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Volume 26 | Issue 3 | December 2018
Editor-in-Chief Advisory Board Cihat fien, Abdallah Adra, Beirut, Lebanon Nilgün Kültürsay, Izmir, Turkey Perinatal Medicine Center, Arif Akflit, Eskiflehir, Turkey Narendra Malhotra, Agra, India Saadet Arsan, Ankara, Turkey Memorial Bahçelievler Hospital, Alexandra Matias, Porto, Portugal Abdel-Latif Ashmaig, Khartoum, Sudan Israel Meizner, Tel Aviv, Israel Istanbul, Turkey Ahmet Baschat, Baltimore, MD, USA Mohammed Momtaz, Cairo, Egypt Christoph Berg, Bonn, Germany Giovanni Monni, Cagliari, Italy Editors Julene Carvalho, London, UK Lütfü Öndero¤lu, Ankara, Turkey Murat Yayla Rabih Chaoui, Berlin, Germany Soner R. Öner, Izmir, Turkey Frank Chervenak, New York, NY, USA Clinics of Obstetrics & Okan Özkaya, Isparta, Turkey Filiz Çayan, Mersin, Turkey Halil Gürsoy Pala, ‹zmir, Turkey Gynecology, Ac›badem Vincenzo D’Addario, Bari, Italy Alexander Papitashvilli, Tbilisi, Georgia International Hospital, Nur Daniflmend, Istanbul, Turkey ‹brahim Polat, Istanbul, Turkey Cansun Demir, Adana, Turkey Istanbul, Turkey Ritsuko Pooh, Osaka, Japan Jan Deprest, Leuven, Belgium Ruben Quintero, Miami, FL, USA Tony Duan, Shanghai, PRC Olufl Api Nebojsa Radunovic, Belgrade, Serbia Joachim Dudenhausen, Berlin, Germany Guiseppe Rizzo, Rome, Italy Department of Obstetrics & Alaa Ebrashy, Cairo, Egypt Stephen Robson, Newcastle, UK Gynecology, School of Hakan Erenel, Istanbul, Turkey Roberto Romero, Detroit, MI, USA Sertaç Esin, Adana, Turkey Medicine, Istanbul Medipol Levent Salt›k, Istanbul, Turkey Elif Gül Yapar Eyi, Ankara, Turkey University, Istanbul, Turkey Haluk Sayman, Istanbul, Turkey Ali Gedikbafl›, Istanbul, Turkey Mekin Sezik, Isparta, Turkey Ulrich Gembruch, Bonn, Germany Anne Greenough, London, UK Jiri Sonek, Dayton, OH, USA 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, Tours, France Alper Tanr›verdi, Ayd›n, Turkey Oliver Kagan, Tübingen, Germany Ebru Tar›m, Adana, Turkey Burçin Kavak, Elaz›¤, Turkey Basky Thilaganathan, London, UK Perinatal Journal is currently U¤ur Keskin, Ankara, Turkey Ilan Timor-Tritsch, New York, NY, USA Liliana Voto, Buenos Aires, Argentina indexed in the following abstracting Asma Khalil, London, UK Esin Koç, Ankara, Turkey Simcha Yagel, Jerusalem, Israel and indexing services: TÜB‹TAK Özge Korkmaz, ‹stanbul, Turkey Ahmet Yal›nkaya, Diyarbak›r, Turkey ULAKB‹M TR Index Health Sciences Selahattin Kumru, Antalya, Turkey Emre Zafer, Ayd›n, Turkey Database, EBSCOhost, EBSCO As›m Kurjak, Zagreb, Croatia Ivica Zalud, Honolulu, HI, USA (Academic Search Complete), Names are in alphabetical order. For the institutional details of the Advisory Board Members please see Editorial and Google Scholar. Board link which is available under the Information tab on the home page (www.perinataljournal.com).
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Volume 26 | Issue 3 | December 2018 iii T A L J O A U N R I N R A E L P Contents
P L E R A Volume 26, Issue 3, December 2018 I N N R A U T A L J O www.perinataljournal.com
Original Article Comparison of obstetric outcomes of pregnant women with isolated proteinuria according to proteinuria severity 107 ‹zole proteinüri saptanan gebe kad›nlar›n obstetrik sonuçlar›n›n proteinüri fliddetine göre karfl›laflt›r›lmas› Mehmet Özgür Akkurt, Bora Coflkun, Tu¤berk Güçlü, Kaan Pakay, Engin Korkmazer Myomectomy during cesarean section: is it a safe procedure? 112 Sezaryen do¤um esnas›nda miyomektomi: Güvenli bir uygulama m›? Alper Baflbu¤, Esma Y›ld›r›m, Ali Yavuzcan, Aflk› Ellibefl Kaya, Fikret Gökhan Göynümer Conventional Doppler myocardial performance index, tricuspid and mitral annular plane systolic excursions in the assessment of fetal heart functions 117 Fetal kalp fonksiyonlar›n›n de¤erlendirilmesinde konvansiyonel Doppler miyokardiyal performans indeksi, triküspid ve mitral kapak anüler düzlem sistolik hareketleri fiebnem Paytoncu The distribution of primary cesarean section indication at a university hospital: ten-year experience and potential lessons to be taken to decrease cesarean section rates 124 Bir üniversite hastanesinin primer sezaryen endikasyon da¤›l›m›: On y›la ait tecrübe ve sezaryen do¤um oranlar›n› azaltmaya yönelik ç›kar›labilecek dersler Semir Köse, Asl› Akdöner, Sabahattin Altunyurt Retrospective analysis of the preeclampsia cases delivered in our clinic between 2013 and 2017 135 Klini¤imizde 2013–2017 y›llar› aras›nda do¤um yapm›fl olan preeklampsi olgular›n›n retrospektif de¤erlendirilmesi Gülfem Baflol, Navdar Do¤ufl Uzun, Fulya Uzun, Ahmet Kale, Hasan Terzi Evaluation of the use of iodized salt by pregnant women and their knowledge on the use of iodized salt 141 Gebe kad›nlar›n iyotlu tuz kullan›m›n›n ve iyotlu tuz kullan›m›na iliflkin bilgilerinin belirlenmesi Emine Özge Avc›, Baht›flen Kartal, Evrim Bayraktar The impact of using thromboprophylactic medication by pregnant women on the hemodynamics of fetus and uterus 148 Gebelerde tromboprofilaktik ilaç kullan›m›n›n fetüs ve uterus kan ak›fl dinamiklerine etkisi Emre Zafer
Case Report Cesarean scar pregnancies and their management: case series 155 Sezaryen skar gebelikleri ve yönetimleri: Olgu serisi Elif Ganime Aydeniz, Umut Sar›, Talat Umut Kutlu Dilek Gestational management of the patient with osteogenesis imperfecta: a case report 162 Osteogenezis imperfekta hastas›n›n gebelik yönetimi: Olgu sunumu Gülflen Do¤an Durda¤, Hakan Kalayc›, Seda Yüksel fiimflek, Songül Alemdaro¤lu, Gonca Çoban, Ferhat fiaml›
Letter to Editor Letter to the Editor: Antenatal steroids and their administration time for preventing morbidity in preterm labor 167 Editöre Mektup: Preterm do¤umda morbiditenin önlenmesinde antenatal steroidler ve uygulama zaman› Talat Umut Kutlu Dilek, Elif Ganime Aydeniz
Index 170
Acknowledgement of Reviewers 173
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 2018;26(3):107–111 I N N R A U T A L J O
Comparison of obstetric outcomes of pregnant women with isolated proteinuria according to proteinuria severity
Mehmet Özgür Akkurt1, Bora Coflkun2, Tu¤berk Güçlü1, Kaan Pakay1, Engin Korkmazer1 1Perinatology Clinic, Bursa Postgraduate Training and Research Hospital, Bursa, Turkey 2Gynecology and Obstetrics Clinic, Gülhane Training and Research Hospital, Ankara, Turkey
Abstract Özet: ‹zole proteinüri saptanan gebe kad›nlar›n obstetrik sonuçlar›n›n proteinüri fliddetine göre karfl›laflt›r›lmas› Objective: To compare the obstetric outcomes of women who were Amaç: ‹zole gestasyonel proteinüri (‹GP) saptanan kad›nlar›n found to have isolated gestational proteinuria (IGP) according to obstetrik sonuçlar›n›n 24 saatlik proteinüri fliddetine göre karfl›- the severity of 24-hour proteinuria. laflt›r›lmas›. Methods: The women who were found to have IGP between January Yöntem: Retrospektif çal›flmam›za Bursa Yüksek ‹htisas E¤itim ve 1, 2014 and June 1, 2018 at the Bursa Yüksek ‹htisas Training and Araflt›rma Hastanesinde 1 Ocak 2014 – 1 Haziran 2018 tarihleri Research Hospital were included in our retrospective study. The study aras›nda ‹GP saptanan kad›nlar dahil edildi. Çal›flma popülasyonu population was divided into 3 groups according to the proteinuria proteinüri fliddetine göre 3 gruba ayr›ld›: Grup 1, fizyolojik düzey- severity: Group 1: Proteinuria at physiological level (<300 mg/day, n= de proteinüri (<300 mg/gün, n= 60); Grup 2, hafif proteinüri (300– 60); Group 2: Mild proteinuria (between 300 mg and 3000 mg/day, 3000 mg/gün aras›, n=49); Grup 3, nefrotik düzeyde proteinüri n=49); Group 3: Proteinuria at nephrotic level (≥3000 mg/day, n=28). (≥3000 mg, n=28). Results: There was no difference among 3 groups in terms of mater- Bulgular: Her 3 grup aras›nda maternal yafl, gravida ve yaflayan nal age, gravida and the number of living children. The mean protein- çocuk say›s› aç›s›ndan fark bulunmad›. Nefrotik düzeydeki grupta uria amount was the highest in the group with nephrotic level ortalama proteinüri miktar› en fazla saptand› (s›ras›yla Grup 1’de (216±73 mg/day in Group 1, 849±119 mg/day in Group 2, and 9055± 216±73 mg/gün, Grup 2’de 849±119 mg/gün, Grup 3’de 1011 mg/day in Group 3, respectively; p<0.05). Preeclampsia (PE) 9055±1011 mg/gün; p<0.05). Grup 3’de preeklampsi (PE) gelifl- incidence was higher in Group 3 (6.6% in Group 1, 47% in Group 2 me s›kl›¤› daha fazla idi (s›ras›yla Grup 1’de %6.6, Grup 2’de and 64% in Group 3, respectively; p<0.05). The period elapsed %47, Grup 3’de %64; p<0.05). IGP ile PE tan›s› aras›nda geçen between the diagnoses of IGP and PE was the shortest in Group 3 süre Grup 3’de daha k›sa saptand› (s›ras›yla Grup 1’de 21.2±4.9 (21.2±4.9 days in Group 1, 16.4±4.7 days in Group 2, and 7.8±2.2 days gün, Grup 2’de 16.4±4.7 gün, Grup 3’de 7.8±2.2 gün; p<0.05). in Group 3, respectively; p<0.05). There was no significant correla- Proteinüri fliddeti ile do¤um a¤›rl›¤› ve IGP (r=0.68) ile PE tan›- tion between proteinuria severity and birth weight and the period s› aras›nda geçen süre aras›nda (r=0.79) anlaml› korelasyon sap- elapsed between the diagnoses of IGP (r=0.68) and PE (r=0.79). tanmad›. Conclusion: While IGP increases the incidence of poor perinatal Sonuç: IGP, preeklampsi, intrauterin geliflim k›s›tl›l›¤›, düflük do- outcomes such as intrauterine growth retardation, low birth weight ¤um a¤›rl›¤›, iyatrojenik erken do¤um gibi kötü perinatal sonuçla- and iatrogenic preterm birth, it was also found that PE incidence is r›n s›kl›¤›n› art›rmakla beraber, nefrotik düzeyde proteinüri sapta- higher, diagnosis week is earlier and the period between IGP and PE nan kad›nlarda, daha az fliddetli proteinürisi olan kad›nlara göre diagnoses are shorter in women with proteinuria at nephrotic level PE insidans› daha fazla, tan› haftas› daha erken, ‹GP-PE aras›nda- than those with less severe proteinuria. ki süre daha k›sa saptanm›flt›r. Keywords: Low birth weight, interval, isolated gestational pro- Anahtar sözcükler: Düflük do¤um a¤›rl›¤›, interval, izole gestasyo- teinuria, preeclampsia. nel proteinüri, preeklampsi.
Correspondence: Mehmet Özgür Akkurt, MD. Perinatology Clinic, Bursa Postgraduate Available online at: Training and Research Hospital, Bursa, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263002 doi:10.2399/prn.18.0263002 Received: September 2, 2018; Accepted: October 19, 2018 QR (Quick Response) Code: Please cite this article as: Akkurt MÖ, Coflkun B, Güçlü T, Pakay K, Korkmazer E. Comparison of obstetric outcomes of pregnant women with isolated proteinuria according to proteinuria severity. Perinatal Journal 2018;26(3):107–111. ©2018 Perinatal Medicine Foundation Akkurt MÖ et al.
Introduction was based on the method of analyzing retrospective During pregnancy, detecting proteinuria ≥300 mg/dl in records, the approval of ethics committee was not 24-hour urine and/or finding proteinuria +1 and above obtained. The women with hypertension during the in the urinalysis by dipstick method is considered abnor- diagnosis, those with the history of renal and vascular dis- mal and defined as isolated gestational proteinuria eases, the women diagnosed with diabetes before preg- (IGP).[1] Although clean and fresh urine sample can be nancy, multiple pregnancies, the pregnant women with collected by urinary dipstick method, it is affected by fetuses which had chromosomal or non-chromosomal many clinical conditions such as protein content, infec- genetic diseases and structural malformations, and the tion and/or blood contamination in urine.[2] Therefore, pregnant women who had risk factors for preeclampsia determining protein amount in 24-hour urine is the such as molar pregnancy were excluded from the study. most appropriate method for preeclampsia.[3] Without the history of a hypertensive disease, pro- It has not been clarified yet if proteinuria is an indica- teinuria and/or end organ damage accompanying to sys- tor of preeclampsia which will develop in the following tolic blood pressure being 140 mmHg and above and/or steps of pregnancy or a physiological change in the kid- diastolic blood pressure being 90 mmHg and above in neys associated with the pregnancy or not. Although pro- the last 2 measurements with 4-hour intervals in the fol- teinuria is accepted the late finding of preeclampsia low-ups after 20 weeks of gestation was defined as today, Morikawa et al. suggest that isolated proteinuria is preeclampsia. The study group was separated into 3 an early clinical finding of PE.[4] Until the preeclampsia groups according to the 24-hour proteinuria severity: report prepared by ACOG (American College of Group 1: Physiological proteinuria (<300 mg/day); Obstetricians and Gynecologists) in 2013, proteinuria Group 2: Mild proteinuria (300–3000 mg/day); Group 3: was among the diagnostic criteria of preeclampsia.[5] After Proteinuria at nephrotic level (3000 g and above). The this report, proteinuria was removed from the absolute maternal data (age, gravida, living child, 24-hour urine criteria of preeclampsia. In this report, it was highlighted level, the week of proteinuria diagnosis, the week of that in 10% and 20% of pregnant women who were preeclampsia diagnosis, the period elapsed between the found to have preeclampsia or eclampsia, respectively, diagnoses of proteinuria and preeclampsia) and perinatal did not have proteinuria during the diagnosis.[5] data (the incidence of intrauterine growth retardation Hypertensive diseases are still among the major rea- [IUGR], abdominal circumference [percentile], birth sons of maternal and perinatal deaths, and isolated pro- time, delivery type, birth weight, the rate of cesarean sec- teinuria is one of the risk factors defined for PE. tion due to fetal stress, newborn’s hospitalization dura- Therefore, following up such patients in terms of PE tion at intense care unit, 1-minute and 5-minute APGAR development is very important. Our aim in this study is scores and perinatal mortality rate) were obtained from to analyze the perinatal outcomes of pregnant women the files of mothers and newborns and these data were who were found to have proteinuria in 24-hour urine compared among the groups. and to investigate whether proteinuria severity and the The statistical analysis was performed by using SPSS period for PE development are associated or not. 22.0 (IBM SPSS, version 22, IBM Corp. Armork, NY, USA). The descriptive data were expressed as mean and standard deviation. Kolmogorov-Smirnov test was used Methods to determine the distribution of variables. For the analy- Our study was conducted at Bursa Yüksek ‹htisas sis of quantitative and qualitative data, Mann-Whitney U Training and Research Hospital which is the biggest ter- and chi-square tests were used respectively. Fisher’s test tiary center in South Marmara. Pregnant women with was used when chi-square test could not meet the condi- isolated proteinuria during 54 months between January tions. Spearman’s test was used for the correlation analy- 1, 2014 and June 30, 2018 were included in the study. sis and p<0.05 was considered significant. Proteinuria was measured in 24-hour urine of pregnant women who were found to have proteinuria +1 or above in the dipstick urinalysis according to the hospital proto- Results col. The pregnant women with proteinuria level of 300 Isolated proteinuria was found in 77 pregnant women mg and above were included in the study. Since the study who admitted to our clinic during the study period. The
108 Perinatal Journal Comparison of obstetric outcomes of pregnant women with isolated proteinuria according to proteinuria severity
Table 1. The comparison of maternal and perinatal characteristics according to 24-hour proteinuria severity.
Proteinuria level
Group 1 Group 2 Group 3 <300 mg 300–3000 mg ≥3000 mg (n=60) (n=49) (n=28) p-value
Maternal age (years) 27.6±4.1 28.9±4.7 26.4±3.2 0.12 Gravida 3.1±1.0 3.5±1.0 3.2±0.9 0.32 Number of living children 1.7±0.7 2.0±0.7 1.6±0.5 0.15 24-hour proteinuria amount (mg) 216±73 849±119 9055±1011 0.003 Week of proteinuria diagnosis 32.4±4.3 30.9±5.3 28.9±3.4 0.09 Preeclampsia incidence (n) 4 (%6.6) 23 (%47) 18 (%64) 0.004 Week of preeclampsia diagnosis 37.2±2.5 33.9±5.3 30.1±4.5 0.001 Diagnosis interval of proteinuria-preeclampsia (day) 21.2±4.9 16.4±4.7 7.8±2.2 0.003 Incidence of growth retardation (n) 6 (%10) 9 (%18) 16 (%57) 0.001 Abdominal circumference (percentile) 35.4±5.9 24.8±4.6 10.5±3.1 0.03 Delivery time (week) 38.4±2.1 35.5±5.1 31.6±3.4 0.009 Birth weight (g) 3049±150 2570±371 1345±142 0.001 Vaginal delivery 36 (%60) 14 (%28.5) 4 (%14) 0.04 Cesarean section due to fetal stress 4 (%6.6) 7 (%14) 8 (%28) 0.03 1-minute APGAR 8.9±0.3 8.3±0.5 7.7±0.4 0.08 5-minute APGAR 9.5±0.2 9.2±0.4 8.6±0.3 0.16 Perinatal death (n) 0 (%0) 1 (%2) 2 (%7) 0.03
proteinuria was at nephrotic level in 28 of them (≥3000 than the control group. When perinatal outcomes were mg/day) and at mild level in 49 of them. The patients compared, the rate of cesarean section due to fetal stress with isolated proteinuria were separated into 3 groups and perinatal mortality rate was significantly higher in according to their severity and when compared to the the group with proteinuria at nephrotic level (Table 1). control group (n=60), no difference was found among 3 When the correlation between 24-hour urine severity groups in terms of maternal age, gravida and the num- and birth weight, the week of preeclampsia diagnosis and ber of living child. Compared to the other groups, the the period elapsed between the diagnoses of proteinuria mean proteinuria level was the highest in the group with and preeclampsia was analyzed, a significant correlation nephrotic level (216±73 mg/day in Group 1, 849±119 was found between proteinuria severity and birth weight mg/day in Group 2, and 9055±1011 mg/day in Group 3, and diagnosis interval (Table 2). respectively; p<0.05). In 4 pregnant women included in our study, proteinuria was found 10 g and above in 24- Table 2. The relationship between proteinuria severity and birth hour urine (range: 10.98 to 21.45 g/day). While all of weight, week of preeclampsia diagnosis and development these pregnant women also had hypertensive diseases, 2 period. of them had HELLP (hemolysis, elevated liver enzymes, Week of Diagnosis thrombocytopenia). Birth preeclampsia interval of In the group with proteinuria at nephrotic level, weight diagnosis proteinuria- preeclampsia preeclampsia and growth retardation rates were also Proteinuria <300 mg/day r=0.25 r=-0.38 r=0.16 higher. Preeclampsia also developed at the earlier weeks (n=60) of gestation in this group. The period elapsed between Proteinuria ≥300 mg/day r=0.68* r=0.22 r=0.79* the diagnoses of proteinuria and preeclampsia was short- (n=77) The relationship was calculated by Spearman’s correlation coefficient. Statistically er in the group with proteinuria at nephrotic level com- significant values were expressed by the symbol *. While a moderate and signifi- pared to the other groups. In both groups with protein- cant correlation and significant correlation was found between proteinuria at nephrotic level and birth weight, there was a strong and significant correlation in uria, IUGR rate was higher and birth weight was lower the diagnosis interval between proteinuria and preeclampsia.
Volume 26 | Issue 3 | December 2018 109 Akkurt MÖ et al.
Discussion review and this rate was 34% in the study of Ekiz et al.[7] Distinguishing isolated gestational proteinuria and In the study of Yamada et al., the authors found that PE preeclampsia is very important for the management of developed in 25% of the patients with IGP, and 20% of [8] gestation. In a study performed,[6] incidences for preterm all PE patients developed PE after IGP was diagnosed. labor, low birth weight, gestational diabetes and renal dis- In our study, we diagnosed PE in later periods in 53% of ease in women with IGP were found similar with the the women with proteinuria level of 300 mg and above. healthy women, and these women had term labor. On the In the sub-group analysis according to the proteinuria other hand, preeclampsia is associated with increased severity, we found that PE was concomitant in 64% of maternal and perinatal morbidity. Our study is a retro- those with proteinuria at nephrotic level and in 47% of spective case-controlled study performed in a tertiary those with less severe proteinuria (between 300 and 3000 center. According to our results, the risk of increased mg). In addition, the week of PE diagnosis was earlier preeclampsia and intrauterine growth retardation increas- and the period elapsed between the diagnoses of isolated es in pregnant women who are found to have isolated pro- proteinuria and preeclampsia was shorter in the group with proteinuria at nephrotic level. Many studies investi- teinuria. Also, there is a significant correlation between gated the risk factors for this progression. Twin preg- proteinuria and birth weight and the period elapsed nancy, pregnancy after 40-year-old, preeclampsia histo- between the diagnoses of proteinuria and preeclampsia. ry and nulliparous women are also in the risk group.[7,13] The most common method to determine the pres- In addition to these studies, we also found a significant ence of proteinuria is the urinalysis by dipstick test. correlation between proteinuria severity and the week of However, false positivity rate increases in some clinical preeclampsia diagnosis and diagnosis interval. conditions such as concentrated urine or concurrent [11] [7] The single-center study (n=37) of Morikawa et al. infection. Although collecting urine in 24 hours and which included a limited number of pregnant women analyzing it as in our study is the golden standard for with IGP and the multi-centered large-scale study IGP, it usually cannot be tolerated by the patients since [8] (n=130) of Yamada et al. similarly found PE about 2 the procedure takes long. As found by Yamada et al., weeks after diagnosing IGP. Unlike other studies, we protein/creatinine rate above 0.27 in the spot urine is an found in our study that PE developed about 8 days later easy and useful method for the diagnosis of IGP.[8] in the cases with proteinuria at nephrotic level and about While the incidence of isolated proteinuria varied in 16.5 days later in the cases with less severe proteinuria. the previous studies, it was seen in about 2% (range: 0.3 Our study contributes to the literature and shows that to 4%) of pregnancies and its importance could not be the period of PE development is also significantly corre- [7–9] understood clearly. Proteinuria is not seen during the lated with the proteinuria severity. diagnosis in approximately 15–26% of pregnant women [7] Similar to the study of Ekiz et al., we showed that with new-onset hypertension, but it is found in the fur- [10,11] IGP is not only associated with the increased PE risk but ther phases of the pregnancies. As argued by Akaishi also with the increased risk of growth retardation and et al., preeclampsia develops in 2 different conditions: (1) low birth weight. This shows that further wide-scale when proteinuria is diagnosed much earlier than hyper- studies investigating the relationship between IGP and tension, or (2) proteinuria and hypertension are diag- [9] increased poor obstetric outcomes are needed. The nosed at the same time. Increased body mass index, major limitation of study is its retrospective nature. twin pregnancy, nulliparity, young maternal age which Being single-centered and having limited number of are among the well-known risk factors for PE are also [12] patients are the factors affecting the incidence of the risk factors for GP, and supports this hypothesis. preeclampsia. In addition, since it is retrospective, we The progression rate of PE in women with IGP could not obtain some information such as increased varies among the studies. The reasons for this difference body-mass index, history of previous PE, weight gain among the studies include the size of population and during pregnancy, the history of aspirin use, increased mean week of gestation, PE incidence and the risk fac- resistance in uterine artery Doppler blood flow which tors of women in the study population. Morikawa et al.[11] may contribute to the development of preeclampsia. found PE in about 51% of the pregnant women diag- Also, we did not investigate maternal outcomes as we nosed with isolated proteinuria in their retrospective focused on perinatal outcomes. However, the studies in
110 Perinatal Journal Comparison of obstetric outcomes of pregnant women with isolated proteinuria according to proteinuria severity
the literature which estimate PE development according 4. Morikawa M, Yamada T, Minakami H. Outcome of pregnan- to the proteinuria severity are limited. cy in patients with isolated proteinuria. Curr Opin Obstet Gynecol 2009;21:491–5. 5. American College of Obstetricians and Gynecologists; Task Conclusion Force on Hypertension in Pregnancy. Hypertension in preg- nancy. Report of the American College of Obstetricians and According to the findings of our study, women with IGP Gynecologists’ Task Force on Hypertension in Pregnancy. are in the risk group in terms of increased poor perinatal Obstet Gynecol 2013;122:1122–31. outcomes. In these women, the risk for preeclampsia, 6. Holston AM, Qian C, Yu KF, Epstein FH, Karumanchi SA, low birth weight and iatrogenic preterm labor is Levine RJ. Circulating angiogenic factors in gestational pro- increased. PE incidence is higher, diagnosis week is ear- teinuria without hypertension. Am J Obstet Gynecol 2009; 200:392.e1–10. lier and the period elapsed between the diagnoses of IGP 7. Ekiz A, Kaya B, Polat I, Avci ME, Ozkose B, Kicik Caliskan R, and PE is shorter in women with proteinuria at nephrot- et al. The outcome of pregnancy with new onset proteinuria ic level compared to the women with less severe protein- without hypertension: retrospective observational study. J uria. Therefore, we recommend follow up the women Matern Fetal Neonatal Med 2016;29:1765–9. with proteinuria at nephrotic level closely due to the 8. Yamada T, Obata-Yasuoka M, Hamada H, Baba Y, Ohkuchi increased risk of PE and growth retardation and expect A, Yasuda S, et al. Isolated gestational proteinuria preceding the diagnosis of preeclampsia – an observational study. Acta the development of PE about 8 days after IGP diagnosis Obstet Gynecol Scand 2016;95:1048–54. at nephrotic level. 9. Akaishi R, Yamada T, Morikawa M, Nishida R, Minakami H. Clinical features of isolated gestational proteinuria progressing Conflicts of Interest: No conflicts declared. to pre-eclampsia: retrospective observational study. BMJ Open 2014;4:e004870. References 10. Saudan P, Brown MA, Buddle ML, Jones M. Does gestation- al hypertension become pre-eclampsia? Br J Obstet Gynaecol 1. Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and 1998;105:1177–84. regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol 2013;170:1–7. 11. Morikawa M, Yamada T, Yamada T, Cho K, Yamada H, Sakuragi N, et al. Pregnancy outcome of women who devel- 2. Levine RJ, Ewell MG, Hauth JC, Curet LB, Catalano PM, oped proteinuria in the absence of hypertension after mid-ges- Morris CD, et al. Should the definition of preeclampsia tation. J Perinat Med 2008;36:419–24. include a rise in diastolic blood pressure of >/=15 mm Hg to a 12. Kuyucu M, Ar›nkan SA, Herkilo¤lu D, Muhcu M. Assessment level <90 mm Hg in association with proteinuria? Am J Obstet of maternal and perinatal outcomes in pregnant women with Gynecol 2000;183:787–92. isolated proteinuria. Perinatal Journal 2016;24:129–35. 3. Thadhani RI, Maynard SE. Proteinuria in pregnancy: evalua- 13. Macdonald-Wallis C, Lawlor DA, Heron J, Fraser A, Nelson tion and management. In: Post T, editor. UpToDate. SM, Tilling K. Relationships of risk factors for pre-eclampsia [Internet]. Waltham, MA: UpToDate; 2017 [cited August 15, with patterns of occurrence of isolated gestational proteinuria 2017]. Available from: www.uptodate.com during normal term pregnancy. PLoS One 2011;6:e22115.
Volume 26 | Issue 3 | December 2018 111 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 2018;26(3):112–116 I N N R A U T A L J O
Myomectomy during cesarean section: is it a safe procedure?
Alper Baflbu¤, Esma Y›ld›r›m, Ali Yavuzcan, Aflk› Ellibefl Kaya, Fikret Gökhan Göynümer Department of Obstetrics and Gynecology, Faculty of Medicine, Düzce University, Düzce, Turkey
Abstract Özet: Sezaryen do¤um esnas›nda miyomektomi: Güvenli bir uygulama m›? Objective: To evaluate the relationship between intraoperative and Amaç: Sezaryen do¤um esnas›nda yap›lan miyomektomi uygula- postoperative complications of the myomectomy procedure per- mas›n›n intraoperatif ve postoperatif komplikasyonlar› aras›ndaki formed during cesarean section. iliflkiyi de¤erlendirmek. Methods: Our study included 280 patients who had undergone cesare- Yöntem: Çal›flmam›za, Düzce Üniversitesi Kad›n Hastal›klar› ve an section at Obstetrics and Gynecology Clinic of Düzce University. Do¤um Klini¤i’nde sezaryen do¤um gerçeklefltirmifl 280 hasta da- The study group was comprised of 45 patients who had undergone hil edildi. Çal›flma grubu, sezaryen do¤um esnas›nda miyomekto- myomectomy during cesarean section. The remaining 235 patients mi olan 45 hastadan olufltu. Sadece sezaryen do¤um gerçeklefltiren having had only cesarean section constituted the control group. kalan 235 hasta ise kontrol grubunu oluflturdu. Results: When the groups were compared, the duration of the Bulgular: Gruplar karfl›laflt›r›ld›¤›nda, hem miyomektomi hem de operation was longer in the group with both myomectomy and sezaryen olan grupta operasyon süresi daha uzundu (49.5 dk’ya cesarean section (49.5 min vs. 44.3 min; p=0.002). No statistically karfl› 44.3 dk; p=0.002). Postoperatif hemoglobin seviyeleri, he- significant difference was found between the groups in terms of moglobin seviyelerinde azalma veya intraoperatif ve postoperatif postoperative hemoglobin levels, decrease in hemoglobin levels or komplikasyonlarda azalma bak›m›ndan gruplar aras›nda istatistik- intraoperative and postoperative complications. sel olarak anlaml› fark yoktu. Conclusion: Myomectomy during cesarean section was not associ- Sonuç: Sezaryen esnas›nda miyomektomi, artm›fl kan transfüzyo- ated with increased blood transfusion, postpartum hemorrhage or nu, postpartum hemoraji veya postoperatif komplikasyonlarla ilifl- postoperative complications and only differed from the cesarean sec- kilendirilmemifltir ve sezaryen olan grupla sadece operasyon süre- tion group in the duration of the operation. Myomectomy during si bak›m›ndan farkl›l›k göstermifltir. Sezaryen esnas›nda deneyimli cesarean section performed by experienced surgeons can be a safe cerrahlar taraf›ndan gerçeklefltirilen miyomektomi güvenli bir cer- surgical procedure. rahi uygulama olabilir. Keywords: Cesarean section, hemorrhage, myomectomy, leiomy- Anahtar sözcükler: Sezaryen do¤um, hemoraji, miyomektomi, le- oma. yomiyom.
