeti comes even though there is no diagnosis of gestational diabetes and tan›s› olmad›¤› halde, etkili olmas› ve gebelikte kilo art›fl›n›n kontrol finding that keeping weight gain during pregnancy under control is alt›na al›nmas›n›n gebelik sonuçlar›n› iyilefltirmesinin saptanmas›, improving gestational outcomes reveal the importance of this mat- konunun önemini daha da gözler önüne sermektedir. Tek de¤ere ter. While 75-g OGTT procedure based on single value increases dayal› 75 g OGTT uygulamas›, iki aflamal› önce tarama ve akabinde the number of cases who are established the diagnosis of gestational tan› testi uygulamas›na oranla gebelik diyabeti tan›s› alan olgu say›- diabetes compared to the two-step screening and diagnosis test, diet- s›n› art›rmakla beraber; bu tan›y› alan olgularda diyet-egzersiz uygu- exercise practice in cases with such diagnosis is a condition which lamas›n›n, gebede kilo art›fl›n› kontrol alt›na alan ve ayr›ca gebelik keeps weight gain during pregnancy under control and also has a sonuçlar› üzerine olumlu etki sa¤layan bir durumdur. Kan flekerinin positive impact on gestational outcomes. Glycemia being above the 1–2 haftal›k izlemleri ile gliseminin istenen s›n›rlar›n üzerinde olma- desired range with 1–2 weeks of follow-up of the blood glucose will s›, medikal tedaviyi gerektirecektir. Bu ise beklenen ve istenen bir require medical treatment. This is an expected and desired target. hedef olmaktad›r. Bu nedenlerle, her gebeye tek de¤ere dayal› 75 g Therefore, applying 75-g OGTT based on single value has become OGTT uygulanmas› yeni klinik uygulama olarak yerini alm›flt›r ve the new clinical practice and it is recommended. This clinical prac- tavsiye edilmektedir. Bu klinik uygulama rehberi, Türk Perinatolo- tice guideline was prepared by the Diabetes and Pregnancy Study ji Derne¤i Diyabet ve Gebelik Çal›flma Grubu taraf›ndan haz›rlan- Group of Turkish Perinatology Society. m›flt›r. Keywords: Diabetes, OGTT, pregnancy. Anahtar sözcükler: Diyabet, gebelik, OGTT.
Correspondence: Dr. Cihat fien. Department of Perinatology, Cerrahpafla Medical School, Available online at: Istanbul University, Istanbul, Turkey. e-mail: [email protected] www.perinataljournal.com/20160242009 doi:10.2399/prn.16.0242009 Received: March 29, 2016; Accepted: March 29, 2016 QR (Quick Response) Code: Please cite this article as: fien C, Yayla M, Api O, Yapar Eyi EG, Artunç Ülkümen B; Diabetes and Pregnancy Study Group of Turkish Perinatology Society. Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society. Perinatal Journal 2016;24(2):110–127. ©2016 Perinatal Medicine Foundation Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
This clinical practice guideline was prepared by the have impact on prevalence.[7] At the same time, the dif- Diabetes and Pregnancy Study Group of Turkish ferences in GD screening models, the threshold values Perinatology Society to clarify controversial issues in used, and diagnostic criteria create differences in GD Turkey and facilitate clinical practice in the light of new prevalence. However, even though different methods scientific data obtained on pregnancy and diabetes and diagnostic criteria are used, it is definite that the recently. prevalence of Type 2 DM and also GD has increased Gestational diabetes (GD) which is one of the most in time highly, especially within last 20 years.[5,8] common medical complications of pregnancy is “the dysfunction of glucose metabolism which develops in the second half of pregnancy and disappears when pregnan- Pathophysiology and Risk Factors cy ends”.[1] Dysfunction of glucose metabolism may have Together with pregnancy, endocrine and metabolic various levels. While diet is sufficient generally, some changes occur right after conception. The main pur- may need insulin. pose of these changes occurring in maternal metabo- [9] In the common definition made by IADSPG (The lism is to provide sufficient nutrient to fetus. International Association of Diabetes and Pregnancy Particularly in the last trimester where fetal growth is Study Group), WHO (The World Health Organization) the fastest and therefore fetal nutrition need is the and ADA (The American Diabetes Association), those highest, the changes in maternal carbonhydrate and who are pregestational diabetic and noticed during the lipid metabolism become more distinct. During preg- pregnancy for the first time were distinguished from the nancy, plasma levels of lipolytic hormones increase and diabetes cases developing during pregnancy, and two dif- generally maternal fat use elevates, “glucose” is for the ferent definitions were set as “gestational diabetes” and use of fetus basically.[9] Maternal insulin resistance [2–4] “overt diabetes”. In this case, “gestational diabetes” begins at second trimester with the effect of metabolic defines the change which really appears during pregnan- and hormonal changes and becomes distinctive at third cy and is diagnosed at the second half of pregnancy by trimester. In this way, insulin resistance increases tests and developing in the presence of “pancreas which much more with the increase of the levels of hPL cannot deal with the diabetogenic changes” of pregnan- [5] (human placental lactogen), hPGH (human placental cy. The pregnancy itself is the condition of “physiolog- ical insulin resistance”. “Overt diabetes” defines the dia- growth hormone), estrogen, progesterone, CRH, cor- betes cases which have the metabolic processes at the tisol, prolactin, somatostatin and probably tumor α early periods of pregnancy almost same with non-gesta- necrosis factor (TNF- ) that have diabetogenic effects. tional condition, and identified even in the first trimester All these changes reach their peak level approximately where insulin resistance is not clear yet. The cases which at the 30 weeks of gestation. Insulin resistance which do not meet “overt diabetes” criteria in the tests per- develops as a result of normal physiological changes formed during gestational period but not found to have a during pregnancy is required for sufficient nutrition normal carbohydrate metabolism, either, are diagnosed and growth of fetus.[9] Since maternal pancreas cannot as “gestational diabetes” and their follow-up and treat- deal with this situation when increased insulin resist- ment are carried out accordingly. ance is encountered, these physiological changes result in GD which is a pathological condition.[5] In fact, Prevalence pathophysiological mechanisms developing in the for- About 3–25% of pregnant women are established with mation of GD show similarities substantially with GD diagnosis.[6] The main reason for different GD Type 2 DM. In both cases, a substantial increase occurs incidence rates among the population investigated is in the insulin resistance as the week of gestation the difference in the incidence rate of Type 2 diabetes advances and insulin response is not sufficient. mellitus (DM) in the society.[7] Also, maternal obesity Risk factors for gestational diabetes are defined and increasing at young ages, decreased physical activity, it was asserted to perform glucose screening/diagnostic increased consumption of convenience food, and tests in pregnant women having these risk factors. advanced maternal age and race are other factors which These risk factors are listed in Table 1.
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Table 1. Risk factors for gestational diabetes. When planning gestational diabetes screening pro- gram, the characteristics of the population under inves- • Type 2 DM history in the family (especially in first degree relatives) [10,11] tigation are also important. For instance, only 10% of • GD history in previous pregnancy[11] • Obesity (body mass index, BMI ≥30/m2)[10–12] the population in the USA is evaluated within low risk - It is remarkable that 60–80% of GD cases are obese. Also, GD risk group. Therefore, it is wise to perform tests on every increases as BMI increases.[11] Cardiometabolic risk factors such as pregestational hypertension and borderline high blood pressure val- pregnant woman instead of carrying out a risk-orient- [20] ues were also associated with increased GD risk.[12] ed screening in the USA. Besides, considering the - Obesity is associated with inflammatory changes. There is an risk factors mentioned above, there are few pregnant increase in inflammatory cytokines, especially in the levels of TNF-α, IL-6, NFκB, PAI-1 and CRP.[13] Glucose levels chronically increased women left. Hence, it does not seem logical to perform with obesity cause the modification of building blocks such as nucle- ic acids and proteins into advanced glycation end products (AGE). screening based on risk factors. The accumulation of AGE which is fast and higher than physiologi- cal levels causes permanent damages in the tissues. Today, AGE for- mation is held responsible in the physiopathology of many diseases Screening and Diagnosis: Why Important? in diabetes cases including neurodegenerative diseases, metabolic syndrome and vasculopathies.[14] As a respond to AGE formation, a Clinically identifying gestational diabetes is significant series of inflammatory response is initiated with NFκB pathway, and the tissue damage created with the activation of T-cells and the basically for preventing gestational complications, release of inflammatory cytokines in particular results with vascu- improving fetal and neonatal outcomes and to prevent lopathy and fibrosis.[15,16] Therefore, the development of complica- tions such as myocardial infarction (MI), atherosclerosis, stroke etc. its long-term effects on next generations. While some of is not a surprise in obesity and DM patients.[16] The same mechanism the complications developing associated with GD may explain the appearance of vascular complications basically such as insufficient placentation, preeclampsia, IUGR, sudden infant appear in the early period, some of them are seen in the death under poor conditions caused by chronic hyperglycemia as long-term. Preterm labor, macrosomia, birth trauma well as obesity during pregnancy. • Obesity is a preventable risk factor. Therefore, it should be taken and sudden infant death can be listed among the fetal seriously and patient should be informed during preconceptional complications associated with GD.[21–23] Among the early period and ensured to lose weight. • Ethnical group[10,11] complications in the newborns of GD mothers, there - In the diabetes prevalence studies performed in Turkey, DM preva- are polycythemia, hyperviscosity, hypoglycemia, lence was found as 13.7% according to the results of TURDEP-II per- formed with the participation of 26,000 individuals who were 20- hypocalcemia, hyperbilirubinemi, respiratory distress [24,25] year-old and above in 2010.[17] Almost half of the cases in Diabetes syndrome (RDS). Among the long-term complica- Mellitus group consist of newly-diagnosed cases. Diabetes prevalence varies according to the regions in Turkey. While Northern Anatolia tions, obesity, metabolic syndrome, Type 2 DM and Region has the lowest prevalence rate (14.5%), Eastern Anatolia increase in hyperactivity prevalence were found in the Region has the highest prevalence rate (18.2%). Eastern Anatolia [26,27] Region was found to be the region with the lowest awareness for dia- infants of GD mothers. Preeclampsia risk, increased betes as well as the region having the highest prevalence rate.