ISSN 1300-5251 PERINATAL JOURNAL

TOLO ‹NA J‹ R D E E P R N K E R ⁄ Ü ‹ T

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• Volume 13 / Issue 4 / 2005 T U Y

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K E I I S C H O P S E Y R G The Official Publication of Turkish Perinatology Society INATOLO

1993 ISSN 1300-5251 PERINATAL JOURNAL

Volume 13 / Issue 4 / December 2005

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Perinatal Journal

Volume 13 / Issue 4 / December 2005

Contents

Viewpoint Delivery Methods in Multifetal 187 Mehmet Okan Özkaya, Mekin Sezik, Hakan Kaya Research Articles Umbilical Artery Acid-Base Status and Lactate 191 Levels in Term and Preterm Healthy Newborns: Relation to Delivery Mode Ener Ça¤r› Dinleyici, Neslihan Tekin, Mehmet Arif Akflit, Baflar Tekin, Ömer Çolak Relationship Between Umbilical Artery Doppler Investigations and 198 Perinatal Outcome in Patients with HELLP Syndrome Mekin Sezik, Mehmet Okan Özkaya, Hülya Toyran Sezik, Elif Gül Yapar, Hakan Kaya Misoprostol for Second and Third-Trimester Labor Induction in 203 Women with Previous Cesarean Delivery Halil Aslan, Altan Cebeci, Yavuz Ceylan Vaginal Birth After Cesarean Section: Is It Safe? 208 Emre Sinan Güngör, Egemen Ertafl, Perran Moröy, fievki Çelen, Nuri Dan›flman, Leyla Mollamahmuto¤lu Retrospective Analysis of Multiple Pregnancies 213 Mahmut Erdemo¤lu, Ahmet Kale, Nurten Akdeniz, Ahmet Yal›nkaya, Y›lmaz Özcan, Murat Yayla Case Reports The Predictive Value of Middle Cerebral Artery Peak Systolic Velocity in 218 Repeated Intrauterine Transfusion: A Case Report Yeflim Bülbül Baytur, Ümit Sungurtekin ‹nceboz, Tayfun Özçak›r, Y›ld›z Uyar, Hüsnü Ça¤lar Death of One in Twin Pregnancy: Report of Four Cases 223 Semih Mun, Tolga M›zrak, Cüneyt Eftal Taner, Gülflen Derin, Cem Büyüktosun Impetigo Herpetiformis: A Case Report 227 ‹ncim Bezircio¤lu, Merve Biçer, Levent Karc›, Füsun Özder, Ali Balo¤lu Treatment of Viable Cesarean Scar with Intraamniotic 232 Methotrexate Injection Orhan Ünal, Olufl Api, Bülent Kars, Salim Korucu, Çi¤dem Korucu, Sadullah Bulut Index Subject and Author Index 247

Perinatal Journal • Vol: 13, Issue: 4/December 2005 187

VIEWPOINT

Delivery Methods in Multifetal Pregnancies

Mehmet Okan Özkaya, Mekin Sezik, Hakan Kaya

1Department of Gynecology and , Faculty of Medicine, Süleyman Demirel University, Isparta