Introduction assessment. In various publications this rate ranges from 0.37% to 12%.[3–5] Given that maternal age for pregnan- Leiomyomas are the most common uterine neoplasms cy is increasing and that the incidence of myoma increas- and are detected using various imaging modalities in es with age, obstetricians are more likely to encounter almost 40% of women during their reproductive peri- pregnant patients with myomas and be required to treat od.[1] Most of these women are asymptomatic, but 1 in 4 complications related to them.[6,7] [2] requires treatment. The incidence of uterine leiomy- Myomectomy during cesarean section (C/S) is still omas during pregnancy varies depending on the time of a controversial subject. The main concern here is the
Correspondence: Alper Baflbu¤, MD. Düzce Üniversitesi T›p Fakültesi, Kad›n Available online at: Hastal›klar› ve Do¤um Anabilim Dal›, Düzce, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263003 doi:10.2399/prn.18.0263003 Received: July 23, 2018; Accepted: October 23, 2018 QR (Quick Response) Code: Please cite this article as: Baflbu¤ A, Y›ld›r›m E, Yavuzcan A, Ellibefl Kaya A, Göynümer FG. Myomectomy during cesarean section: is it a safe procedure? Perinatal Journal 2018;26(3):112–116. ©2018 Perinatal Medicine Foundation Myomectomy during cesarean section: is it a safe procedure?
excessive bleeding and increased morbidity that may blood transfusion was made according to the patient's occur during the operation.[8] Many sources still object symptoms, including tachycardia, hypotension or to routinely performed myomectomy during C/S for changes in postoperative hemoglobin level. [9,10] these reasons. Recent literatures states that, howev- All C/S operations were performed using transverse er, studies and meta-analyses have been carried out lower uterine segment incisions, while myomectomy suggesting that C/S myomectomy is a safe surgical was carried out using the serosal incision technique. If procedure and that positive results may be obtained for the myoma was close to the C/S incision, it was excised subsequent pregnancy outcomes.[11,12] For this reason, from that incision, otherwise it was removed from a this combined surgical procedure has been introduced [13] different incision. more frequently by many surgeons. Between the dates mentioned above, there were In this study, we aimed to examine C/S myomecto- 4280 births in our hospital and 2300 of them were via my cases performed at our center and evaluate the effects C/S. Forty-five of these patients had undergone of this procedure on intraoperative and postoperative myomectomy during C/S and these were included in morbidity. the study group. The control group was randomly selected and included 10% of the patients having had Methods only C/S. This study is a retrospective cohort study conducted at a The operations were performed by surgeons expe- single medical center. Cesarean section patients admit- rienced in the field of myomectomy operations and ted to the Düzce University Medical Faculty Hospital trained in the management of postpartum hemorrhage. between January 2015 and June 2018 were included in the study. Records of patients who were operated on Statistical analysis within this period were obtained from patient files and Descriptive statistics for continuous variables were the hospital's automation system. This study was expressed as mean ± standard deviation or median (min- approved by the local ethics committee (IRB no. imum–maximum) and nominal variables were expressed 2018/0069). as number and percentage (%). For each group, differ- Study population was divided into 2 groups. Group 1 ences in mean values and differences in median values included those who had undergone myomectomy during were evaluated using the Student’s t-test and Mann- C/S and Group 2 (control group) included those who Whitney U-test, respectively. The chi-square distribu- had undergone C/S only. Patient data recorded included tion test was used to compare categorical data, with p- age, gravida, parity, gestational week of operation, dura- values of ≤0.05 considered as statistically significant. tion of operation, length of hospital stay, indications for Statistical analysis was performed using SPSS for cesarean section and localization and number of Windows version 22 software (SPSS, Inc., Chicago, IL, myomas. Informed consent was obtained from patients USA). diagnosed with myomas before the cesarean section. Our primary goal in this study was to evaluate the Results effect of myomectomy performed during C/S on intra- Between January 2015 and June 2018, a total of 4280 operative and postoperative outcomes. For this pur- deliveries occurred in our hospital, of which 2300 were pose, we evaluated blood loss during the operation, uterine atony, major organ injuries and need for blood delivered via C/S. Myomectomy was performed during transfusion or relaparotomy. C/S in 1.95% (n=45) of the 2300 C/S cases. The char- acteristics of these patients are summarized in Table 1. Estimated blood loss was calculated according to There were no significant differences found between the formula: the two groups in terms of baseline characteristics. Δ hemoglobin concentration = baseline hemoglobin When cesarean indications were considered, a pre- concentration – postoperative 6th hour hemoglobin vious cesarean was the first among all indications concentration (37.8% vs. 48.1%), followed by non-cephalic presenta- The duration of surgery was calculated in minutes tion and cephalopelvic disproportion (Table 2). The – from skin incision to skin closure. The decision for groups were similar in terms of indications for C/S.
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When the myomectomy during C/S group was Table 1. Baseline characteristics of patients. compared with the C/S group, the duration of opera- Myomectomy Non-myomectomy tion in the C/S myomectomy group was longer and group group p- this difference was statistically significant (49.5 min vs. (n=45) (n=235) value Δ 44.3 min; p=0.002). Preoperative, postoperative and Age (year) 30 (21–44) 30 (19–41) 0.987 hemoglobin concentrations were similar, with no sta- Gravidity 3 (1–7) 3 (1–9) 0.649 tistically significant difference found between the Parity 1 (0–4) 1 (0–5) 0.871 groups (p=0.056, p=0.548, p=0.177, respectively). Abortion 0 (0–4) 0 (0–4) 0.542 Although the need for transfusion was greater in the BMI (kg/m2) 32 (22–44) 32.5 (19–46) 0.987 C/S myomectomy group, this difference was not statis- Gestational age (week) 37 (29–40) 37 (31–41) 0.741 tically significant (6.7% vs. 2.6%; p=0.152). There was Values are stated as median (minimum–maximum). no difference between groups in terms of hospitaliza- tion time. No relaparotomy, visceral organ injury or major vascular complications developed in either Table 2. Indications for C/S in both groups. group (Table 3). Myomectomy Non-myomectomy A hematoma developed in the suture line of the group group p- myomectomy site in two patients in the C/S myomec- (n=45) (n=235) value tomy group. One of these patients had a myoma 6 cm Previous C/S 17 (37.8%) 113 (48.1%) 0.103* in diameter on the anterior wall which was removed Maternal request 4 (8.9%) 30 (12.8%) 0.621 transendometrially. No additional surgical interven- Non-cephalic presentation 9 (20%) 27 (11.5%) 0.143* tion was performed on these patients and with only Cephalopelvic disproportion 9 (20%) 33 (14.0%) 0.360 expectant management, these hematomas were sponta- Fetal distress 6 (12.3%) 22 (9.4%) 0.412 neously resolved over time. Values are stated as number (%). *<.05 indicates statistical significance.
Discussion Table 3. Intraoperative and postoperative outcomes. The end result of our study was that the myomectomy performed during C/S was not associated with a decrease Myomectomy Non-myomectomy group group p- in hemoglobin level, an increase in the need for transfu- (n=45) (n=235) value sion, increased uterine atony or postoperative morbidity, Operation time (min) 49.53±13.63 44.31±9.72 0.002* and only differed from the C/S group in the prolonga- Preoperative Hb level (g/dl) 11.22±1.64 11.72±1.07 0.056 tion of the operation time. Postoperative Hb level (g/dl) 10.05±1.17 10.17±1.35 0.548 Most myomas are asymptomatic during pregnancy. Δ Hemoglobin level (g/dl) 1.59±0.66 1.40±0.44 0.177 In symptomatic pregnancies, pain, a feeling of pelvic Uterine atony 3 (6.7%) 7 (3.0%) 0.222 pressure, or vaginal bleeding may occur due to myoma Transfusion requirement 3 (6.7%) 6 (2.6%) 0.152 size or degenerative changes associated with pregnancy. Relaparotomy 0 0 N.A Obstetric complications such as abortion, preterm birth, Visceral organ injury 0 0 N.A placental abruption, dystocia and increased frequency of Major vascular complications 0 0 N.A Cesarean deliveries may also be associated with the uter- Hospital stay (hours) 37.54±10.02 36.26±10.96 0.439 ine leiomyomas seen in pregnancy.[14] Akkurt et al. Values are stated as mean±SD or as number (%). *<.05 indicates statistical signifi- cance. N.A: not available. reported that C/S myomectomy may have positive effects on subsequent pregnancies, that myoma recur- rence was not common after the operation and that there identify the cleavage plane to be used for myomecto- was no serious operation-related adhesion formation.[15] my.[16,17] Due to the increased elasticity of the pregnant In this respect, C/S myomectomy can have a number of uterus, the suturation process can be performed more advantages. The incision required for myomectomy dur- easily without damaging the tissue, and at the same time ing C/S will be smaller than the incision made for the postpartum uterine contractions and uterine involution non-pregnant uterus, and technically it may be easier to contribute to reduction of hemorrhaging.[18] In our study,
114 Perinatal Journal Myomectomy during cesarean section: is it a safe procedure?
we did not find any difference in terms of postoperative tistical power to detect differences between groups, hemoglobin levels or estimated blood loss between the resulting in a type II error. Dedes et al. did not report C/S myomectomy patients and the C/S patients without significant differences in estimated blood loss, decline in myomas. hemoglobin, and need for additional uterotonics.[24] Another advantage of the myomectomy performed Hence, it remains unclear whether the number, site, and during C/S is that two separate operations are performed size of leiomyomas should influence decision-making. in one session. Moreover, the possible risks of re-opera- Future studies with multivariable analyses of these char- tion are prevented, while at the same time the cost is also acteristics should specifically investigate the effect of reduced.[19] As a matter of fact, in their study, Liu et al. myomectomy during cesarean delivery on intraoperative reported that 40% of the myoma cases where myomec- and postoperative outcomes. tomy was not performed during C/S, were re-operated Hat›rnaz et al. reported that the disadvantages of the on within 6 to 38 months postoperatively.[20] C/S myomectomy include increased operative time, Some factors to consider for myomectomy during extensive myometrial damage and possible post-opera- tive adhesion formation, which they stated are more C/S include the number, size and localization of the often related to the serosal surface incision for myomec- myomas, the possible effects on uterine contractility, the tomy. Therefore, they described the endometrial surface experience of the surgeon and the facilities at the health myomectomy incision techniques they performed in institution where the operation is performed. For this order to reduce these complications and which short- reason, in order to safely perform C/S myomectomy, ened the operation time compared to the classic C/S experience in appropriate surgical techniques should be myomectomy. They were also able to reduce blood loss attained and training in surgical and medical methods to [13] and adhesion formation on the endometrial surface. reduce bleeding should be obtained. If these considera- Two of our patients had undergone endometrial tions are taken into account, myomectomy can be per- myomectomy with anterior placement of intramural formed safely during C/S. Senturk et al. in their evalua- myomas, and one of them developed a hematoma in the tion of 212 C/S myomectomies reported that at first they myoma localization, but this hematoma was monitored applied this procedure to the smaller myomas, and after under expectant management. The patient did not need gradually gaining more experience, they excised the larg- a blood transfusion and the resulting hematoma was er and more numerous myomas during the C/S. In that spontaneously resorbed. study, they also evaluated 66 C/S myomectomy patients The study we conducted had some limitations. These having myomas of 5 cm or more in diameter along with mainly included the retrospective nature of the study, 31 non-myomectomy patients and reported that no dif- the relatively low number of patients involved. We per- ferences were found between the C/S myomectomy formed a power analysis on the data relative to the trans- group and the non-myomectomy group in terms of low- fusion requirement. This data indicate that a sample of ered hemoglobin levels, necessary blood transfusions or 220 patients in each arm could detect an efficacy of operation-related complication rates.[21] We achieved myomectomy between the groups, with 80% power and similar results in our study. an error of 5%. There were 235 patients in the non- Intraoperative hemorrhage is the most common myomectomy group but we had 45 patients in the [11] complication of C/S myomectomy. For this reason, myomectomy group. Therefore we planned to include some sources suggest applying vasopressin infusion, all eligible patients in myomectomy group. Lack of bilateral uterine artery ligation or uterine tourniquet to information on long-term patient outcomes and subse- [22,23] reduce blood loss. We applied oxytocin infusion and quent pregnancies was among the limitations of the methylergonovine injection, but did not use any of the study. Another limitation was that patients who had above methods in our patients. Only 6.7% of the myomas detected during C/S and did not undergo patients with C/S myomectomy required blood transfu- myomectomy were not included in the study. In our sions and there was no difference in the hemoglobin view, the strongest aspect of our study was that the oper- level drop between C/S myomectomy and the non- ations were performed by surgeons trained in surgical myomectomy operations; nevertheless, the small sample treatment of obstetric hemorrhage and having a high size used in this study could have led to insufficient sta- volume of surgical experience.
Volume 26 | Issue 3 | December 2018 115 Baflbu¤ A et al.
Conclusion 12. Hassiakos D, Christopoulos P, Vitoratos N, Xarchoulakou E, Vaggos G, Papadias K. Myomectomy during cesarean section: Myomectomy C/S carried out by experienced surgeons a safe procedure? Ann N Y Acad Sci 2006;1092:408–13. may be a safe surgical procedure and can be applied 13. Hat›rnaz fi, Güler O, Baflarano¤lu S, Tokgöz C, K›l›ç GS. without increasing intraoperative and postoperative Endometrial myomectomy: a novel surgical method during complications. Moreover, in this instance, the patient cesarean section. J Matern Fetal Neonatal Med 2018;31:433– does not need a second operation after C/S. Large-scale 8. prospective randomized controlled studies are needed 14. Lee HJ, Norwitz ER, Shaw J. Contemporary management of that include long-term outcomes and the method of fibroids in pregnancy. Rev Obstet Gynecol 2010;3:20–7. delivery in subsequent pregnancies. 15. Akkurt MO, Yavuz A, Eris Yalcin S, Akkurt I, Turan OT, Yalcin Y, et al. Can we consider cesarean myomectomy as a Conflicts of Interest: No conflicts declared. safe procedure without long-term outcome? J Matern Fetal Neonatal Med 2016;9:1–6. References 16. Sparić R. Uterine myomas in pregnancy, childbirth and puer- perium. [Article in Serbian] Srp Arh Celok Lek 2014;142:118– 1. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. 24. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 17. ‹ncebiyik A, Hilali NG, Camuzcuoglu A, Vural M, 2003;188:100–7. Camuzcuoglu H. Myomectomy during cesarean: a retrospec- 2. Boynton JR, Rich-Edwards J, Malspeis S, Missmer SA, Wright tive evaluation of 16 cases. Arch Gynecol Obstet 2014;289: R. A prospective study of hypertension and risk of uterine 569–73. leiomyomata. Am J Epidemiol 2005;161:628–38. 18. Lee JH, Cho DH. Myomectomy using purse-string suture 3. Laughlin SK, Baird DD, Savitz DA, Herring AH, Hartmann during cesarean section. Arch Gynecol Obstet 2011;283 Suppl KE. Prevalence of uterine leiomyomas in the first trimester of 1:S35–S7. pregnancy: an ultrasound-screening study. Obstet Gynecol 19. Sparić R, Kadija S, Stefanović A, Spremović Radjenović S, 2009;113:630–5. Likić Ladjević I, Popović J, et al. Cesarean myomectomy in 4. Exacoustòs C, Rosati P. Ultrasound diagnosis of uterine modern obstetrics: more light and fewer shadows. J Obstet myomas and complications in pregnancy. Obstet Gynecol Gynaecol Res 2017;43:798–804. 1993;82:97–101. 20. Liu WM, Wang PH, Tang WL, Wang IT, Tzeng CR. 5. Kwawukume EY. Myomectomy during cesarean section. Int J Uterine artery ligation for treatment of pregnant women with Gynaecol Obstet 2002;76:183–4. uterine leiomyomas who are undergoing cesarean section. 6. Kaymak O, Ustunyurt E, Okyay RE, Kalyoncu S, Molla- Fertil Steril 2006;86:423–8. mahmutoglu L. Myomectomy during cesarean section. Int J 21. Senturk MB, Polat M, Do¤an O, Pulato¤lu Ç, Yard›mc› OD, Gynaecol Obstet 2005;89:90–3. Karakufl R, et al. Outcome of cesarean myomectomy: is it a 7. Coronado GD, Marshall LM, Schwartz SM. Complications in safe procedure? Geburtshilfe Frauenheilkd 2017;77:1200–6. pregnancy, labor, and delivery with uterine leiomyomas: a 22. Topçu HO, ‹skender CT, Timur H, Kaymak O, Memur T, population-based study. Obstet Gynecol 2000;95:764–9. Dan›flman N. Outcomes after cesarean myomectomy versus 8. Park BJ, Kim YW. Safety of cesarean myomectomy. J Obstet cesarean alone among pregnant women with uterine leiomy- Gynaecol Res 2009;35:906–11. omas. Int J Gynaecol Obstet 2015;130:244–6. 9. Neiger R, Sonek JD, Croom CS, Ventolini G. Pregnancy- 23. Lin JY, Lee WL, Wang PH, Lai MJ, Chang WH, Liu WM. related changes in the size of uterine leiomyomas. J Reprod Uterine artery occlusion and myomectomy for treatment of Med 2006;51:671–4. pregnant women with uterine leiomyomas who are undergoing 10. Vitale S G, Padula F, Gulino F A. Management of uterine cesarean section. J Obstet Gynaecol Res 2010;36:284–90. fibroids in pregnancy: recent trends. Curr Opin Obstet 24. Dedes I, Schäffer L, Zimmermann R, Burkhardt T, Haslinger Gynecol 2015;27:432–7. C. Outcome and risk factors of cesarean delivery with and 11. Song D, Zhang W, Chames MC, Guo J. Myomectomy during without cesarean myomectomy in women with uterine cesarean delivery. Int J Gynaecol Obstet 2013;121:208–13. myomatas. Arch Gynecol Obstet 2017;295:27–32.
116 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 2018;26(3):117–123 I N N R A U T A L J O
Conventional Doppler myocardial performance index, tricuspid and mitral annular plane systolic excursions in the assessment of fetal heart functions
fiebnem Paytoncu Pediatric Cardiology Clinic, Merkezefendi State Hospital, Manisa, Turkey
Abstract Özet: Fetal kalp fonksiyonlar›n›n de¤erlendirilmesinde konvansiyonel Doppler miyokardiyal performans indeksi, triküspid ve mitral kapak anüler düzlem sistolik hareketleri Objective: Tei index and TAPSE & MAPSE are very useful and Amaç: Tei indeksi, global miyokardiyal sistolik ve diastolik fonksi- reliable non-invasive methods to assess the global myocardial sys- yonlar›n, TAPSE ve MAPSE, sa¤ ve sol ventriküler longitüdinal mi- tolic and diastolic functions, and right and left ventricular longitu- yokardiyal fonksiyonlar›n de¤erlendirilmesinde oldukça yararl›, gü- dinal myocardial functions, respectively. In this study, we aimed to venilir, non-invaziv yöntemlerdir. Bu çal›flmada fetal sa¤ ve sol ven- assess fetal right and left ventricle (RV and LV) functions by trikül (RV ve LV) fonksiyonlar›n›n miyokardiyal performans indek- myocardial performance index (Tei index) and tricuspid and mitral si (Tei indeksi); triküspid ve mitral kapak anüler düzlem sistolik ha- annular plane systolic excursions (TAPSE and MAPSE). reketleri (TAPSE ve MAPSE) ile de¤erlendirilmesi amaçlanm›flt›r. Methods: The findings of fetal echocardiographies performed in Yöntem: Aral›k 2015 – Nisan 2017 tarihleri aras›nda kontrol amaç- our center for control purposes between December 2015 and April l› olarak merkezimizde yap›lan fetal ekokardiyografik bulgular ince- 2017 were assessed. By obtaining appropriate positions in 152 fetus- lendi. Uygun gestasyonel haftadaki 152 fetüste, uygun pozisyonlar es which are at eligible weeks of gestation, Tei index and TAPSE elde edilerek Tei indeksi ölçümleri, TAPSE ve MAPSE ölçümleri and MAPSE measurements were recorded. Repeating echocardio- kaydedildi. Tekrarlanan ekokardiyografiler çal›flma kapsam› d›fl›nda graphies were excluded from the study. b›rak›ld›. Results: Of all fetuses included in the study, LV Tei index was Bulgular: Çal›flmaya al›nan tüm fetüslerin; LV Tei indeksi 0.47±0.16, RV Tei index was 0.52±0.17, TAPSE was 0.47±0.1 cm, and 0.47±0.16, RV Tei indeksi 0.52±0.17, TAPSE 0.47±0.1 cm, MAP- MAPSE 0.36±0.07 cm. Seventy-two fetuses were at 20+3–26 weeks of SE 0.36±0.07 cm idi. Yetmifl iki fetüs 20+3–26. hafta, 80 fetüs gestation, and 80 fetuses were at 26+3–37+3 weeks of gestation. Both 26+3–37+3 hafta aras›nda bulunuyordu. Ölçümler bu iki grup için groups were measured separately and they were compared. While there ayr› ayr› gerçeklefltirildi ve karfl›laflt›r›ld›. ‹lerleyen gestasyon haf- was no significant increase in LV and RV Tei indices and mitral valve tas›nda LV ve RV Tei indeks ve mitral kapak gradiyentinde an- gradient during the advanced weeks of gestation, significant difference laml› art›fl bulunmazken, TAPSE ve MAPSE de¤erlerinde anlam- was observed in TAPSE and MAPSE values (p=0.001 for both). l› art›fl oldu¤u görüldü (her ikisi için p=0.001). Conclusion: Tei index, and TAPSE and MAPSE are reliable non- Sonuç: Tei indeksi, global kalp fonksiyonlar›n›n, TAPSE ve invasive methods for global heart functions and annular plane sys- MAPSE ise sa¤ ve sol ventriküllerin anüler düzlem sistolik longi- tolic longitudinal functions of right and left ventricles, respectively, tüdinal fonksiyonlar›n›n non-invaziv olarak de¤erlendirilmesinde, which are easily used on fetuses as well as children who are healthy sa¤l›kl› ve konjenital kalp hastal›¤› bulunan çocuklarda oldu¤u gi- or with congenital heart disease; and these methods also can be used bi, fetüslerde de kolay uygulanabilen, rutinde de kullan›labilecek, in the routine practice. güvenilir yöntemlerdir. Keywords: Fetal heart functions, Tei index, TAPSE, MAPSE. Anahtar sözcükler: Fetal kalp fonksiyonlar›, Tei indeksi, TAPSE, MAPSE.
Correspondence: fiebnem Paytoncu, MD. Pediatric Cardiology Clinic, Merkezefendi Available online at: State Hospital, Manisa, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263004 doi:10.2399/prn.18.0263004 Received: October 12, 2018; Accepted: December 3, 2018 QR (Quick Response) Code: Please cite this article as: Paytoncu fi. Conventional Doppler myocardial performance index, tricuspid and mitral annular plane systolic excursions in the assessment of fetal heart functions. Perinatal Journal 2018;26(3):117–123. ©2018 Perinatal Medicine Foundation Paytoncu fi
Introduction 2015 and April 2017 were assessed. The pregnant Myocardial performance index (Tei index), which was women who were 18–40 (mean: 27.7±5.17) years old, first defined in healthy individuals and adult patients of which 72 (47.4%) were at 20+3 – 26 weeks of gestation with dilated cardiomyopathy and for which many studies and 80 (52.6%) at 26+3 – 37+3 weeks of gestation were have been performed so far on children who were nor- assessed by fetal echocardiography. By obtaining appro- mal, healthy and had congenital heart disease, is an priate positions in 152 fetuses which were at 20+3 – 37+3 echocardiographic assessment method which is obtained weeks of gestation and did not have congenital heart by Doppler echocardiographic measurements and has a disease, dysrhythmia, myocarditis, pericardial effusion significant role for the assessment of global myocardial and valve insufficiency, Tei index measurements, and systolic and diastolic functions.[1–5] pulse wave Doppler measurements of atrioventricular For about two decades, echocardiography, radionu- and semilunar valves were performed. The pregnant clide studies and various methods such as magnetic res- women were asked to be full before the fetal echocar- onance imaging as well as right ventricular functions diography which were considered to be “neglected” in the past have been the subjects of many studies. Tricuspid annular Echocardiography plane systolic excursion (TAPSE) is an echocardiograph- Echocardiography measurements of all fetuses were ic method which has been studied well in all age groups, performed by the same investigator (Dr. fiP) via Phase a wide range of patient groups and healthy children, of Array pediatric transducer S8-3 mHz of 2005 HD11- which mean and z-score values have been determined for XE device (©Philips Medical System Nederland BV, age groups, which is reliable and easy to perform, can be Best, the Netherlands). The measurements were done obtained by M-mode measurements, useful for the separately for each valve. Sample volume was obtained assessment of right ventricular longitudinal myocardial by placing on the farthest ends of atrioventricular valve function and which is independent from heart rate, ven- leaflets on apical 4 chamber position. The mean of tricle size and geometry.[6–8] three consecutive valve flow measurements was calcu- Mitral annular plane systolic excursion (MAPSE) is a lated. All valve flow rates were obtained while sweep reliable and easy-to-perform non-invasive method to rate was 50 mm/sec. E and A waves of mitral and tri- assess left ventricular longitudinal myocardial functions cuspid valves, E/A rates, aortic and pulmonary artery which is performed on adults and children who are flows were obtained. Fetal heart rates were measured healthy or have disease, obtained by M-mode measure- four times when calculating the flows of mitral valve, ments, of which mean and z-score values have been aortic valve, tricuspid valve and pulmonary valve. determined, and for which many studies have been per- [9–11] Ejection fraction (EF) and fractional shortening (FS) formed so far. values, TAPSE and MAPSE measurements, and mini- There are a limited number of studies where annular mum and maximum heart rates were recorded. plane systolic excursions of atrioventricular valves (TAPSE and MAPSE) and Tei index are assessed in Statistical analysis healthy fetuses by M-mode echocardiography during [12–15] All data were recorded to Excel (2010; Microsoft fetal period. Office Corp., Redmond, WA, USA), and transferred In this study, we aimed to assess fetal right and left to SPSS 15.0 SPSS for Windows v.15.0; IBM-SPSS ventricle (RV and LV) functions by conventional Doppler Inc., Chicago, IL, USA) for statistical analysis. The myocardial performance index (Tei index) and tricuspid difference between mean values among independent and mitral annular plane systolic excursions (TAPSE and groups was analyzed by independent sample test. The MAPSE) in healthy fetuses, to compare the data we obtained and investigate the relationship between them. values were given as standard +/- deviation (SD). Pearson correlation and linear regression analyses were used to find the relationship between the vari- Methods ables. As the correlation coefficient, r<0.25 was con- Patient group sidered poor, 0.25–0.49 was considered average, The findings of fetal echocardiographies performed in 0.50–0.74 was considered strong and >0.75 was consid- our center for control purposes between December ered very strong.
118 Perinatal Journal Conventional Doppler myocardial performance index, tricuspid and mitral annular plane systolic excursions
Table 1. General characteristics of all fetuses..
Second trimester Third trimester All fetuses Variable (Group 1) (Group 2) (Group 1+2)
Mean gestational age (week) 23.82±1.41 29.95±2.89 27.05±3.83 LV Tei index 0.46±0.16 0.47±0.15 0.47±0.16 RV Tei index 0.51±0.16 0.53±0.18 0.52±0.17 MV E/A 0.59±0.07 0.65±0.1 0.624±0.09 TV E/A 0.63±0.07 0.67±0.08 0.656±0.08 Minimum heart rate (/min) 139.23±7.24 135.62±8.77 137.2±7.99 Maximum heart rate (/min) 149.37±6.48 148.17±7.5 148.73±7.05 TAPSE (cm) 0.44±0.08 0.52±0.11 0.47±0.1 MAPSE (cm) 0.32±0.07 0.39±0.07 0.36±0.07 EF (%) 74.99±4.48 75.01±4.93 75±4.70 FK (%) 39.56±3.84 40.1±4.52 39.84±4.20
Results 0.39±0.07 cm. The variables of the groups are shown in Mean parameter values of all fetuses included in the Table 1. study were as following: LV Tei index: 0.47±0.16, RV When we investigated to find whether there is any Tei index: 0.52±0.17, EF: 75±4.7%, FS: 39.84±4.2%, statistically significant difference between two groups in TAPSE: 0.47±0.1 cm, MAPSE: 0.36±0.07 cm, mitral terms of all parameters assessed during advanced weeks E/A: 0.624±0.09, tricuspid E/A: 0.656±0.08, aortic of gestation, we found that there was no significant dif- valve flow: 71.43±12.53 cm/sec, pulmonary valve flow: ference among LV Tei index, RV Tei index, and mitral 66.16±8.61 cm/sec, minimum heart rate: 137.2± valve mean gradient values while there was a significant 7.99/min, maximum heart rate: 148.73±7.05/min. The increase in TAPSE and MAPSE values (p=0.001 and fetal assessments were done during the first pregnancy p=0.001, respectively) (Figs. 1–4). Also, we found a sig- in 21.7% of the patients, during the second pregnancy nificant increase in aortic and pulmonary valve flows and in 30.3% of them, during the third pregnancy in tricuspid valve mean gradient value (p=0.002, p=0.017 14.5% of them, during the fourth pregnancy in 8.6% of them, during the fifth pregnancy in 0.7% of them, and during the sixth pregnancy in 1.3%. Pregnancy information could not be obtained in 23% of the patients. The mean values in the second trimester group (Group 1) were as following: LV Tei index: 0.46±0.16, RV Tei index: 0.51±0.16, mitral valve E/A: 0.59±0.07, tricus- pid valve E/A: 0.63±0.07, minimum heart rate: 139.23± 7.24/min, maximum heart rate: 149.37±6.48/min, aortic valve flow: 68.05±12.5 cm/sec, pulmonary valve flow: 64.37±8.98 cm/sec, TAPSE: 0.44±0.08 cm, and MAPSE: 0.32±0.07 cm. The mean values in the third trimester group (Group 3) were as following: LV Tei index: 0.47±0.15, RV Tei index: 0.53±0.18, mitral valve E/A: 0.65±0.1, tricuspid valve E/A: 0.67±0.08, minimum heart rate: 135.62± 8.27/min, maximum heart rate: 148.17±7.5/min, aortic valve flow: 74.38±11.86 cm/sec, pulmonary valve flow: 67.72±8.0 cm/sec, TAPSE: 0.52±0.11 cm, and MAPSE: Fig. 1. Difference between the groups in terms of LV Tei index.
Volume 26 | Issue 3 | December 2018 119 Paytoncu fi
Fig. 2. Difference between the groups in terms of RV Tei index. Fig. 3. Difference between the groups in terms of TAPSE value. and p= 0.001, respectively). In terms of heart rates, min- ly significant correlation between TAPSE and RV Tei imum heart rate was significantly different between two index (r=0.322; p=0.001). However, there was a negative, groups (p=0.006) while maximum heart rate was similar poor and statistically significant correlation between in both groups. The correlations between RV and LV MAPSE and LV Tei index (r=-0.157; p=0.208). Tei indexes and the week of gestation were r=0.091; Mean TAPSE and MAPSE values and LV and RV p=0.298 and r= 0.137; p=0.097, respectively. There was a Tei indices ± SD of the fetuses between 22 and 32 weeks strong and statistically significant correlation between of gestation are shown in Table 2. TAPSE and the week of gestation (r=0.537; p=0.001). There was also a strong and statistically significant cor- relation between MAPSE and the week of gestation (r=0.523; p=0.001). There was an average and statistical-
Table 2. The mean TAPSE, MAPSE, RV and LV Tei index values of the fetuses between 22 and 32 weeks of gestation.
Week of TAPSE MAPSE LV Tei RV Tei gestation (cm) (cm) index index
22 0.39±0.07 0.39±0.12 0.49±0.14 0.53±0.17 23 0.43 0.25 0.56 0.53 24 0.44±0.06 0.32±0.05 0.42±0.19 0.48±0.20 25 0.42 0.25 0.48 0.61 26 0.47±0.07 0.37±0.08 0.55±0.10 0.61±0.14 27 0.45 0.37 0.50 0.58 28 0.55±0.05 0.33±0.0 0.45±0.15 0.57±0.24 29 0.51 0.39 0.42 0.53 30 0.47±0.12 0.35±0.04 0.52±0.17 0.49±0.11 31 0.56 0.28 0.46 0.65 32 0.57±0.07 0.370.01 0.52±0.17 0.46±0.15 Fig. 4. Difference between the groups in terms of MAPSE value.