[17] operative labor risk and polyhydramnios can be listed - Compared to TURDEP-I[18] study performed in 1998, the results [28,29] found by TURDEP-II prevalence study showed that the diabetes among the maternal risks. Also, the risk for Type 2 prevalence rate increased for 90% and obesity for 44% in Turkey.[17] DM, metabolic syndrome and coronary artery disease - Another issue revealed by TURDEP-II study is that diabetes preva- [30,31] lence rate increased significantly in those who are in reproductive increased in the long-term in GD mothers. period.[17] Identifying GD in the early period decreases - Considering the world population, diabetes prevalence is about 8.4%.[19] In the light of these data, our country is among the regions preeclampsia risk for 40% and macrosomic infant risk with the highest prevalence according to comparative worldwide for 50%. Additionally, shoulder dystocia and brachial diabetes prevalence studies. - It is known that GD prevalence is high among those originated from plexus palsy risks decrease for 60%. Early detection of South Asia, black Caribbean and Middle East. GD also decreases stillbirth risk.[32] • Being older than 25.[10] • Smoking[10] • Macrosomic infant history[5,11] Frequent Obstetric and Perinatal • History of unexplained perinatal loss and baby with malformation[5] • Maternal birth weight being >4.1 kg or <2.7 kg[5] Problems in Gestational Diabetes • A medical condition that will cause susceptibility to diabetes development (such as Cushing’s syndrome, polycystic ovary syndrome, glucocorticoid It is known that the presence of chronic hyperglycemia use, presence of hypertension etc.)[5] ongoing especially in the last 4–6 weeks of gestation is • Gaining too much weight between pregnancies or during pregnancy.[5,11] associated with sudden fetal death associated with possi- [33,34] • Multiple pregnancy[11] ble acidosis even in normal fetuses anatomically. • Short height[11] Even in GD cases with well-controlled metabolism, fetal [11] • Sedentary life-style macromosia, neonatal hypoglycemia, polycytemia and
112 Perinatoloji Dergisi Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
jaundice risks increased although there is no increase in growth restriction (IUGR) and presentation anom- perinatal mortality.[21] Also, cesarean section is recom- alies. The rate of cesarean is even higher in macrosom- mended when estimated fetal weight is ≥4500 g.[1] ic fetuses in cases where glucose control cannot be established adequately. As the diabetes control gets Macrosomia worse, the cesarean rate increases accordingly. The most significant factors here except fetal weight are the It is the most common complication seen in gestation- failure of labor induction and fetal asphyxia. Cesarean al diabetes. Maternal factors associated with macroso- section is recommended in diabetic pregnancies with mia are hyperglycemia, mother being overweight, fetal weights estimated 4000 g and above.[1] Normal being obese during pregnancy (>18 kg), advanced [35,36] vaginal delivery is recommended in other cases, and maternal age and multiparity. While the rate of applying cervical prostaglandin in cases where labor women delivering baby over 4500 g is 2% in the gen- induction is required is the only logical method to eral obstetric population, it is 4% among women with choose. GD diagnosis.[37] It is reported that 20–30% of the Timing of delivery is also a problematic issue for infants of women with GD diagnosis but not undergo- [38] diabetic pregnancies. In cases with pregestational dia- ing treatment born above 4000 g. betes where glucose is well controlled, planning deliv- Fetal growth rate increases particularly in the sec- ery after 39 weeks is suitable.[42] However, either with ond half of pregnancy. Maternal hyperglycemia (post- or without insulin, no safe delivery week has been prandial hyperglycemia in particular) in this period determined to recommend in the perspective of evi- causes fetal hyperinsulinemia and fetal growth is trig- dence-based medicine for GD cases.[1] Therefore, 39 gered. Macrosomic fetuses of diabetic pregnant women weeks of gestation should be aimed as in cases with are different anthropometrically from the macrosomic overt diabetes. fetuses of normal pregnant women. There is excessive The frequency of fetal well-being tests is quite con- fat accumulation in the shoulders and bodies of these troversial. In GD cases with well-controlled metabo- fetuses. This increases the prevalence of shoulder dys- [39] lism, each physician and clinic may decide according to tocia, brachial plexus injuries and clavicle fracture. their own practices. However, GD and pregestational Similarly, cephalopelvic disproportion resulted in diabetes cases with poor glycemic control are under cesarean section is more frequent. Macrosomia is risk in terms of fetal asphyxia and the tests showing closely associated with neonatal hypoglycemia in par- fetal well-being should certainly be performed in this ticular. Unexplained sudden intrauterine death near group.[1] Tests showing fetal well-being can be begun term and asymmetric septal hypertrophy causing car- between 28 and 32 weeks according to the glycemic diac ventricle dysfunction are more frequent in these [40] control medical complications (nephropathy, vascu- infants. lopathy etc.) of patients.
Shoulder Dystocia and Birth Trauma Hypertension - Preeclampsia Macrosomia causes increase in the prevalence of shoul- They develop particularly during the late periods of der dystocia which may result in brachial plexus injury pregnancy. While the association between gestational and clavicular fractures in newborns of patients with diabetes and preeclampsia is revealed, the responsible GD. The prevalence of shoulder dystocia is 6–10 times [1] mechanisms are still unclear. It is considered that the higher in the infants of diabetic mothers. Brachial endothelial dysfunction in such cases cannot produce plexus injuries may cause a permanent damage in [41] prostacycline (PGI2) sufficient enough to meet elevat- 5–22% of the babies. ed angiotensin-2 and vasopressine. It is seen in 5–10% in all pregnancies. Preeclampsia is seen more frequent- Interventional and Cesarean Deliveries ly in diabetic pregnant women with vascular problems The rates of interventional and cesarean deliveries such as proteinuria in particular. The increase of peri- have increased depending on macrosomia, intrauterine natal mortality is 20 times higher than those with nor-
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mal blood pressure and it is considered as the main rea- Neonatal Metabolic Disorders son for maternal and fetal loss. While the relationship The prevalence of hypoglycemia, hypocalcemia, hypo- of insulin resistance with high blood pressure and obe- magnesemia, polycythemia and hyperbilirubinemia of sity was shown and this relationship was clearly defined babies born from women with gestational diabates is in men and non-pregnant women, the relationship of increased. glucose intolerance with the problems concurrent with hypertension in pregnant women could not be deter- Hypoglycemia mined with so accurate borders.[43] In the studies per- The incidence rate of hypoglycemia was found as formed, mean artery blood pressures of patients whose 25–40%.[47] The incidence rate of hypoglycemia was gestational diabetes is found in the early periods of reported high also in mothers with well-controlled [48] pregnancy and requiring insulin treatment were high- plasma glucose concentration. It is considered that er than the patients with normal glucose tolerance and intrapartum glycemic control in particular determines are regulated with diet. Also, there are authors claim- the hypoglycemia risk of newborn. If hypoglycemia is ing that pregnancy-induced hypertension is the clinical not detected and intervened on time, it may lead to reflection of insulin resistance. The relationship seizure, coma and brain damage. Therefore, glucose between increasing glucose level and the severity of follow-up should be monitored carefully following the preeclampsia has been shown in the studies.[44] This delivery until it is ensured that the metabolic control of problem is also the main reason of the premature labor the infant of diabetic mother. in diabetic pregnant women. Today, findings have Polycythemia and hyperviscosity been accumulating and it is considered that the insulin It is seen in 5–10% of diabetic pregnant women and resistance has a role in the development of preeclamp- closely related with glycemic control. Due to the sia, at least partially. It can be also thought that treat- decrease in oxygenation, erythropoietin levels of the ing insulin resistance with this mechanism will umbilical cords of infants of diabetic mothers are typi- decrease preeclampsia risk and even other anti-inflam- cally high and therefore the rate of polycythemia is matory effects of balancing carbohydrate metabolism increased in such infants.[24] Polycythemia leads to of insulin may be protective against the development of increase in the prevalence of postnatal hyperbilirubine- preeclampsia. In a meta-analysis including 11 random- mia and this also causes the increase in phototherapy ized controlled studies, the effects of insulin and met- need.[41] Another potential problem is the tissue damage formin treatment were compared and a significant and ischemia associated with hyperviscosity.[6] decrease was found in the pregnancy-induced hyper- tension with metformin treatment. Also, no difference Neonatal hypocalcemia and hyperbilirubinemia was found in terms of preeclampsia between the groups Neonatal hypocalcemia is a problem seen almost in undergoing insulin or metformin treatment. 50% of the infants of diabetic mothers. It usually Therefore, the activities of insulin and metformin were appears in the first 3 days of life. The incidence of found similar on the prevalence of preeclampsia in hyperbilirubinemia is two times higher than health terms of treatment activity.[45] pregnancies and found 25% of the infants of diabetic mothers.[6] Another reason is the preterm labor associ- ated with diabetes. Polyhydramnios Polyhydramnios is seen in about 1/3 of the diabetic pregnancies. In such case, pregnant women should def- Postnatal Long-term Risks initely be evaluated in terms of fetal malformations Long-term risks for mother (particularly for the malformations of central nervous Diabetes develops in about half of the women with ges- system and gastrointestinal system). However, it is tational diabetes within 22–28 years in the future.[1] How considered that the presence of polyhydramnios in dia- short will the diabetes develop depends on the personal betic cases does not cause an additional increase in risk factors. Risks such as ethnic group, obesity, age and perinatal morbidity or mortality.[46] polycystic ovarian syndrome cause diabetes to develop