Introduction nancies doesn’t seem significant. The frequency of the multifetal pregnancies is In twin pregnancies, the possibility that the significantly increased as a result of the assisted fetus is delivered in vertex-vertex corresponds to reproduction techniques.1,2 With ovulation induc- 62%, 38% vertex-nonvertex, and 20% non vertex- 5 tion, twin births frequency multiplies 10 times nonvertex. In particular, if the first fetus is deliv- approximately.2 The twin pregnancies form 1% of ered in reverse presentation the delivery method is overall pregnancies while perinatal mortality rate is controversial. During a well-controlled study, the about 10%.3 situations where the fetus is 1500 g and below, the breech delivey increases the neonatal mortality at The type of the delivery method is one of the 9.5 times.6 However, the breech delivery above most problematic issues in multifetal pregnancies. 1500 g. (Apgar scores and neonatal mortality) There are numerous controversies within the mul- seems as safe.7 In another multicentered study, tifetal pregnancies for the delivery method. Most when fetus in breech presentation is below 1500 g, recent and comprehensive studies are will be enu- Apgar score in fifth minute is reported low merated in following section. (p=0.008, OR 2.4, 95% CI 1.2-4.7). Within the same study, if the fetus is above 1500 g., there is no Planned Cesarean change in Apgar score for the vaginal confinement The fact that whether all twin pregnancies (p=0.76, OR 1.1, 95% CI 0.6-2.1) and reported that which are delivered by cesarean decrease the peri- vaginal confinement could be made in these preg- 7 natal mortality is a controversial subject. There nants. exists some particular proof that the babies deliv- American College of Obstetricians and Gyne- ered by cesarean weight 1000 g and below and cologists (ACOGg) brings out that the cesarean that is advantageous for Apgar scores perinatal should be preferred if twin presentation isn’t ver- mortality.4 As a result of a large scale meta-analy- tex independent from the weight of the fetus.8 In sis on this subject, it is found that planned cesare- a meta-analysis that confirms this idea, it was an increases Apgar score only in fifth minute for found that Apgar Score risk was increased at 50 % breech presentation of the first fetus, however, in fifth minute of , (OR 0.47, 95 %, CI 0.26- there isn’t any difference between planned cesare- 0.88) and 1/3 when the first fetus is in breech pre- an and normal confinement in perinatal mortality sentation (OR 0.33, %95 CI 0.17-0.65).9 and morbidity.5 Consequently, except the exces- In consequence, for twin pregnancies, if the sive preterm twin cases, delivering all twin preg- first fetus is in breech presentation and below 1500

Correspondence: Dr. Mehmet Okan Özkaya, Süleyman Demirel Üniversitesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Isparta e-mail: [email protected] 188 Özkaya MO et al., Delivery Methods in Multifetal Pregnancies

g. the cesarean, is safer. In these studies, when the while second fetus is in nonvertex, to implement first fetus is in breech presentation, for Apgar Score cesarean to both fetus, vaginal delivery for the first and neonatal mortality, vaginal and cesarean con- fetus and cesarean to the second fetus and vaginal 5 finements give similar results. Besides, in well-con- method for both fetus. Within this study, vaginal trolled studies and meta-analysis, Apgar scores in delivery is in particular specified as safe for 1500 g and above. cesarean are better in fifth minute. Therefore, in twin pregnancies the first fetus is in breech pre- In consequence, for twin pregnancies that the sentation, the cesarean is safer regardless of the second fetus is nonvertex, left to the normal deliv- ery, the need for emergency cesarean is and weight. important issue. Even though no significant risk was assessed in retroactive studies, the Presentation of the Second Fetus "vertex–breech" presentations should be planned Another issue is related with the delivery meth- by taking into account the other factors as well as ods that second fetus is nonvertex. According to the patient. For these controversial situations, the another study, the presentation and fetal position weight of the fetus and the unfitness between the of the second fetus don’t have any difference for weights should be also considered. perinatal results except Apgar score in first In consequence, for twin pregnancies, if the minute.10 Breech presentation of the second fetus first fetus is in breech presentation and below 1500 may not be a cesarean indication itself. However, g. the cesarean, is safer. In these studies, when the in the cases left to the normal parturitions, there is first fetus is in breech presentation, for Apgar Score a 10% "urgent cesarean for second fetus" rate.11 The and neonatal mortality, vaginal and cesarean con- breech presentation of the second fetus multiplies finements give similar results. Besides, in well-con- 4 times the urgent cesarean rate. trolled studies and meta-analysis, Apgar scores in There are various publications that show that cesarean are better in fifth minute. Therefore, in the second fetus has more risks, because of the twin pregnancies the first fetus is in breech pre- delivery complications.12 In twins, the emergency sentation, the cesarean is safer regardless of the cesarean is found associated with weight. and infectious morbidity.13 In a recent and com- prehensive study, it is showed that the vertex- Weight Difference between the breech twins delivered by cesarean method have a neonatal mortality rate comparable with vertex- Another controversial issue for the twin preg- vertex twins delivered by vaginal presentation.14 nancies is that whether the birth weight differences Yet, in the same study, interrelated with the previ- matters in delivery method. In a recent study, it is ous findings, highest neonatal mortality rate is in found that the vaginal birth increases the neonatal vertex-breech presentations and it was observed in mortality when the difference in fetus weights 17 vaginal-emergency cesarean group (2.7/1000 ges- exceeds 40%. It was stated that the increase in tation). In another study supporting the same find- risk started at 20% and becomes significant at 40%. ings, it is observed that neonatal mortality and Generally, the risk of the difference between the morbidity in which were delivered by vaginal fetus weights brings out the fetal mortality and method or the first fetus vaginal and second by smaller fetus has more perinatal mortality risk. For cesarean, are found higher than that both fetus are perinatal results, 30% and more is assessed as clin- delivered by cesarean.15 In another study, it is com- ically significant.18 In another study the twins pared delivering second fetus by cesarean in non- below 1500 g limit were observed and for both vertex position and both fetus by vaginal method. cesarean and vaginal deliveries, the fetus with Apgar scores were higher in cesarean group and lower weight bears more risk in respiratory distress neonatal mortality was lower. Within the extent of syndrome, and chronic respiratory system syn- the study, vaginal delivery is stated as dangerous drome.19 Cesarean method seems more logic if the for those type of twin pregnancies.16 However, in a difference between birth weights of the twins is study by Winn et al, it is reported that there is no more than 20-30%. But there isn’t any proof sup- difference in neonatal mortality and birth trauma porting this approach. Perinatal Journal • Vol: 13, Issue: 4/December 2005 189