120 Perinatal Journal Conventional Doppler myocardial performance index, tricuspid and mitral annular plane systolic excursions
Discussion applied by the ventricles. A wave is atrial, active or late Assessing fetal myocardial functions properly is criti- wave, and it reflects the atrial contraction during ven- cally significant to identify high-risk fetuses.[12,16] When tricular filling. Chronic hypoxia and cardiac overload [22] assessing systolic and diastolic functions, Tei index can be given as the examples changing this rate. which is independent from the size and shape of ven- While mitral E/A was 0.624±0.09 and tricuspid E/A tricle and heart rate is one of the important parameters was 0.656±0.08 in our study, Parasuraman et al. report- determining the fetal heart health. Some studies have ed LV E/A and RV E/A values 0.68±0.07 and [13] reported that it increases in advanced weeks of gesta- 0.716±0.109, respectively. In the intrauterine growth tion while some other studies have argued that there is retardation, the rates are lower in the fetuses with same no such correlation and there is even a negative corre- gestational ages compared to the normal ones. The lation.[12,16,17] In our study, we did not observe a signifi- values found were at 10–25 percentile values for mitral cant increase in advanced weeks of gestation. When E/A and tricuspid E/A according to the reference val- [13] calculating Tei index, some authors measured ventricle ues determined by Parasuraman et al. Also, the aor- entrance (mitral and tricuspid valves) and exit (aortic tic valve flow was 71.43±12.53 cm/sec and pulmonary and pulmonary) pulsed Doppler records separately valve flow was 66.16±8.61 cm/sec in the entire group. while some authors only measured time intervals that These values were at 10–25 percentile values for aortic they obtained from a single Doppler record placed on and pulmonary valve flows according to the reference an appropriate position. In our study, we measured values determined in a previous report. Messing et al. aortic and mitral, tricuspid and pulmonary valve flows compared conventional fetal TAPSE and spatiotempo- consecutively and separately and we took the mean ral image correlation (STIC)-TAPSE methods, and they reported high correlation for both methods value of three different measurements. Friedman et al. [23] studied Tei index on 74 healthy pregnant women (r=0.904). In their study, conventional fetal TAPSE whose mean gestational age was 24±3.4 (range: 18–31) value was 0.36±0.11 cm at 21 weeks of gestation while weeks, and they found the mean LV Tei index it was 0.86±0.15 cm at 39 weeks of gestation. The mean 0.53±0.13.[12] Tsutsumi and Eidem et al. reported LV TAPSE and MAPSE values according to the gestation- Tei index 0.62±0.07 (range: 18–26) week and al age reported by Koestenberger et al. in different 0.35±0.03 in their studies, respectively.[16,18] Mori et al. studies and the mean TAPSE and MAPSE values we found in our study according to the week of gestation reported RV Tei index 0.35±0.07 and showed that it [11,15] did not change during gestation.[19] In our study, mean were consistent. It has been reported that TAPSE RV Tei index was 0.52±0.17 and LV Tei index was value was higher than MAPSE value at any week of 0.47±0.08 in the entire group. In the following weeks, gestation due to the fact that dominant ventricle is the right ventricle in fetus and due to the structural char- RV and LV Tei index did not exhibit any statistically [24] significant increase. acteristics of myocardial fibril distribution. In our study, we found TAPSE value higher than MAPSE It has been reported that Tei index values increased value, and TAPSE/MAPSE ratio was 1.37 at the sec- in fetal ventricular dysfunction cases (such as intrauter- ond trimester while it was 1.33 at the third trimester. It ine growth retardation, twin-to-twin transfusion syn- is known that TAPSE value decreases in pathological drome, maternal diabetes mellitus, preeclampsia, and [25,26] conditions. It has been reported that MAPSE value congenital heart diseases).[20,21] Diastolic dysfunction decreases in adult patients, and cardiovascular disease which provides information about compliance and [9,27] and extracardiac pathological conditions. relaxation capacity of myocytes can be assessed by the flow pattern of tricuspid and mitral valves. In our study, mean mitral and tricuspid E/A values for the Conclusion entire group were 0.62±0.09 and 0.65±0.08, respective- Tei index, and TAPSE and MAPSE are reliable non- ly. E/A rate is usually <1, and it exhibits a constant invasive methods for global heart functions and annu- increase during gestation. E wave is early or passive lar plane systolic longitudinal functions of right and filling wave and it is associated with the relaxation left ventricles, respectively, which are easily used on function of myocardium and the negative pressure fetuses as well as children who are healthy or with con-
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genital heart disease; and these methods also can be 10. Tomomasa T, Kazuhino M, Miki I, Hayabuchi Y. Mitral annu- used in the routine practice. Knowing normal values in lar plane systolic excursion / left ventricular lenght (MAPSE/L) as a simple index for assessing left ventricular longitudinal func- healthy fetuses and children will help to understand tion in children. Echocardiography 2016;33:1703–9. cardiac and extracardiac pathological conditions better 11. Koestenberger M, Nagel B, Ravekes WA, Avian A, Heinzl B, where these parameters increase and decrease. We Frithsch PW, et al. Left ventricular long-axis function: refer- believe that TAPSE, MAPSE, LV Tei and RV Tei val- ence values of mitral annular plane systolic excursion in 558 ues that we found according to the gestational age will healthy children of Z-score values. Am Heart J 2012;164:125– provide an insight for the studies to be performed by 31. advanced techniques. 12. Friedman D, Buyon J, Kim M, Glickstein JS. Fetal cardiac function assessed by Doppler myocardial performance index (Tei index). Ultrasound Obstet Gynecol 2003;21:33–6. Conflicts of Interest: No conflicts declared. 13. Parasuraman R, Osmond C, Howe DT. Gestation-spesific ref- erence intervals for fetal cardiac Doppler indices from 12 to 40 References weeks of gestation. Open Journal of Obstetrics and Gynecology 1. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer 2013;3:97–104. RJ, et al. New index of combined systolic and diastolic myocar- 14. Bravo-Valenzuela NJ, Peixoto AB, Nardozza LM, Souza AS, dial performance: a simple and reproducible measure of cardiac Araujo Junior E. Applicability and technical aspects of two- function – a study of normal and dilated cardiomyopathy. J dimensional ultrasonography for assessment of fetal heart func- Cardiol 1995;26:357–66. tion. Med Ultrason 2017;19:94–100. 2. Eto G, Ishii M, Tei C, Tsutsumi T, Akagi T, Kato H. 15. Koestenberger M, Nagel B, Ravekes W, Gamillscheg A, Assessment of global left ventricular function in normal chil- Binder C, Avian A, et al. Longitudinal systolic left ventricular dren and in children with dilated cardiomyopathy. J Am Soc function in preterm and term neonates: reference values of Echocardiogr 1999;12:1058–64. mitral annular plane systolic excursion (MAPSE) and calcula- tion of Z-scores. Pediatric Cardiol 2015;36:20–6. 3. Song B, Qi Q, Liu R, Xing W, Tang H, Li Y. Clinical value of Tei index in pediatric patients with repaired tetralogy of Fallot. 16. Tsutsumi T, Ishii M, Eto G, Hota M, Kato H. Serial evalua- Int J Clin Exp Med 2015;8:7971–6. tion for myocardial performance in fetuses and neonates using a new Doppler index. Pediatr Int 1999;41:722–7. 4. Cui W, Roberson DA. Left ventricular Tei index in children: Comparison of tissue Doppler imaging, pulsed wave Doppler, 17. Nair A, Radhakrishnan S. Fetal left ventricular myocardial per- formance index: defining normal values for Indian population and M-mode echocardiography normal values. J Am Soc and review of literature. Ann Pediatr Cardiol 2016;9:132–6. Echocardiogr 2006;19:1438–45. 18. Eidem BW, Edwards JM, Cetta F. Quantitative assessment of 5. K›r M, Ünal N, Sa¤›n Saylam G, Karadafl U, fiahin M. fetal ventricular function: establishing normal values of the Ventriküler septal defektli çocuklarda sol ventrikül fonksiyon- myocardial performance index in the fetus. Echocardiography lar›n›n miyokardiyal performans indeksi (Tei indeksi) 2001;18:9–13. kullan›larak de¤erlendirilmesi. Dokuz Eylül Üniversitesi T›p Fakültesi Dergisi 2008;22:113–9. 19. Mori Y, Rice MJ, McDonald RW, Reller MD, Wanitkun S, Harada K, et al. Evaluation of systolic and diastolic ventricular 6. Koestenberger M, Nagel B, Ravakes W, Urlesberger B, Raith performance of the right ventricle in fetuses with ductal con- W, Avian A, et al. Systolic right ventricular function in preterm striction using the Doppler Tei index. Am J Cardiol and term neonates: reference values of the tricuspid annular 2001;88:1173–8. plane systolic excursion (TAPSE) in 258 patients and calcula- 20. Battista MC, Calvo E, Chorvatova A, Comte B, Corbeil J, tion of Z-score values. Neonatology 2011;100:85–92. Brochu M. Intra-uterin growth restriction and the program- 7. Paytoncu fi. Tricuspid annular plane systolic excursion ming of left ventricular remodeling in female rats. J Physiol (TAPSE) and cardiac Z score values in 827 healthy Turkish 2005;565:197–205. children: single center results. Türkiye Klinikleri Journal of 21. Mahajan A, Henry A, Meriki N, Hernandez-Andrade E, Crispi Cardiovascular Sciences 2015;27:95–102. F, Wu L, et al. The (Pulsed-wave) Doppler fetal myocardial 8. Halimić M, Terzić S, Kadić A, Begić Z, Vukas E, Mišanović V, performance index: technical challenges, clinical applications et al. Right ventricular systolic longitudinal function in infants: and future research. Fetal Diagn Ther 2015;38:1–13. correlation of TAPSE with gestational age and body weight. 22. Hernandez-Andrade E, Benavides-Serralde JA, Cruz-Martinez Journal of Pediatric and Neonatal Individualized Medicine R, Welsh A, Mancilla-Ramirez J. Evaluation of conventional 2018;7:e070216. Doppler fetal cardiac function parameters: E/A ratios, outflow 9. Kai H, Dan L, Herrmann S, Niemann M, Gaudron PD, tracts and myocardial performance index. Fetal Diagn Ther Voelker W, et al. Clinical implication of mitral annular plane 2012;32:22–9. systolic excursion for patients with cardiovascular disease. Eur 23. Messing B, Gilboa Y, Lipschuetz M, Valsky DV, Cohen SM, Heart J Cardiovasc Imaging 2013;14:205–12. Yagel S. Fetal tricuspid annular plane systolic excursion (f-
122 Perinatal Journal Conventional Doppler myocardial performance index, tricuspid and mitral annular plane systolic excursions
TAPSE): evaluation of fetal right heart systolic function with annular plane systolic excursion (TAPSE) and magnetic reso- conventional M-mode ultrasound and spatiotemporal image nance imaging data. Congenit Heart Dis 2012;7:250–8. correlation (STIC) M-mode. Ultrasound Obstetr Gynecol 26. Mercer-Rosa L, Parnell A, Forfia PR, Yang W, Goldmuntz E, 2013;42:182–8. Kawut SM. Tricuspid annular plane systolic excursion in the 24. Gardiner HM, Pasquini L, Wolfenden J, Barlow A, Kulinskaya assessment of right ventricular function in children and adoles- E, Henein M. Myocardial tissue Doppler and long axis function cents after repair of tetralogy of Fallot. J Am Soc Echocardiogr in the fetal heart. Int J Cardiol 2006;113:39–47. 2013;26:1322–9. 25. Koestenberger M, Nagel B, Avian A, Ravekes W, Sorantin E, 27. Bergenzaun L, Öhlin H, Gudmundson P, Willenheimer R, Cvirn G, et al. Systolic right ventricular function in children Chew MS. Mitral annular plane systolic excursion (MAPSE) in and young adults with pulmonary artery hypertension second- shock: a valuable echocardiographic parameter in intensive care ary to congenital heart disease and tetralogy of Fallot: tricuspid patients. Cardiovasc Ultrasound 2013;11:16.
Volume 26 | Issue 3 | December 2018 123 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 2018;26(3):124–134 I N N R A U T A L J O
The distribution of primary cesarean section indication at a university hospital: ten-year experience and potential lessons to be taken to decrease cesarean section rates
Semir Köse1, Asl› Akdöner2, Sabahattin Altunyurt3 1Perinatology Clinic, Buca Obstetrics and Pediatrics Hospital, ‹zmir, Turkey 2Clinic of Gynecology and Obstetrics, Bitlis Güroymak State Hospital, Bitlis, Turkey 3Department of Gynecology and Obstetrics, Faculty of Medicine, Dokuz Eylül University, ‹zmir, Turkey
Abstract Özet: Bir üniversite hastanesinin primer sezaryen endikasyon da¤›l›m›: On y›la ait tecrübe ve sezaryen do¤um oranlar›n› azaltmaya yönelik ç›kar›labilecek dersler Objective: Although cesarean section can be a life-saving practice for Amaç: Gebe ve fetüs için hayat kurtar›c› olabilmesine ra¤men sezar- pregnant woman and fetus, great increase in the rates of cesarean sec- yen do¤um oranlar›nda son y›llardaki büyük art›fl, endikasyonlar›n›n tion in the recent years has made its indications questionable. Primary sorgulanmas›n› gündeme getirmifltir. Primer sezaryen (PS) do¤um cesarean section (PCS) is the main source of total cesarean section toplam sezaryen do¤um havuzunun ana kayna¤›d›r. Araflt›rmam›zda pool. In our study, we aimed to investigate the distributions of PCS PS endikasyon da¤›l›mlar›n›n incelenmesi ve gruplara ait olgu özel- indications and to determine the case characteristics of the groups. liklerinin belirlenmesi amaçlanm›flt›r. Methods: A full cohort of delivery room records for PCS carried Yöntem: Dokuz Eylül Üniversitesi Hastanesi’nde 1 Ocak 2007 ile out between January 1, 2007 and January 1, 2017 at the Hospital of 1 Ocak 2017 tarihleri aras›nda gerçeklefltirilmifl olan PS do¤umlara Dokuz Eylül University was analyzed. PCS cases were separated ait do¤umhane kay›tlar›n›n tam bir kohortu incelendi. PS olgular› into two groups as singleton and multiple pregnancies first, and then daha sonra tekil gebelikler ve ço¤ul gebelikler, tekil gebelikler de singleton pregnancies were separated into term-preterm and primi- term-preterm ve primipar-multipar olarak ikiye ayr›larak ileri alt parous-multiparous groups for advanced sub-group analyses. grup analizleri yap›ld›. Results: A total of 3284 PCS cases from a ten-year period were Bulgular: On y›ll›k bir dönemden 3284 PS do¤uma ait bilgilere accessed. Of the cases, 263 (8.0%) were twin pregnancy, 11 (0.3%) ulafl›ld›. Olgular›n 263’ü (%8.0) ikiz gebelik, 11’i (%0.3) üçüz ge- were triplet pregnancy, and 3010 (92.7%) were singleton pregnancy. belik olup 3010 olgu (%92.7) ise tekil gebeliklere aitti. Preterm ol- Of 494 (15.0%) preterm cases, 105 (21.3%) were in multiple preg- gu say›s› 494 (%15.0) olup bu olgular›n 105’i (%21.3) ço¤ul gebe- nancy group and 389 (78.7%) were in the singleton pregnancy group. likler, 389 olgu (%78.7) tekil gebelikler grubunda yer al›yordu. While dystocia (41.6%) was the most common indication among Term olgularda distosi (%41.6), preterm olgularda ise fetal distres term cases, it was fetal distress (35.4%) among the preterm cases. (%35.4) en s›k rastlanan endikasyonlar olarak saptand›. Pariteye When the cases were compared according to the parity, the rank and göre karfl›laflt›r›ld›¤›nda endikasyon s›ralamas› ve s›kl›klar› önemli frequency of the indication were varying significantly. Dystocia de¤iflkenlikler göstermekte idi. Primipar olgularda distosi (%40.2), (40.2%) was the most common indication among the primiparous multipar olgularda ise fetal distres (%23.0) en büyük endikasyon cases while it was fetal distress (23.0%) among the multiparous cases. grubunu oluflturmakta idi. Conclusion: Dystocia, which is the greatest indication among PCS Sonuç: PS kategorilerinin en büyü¤ü olan distosi, tan› kriterleri- categories, is the hardest indication to standardize due to the fact nin tart›flmal› olmas› ve bu kriterlerin saptanmas›ndaki öznellik that its diagnosis criteria are controversial and determining these cri- boyutu nedeniyle en zor standardize edilecek endikasyon olarak teria is very subjective. A different path should be followed for the öne ç›kmaktad›r. Fetal distres preterm do¤um olgular›nda en s›k solution of fetal distress issue since it is the most common indication rastlanan endikasyon grubu olmas› nedeni ile çözümünde farkl› bir in preterm labor cases. Breech presentations and the suspected yol izlenmesi gereken bir bafll›kt›r. Makat prezentasyonlar ve mak- macrosomic infant seem to be the first goal of the measures to be rozomik bebek flüphesi olgular› sezaryen do¤um ihtiyac›n› azalt- taken to decrease the need of cesarean section. maya yönelik tedbirlerin ilk hedefi olarak görünmektedir. Keywords: Primary cesarean section, dystocia, fetal distress, macro- Anahtar sözcükler: Primer sezaryen, distosi, fetal distres, makro- somia. zomi.
Correspondence: Semir Köse, MD. Perinatology Clinic, Buca Obstetrics and Pediatrics Available online at: Hospital, ‹zmir, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263005 doi:10.2399/prn.18.0263005 Received: June 16, 2018; Accepted: December 3, 2018 QR (Quick Response) Code: Please cite this article as: Köse S, Akdöner A, Altunyurt S. The distribution of primary cesarean section indication at a university hospital: ten-year experience and potential lessons to be taken to decrease cesarean section rates. Perinatal Journal 2018;26(3):124–134. ©2018 Perinatal Medicine Foundation The distribution of primary cesarean section indication at a university hospital
Introduction Delivering all twin pregnancies by cesarean section is an important question of debate whether it decreases peri- The rates of cesarean section have been increasing in natal mortality or not.[14] One of the focuses in the stud- Turkey as in the entire world and even much more rap- [1,2] ies to decrease PCS rates safely is the safety of external idly. According to OECD data, Turkey has become cephalic version in breech presentations.[15] In breech the number one country as of 2015 with the highest rate presentations, trying vaginal labor in both nulliparous for cesarean section with its rate of 531 cesarean section [2] and multiparous pregnant women is an important ques- out of 1000 live births. Cesarean sections can be cate- [16,17] tion of debate. Large infant (macrosomic fetus) is gorized in two groups which are primary and repeat.[3] included in the top 5 PCS indication category in clinical Primary cesarean section is defined as the first occur- [1,9] practice. Another aspect of macrosomic fetus category rence of cesarean section, and it is called “repeat” when is that it may be included in a different scenario in PCS the patient has a history of cesarean section or “former” labors due to dystocia except PCS labors directly due to cesarean section as it is preferred in Turkey. macrosomic fetus. While fetal weights which is 4500 g Therefore, primary cesarean sections (PCS) are the and above for diabetic pregnant women and 5000 g and main source of total cesarean section pool.[3] Barber et al. above for non-diabetic pregnant women are required for reported that PCS cases are responsible for 50% of the the macrosomia definition in the standard treatment increase in cesarean section rates.[4] PCS’ have widely- guidelines, an expected birth weight of 4000 g is chosen accepted indications;[1,3] however, the distribution of the as a more common cautionary threshold in practice.[18,19] indications may vary depending on the countries, centers The medicolegal concerns related with shoulder dysto- and even the physicians.[5] cia especially and brachial plexus paralysis and asphyxia Cesarean section has higher morbidity and mortality which may develop afterwards compel many obstetri- rates than the vaginal labor.[6] Cesarean section increases cians to make the decision for cesarean section as from [18,19] the risks of uterine rupture, placenta previa, placenta expected fetal weight of 400 g. Evaluating PCS indi- accreta, hemorrhage, hysterectomy and maternal mor- cation category due to macrosomic fetus and determin- tality in the further pregnancies.[7] Therefore, decreasing ing its relative weight will support the efficacy of labor PCS rates in a safe way without risking maternal and induction efforts to decrease PCS rates safely in preg- fetal health is among the primary health targets in the nancies with fetuses over the expected weights which are world[8] and Turkey.[9] close to the term, and the determination of sub-groups where it can be successful. PCS indications are considered in two main topics which are maternal and fetal indications.[10,11] The analy- sis of the distribution of these indications has a critical Methods significance to determine effective strategies for decreas- This study analyzed the full cohort of delivery room ing PCS needs. Among these indications, the most com- records for PCS cases carried out between January 1, mon and subjective one is dystocia[1,10] and it is an indica- 2007 and January 1, 2017 at the Department of tion also used as non-progressive labor or cephalopelvic Obstetrics and Gynecology of Dokuz Eylül University. disproportion in the clinical practice. Electronic fetal For that purpose, all PCS cases with indications which monitorization (EFM), which is routinely used for the were seen clearly were included in the study. PCS cases evaluation and follow-up of the well-being of fetus dur- were separated into two groups as singleton and multi- ing labor, is criticized for increasing PCS rates without ple pregnancies, and then singleton pregnancies were providing any significant improvement in the newborn separated into term-preterm and primiparous-multi- outcomes.[12] The changes and patterns seen in fetal heart parous groups for advanced sub-group analyses. Former rates during labor follow-up and interpreted as fetal dis- cesarean section and postmortem cesarean section cases tress are the second greatest category among PCS indi- were excluded from the study. In order to comply with cations.[1,8,11] Multiple pregnancies increase as assisted the terminology in the literature, exceptional cases reproductive technologies improve and become preva- below 500 g and 24 weeks of gestation were not includ- lent.[13] Multiple pregnancies and breech presentations ed. The study was approved by Ethics Committee for constitute a significant part of PCS indications, and rep- Non-Invasive Researches of Dokuz Eylül University resent an aspect of obstetrics which diminishes slowly. (4087-GOA-2018/16-06).
Volume 26 | Issue 3 | December 2018 125 Köse S, Akdöner A, Altunyurt S
Statistical analyses ferred as two sub-definitions for dystocia indication. Statistical analyses were performed by using SPSS v.22 Due to maternal problems, PCS practices were catego- (SPSS Inc., Chicago, IL, USA). The compatibility of rized under 6 main topics (Table 1). The greatest indi- variables to normal distribution was analyzed by visual cation category in this group was severe preeclampsia and analytical methods (Kolmogorov-Smirnov / Shapiro- (78 cases, 2.4%). Indication types with lower than 1% Wilk tests). Descriptive statistics were presented by frequency were categorized under 15 topics (Table 1). selecting mean and standard deviation values for the Placenta previa marginalis was the greatest group variables exhibiting normal distribution. The mean val- among these rare reasons. When they were all consid- ues of constant variables were compared by one-way ered, 25 indication types were seen (Table 1). ANOVA test among the groups more than two. The In term cases, dystocia was found to be the most homogeneity of variances was analyzed by Levene’s test. common indication category in all years (Table 2 and When significant difference was found between the Fig. 1). The frequency of dystocia indication was the groups, post-hoc pairwise comparisons were done by highest (48.4%) in 2011 while it was the lowest (19.5%) Tukey and Games-Howell tests. When constant vari- in 2016 (Table 2). The ranking of dystocia, fetal dis- ables did not exhibit any normal distribution, they were tress, breech presentation, twin pregnancy and macro- compared by Kruskal-Wallis test. The presence of dif- somic fetus changed after first 2 years and macrosomic ference among the groups in frequency analyses were fetus category reached to rank 4 in 2009, 2010 and compared by using either chi-square or Fisher’s test. 2011, and rank 2 in 2016 (Table 2 and Fig. 1). Twin When p value was below 0.05, the results were consid- pregnancies regressed to rank 5 as of 2009, and stayed ered statistically significant. at this rank except 2012 where it was not within top 5 (Table 2). Although the absolute number of twin preg- nancies seemed to decrease beginning from 2010, the Results decrease was not statistically significant: Ninety-six A total of 3284 PCS labors were carried out between cases between 2007 and 2010 vs. 69 cases between 2011 January 1, 2007 and January 1, 2017 in a period of ten and 2016 (p=0.06). years. Of these cases, 263 (8.0%) were twin pregnancy, In preterm cases, fetal distress was found to be the 11 (0.3%) were triplet pregnancy, and 3010 (92.7%) most common indication category except 2009 (Table 2 were singleton pregnancy. The total number of preterm and Fig. 2). While fetal distress had a rate of 3.3% cases was 494 (15.0%), and 105 (21.3%) of them were in among all PCS’ in preterm cases in 2007, it increased to multiple pregnancy group while 389 (78.7%) of them 8.0% in 2016. Dystocia, which was the greatest category were in the singleton pregnancy group. While 38.3% of of term cases, could only manage to be in top 5 groups the multiple pregnancies resulted in preterm labor, only of preterm cases between 2007 and 2012 (Table 2). 12.9% of the singleton pregnancies resulted in preterm Although the ranks changed in some years, fetal distress, labor. When all cases were considered, mean gestational breech presentation and twin pregnancies were top three age was 29.2±5.3 (range: 15.0 to 51.0), and mean birth categories in preterm cases (Table 2 and Fig. 2). Unlike weight of newborns was 3123±812 (range: 502 to 5580) term cases, placental attachment anomalies and detach- g. Of the cases, 2106 (64.1%) were primigravida and ment were always in top 5 categories in preterm preg- 1178 (35.9%) were multigravida. Considering the cases nancies. in terms of previous history of live birth, 2604 (79.3%) When primiparous and multiparous cases were com- cases were primiparous and 680 (20.7%) cases were mul- pared, top 5 indication ranks and their frequencies were tiparous. 16.7% of the pregnant women (548 cases) were varying significantly. While the top five indications for 35 years old or above. primiparous cases were dystocia (40.2%), fetal distress PCS indication categories are presented in Table 1. (18.9%), breech presentation (11.2%), twin pregnancies The number of obstetric indication categories with fre- (8.3%) and macrosomic fetus (5.6%), they were fetal dis- quency of 1% and above was 9 (Table 1). The greatest tress (23.0%), dystocia (19.9%), breech presentation category in this group and the greatest group among (14.5%), macrosomic fetus (13.6%) and twin pregnan- PCS’ was dystocia (36.0%). In our clinic, cephalopelvic cies (6.6%) for multiparous cases. When the groups with disproportion and non-progressive labor were pre- maternal age above and below 35-year-old were com-
126 Perinatal Journal The distribution of primary cesarean section indication at a university hospital
Table 1. The distribution of indications of primary cesarean section cases in total cohort.
Number of cases (%) Indication categories for primary cesarean section 3284 (100)
Dystocia Cephalopelvic disproportion 795 (24.2) 1182 (36.0) Non-progressive labor 387 (11.8) Fetal distress 648 (19.7) Breech presentation 390 (11.9) Twin pregnancies 263 (8.0) Macrosomic fetus 239 (7.3) Fetal anomaly 109 (3.3) Transverse fetal position 44 (1.3) Placenta previa partialis and totalis 42 (1.3) Ablatio placentae 35 (1.1) Maternal problems Severe preeclampsia 78 Cardiac diseases 36 Lumbar disc herniation 14 159 (4.8) Neuromuscular diseases 11 Vaginismus 11 Other various diseases 9 Rare indications (with <1% rate) Placenta previa marginalis 27 (0.8) Previous uterine surgery 21 (0.6) Feet presentation 21 (0.6) Genital wart 20 (0.6) Oblique fetal position 18 (0.5) Cord prolapse 12 (0.4) Eclampsia 11 (0.3) Triplet pregnancy 11 (0.3) Face presentation 10 (0.3) HELLP syndrome 9 (0.3) Hand presentation 5 (0.2) Arm prolapse 2 (<0.1) Forehead presentation 2 (<0.1) Genital herpes 2 (<0.1) Asynclitism 2 (<0.1)
pared, top 3 categories were same (dystocia, fetal dis- significantly higher in dystocia group than fetal distress tress, breech presentation); however, 4th category was (p<0.0001) and breech presentation (p<0.0001) groups. twin pregnancies in the group with maternal age of <35 Primiparous case rate was higher in fetal distress, while it was macrosomic fetus in the group with mater- breech presentation and macrosomic fetus groups than ≥ nal age of 35. The rate of macrosomic fetus was 6.9% dystocia and twin pregnancy groups (Table 4). Male in cases with the maternal age of <35 and 8.9% in cases fetus rate was higher in macrosomic fetus group than ≥ with the maternal age of 35. Dystocia was the greatest breech presentation group. Preterm case rate was higher category in both groups (36.4% vs. 34.1%; p=0.422), and in twin pregnancy and fetal distress groups than the other first 5 indication ranking did not change. groups. Preterm case rate was also higher in twin preg- When maternal, fetal and obstetric characteristics of nancy group than the fetal distress group (p=0.008) top 5 indication groups were compared among the (Table 4). The rate of pregnancy obtained by assisted groups, there was no significant difference among the reproductive technologies was higher than all other groups in terms of mean maternal age (Table 3). groups; the rates of pregnancies obtained by spontaneous Newborn weight was significantly higher in macrosomic pregnancy and in vitro fertilization / intrauterine insemi- fetus group than all other groups (p<0.0001), and it was nation were not different among other groups (Table 4).
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Table 2. Distribution of top 5 indication categories of primary cesarean section in term and preterm cases by years.
Years / Number of primary cesarean Top 5 indication groups in term cases Top 5 indication groups in preterm cases section cases (% in cohort) Number of cases (%) Number of cases (%)
2007 / 436 (13.2) 1. Dystocia 189 (43.3) 1. Fetal distress 17 (3.9) 2. Fetal distress 62 (14.2) 2. Twin pregnancy 14 (3.2) 3. Breech presentation 43 (9.9) 3. Breech presentation 7 (1.6) 4. Twin pregnancy 26 (5.6) 4. Dystocia 3 (0.7) 5. Macrosomic fetus 19 (4.4) 5. Placenta previa 2 (0.5)
2008 / 381 (11.6) 1. Dystocia 124 (32.5) 1. Fetal distress 23 (6.0) 2. Fetal distress 74 (19.4) 2. Twin pregnancy 15 (4.1) 3. Breech presentation 48 (12.6) 3. Breech presentation 3 (0.8) 4. Twin pregnancy 26 (6.8) 4. Transverse fetal position 2 (0.5) 5. Macrosomic fetus 10 (2.6) 5. Ablatio placentae 2 (0.5)
2009 / 329 (10.0) 1. Dystocia 90 (27.4) 1. Twin pregnancy 19 (5.8) 2. Fetal distress 79 (24.0) 2. Fetal distress 18 (5.5) 3. Breech presentation 32 (9.7) 3. Breech presentation 9 (2.7) 4. Macrosomic fetus 24 (7.3) 4. Triplet pregnancy 2 (0.6) 5. Twin pregnancy 16 (4.9) 5. Ablatio placentae 2 (0.6)
2010 / 538 (16.4) 1. Dystocia 204 (37.9) 1. Fetal distress 24 (4.5) 2. Fetal distress 84 (15.6) 2. Twin pregnancy 17 (3.2) 3. Breech presentation 40 (7.4) 3. Breech presentation 9 (1.7) 4. Breech presentation 32 (5.9) 4. Ablatio placentae 5 (0.9) 5. Twin pregnancy 28 (5.2) 5. Fetal anomaly 4 (0.7)
2011 / 337 (10.3) 1. Dystocia 163 (48.4) 1. Fetal distress 20 (5.9) 2. Fetal distress 33 (9.8) 2. Breech presentation 6 (1.8) 3. Breech presentation 29 (8.6) 3. Twin pregnancy 5 (1.5) 4. Macrosomic fetus 16 (4.8) 4. HELLP syndrome 2 (0.6) 5. Twin pregnancy 10 (2.9) 5. Placenta previa 2 (0.6)
2012 / 183 (5.6) 1. Dystocia 70 (38.2) 1. Fetal distress 12 (6.6) 2. Fetal distress 17 (9.3) 2. Breech presentation 6 (3.3) 3. Breech presentation 15 (8.2) 3. Twin pregnancy 4 (2.2) 4. Fetal anomaly 9 (4.9) 4. Dystocia 3 (1.6) 5. Macrosomic fetus 8 (4.4) 5. Ablatio placentae 2 (1.1)
2013 / 217 (6.6) 1. Dystocia 81 (37.3) 1. Fetal distress 9 (4.1) 2. Breech presentation 24 (11.1) 2. Breech presentation 7 (3.2) 3. Fetal distress 18 (8.3) 3. Twin pregnancy 5 (2.3) 4. Macrosomic fetus 17 (7.8) 4. Ablatio placentae 2 (0.9) 5. Twin pregnancy 10 (4.6) 5. Placenta previa 2 (0.9)
2014 / 290 (8.8) 1. Dystocia 96 (33.1) 1. Fetal distress 14 (4.8) 2. Macrosomic fetus 47 (16.2) 2. Breech presentation 8 (2.8) 3. Fetal distress 35 (12.1) 3. Twin pregnancy 6 (2.1) 4. Breech presentation 28 (9.7) 4. Fetal anomaly 4 (1.4) 5. Twin pregnancy 12 (4.1) 5. HELLP syndrome 2 (0.7)
2015 / 286 (8.7) 1. Dystocia 87 (30.4) 1. Fetal distress 15 (5.2) 2. Fetal distress 45 (15.7) 2. Twin pregnancy 5 (1.7) 3. Breech presentation 30 (10.5) 3. Breech presentation 4 (1.4) 4. Macrosomic fetus 19 (6.6) 4. Cord prolapse 2 (0.7) 5. Twin pregnancy 16 (5.6) 5. Placenta previa 2 (0.7)
2016 / 287 (8.7) 1. Dystocia 56 (19.5) 1. Fetal distress 23 (8.0) 2. Macrosomic fetus 47 (16.3) 2. Breech presentation 7 (2.4) 3. Breech presentation 38 (13.2) 3. Twin pregnancy 4 (1.4) 4. Fetal distress 26 (9.1) 4. Placenta previa 4 (1.4) 5. Twin pregnancy 21 (7.3) 5. Ablatio placentae 4 (1.4)
128 Perinatal Journal The distribution of primary cesarean section indication at a university hospital
Fig. 1. Top 5 indication categories of primary cesarean section in term cases.