114 Perinatoloji Dergisi Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
faster. The possibility of developing Type 2 DM in the effect of being obese on fetal birth weight was patients requiring insulin during pregnancy is higher.[49] found to be an additional 174 g, it was 339 g in preg- For example, diabetes develops within 5 years following nant women who were GD.[55] [1] the pregnancy in 60% of Latin American women. Four groups were created in a cohort study investi- It was found in the studies performed that those gating the risk factors for metabolic syndrome (obesi- with gestational diabetes were under risk also in terms ty, hypertension, dyslipidemia, glucose intolerance) of metabolic syndrome, atherosclerosis and cardiovas- during childhood.[27] The groups were macrosomic cular dysfunction after postpartum third month.[50] baby and normal glucose tolerance (LGA+control), Hyperinsulinemia during pregnancy displays macrosomic baby and GD (LGA+GD), normal birth 30–50% decrease just after delivery. The decrease weight and normal glucose tolerance (AGA+control), slowly continues within following 6–12 weeks. Blood and normal birth weight and GD (AGA+GD). The glucose levels return to normal levels in the early post- development of insulin resistance during childhood natal period in most of the patients with GD. was found 10 times higher in LGA+GD group. The risk of developing metabolic syndrome at any period Therefore, evaluating patients between postpartum 6 was not found to be different in LGA and AGA control and 12 weeks in terms of glucose metabolism is very group, but it was found 3.6 times higher in LGA+GD important for determining the risk for the develop- group than AGA+GD group.[27] ment of Type 2 DM within following 5–10 years and establishing patient follow-up strategy.[51,52] It was found in the studies performed that the chil- dren of women with pregestational and gestational dia- Long-term risks for fetus betes had higher rates of attention-deficit hyperactivi- The investigators monitoring the infants of diabetic ty disorder and weaker motor functions during school [6] mothers for future diabetes development reported that ages. No change was observed in cognitive functions. diabetes develop in such infants 20 times more than the [42] infants of non-diabetic mothers. Obesity prevalence is Benefits of Glucose Tests also increased in these infants. The mechanisms of The purpose of screening tests during pregnancy is not maternal diabetes leading to future obesity in fetus are to diagnose but to determine the group under risk. It is not known clearly. In a prospective study comparing the still controversial if it is necessary to carry out diabetes infants of GD, Type 1 DM and non-diabetic pregnant women, it was found that more than 1/3 of the babies screening during pregnancy or not, if it should be done born from women with GD were overweight or obese to all pregnant women or only those under risk, and when they reach 11-year-old. This rate was found to be which method will be used for these tests. However, cur- two times higher than those delivered by Type 1 DM or rent data with the evidence-based medicine perspective non-diabetic women.[53,54] Also, as another important show us that performing screening and diagnostic tests point of this study, it was found that the maternal obesi- for GD is very significant in order to identify GD and do ty during early pregnancy period is the most significant appropriate management plans, to decrease early period factor determining the risk for infants of women with neonatal and maternal morbidities such as macrosomia, GD being overweight at 2-, 8- and 11-year-old (and shoulder dystocia and preeclampsia and to determine therefore the insulin resistance at early period). It was metabolic syndrome and related risks on time which are reported that smoking during pregnancy is also associat- expected for mother and infant in the long-term. ed with the risk for childhood obesity. This result was Screening and diagnostic tests performed in the found independent from GD treatment and macrosom- second trimester are done according to preferred test [54] ic birth. The results of this study are remarkable for or by drinking 75-g liquid containing glucose as a sin- revealing how the preventable reasons of obesity becom- gle step test or 50-g and then 100-g if necessary as a ing a serious public health issue is important. two-step test and then evaluating venous plasma blood In the HAPO (Hyperglycemia and Adverse sample. These tests have no serious maternal or fetal Pregnancy Outcome) study, which is one of the most effects. Only certain patients may have problem for significant studies on gestational diabetes performed, consuming hyperosmolar liquid (more distinct in 100-
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g glucose).[5] Therefore, 75-g glucose tolerance test is cases who undergo diagnostic test. With 140 mg/dl considered as diagnostic test at a single step. threshold value, the sensitivity was calculated as 80% When test results indicate GD, first the diet-exer- and specificity as 90%, and the diagnosis of approxi- [59] cise is planned according to the week of gestation and mately 20% of the cases are overlooked. then medical treatment later if necessary. Also, the In 10% of the cases, serum glucose level in glucose family should be informed about perinatal risks that are tolerance test is between 130 and 140 mg/dl. associated with GD and fetal monitorization is Therefore, when the threshold value is decreased to required in case of necessity and the increase of prena- 130 mg/dl in glucose tolerance test, the sensitivity of tal examination frequency.[5] In a study in which the the test increases to 90; however, the number of cases with and without screening were modeled, it was patients referred to diagnostic tests increases for 60%. shown that performing the test in populations with In a study conducted in 2002, the sensitivity and speci- high GD and Type 2 DM prevalence was beneficial ficity values were identified for GD screening methods both for preventing Type 2 DM and costs.[44] Without and these values were given in Table 2.[60] Finally, ADA any significant decrease in the number of patients and ACOG recommend glucose threshold value in which are required to be evaluated with laboratory serum as 140 mg/dl.[1,2] screening method, not screening patients with low risk may lead to overlook some patients with GD. Two-Step Glucose Test Threshold values checked in venous serum and evalua- Glucose Tests tion of 50-g GTT are as below:[1] No diagnostic test is Maternal venous plasma changes under normal condi- required for 50-g GTT <140 mg/dl. In this case, nega- tions are as follows when performing glucose tolerance tive predictive value is about 85–90%. So, the risk for test: preprandial blood glucose (PBG) is between 80 and overlooking GD in glucose values below 140 mg/dl is 90 mg/dl. Within approximately 4–5 minutes, the solu- 10–15%.[1] tion containing 75-g glucose is drunk and BG level If 50-g GTT is between 140–180 mg/dl, diagnostic increases up to 130–140 mg/dl within 30–40 minutes, it 3-hour 100-g OGTT is applied. GD diagnosis is estab- decreases slightly below PBG level within 120–150 min- [56,57] lished in case that two of the values are positive in 100-g utes; at the end of 180 minutes, PBG level is reached. In the individuals with normal carbohydrate metabo- OGTT: If PBG is >95 mg/dl, 1-hour BG is >180 mg/dl, lism, normal glucose levels are reached within about 2 2-hour BG is >155 mg/dl, 3-hour BG is >140 mg/dl and ≥ hours. These tests have no risk for fetuses.[5] 50-g GTT is 180 mg/dl, the patient is directly estab- lished GD diagnosis and the treatment is initiated. It is still debated which screening should be done for GD (screening everyone or risk-based approach) and which test should be used.[58] The reason for this Single-Step Glucose Test dispute is that there is no distinct definition in the In 2010, IADPSG (International Association of world in terms of the criteria for screening everyone Diabetes and Pregnancy Study Group) recommended and it is not clear which glucose intolerance case will new criteria for GD diagnosis. These diagnosis criteria provide treatment benefit. At this point, screening test should be selected by considering the purposes of screening and cost-benefit balance. Table 2. Sensitivity and specificity of the methods used in GD diag- nosis.[60] There are publications stating that GD diagnosis is delayed and there are high false results which are about Screening method Sensitivity Selectivity 10–20% by applying 100-g OGGT to those who had (%) (%) [59] abnormal results from 50-g glucose test. Risk factors 50 66 There is difference of opinion on the threshold value Random glucose measurement 40 90 of 50-g glucose tolerance test. When threshold value is HbA1c 40 90 considered as 140 mg/dl, 3-hour OGTT is performed in 50-g GTT (1-hour 140 mg/dl) 59 91 75-g OGTT 79 83 10–15% of cases and GD is detected in 20–40% of the
116 Perinatoloji Dergisi Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
was determined with HAPO study where the results of not so much, and applying diet-exercise program to a multinational 25,000 pregnant women were investigat- wider pregnancy group providing positive effects not ed.[61] New IADPSG criteria were mainly prepared by only on glucose levels but also gestational outcomes focusing on the perinatal risk of parameters which are should not be overlooked. >90 percentile. Accordingly, it is recommended to Since Type 2 diabetes is frequently seen in Turkey, check PBG and HbA1c or spot blood glucose (sBG). If it can be tolerated easily and done at a single step and PBG is >126 mg/dl and HbA1c is >6.5% or sBG is it is also a diagnostic test, applying 75-g OGTT based >200 mg/dl, it is recommended to consider it as overt on single value positivity to all pregnant women should diabetes and treat accordingly. If the results are not be addressed as the most appropriate approach. consistent with overt diabetes, but PBG is ≥92 mg/dl yet below 126 mg/dl, it is recommended to treat by considering it as GD. If PBG is below 92 mg/dl, it is To Whom and When to Apply Glucose Test? recommended to test with 75-g OGTT between 24 In the United States of America, it is logical to screen and 28 weeks of gestation. The diagnosis criteria of 75- each pregnant woman since they have at least one of g OGTT can be listed as follows: If PBG is below 126 the risk factors that may have an affect on balancing mg/dl, it is consistent with overt diabetes. If at least carbohydrate metabolism during pregnancy in 90% of one of the values below is positive, it is consistent with pregnant women.[1] Also, there is no risk factor in about GD diagnosis: PBG ≥92 mg/dl, 1-hour BG ≥180 20% of pregnant women found to have GD.