Delivery in Vertex-Vertex Presentations Perinatal mortality is augmenting 2 times in triplets 21 Another issue is whether normal confinement (115/1000 to 223/1000). In multiple pregnancies, perinatal and neonatal mortality are observed for in vertex-vertex presentations is always reliable. the fetus that have 1500 and lower fetal weight and Vertex-vertex presentations may leave for normal earlier than 27 months.22 As fetal and maternal delivery method. However, this isn’t always safest prognosis worsen and increase premature risk solution. In another study that examines the repre- while the number of the fetus multiplies, studies sentation and delivery method in term twins, in aiming to reduce the iatrogenic multiple pregnan- case where emergency cesarean is needed for sec- cies, gain importance. ond fetus in vertex-vertex representation (vaginal – cesarean delivery) highest neonatal mortality References (3.8/1000 live birth) has been observed.14 Further 1. Vintzileos AM, Ananth CV, Kontopoulos E, Smulian JC. Mo- problems that the fetus cannot be engaged, delay- de of delivery and risk of and infant mortality in ing the birth may become a problem in vertex-ver- triplet gestations: United States, 1995 through 1998. Am J tex presentations. In vertex-vertex presentations in Obstet Gynecol 2005; 192: 464-9. 2. Barrett JFR. Delivery of the term twin. Best Pract Res Clin which no weight difference could be detected, Obstet Gynaecol 2004; 18: 625-30. there is a need for studies related to evaluate the 3. Hogle KL, Hutton EK, McBrien KA, Barrett JF, Hannah ME. necessity for cesarean in pre natal period. Cesarean delivery for twins: a systematic review and meta- analysis. Am J Obstet Gynecol 2003; 188: 220-7. 4. Zhang J, Bowes WA Jr, Grey TW, McMahon MJ. Twin deli- Triplet Pregnancies very and neonatal and infant mortality: a population-based study. Obstet Gynecol 1996; 88: 593-8. Except the twin fetal pregnancies, triplet and 5. Winn HN, Cimino J, Powers J, Roberts M, Holcomb W, Ar- other multiple pregnancies are subject to a discus- tal R, et al. Intrapartum management of nonvertex second- born twins: a critical analysis. Am J Obstet Gynecol 2001; sion on delivery method. In preliminary study, in 185: 1204-8. case where first triplet is vertex, the fetus is deliv- 6. Blickstein I. Cesarean section for all twins? J Perinat Med ered by vaginal method, and one-third of all 2000; 28: 169-74. triplets in the study (n= 23) are delivered (8 7. Blickstein I, Goldman RD, Kupferminc M. Delivery of bre- ech first twins: a multicenter retrospective study. Obstet triplets) were delivered by vaginal parturition. Gynecol 2000; 95: 37-42. There is no difference in neonatal morbidity and 8. American College of Obstetricians and Gynecologists Com- mortality between vaginal and cesarean.20 In con- mittee on Practice Bulletins-Obstetrics; Society for Maternal- Fetal Medicine; ACOG Joint Editorial Committee. ACOG trary to this, another triplet pregnancy study educational bulletin. Special problems of multiple gestati- showed that delivering overall three fetus by on. Number 253, November 1998 (Replaces Number 131, August 1989). American College of Obstetricians and Gyne- cesarean diminishes the neonatal mortality.1 For cologists. Int J Gynaecol Obstet 1999; 64: 323-33. triplet pregnancies, cesarean will continue its 9. Hogle KL, Hutton EK, McBrien KA, Barrett JF, Hannah ME. validity as suggested delivery method until the reli- Cesarean delivery for twins: a systematic review and meta- analysis. Am J Obstet Gynecol 2003; 188: 220-7. ability of normal birth proves itself in larger scale 10. Greig PC, Veille JC, Morgan T, Henderson L. The effect of studies. presentation and mode of delivery on neonatal outcome in In multiple pregnancies, while the number of the second twin. Am J Obstet Gynecol 1992; 167: 901-6. 11. Wen SW, Fung KF, Oppenheimer L, Demissie K, Yang Q, fetus multiplies, the mortality and morbidity for Walker M. Neonatal mortality in second twin according to both mother and the fetus. In a comprehensive cause of death, gestational age, and mode of delivery. Am study, 44605 pregnancy cases were assessed and J Obstet Gynecol 2004; 191: 778-83. 1.3% twin, 0,1% triplet frequency was estimated. 12. Smith GC, Pell JP, Dobbie R. Birth order, gestational age, and risk of delivery related perinatal death in twins: retros- The most frequent perinatal complication, early pective cohort study. BMJ 2002; 325: 1004. parturition occurred in triplets 2 times comparing 13. Hibbard JU, Ismail MA, Wang Y, Te C, Karrison T, Ismail to the twins. Maternal mortality is estimated MA. Failed vaginal birth after a cesarean section: how risky is it? I. Maternal morbidity. Am J Obstet Gynecol 2001; 184: 35.8/100.000 for twins and 99/100.000 for triplets. 1365-71. 190 Özkaya MO et al., Delivery Methods in Multifetal Pregnancies