Fig. 2. Top 3 indication categories of primary cesarean section in preterm cases.
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Table 3. Comparison of maternal, fetal and obstetric characteristics in top 5 indication categories.
Dystocia Fetal distress Breech presentation Twin pregnancy Macrosomic fetus Characteristics (n=1182) (n=648) (n=390) (n=263) (n=239) p-value
Maternal age (year) 29.2±4.9 28.8±5.2 29.1±5.4 29.6±5.7 29.3±5.4 0.793 (15–47) (16–46) (17–44) (17–51) (17–42) Newborn weight (g) 3417±462 2640±893 2945±760 4138±316 <0.0001 (1400–5160) (502–4750) (700–4900) (3590–5580) Parity condition 0 1047 (88.6) 492 (75.9) 292 (74.9) 218 (82.8) 147 (61.5) <0.0001 ≥1 135 (11.4) 156 (24.1) 98 (25.1) 45 (17.2) 92 (38.5) Fetal sex Female 537 (45.4) 298 (46.0) 197 (50.5) 99 (41.4) 0.026 Male 638 (54.6) 350 (54.0) 193 (49.5) 140 (58.6) Week of gestation Preterm 22 (1.9) 175 (27.0) 63 (16.2) 94 (35.7) 0 (0.0) <0.0001 Term 1160 (98.1) 473 (73.0) 327 (83.8) 169 (64.3) 239 (100) <0.008 Conception type Spontaneous 1142 (96.6) 628 (96.9) 379 (97.2) 163 (62.0) 235 (98.3) <0.0001 Assisted 40 (3.4) 20 (3.1) 11 (2.8) 100 (38.0) 4 (1.7) reproductive technology (IUI/IVF)
When the changes in categories of the top 5 indica- 2013 (p<0.0001) and then remained same relatively tion group for PCS cases were analyzed by the years, it among other groups (Table 1 and Fig. 1). There was was seen that dystocia group started to decrease after no significant change in the rate of PCS due to breech 2011, and regressed to 19.5% from 48.4% (p<0.0001) presentation during the study period; it reached its low- (Table 1 and Fig. 1). Fetal distress category expanded est level (7.4%) in 2010 and its highest level (13.2%) in between 2007 and 2009, narrowed between 2010 and 2016; however, this change was not statistically signifi-
Table 4. Procedures to be performed and actions to be taken to decrease the rates of primary cesarean section safely.
Indication category of primary cesarean section and the rate in total number Recommendation and procedure
Dystocia Improving diagnosis criteria and determining reliable threshold values for the definition of failure to progress Accurate timing for hospitalization at delivery room Active labor follow-up Determining induction and augmentation criteria
Fetal distress Determining induction and augmentation criteria Standard guidelines and management algorithms for correct interpretation of fetal heart rate traces Amnioinfusion applications for repetitive variable decelerations Preventing preterm labor Protecting placental function and preventing fetal growth retardation
Breech presentation External cephalic version efforts
Twin pregnancies Proper selection and correct implementation of fertility support treatments Optimizing embryo transfer numbers Maintaining vaginal labor option in vertex-vertex presentations
Macrosomic fetus Proper nutrition during pregnancy Training for movement and lifestyle during pregnancy Glucose intolerance and diabetes screening Strict glycemic control in gestational diabetes cases Screening and following up thyroid functions
Severe preeclampsia and eclampsia Preeclampsia prediction and prophylaxis studies
Fetal anomalies Randomized controlled studies for the safety of vaginal labor in fetal anomaly types Establishing centers specialized on the delivery of fetuses with anomaly
130 Perinatal Journal The distribution of primary cesarean section indication at a university hospital
cant (p=0.109). Twin pregnancies remained stable tal outcomes.[22] In a report presented by Safe Labor between 2007 and 2010; it decreased as absolute num- Consortium in the USA argued that the definitions of ber after 2010, but its rate within other groups did not labor progression should be updated and they should be change relatively (p=0.051). PCS labors performed due extended slightly.[23] Unlike the information based on to the indication of macrosomic fetus increased greatly classical Friedman's curves, it was observed that 0.5 cm/h during 2013–2014, and reached its highest level dilatation rate is normal sub-limit for cervical dilatation (16.3%) in 2016 (p<0.0001) (Table 1 and Fig. 1). during active phase in both nulliparous and multiparous cases, and it can be seen during safe labor.[23] In another Discussion study investigating the first stage of labor, it was con- cluded that the definition of failure to progress under 5 In order to understand to what extent the rates of cesare- cm should not be used.[24] Safe Labor Consortium rec- an section labors can be decreased, it is necessary to ommends 6 cm for this diagnosis.[23] Similar studies were determine the reasons for primary cesarean section. In conducted for the definition of duration of the second their major retrospective cohort analysis within the stage of labor and it was reported that keeping the scope of Safe Labor Consortium in the USA, Boyle et al. maternal pushing effort as long as fetal heart rates are assessed 34,484 indications of primary cesarean sec- reassuring decreases the rates of cesarean section labors [1] tion. As the most common PCS indications, they due to dystocia without any worsening in maternal and reported non-progressive labor (35.4%), non-reassuring fetal outcomes.[25] When considered from this point of fetal heart rate trace (27.3%) and fetal malpresentations view, dystocia is one of the most subjective indications (18.5%), and stated that the distributions varied accord- due to the reasons such as being controversial in terms of [1,2] ing to the parity. 45.6% of all PCS labors were carried diagnosis criteria among PCS indications and being out on cases which were primiparous term singleton open for personal opinions for considering whether a pregnancies and had cephalic presentation. This rate case have these criteria or not.[10] The lack of reliable and represents PCS cases which can be prevented somehow. high quality evidences particularly for the definition of In a study conducted on more than 200,000 cesarean non-progressive labor makes this diagnosis subjective.[10] section cases in 19 hospitals between 2002 and 2008 in In this regard, it would be widely accepted that dystocia the USA, dystocia (47.1%) was found as the most com- is one of the most difficult topics for decreasing the mon indication of intrapartum cesarean section labors.[20] number of PCS (Table 4). Dystocia was followed by non-reassuring fetal heart rate The greatest 2nd category among PCS indications is traces (27.1%) and malpresentations (7.5%). In cesarean the cesarean sections carried out due to fetal distress and sections performed before labor started, previous history non-reassuring fetal heart rate traces.[8] Labor follow-up of cesarean section (45%) was followed by breech and by EFM has been almost a routine practice in the world [20] other malpresentations (17.1%). Our study was consis- and Turkey and this increased PCS rates without any tent with the literature and top 3 categories of PCS indi- provable improvement in the neonatal outcomes.[12] In cations were dystocia, fetal distress and breech presenta- our study, we analyzed and interpreted fetal distress tion (Table 1 and Fig. 1). cases according to triple category system of ACOG Dystocia is consisted of the combination of two sub- except for 2007. After its recommendation update, indications, which are the opinion of cephalopelvic dis- ACOG grouped fetal heart rate traces under 3 cate- proportion and failure to progress.[10] Failure to progress gories.[26] Category 3 is an abnormal category which also has two sub-phases which are the failure of progress requires intervention, because fetal heart rate patterns in during the active stage of labor and failure to descend at this category may be associated with the pH of abnormal the second stage of labor.[21] Failure to progress is partial- neonatal umbilical cord, encephalopathy, and cerebral ly subjective and controversial diagnosis. Instead of wait- palsy.[26] When corrective primary approaches (position- ing for 2 hours, which was the criterion used traditional- ing pregnant woman on side-lying, investigating and ly before proceeding with cesarean section when there eliminating hypotension and tachysystole, and ruling out were sufficient uterine contractions, waiting for 4 hours acute reasons such as cord prolapse) do not improve fetal has helped to decrease the number of failure to progress heart rates, rapid interventions including cesarean sec- diagnosis without any worsening in maternal and perina- tion are required.[26] Fetal heart rate traces which are
Volume 26 | Issue 3 | December 2018 131 Köse S, Akdöner A, Altunyurt S
recorded most frequently during labor are the patterns tion can be quite misleading, and together with medicole- included in Category 2.[8,27] These traces are usually tem- gal concerns, 4000 g is preferred as the threshold in the porary and requires follow-up, but they frequently turn daily obstetric practices for the suspicions about macro- into Category 1 safe traces.[28] Category 3 traces being somic fetus. In our study, 162 (67.8%) of 239 cases which rare is interpreted in a way that PCS labors due to fetal underwent PCS due to macrosomic fetus were 4000 g distress are carried out mostly by Category 2 indica- and above, 77 (32.2%) cases were below 4000 g. tion.[4] The decision of emergency cesarean section in the Considering the cases completely consistent with ACOG presence of Category 2 fetal heart rate traces is based on criteria, there were 3 cases which were non-diabetic and medicolegal concerns. Lack of valid scientific evidences over 5000 g and 7 cases which were diabetic and over on the capacity of these traces to predict newborn’s con- 4500 g. These numbers indicate the margin of error for dition and the absence of studies supporting the efficien- estimated fetal weight measurements and the use of lower cy of corrective intrauterine approaches indicates that it threshold values in routine clinical practice such as 4000 is not easy to decrease the number of PCS practices g. In the retrospective cohort analysis of Boyle et al. under this matter in the near future. Doppler evaluation including 38,484 PCS cases, newborn weight was below of prenatal arterial and venous areas and cerebroplacen- 4000 g in 41.9% of the cases which underwent cesarean tal rate evaluations in cases which require labor induc- section due to suspected macrosomia.[1] tion in particular offered first promising evidences to One of the views on decreasing cesarean section [29] help interpreting these traces in a more rational way. rates due to macrosomia and macrosomia suspicion is Important evidences have been accumulated about the to compare labor induction and follow-up options in efficacy of amnioinfusion practices for repetitive variable pregnancies which are found to have fetuses large for decelerations which have almost never been carried out, gestational age. A prospective randomized controlled and activities to decrease the need for cesarean section study on this issue reported that labor induction com- [8] labors. pared to follow-up approach decreased the rates of Breech presentation is considered as one of the most shoulder dystocia and the need for cesarean section in objective categories,[9,10] and we have not observed any sig- fetuses which are close to the term and large for gesta- nificant change in the rate of PCS due to breech presen- tional age.[19] The fetus to be born being 4000 g and tation during the study period. The rates of perinatal above seems to be among other indications and affect asphyxia, increase in the need for newborn intense unit, them. In the cases which underwent PCS due to dysto- newborn trauma and neonatal death are significantly high cia, 90 (6.1%) fetuses were ≥4000 g and 338 (28.6%) in vaginally-delivered pregnancies, and therefore vaginal fetuses were ≥3700 g. Considering the entire cohort, delivery is avoided in breech presentation cases.[16,17] For 277 (8.5%) cases were born ≥4000 g, and 705 (21.4%) such reasons, vaginal delivery in breech presentation cases were born ≥3700 g. Fetuses having such weights cases is one of the vanishing skills of the obstetrics. With may contribute to all diagnosis groups, and particular- external cephalic version, rotating to vertex position and ly non-progressive labor and cephalopelvic dispropor- efforts to get a chance for vaginal delivery have become a tion. The rates of preferring cesarean section deliveries discussion topic again.[8,10] Breech presentation cases are in twin pregnancies have increased gradually, and this among the preventable PCS indications due to the pres- increase has reached to 70% even in cases where pre- ence of this option and relatively successful results report- senting fetus is on vertex position.[32] As in head presen- ed.[10] Macrosomia or large infant suspicion is not accept- tation of presenting fetus, it is known that cesarean sec- ed as a cesarean section indication directly.[8] ACOG rec- tion does not improve perinatal outcomes in twin preg- ommends cesarean section for fetuses equal to or over nancies.[8] In twin pregnancies, particularly in cases 4500 g in diabetic cases and only for fetuses equal to or where first fetus is on vertex position, vaginal delivery over 5000 g in non-diabetic cases in order to prevent should be recommended to pregnant women. During birth traumas such as shoulder dystocia and permanent obstetrics specialization and residency, sufficient train- brachial plexus paralysis.[30] Even for these thresholds, the ing and upskilling on delivery of twin pregnancies positive impacts of cesarean section on neonatal out- should be provided, and continuing education pro- comes are controversial.[31] Ultrasonographic measure- grams should be established to preserve this experience ment of estimated fetal weights in the last weeks of gesta- (Table 4).
132 Perinatal Journal The distribution of primary cesarean section indication at a university hospital
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ACOG Practice Bulletin No. 144: Multifetal gestations: twin, triplet, and higher-order mul- Conclusion tifetal pregnancies. Obstet Gynecol 2014;123:1118–32. World Health Organization reported that ideal rate of 14. Özkaya MO, Sezik M, Kaya H. Mode of delivery in multiple cesarean section is about 15%, and recommended to pregnancies. Perinatal Journal 2005;13:187–90. [21] keep PCS rates under control to reach this rate. 15. Hofmeyr GJ, Kulier R, West HM. External cephalic version Investigating PCS indication categories is the first step for breech presentation at term. Cochrane Database Syst Rev to take in order to reach this goal. The data to be 2015;4:CD000083. obtained in this way may contribute to the develop- 16. Baksu A, fiaflmazlar A, Tekelio¤lu M, Özsoy S, Göker N. ment of strategies to decrease PCS rates. Makat prezentasyonlar›nda do¤um fleklinin fetal ve maternal sonuçlarla iliflkisi . Perinatoloji Dergisi 2004;12:117–22. 17. Y›ld›r›m G, Özdemir ‹A, Aslan H, Gülk›l›k A. Early neonatal Conflicts of Interest: No conflicts declared. outcomes of term breech delivery. Perinatal Journal 2006;14: 66–72. References 18. Boulvain M, Irion O, Dowswell T, Thornton JG. Induction of 1. Boyle A, Reddy UM, Landy HJ, Huang CC, Driggers RW, labour at or near term for suspected fetal macrosomia. Laughon SK. Primary cesarean delivery in the United States. Cochrane Database Syst Rev 2016;5:CD000938. Obstet Gynecol 2013;122:33–40. 19. Boulvain M, Senat MV, Perrotin F, Winer N, Beucher G, 2. Organisation for Economic Co-operation and Development Subtil D, et al.; Groupe de Recherche en Obstétrique et [Internet]. Health data 2015—frequently requested data. Gynécologie (GROG). Induction of labour versus expectant Available from: https://data.oecd.org/healthcare/caesarean- management for large-for-date fetuses: a randomised con- sections.htm trolled trial. Lancet 2015;385:2600–5. 3. Solheim K, Esakoff T, Little S, Cheng YW, Sparks TN, 20. Zhang J, Troendle J, Reddy UM, Laughon SK, Branch DW, Caughey AB. The effect of cesarean delivery rates on the future Burkman R, et al.; Consortium on Safe Labor. Contemporary incidence of placenta previa, placenta accreta, and maternal cesarean delivery practice in the United States. Am J Obstet mortality. J Matern Fetal Neonatal Med 2011;24:1341–6. Gynecol 2010;203:326.e1–326.e10.
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21. Dresang LT, Leeman L. Cesarean delivery. Prim Care 2012; 28. American College of Obstetricians and Gynecologists. ACOG 39:145–65. Practice Bulletin No. 106: Intrapartum fetal heart rate moni- 22. Rouse DJ, Weiner SJ, Bloom SL, Varner MW, Spong CY, toring: nomenclature, interpretation, and general management Ramin SM, et al.; Eunice Kennedy Shriver National Institute principles. Obstet Gynecol 2009;114:192–202. of Child Health and Human Development (NICHD) 29. DeVore GR. The importance of the cerebroplacental ratio in Maternal-Fetal Medicine Units Network (MFMU). Failed the evaluation of fetal well-being in SGA and AGA fetuses. Am labor induction: toward an objective diagnosis. Obstet Gynecol J Obstet Gynecol 2015;213:5–15. 2011;117:267–72. 23. Zhang J, Landy HJ, Branch DW, Burkman R, Haberman S, 30. American College of Obstetricians and Gynecologists. Fetal Gregory KD, et al.; Consortium on Safe Labor. Contemporary macrosomia: ACOG practice bulletin no. 22. Washington, patterns of spontaneous labor with normal neonatal outcomes. DC: ACOG; 2000. Obstet Gynecol 2010;116:1281–7. 31. Little SE, Edlow AG, Thomas AM, Smith NA. Estimated fetal 24. Zhang J, Troendle J, Mikolajczyk R, Sundaram R, Beaver J, weight by ultrasound: a modifiable risk factor for cesarean Fraser W. The natural history of the normal first stage of labor. delivery? Am J Obstet Gynecol 2012;207:309.e1–6. Obstet Gynecol 2010;115:705–10. 32. Lee HC, Gould JB, Boscardin WJ, El-Sayed YY, Blumenfeld 25. Shields SG, Ratcliffe SD, Fontaine P, Leeman L. Dystocia in YJ. Trends in cesarean delivery for twin births in the United nulliparous women. Am Fam Physician 2007;75:1671–8. States: 1995-2008. Obstet Gynecol 2011;118:1095–101. 26. Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. 33. Declercq E, Menacker F, Macdorman M. Maternal risk pro- The 2008 National Institute of Child Health and Human files and the primary cesarean rate in the United States, Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. 1991–2002. Am J Public Health 2006;96:867–72. Obstet Gynecol 2008;112:661–6. 34. Darney BG, Snowden JM, Cheng YW, Jacob L, Nicholson 27. Cahill AG, Roehl KA, Odibo AO, Macones GA. Association JM, Kaimal A, et al. Elective induction of labor at term com- and prediction of neonatal acidemia. Am J Obstet Gynecol pared with expectant management: maternal and neonatal out- 2012;207:206.e1–8. comes. Obstet Gynecol 2013;122:761–9.
134 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 2018;26(3):135–140 I N N R A U T A L J O
Retrospective analysis of the preeclampsia cases delivered in our clinic between 2013 and 2017
Gülfem Baflol, Navdar Do¤ufl Uzun, Fulya Uzun, Ahmet Kale, Hasan Terzi Clinic of Gynecology and Obstetrics, Derince Training and Research Hospital, Health Sciences University, Kocaeli, Turkey
Abstract Özet: Klini¤imizde 2013–2017 y›llar› aras›nda do¤um yapm›fl olan preeklampsi olgular›n›n retrospektif de¤erlendirilmesi Objective: The aim of our study is to analyze and compare obstetric, Amaç: Çal›flmam›z›n amac›, erken bafllang›çl› ve geç bafllang›çl› pre- maternal and fetal outcomes of the cases who delivered with the diag- eklampsi tan›s› ile do¤umu gerçekleflen olgular›n obstetrik, maternal noses of early-onset and late-onset preeclampsia. ve fetal sonuçlar›n› de¤erlendirmek ve karfl›laflt›rmakt›r. Methods: The data of 149 patients with preeclampsia who delivered Yöntem: Ocak 2013 – A¤ustos 2017 aras›nda do¤um yapan preek- between January 2013 and August 2017 were collected and analyzed lampsili 149 hastaya ait veriler Derince E¤itim ve Araflt›rma Hasta- at Derince Training and Research Hospital. Of the cases, 65 were nesi’nde topland› ve analiz edildi. 65 kad›na erken bafllang›çl› ve 84 established with the diagnosis of early-onset preeclampsia and 84 kad›na geç bafllang›çl› preeklampsi tan›s› konulmufltu. Her iki gru- were established with the diagnosis of late-onset preeclampsia. The bun demografik özellikleri, biyokimyasal de¤ifliklikleri, perinatal, demographic characteristics, biochemical changes, and perinatal, maternal ve obstetrik sonuçlar› karfl›laflt›r›ld›. maternal and obstetric outcomes of both groups were compared. Bulgular: Erken ve geç bafllang›çl› preeklampsi hastalar›n›n ara- Results: Between the patient groups with early-onset and late-onset s›nda yafl, gravida, parite, sistolik ve diastolik kan bas›nçlar›, labo- preeclampsia, there was no statistically significant difference in terms ratuvar de¤erleri (karaci¤er fonksiyon testleri, hemogram, trom- of age, gravida, parity, systolic and diastolic blood pressures, labora- bosit say›lar›), do¤um flekilleri aç›s›ndan istatistiksel olarak anlam- tory values (liver function tests, hemogram, thrombocyte count), and l› fark saptanmad› (p>0.05). Serum kreatinin de¤erleri aras›nda is- delivery types (p>0.05). There was statistically significant difference tatistiksel olarak anlaml› fark saptand› (p=0.045). Her iki grup ara- between serum creatinine values (p=0.045). There was statistically s›nda, yenido¤an a¤›rl›¤›, düflük do¤um a¤›rl›kl› bebek, yenido¤an significant difference between two groups against early-onset yo¤un bak›m ihtiyac›, maternal komplikasyon, intrauterin ölüm preeclampsia in terms of newborn weight, low birth weight infant, aç›s›ndan erken bafllang›çl› preeklampsi aleyhine istatistiksel ola- newborn's need for intensive care, maternal complication and rak anlaml› fark saptand› (p<0.001). intrauterine death (p<0.001). Sonuç: Verilerimiz erken bafllang›çl› preeklampsi hastalar›nda pe- Conclusion: Our data show that the rates of perinatal and maternal rinatal ve maternal komplikasyonlar›n daha yüksek oldu¤unu gös- complications are higher in the patients with early-onset preeclamp- termektedir. Preeklampsi tan›s› konan kad›nlarda erken tan› ve do- sia. We believe that using new predictive biomarkers is necessary for ¤um karar› için yeni öngörücü biyobelirteçlerin kullan›lmas›n›n early diagnosis and labor decision in women with preeclampsia diag- gerekli oldu¤unu düflünüyoruz. Genetik faktörler, ›rksal ve etnik nosis. Considering the genetic factors and racial and ethnic differ- farkl›l›klar göz önüne al›nd›¤›nda, preeklampsi ile iliflkili maternal ences, multi-centered studies are needed to evaluate preeclampsia- ve fetal komplikasyonlar› de¤erlendirmek için çok merkezli çal›fl- related maternal and fetal complications. malara ihtiyaç vard›r. Keywords: Preeclampsia, early-onset preeclampsia, late-onset Anahtar sözcükler: Preeklampsi, erken bafllang›çl› preeklampsi, geç preeclampsia, maternal outcomes, newborn outcomes. bafllang›çl› preeklampsi, anneye ait sonuçlar, yenido¤ana ait sonuçlar.
Correspondence: Navdar Do¤ufl Uzun, MD. Clinic of Obst. & Gyn., Derince T&R Available online at: Hospital, Health Sciences University, Kocaeli, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263008 doi:10.2399/prn.18.0263008 Received: July 18, 2018; Accepted: December 15, 2018 QR (Quick Response) Code: Please cite this article as: Baflol G, Uzun ND, Uzun F, Kale A, Terzi H. Retrospective analysis of the preeclampsia cases delivered in our clinic between 2013 and 2017. Perinatal Journal 2018;26(3):135–140. ©2018 Perinatal Medicine Foundation Baflol G et al.
Introduction In pregnancies complicated with preeclampsia, many life-threatening maternal complications from ablatio Preeclampsia is a gestational disease affecting about placentae, intracranial bleeding, liver failure, kidney fail- 5–10% of pregnant women and increasing the rates of [1] ure, and disseminated intravascular coagulation to death maternal and fetal mortality significantly. Hypertensive can be seen.[12] As it is a progressive disease, the only disorders are responsible for 14% of maternal mortality [2] treatment option is to complete the pregnancy by deliv- rates in the world. Due to the insufficient access to ery in order to prevent fetal and maternal complications. antenatal care services in the underdeveloped and devel- Delivery timing and delivery type should be determined oping countries, mortality rate related with preeclampsia [3] according to the gestational age, preeclampsia severity, and its complications increases much more. and maternal and fetal well-being.[5,10,13] Measuring blood pressure during prenatal period, The aim of this study is to compare patients who the early gestational period or second trimester is quite were diagnosed with early-onset and late-onset important to establish the diagnosis of preeclampsia [4] preeclampsia and delivered in our clinic according to which may develop during pregnancy. High blood their biochemical changes and prenatal and maternal pressure and the presence of proteinuria which are found outcomes. after 20 weeks of gestation in a pregnant woman used to be known normotensive is defined as preeclampsia. However, the presence of proteinuria is not always a Methods must for preeclampsia diagnosis. In the lack of protein- The medical records of 223 patients who were diag- uria, preeclampsia finding can also be established in cases nosed with preeclampsia and delivered in the Clinic of where systemic findings (renal failure, liver dysfunction, Gynecology and Obstetrics of Derince Training and pulmonary edema, cerebral and visual symptoms, Research Hospital, Health Sciences University between hemolysis and the presence of thrombocytopenia) 2013 and 2018 were analyzed retrospectively. The med- [5] accompany hypertension. ical records of 149 patients whose files were accessed The week of gestation when preeclampsia is identi- from hospital database and patient files were analyzed fied is the most important clinical variable to predict and 13 of them were excluded from the study due to both maternal and prenatal outcomes. When preeclamp- their concomitant diseases (diabetes, autoimmune dis- sia develops before 32 weeks of gestation, it causes 20 ease, chronic hypertension). times higher maternal mortality than the term pregnan- The diagnosis of preeclampsia was established [6] cy. Increased maternal and fetal risks observed in the according to the criteria of ACOG (American College of early-onset preeclampsia support the opinion that the Obstetricians and Gynecologist).[5] According to these pathophysiology of early-onset preeclampsia is differ- criteria, (1) the presence of 140–159 mmHg or higher [7] ent. It has been also reported that the risks of develop- persistent systolic blood pressure (BP) or 90–109 mmHg ing cardiovascular disease in the further lives of women or higher diastolic BP which develops after 20 weeks of who were diagnosed with early-onset preeclampsia are gestation in a woman who previously had normal blood increased.[8] Moreover, early-onset preeclampsia also pressure, (2) concomitant systemic findings (proteinuria affects fetal prognosis negatively. Placental dysfunction, >300 mg/24-hour, thrombocytes <100,000/ dL, at least intrauterine growth retardation, abnormal uterine and 2 times increase of transaminase level, creatinine value umbilical artery Doppler evaluation, low birth weight >1.1 mg/dL, presence of pulmonary edema, presence of and multiple organ dysfunctions may be concurrent with cerebral or visual symptoms) in addition to blood pres- fetal outcomes associated with prenatal death.[9] Late- sure of 160/100 mmHg or above with an interval of 15 onset preeclampsia is considered mainly as a maternal minutes, and (3) measuring blood pressure ≥160/100 disorder. It is frequently associated with a normal pla- mmHg with 4-hour interval in addition to minimum centa, normal fetal development, normal uterine and one systemic finding were considered preeclampsia. umbilical artery Doppler evaluation, normal birth When it was found that hemolysis, lactate dehydroge- weight and more positive maternal and neonatal out- nase was >600 IU/L, total bilirubin was >1.2 mg/dl, comes.[9,10] Therefore, the opinion that early-onset aspartate aminotransferase (AST) was >70 IU/L, and preeclampsia mostly has more severe clinical course thrombocytes were <100,000 cell/mm3 in a patient with gains importance.[11] preeclampsia, the diagnosis of HELLP syndrome was
136 Perinatal Journal Retrospective analysis of the preeclampsia cases delivered in our clinic between 2013 and 2017
established. The cases found to have new-onset grand Of the pregnant women in both groups, the weeks of mal seizures were considered eclampsia. gestation when the patients were diagnosed with All blood pressure measurements were carried out by preeclampsia, their blood pressure measurements when a sleeve sphygmomanometer at sitting position as the they were diagnosed with preeclampsia, weeks of gesta- arm is on heart level. tion at labor, delivery types, birth weights, fetal (low Although the presence of proteinuria is not among the birth weight, newborn’s need for intensive care unit, definitive diagnosis criteria of preeclampsia, we included intrauterine death) and maternal (eclampsia, detach- proteinuria values of our patients in our study. The protein ment, HELLP syndrome) complications were recorded. amount in 24-hour urine obtained from patients was meas- The data of the patients on hemogram, routine bio- ured with precipitation method by using trichloroacetic chemistry (liver function tests, kidney function tests, acid (TCA) (the collected urine amount was measured total), and the presence of proteinuria which were and 5 ml of it was put in graduated conic tube; by adding obtained by file screening were recorded. 2.5 ml TCA, it was centrifuged at 3500–4000 rpm; the All data obtained from the study were analyzed by precipitation level obtained was measured and its equiv- using “Statistical Packages for the Social Science” alent value in nomogram was recorded as g/l). Presence (SPSS) 11.5 (SPSS Inc., Chicago, IL, USA) statistics of protein more than 300 mg/L in 24-hour urine was software on Windows operating system. After definitive considered proteinuria. The presence of proteinuria was statistical analyses (frequency, percentage distribution, evaluated by dipstick test in patients who admitted under mean±standard deviation), the conformity of variables to emergency conditions and taken to delivery room for normal distribution was evaluated by Shapiro-Wilks labor. In dipstick proteinuria test, the presence of pro- test. Pearson’s chi-squared test was used for the compar- ≥ tein 1+ was considered proteinuria. isons of categorical variables. p<0.05 was considered sta- Week of gestation was determined according to tistically significant. crown-rump length (CRL) measurement performed between 8 and 16 weeks of gestation.[10] The patients were categorized in 2 groups according to the week of Results gestation when preeclampsia developed. The The demographic characteristics and laboratory find- preeclampsia developed before 34 weeks of gestation ings of the patients in the early-onset preeclampsia and was defined early-onset, and it was defined late-onset late-onset preeclampsia groups included in the study are when it developed after 34 weeks of gestation.[14] shown in Table 1. Fifty-one (78.5%) patients diagnosed
Table 1. Comparison of two groups in terms of demographic data, blood pressure measurements and laboratory parameters.
Early-onset PE Late-onset PE n=65 n=84
Mean±SD Min–max Mean±SD Min–max p-value
Age (year) 30.1±6.7 - 29.8±6.2 - 0.793 Gravida 2.1±1.5 - 2.4±1.6 - 0.366 Parity 0.9±1.2 - 1.08±1.3 - 0.385 Week of gestation at diagnosis 31.3±2.6 23–34 36.9±1.4 35–40 <0.001 SBP (mm/Hg) 161.5±17.7 130–220 153.9±14.1 130–190 0.007 DBP (mm/Hg) 100.9±10.9 80–130 99.2±9.2 80–120 0.301 SGOT (IU/L) 26.3±43.3 6–234 20.3±27.8 6–167 0.153 SGPT(IU/L) 29.4±34.5 10–198 33.8±104.9 9–969 0.196 Creatinine (mg/dl) 0.6±0.1 0.3–1.4 0.6±0.1 0.4–0.9 0.045 LDH (IU/L) 289.8±122.7 148–762 316.5±305.8 148–2471 0.223 Hemoglobine (g/dl) 11.8±1.4 8.3–14.3 11.7±1.5 6.8–14.8 0.608 Thrombocyte (cell/m3) 204.5±73.8 32–448 229.0±86.5 47–528 0.085
DBP: diastolic blood pressure; LDH: lactate dehydrogenase; PE: preeclampsia; SGOT: serum glutamic oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase; SBP: systolic blood pressure.