[5] As a mg/dl and 2-hour BG ≥153 mg/dl. result of the systematic review done by USPSTF (States Preventive Services Task Force), it was stated Which Glucose Test Should We Do? that it is required to screen everyone after 24 weeks of gestation, but it does not help to screen everyone dur- IADPSG criteria differ with the recommendation that ing early gestation period and that it is more significant performing screening in the first trimester according to perform risk-based screening during the first prena- to the algorithms used previously and testing with 75- [61] tal visit. g OGTT again in the second trimester if the result is negative in the first one.[2] ACOG recommends carry- If the patient has a risk factor for Type 2 DM (obe- ≥ 2 ing out screening in the risk group during the first sity, BMI 30 kg/m , history of GD or impaired glu- trimester. When IADPSG criteria were applied, the cose metabolism, polycystic ovarian syndrome etc.), rate of diagnosed GD cases increased to 18% but they screening during the first prenatal visit would be a log- [5] were not adopted by ACOG.[1] ical approach. Performing PBG evaluation in the risk group during first antenatal visit and 75-g OGTT dur- Since there was no optimal approach for the diag- ing 24–26 weeks of gestation if PBG is <92 mg/dl nosis of gestational diabetes, NIH (National Institutes of Health) held a consensus meeting with the aim of would be more appropriate. If the first screening is determining the most appropriate diagnostic approach.[32] The results of related 97 studies (6 ran- domized controlled studies, 63 prospective cohort Table 3. Points to consider in OGTT. studies and 28 retrospective cohort studies) were inves- tigated and continuous and positive relationship was • The test should be carried out in the morning. • Fasting is required for at least 8 hours and max. 14 hours. found between increasing glucose values and macroso- • Patient should be on diet for at least 3 days uninterruptedly (min. 150 mia, and between primary cesarean rates and increas- mg carbohydrate daily). If pregnant woman is on a diet poor for ing glucose values at 75-g OGTT. 50-g OGTT has carbohydrate before the test, the insulin response to the test is less than higher negative predictive value as well as suboptimal the expected and false positivity rate increases. • During the test, pregnant woman should be in sitting position and positive predictive values. should not make any effort. It was reported in a prospective randomized con- • Pregnant woman should not smoke for 12 hours before the test. trolled study doing cost analysis by comparing single- • Patient should rest for 30 minutes before preprandial glucose measurement. step and two-step screening that two-step screening is • After preprandial glucose measurement, patient should drink 75-g glucose solution within 5 minutes. more convenient for costs.[62] The cost difference being
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negative or no screening is performed in the early peri- seem convenient to use it in Turkey for screening pur- od, the screening should be carried out at 24–28 weeks poses. However, it is accepted as the “golden standard” of gestation.[5] for the follow-up of glycemic control. There are some matters to consider when conduct- In regions where healthcare service cannot be pro- ing glucose tolerance tests (Table 3). It is significant to vided sufficiently, checking PBG between 24 and 28 provide an environment close to basic physiological weeks of gestation can be a practical approach. In a conditions in order to standardize tests and measure- study conducted in China by compiling the data of 15 ments and to rule out other factors. hospitals where 24,584 pregnant women were screened, it was reported that performing diagnostic 75g OGTT on pregnant women whose PBG is What to Do in Pregnant Women Who between 4.4 and 5.0 mmol/L (79–90 mg/dL) will Cannot Tolerate Oral Glucose Test? reduce the requirement of 2-hour diagnostic test by Performing serial glucose measurement would be log- half.[65] However, when applying screening tests, a spe- ical approach in order to rule out hyperglycemic con- cific approach should be determined by considering ditions in pregnant women who cannot tolerate stan- the characteristics of population. It cannot be general- dard oral glucose tolerance test.[5] In pregnant women ized in this study since ethnical characteristics affect who have risk factors for GD in particular and cannot Type 2 DM prevalence and also different threshold [67] tolerate screening tests, it is necessary to perform ran- values were used in the study conducted in China. dom PBG and postprandial BG measurements. This approach is also convenient for patients who under- [5] May Glucose Tests be Harmful for Mother went gastric bypass operation. According to the and Fetus? review of Coustan et al., GD risk is very low in preg- nant women whose PBG is lower than 85 mg/dl at 24 It was shown that consuming concentrated hyperosmo- weeks of gestation.[61] However, additional tests and lar glucose solutions for GD screening and diagnostic measurements are required in values above this value.[5] tests may cause gastrointestinal osmotic imbalance which results with gastric irritation, delay in gastric dis- Also, the methods such as glucose screening in urine charge, nausea, and vomiting in less number of and random blood glucose measurement were evaluated patients.[5] In a study performed by Agarwal et al., it was in terms of screening activity but no significant result reported that 9.8% of 5142 pregnant women could not was found. HbA1c is significant for evaluating treatment complete 100-g OGTT. The major reason for being activity rather than screening and it gives information unable to complete the test was the vomiting of pregnant about metabolic process for at least 60 days. women. In 2% of the cases, various reasons were found such as children of pregnant women drinking the solu- HbA1c tion, eating food during test, not giving blood at required times and being unable to complete test in term In the studies performed, a proper threshold value with [68] of time. It was reported that OGTT has no side effects good sensitivity and specificity during GD screening [5,69] other than those stated above. could not be found for HbA1c. In four different stud- ies conducted on this matter, HbA1c threshold values were found 5.0, 5.3, 5.5 and 7.5, but no clear result was 2014 Cochrane Review: Different Results? obtained for detecting GD according to these val- In the Cochrane[70] review performed in 2014 and inves- [63–66] ues. In the study of Agarwal et al. performed on tigated the impact of GD screening on improving the 442 patients, it was concluded that HbA1c is a weak health of mother and neonate, few high quality evidences test for GD screening.[63] The population size in the on the improvement of maternal and neonatal health by study of Uncu et al. was 42 pregnant women and it was GD screening were found based on the data of 3972 stated that HbA1c did not provide any additional con- women and 4 studies (Bergus and Murphy, 1992; tribution.[64] For the reasons such as inconsistencies in Murphy et al., 1994; Griffin et al., 2000; Martinez the standardization of HbA1c, failure to measure at all Collado et al., 2003) which were consistent with the cri- clinics, technical problems and high costs, it does not teria among 31 studies.[71–74] These studies were carried
118 Perinatoloji Dergisi Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
out in limited regions. When thinking on GD risk and new threshold values should be used in screening mod- screening approach, the characteristics of the population els. In the light of the results of HAPO study, new investigated (such as ethnic group, nourishment habits IADPSG criteria were defined.[76] While single positive etc.) should be considered and interpreted accordingly. value being sufficient for the diagnosis and also the It would be useful to assess carefully these studies includ- threshold values being slightly lower increase the sen- ed in 2014 Cochrane review by considering their weak sitivity in the new IADPSG criteria, the prevalence of aspects and to remain distant towards the results and diagnosed GD cases increase to 18%.[1] These thresh- interpretations of this review in the current situation. old values correspond to mean glucose levels where Consequently, it seen that further studies are birth weight, umbilical cord C-peptide levels and required to determine which screening would be more macrosomia risk increase for 1.75 times. In cases estab- appropriate. Since only a particular part of the preg- lished with GD diagnosis according to these threshold nant population screened is established GD diagnosis, values, macrosomia, preeclampsia and preterm labor it is required to do sub-group analyses which are statis- risks increase 2 times. However, further studies are tically powerful to do comparison and have sufficient needed to get more information how gestational out- population. Also, other studies are required for deter- comes will improve or if they will improve or not mining the activity of other methods (such as capillary depending on the treatment in GD cases diagnosed blood sugar test, glucosuria etc.) which can be used according to IADPSG criteria. It was observed that instead of glucose tolerance tests that are applied sim- perinatal complications decreased from 4% to 1% in pler yet cannot be tolerated by some patients.[70] the study of Crowther et al. for randomized treatment activity on control group and the cases diagnosed with HAPO Study: Why Important? 75-g OGTT during 24–28 weeks. It was found that glucose control, diet and treatment program with HAPO study is an epidemiological research designed to insulin in required cases decreased perinatal morbidity seek an answer about how various levels of glucose intol- significantly.[48] A similar randomized study was con- erance affects fetal and perinatal outcomes during preg- ducted by Landon et al. on a milder case group in nancies. It is a study planned internationally and includ- 2009.[77] In that study, 50-g and 100-g glucose tests ing 25,505 pregnant women from various ethnical were used during 24–31 weeks of gestation on preg- groups. Its primary results were determined as macroso- nant group who had abnormal values in tests but the mia, primary cesarean rate, neonatal hypoglycemia and level of preprandial BG was below 95 g. While perina- hyperinsulinemia. Preterm labor, preeclampsia, new- tal losses (no perinatal death case) and severe newborn born intensive care unit, shoulder dystocia, birth trauma complications did not decrease with the treatment pro- and neonatal adiposity were considered as secondary gram applied in this study, a particular improvement [75] results. A continuous relationship was found between was observed in the rates of birth weight, shoulder dys- glucose levels (even below maternal diabetes limits) and tocia, cesarean and preeclampsia. Finding treatment perinatal outcomes such as birth weight and umbilical activity even in mild cases with this study shows that cord C-peptide levels. While there is no particular glucose level and perinatal outcomes are directly asso- threshold glucose level in predicting gestational out- ciated even without a particular threshold value of comes, it was found that there is a direct association with HAPO study.[75] While the rates of cases diagnosed gestational outcomes and complications as preprandial with GD increased twice by using 75-g and single value or 1-hour and 2-hour glucose levels increase (even with- seem as an advantage, they seem as an advantage in normal limits). Even though the outcomes of this assessing the results of Landon et al.’s study.[77] study are below overt diabetes levels, the more blood The direct association between perinatal outcomes glucose levels are kept under control, the more it reflects and glucose level found in HAPO study (also in low positively to the gestational outcomes. glucose level) show the significance and efficiency of However, observing poor gestational outcomes also diet-exercise program. In this sense, applying 75-g and in pre- and postprandial blood glucose levels that is single value OGTT to all pregnant women doubles the identified within “normal” levels make us consider that rates of gestational diabetes but it also helps to apply
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diet-exercise program to pregnant women and there- fetal macrosomia, it was argued that the patients with fore to improve perinatal outcomes. Although its activ- 50-g screening result over 140 mg/dl should be fol- ity on short-term outcomes was revealed by the studies lowed up closely in terms of fetal macrosomia like the published by Crowther et al.[48] and Landon et al.,[77] patients with gestational diabetes even though their there has been no study showing its activity on long- 100-g OGTT results are not positive.[82] In another term outcomes. It will become clearer with further study investigating the etiological factors in macro- studies to be performed on the activity of this new somic fetuses, maternal age being above 35, high pari- diagnosis and treatment approach. ty, high average of maternal height, weight gained dur- ing pregnancy being over 12 kg, high level of HbA1c, presence of polyhydramnios in current pregnancy and What Should We Recommend to Our the medical history with macrosomic infant were con- Patients in Terms of Glucose Test? sidered as the factors increasing macrosomia risk in As Perinatal Medicine Foundation and Turkish fetus.[83] Perinatology Society, we have tried to establish a screening model for GD screening in our country Type 1 / Type 2 Diabetes During Pregnancy within the perspective of evidence-based medicine. In Diabetes is the disorder of carbohydrate metabolism Turkey, single-step 75-g diagnostic test seems more affecting life considerably. It is a chronic disease lead- appropriate in terms of costs and patient compliance. ing long-term complications such as retinopathy, Considering GD complications in particular, diagnos- nephropathy and vascular diseases. It is seen in 2–5% ing under the light of our current information in order of women in England. While 5% of this group is Type to protect fetus and mother from these complications 2 DM, Type 1 DM is 7.5% and gestational diabetes is is an evidence-based and scientific approach. 87.5%. It is known that the rates of Type 1 and Type 2 diabetes gradually increase. Type 2 diabetes is fre- Studies on this Subject in Turkey quently seen in Africa, Caribbean, South Asia, Middle [6–8] It was shown in a study investigating the effects of high East and China in particular. pregestational maternal body mass index on gestation- Miscarriage, preeclampsia and preterm delivery are al outcomes that pregestational BMI is related with seen frequently in diabetic pregnant women (Type 1 more operative delivery and more neonatal prob- and Type 2). Besides, it should be remembered that lems.[78] GD prevalence was found as 21.1% in the retinopathy may get worse during pregnancy. study of Göymen et al.[79] It was claimed in the same Postpartum compliance problems such as stillbirth, study that there was no different in terms of GD rates congenital anomalies, macrosomia, birth trauma, peri- [79] natal mortality and hypoglycemia are seen more fre- when two-step or single-step screening is performed. quently.[22,23,31] In a study investigating maternal serum leptin and mal- ondialdehyde (MDA) levels in GD diagnosis and One of the first steps of making a successful follow- screening, it was reported that leptin, MDA and up in diabetic patients is to establish a good communi- HbA1c levels increased significantly in GD cases, but cation between healthcare professionals and patient. It is useful to provide detailed information on diabetes the findings found was increasing the specificity of the [80] and pregnancy as well as delivering this information to tests performed during the GD screening. In anoth- patient in written. In this way, patient has a referring er study comparing maternal serum adiponectin and source when required. leptin measurements in GD diagnosis and screening, it Perinatal Medicine Foundation and Turkish was shown that adiponectin was more sensitive but had Perinatology Society emphasize and recommend that equal specificity in the group which underwent 75-g the practices listed in Table 4 are significant to obtain OGTT. Adiponectin was found significantly low in the good perinatal outcomes in cases with overt diabetes group which underwent two-step screening.[81] and pregnancy (Recommendations 1–7). In a study evaluating 50-g screening and 100-g OGTT results of 690 pregnant women in terms of Conflicts of Interest: No conflicts declared.
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Table 4. Pregnancy and diabetes management.
Before pregnancy • Patient should be informed about the importance of regulating glucose level well before pregnancy and also maintaining this level after pregnancy. In this way, the awareness that it is possible to prevent miscarriage, congenital malformation, stillbirth and newborn death should be raised. - Significance of diet, weight and exercise - Hypoglycemia developing during pregnancy - How nausea-vomiting during pregnancy may affect glucose control - How the condition of large for gestational age may increase birth trauma, labor induction and cesarean possibilities - How it is important to manage the condition of diabetic retinopathy before (treating if necessary) and during pregnancy - The importance of maintaining glucose level well during labor in order to prevent newborn hypoglycemia and providing early lactation of infant after birth - Conditions which may develop and require special or intensive care in infant after birth even temporarily. • It should be informed in detail to such patients beginning from adolescence period that an unplanned pregnancy would be an undesired condition and it is very significant to conduct a well planned birth control and if it will be discontinued, to refer to doctor and make a pregestational plan.. • Diabetic patients planning pregnancy should be informed that: - Risks associated with diabetes during pregnancy is also associated with diabetes period - It is important to conduct conception until a well glucose control (HbA1c being below 6.1%) is provided - Glucose level targets, glucose monitoring, treatment options if necessary, and treatment options for problems associated with diabetes and pregnancy should be discussed - A closer cooperation is required during pregnancy and management plans such as emergency cases should be discussed in details. - Diet should be arranged for those planning to get pregnant - Weight loss program should be applied and informed about its significance for those planning to get pregnant and have BMI above 27 - It is important to have 5 mg/day folic acid certainly by those planning to get pregnant in order to decrease the risk for neural tube defect - It is very important to do glucose measurements by themselves and they should be recorded by times. - Type 1 diabetics in particular have to do ketonuria check with sticks when their glucose levels elevate or when they do not feel well. Reliability of diabetic drugs during pregnancy • They should be informed that metformin used alone or as a support for insulin is an effective drug to get glucose levels. Other diabetic drugs should be discontinued before pregnancy and insulin should be used instead. • It should be known that it was not shown in clinical studies that rapid-acting insulin analogues (aspart or lispro) used during pregnancy have negative effects on fetus or newborn. • It should be stated to those undergoing insulin treatment or planning to get pregnant that there is insufficient data on the use of long-acting insulin analogues during pregnancy and therefore NPH insulin has been still an option preferred. Treatment reliability of diabetic complications during pregnancy • ACE inhibitors and angiotensin-2 receptor antagonists should be discontinued before pregnancy or they should be discontinued as soon as possible when pregnancy is detected. Instead, other alternative treatments should be performed. • Statins should be discontinued as soon as possible when pregnancy is detected. Retina evaluation before pregnancy • Diabetic patients are absolutely required to have retina examination before pregnancy (if it is not performed within last 6 months). • It is useful to perform this examination first by drop and then digital imaging Renal examination before pregnancy • It is significant to examine kidneys including microalbuminuria before discontinuing birth control. If creatinine is ≥120 or GFR is below 45, it should be re-evaluated after nephrology consultation.
Gestational follow-up • Where possible, preprandial glucose level should be kept about 65–95 mg/dl and 1-hour glucose below 140 mg/dl, and importance of these levels should be explained. • Patients with overt diabetes using insulin should be informed about the possibility of hypoglycemia attacks during first trimester in particular and the precautions. • The cases whose glucose levels cannot be managed despite insulin use should be explained that using insulin pump is another method. • Conditions where diabetic ketoacidosis is in question should be evaluated in hospital immediately and they should be put under care. • It should be explained that diabetic retinopathy does not inhibit vaginal labor. • The necessity of performing fetal cardiac examination during 13–14 weeks and also 18–22 weeks of gestation should be explained to all diabetic pregnant women. • Unless there is fetal growth restriction, it is not necessary to do fetal well-being test routinely in diabetic pregnant women before 38 weeks of gestation. • It should be explained to pregnant women with overt diabetes that they should visit for diabetes control with 1–2 weeks of interval. Gestational follow-up • First examination: Explaining the importance of and teaching glucose control, detailed anamnesis check for diabetes, drugs used, retina/kidney assessment • Evaluating pregnancy at 7–9 weeks of gestation • 13–14 weeks of fetal anatomy and fetal ECHO examination, diabetes and gestational interactions, delivery and lactation and newborn information • Reevaluating if retinopathy/nephropathy is found • Fetal anatomy and fetal ECHO examination at 20–22 weeks of gestation
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Table 4. [continued] Pregnancy and diabetes management.