Volume 26 | Issue 3 | December 2018 137 Baflol G et al.
with early-onset preeclampsia and 84 (100%) patients the idea that early-onset preeclampsia and late-onset diagnosed with late-onset preeclampsia had proteinuria preeclampsia may be different diseases associated with (p<0.001). Compared to the infants of pregnant women different biochemical markers, risk factors, clinical diagnosed with late-onset preeclampsia, the infants of characteristics and hemodynamic conditions.[17,18] pregnant women diagnosed with early-onset preeclamp- Although the etiology of preeclampsia has not been sia had higher rates of newborn's need for intensive care fully clarified yet, one of the most prominent hypothe- and intrauterine death, which was statistically signifi- ses is placental angiogenesis and uteroplacental failure cant. Similarly, maternal complication rate was higher in associated with the incomplete placental develop- the group diagnosed with early-onset preeclampsia ment.[19] In the early-onset preeclampsia, abnormal pla- (Table 2). centation and insufficient remodeling in spiral artery are seen specifically; however, these conditions are Discussion rarely seen in late-onset preeclampsia.[20] Preeclampsia is a progressive disease specific to the last The previous studies showed that early-onset half of pregnancy. Examining symptoms and findings preeclampsia is significantly associated with high rates specific to the disease during routine antenatal visits is of perinatal mortality and morbidity.[20] Quaker et al. important in terms of preventing maternal and fetal found that stillbirth rate decreases as the week of ges- [5] mortality and morbidity. tation progresses. In their studies, the authors reported In our study, we defined the preeclampsia developing that the rate of stillbirth associated with preeclampsia before 34 weeks of gestation as “early-onset” while the is 0.52%, and that the risk of fetal death associated with preeclampsia developing after 34 weeks of gestation as preeclampsia starts when preeclampsia becomes clear “late-onset”. While some studies have used this classifi- clinically.[21] In the study of Kumru et al., the authors cation,[10,11,15] some studies defined early-onset preeclamp- found the rate of intrauterine death 6.1% in severe [16] sia when it developed before 37 weeks of gestation. preeclampsia cases.[22] Consistent with the literature, we In our study, 43.6% (n=65) of preeclampsia patients observed intrauterine death in 4 (6.2%) of the cases were early-onset and 56.4% (n=85) of them were late- with early-onset preeclampsia in our study while there onset. The studies performed in the past years support was no stillbirth in late-onset preeclampsia group.
Table 2. Labor characteristics and maternal and fetal outcomes of two groups.
Early-onset PE Late-onset PE n=65 n=84
Mean±SD Min–max Mean±SD Min–max p-value
Week of gestation during labor 33.3±2.8 26–39 38.1±1.3 35–42 <0.001 Newborn’s birth weight (g) 1959.0±581.7 510–2880 3240±565.1 2015–5210 <0.001
n% n%
Delivery type NSD 4 6.2 10 11.9 CS 61 93.8 74 88.1 0.270 Primary CS 50 78.1 59 70.2 0.347 Fetal complication Low birth weight 17 26.2 10 12.0 0.270 Newborn’s need for ICU 25 38.5 4 4.8 <0.001 Intrauterine death 4 6.2 0 0 <0.001 Maternal complication <0.001 Eclampsia 3 4.6 1 1.2 Abruptio 3 4.6 0 0 HELLP syndrome 0 0 1 1.2
CS: cesarean section; ICU: intensive care unit; NSD: normal spontaneous delivery; PE: preeclampsia.
138 Perinatal Journal Retrospective analysis of the preeclampsia cases delivered in our clinic between 2013 and 2017
Some investigators argue that early-onset preeclamp- if fetal and maternal conditions are stable during early sia is a part of severe preeclampsia.[21] In our study, we weeks of gestation in order to avoid fetal sequels associ- found significantly high rate of maternal complication in ated with premature labor. However, conservative treat- the early-onset preeclampsia group. We found ablatio ment may also cause complications such as maternal placentae and eclampsia in 3 (4.6%) of the patients in the mortality and intrauterine death since the preeclampsia early-onset preeclampsia group, but they were uncon- is a progressive disease. In our study, we did not find trollable complications as these patients were not being maternal mortality in either group despite the increased followed up. While there was no difference between the newborn’s need for intensive care due to the increased incidences of early-onset and late-onset preeclampsia rate of premature labor. [23] complicated with HELLP syndrome, we found There is different information in the literature about HELLP syndrome only in 1 patient in the late-onset delivery types of preeclampsia cases. Zhang et al. carried preeclampsia group in our study. out labors by cesarean section in more than half of their In 2014, Doddamani et al. reported in their study patients with preeclampsia and eclampsia.[12] Kumru et that perinatal mortality rate increase in direct propor- al.[22] reported labor by cesarean section in 51.5% of the tion to the severity of preeclampsia and that the new- severe preeclamptic cases. In our study, cesarean section [24] born’s need for intensive care is 26.6%. In terms of rate is quite higher than the rates reported in the litera- the newborn's need for intensive care unit, we found ture. The primary cesarean section rate in study was this rate 38.5% in the cases with early-onset 78.1% in the early-onset preeclampsia group and 70.2% preeclampsia and 4.8% in the cases with late-onset in the late-onset preeclampsia group. We believe that preeclampsia. We believe that the high rate of new- the patients that we followed up due to preeclampsia born’s need for intensive care in the early-onset should be reconsidered in terms of delivery type in the preeclampsia group according to the literature is asso- light of the literature. ciated with the high rate of cesarean section. It is known that preeclampsia is a multisystemic dis- A retrospective cohort study conducted in 2002 ease which can develop with liver and kidney dysfunc- reported that birth weights of the newborns of moth- tions. During gestation, blood urea nitrogen (BUN), ers diagnosed with preeclampsia were lower compared creatinine and uric acid levels are reliable markers to to the weeks of gestation in a statistically significant evaluate the glomerular filtration rate. The studies per- level, but the birth weights of the newborns delivered formed in the past years showed that blood urea nitro- by preeclamptic pregnant women at 37 weeks of gesta- [20] gen, creatinine and uric acid are significantly higher in tion were within normal range. In our study, 17% of pregnant women who were diagnosed with early-onset the pregnant women with early-onset preeclampsia and late-onset preeclampsia presenting with severe and 10% of the pregnant women with late-onset hypertension than the healthy pregnant women. preeclampsia delivered newborns with low birth However, there is no statistically significant difference weights. However, these results did not reach a statis- in the renal functions between the early-onset and late- tically significant level (p<0.270). The literature does [26] onset preeclampsia patients. In our study, we found not support this result of our study. We think that this creatinine levels statistically higher in the early-onset result depends on the impacts of ethnic, environmental preeclampsia group (p=0.045). We think that this sta- and genetic factors on newborn birth weights and the tistical difference in the creatinine levels is caused by low number of patients included in our study group. higher maternal complication rates in the early-onset It is known that the only treatment option of preeclampsia group. However, new biomarkers are preeclampsia is to complete the pregnancy by delivery. needed to predict the early diagnosis of preeclampsia However, if the labor is completed on time and delayed, and to guide us for labor decision. maternal (cerebral hemorrhage, hepatic rupture, kidney failure, pulmonary edema, DIC, ablatio placentae, etc.) and fetal complications (intrauterine growth retardation, Conclusion intrauterine death, etc.) become inevitable.[5,10] NICE In our study, we showed that perinatal outcomes clinical guidelines[25] and ACOG[5] recommend conserva- (intrauterine death, newborn’s need for intensive care) tive treatment by close fetal and maternal monitorization and maternal complications (ablatio placentae, eclampsia)
Volume 26 | Issue 3 | December 2018 139 Baflol G et al.
are higher in the patients with early-onset preeclampsia. 13. Vreeburg SA, Jacobs DJ, Dekker GA, Heard AR, Priest KR, We believe that the patients should be followed up close- Chan A. Hypertension during pregnancy in South Australia, ly in primary and secondary hospitals in terms of early part 2: risk factors for adverse maternal and / or perinatal out- come – results of multivariable analysis. Aust N Z J Obstet diagnosis in order to decrease the rates of maternal com- Gynaecol 2004;44:410–8. plications associated with preeclampsia much more. In 14. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu order to decrease the newborn’s need for intensive care KF, et al. Circulating angiogenic factors and the risk of that we found higher rates in our study compared to the preeclampsia. N Engl J Med 2004;350:672–83. literature and to prevent associated fetal complications, 15. Tranquilli AL, Dekker G, Magee L, Roberts J, Sibai BM, hospitalizing patients and following up closely, determin- Steyn W, et al. The classification, diagnosis and manage- ing time and type of delivery according to the progression ment of the hypertensive disorders of pregnancy: a revised will contribute to the decrease of maternal and fetal mor- statement from the ISSHP. Pregnancy Hypertens 2014;4: tality rates. 97–104. 16. Wikström AK, Larsson A, Eriksson UJ, Nash P, Olovsson M. Conflicts of Interest: No conflicts declared. Early postpartum changes in circulating pro- and anti-angio- genic factors in early-onset and late-onset pre-eclampsia. Acta References Obstet Gynecol Scand 2008;87:146–53. 1. Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in 17. Raymond D, Peterson E. A critical review of early-onset and the rates of preeclampsia, eclampsia, and gestational hyper- late-onset preeclampsia. Obstet Gynecol Surv 2011;66:497– tension, United States, 1987–2004. Am J Hypertens 2008; 506. 21:521–6. 18. Sibai BM, Mercer B, Sarinoglu C. Severe preeclampsia in the 2. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AN, Daniels second trimester: recurrence risk and long-term prognosis. J; et al. Global causes of maternal death: a WHO systematic Am J Obs Gynecol 1991;165:1408–12. analysis. Lancet Glob Health 2014;2:e323–33. 19. Roberts JM, Escudero C. The placenta in preeclampsia. 3. Duley L. The global impact of pre-eclampsia and eclampsia. Pregnancy Hypertens 2012;2:72–83. Semin Perinatol 2009;33:130–7. 20. Lisonkova S, Joseph KS. Incidence of preeclampsia: risk fac- 4. Beksaç MS. Preeklampsinin önceden belirlenmesi ve önlen- tors and outcomes associated with early- versus late-onset dis- mesi. Perinatoloji Dergisi 1993;1:31–4. ease. Am J Obs Gynecol 2013;209:544.e1–544.e12. 5. Roberts JM, August PA, Bakris G, Barton JR, Bernstein IM, Druzin M, et al.; Task Force on Hypertension in Pregnancy. 21. Harmon QE, Huang L, Umbach DM, Klungsøyr K, Engel Hypertension in pregnancy. Washington, DC: The American SM, Magnus P, et al. Risk of fetal death with preeclampsia. College of Obstetricians and Gynecologists; 2013. Obstet Gynecol 2015;125:628–35. 6. MacKay AP, Berg CJ, Atrash HK. Pregnancy-related mortal- 22. Kumru P, Kartal ÖP, Köse G, Aka N, Büyüko¤lu B. ity from preeclampsia and eclampsia. Obstet Gynecol 2001;97: Preeklampsi, eklampsi ve HELLP sendromu olgular›m›z›n 533–8. de¤erlendirilmesi. Türkiye Klinikleri Journal of Clinical 7. Dissanayake VH, Samarasinghe HD, Morgan L, Jayasekara Obstetrics and Gynecology 2005;15:72–80. RW, Seneviratne HR, Broughton Pipkin F. Morbidity and 23. Yildirim G, Gungorduk K, Gul A, Asicioglu O, Sudolmus S, mortality associated with pre-eclampsia at two tertiary care Gungorduk OC, et al. HELLP syndrome: 8 years of experi- hospitals in Sri Lanka. J Obstet Gynaecol Res 2007;33:56–62. ence from a tertiary referral center in western Turkey. 8. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclamp- Hypertens Pregnancy 2012;31:316–26. sia and risk of cardiovascular disease and cancer in later life: sys- tematic review and meta-analysis. BMJ 2007;335(7627):974. 24. Doddamani GB, Doddamani UG. Prenatal outcome in pre- eclampsia: a prospective study. Scholars Journal of Applied 9. Obed S, Patience A. Birth weight and ponderal index in pre- Medical Sciences 2014;2:291–3. eclampsia: a comparative study. Ghana Med J 2006;40:8–13. 10. Heard AR, Dekker GA, Chan A, Jacobs DJ, Vreeburg SA, 25. National Collaborating Centre for Women’s and Children’s Priest KR. Hypertension during pregnancy in South Australia, Health (UK). Hypertension in pregnancy: the management part 1: pregnancy outcomes. Aust N Z J Obstet Gynaecol 2004; of hypertensive disorders during pregnancy. NICE Clinical 44:404–9. Guidelines, No. 107. London: RCOG Press; 2010. Available 11. Von Dadelszen P, Magee LA, Roberts JM. Subclassification of from: https://www.ncbi.nlm.nih.gov/books/ NBK62652/ preeclampsia. Hypertens Pregnancy 2003;22:143–8. 26. Li XL, Guo PL, Xue Y, Gou WL, Tong M, Chen Q. An 12. Zhang J, Meikle S, Trumble A. Severe maternal morbidity analysis of the differences between early and late preeclamp- associated with hypertensive disorders in pregnancy in the sia with severe hypertension. Pregnancy Hypertens 2016;6: United States. Hypertens Pregnancy 2003;22:203–12. 47–52.
140 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 2018;26(3):141–147 I N N R A U T A L J O
Evaluation of the use of iodized salt by pregnant women and their knowledge on the use of iodized salt
Emine Özge Avc›1, Baht›flen Kartal2, Evrim Bayraktar3 1Department of Nursing Services, Nevflehir State Hospital, Nevflehir, Turkey 2Department of Nursing, Faculty of Health Sciences, Tokat Gaziosmanpafla University, Tokat, Turkey 3Department of Nursing, Faculty of Health Sciences, Erciyes University, Kayseri, Turkey
Abstract Özet: Gebe kad›nlar›n iyotlu tuz kullan›m›n›n ve iyotlu tuz kullan›m›na iliflkin bilgilerinin belirlenmesi Objective: The aim of our study is to evaluate the use of iodized salt Amaç: Çal›flma gebe kad›nlar›n iyotlu tuz kullan›m›n› ve iyotlu tuz by pregnant women and their knowledge on the use of iodized salt. kullan›m›na iliflkin bilgilerini belirlemek amac›yla yap›lm›flt›r. Methods: The study is of descriptive type. The sample of the study Yöntem: Çal›flma tan›mlay›c› tiptedir. Çal›flman›n örneklemini 347 consisted of 347 pregnant women. The data of the study was collect- gebe oluflturmufltur. Çal›flman›n verileri araflt›rmac›lar taraf›ndan ed by using a data form developed by researchers. The data obtained gelifltirilen bir veri formu kullan›larak toplanm›flt›r. Çal›flmadan el- by the study was analyzed by means of SPSS package software. de edilen veriler bilgisayar ortam›nda SPSS paket program›nda de- Results: Of the pregnant women included in the study, the mean age ¤erlendirilmifltir. was 27.38±6.44 years old, 41.8% were living in urban areas, 34.6% Bulgular: Gebelerin yafl ortalamas›n›n 27.38±6.44 oldu¤u, were graduated from secondary school, 80.7% were housewives, %41.8’inin ilde yaflad›¤›, %34.6’s›n›n ortaokul mezunu, %80.7’sinin 50.4% had income equal to their expenses, and 43.8% had husbands ev han›m›, %50.4’ünün gelirinin giderine denk oldu¤u, %43.8’inin who were workers. It was found that 74.1% of the pregnant women eflinin iflçi oldu¤u belirlenmifltir. Gebelerin %74.1’inin iyot yetersiz- had no knowledge on iodine deficiency and associated diseases, li¤i ve hastal›klar› hakk›nda bilgisinin olmad›¤›, %35.7’sinin iyot ek- 35.7% of them did not know the importance of protection against sikli¤inden korunman›n önemini, %65.7’sinin gebelikte iyotlu tuz iodine deficiency, and 65.7% of them did not know the necessity of kullanman›n gerekli oldu¤unu bilmedi¤i belirlenmifltir. Ayr›ca ge- using iodized salt during pregnancy. Also, we found that 44.1% of the belerin %44.1’inin iyotlu tuz kullanmad›¤›, iyotlu tuz kullanan ge- pregnant women included in the study did not use iodized salt, 56.2% belerin %56.2’sinin iyotlu tuzu do¤ru saklamad›¤›, %16.7’sinin tu- of those using iodized salt did not keep it in a proper way, and 16.7% zu yeme¤e pifltikten sonra ilave etti¤i bulunmufltur. Gebelerin of them added iodized salt into their meal after prepared. It was seen %68.6’s› gebelikte iyotlu tuz kullan›m›na iliflkin bilgi almad›¤›n› be- that 68.6% of the pregnant women did not receive information for lirtmifltir. the use of iodized salt during pregnancy. Sonuç: Sonuç olarak gebelikte iyotlu tuz kullan›m›n›n ve iyotlu Conclusion: In conclusion, we found that the use of iodized salt dur- tuz kullan›m›na iliflkin bilgilerin yetersiz oldu¤u belirlenmifltir. ing pregnancy and knowledge on the use of iodized salt are insufficient. Gebelerin iyotlu tuz kullan›m›, yeme¤e tuz ilave etme zaman› ve We can say that pregnant women need training on the use of iodized tuzu muhafaza etme hakk›nda e¤itime gereksinimi oldu¤u söyle- salt, the time for adding salt into meals and methods for preserving salt. nebilir. Keywords: Pregnancy, iodized salt, iodine insufficiency. Anahtar sözcükler: Gebelik, iyotlu tuz, iyot yetersizli¤i.
Introduction common disorders among endocrine system diseases [1] Cardiovascular system (14.6%) and endocrine system with a rate of 5.6%. diseases (14.5%) are the leading diseases threatening Physiological changes during pregnancy affect the women's health. Thyroid gland diseases are the most activities of thyroid gland. The incidence of hypothy-
Correspondence: Emine Özge Avc›, MD. Department of Nursing Services, Nevflehir State Available online at: Hospital, Nevflehir, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263009 doi:10.2399/prn.18.0263009 Received: July 2, 2018; Accepted: December 18, 2018 QR (Quick Response) Code: Please cite this article as: Avc› EÖ, Kartal B, Bayraktar E. Evaluation of the use of iodized salt by pregnant women and their knowledge on the use of iodized salt. Perinatal Journal 2018;26(3):141–147. ©2018 Perinatal Medicine Foundation Avc› EÖ, Kartal B, Bayraktar E
roidism during pregnancy is reported 2–3%.[2] However, planning pregnancy, pregnant women and breastfeeding the incidence of undiagnosed hypothyroidism and hyper- women whose salt intake should be restricted due to var- thyroidism is higher. The rate of hypothyroidism during ious reasons should certainly be met.[17] pregnancy is consistent with the literature in two studies Although it has been 20 years for the obligatory [3,4] performed in Turkey; however, Güzel et al. found it iodization of salt, it is seen in various studies that iodine [5] 15.8% in their studies. Hypothyroidism during pregnan- deficiency is still a risk for the health of mothers and chil- cy affects maternal and fetal health negatively. The most dren. This shows us that the process of iodizing salt is common reason for hypothyroidism is iodine deficiency. not sufficient alone to eliminate iodine deficiency, and The synthesis of thyroid hormones depends on the pene- that it is necessary to inform individuals / pregnant tration of sufficient amount of iodine into thyroid, normal women about the use of iodized salt. It is considered that iodine metabolism in the thyroid and normal thyroglobu- determining the use of iodized salt by pregnant women line synthesis.[6] Insufficient iodine intake may cause mater- and their knowledge on the use of iodized salt in order to nal hypothyroidism, insufficient fertilization, preeclamp- prevent thyroid dysfunctions associated with iodine sia, postpartum hemorrhage, anemia, miscarriage risk, low insufficiency and to protect the health of mothers and birth weight, stillbirth, congenital anomalies, fetal neuro- newborns would guide the initiatives to be planned for logical development disorders, microcephaly, cretinism identifying and resolving the problem. and similar outcomes.[7–9] It may also cause goiter and con- [7–9] genital hypothyroidism in the newborn. It is reported Methods that iodine deficiency is the most common reason for pre- ventable mental retardation in the world.[10] It is also The study is of descriptive type and it was conducted in reported that there is an increase in the mortality risk of the Maternity Clinic of Nevflehir State Hospital of [11,12] Nevflehir Public Hospital Association. The sample of the newborns associated with the iodine deficiency. study consisted of 3637 pregnant women who admitted to Congenital hypothyroidism is one of the most common [13] this hospital in a year. The sample size was calculated by endocrine diseases of newborns. Chronic thyroid hor- using the method of sampling from known population. mone deficiency is seen in one per 3500–4000 newborns in the world and per 2525 children in Turkey.[14,15] As the number of individuals in the population is known, sample size was calculated by the following for- Iodine need increases during pregnancy and there- mula: fore iodine intake should be increased to meet increasing need.[2] World Health Organization recommends 250 • n=(Nt^2 pq)/(d^2 (N-1)+t^2 pq) and the sample size mcg of iodine intake daily for pregnant women.[16] was calculated 347. In the formula: Urinary iodine, which is the best indicator for iodine • N: Number of individuals in the target population level, should be >100–200 mcg/L in pregnant women, (3637) and therefore it is recommended to take 250–300 mcg • n: Number of individuals to be sampled iodine daily by means of iodized salt, sea products and • p: Prevalence of the case investigated (probability of iodine-rich foods.[2] However, it is seen that mean daily occurrence) (0.50) iodine intake is 66.4 mcg for pregnant women and 65.7 • q: Non-prevalence of the case investigated (probabil- mcg for breastfeeding women in Turkey.[17] It has been ity of non-occurrence) (0.50) found in the studies performed in Turkey that pregnant • t: Theoretical value found from t table at a particular women have iodine deficiency.[2,18–21] independent level and identified margin of error was In Turkey, iodine deficiency is an endemic problem in considered 1.96 at 95% significance level. all regions and iodine deficiency is associated with the • d: Desired level according to the prevalence ± devia- insufficient intake by diet. “The Program of Preventing tion, 0.05 margin of error (5% deviation) Iodine Deficiency Diseases and Iodizing Salt” has been Random sampling method was used to collect the carried out since 1995 in Turkey to fight against iodine data. The data of the research was collected by using a deficiency, and it has been made obligatory to iodize table data collection form prepared by reviewing the literature salt by legal regulations as of 1998 in accordance with this by the researchers. Pregnant women who knew Turkish program. Food industry salt is not iodized. It is highlight- and had no problems with verbal communication were ed that the iodine needs (200–250 mcg/day) of women included in the study. The data was collected by face to
142 Perinatal Journal Evaluation of the use of iodized salt by pregnant women and their knowledge on the use of iodized salt
face interview in the maternity clinic by the researchers. While 45.9% of the pregnant women using iodized The participation in the study was on voluntary basis, and salt kept it in glass jar with lid and 69.6% of them paid the purpose of the study and participation on voluntary attention to keep iodized salt away from the sunlight, basis were explained to the pregnant women. Pregnant only 46.1% of them could properly explain why it women who accepted to participate were applied data should be kept away from sunlight (as vitamin/mineral collection form. SPSS package software was used to ana- would be lost, chemical structure of iodine would be lyze the study data. Descriptive statistics (number and damaged) (Table 2). percentage) were used to evaluate the data. It was paid attention to comply with ethical principles in all stages of the study. Before starting the study, the Table 1. The distribution of pregnant women in terms of iodized ethics committee approval (no. 2014.12.05) was obtained salt use (n=347). from Ethics Committee of Nevflehir Hac› Bektafl Veli n% University and written approval was obtained from Nevflehir State Hospital of Nevflehir Public Hospital Use of iodized salt I use 194 55.9 Association. Also, before filling data forms, the verbal I do not use 153 44.1 consents of pregnant women were obtained after Paying attention to purchase iodized salt informing them about the purpose of the research. Yes 132 38.0 No 215 62.0 Salt type used at home Results Rock salt 144 41.5 Sea salt 7 2.0 Of the pregnant women who participated in the study, Himalayan salt 2 0.6 24.2% were between 21 and 25 years old, 41.8% were liv- Iodized salt 194 55.9 ing in city center, 34.6% were graduated from secondary The reason for using iodized salt (n=194) school, 80.7% were housewives, 50.4% had income equal I do not know why I have to use it 78 40.2 I believe that it is healthier 67 34.5 to their expenses, and 43.8% had husbands who were Because it is beneficial 32 16.5 workers. It was also found that it was first pregnancy in Because it is good for goiter 17 8.8 27.7% of the pregnant women, 35.4% of them had 4 and The frequency of using iodized salt (n=194) Always 142 73.2 more pregnancy, 11% of them had preterm labor, 27.7% From time to time 48 24.7 of them had the history of miscarriage/curettage, and I started to use during pregnancy 4 2.1 3.5% of them had stillbirth. It was found that 4.9% of the pregnant women had thyroid disorder, all pregnant women who had thyroid Table 2. The distribution of iodized salt according to proper using / kee- disorder had hypothyroidism (n=17), and 9.8% of them ping conditions among pregnant women using iodized salt. had a history of thyroid disorder in their families and the n% mothers of 76.5% of these pregnant women had a histo- Location where iodized salt is kept (n=194) ry of disease. Original packaging 6 3.1 Of the pregnant women who participated in the Glass jar with lid 89 45.9 Light-proof jar with lid 85 43.8 study, 35.7% stated that they did not know the impor- Open salt shaker 14 7.2 tance of protecting themselves against iodine deficiency Paying attention to keep iodized salt away from sunlight (n=194) and 65.7% stated that they did not know the necessity of Pays attention 135 69.6 using iodized salt during pregnancy. Of the pregnant Does not pay attention 59 30.4 women who knew the necessity of using iodized salt dur- The reason for keeping iodized salt away from sunlight (n=194) No reason 27 13.9 ing pregnancy, 43.6% stated that it was necessary for the I do not know 37 19.1 brain development of baby. Although 55.9% of the preg- To keep away from moisture 36 18.6 Because vitamin/mineral would be lost 18 9.3 nant women reported that they were using iodized salt, Because chemical structure of iodine would be damaged 68 35.0 62% of them said that they did not pay attention if the Its odor would change under sunlight 8 4.1 salt they purchase is iodized or not. Also, 40.2% of the Time to add salt into meals (n=347) pregnant women using iodized salt said that they did not After the meal is cooked 58 16.7 During the cooking 289 83.3 know why they need to use iodized salt (Table 1).
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Of the pregnant women, 69.7% use tap water as Table 3. The distribution of pregnant women in terms of iodine in- take and nourishment characteristics (n=347). drinking water, 92.5% use tap water in their meals while 72.1% do not know iodine-rich foods. Of those n% who know iodine-rich foods, 79.4% believe that sea Using tap water (n=347) products are iodine-rich, but 73.2% of the pregnant Bottle water 87 25.1 women do not pay attention to consume iodine-rich Tap water 242 69.7 foods during pregnancy (Table 3). Purified water 18 5.2 Water added into meals (n=347) On the other hand, it was found that the pregnant Bottle water 8 2.3 women rarely consume foods which are poor in iodine Tap water 321 92.5 (kale, cabbage, turnip, white turnip), and only consume Purified water 18 5.2 milk and dairy products more frequently as iodine-rich The knowledge about iodine-rich foods (n=97) She knows 97 27.9 foods. She does not know 250 72.1 Of the pregnant women, 31.4% stated that they The foods known as iodine-rich (n=97) were informed about the use of iodized salt during Dairy products 7 7.2 Sea products 77 79.4 pregnancy and 67.9% of these pregnant women were Green vegetables 8 8.2 informed by healthcare professionals. Also, 58.7% of Legumes 4 4.1 the pregnant women stated that they were informed Red meat and meat products 1 1.0 about the benefits of iodine on health. Paying attention to consume iodine-rich foods during pregnancy (n=347) Yes 93 26.8 No 254 73.2 Discussion Iodine-rich foods consumed by pregnant women (n=93) Dairy products 6 6.5 Preventing iodine deficiency is important to protect the Sea products 75 80.6 health of mother and baby. Using iodized salt has an Green vegetables 8 8.6 important role on the prevention of iodine deficiency Legumes 3 3.2 Red meat and meat products 1 1.1 diseases.[22] The Communique of Turkish Food Codex on Edible Salt was published in 1998.[23] With this com- munique, it was obliged to enrich table salt by iodine in Turkey. In our study, 55.9% of the pregnant women shows that pregnant women have insufficient knowledge stated that they use iodized salt. It is seen in the studies about the use of iodized salt. Iodine deficiency is a signif- on the use of iodized salt during pregnancy that the rate icant condition for the health of mother, fetus and new- of using iodized salt varies between 26.1% and 96% born. Iodine deficiency may cause insufficient fertiliza- among the pregnant women.[3,21,24–28] In our study, we tion, preeclampsia, postpartum hemorrhage, anemia, and found that almost half of the pregnant women were not miscarriage risk in women, and low birth weight, still- using iodized salt. This result of our study is important birth, congenital anomalies, microcephaly, cretinism and in terms of showing the fact that the knowledge on the similar outcomes in fetuse.s It may also cause goiter and [9] use of iodized salt by pregnant women is insufficient or hypothyroidism in the newborn. In our study, 70.9% of these pregnant women are not aware of its importance. the pregnant women stated that they did not know the In our study, 51% of the pregnant women stated that importance of protection against iodine deficiency and they did not do anything for it. This rate was 12% in the they are using iodized salt as it is more beneficial and [3] healthier. In the study of fienbayram, 50% of pregnant study of fienbayram. Compared to the study of women explained the reason for using iodized salt as it is fienbayram, we believe that this difference in the rates beneficial and healthy.[3] Seventy-seven percent of the might be because of the low education and employment pregnant women in the study of Kirkizo¤lu and Pekcan[29] levels of women in our study. and 93.9% of the pregnant women in the study of Köksal Iodized salt should be kept in a cool, dry environ- and Pekcan[26] stated that they did not know why they ment without light and in dark colored glass containers should use iodized salt. In our study, almost half of the in order to prevent iodine loss.[30] In our study, 45.9% of pregnant women use iodized salt and half of those using the pregnant women expressed that they are keeping salt iodized salt do not know why they use it. This result in glass jar with lid. While 71.6% of the pregnant
144 Perinatal Journal Evaluation of the use of iodized salt by pregnant women and their knowledge on the use of iodized salt
women in the study of Ak›n were keeping salt in glass hypothyroidism was 2.8%.[4] This rate was 15.8% in the jar,[25] 76% of the pregnant women in the study of Özkan study of Güzel et al.,[5] 2.8% in the study of fienbayram,[3] were keeping salt in a cool, closed environment without and 1.8% in the study of Fadayev et al.[33] According to any sunlight.[28] 19.1% of the pregnant women in the 2017 report of Turkish Endocrinology and Metabolism study of fienbayram and 13.9% of the pregnant women Society, hypothyroidism prevalence during pregnancy in the study of Ulu stated that they were keeping salt in was 0.3–0.5% for overt hypothyroidism and 2–3% for light-proof jars which are the ideal containers.[3,27] In our sub-clinical hypothyroidism.[2] Hypothyroidism rate of study and many other studies, we can see that most of the pregnant women in our study was higher than other pregnant women do not keep salt under proper condi- studies. The iodine concentration of local drinking water tions. Iodine loss occurs in salts which are not kept under is also another indicator of the iodine content of soil. proper conditions, and it results in the problems associ- While the iodine content in iodine-poor regions is usu- ated with iodine deficiency even iodized salt is used. ally below 2 μg/L, it is 9.0 μg/L and above in the regions [28] Iodine is a substance which is affected by heat, mois- which are not iodine-poor. The Public Health ture and other climatic conditions. Since iodized salt Laboratory of the region where the study was conducted loses approximately 50% of its content when cooked, it reports that the tap water of the city has insufficient is recommended to add iodized salt after the meal is pre- iodine. In our study, 92.5% of the pregnant women stat- pared.[31] In our study, 83.3% of the pregnant women ed that they use tap water. Of the pregnant women, reported that they add salt into the meal during cooking. 46.6% in the study of Ak›n, 50.5% in the study of Özkan Of the pregnant women, 67.7% in the study of Ulu[27] and 37.8% in the study of Ulu were using tap water.[25,27,28] and 91.5% in the study of Özkan[28] stated that they add Absence of iodine in the tap water is important in terms salt into meal before starting to cook. In the study of of revealing iodine deficiency and iodine-related prob- fienbayram, 16.3% of the pregnant women said that they lems. This finding of the study highlights the importance add salt into the pot after the meal is cooked.[3] It is seen of planning and providing training about the use of both in our study and other studies conducted on this iodized salt to people who live in iodine-poor regions. topic that iodized salt is not added during the recom- The iodine need of fetus is met by maternal iodine trans- mended times. The presence of iodine deficiency despite ferred transplacentally.[34] Iodized salt, sea products and the high consumption of salt in Turkey shows that the particularly fish, milk and dairy products are the most salt used is not iodized and/or individuals have insuffi- important iodine resources.[35] The rate of the cases con- cient knowledge about the proper use of iodized salt. suming dairy products daily is 56.5% in our study. Iodine is a trace element which penetrates into the According to the results of 2016 Turkish Nourishment structure of thyroid hormones and is essential for the and Health Survey (TBSA), the rate of those drinking [17] normal activity of thyroid hormones that are necessary milk daily was 28.4%. Yavuz and Aykut found in their for the normal growth and neurological development of study that 48.8% of the pregnant women were consum- [36] fetus during the pregnancy.[32] According to the report of ing appropriate amounts of milk and dairy products. WHO/ICCIDD in 2007, the best method for iodine While 82.9% of the pregnant women in the study of [37] replacement in pregnant women is to iodize salt.[16] No¤ay were consuming milk, this rate was 69.6% in [25] Turkey is a region with moderate/severe level of iodine the study of Ak›n. The studies carried out have similar deficiency and endemic goiter.[2] Iodine need increases results compared to our study, and the rate of pregnant during pregnancy, and iodine deficiency during preg- women consuming milk and dairy products is insuffi- nancy may disrupt thyroid hormone production, affect cient. Consuming insufficient amount of milk and dairy physical and mental development of fetus negatively, and products is a significant indicator showing insufficient increase mortality risk of newborn.[11] In our study, intake of iodine resources. 25.4% of the pregnant women expressed that the use of Antithyroid compounds in some foods may cause iodized salt during pregnancy is necessary and 8.8% of iodine deficiency by blocking iodine transfer in thyroid them associated this necessity with thyroid gland. gland. The most important resources for antithyroid In our study, 4.9% of the pregnant women had compounds are cauliflower, cabbage, Brussels sprout, hypothyroidism. Bostanc› and Taflkesen reported in their turnip, white turnip and similar vegetables.[27] The preg- study conducted on pregnant women that the rate of nant women in our study rarely consume these vegeta-
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bles. In the study of Akin, the authors reported that salt into their meal after prepared. We found that 68.6% 45.1% of the pregnant women consume cabbage, 13.4% of the pregnant women did not receive information for of them consume white turnip and 38.2% of them con- the use of iodized salt during pregnancy. In conclusion, [25] sume turnip. Excessive consumption of these vegeta- we found that the use of iodized salt during pregnancy bles cause insufficient intake or use of iodine by the and knowledge on the use of iodized salt are insufficient. body; however, the consumption of these vegetables is Beginning from the pregestational period, pregnant not considered as risky as causing iodine deficiency in women and their families should be informed about the terms of consumption frequency. Iodine mainly exists in use and importance of iodized salt during pregnancy, the soil; most of the iodine in the world is taken from the studies should be planned to determine the knowledge of surface by glaciers, snow and rains and carried into healthcare professionals about the use of iodized salt, oceans by winds, rivers and floods. Therefore, seaweeds and sea products are rich in iodine.[35] In our study, nurses should perform house visits to inform pregnant 14.1% of the pregnant women were consuming fish for women and observe the use of iodized salt conditions on- a few days per week. According to 2010 data of Turkish site and repeat their trainings if necessary. Nourishment and Health Survey, 79% of the pregnant women consume fish at least once during their pregnan- Conflicts of Interest: No conflicts declared. cy.[17] Ak›n et al. reported in their study that 73.9% of the [25] References pregnant women consume sea products. In the study of No¤ay, 87.1% of the pregnant women were consum- 1. Türkiye Kad›n Sa¤l›¤› Araflt›rmas›. T.C. Sa¤l›k Bakanl›¤› ing fish and only 52.9% of them were consuming fish for Sa¤l›k Araflt›rmalar› Genel Müdürlü¤ü. Ankara; 2014. ISBN: 978-975-590-491-7. 1–2 times a week.[37] In the previous studies and our 2. Tiroid Hastal›klar› Tan› ve Tedavi K›lavuzu. Ankara: Türkiye study, it is seen that pregnant women do not consume Endokrinoloji ve Metabolizma Derne¤i: 2017. s. 114–7. iodine-rich sea products regularly and sufficiently. Of 3. fienbayram S. Gebeli¤in ilk üç ay›nda olan kad›nlar›n iyot the pregnant women, only 31.4% stated that they were eksikli¤i ve tiroid fonksiyonlar› aç›s›ndan de¤erlendirilmesi. informed about the use of iodized salt during pregnancy Ankara: Baflkent Üniversitesi T›p Fakültesi Aile Hekimli¤i and 67.9% of these informed pregnant women received Anabilim Dal›; 2007. this information from healthcare professionals. In the 4. Bostanc› MS, Taflkesen F. Gebelikte tiroid fonksiyon bozuk- study of fienbayram, these rates were 73% and 37%, luklar› ve sonuçlar›n›n de¤erlendirilmesi. Klinik ve Deneysel respectively.[3] The fact that approximately one third of Araflt›rmalar Dergisi 2011;2:196–201. the pregnant women were informed about the use of 5. Güzel E, Sivri Ayd›n D, Çilesiz Göksedef BP, Boran AB. iodized salt and two third of informed pregnant women Gebelerde tiroid fonksiyon bozuklu¤u s›kl›¤›. Perinatoloji Dergisi 2015;23:96–100. received this information from healthcare professionals 6. Akdemir N, Birol L. Endokrin sistem hastal›klar› ve indicates that the information they receive may be insuf- hemflirelik bak›m›. ‹ç hastal›klar› ve hemflirelik kitab›. ficient and incorrect. The low level of iodized salt use Geniflletilmifl 2. bask›. Ankara: Sistem Ofset; 2005. s. 683. and insufficient level of knowledge about the significance 7. Atafl A, Çakmak A, Karazeybek H. Konjenital hipotiroidizm. of iodized salt can be explained with the insufficient Journal of Current Pediatrics 2007;5:70–6. information received. 8. Tazegül A, fiimflek B. Gebelikte tiroid hastal›klar›. Selçuk T›p Dergisi 2010;26:63–7. Conclusion 9. Aykut M. Toplum Beslenmesi. Öztürk Y, Günay O, editör- ler. Halk sa¤l›¤›. Genel bilgiler. Kayseri: Erciyes Üniversite- We found in our study that 74.1% of the pregnant si Yay›nlar›; 2011. s. 1247–417. women had no knowledge on iodine deficiency and asso- 10. Zimmermann MB, Jooste PI, Pandav CS. Iodine deficiency ciated diseases, 35.7% of them did not know the impor- disorders. Lancet 2008;372(9645):1251–62. tance of protection against iodine deficiency, and 65.7% 11. Erbafl T. ‹yot eksikli¤i ve guatr. Atabey E., editör. Hacettepe of them did not know the necessity of using iodized salt Ü. T›p Fak. Endokrinoloji Uluslararas› Kat›l›ml› T›bbi Jeoloji Sempozyumu Kitab›. Ankara; 2008. s. 94–5. during pregnancy. Also, we found that 44.1% of the 12. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight pregnant women included in the study did not use GJ, Gagnon J, et al. Maternal thyroid deficiency during iodized salt, 56.2% of those using iodized salt did not pregnancy and subsequent neuropsychological development keep it in a proper way, and 16.7% of them added iodized of the child. N Engl J Med 1999;341:549–55.