• Fetal development and amniotic fluid examination at 28 weeks of gestation, re-check if retinopathy/nephropathy is not detected in the first examination • Fetal development and amniotic fluid check at 32 weeks of gestation • Informing about fetal growth and amniotic fluid examination at 36 weeks of gestation, delivery timing-method and delivery management, analgesia/ anesthesia, labor and then hypoglycemia management, infant care after delivery, lactation and its effect on glucose control, and conception • Fetal well-being tests in pregnant woman with approaching delivery at 38 weeks and inducting labor or planning cesarean if necessary • Fetal well-being tests at 39 weeks of gestation • Fetal well-being tests at 40 weeks of gestation • Fetal well-being tests at 41 weeks of gestation Preterm labor • Checking if diabetes constitutes contraindication for the administration of steroid or tocolyis (without using beta mimetics) if necessary • Additional insulin will be required if steroid is administered, and glucose check should be performed more strictly Timing and management of delivery • In cases with normal fetal growth, delivery can be done by labor induction after 38 weeks of gestation and if necessary, cesarean can be planned • If fetal macrosomia is in question, pregnant woman should be informed about the risks of vaginal delivery, labor induction and cesarean. • In diabetic pregnant women, it would be beneficial to carry out evaluation and inform in terms of anesthesia in third trimester. • If general anesthesia is applied, it should be known that glucose check is required every 30 minutes and it should be monitored until the effect of anesthesia diminish after delivery. Managing labor • Capillary glucose level should be checked every hour during labor and it should be kept at 75–125 mg/dl. • Applying dextrose infusion as well as insulin as of the onset of labor • If glucose level cannot be maintained at 75–125 mg/dl also in other cases, applying insulin together with dextrose infusion Newborn management • Diabetic pregnant women should deliver in a hospital capable of newborn resuscitation for 24 hours. • Babies of diabetic mothers should be kept near their mothers. If any clinical complication or abnormal finding develops, then they should be monitored under special or intensive care conditions. • Glucose control of the infants of diabetic mothers should be performed every 2–4 hours routinely and if there is any clinical finding, they should be controlled for polycythemia, hyperbilirubinemia, hypocalcemia and hypomagnesemia. • If there is any cardiomyopathy finding including congenital cardiac anomaly or murmur, fetal ECHO should be carried out. • Infants of diabetic mothers with following findings should be monitored in newborn intensive care units: - Hypoglycemia with clinical finding - Respiratory distress - Cardiomyopathy or cardiac failure due to congenital cardiac anomaly - Newborn encephalopathy - Polycythemia finding (need for partial blood exchange) - Intravenous fluid need - Need for gavage - Need for intense phototherapy and bilirubin control - Those born before 34 weeks • Each obstetrics clinic should have and provide written information form for preventing, identifying and managing newborn hypoglycemia. • Despite all kinds of efforts, if blood glucose level decreases below 36 mg in two consecutive measurements and if there is any abnormal clinical finding, gavage or intravenous dextrose application should be performed. • If clinical finding of hypoglycemia is observed, glucose control should be performed immediately and dextrose should be rapidly administered intravenously. • Newborns of diabetic mothers should be fed right after delivery (within 30 min.) and then every 2–3 hours. • Those with Type 2 diabetes may continue using metformin but other drugs should not be used during lactation. • The drugs for diabetic complications discontinued before and during pregnancy should be continued. Effects of lactation on glucose control • Those with overt diabetes should decrease insulin doses right after delivery and they should be managed with frequent glucose control until the optimum level is obtained. • Those with overt diabetes and using insulin should be informed that hypoglycemia risk will increase after delivery and they should keep available food or snack as they may be required before and after lactation. • If those with gestational diabetes are using drug, they should discontinue their treatment right after delivery. Postpartum follow-up and information • After delivery, those with overt diabetes should be referred to the clinic that they are followed up. • The glucose levels of puerperants with gestational diabetes should be checked before discharging. • Those with gestational diabetes should be warned and informed about the risk for developing hypoglycemia. • Those with gestational diabetes should be checked for weight during postpartum period, diet-exercise applications should be maintained and their preprandial glucose levels should be checked at 6 weeks (not OGTT). • Those with gestational diabetes should be warned and informed that they may be diabetic later. They should undergo preprandial blood glucose check or OGTT in advance when they plan pregnancy.
122 Perinatoloji Dergisi Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
Recommendation 1 Recommendation 4
Informing each pregnant woman about pregnancy Diagnosis in gestational diabetes and diabetes Diabetes • In the first visit, they should be informed in detail Yes about pregnancy process and this should be provid- diagnosis criteria ed also in written. Gestational diabetes should cer- No tainly be explained as well as other gestational prob- lems. For that purpose, the matters below should Overt Evaluating absolutely be discussed with pregnant woman, and; diabetes gestational diabetes • If the diagnosis of gestational diabetes is established, glucose level can be taken under control with diet and exercise in many cases, Gestational diabetes No Yes risk factor • If diet and exercise are insufficient, 10–20% of cases may require taking insulin or tablets, • More frequent follow-up and procedures may be 75-g OGTT required during pregnancy and delivery in those established with the diagnosis of gestational diabetes, Preprandial blood glucose At first ≥92 mg At weeks • If gestational diabetes cannot be detected, it should antenatal 1-hour blood glucose 24–28 be informed that the risk for birth complication examination ≥180 mg OGTT such as shoulder dystocia can be decreased. OGTT 2-hour blood glucose ≥153 mg Recommendation 2 Single value positive Recommendations for gestational diabetes diagnosis Diagnosis: Gestational Diabetes • If there are risk factors in the first prenatal visit, OGTT should be performed with 75-g glucose. • If there is no risk factor, OGTT should be performed PBG: 92–126 mg Gestational diabetes with 75-g glucose at 24–28 weeks of gestation. PBG: ≥126 mg Overt diabetes • At postpartum 6–12 weeks, patients should be HbA1C: ≥6.5% Overt diabetes screened for diabetes by using diagnosis criteria in Blood glucose: ≥200 mg Overt diabetes those non-pregnant women with OGTT. • Women with gestational diabetes history should be screened for diabetes through entire lifetime at least once every 3 years. Recommendation 5 • Changing life-style should be recommended for those with gestational diabetes history in order to Detailed information and education stated below should prevent diabetes. be provided to pregnant women established with gestational diabetes on diet-exercise-medical treatment. • Recommending GD pregnant women to take food Recommendation 3 with low glucose index and to prefer food rich in protein and unsaturated fatty acid and fish Risk factors for gestational diabetes • Pregnant women with gestational diabetes and BMI • GD presence in previous pregnancy over 27 to have a diet not exceeding daily 25 • Pregestational glucose intolerance diagnosis kcal/kg/day and 1750 calories for a pregnant woman • T2DM history in the family (especially in first degree who is 70 kg and to do a daily exercise program for relatives) approx. 30 minutes (morning–evening if possible) • Macrosomia and polyhydramnios history in previous • To undergo insulin or tablet treatment in cases whose pregnancy glucose level cannot be maintained within 1–2 weeks • Mother gaining too much weight in previous pregnancy despite diet and exercise, (>20 kg) • If it is found in fetal examinations that abdominal cir- • Preprandial blood glucose >95 mg/dl and presence of cumference is over 70 percentile, insulin or oral treat- glucosuria ment may be required 2 • Overweight (BMI >25 kg/m ) • Treatment options with insulin (crystallized insulin or • Advanced age (>25-year-old) rapid-acting insulin analogues – aspart or lispro) and/or • Polycystic ovary syndrome drugs such as metformin and glyburide
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Recommendation 6
Follow-up during pregnancy • Evaluating blood glucose levels: Weekly preprandial and postprandial 1-hour regular blood glucose follow-up, monthly HbA1C measurement • Assessment of complications: Fundus examination at first trimester, follow-up at every trimester if necessary, follow-up of blood pressure and urinary albumin and creatinine at every visit. Consultation with specialists from related fields in case of any complication. • Assessing biochemical parameters: Analysis of thyroid functions, renal functions and urine, lipid profile, examination of hepatic functions (at the beginning, and according to the condition later), urinary albumin follow-up every visit. • Weight follow-up (weekly) and fetal growth follow-up (with 2–4 weeks of interval) • Training: Blood glucose, hypoglycemia treatment and insulin administration training should be repeated every trimester • Feeding: Daily 300 kcal is added in second and third trimesters to general calorie calculation. • Fetal development and amniotic fluid should be monitored, and anomaly screening and fetal cardiac anomalies should be investigated in Type 1 diabetes cases in particular. Follow-up criteria for gestational diabetes Follow-up during pregnancy • Evaluating glucose regulation: Preprandial and postprandial 1-hour blood glucose (a few times a week), HbA1C (every trimester). • Following up blood pressure and urinary albumin (every visit) • Weight follow-up (weekly) and fetal growth follow-up (with 2–4 weeks of interval) • Evaluating biochemical parameters: Thyroid functions, renal functions and urinalysis, lipid levels, hepatic functions etc. (in the beginning, then according to patient) • Training is necessary to complete delivery successfully. Postpartum follow-up At hospital • Measurement of preprandial and postprandial maternal 1-hour blood glucose • Newborn follow-up (within first 4 hours after birth, long-term if hypoglycemia is present) At home • Measurement of preprandial and postprandial 1-hour blood glucose (until first postpartum visit) • If follow-up results are normal in terms of diabetes during 3–6 months, evaluation 1 year later in the beginning and once every 3 years for the lifetime • Significance of diet and exercise and lifestyle.