146 Perinatal Journal Evaluation of the use of iodized salt by pregnant women and their knowledge on the use of iodized salt
13. Yordam N, Çal›ko¤lu AS, Hatun fi, Kandemir N, O¤uz H, Yüksek Lisans Tezi, Selçuk Üniversitesi Sa¤l›k Bilimleri Teziç T, et al. Screening for congenital hypothyroidism in Enstitüsü, Hemflirelik Anabilim Dal›, Konya, 2012. Turkey. Eur J Pediatr 1995;154:614–6. 26. Köksal E, Pekcan G. Gebe kad›nlar ile yeni do¤anlar›n›n 14. MacGillivray M. Congenital hypothyroidism, In: Pescovitz idrarla iyot at›m durumlar›n›n iliflkisi. Sürekli T›p E¤itimi OE, EA, editor. Pediatric endocrinology. Philadelphia, PA: Dergisi 2009;18:68–70. Lipincott Williams and Wilkins; 2004. p. 490–507. 27. Ulu H. Gebe kad›nlarda ve yenido¤an bebeklerinde idrar 15. Cinaz P, Yeflilkaya E, Acar D, Bideci A, Çamurdan O, Ayval› iyot düzeyleri ve tiroid fonksiyon testleri sonuçlar›n›n E. Yenido¤an konjenital hipotiroidizm tarama sonuçlar›n›n de¤erlendirilmesi. Uzmanl›k Tezi, Selçuk Üniversitesi T›p de¤erlendirilmesi. ‹stanbul T›p Fakültesi Dergisi 2008;71: Fakültesi Aile Hekimli¤i Anabilim Dal›, Konya, 2012. 78–83. 28. Özkan P. Ayd›n ilindeki yenido¤an ve annelerinde idrar iyot 16. Assessment of iodine deficiency disorders and monitoring düzeyleri ve tiroid fonksiyon testleri. Uzmanl›k Tezi, Adnan their elimination. A guide for programme managers. Menderes Üniversitesi T›p Fakültesi Çocuk Sa¤l›¤› ve Geneva: World Health Organization; 2007. Hastal›klar› Anabilim Dal›, Ayd›n, 2008. 17. Türkiye Beslenme ve Sa¤l›k Araflt›rmas› (TBSA) 2010. 29. Kirkizo¤lu E, Pekcan G. Ankara ili Çubuk ilçesi Kuruçay ve Ankara: Hacettepe Üniversitesi Sa¤l›k Bilimleri Fakültesi K›fllac›k köylerinde iyot yetersizli¤i hastal›¤› prevalans›, Beslenme ve Diyetetik Bölümü; 2014. s. 53. idrarla iyot at›m› ve iyotlu tuz kullan›m›. Beslenme ve Diyet 18. Oguz Kutlu A, Kara C. Iodine deficiency in pregnant women Dergisi 2001;30:12–8. in the apparently iodine-sufficient capitalcity of Turkey. 30. Ayaz A. Tuz tüketimi ve sa¤l›k. Hacettepe Üniversitesi- Clin Endocrinol (Oxf) 2012;77:615–20. Sa¤l›k Bilimleri Fakültesi Beslenme ve Diyetetik Bölümü, 19. Egri M, Ercan C, Karaoglu L. Iodine deficiency in pregnant Ankara: Klasmat Matbaac›l›k; 2008. s. 18. women in eastern Turkey (Malatya Province): 7 years after 31. Baysal A. Beslenme. 10. bask›. Ankara: Hatibo¤lu Yay›nevi; the introduction of mandatory table salt iodization. Public 2004. s. 268–75. Health Nutr 2009;12:849–52. 32. Alvarez-Pedrerol M, Ribas-Fitó N, García-Esteban R, 20. Kurto¤lu S, Akcakus M, Kocaoglu C, Gunes T, Budak N, Rodriguez A, Soriano D, Guxens M, et al. Iodine sources and Atabek ME, et al. Iodine status remains critical in mother iodine levels in pregnant women from an area without and infant in Central Anatolia (Kayseri) of Turkey. Eur J known iodine deficiency. Clin Endocrinol (Oxf) 2010;72:81– Nutr 2004;43:297–303. 6. 21. Anaforo¤lu ‹, Algün E, ‹nceçay›r Ö, Topbafl M, Erdo¤an 33. Fadayev V, Lesnikova S, Melnichenko G. Prevalence of thy- MF. Iodine status among pregnant women after mandatory roid disorders in pregnant women with mild iodine deficien- salt iodisation. Br J Nutr 2016;115:405–10. cy. Gynecol Endocrinol 2003;17:413–8. 22. Sa¤l›k Bakanl›¤› Sa¤l›k E¤itimi Genel Müdürlü¤ü. Gebelik ve 34. Kurto¤lu S. ‹yot eksikli¤i sorununun de¤erlendirilmesi ve emziklilik döneminde beslenme. Beslenme modülleri. E¤itim- çözüm yollar›. Türk Pediatri Arflivi 1997;32:4–13. ciler için e¤itim rehberi. Ankara: ‹lkay Ofset Matbaac›l›k; 35. Aile ve Tüketici Hizmetleri. Sa¤l›kl› yaflam ve besinler. 2008. s. 44. Ankara: Milli E¤itim Bakanl›¤›; 2011. s. 30. 23. T.C Resmi Gazete. Say›: 23397. s. 29–31. 36. Yavuz S, Aykut M. Kayseri Melikgazi E¤itim Araflt›rma 24. Çak›r Ç, Teziç T, Zorlu P, O¤uz Kutlu A, F›rat S. Anne Sa¤l›k Grup Baflkanl›¤› bölgesinde gebe kad›nlar›n gebelikte idrar iyot düzeyleri ile anne kan›nda ve kordon kan›nda beslenme konusundaki bilgi düzeyleri ve beslenme durumu. TSH, ST4 düzeylerinin karfl›laflt›r›lmas›. Türkiye Klinikleri Sa¤l›k Bilimleri Dergisi 2014;23:10–20. Journal of Pediatrics 2002;11:126–30. 37. No¤ay NH. Gebe kad›nlar›n beslenme durumunun de¤erlen- 25. Ak›n R. Gebe kad›nlarda trimesterlere göre idrarda iyot dirilmesi. Elektronik Meslek Yüksekokullar› Dergisi 2011;1: düzeyleri ve beslenme durumlar›n›n de¤erlendirilmesi. 51–7.
Volume 26 | Issue 3 | December 2018 147 A L J O A T U N R I N R A E L P Original Article
P L E R A Perinatoloji Dergisi 2018;26(3):148–154 I N N R A U T A L J O Perinatal Journal 2018;26(3):148–154 künyeli yaz›n›n Türkçe sürümüdür.
The impact of using thromboprophylactic medication by pregnant women on the hemodynamics of fetus and uterus
Emre Zafer Department of Gynecology and Obstetrics, Faculty of Medicine, Ayd›n Adnan Menderes University, Ayd›n, Turkey
Abstract Özet: Gebelerde tromboprofilaktik ilaç kullan›m›n›n fetüs ve uterus kan ak›fl dinamiklerine etkisi Objective: To define potential effects of anticoagulants at prophy- Amaç: Gebelikleri süresince çeflitli nedenlerle profilaktik dozda lactic doses due to various reasons during pregnancy on the blood antikoagülasyon bafllanan olgular›n fetal ve uterin kan dolafl›mla- flow of fetus and uterus. r›ndaki olas› etkileri tan›mlamak. Methods: In this prospective monocenter study, blood flow param- Yöntem: Prospektif yap›lan bu tek merkezli çal›flmada antikoagü- eters of umbilical artery (UmA), middle cerebral artery (MCA) and lan (düflük molekül a¤›rl›kl› heparin-DMAH ve/veya asetilsalisilik uterine artery (UtA) of pregnant women, who were at second and asit-ASA) kullanan, ikinci ve üçüncü trimesterdeki gebelerde; um- third trimesters and were using anticoagulants (low-molecular- bilikal arter (UmA), orta serebral arter (MCA) ve uterin arter weight heparin-LMWH and/or acetylsalicylic acid-ASA), were eval- (UtA) kan ak›fl parametreleri Doppler ultrasonografi ile de¤erlen- uated by Doppler ultrasonography. The pregnant women who were dirildi. Antikoagülan kullanmayan ve benzer yafl ve gestasyonel at similar ages and weeks of gestation and not using anticoagulants haftadaki gebeler ise kontrol grubu olarak seçildi. ‹ki grup klinik, were selected as the control group. Two groups were compared by demografik ve Doppler bulgular› aç›s›ndan “ba¤›ms›z grup t testi” “independent samples t-test” and “Mann–Whitney U test” in terms ve “Mann–Whitney U testi” ile karfl›laflt›r›ld›. Alt grup analizinde, of clinical, demographic and Doppler findings. In the sub-group sadece DMAH ve DMAH ile beraber ASA kullananlar kontrol analysis, only the cases using LMWH and LMWH+ASA were com- grubu ile karfl›laflt›r›ld›lar. pared to the control group. Bulgular: Çal›flmaya toplam 63 olgu dahil edildi. Antikoagülan Results: A total of 63 cases were included in the study. No statistical- kullanan 36 (%57.1) gebe ile herhangi bir antikoagülan kullanma- ly significant difference was found in the comparison of demograph- yan 27 (%42.9) gebenin kötü obstetrik özgeçmifl varl›¤› d›fl›ndaki ic and clinical data of 36 (57.1%) pregnant women using anticoagu- (p<0.001) demografik ve klinik verilerinin karfl›laflt›r›lmas›nda ista- lant and 27 (42.9%) pregnant women not using any anticoagulant tistiksel aç›dan anlaml› bir fark bulunmad›. Çal›fl›lan damarlardaki except the presence of poor obstetric history (p<0.001). There was no Doppler verileri aç›s›ndan da iki grup aras›nda fark izlenmedi difference between two groups in terms of Doppler data on the arter- (p>0.005). Ancak trimester ay›r›m› yap›ld›¤›nda antikoagülan gru- ies studied (p>0.005). However, when the groups were compared in bunun 3. trimester MCA PSV de¤erlerinin kontrol grubundan an- terms of their trimester period, it was found that 3rd trimester MCA laml› derecede farkl› oldu¤u izlendi (p=0.037). Antikoagülan alt PSV values of anticoagulant group was significantly different than of grup analizinde ise DMAH ve ASA’n›n birlikte kullan›m›n›n MCA the control group (p=0.037). It was found in the anticoagulant sub- PSV de¤erlerinde anlaml› de¤iflime neden oldu¤u bulundu group analysis that the concomitant use of LMWH and ASA caused (p=0.006). a significant change in MCA PSV values (p=0.006). Sonuç: Gebelikte DMAH veya ASA kullan›m›n›n umbilikal, fetal Conclusion: We found that the use of LMWH or ASA during orta serebral arter ve uterin arter ak›fl dinamiklerinde Doppler ile pregnancy did not cause any significant change which can be seen by izlenebilir anlaml› bir de¤iflikli¤e yol açmad›¤› izlendi. Ancak her Doppler in the hemodynamics of umbilical artery, fetal middle cere- iki antikoagülan›n birden kullan›m›n›n, gebeli¤in 3. trimesterinde bral artery and uterine artery. However, we considered that the con- MCA üzerinde daha fark edilebilir bir etki gösterebilece¤i düflü- comitant use of both anticoagulants has a more distinguishable effect nüldü. on MCA value during 3rd trimester of pregnancy.
Keywords: Anticoagulant, pregnancy, Doppler, umbilical artery, Anahtar sözcükler: Antikoagülan, gebelik, Doppler, umbilikal ar- uterine artery, middle cerebral artery. ter, uterin arter, orta serebral arter.
Correspondence: Emre Zafer, MD. Department of Gynecology and Obstetrics, Faculty of Available online at: Medicine, Ayd›n Adnan Menderes University, Ayd›n, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263010 doi:10.2399/prn.18.0263010 Received: November 14, 2018; Accepted: December 18 2018 QR (Quick Response) Code: Please cite this article as: Zafer E. The impact of using thromboprophylactic medication by pregnant women on the hemodynamics of fetus and uterus. Perinatal Journal 2018;26(3):148–154. ©2018 Perinatal Medicine Foundation The impact of using thromboprophylactic medication by pregnant women on the hemodynamics of fetus and uterus
Introduction ing to the user due to technical reasons such as angle of insonation and broadness of samples, their standardiza- Thromboprophylaxis during pregnancy usually aims tion is quite simple. However, apart from the techniques one of two major goals: Maternal thromboembolism of ultrasonography use, these parameters can be affect- prophylaxis and preventing poor obstetric outcomes. ed by the clinical characteristics of patients. Therefore, The potential roles of coagulative changes in maternal- it is worth investigating how anticoagulants affect fetal fetal combination and congenital thrombophilia on and placental hemodynamics during the pregnancy. recurrent first trimester miscarriages, second-third While there is particularly a considerable amount of trimester fetal deaths, ablatio placentae and even pregnant women who use anticoagulant due to the sub- intrauterine growth retardation have been investigated [8] [1] jective criterion of “poor obstetric history”, potential frequently. By the recommendations published by dif- effects of anticoagulants on Doppler parameters can be ferent professional societies and organizations on this crucial. popular topic, it has been aimed to prevent anticoagu- lant use during pregnancy through incorrect and/or Therefore, we aimed to compare uterine, umbilical missing indications.[2,3] and fetal middle cerebral artery Doppler parameters between the pregnant women who started to use antico- The usage areas of Doppler ultrasonography have agulant due to the subjective criterion of poor obstetric been expanding day by day thanks to its superiority in history and the pregnant women who did not use anti- analyzing hemodynamics. Changes in fetal-placental coagulant and to investigate the effects of anticoagulant and uterine hemodynamics can be identified without at prophylactic dose on the outcomes in this study. requiring an invasive procedure on many positions of circulation system, particularly umbilical artery, fetal middle cerebral artery and uterine artery, for topics such Methods as intrauterine growth retardation, fetal anemia follow- Study population up and management, preeclampsia and even the predic- The study group consisted of the cases who admitted [4,5] tion of poor obstetric outcomes. to the maternity clinic of Application and Research Uterine artery provides blood flow to uterine and Hospital, Medicine Faculty, Ayd›n Adnan Menderes therefore to placenta during pregnancy. In recent years, University and for whom thromboprophylaxis was ini- uterine artery Doppler (UtAD) ultrasonography has tiated by another center during the first trimester of been used particularly for the prediction of the develop- their pregnancies. The inclusion criterion was “contin- ment of severe preeclampsia.[6] Significant parameters uing to use low-molecular-weight heparin (LMWH) at reflecting placental resistance in particular are obtained prophylactic dose and/or low-dose acetylsalicylic acid with the analysis of umbilical artery by Doppler ultra- (ASA) at second or third trimester since the first sonography (UmAD). Thanks to these parameters, trimester”. The exclusion criteria were determined as fetal-neonatal mortality in the management of intrauter- pregnancies below 18-year-old, multiple pregnancies, ine growth retardation can be decreased significantly.[4] known fetal genetic or other anomalies, using antico- Hemodynamics of fetal middle cerebral artery (MCA) agulant due to indications (i.e. deep vein thrombosis or are very important for the antenatal follow-up and man- prosthetic heart valve, anticardiolipin antibody positiv- agement of clinical problems such as feto-maternal ity, presence of lupus anticoagulant) except poor hemorrhages and Rh incompatibility in terms of the obstetric history, using anticoagulant irregularly, and brain sparing effect defined as centralization and there- starting to use anticoagulant before pregnancy or after fore the intrauterine follow-up of fetal anemia.[7] It is also first trimester. very important to predict the poor obstetric outcomes as The approval of Ethics Committee of Non- a component of “cerebro-placental ratio” (CPR) which Invasive Clinical Researches, Medicine Faculty, Ayd›n [5] has been investigated frequently in the recent years. Adnan Menderes University (protocol no. 2015/38) Although the parameters measured by Doppler was obtained before the study. During routine obstet- ultrasonography technique, which is commonly used in ric ultrasonography, umbilical, uterine and middle obstetrics and reassures clinical evaluation, vary accord- cerebral artery Doppler ultrasonography evaluations
Volume 26 | Issue 3 | December 2018 149 Zafer E
were done in all patients and the values were recorded numerical variables without normal distribution, and together with other demographic and clinical data. As descriptive statistical data were presented as median clinical and demographic data, age, gravida, parity, (25th–75th percentile). Chi-square test was used for week of gestation, smoking habit, blood pressure, anti- the analysis of categorical data. The cases where “p- coagulant use and type, medication use for chronic rea- value” is below 0.05 were considered statistically sig- sons other than anticoagulants, presence of poor nificant. obstetric history and obstetric and non-obstetric prob- lems in the current pregnancy were investigated. Two Results or more first trimester pregnancy loss in previous preg- nancies, second or third trimester fetal death, ablatio A total of 56 cases using anticoagulant and 27 cases not placentae, and hypertensive diseases during gestation using anticoagulant were analyzed for the study. Of the were considered “poor obstetric history”. The condi- cases using anticoagulant, 2 were excluded from the tions in pregnancy during study such as pregestational study due to DVT history, 5 due to multiple pregnan- or gestational diabetes, hypertensive diseases of gesta- cy, 4 due to anticoagulant use after first trimester and 9 tion, chronic hypertension, ablatio placentae, and due to irregular use of anticoagulant. The data of epilepsy were classified as “presence of current clinical remaining 36 (57.1%) cases using anticoagulant were problems”. Presence of congenital thrombophilia (i.e. analyzed as study group. Similarly, the data of 27 factor V Leiden mutation) was not taken into consid- (42.9%) pregnant women not using any type of antico- eration. agulant were recorded as the control group. The study population consisted of a total of 63 pregnant women. Doppler ultrasonography Except the parameter of “presence of poor obstetric Doppler measurements were carried out by an ultra- history” (p<0.001), no statistically significant difference sonography device with 7 MHz convex probe (C3-7IM, was found in the comparison of demographic and clin- Accuvix V20, Samsung- Medison, Gyeonggi, South ical data of the study group using anticoagulant and the Korea). For UtAD measurements, it was paid attention control group not using any anticoagulant (p>0.05, to keep insonation angle below 30 degrees at every meas- Table 1). No significant difference was found when the urement. Pulsatility index (PI), resistance index (RI), and groups were compared in terms of Doppler parameters systole/diastole ratio (S/D) were recorded bilaterally. analyzed (UmA PI, UmA SD, UtA PI, MCA PI and The mean of right and left measurements was taken dur- MCA PSV) (p>0.05, Table 2). ing the analysis. In UmAD samplings, the sampling was When the cases were compared only in terms of done on the area close to the placental end, and PI, RI third trimester Doppler data, it was found that MCA and S/D values were recorded. Insonation angle was kept PSV values of the study group were lower than the con- below 10 degrees in MCA measurements, and peak sys- trol group (p=0.037, Table 3). tolic velocity (MCA PSV) and PI values were recorded. When the cases were analyzed by grouping accord- Statistics ing to the anticoagulant type they used, LMWH, ASA When the statistical power analysis was performed for and LMWH+ASA sub-groups were identified. the study by taking the study of Bar et al. as reference, However, the cases using only ASA were not included it was calculated that at least 20 cases should be studied in the analysis as their number was low (n=4). It was in each group to conduct the research as effect size observed that MCA PSV values of the cases using would be 0.3, alpha would be 0.05 and statistical power LMWH+ASA were lower than those of the control would be 80% for UmA PI variable.[9] Kolmogorov- group (p=0.006). There was no significant difference in Smirnov test was used for the normal distribution other sub-groups and other parameters (Table 4). analysis of numerical variables. The comparison When sub-analysis was performed according to the between the groups for numerical variables exhibiting anticoagulant type and trimester simultaneously, the normal distribution was done by “independent samples only sub-group reaching sufficient number for statisti- t-test” and the data were presented as mean±standard cal analysis was the sub-group consisting of cases at deviation. Mann-Whitney U test was used to compare their third trimester and using only LMWH (n=15).
150 Perinatal Journal The impact of using thromboprophylactic medication by pregnant women on the hemodynamics of fetus and uterus
Table 1. Comparison of the demographic and clinical data of the groups.
Anticoagulant group Control group (n=36) (n=27) p-value
Age (year)* 31.05±6.06 30.14±5.97 0.556 Week of gestation† 30 (26–34) 32 (28–34) 0.611 Second trimester‡ 12 (33.3) 6 (22.2) Third trimester‡ 24 (66.6) 21 (77.8) Parity† 1 (0–1) 1 (0–2) 0.953 Systolic blood pressure (mmHg)† 110 (104.2–118.7) 110 (100–130) 0.713 Diastolic blood pressure (mmHg)† 70 (61.25–70.0) 70 (65–80) 0.360 Cases with poor obstetric history‡ 26 (72.2) 6 (22.2) <0.001 Cases with obstetric and other medical problems in this pregnancy‡ 11 (30.6) 17 (63.0) 0.021 Smoker cases‡ 6 (14.8) 4 (16.7) 1.000 Cases using non-anticoagulant medication due to chronic disease‡ 4 (11.1) 10 (37.0) 0.032 Anticoagulant type‡ 36 (100) – LMWH only 20 (55.5) LMWH+ASA 11 (30.5) ASA only 5 (14)
*Mean±standard deviation; †median (25th–75th percentile); ‡n (%). ASA: acetylsalicylic acid; LMWH: Low-molecular-weight heparin.
There was no significant difference between this sub- Table 2. Comparison of Doppler parameters between two groups. group and the control group in terms of Doppler data (p>0.05, no data was presented). Anticoagulant group Control group (n=36) (n=27) p-value
MCA PSV* 38.59±9.02 43.17±10.5 0.071 Discussion MCA PI† 1.85 (1.58–2.06) 2.11 (1.55–2.43) 0.209 UmA PI† 1.09 (0.96–1.47) 1.25 (1.00–1.36) 0.484 In this study, we aimed to analyze potential changes in UmA SD† 3.06 (2.69–4.20) 3.38 (2.67–4.00) 0.526 Doppler dynamics of uterine, fetal middle cerebral and UtA PI* 1.27±0.50 1.21±0.39 0.576 umbilical arteries in pregnant women who started to use *Mean±standard deviation; †median (25th–75th percentile). MCA PSV: medium anticoagulant due to the subjective criterion of “poor cerebral artery peak systolic velocity; PI: pulsatility index; SD: systole/diastole; ratio; UmA: umbilical artery Doppler; UtA: uterin artery Doppler. obstetric history”. We observed that the concomitant use of low-molecular-weight heparin (LMWH) and acetyl- salicylic acid (ASA) may be associated with the low MCA In the obstetrics practice, the area of use of Doppler PSV values. ultrasonography has become quite popular and it has Anticoagulants are commonly used in many poor proved its positive contribution on perinatal outcomes obstetric problems such as intrauterine fetal death, abla- in many clinical scenarios. Although different results tio placentae, early-severe preeclampsia and intrauterine growth retardation but early pregnancy losses in partic- Table 3. Comparison of third trimester Doppler data between the ular. Moreover, it is also known that anticoagulant is anticoagulant group and the control group. prescribed in pregnancies achieved by assisted reproduc- tive technologies. However, it has not been shown that Control group Anticoagulant group such common use of anticoagulants improved the out- (n=20) (n=24) p-value comes.[10,11] Although various professional obstetrics soci- MCA PSV* 47.37±7.49 42.3±6.61 p=0.037 eties published bulletins providing evidence-based rec- MCA PI† 2.1 (1.5–2.46) 1.9 (1.65–2.3) p=0.524 UmA PI† 1.2 (1.0–1.4) 1.0 (0.9–1.4) p=0.364 ommendations on anticoagulant indications, its off-label UmA SD† 3.1 (2.4–3.9) 2.9 (2.5–3.3) p=0.364 [8] use is quite common. In addition, when anticoagulant UtA PI† 1.2 (0.9–1.4) 1.3 (1.0–1.5) p=0.448 is prescribed upon the subjective criterion of “poor One third trimester control case was not included due to missing data. *Mean±stan- obstetric history”, it is very difficult to convince patients dard deviation; †median (25th–75th percentile). MCA PSV: medium cerebral artery peak systolic velocity; PI: pulsatility index; SD: systole/diastole; ratio; UmA: umbilical to discontinue this medication. artery Doppler; UtA: uterin artery Doppler.
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Table 4. Distribution of Doppler data according to anticoagulant type.