References Recommendation 7 1. Committee on Practice Bulletins--Obstetrics. Practice Bulletin Treatment in gestational diabetes No. 137: gestational diabetes mellitus. Obstet Gynecol 2013; Capillary glucose 122:406–16. measurements 2. International Association of Diabetes and Pregnancy Study PBG <95 mg Groups Consensus Panel, Metzger BE, Gabbe SG, Persson Random postprandial Diet-exercise B, Buchanan TA, Catalano PA, Damm P, et al. International <140 mg association of diabetes and pregnancy study groups recom- mendations on the diagnosis and classification of hyper- glycemia in pregnancy. Diabetes Care 2010;33:676–82. PBG <95 mg Diet-exercise 3. World Health Organization. Diagnostic criteria and classifi- Random postprandial Insulin in meals >140 mg cation of hyperglycaemia first detected in pregnancy. Geneva: World Health Organization; 2013. 4. American Diabetes Association. Diagnosis and classification ≥ PBG 95 mg Insulin and of diabetes mellitus. Diabetes Care 2014;37 Suppl 1:S81–90. Random postprandial NPH in meals >140 mg 5. Coustan DR, Jovanovic L. Diabetes mellitus in pregnancy: screening and diagnosis. In: Nathan DM, Greene MN, Barrs
124 Perinatoloji Dergisi Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
VA, editors. UpToDate [Internet]. Waltham, Mass.: 19. International Diabetes Federation (IDF). Diabetes atlas. 6th UpToDate; 2014 [cited December 11, 2014]. Available ed. Brussels, Belgium: International Diabetes Federation; from: www.uptodate.com 2013. 6. Moore TR, Hauguel-De Mouzon S, Catalano P. Diabetes in 20. Danilenko-Dixon DR, Van Winter JT, Nelson RL, Ogburn pregnancy. In: Creasy RK, Resnik R, Greene MF, Iams JD, PL Jr. Universal versus selective gestational diabetes screen- Lockwood CJ, Moore TR, editors. Creasy and Resnik’s ing: application of 1997 American Diabetes Association rec- maternal-fetal medicine: principles and practice. 7th ed. ommendations. Am J Obstet Gynecol 1999;181:798–812. Philadelphia, PA: Saunders-Elsevier; 2014. p. 988–1021. 21. Horvath K, Koch K, Jeitler K, Matyas E, Bender R, Bastian 7. Ferrara A. Increasing prevalence of gestational diabetes mel- H, et al. Effects of treatment in women with gestational dia- litus: a public health perspective. Diabetes Care 2007;30 betes mellitus: systematic review and meta-analysis. BMJ Suppl 2:S141–S6. 2010;340:c1395. 8. Centers for Disease Control and Prevention. National 22. Jovanovic L, Knopp RH, Kim H, Cefalu WT, Zhu XD, Lee Diabetes Statistics Report: estimates of diabetes and its burden YJ, et al. Elevated pregnancy losses at high and low extremes in the United States, 2014. Atlanta, GA: U.S. Department of of maternal glucose in early normal and diabetic pregnancy: Health and Human Services; 2014. evidence for a protective adaptation in diabetes. Diabetes Care 2005;28:1113–7. 9. Petraglia F, D’Antona D. Maternal endocrine and metabol- ic adaptation to pregnancy. In: Lockwood CJ, Snyder PJ, 23. Schwartz R, Grupposo PA, Petzold K, Brambilla D, Eckler K, editors. UpToDate [Internet]. Waltham, Mass.: Hiilesmaa V, Teramo KA. Hyperinsulinemia and macroso- UpToDate; 2014 [cited January 06, 2014]. Available from: mia in the fetus of the diabetic mother. Diabetes Care www.uptodate.com 1994;17:640–8. 10. Solomon CG, Willett WC, Carey VJ, Rich-Edwards J, 24. Widness JA, Teramo KA, Clemons GK, Voutilainen P, Hunter DJ, Colditz GA, et al. A prospective study of pre- Stenman UH, McKinlay SM, et al. Direct relationship of gravid determinants of gestational diabetes mellitus. JAMA antepartum glucose control and fetal erythropoietin in 1997;278:1078–83. human type 1 (insulin-dependent) diabetic pregnancy. Diabetologia 1990;33:378–83. 11. Chasan-Taber L. Gestational diabetes: is it preventable? American Journal of Lifestyle Medicine 2012;6:395–406. 25. Cordero L, Treuer SH, Landon MB, Gabbe SG. Management of infants of diabetic mothers. Arch Pediatr 12. Hedderson MM, Darbinian JA, Quesenberry CP, Ferrara A. Adolesc Med 1998;152:249–54. Pregravid cardiometabolic risk profile and risk for gestation- al diabetes mellitus. Am J Obstet Gynecol 2011;205:55.e1–7. 26. Pettitt DJ, Lawrence JM, Beyer J, Hillier TA, Liese AD, Mayer-Davis B, et al. Association between maternal diabetes 13. Moller DE. Potential role of TNF-alpha in the pathogene- in utero and age at offspring’s diagnosis of type 2 diabetes. sis of insulin resistance and type 2 diabetes. Trends Diabetes Care 2008;32:2126–30. Endocrinol Metab 2000;11:212–7. 27. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syn- 14. Bao W, Min D, Twigg SM, Shackel NA, Warner FJ, Yue drome in childhood: association with birth weight, maternal DK, et al. Monocyte CD147 is induced by advanced glyca- obesity and gestational diabetes mellitus. Pediatrics tion end products and high glucose concentration: possible 2005;115:e290–6. role in diabetic complications. Am J Physiol Cell Physiol 28. Pettitt DJ, Knowler WC, Baird HR, Bennett PH. 2010;299:1212–9. Gestational diabetes: infant and maternal complications of 15. Artunc-Ulkumen B, Pala HG, Pala EE, Yavasoglu A, pregnancy in relation to third-trimester glucose tolerance in Yigitturk G, Erbas O. Exenatide improves ovarian and the Pima Indians. Diabetes Care 1980;3:458–64. endometrial injury and preserves ovarian reserve in strepto- 29. Evers IM, de Valk HW, Visser GH. Risk of complications of zocin induced diabetic rats. Gynecol Endocrinol 2015;31: pregnancy in women with type 1 diabetes: nationwide 196–201. prospective study in the Netherlands. BMJ 2004;328:915. 16. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the 30. Landon MB, Mele L, Spong CY, Carpenter MW, Ramin link between insulin resistance, obesity and diabetes. Trends SM, Casey B, et al.; Eunice Kennedy Shriver National Immunol 2004;25:4–7. Institute of Child Health, and Human Development 17. Satman I, Omer B, Tutuncu Y, Kalaca S, Gedik S, Dinccag (NICHD) Maternal–Fetal Medicine Units (MFMU) N, Karsidag K, et al.; TURDEP-II Study Group. Twelve- Network. The relationship between maternal glycemia and year trends in the prevalence and risk factors of diabetes and perinatal outcome. Obstet Gynecol 2011;117:218–24. prediabetes in Turkish adults. Eur J Epidemiol 2013;28:169– 31. Sibai BM, Caritis S, Hauth J, Lindheimer M, VanDorsten 80. JP, MacPherson C, et al. Risks of preeclampsia and adverse 18. Satman I, Yilmaz T, Sengül A, Salman S, Salman F, et al. neonatal outcomes among women with pregestational dia- Population-based study of diabetes and risk characteristics in betes mellitus. National Institute of Child Health and Turkey: results of the turkish diabetes epidemiology study Human Development Network of Maternal-Fetal Medicine (TURDEP). Diabetes Care 2002;25:1551–6. Units. Am J Obstet Gynecol 2000;182:364–9.
Volume 24 | Issue 2 | August 2016 125 fien C et al.
32. National Institutes of Health consensus development con- 47. Casey BM, Lucas MJ, MCIntire DD, Leveno KJ. Pregnancy ference statement: diagnosing gestational diabetes mellitus, outcomes in women with gestational diabetes compared with March 4-6, 2013. Obstet Gynecol 2013;122:358–69. the general obstetric population. Obstet Gynecol 1997;90: 33. Centers for Disease Control (CDC). Perinatal mortality and 869–73. congenital malformations in infants born to women with 48. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, insulin-dependent diabetes mellitus--United States, Canada, Robinson JS; Australian Carbohydrate Intolerance Study in and Europe, 1940-1988. MMWR Morb Mortal Wkly Rep Pregnant Women (ACHOIS) Trial Group. Effect of treat- 990;39:363–5. ment of gestational diabetes mellitus on pregnancy out- 34. Whitelaw B, Gayle C. Gestational diabetes. Obstet Gynaecol comes. N Engl J Med 2005;352:2477–83. Reprod Med 2011;21:41–6. 49. Tamas G, Kerenyi Z. Current controversies in the mecha- 35. Caughey A. Gestational diabetes mellitus: obstetrical issues and nisms and treatment of gestational diabetes. Curr Diab Rep management. In: Greene MF, Barss VA, editors. UpToDate 2002;2:337–46. [Internet]. Waltham, Mass.: UpToDate; 2014 [cited 50. Coustan DR. Gestational diabetes mellitus: glycemic control December 15, 2014]. Available from: www.uptodate.com and maternal prognosis. In: Nathan DM, Greene MN, Barrs 36. Hillier TA, Pedula KL, Vesco KK, Schmidt MM, Mullen VA, editors. UpToDate [Internet]. Waltham, Mass.: JA, LeBlanc ES, et al. Excess gestational weight gain: modi- UpToDate; 2014 [cited January 15, 2015]. Available from: fying fetal macrosomia risk associated with maternal glucose. www.uptodate.com Obstet Gynecol 2008;112:1007–14. 51. Gaudier FL, Hauth JC, Poist M, Corbett D, Cliver SP. 37. Ales KL, Santini DL. Should all pregnant women be Recurrence of gestational diabetes mellitus. Obstet Gynecol screened for gestational glucose intolerance? Lancet 1992;80:755–8. 1989;1(8648):1187–91. 52. American Diabetes Association. 12. Management of diabetes 38. Garner P, Okun N, Keely E, Wells G, Perkins S, Sylvain J, in pregnancy. Diabetes Care 2016;39 Suppl 1:S94–98. et al. A randomized controlled trial of strict glycemic control 53. Kim C, Newton KM, Knopp RH. Gestational diabetes and and tertiary level obstetric care versus routine obstetric care the incidence of type 2 diabetes: a systematic review. in the management of gestational diabetes: a pilot study. Am Diabetes Care 2002;25:1862–8. J Obstet Gynecol 1997;177:190–5. 54. Boerschmann H, Pflüger M, Henneberger L, Ziegler AG, 39. McFarland MB, Trylovich CG, Langer O. Anthoropometric Hummel S. Prevalence and predictors of overweight and differences in macrosomic infants in diabetic and nondiabet- insulin resistance in offspring of mothers with gestational ic mothers. J Matern Fetal Med 1998;7:292–5. diabetes mellitus. Diabetes Care 2010;33:845–9. 40. Kenzel W, Misselwitz B. Unexpected fetal death during 55. McIntyre HD, Cruickshank JK, McCance DR, Dyer AR, pregnancy-a problem of unrecognized fetal disorders during Metzger BE, et al.; HAPO Study Cooperative Research antenatal care. Eur J Obstet Gynecol Reprod Biol 2003;110 Group. The hyperglycemia and adverse pregnancy outcome Suppl 1:86–92. study: associations of GDM and obesity with pregnancy out- 41. Hollander MH, Paarlberg KM, Huisjes AJM. Gestational comes. Diabetes Care 2012;35:780–6. diabetes: a review of the current literature and guidelines. 56. Vasudevan DM, Sreekumari S, Vaidyanathan K. Regulation Obstet Gynecol Surv 2007;62:125–39. of blood glucose, insulin and diabetes mellitus. In: Textbook 42. Witkop CT, Neale D, Wilson LM, Bass EB, Nicholson of biochemistry. Section C: Clinical and applied biochem- WK. Active compared with expectant delivery management istry. 7th ed. New Delhi: Jaypee Brothers Publishers; 2013. in women with gestational diabetes: a systematic review. p. 311–34. Obstet Gynecol 2009;113:206–17. 57. Paulev P-E, Zubieta-Calleja G. New human physiology. 43. Berkowitz KM. Insulin resistance and preeclampsia. Clin Textbook in medical physiology and pathophysiology: Perinatol 1998;25:873–85. essentials and clinical problems [Internet]. 2nd ed. 44. Yogev Y, Xenakis EM, Langer O. The association betvveen Copenhagen: University of Copenhagen; 2004. Chapter 27, preeclampsia and the severity of gestational diabetes: the Blood glucose and diabetes; [cited 2015 Jan 15]. Available impact of glycemic control. Am J Obstet Gynecol 2004;191: from: http://www.zuniv.net/physiology/ book/chapter27.html 1655–60. 58. Coustan D, Nelson C, Carpenter MW, Carr SR, Rotondo 45. Li G, Zhao S, Cui S, Li L, Zu Y, Li Y. Effect comparison of L, Widness JA. Maternal age and screening for gestational metformin with insulin treatment for gestational diabetes: a diabetes: a population-based study. Obstet Gynecol 1989;73: meta-analysis based on RCTs. Arch Gynecol Obstet 2015; 557–61. 292:111–20. 59. Ray R, Heng BH, Lim C, Ling SL. Gestational diabetes in 46. Shoham I, Wiznitzer A, Silberstein T, Fraser D, Holcberg Singaporean women: use of the glucose challenge test as a G, Katz M, et al. Gestational diabetes complicated by screening test and identification of high risk factors. Ann hydramnios was not associated with increased risk of perina- Acad Med Singapore 1996;25:504–8. tal morbidity and mortality. Eur J Obstet Gynecol Reprod 60. Hana FW, Peters JR. Screening for gestational diabetes; Biol 2001;100:46–9. past, present and future. Diabet Med 2002;19:351–8.