Control group LMWH only LMWH+ASA (n=36) (n=27) (n=11)
MCA PSV* 43.1±10.5 42.3±8.1 (p=0.751) 32.7±8.5 (p=0.006) MCA PI† 2.1 (1.5–2.4) 1.9 (1.6–2.3) (p=0.748) 1.8 (1.6–1.9) (p=0.219) UmA PI† 1.2 (1.0–1.4) 1.0 (0.9–1.5) (p=0.335) 1.1 (1.0–1.5) (p=0.973) UmA SD† 3.9 (2.7–4.0) 2.9 (2.6–4.0) (p=0.394) 3.1 (2.9–4.7) (p=0.666) UtA PI† 1.2 (1.0–1.4) 1.0 (0.9–1.4) (p=0.235) 1.4 (1.1–1.6) (p=0.149)
*Mean±standard deviation; †median (25th–75th percentile). ASA: Low-dose acetylsalicylic acid; LMWH: Low-molecular-weight heparin; MCA PSV: medium cerebral artery peak sys- tolic velocity; PI: pulsatility index; SD: systole/diastole; ratio; UmA: umbilical artery Doppler; UtA: uterin artery Doppler. can be obtained due to “user factor” as in all ultrasono- values of 64 pregnant women with thrombophilia using graphic evaluations, it is possible to standardize it by LMWH compared to the control group.[18] Similarly, measurement criteria and user trainings.[12] However, we did not observe any significant change in UtAD apart from the user factor, the impact of demographic parameters of pregnant women by anticoagulant at and clinical variables on Doppler parameters is a topic prophylactic doses in our study. which is investigated less. In a cross-sectional study In a recent study conducted on 139 pregnant women published very recently, it has been shown that demo- with hereditary thrombophilia, the authors reported that graphic and clinical characteristics may significantly there was no difference between the cases using LMWH [13] affect Doppler parameters. Although there are some and the cases using LMWH+ASA in terms of uterine studies investigating the impacts of medications, which and umbilical artery Doppler parameters.[19] Therefore, it affect artery physiology or intravascular volume during can be considered that uterine and umbilical artery [14,15] pregnancy, on Doppler data, there are fewer stud- Doppler values are not different among the pregnant ies on the potential relationship between anticoagulant women using LMWH and/or the pregnant women use during pregnancy and Doppler parameters. using LMWH+ASA. We also found in our study that For example, a study conducted on 178 pregnancies the anticoagulant use due to subjective criteria did not of 51 cases with hereditary thrombophilia using cause a significant change in UtAD and UmAD values. LMWH reported that fewer abnormal Doppler results The number of studies concluding that ASA use (UmA and MCA) were observed in the cases using during pregnancy has no significant impact on anticoagulant compared to those not using anticoagu- Doppler parameters is high. For example, a prospec- lant. This study claimed that LMWH might have an tive research reported that there was no significant dif- impact on Doppler values in the group with hereditary ference between placebo and ASA in terms of UmAD thrombophilia. However, the population of this study values.[9] Similarly, it was reported that UmAD and [16] also includes thromboembolism unlike our study. UtAD values of pregnant women who had anticardi- Bar et al. compared the pregnant women who start- olipin antibody positivity and used ASA were not dif- ed to use LMWH due to poor obstetric history to the ferent than normal pregnant women.[20] pregnant women who started to use LMWH+ASA due MCA Doppler ultrasonography, which has impor- to hereditary thrombophilia concurrent with poor tant areas of use in pregnancy, is important for the man- obstetric history.[17] They reported a significant agement of fetal and fetoplacental problems which are decrease in UtA PI values of the group using especially defined as brain sparing effect and concomi- LMWH+ASA. Although this prospective study did not tantly developed with the transformation of cerebral provide any data on MCA, it indicates that the use of high resistant flow into low resistant. In their random- LMWH+ASA during pregnancy may cause changes ized study, Grab et al. concluded that the use of ASA did measurable by Doppler. However, in a similar study, not cause a significant difference in MCA and other Çok et al. reported different observations by LMWH (UmA, UtA) Doppler values.[21] In their study, the only. This retrospective research reported that there authors selected pregnant women with the history of was no significant difference in midtrimester UtAD intrauterine growth retardation or chronic hypertension
152 Perinatal Journal The impact of using thromboprophylactic medication by pregnant women on the hemodynamics of fetus and uterus
as the study group. In our study, the number of pregnant 3. ACOG Practice Bulletin No. 197: Inherited thrombophilias women using ASA only was very low so it was not possi- in pregnancy. Obstet Gynecol 2018;132:e18–e34. ble to derive a statistically significant result; however, we 4. Alfirevic Z, Stampalija T, Dowswell T. Fetal and umbilical observed a significant decrease in MCA PSV median val- Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev 2017;6:CD007529. ues of the cases using LMWH+ASA than those not using 5. Vollgraff Heidweiller-Schreurs CA, De Boer MA, Heymans medication. On the other hand, Younis et al. reported in MW, Schoonmade LJ, Bossuyt PMM, Mol BWJ, et al. their study that MCA Doppler values were normal in the Prognostic accuracy of cerebroplacental ratio and middle cere- pregnant women who had thrombophilia and used bral artery Doppler for adverse perinatal outcome: systematic LMWH+ASA.[22] However, their results should be inter- review and meta-analysis. Ultrasound Obstet Gynecol 2018; preted carefully as they did not have a control group. 51:313–22. 6. Velauthar L, Plana MN, Kalidindi M, Zamora J, Thilaganathan When the studies published in English in PubMed B, Illanes SE, et al. First-trimester uterine artery Doppler and database are reviewed, it can be seen that a couple of adverse pregnancy outcome: a meta-analysis involving 55,974 studies published in this database on this topic were women. Ultrasound Obstet Gynecol 2014;43: 500–7. conducted usually on pregnant women with the histo- 7. Mari G, Norton ME, Stone J, Berghella V, Sciscione AC, ry of thrombophilia and thromboembolism or with the Tate D, et al.; Society for Maternal-Fetal Medicine. Society problems such as intrauterine growth retardation dur- for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia – diagnosis and management. ing study period. We could not find any study investi- Society for Maternal-Fetal Medicine. Am J Obstet Gynecol gating the potential impact of off-label anticoagulant 2015;212:697–710. use on the Doppler parameters during pregnancy. 8. Shen YM, Tsai J, Taiwo E, Gavva C, Yates SG, Patel V, et Therefore, the heterogeneity of pregnant women pop- al. Analysis of thrombophilia test ordering practices at an ulation among other studies and our study makes it dif- academic center: a proposal for appropriate testing to reduce ficult for making a clear deduction. One of the limita- harm and cost. PLoS One 2016;11:e0155326. tions of our study is the sampling size. Even though we 9. Bar J, Hod M, Pardo J, Fisch B, Rabinerson D, Kaplan B, et al. Effect on fetal circulation of low-dose aspirin for preven- reached sufficient number of cases by performing sta- tion and treatment of pre-eclampsia and intrauterine growth tistical power analysis before the study, this number restriction: Doppler flow study. Ultrasound Obstet Gynecol may not be enough to provide a reliable result when a 1997;9:262–5. secondary analysis is performed by grouping according 10. Alfirevic Z, Roberts D, Martlew V. How strong is the asso- to anticoagulant sub-types. Thus, this factor should be ciation between maternal thrombophilia and adverse preg- taken into consideration when interpreting our results. nancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol 2002;101:6–14. 11. Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Conclusion Greaves M, et al.; Scottish Pregnancy Intervention Study (SPIN) collaborators. SPIN (Scottish Pregnancy Intervention) Apart from the current indications, we did not find a sig- study: a multicenter, randomized controlled trial of low-molec- nificant difference in umbilical artery, uterine artery and ular-weight heparin and low-dose aspirin in women with recur- fetal cerebral artery Doppler parameters of pregnant rent miscarriage. Blood 2010;115:4162–7. women using LMWH due to the subjective criterion of 12. Deane C. Doppler ultrasound: principles and practice. In: “poor obstetric outcome” compared to the control group. Nicolaides K, Rizzo G, Hecher K, Ximenes R, editors. However, the concomitant use of LMWH and ASA may Doppler in obstetrics. Diploma in Fetal Medicine and ISUOG Educational Series. London: Fetal Medicine Foundation; cause changes measurable by Doppler ultrasonography in 2002. p. 4–24. Available from: https://fetalmedicine.org/var/ the hemodynamics of fetal middle cerebral artery. uploads/Doppler-in-Obstetrics.pdf 13. Ciobanu A, Wright A, Syngelaki A, Wright D, Akolekar R, Conflicts of Interest: No conflicts declared. Nicolaides KH. Fetal Medicine Foundation reference ranges for umbilical artery and middle cerebral artery pulsatility index References and cerebroplacental ratio. Ultrasound Obstet Gynecol 2018 Oct 24. doi: 10.1002/uog.20157 1. Scheres LJJ, Bistervels IM, Middeldorp S. Everything the 14. Pedersen BW, Ringholm L, Damm P,Tabor A, Søgaard K, clinician needs to know about evidence-based anticoagula- Hellmuth E, et al. Stable fetal hemodynamics measured by tion in pregnancy. Blood Rev 2018;33:82–97. Doppler flow after initiation of anti-hypertensive treatment 2. ACOG Practice Bulletin No. 196 Summary: thromboem- with methyldopa in pregnant women with diabetes. J Matern bolism in pregnancy. Obstet Gynecol 2018;132:243–8. Fetal Neonatal Med 2016;29:550–3.
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15. Carr DB, Gavrila D, Brateng D, Easterling TR. Maternal influence fetal growth or uterine and umbilical arterial hemodynamic changes associated with furosemide treat- Doppler in women with a history of early-onset uteroplacen- ment. Hypertens Pregnancy 2007;26:173–8. tal insufficiency and an inheritable thrombophilia? Secondary 16. Magriples U, Ozcan T, Karne A, Copel JA. The effect of anti- randomised controlled trial results. BJOG 2016;123:797–805. coagulation on antenatal ultrasound findings in pregnant 20. Blumenfeld Z, Weiner Z, Lorber M, Sujov P, Thaler I. women with thrombophilia. J Matern Fetal Neonatal Med Anticardiolipin antibodies in patients with recurrent pregnan- 2006;19:27–30. cy wastage: treatment and uterine blood flow. Obstet Gynecol 17. Bar J, Mashiah R, Cohen-Sacher B, Hod M, Orvieto R, Ben- 1991;78:584–9. Rafael Z, et al. Effect of thrombophylaxis on uterine and 21. Grab D, Paulus WE, Erdmann M, Terinde R, Oberhoffer R, fetal circulation in pregnant women with a history of preg- Lang D, et al. Effects of low-dose aspirin on uterine and fetal nancy complications. Thromb Res 2001;101:235–41. blood flow during pregnancy: results of a randomized, place- 18. Cok T, Tarim E, Iskender C. Comparison of uterine artery bo-controlled, double-blind trial. Ultrasound Obstet Gynecol Doppler in pregnant women with thrombophilia treated by 2000;15:19–27. LMWHs and without thrombophilia. Arch Gynecol Obstet 22. Younis JS, Ohel G, Brenner B, Haddad S, Lanir N, Ben-Ami 2012;286:575–9. M. The effect of thrombophylaxis on pregnancy outcome in 19. Abheiden C, Van Hoorn ME, Hague WM, Kostense PJ, van patients with recurrent pregnancy loss associated with factor Pampus MG, de Vries J. Does low-molecular-weight heparin V Leiden mutation. BJOG 2000;107:415–9.
154 Perinatal Journal A L J O A T U N R I N R A E L P Case Report
P L E R A Perinatal Journal 2018;26(3):155–161 I N N R A U T A L J O
Cesarean scar pregnancies and their management: case series
Elif Ganime Aydeniz1, Umut Sar›2, Talat Umut Kutlu Dilek3 1Reproductive Medicine Clinic, Department of Obstetrics and Gynecology, Faculty of Medicine, Ac›badem Mehmet Ali Ayd›nlar University, Istanbul, Turkey 2Obstetrics and Gynecology Clinic, Ac›badem Mehmet Ali Ayd›nlar University Atakent Hospital, Istanbul, Turkey 3High Risk Pregnancy Clinic, Department of Obstetrics and Gynecology, Faculty of Medicine, Ac›badem Mehmet Ali Ayd›nlar University, Istanbul, Turkey
Abstract Özet: Sezaryen skar gebelikleri ve yönetimleri: Olgu serisi Objective: To manage early trimester ectopic scar pregnancies, Amaç: Erken trimester ektopik skar gebeliklerini, tedavisini, takibi- treatment, follow up and protecting fertility. ni ve koruyucu fertilitesini yönetmek. Case: Cesarean scar pregnancy diagnosis was done by ultrasound in Olgu: Befl olguya daha önce tan›mlanm›fl sonografi kriterlerine gö- five cases by previously described sonographic criteria. Missed period, re ultrason ile sezaryen skar gebeli¤i tan›s› konuldu. Gecikmifl adet, vaginal bleeding and, pelvic pain are major admittance symptoms. We vajinal kanama ve pelvik a¤r›, baflvuru an›ndaki majör semptomlar- performed local therapies for all cases including aspiration by OPU d›. Tüm olgularda, OPU i¤ne ile aspirasyon, intrasak metotreksat needle, intrasac methotrexate and intracardiac potassium chloride and ile intrakardiyak potasyum klorür ve sistemik metotreksat (50 systemic methotrexate (50 mg/kg). We did not need extra surgery and mg/kg) dahil yerel tedaviler uygulad›k. Ekstra cerrahi müdahaleye blood transfusion. ve kan transfüzyonuna ihtiyaç duymad›k. Conclusion: Every woman who had a cesarean section history must Sonuç: Sezaryen do¤um geçmifli olan tüm kad›nlar, gecikmifl adet be checked carefully due to cesarean section pregnancy following ve pozitif gebelik testini takiben sezaryen gebelik nedeniyle dikkatli delayed menstruation and positive pregnancy test. Various cesarean bir flekilde kontrol edilmelidir. Birçok sezaryen gebelik tedavisi yön- section pregnancy treatment modalities have been reported; howev- temi bildirilmifltir, ancak bu konuda en uygun yaklafl›m halen tart›fl- er, the best approach for this is still under debate. Local treatment of mal›d›r. Sezaryen skar gebeli¤inin lokal tedavisi, dikkatli bir flekilde cesarean scar pregnancy could be achieved by combination of local seçilmifl olgularda yerel tekniklerin kombinasyonuyla baflar›l› flekil- techniques in carefully selected cases. de gerçeklefltirilebilir. Keywords: Cesarean scar pregnancy, ectopic pregnancy, fertility, Anahtar sözcükler: Sezaryen skar gebeli¤i, ektopik gebelik, fertili- methotrexate. te, metotreksat.
Introduction bidity such as uterine rupture, hemorrhage and hys- [1] Cesarean scar ectopic pregnancy (CSP) is one of the rare terectomy is possible in case of undiagnosed cases. The types of ectopic pregnancies. CSP incidence has been diagnosis is usually made by ultrasound, showing the fol- reported as 1/1800–1/2200 pregnancies. But, it is lowing with these criteria such as an empty uterine cav- increasing progressively due to the increased cesarean ity and cervical canal, a gestational sac located anterior- section rates and assisted reproductive techniques. Early ly at the isthmus, and evidence of a functional tro- diagnosis is crucial to avoid severe complications such as phoblastic/placental circulation on color Doppler at the uterine rupture and severe hemorrhage. Maternal mor- late pregnancy weeks.[2,3] Invasion of the bladder is possi-
Correspondence: Elif Ganime Aydeniz, MD. Reproductive Medicine Clinic, Department of Available online at: Obstetrics and Gynecology, Ac›badem Mehmet Ali Ayd›nlar University, Istanbul, Turkey. www.perinataljournal.com/20180263001 e-mail : [email protected] doi:10.2399/prn.18.0263001 QR (Quick Response) Code: Received: August 2, 2018; Accepted: September 23, 2018 Please cite this article as: Aydeniz EG, Sar› U, Dilek TUK. Cesarean scar pregnancies and their management: case series. Perinatal Journal 2018;26(3):155–161. ©2018 Perinatal Medicine Foundation Aydeniz EG, Sar› U, Dilek TUK
ble complication. Morbidly adherent placenta is anoth- Case 1 er end of abnormal placentation spectrum. Also, there is Thirty-three-year-old woman who had gravida 4 para 2 a focal thinning in myometrium at cesarean area. admitted to our outpatient clinic with symptoms of Pregnancy may protrude through the scar and if preg- amenorrhea. She has a history of two deliveries by nancy is viable it can implant on abdominal organs. cesarean section 8 and 6 years ago and the history of Magnetic resonance imaging can used to assess depth of cesarean scar pregnancy 2 years ago. She presented at 5 [4] placental invasion. weeks pregnancy at her first visit. Beta HCG levels are There is only one patient which was reported who raised as 417, 2357, 3512 mIU/ml. In the first visit, ultra- reached 35 weeks of gestation. She was complicated with sound revealed gestational sac with yolk sac (Fig. 1a) massive hemorrhage and disseminated intravascular which located between the isthmus cervix borders (Fig. coagulopathy at cesarean operation and she underwent 1b) in the previous cesarean section scar. Longest diam- hysterectomy for life saving purposes.[5] eter of gestational sac was 6 mm with yolk sac. There are no guidelines for the optimal treatment of Endometrium was 5.6 mm. Systemic methotrexate was 2 CSP in patients who are hemodynamically stable. There performed intramuscularly (50 mg/m ). HCG level was are many conservative treatment modalities described in 7267 mIU/ml at methotrexate administration day. the literature including systematic methotrexate, local Dislocated gestational sac was detected by ultrasound at methotrexate, combined intra cardiac potassium chlo- the control exam. Ultrasound-guided evacuation of ges- ride injection and systemic methotrexate, bilateral uter- tational sac was performed. HCG levels dropped down ine artery embolization (UAE), and combined UAE and sharply following evacuation. local methotrexate. Uterine artery embolization could be Case 2 indicated for the intractable bleeding.[6–9] Potassium chlo- ride injections by vaginal route can performed by ultra- Thirty-two-year-old gravida 3 para 1 woman admitted sound-guided needle, if fetal cardiac activity is posi- to emergency service with bleeding and amenorrhea. tive.[10–13] We reported five cases of cesarean scar preg- She has a history of delivery by cesarean section at 35 nancies which treated by various local therapies. weeks of gestation. Also, she reported pressure in the midline just over bladder. HCG level was 22,976 mIU/ml. Ultrasound revealed both embryo and yolk sac Case Report which located in the lower uterine segment and gesta- Clinical features, treatments and outcomes of cases tional sac has been extended to the former cesarean sec- summarized in Table 1. tion scar (Fig. 2a). Crown-rump length (CRL) was 4.76
Table 1. Clinical features of cesarean scar pregnancy cases.
Number of previous HCG at Case Age C-section diagnosis Sac diameter Treatment Prognosis
1 33 2 3512 6 mm with yolk sac Systemic Mtx+ US Successful term delivery guided evacuation in the next pregnancy
2 32 1 22,976 CRL: 4.76 mm, Systemic and local Successful term delivery cardiac activity (+) Mtx by OPU needle in the next pregnancy
3 40 1 9000 8 mm Local Mtx by OPU needle + Successful, no US guided evacuation further therapy
4 48 1 33,734 40 mm US guided evacuation and Successful, no haemostatic balloon further therapy
5 24 2 62,316 CRL: 8 mm, Systemic Mtx+ US Successful, no cardiac activity (+) Guided Intracardiac KCl further therapy
Mtx: methotrexate; KCl: potassium chloride; OPU: oocyte pick-up; US: ultrasound.
156 Perinatal Journal Cesarean scar pregnancies and their management: case series
a b
Fig. 1. The gestational sac with yolk sac (a) located between the isthmus cervix borders (b) in the previous cesarean section scar. mm and cardiac activity was seen (Fig. 2b). In the power transvaginal oocyte pick-up (OPU) needle. One week Doppler, low resistance-high velocity peripheral blood later fetal cardiac activity was negative and bleeding was flow was seen around gestational sac in the previous started. Evacuation of cavity was not performed. HCG cesarean section incision site (Fig. 2b). Gestational sac level decreased progressively. One month later after even bulged to the bladder not invaded (Fig. 3) CRL intracavitary methotrexate administration, disrupted increased to 8 mm progressively one week later. gestational sac was seen as 27×24 mm (Fig. 4a) diame- Sequential systemic methotrexate (1 mg/kg) performed ter. However, obvious peripheral blood flow was seen four times intramuscularly with folinic acid rescue. (Fig. 4b). Two months later following methotrexate, Intracavitary methotrexate (1 mg/kg) was performed by HCG level was 13 mIU/ml. Gestational sac disappeared
a b
Fig. 2. Both embryo and yolk sac located in the lower uterine segment and gestational sac extended to the former cesarean section scar (a) and cardiac activity (b). In the power Doppler, low resistance-high velocity peripheral blood flow was seen around gestational sac in the pre- vious cesarean section incision site (b-bottom).
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Fig. 3. Gestational sac even bulged to the bladder not invaded. CRL increased to 8 mm progressively one week later. and replaced with hematoma. Its diameter was 3×4 cm was aspirated by same needle. After methotrexate, gesta- (Fig. 4c). 4 months later following local treatment, tional sac dislocated through to cervical canal and vagi- uterus was normal and hematoma resolved (Fig. 4d). nal bleeding begun. In the follow-up, ultrasound-guided One year later, patient became pregnant again sponta- aspiration of gestational sac was performed by Pipelle neously. Gestational sac located at fundus. cannula because of gestational sac did not abort.
Case 3 Case 4 Forty-year-old gravida 2 para 1 woman admitted with Thirty-eight-year-old gravida 2 para 1 women admit- secondary amenorrhea. We performed transvaginal ted with bleeding and pain. She has a history of one ultrasound to reveal 8 mm gestational sac, which possi- lower segment cesarean section delivery. Bright blood bly placed within the former cesarean section scar and from external cervical os was seen during speculum protrude to the bladder. Her abdomen was soft and not exam. Cervix was tender by digital exam. Serum HCG distended. There was no vaginal bleeding and the cervix titer was 33,734 mIU/ml. Ultrasound revealed gesta- was closed on speculum examination. Intracavitary tional sac just located over former cesarean section site methotrexate (1 mg/kg) was introduced by OPU needle and extend to the isthmic region of uterus. It has 4 cm (16 Gauge) by transvaginal ultrasound guide. Then it largest diameter. Hemoglobin level was 12.8 g/dl at the
158 Perinatal Journal Cesarean scar pregnancies and their management: case series
a b
c d
Fig. 4. Disrupted gestational sac was seen as 27×24 mm (a). The obvious peripheral blood flow was seen (b). Two months later following meto- trexate, gestational sac disappeared and replaced with hematoma. (c). 4 months later following local treatment, uterus was normal and he- motoma resolved (d). first admittance. After the 6 hours follow-up it was before. Basal serum HCG level was 62,316 mIU/ml. drop down to the 11.4 g/dl. Suction curettage was per- Transvaginal ultrasound revealed a bulging cystic mass formed by number 4 Karman cannula with negative located in the isthmic region. It was 42×33 mm and con- pressure under ultrasound guidance. Transcervical 16 sisted of cardiac activity visible embryo (CRL: 8 mm). F Foley catheter was inserted and balloon was inflated Both cervical canal and uterine cavity were empty. 30 cc sterile saline and traction was performed to Continuity of anterior uterine wall was disappeared and achieve haemostasis. It was remained 12 hours and myometrium was thin and irregular in the gestational sac deflated carefully and removed. Patient was discharged region. By the diagnosis of cesarean section pregnancy, 24 hours following the suction curettage. Serum HCG as a first step intracardiac 2 ml 10% potassium chloride titer was 2460 mIU/ml postoperative 7th day and 161 applied by 20 G spinal needle under the real-time ultra- mIU/ml postoperative 17th day. sound guidance transabdominally. In the second step, systemic methotrexate was performed intramuscularly (1 Case 5 mg/kg) in Day 1-3-5-7 with folinic acid rescue (0.1 Twenty-four-year-old gravida 3 para 2 woman referred mg/kg). HCG level was 70,074 mIU/ml in the day 3. by possible diagnosis of cervical pregnancy. She has two Scar pregnancy started to shrinkage and disappeared 3–4 previous cesarean section operation, last one 10 months weeks later following the last dose of methotrexate.
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Discussion effects. Totally in twenty days HCG levels decreased We reported clinical outcomes of five cases of cesarean progressively, but we needed systemic methotrexate and scar pregnancy following local treatment by methotrex- folinic acid in two cases (Cases 1 and 5). Ultrasound- ate. Cesarean scar pregnancy is a rare type of ectopic guided evacuation performed 3 cases (Cases 1, 3 and 4). pregnancy. In recent years, ectopic scar pregnancies Ultrasound-guided or blind curettage or evacuation is have progressively increased due to the assisted repro- not successful alone. Following the local methotrexate ductive techniques and previous abdominal delivery. administration, greater than 35% reduction in HCG Furthermore, loss of fertility, life threatening bleeding, after uterine artery embolization and local methotrexate morbidly adherent placenta and maternal death are injection can be used as an indicator to perform dilation [17,18] among the maternal morbidities related with cesarean and curettage as complementary treatment. There scar pregnancy.[8–13] Delayed diagnosis and treatment was no severe hemorrhage in our patients in this may increase uterine rupture risk and causes severe respect, for this reason blood transfusion was not hemorrhage. To diagnose the ectopic pregnancy, phys- required. In the Case 4 from our small series, we per- ical examination is the first step and transvaginal ultra- formed balloon compression by Foley catheter and it sound is easy and cheap route to determine the location was removed 12 hours later to achieve hemostasis [19] of gestational sac. Magnetic resonance imaging for dif- (Table 1). Wu et al utilized from the Cook Cervical ferential diagnosis is rarely indicated.[14] Ripening Balloon to prevent hemorrhage during or fol- Generally single agent pharmacologic therapy is the lowing the ultrasound-guided evacuation in 15 cases first choice, rarely surgery indicated. Treatment by with scar pregnancy. They successfully stopped hemor- methotrexate is the best for early-diagnosed cases. If the rhage in all cases following the evacuation without any fetal cardiac activity present, we need intra-cardiac surgery and blood transfusion. potassium chloride to sustain treatment success. Every woman who had a cesarean section history Sometimes medical treatment may be failed because of must be checked carefully due to cesarean section preg- very high HCG levels and in the presence of cardiac nancy following delayed menstruation and positive activity. Dilatation and suction curettage or laparoscop- pregnancy test. Various cesarean section pregnancy ic resection in first trimester may be treatment choices treatment modalities have been reported, however the if the initial treatment fails. If gestational sac bigger than best approach for this is still under debate. Management 2.5 cm and HCG level is bigger than 10,000 IU/ml fur- and follow-up should be individualized for each patient. thermore there is fetal cardiac activity positive at ectopic [14] focus we absolutely need KCl injection. Conclusion Uterine closure at cesarean section may be a factor In conclusion, local treatment of cesarean scar pregnan- for uterine rupture and future cesarean scar pregnancy. cy could be achieved by combination of local techniques Uterine double-layer closure may be safe for avoiding in carefully selected cases. from complications like scar pregnancies.[15] Multiple pregnancies, absence of the first stage of labor, and Conflicts of Interest: No conflicts declared. cephalopelvic disproportion might be the risk factors for the occurrence of CSP.[16] In some cases, surgical resec- References tion for removing ectopic pregnancy and repair former 1. Fylstra DL. Ectopic pregnancy within a cesarean scar: a review. cesarean section defect are logical options. Although we Obstet Gynecol Surv 2002;57:537–43. did not need hysterectomy in our patients, hysterectomy 2. Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson is a treatment choice for the severe hemorrhage follow- CJ. First-trimester diagnosis and management of pregnancies ing initial treatment. Also, patients must be counseled implanted into the lower uterine segment Caesarean section about abnormal placentation for next pregnancies. scar. Ultrasound Obstet Gynecol 2003;21:220–7. 3. Marcus S, Cheng E, Goff B. Extrauterine pregnancy resulting In our small case series, we achieved elimination of from early uterine rupture. Obstet Gynecol 1999;94:804–5. cesarean scar pregnancy by local treatment with 4. Fylstra DL, Pound-Chang T, Miller MG, Cooper A, Miller methotrexate due to early diagnosis. Local treatment is KM. Ectopic pregnancy within a cesarean delivery scar: a case better than systemic treatment because of fewer side report. Am J Obstet Gynecol 2002;187:302–4.
160 Perinatal Journal Cesarean scar pregnancies and their management: case series
5. Herman A, Weinraub Z, Avrech O, Maymon R, Ron-El R, 13. Rodi IA, Sauer MV, Gorrill MJ, Bustillo M, Gunning JE, Bukovsky Y. Follow up and outcome of isthmic pregnancy Marshall JR, et al. The medical treatment of unruptured located in a previous caesarean section scar. Br J Obstet ectopic pregnancy with methotrexate and citrovorum rescue: Gynaecol 1995;102:839–41. preliminary experience. Fertil Steril 1986;46:811–3. 6. Rotas MA , Haberman S, Levgur M. Cesarean scar ectopic 14. Rotas M, Haberman S, Levgur M. Caesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstet pregnancies etiology, diagnosis and management. Obstet Gynecol 2006;107:1373–81. Gynecol 2006;107:1373–8. 7. Li N, Zhu F, Fu S, Shi X. Transvaginal ultrasound-guided 15. Vachon-Marceauc C, Demers S, Bujold E, Roberge S, embryo aspiration plus local administration of low-dose Gauthier RJ, Pasquier JC, et al. Single versus double-layer methotrexate for cesarean scar pregnancy. Ultrasound Med uterine closure at cesarean: impact on lower uterine segment Biol 2012;38:209–13. thickness at next pregnancy. Am J Obstet Gynecol 2017;217: 65. e1–65.e5. 8. Einenkel J, Stumpp P, Kosling S, Horn LC, Hockel M. A mis- diagnosed case of cesarean scar pregnancy. Arch Gynecol 16. Shi M, Zhang H, Qi SS, Liu WH, Liu M, Zhao XB, et al. Obstet 2005;271:178–81. Identifying risk factors for cesarean scar pregnancy: a retro- spective study of 79 cases. Ginekol Pol 2018;89:195–9. 9. Vial Y, Petignat P, Hohlfeld P. Pregnancy in a cesarean scar. 17. Liu G, Wu J, Cao J, Xue Y, Dai C, Xu J, et al. Comparison of Ultrasound Obstet Gynecol 2000;16:592–3. three treatment strategies for cesarean scar pregnancy. Arch 10. Doubilet PM, Benson CB, Frates MC, Ginsburg E. Gynecol Obstet 2017;296:383–9. Sonographically guided minimally invasive treatment of 18. Arslan M, Pata O, Dilek TUK, Aban M, Dilek S. Treatment unusual ectopic pregnancies. J Ultrasound Med 2004;23:359– of viable cesarean scar ectopic pregnancy with suction curet- 70. tage. Int J Gynecol Obstet 2005;89:163–6. 11. Stovall TG, Ling FW. Single-dose methotrexate: an expanded 19. Wu C, Li Y, Ye W, Ma W, Zhao D. Cook Cervical Ripening clinical trial. Am J Obstet Gynecol 1993;68:1759–62. Balloon successfully prevents excessive hemorrhage combined 12. Barnhart K, Hummel AC, Sammel MD, Menon S, Jain J, with ultrasound-guided suction curettage in the treatment of Chakhtoura N. Use of “2-dose” regimen of methotrexate to cesarean scar pregnancy. J Obstet Gynaecol Res 2017;43:1043– treat ectopic pregnancy. Fertil Steril 2007;87:250–6. 7.
Volume 26 | Issue 3 | December 2018 161 A L J O A T U N R I N R A E L P Case Report
P L E R A Perinatal Journal 2018;26(3):162–166 I N N R A U T A L J O
Gestational management of the patient with osteogenesis imperfecta: a case report
Gülflen Do¤an Durda¤1, Hakan Kalayc›1, Seda Yüksel fiimflek1, Songül Alemdaro¤lu1, Gonca Çoban1, Ferhat fiaml›2 1Gynecology and Obstetrics Clinic, Adana Application and Research Hospital, Faculty of Medicine, Baflkent University, Adana, Turkey 2Department of Anesthesiology and Reanimation, Adana Application and Research Hospital, Faculty of Medicine, Baflkent University, Adana, Turkey
Abstract Özet: Osteogenezis imperfekta hastas›n›n gebelik yönetimi: Olgu sunumu Objective: Osteogenesis imperfecta (OI) is a genetic disorder in Amaç: Osteogenezis imperfekta (O‹), kollajen sentezinin hatal› ol- which collagen synthesis is defective. It causes skeletal anomalies, and du¤u bir genetik bozukluktur. ‹skelet anomalilerine, kemiklerde ve fragility in bones and tissues. In this case report, we aimed to present dokularda k›r›lganl›¤a sebep olmaktad›r. Bu olgu sunumunda çer- the gestational management of an OI patient and to discuss potential çevesinde, O‹ hastas›n›n gebelik yönetimini sunmak ve karfl›lafl›la- complications. bilecek komplikasyonlar› tart›flmak istedik. Case: Thirty-six-year-old patient diagnosed with Type I OI was fol- Olgu: Tip I O‹ tan›l› 36 yafl›ndaki hasta, spontan gebeli¤i olmas› lowed up in our center due to her spontaneous pregnancy. A muta- üzerine merkezimizde takibe al›nd›. Hastada COL1A1 geninde tion was identified in COL1A1 gene of the patient. It was seen in her mutasyon tespit edildi. Koryon villus örneklemesinden yap›lan analysis by chorionic villus sampling that her fetal karyotype and analizde fetal karyotip ve COL1A1 geninin normal oldu¤u görül- COL1A1 gene were normal, and no pathology was found in the dü, obstetrik ultrasonografi incelemelerinde de patoloji izlenmedi. obstetric ultrasonography examinations. Fetal lung maturation of the Gebelik haftas› ilerledikçe a¤r›, solunum s›k›nt›s› ve dispeptik flika- patient, whose pain, respiratory distress and dyspeptic complaints yetleri artan hastaya 34. haftada amniyosentez yap›larak fetal akci- increased as the week of gestation progressed, was evaluated by per- ¤er matürasyonu de¤erlendirildi. 35. haftada sezaryen ile sa¤l›kl› forming amniocentesis at 34 weeks of gestation, and a healthy baby bir bebek do¤urtuldu. was delivered by cesarean section at 35 weeks of gestation. Sonuç: Genetik yap›n›n aktar›lma endiflesi, anatomik deformite Conclusion: The concern of transferring genetic structure, difficulty nedeniyle gebeli¤i tafl›man›n zorlu¤u, gebelik ve do¤um kompli- of carrying pregnancy due to anatomic deformity and frequent gesta- kasyonlar›n›n daha fazla görülebilmesi O‹’l› hastalardaki temel tional and labor complications are the major problems of OI patients. problemlerdir. Bu hastalara genetik dan›flmanl›k önerilmelidir ve Genetic consultancy should be offered such patients and their follow- takipleri multidisipliner yaklafl›mla yap›lmal›d›r. up procedures should be carried out by a multidisciplinary approach. Keywords: Pregnancy, genetic consultancy, osteogenesis imper- Anahtar sözcükler: Gebelik, genetik dan›flmanl›k, osteogenezis im- fecta, prenatal diagnosis. perfekta, prenatal tan›.
Introduction of type I collagen, which is an important structural Osteogenesis imperfecta (OI), which is also known as protein for bones, tendons, ligaments and many con- glass bone disease, is a genetic disorder with different nective tissues, is defective due to the mutations in dominantly or autosomal recessively inherited sub- COL1A1 and COL1A2 genes, and therefore fragility types. In Types I, II, III and IV patients, the synthesis in bones, decreased bone density and skeletal anom-
Correspondence: Gülflen Do¤an Durda¤, MD. Clinic of Obst. & Gyn., Adana T&R Hospital, Available online at: Faculty of Medicine, Baflkent University, Adana, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263006 Received: October 9, 2018; Accepted: December 10, 2018 doi:10.2399/prn.18.0263006 QR (Quick Response) Code: Please cite this article as: Do¤an Durda¤ G, Kalayc› H, Yüksel fiimflek S, Alemdaro¤lu S, Çoban G, fiaml› F. Gestational management of the patient with osteogenesis imperfecta: a case report. Perinatal Journal 2018;26(3):162–166. ©2018 Perinatal Medicine Foundation Gestational management of the patient with osteogenesis imperfecta
alies are seen in affected individuals. In addition, short patient at 11–14 and 18–22 weeks of gestation. Oral height, scoliosis and spinal deformities, joint laxity, glucose tolerance test was within normal range. The tendency to muscle and connective tissue injury, blue results of blood count, thyroid, liver and kidney func- sclera, odontologic deformities, conductive hearing tion tests were normal. The patient was followed up for loss, hyperthermia, hyperhydrosis, platelet dysfunc- calcium, vitamin D, phosphor, and ferritin. The tion, congenital cardiomyopathy, and fragility in other patient was followed up under the control of physio- tissues such as joint, vessel and skin can be seen. therapy and rehabilitation department and nutritionist, Today, it has been shown that about 20 different and her daily oral vitamin D intake was arranged as genes except COL1A1 and COL1A2 genes, which 2000 IU and diet calcium as 1000 mg. Her weight was have a major role in the pathology, may cause OI. kept under control; the patient who was 48 kg before Although OI has 4 sub-groups classically, up to 15 dif- pregnancy was 54 kg during the delivery. Her blood ferent types have been reported according to clinical pressure measurements were within normal ranges and radiological findings and underlying genetic rea- during all follow-ups. However, she had severe nausea sons.[1] Type I is the common one which has a better and vomiting since the beginning of the pregnancy and prognosis.[2] Type II is the most slow-progressing form. she also had frequently repeating headache. As the Its usual prevalence is up to 6–7 in 100,000 and most of week of gestation progressed, she frequently suffered them are new mutations. stomachache and shortness of breath occasionally. Her complaint of being unable to eat due to gastric irrita- In our case report, we aimed to present the gesta- tion, nausea and vomiting continued during the entire tional follow-up and management of a patient with pregnancy period. The symptoms of the case were fol- type I OI and to discuss potential complications. lowed up until they regressed by routine follow-ups and sometimes several hospitalization after admitting Case Report to emergency service and also by intravenous hydra- Thirty-six-year-old patient diagnosed with Type I OI tion only under observation occasionally. By consider- admitted to our infertility center for preconceptional ing the possibility of preterm labor as the patient did genetic diagnosis. The patient whose height was 148 not have any pain and had contractions in the tocogra- cm and weight was 48 kg had the history of cholecys- phy when she was at 27 weeks and 4 days of gestation, tectomy and many surgeries for bone fracture; she had she was administered 2 doses of 12 mg Betamethasone no known disease other than OI and migraine. In her (Celestone Chronodose, 1 ml, Schering Plough family, only her brother had OI. It was planned to Turkey, Istanbul) with 24-hour interval. The case did transfer healthy embryo by performing intracytoplas- not have any cervical dilatation during the follow-up, mic sperm injection and preimplantation genetic diag- her contractions regressed and the patient was dis- nosis (PGD) in order to eliminate the possibility of OI charged from the hospital and her gestational follow- in her baby to be born. When planning the treatment up was continued. As her complaints increased as the process, the patient got pregnant spontaneously and week of gestation progressed, the patient underwent the gestational follow-up was initiated for her. New amniocentesis after 34 weeks of gestation was complet- generation full gene sequencing analysis was per- ed and her lecithin/sphingomyelin ratio was evaluated. formed for the molecular genetic diagnosis; a mutation This ratio was found 8 and her labor was planned con- was identified in COL1A1 gene located on 17q21.33 sidering that fetal lung maturation was completed. chromosome region [p.R697 (c.2089C>T) (heterozy- When she was at 35 weeks and days of gestation gous)], but her COL1A2 gene located on 7q21.3 according to the last menstrual period, her labor was region was normal. Chorionic villus sampling was per- carried out by cesarean section under general anesthe- formed when she was at 12 weeks and 3 days of gesta- sia considering that the patient, whose contractions tion according to her last menstrual period. Normal increased and had cervical effacement and 2 cm dilata- karyotype was seen in the karyotyping examination and tion, would be less traumatized physically and psycho- sequencing analysis, and also it was found that logically compared to normal delivery. A singleton liv- COL1A1 gene was normal. No anomaly was observed ing female baby with a weight of 2330 g and height of in the detailed ultrasonographic examinations of the 46 cm was born with 1-minute and 5-minute Apgar
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scores of 9 and 10, respectively. It was seen during the COL1A1 and COL1A2 genes, autosomal recessively cesarean section that her skin, subcutaneous tissues, inherited and OI-associated genes (CRTAP and uterus muscle tissues and other connective tissues were LEPRE1) which are responsible for some of the cases very soft and fragile, so suturation was done carefully are studied by also considering the family history. and gently. As the newborn was premature and had OI diagnosis can also be established by USG exam- minimal respiratory distress, it was monitored in the inations carried out during antenatal period. NT intense care unit for 24 hours for observation purposes increase in early pregnancy, echogenicity decrease in and then delivered to the mother. The patient had no long bones, bending and shortening of heights should hemorrhage during postoperative period, her hemo- bring OI to mind. The diagnosis of OI type I can be globin values were stable, and she was administered established by USG at the 17 weeks of gestation at the Enoxaparin (Clexane 4000 anti-Xa IU, Sanofi Turkey, earliest; OI type II can be diagnosed at 13 weeks of ges- Istanbul) on the postoperative 1st day to prevent tation.[3] In types III and IV, there may be bending thromboembolism risk. When the patient had sub- without any shortening in the bone length or decrease febrile fever (37.8°C) on the postoperative second day, in its mineralization, and this may delay the diagnosis her CRP value was checked and found high, and there- as it will be clear in the further weeks of gestation. fore broad-spectrum intravenous antibiotic treatment When type III or IV OI is suspected, the results of was initiated; her urine and blood culture tests were repeating USG examinations should be compared. In normal, and no infection focus was found. The patient order to confirm the diagnosis, fetal magnetic reso- whose CRP value regressed by the treatment was dis- nance imaging may also help in necessary cases.[3] charged from the hospital on the postoperative 4th day Due to the increase of body weight and change of the as her general condition was good and her vital signs center of gravity during pregnancy, musculoskeletal sys- were stable. tem problems such as back pain, spinal deformities, sco- liosis, and disk hernia increase. Bisphosphonates used Discussion routinely by this patient group is contraindicated for the The pregnancy of a patient with the diagnosis of osteo- pregnancy as they may cause fetal skeletal anomalies or congenital malformations, and many studies recom- genesis imperfecta is a difficult process physically and [2,3] psychologically. The concern of transferring defective mend discontinuing them after conception. However, genetic structure to the next generation, difficulty of these problems may be mitigated by calcium and vita- carrying pregnancy due to anatomic deformity, fre- min D support and keeping weight gain under control. quent gestational complications such as antepartum It has been shown that checking the values of calcium, bleeding, ablatio placentae, preterm labor and phosphate, vitamin D, parathyroid hormone, LDH, intrauterine growth retardation, frequent labor com- CK, CRP, and kidney and liver function tests by a 3- month laboratory analysis would help the management plications such as bleeding, uterine atony and stress [4] fractures, thromboembolism and anesthesia risks are of treatment. the problems that can be seen during the pregnancy of The rates of gestational complications such as an OI patient. When offering genetic consultancy to antepartum bleeding, ablatio placentae, preterm labor such patients, the healthcare professionals should know and intrauterine growth retardation are also higher in the family history well, identify gene mutation and find OI patients. It was shown in the previous years that the out by appropriate methods if they are transferred to individuals with OI are more prone to bleeding and [5] fetus or not. A healthy embryo can be transferred by this may be associated with the platelet disorder. PGD to a patient seen before the conception. Ruiter-Ligeti et al. reported that antepartum bleed- However, more common method referred is to inves- ing or ablatio placentae risk may be associated with col- tigate current genetic mutation in mother’s cells lagen defect or coagulation defect, but they did not obtained by chorionic villus sampling or amniocente- find any increase in the risk of postpartum bleeding.[1] sis. Mutation is found in 70% of COL1A1 gene and in In the same study, the authors found the risk of venous 30% of COL1A2 gene in OI cases associated with thromboembolism higher in women with OI and they COL1A1-COL1A2. If no mutation is identified in associated it with the high rates of cesarean section and
164 Perinatal Journal Gestational management of the patient with osteogenesis imperfecta
prolonged immobilization related with postnatal skele- In addition, labor by cesarean section should not be tal problems.[1] considered as free of risk, and it should be remembered Also, the studies showing that calcium metabolism that it may increase the risks such as thrombosis, uter- [2] has a role in the pathogenesis of preeclampsia indicate ine atony, and postpartum bleeding. We decided that that the risks for preeclampsia and intrauterine growth labor by cesarean section would be more appropriate retardation are increased in these patients.[2] for our case considering pelvic or vertebral fracture or uterine rupture risks. The increase in preterm labor risk may be associat- ed with antenatal bleeding, ablatio placentae, prema- For anesthesia, all general, epidural and spinal anes- ture rupture of membrane or intrauterine growth thesia methods can be used; however, both general and retardation as well as maternal complications.[1,6] In our regional methods may have risks. Cardiopulmonary case, tightness and abdominal pain felt by the mother condition of the patient should be evaluated well. In as the uterine got bigger, back and lumbar pain, short- the general anesthesia, difficult intubation due to ness of breath and gastric irritation findings such as skeletal deformities, mandibular or dental fractures severe nausea and reflux made maintaining the preg- may occur; malign hyperthermia risk should also be nancy difficult; therefore, after we confirmed the fetal considered. In regional anesthesia, the procedure relat- ed with spinal deformities is technically difficult, and it pulmonary maturation, we informed the family that [2,3] newborn might need intense care support as it was a may also get hard to adjust block level. premature baby, and we planned the labor by obtain- Breastfeeding of the patients with OI may also be ing the approval of the family. considered contraindication relatively. Although there is Although there is no certain suggestion for the no full consensus, it is recommended to avoid log-term delivery type for patients with OI, cesarean section is breastfeeding periods particularly in patients who have vertebral fracture in order to shorten this process which usually preferred for the delivery as an effort to [10] decrease labor trauma. Maternal fracture incidence may cause a certain decrease in the bone density. does not increase during pregnancy; however, small traumas due to obstetric manipulations may increase Conclusion the fracture risk. Stress fractures related with bone Osteogenesis imperfecta is a condition with high mater- demineralization can be seen both in vaginal labors and nal morbidity risk during pregnancy. Preconceptional cesarean section labors. It has been reported that such consultancy and medical and genetic evaluation should fractures can be minimized by careful positioning dur- be offered to all women with OI. ing delivery or surgery and performing preconception- The type and severity of the disease and general clin- al bisphosphonate treatment.[1,3,6,7] In addition, sponta- ic condition of patient should be considered in order to neous uterine rupture was also reported during labor.[8] minimize the complications, and these patients should be Labor induction is not recommended since it is not followed up at fully equipped tertiary hospitals through a possible to predict how uterine contractions will devel- multidisciplinary approach. op in the presence of defective collagen.[2] Feng et al. reported that a patient with OI who prefers vaginal Conflicts of Interest: No conflicts declared. labor should be managed as if she is a patient with scarred uterus, and they highlighted that postpartum References bleeding risk is high depending on the uterine atony, 1. Ruiter-Ligeti J, Czuzoj-Shulman N, Spence AR, Tulandi T, [3] laceration or thrombocyte disorder. Presentation Abenhaim HA. Pregnancy outcomes in women with osteogen- anomalies and cephalopelvic disproportion associated esis imperfecta: a retrospective cohort study. J Perinatol 2016; with maternal skeletal anomaly can be cesarean section 36:828–31. indications. Labor by cesarean section can also be con- 2. Cozzolino M, Perelli F, Maggio L, Coccia MA, Quaranta M, Gizzo S, et al. Management of osteogenesis imperfecta type I sidered for a fetus established with OI diagnosis in in pregnancy; a review of literature applied to clinical practice. order to minimize the labor trauma. However, the Arch Gynecol Obstet 2016;293:1153–9. studies show that cesarean section do not decrease the 3. Feng Z, Chen Q, Shi C, Wen H, Ma K, Yang HX. A type IV [1,3,9] rates of newborn fractures during labor. osteogenesis imperfecta family and pregnancy: a case report
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and literature review. Chin Med J (Engl) 2012;125:1358– carried to term in a woman with osteogenesis imperfecta type I 60. and bisphosphonate treatment before conception. Taiwan J 4. Pabinger C, Heu C, Frohner A, Dimai HP. Pregnancy- and Obstet Gynecol 2012;51:305–7. lactation-associated transient osteoporosis of both hips in a 32 8. Krishnamoorthy U, Vausse S, Donnai P. Management of year old patient with osteogenesis imperfecta. Bone 2012;51: pregnancy complicated by maternal osteogenesis imperfecta. 142–4. Report of a case with uterine rupture. J Obstet Gynaecol 2002; 22:316. 5. Hathaway WE, Solomons CC, Ott JE. Platelet function and pyrophosphates in osteogenesis imperfecta. Blood 1972;39: 9. Bellur S, Jain M, Cuthbertson D, Krakow D, Shapiro JR, Steiner RD, et al.; Members of the BBD Consortium, 500–9. Nagamani SC. Cesarean delivery is not associated with 6. Yimgang DP, Shapiro JR. Pregnancy outcomes in women with decreased at-birth fracture rates in osteogenesis imperfecta. osteogenesis imperfecta. J Matern Fetal Neonatal Med 2016; Genet Med 2016;18:570–6. 29:2358–62. 10. Mcallion SJ, Paterson R. Musculo-skeletal problems associated 7. Chen CP, Lin SP, Su YN, Huang JP, Chern SR, Su JW, et al. with pregnancy in women with osteogenesis imperfecta. J Uncomplicated vaginal delivery in two consecutive pregnancies Obstet Gynaecol 2002;22:169–72.
166 Perinatal Journal A L J O A T U N R I N R A E L P Letter to the Editor
P L E R A Perinatal Journal 2018;26(3):167–169 I N N R A U T A L J O
Letter to the Editor: Antenatal steroids and their administration time for preventing morbidity in preterm labor
Talat Umut Kutlu Dilek1, Elif Ganime Aydeniz2 1Department of Obstetrics and Gynecology, Faculty of Medicine, Ac›badem Mehmet Ali Ayd›nlar University, Istanbul, Turkey 2Center of Assisted Reproductive Technologies, Ac›badem Mehmet Ali Ayd›nlar University Atakent Hospital, Istanbul, Turkey
Dear Editor, are used for this purpose.[2] The effects of two different Preterm labor is the most significant reason of perina- molecules on lung maturation and intraventricular tal mortality in the world. Although the major reason hemorrhage rate are similar. While dexamethasone is a for morbidity and mortality in preterm fetuses is respi- molecule which is cheap and easy to obtain, the bind- ratory distress of the newborn, short-term outcomes ing rate of betamethasone to albumin is lower and this such as necrotising enterocolitis, intraventricular hem- increases the transplacental transition rate. orrhage, newborn retinopathy and patent ductus arte- Optimal efficacy of antenatal steroids starts 24 riosus and long-term outcomes such as cerebral palsy, hours after the last administration and continues for 7 bronchopulmonary dysplasia and short bowel syn- days, and it starts to wear off afterwards. Therefore, in drome also should be considered. While prevention of cases where preterm labor does not occur, a repeat or preterm labor is the major action to prevent these rescue dose should be administered when same prob- problems, different pharmacological treatments should lem is faced again in the future. Steroid administrations also be taken into account in cases where preterm labor in repeat doses suppress maternal hypothalamic- cannot be prevented. In the last four decades, corticos- hypophyseal axis, disrupt glycemic control in diabetic teroids provided a significant decrease in the neonatal pregnant women by leading hyperglycemia, and may mortality and morbidity rates. In 1994, NICHD cause lung edema by its concomitant use with beta- (National Institute of Child Health and Development) mimetics in particular. In terms of newborn, hypo- recommended using them to prevent prematurity- [1] glycemia and hyperbilirubinemia are the major prob- related respiratory distress in preterm labors. It has lems. As long-term and repeat doses of antenatal been reported that antenatal steroids also decrease the steroids may cause cerebral atrophy, microcephaly and rates of newborn mortality, intraventricular hemor- low birth weight in fetus, administrating repeat doses is rhage and necrotising enterocolitis. In this regard, the [3] use of antenatal steroid between 24 and 34 weeks of not recommended. [4] gestation in pregnant women with high risk of preterm It was shown in a meta-analysis evaluated 30 stud- labor has been recommended, and this recommenda- ies and published in Cochrane database that steroids tion has also been supported by ACOG. Current ante- decreased the rates of perinatal mortality (RR: 0.72), natal steroid administration is conducted by two differ- neonatal death (RR: 0.69), respiratory distress syn- ent protocols, and dexamethasone and betamethasone drome (RR: 0.66), intraventricular hemorrhage (RR:
Correspondence: Talat Umut Kutlu Dilek, MD. Department of Obst. & Gyn., Faculty of Available online at: Medicine, Ac›badem MAA University, Istanbul, Turkey. e-mail: [email protected] www.perinataljournal.com/20180263007 Received: October 31, 2018; Accepted: December 15, 2018 doi:10.2399/prn.18.0263007 QR (Quick Response) Code: Please cite this article as: Dilek TUK, Aydeniz EG. Letter to the Editor: Antenatal steroids and their administration time for preventing morbidity in preterm labor. Perinatal Journal 2018;26(3):167–169. ©2018 Perinatal Medicine Foundation Dilek TUK, Aydeniz EG
Table 1. Administration scheme of antenatal steroid.
Administration 34–37. weeks 22 weeks – 23 weeks Repeat dose Premature rupture Guidelines week Protocol of gestation and 6 days of gestation administration of membrane
ACOG (2017) 24–34 weeks Dexamethasone 6 mg - a It can be It can be administered If the time elapsed Indicated of gestation total of 4 administrations administrated after 23 weeks of after the last dose is every 12 hours or gestation 14 days and more betamethasone 12 mg - 2 administrations every 24 hours
SOGC (2018) 24 weeks – Dexamethasone 6 mg - a Controversial Controversial If the time elapsed Indicated 34 weeks and total of 4 administrations after the last dose is 6 days of every 12 hours or 14 days and more gestation betamethasone 12 mg - 2 administrations every 24 hours
NICE (2015) 26 weeks – Dexamethasone 6 mg - a It can be administered Discuss with the family - Indicated 33 weeks and a total of 4 administrations between 34 weeks between 22 weeks and 23 6 days of every 12 hours or and 35 weeks and weeks and 6 days of gestation; gestation betamethasone 12 mg - 6 days of gestation consider between 24 2 administrations weeks 25 weeks and every 24 hours 6 days of gestation
Turkish 24–34 weeks Dexamethasone 6 mg - By the decision By the decision By the decision Single dose before Ministry of of gestation a total of 4 administrations of obstetrician of obstetrician of obstetrician 32 weeks of Health every 12 hours or gestation, by doctor (2014) betamethasone 12 mg - decision between 32 2 administrations and 34 weeks of every 24 hours gestation
ACOG: American College of Obstetrics and Gynecology; NICE: National Institute of Health Care Excellence; SOGC: Society of Obstetricians and Gynaecologists of Canada.
0.55), necrotising enterocolitis (RR: 0.5), and the need were previously administered corticosteroid in cases for ventilator support (RR: 0.6). where the time elapsed since the last dose is longer Although the use of antenatal corticosteroids before than 14 days and where preterm labor condition arises [7] 24 weeks of gestation is controversial, the lower limit and becomes inevitable in the next 7 days. can be 22–23 weeks of gestation since the outcomes of In conclusion, antenatal steroids should be adminis- newborn intense care get better in the extreme prema- tered in order to decrease neonatal morbidity and mortal- ture group with very low birth weight. While this ity in singleton and multiple pregnancies where preterm group decreases the mortality rates in newborns, it labor is inevitable between 24 and 34 weeks of gestation. [5] does not affect morbidity rates. The lower limit can be as low as 22 weeks of gestation Chorioamnionitis and multiple pregnancies are not depending on the newborn intense care capabilities, and contraindicated for the use of antenatal steroid, and its the upper limit can be extended up to 37 weeks of gesta- administration scheme is similar to singleton pregnan- tion according to the recent literature data. The mode of cies. While the administration threshold for antenatal administration is same in singleton and multiple pregnan- steroids was 34 weeks of gestation until two years ago, cies. It should be remembered that its effects start within it was shown in a randomized controlled study which 24 hours after the last dose and continue for 7 days, and was supported NIH that extending administration time routine repeat doses should be avoided (Table 1). Since up to 37 weeks of gestation led to a decrease in new- almost 2/3of the preterm labor cases still do not result with born respiratory distress.[6] Therefore, ACOG updated preterm labor 1 week later, repeat doses should be referred its guidelines in August 2017 and extended the upper only in cases where preterm labor is inevitable considering limit for administration up to 37 weeks of gestation. In the fetal-neonatal and maternal adverse effects.[8,9] the same guidelines, rescue treatment is recommended for pregnant women below 34 weeks of gestation who Conflicts of Interest: No conflicts declared.
168 Perinatal Journal Letter to the Editor: Antenatal steroids and their administration time for preventing morbidity in preterm labor
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Cesarean scar pregnancies and their management: case series. Investigation of toxoplasma, cytomegalovirus and rubella sero- Elif Ganime Aydeniz, Umut Sar›, Talat Umut Kutlu Dilek. 2018; prevalence in pregnant women admitted to our hospital. Yusuf 26(3):155–161 [Case Report] Madenda¤, Mefkure Eraslan fiahin, ‹lknur Çöl Madenda¤, Erdem fiahin, Gökhan Açmaz, ‹ptisam ‹pek Müderris. 2018;26(1):7–10 Comparison of obstetric outcomes of pregnant women with [Original Article] isolated proteinuria according to proteinuria severity. Mehmet Özgür Akkurt, Bora Coflkun, Tu¤berk Güçlü, Kaan Pakay, Engin Letter to the Editor regarding “The impacts of placental localiza- Korkmazer. 2018;26(3):107–111 [Original Article] tion and fetal sex on the estimation of fetal weight”. Mehmet Ferdi K›nc›, Ulafl Fidan, Kübra Felek, ‹lknur Yeflilç›nar, Özge fiehirli Conventional Doppler myocardial performance index, tricuspid K›nc›, Kaz›m Emre Karaflahin. 2018;26(1):54–55 [Letter to the and mitral annular plane systolic excursions in the assessment Editor] of fetal heart functions. fiebnem Paytoncu. 2018;26(3):117–123 [Original Article] Letter to the Editor: Antenatal steroids and their administration time for preventing morbidity in preterm labor. Talat Umut Evaluation of the fourth ventricle and nomogram of intracranial Kutlu Dilek, Elif Ganime Aydeniz. 2018;26(3):167–169 [Letter to translucency at 11–13 weeks of gestation. Derya Sivri Ayd›n, the Editor] Murat Yayla. 2018;26(2):102–105 [Original Article] Long QT syndrome diagnosed by premature atrial extrasys- Evaluation of the use of iodized salt by pregnant women and their toles: a case report. Oya Demirci, Mucize Eriç Özdemir, Güher knowledge on the use of iodized salt. Emine Özge Avc›, Baht›flen Bolat, Tunç Tuncer. 2018;26(1):51–53 [Case Report] Kartal, Evrim Bayraktar. 2018;26(3):141–147 [Original Article] Maternal serum anti-Müllerian hormone levels in pregnant Fetal cell detection for chromosome analysis from leaking women with gestational diabetes. Begüm Aydo¤an Mathyk, Berna amniotic fluid in pregnancies with rupture of membranes. Emre Aslan Çetin. 2018;26(2):74–77 [Original Article] Zafer, John David Buek, Jean Gilles Tchabo, Bassem Haddad. Myomectomy during cesarean section: is it a safe procedure? 2018;26(1):32–37 [Original Article] Alper Baflbu¤, Esma Y›ld›r›m, Ali Yavuzcan, Aflk› Ellibefl Kaya, Gestational management of the patient with osteogenesis Fikret Gökhan Göynümer. 2018;26(3):112–116 [Original Article] imperfecta: a case report. Gülflen Do¤an Durda¤, Hakan Kalayc›, Nuchal translucency measurement: who is right, who is not? Seda Yüksel fiimflek, Songül Alemdaro¤lu, Gonca Çoban, Ferhat Engin Korkmazer, Emine Arslan, Özgür Akkurt, Muzaffer Temur, fiaml›. 2018;26(3):162–166 [Case Report] Tayfur Çift. 2018;26(2):64–68 [Original Article]
+6 How much can we evaluate fetal anatomy at 11–13 weeks of Perinatal and orthopedic outcomes of patients diagnosed with gestation? Derya Sivri Ayd›n, Murat Yayla. 2018;26(2):57–63 pes equinovarus by mid-trimester fetal ultrasonographic imag- [Original Article] ing. Rauf Meleko¤lu, Sevil Eraslan, Hasan Berkan Sayal, Ebru Çelik, Harika Gözde Gözükara Ba¤. 2018;26(1):38–45 [Original Article] Intrauterine fetal transfusion in cases with immune hydrops fetalis: when and how effective it is? Emre Ekmekci, Emine Postnatal maternal attachment: a retrospective study. Derya Demirel. 2018;26(2):97–101 [Original Article] Yüksel Koçak, Handan Özcan. 2018;26(2):78–86 [Original Article]
Investigation of fetal magnetic resonance imaging indications. Postpartum glucose tolerance test application rates and non- Serenat Erifl Yalç›n, Yakup Yalç›n, Esra Nur Tola, And Yavuz, application causes in gestational diabetes mellitus cases. Engin Mehmet Özgür Akkurt, Mekin Sezik, Mehmet Okan Özkaya. Korkmazer, Emine Arslan, Özgür Akkurt, Muzaffer Temur, Tayfur 2018;26(1):18–24 [Original Article] Çift, Emin Üstünyurt. 2018;26(2):69–73 [Original Article]
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Prenatal diagnosis and follow-up of giant. sacrococcygeal ter- Mathyk, Berna Aslan Çetin, Sibel Gülova, Nazl› Yenigül, Ifl›l Ayhan, atoma: a case report. Mucize Eriç Özdemir, Oya Demirci, Güher Ayfle Ender Yumru. 2018;26(2):92–96 [Original Article] Bolat, Ayflenur Celayir, Suna Cesur. 2018;26(1):46–50 [Case Report] The impact of using thromboprophylactic medication by preg- nant women on the hemodynamics of fetus and uterus. Emre Prenatal diagnosis of fetal urinary system anomalies. Ezgi Zafer. 2018;26(3):148–154 [Original Article] Hürcan, Alper Biler, Atalay Ekin, Gökhan Tosun, Cüneyt Eftal Taner. 2018;26(1):1–6 [Original Article] The prediction of preterm birth threat by uterocervical angle. Retrospective analysis of the preeclampsia cases delivered in Olgu Bafal›, Hüseyin K›yak, Osman ‹nce, Yusuf Baflk›ran, Ali our clinic between 2013 and 2017. Gülfem Baflol, Navdar Do¤ufl Gedikbafl›. 2018;26(1):11–17 [Original Article] Uzun, Fulya Uzun, Ahmet Kale, Hasan Terzi. 2018;26(3):135–140 [Original Article] The predictive value of total leukocyte count and leukocyte dif- ferential for severe preeclampsia. Halenur Bozda¤, Ergül The distribution of primary cesarean section indication at a uni- Demirçivi Bör, Esra Akdeniz. 2018;26(1):25–31 [Original Article] versity hospital: ten-year experience and potential lessons to be taken to decrease cesarean section rates. Semir Köse, Asl› Akdöner, Three-year analysis to determine prognostic factors affecting Sabahattin Altunyurt. 2018;26(3):124–134 [Original Article] success in single-dose methotrexate treatment: a single-center The impact of serum anti-Müllerian hormone levels on experience. Gökçe Turan, P›nar Yalç›n Bahat, ‹brahim Polat. preeclampsia prediction: a case control study. Begüm Aydo¤an 2018;26(2):87–91 [Original Article]
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Author Index
(Volume 26, 2018)
A Ellibefl Kaya A. 112 P Açmaz G. 7 Ender Yumru A. 92 Pakay K. 107 Akdeniz E. 25 Eraslan S. 38 Paytoncu fi. 117 Akdöner A. 124 Eraslan fiahin M. 7 Polat ‹. 87 Akkurt M.Ö. 18, 107 Eriç Özdemir M. 46, 51 S-fi Akkurt Ö. 64. 69 Erifl Yalç›n S. 18 Alemdaro¤lu S. 162 Sar› U. 155 Altunyurt S. 124 F Sayal H.B. 38 Arslan E. 64, 69 Felek K. 54 Sezik M. 18 Aslan Çetin B. 74, 92 Fidan U. 54 Sivri Ayd›n D. 57, 102 Avc› E.Ö. 141 fiahin E. 7 Aydeniz E.G. 155, 167 G fiaml› F. 162 Aydo¤an Mathyk B. 74, 92 Gedikbafl› A. 11 fiehirli K›nc› Ö. 54 Ayhan I. 92 Göynümer F.G. 112 Gözükara Ba¤ H.G. 38 B T Güçlü T. 107 Bafal› O. 11 Taner C.E. 1 Gülova S. 92 Baflbu¤ A. 112 Tchabo J.G. 32 Baflk›ran Y. 11 H Temur M. 64, 69 Baflol G. 135 Haddad B. 32 Terzi H. 135 Bayraktar E. 141 Hürcan E. 1 Tola E.N. 18 Biler A. 1 Tosun G. 1 ‹ Bolat G. 46, 51 Tuncer T. 51 Bozda¤ H. 25 ‹nce O. 11 Turan G. 87 Buek J.D. 32 K U-Ü C-Ç Kalayc› H. 162 Uzun F. 135 Celayir A. 46 Kale A. 135 Uzun N.D. 135 Cesur S. 46 Karaflahin K.E. 54 Coflkun B. 107 Kartal A. 141 Üstünyurt E. 69 Çelik E. 38 K›nc› M.F. 54 Y Çift T. 64, 69 K›yak H. 11 Yalç›n Bahat P. 87 Çoban G. 162 Koçak D.Y. 78 Çöl Madenda¤ ‹. 7 Yalç›n Y. 18 Korkmazer E. 64, 69, 107 Yavuz A. 18 D Köse S. 124 Yavuzcan A. 112 Demirci O. 46, 51 M Yayla M. 57, 102 Demirçivi Bör E. 25 Yenigül N. 92 Demirel E. 97 Madenda¤ Y. 7 Yeflilç›nar ‹. 54 Dilek T.U.K. 155, 167 Meleko¤lu R. 38 Do¤an Durda¤ G. 162 Müderris ‹.‹. 7 Y›ld›r›m E. 112 Yüksel fiimflek S. 162 E Ö Ekin A. 1 Özcan H. 78 Z Ekmekci E. 97 Özkaya M.O. 18 Zafer E. 32, 148
The bold typed references are the ones in which the person is the first author.
172 Perinatal Journal A L J O A T U N R I N R A E L P Acknowledgement
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Acknowledgement of Reviewers
(Volume 26, 2018) The Editorial Staff of the Perinatal Journal expresses their appreciation to the follouing colleagues who have reviewed manuscripts for Volume 26, 2018.*
Olufl Api Muhittin Eftal Avc› Filiz Çayan Sertaç Esin Ali Gedikbafli Fikret Gökhan Göynümer Arif Güngören Selahattin Kumru Mehmet Okan Özkaya Halil Gürsoy Pala ‹brahim Polat Mekin Sezik H. Alper Tanr›verdi Ebru Tar›m Ahmet Baflar Tekin Ahmet Yal›nkaya Elif Gül Yapar Eyi Murat Yayla Emre Zafer
*Names are in alphabetical order.
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