126 Perinatoloji Dergisi Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of Turkish Perinatology Society
61. Moyer VA; U.S. Preventive Services Task Force. Screening 73. Griffin ME, Coffey M, Johnson H, Scanlon P, Foley M, for gestational diabetes mellitus: U.S. Preventive Services Stronge J, et al. Universal vs. risk factor-based screening for Task Force recommendation statement. Ann Intern Med gestational diabetes mellitus: detection rates, gestation at 2014;160:414–20. diagnosis and outcome. Diab Med 2000;17:26–32. 62. Meltzer SJ, Snyder J, Penrod JR, Nudi M, Morin L. 74. Martinez Collado JH, Alvarado Gay FJ, DaneL Beltran JA, Gestational diabetes mellitus screening and diagnosis: a Gonzalez Martinez E. Glucose screening test in pregnant prospective randomised controlled trial comparing costs of women. A comparison between the traditional glucose load one-step and two-step methods. BJOG 2010;117:407–15. and diet. Medicina Interna de Mexico 2003;19:286–8. 63. Agarwal MM, Hughes PF, Punnose J, Ezimokhai M, 75. HAPO Study Cooperative Research Group. The Hyperglycemia Thomas L. Gestational diabetes screening of a multiethnic, and Adverse Pregnancy Outcome (HAPO) Study. Int J Gynecol high-risk population using glycated proteins. Diabetes Res Obstet 2002;78:69–77. Clin Pract 2001;51:67–73. 76. Lowe LP, Metzger BE, Dyer AR, Lowe J, McCance DR, 64. Uncu G, Ozan H, Cengiz C. The comparison of 50 grams Lappin TR, et al.; HAPO Study Cooperative Research glucose challenge test, HbA1c and fructosamine levels in Group. Hyperglycemia and Adverse Pregnancy Outcome diagnosis of gestational diabetes mellitus. Clin Exp Obstet (HAPO) Study: associations of maternal A1C and glucose Gynecol 1995;22:230–4. with pregnancy outcomes. Diabetes Care 2012;35:574–80. 65. Agarwal MM, Dhatt GS, Punnose J, Koster G. Gestational 77. Landon MB, Spong CY, Thom E, Carpenter MW, Ramin diabetes: a reappraisal of HBA1c as a screening test. Acta SM, Casey B, et al.; Eunice Kennedy Shriver National Obstet Gynecol Scand 2005;84:1159–63. Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, 66. Rajput R, ogesh Yadav, Rajput M, Nanda S. Utility of randomized trial of treatment for mild gestational diabetes. HbA1c for diagnosis of gestational diabetes mellitus. N Engl J Med 2009;361:1339–48. Diabetes Res Clin Pract 2012;98:104–7. 78. Dündar Ö, Çiftp›nar T, Tütüncü L, Ergür AR, Atay MV, 67. Zhu WW, Fan L, Yang HX, Kong LY, Su SP, Wang ZL, et Müngen E. The effects of the pre-pregnancy maternal body al. Fasting plasma glucose at 24-28 weeks to screen for ges- mass index on the pregnancy outcomes. Perinatal Journal tational diabetes mellitus: new evidence from China. 2008;16:43–8. Diabetes Care 2013;36:2038–40. 79. Göymen A, Alt›nok T, Uluda¤ S, fien C, Öçer F, Uzun H, et 68. Agarwal MM, Punnose J, Dhatt GS. Gestational diabetes: al. The role of maternal serum adiponectin levels in screen- problems associated with the oral glucose tolerance test. ing and diagnosis of gestational diabetes mellitus. Perinatal Diabetes Res Clin Pract 2004;63:73–4. Journal 2008;16:49–55. 69. Linder K, Schleger F, Ketterer C, Fritsche L, Kiefer- 80. Öncül M, Uluda¤ S, fien C, Göymen A, Uzun H, Güralp O, Schmidt I, Hennige A, et al. Maternal insulin sensitivity is et al. The role of maternal serum leptin and malondialde- associated with oral glucose-induced changes in fetal brain hyde levels in screening and diagnosis of gestational diabetes activity. Diabetologia 2014;57:1192–8. mellitus. Perinatal Journal 2009;17:1–35. 70. Tieu J, McPhee AJ, Crowther CA, Middleton P. Screening 81. Göymen A, Öncül M, Güralp O, fien C, Uluda¤ S, Kanza and subsequent management for gestational diabetes for Gül D, et al. comparison of maternal serum adiponectin and improving maternal and infant health. Cochrane Database leptin measurements in screening and diagnosis of gestation- Syst Rev 2014;2:CD007222. al diabetes mellitus. Perinatal Journal 2008;16:92–9. 71. Bergus GR, Murphy NJ. Screening for gestational diabetes 82. Keskin U, Ercan CM, Güngör S, Karaflahin K, Ergün A, mellitus: comparison of a glucose polymer and a glucose Öztürk M, et al. The effects of gestational diabetes mellitus monomer test beverage. J Am Board Fam Pract 1992;5:241– screening and diagnostic tests on fetal macrosomia. Perinatal 7. Journal 2013;21:133–7. 72. Murphy NJ, Meyer BA, O’Kell RT, Hogard ME. 83. Akyol A, Talay H, Gedikbafl› A, Ark C, Ülker V, Özdemir Ç. Carbohydrate sources for gestational diabetes screening. A The factors effective on the macrosomic deliveries of non- comparison. J Reprod Med 1994;39:977–81. diabetic pregnant women. Perinatal Journal 2014;22:83–7.
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ISSN 1305–3124 PERINATAL PERINATAL JOURNAL JOURNAL PERINATAL Volume 24 | Issue 2 | August 2016 JOURNAL A L J O www.perinataljournal.com A T U N R I N R A E L P Contents Volume 24 | Issue 2 | August 2016
P L E R A I N N R A U T A L J O Original Article The cesarean rates and indications between 2010 and 2014 in the Obstetrics 61 Department of Dr. Zekai Tahir Burak Maternal Health Training and Research Hospital Gökçe Naz Küçükbafl, Özlem Moralo¤lu, fiule Özel, Salim Erkaya, Yasemin Taflc›, Rahime Bedir F›nd›k Comparison of first trimester uterine artery Doppler parameters in hyperemesis 66 gravidarum with normal pregnancy ‹smail B›y›k, Gökhan Ocako¤lu, Emin Üstünyurt, Fatih Y›lmaz, Fatih Keskin An obstetric emergency case: vulvovaginal hematoma – our four-year results 72 Özlem Yörük, Ayflegül Öksüzo¤lu, Elif Gül Yapar Eyi, Burcu K›sa Karakaya, Necati Hançerlio¤lu Evaluation of the measurement of ACTH, fibronectin, pentraxin 3 levels and 77 cervical length in pregnant women under threatened preterm delivery Filiz Aktenk, Burcu Artunç Ülkümen, Yeflim Güvenç, Halil Gürsoy Pala, Arzu Oran Hepatitis B seropositivity of pregnant women and the review of Turkish literature 83 Rabia Zehra Bakar, Banu Dane Posterior fossa anomalies: related anomalies and the methods of 89 pregnancy termination Emine Ayd›n, Mert Turgal, Sema Can, Özgür Özyüncü 96 Modified transabdominal cervico-isthmic cerclage: analysis of 16 cases Ebru Çelik Kavak, Salih Burçin Kavak, Yakup Baykufl, Hüsnü Çelik Results of fetal anomaly screening performed at 11–14 weeks 100 of gestation at a tertiary center Tu¤ba K›nay, Metin Kaplan, Mehmet Metin Altay, fiafak Özdemirci, Sinan Karadeniz, Ahmet Okyar Erol
Case Report Intrafetal laser therapy in acardiac twin pregnancy: a case report 106 Resul Ar›soy, Oya Pekin, Kaan Pakay, Emre Erdo¤du, Oya Demirci, Murat Muhçu Volume
Clinical Guidelines Diabates in pregnancy: diagnosis and treatment. Practice Guidelines of 110
Turkish Perinatology Society 24
Cihat fien, Murat Yayla, Olufl Api, Elif Gül Yapar Eyi, Burcu Artunç Ülkümen; | Issue Diabetes and Pregnancy Study Group of Turkish Perinatology Society 2
| August 2016 The Official Publication of Perinatal Medicine Foundation Turkish Perinatology Society Turkish Society of Ultrasound in Obstetrics and Gynecology