14. Kontopoulos EV, Ananth CV, Smulian JC, Vintzileos AM. tet Gynecol 1995; 172: 955-9. The impact of route of delivery and presentation on twin 19. Shinwell ES, Blickstein I, Lusky A, Reichman B. Effect of neonatal and infant mortality: a population-based study in the USA, 1995-97. J Matern Fetal Neonatal Med 2004; 15: birth order on neonatal morbidity and mortality among 219-24. very low birthweight twins: a population based study. Arch 15. Yang Q, Wen SW, Chen Y, Krewski D, Fung KF, Walker M. Dis Child Fetal Neonatal Ed 2004; 89: 145-8. Neonatal death and morbidity in vertex-nonvertex second 20. Alamia V Jr, Royek AB, Jaekle RK, Meyer BA. Preliminary twins according to mode of delivery and birth weight. Am experience with a prospective protocol for planned vaginal J Obstet Gynecol 2005; 192: 840-7. delivery of triplet gestations. Am J Obstet Gynecol 1998; 179: 16. Usta IM, Rechdan JB, Khalil AM, Nassar AH. Mode of deliv- ery for vertex-nonvertex twin gestations. Int J Gynaecol 1133-5. Obstet 2005; 88: 9-14. 21. Dafallah SE, Yousif EM. A comparative study of twin and 17. Kontopoulos EV, Ananth CV, Smulian JC, Vintzileos AM. triplet pregnancy. Saudi Med J 2004; 25: 502-6. The influence of mode of delivery on twin neonatal mor- tality in the US: variance by birth weight discordance. Am J 22. Kamac› M, Zetero¤lu fi, fiahin HG, fiengül M, Gülümser S, Obstet Gynecol 2005; 192: 252-6. Bolluk G. Ço¤ul gebeliklerde do¤um yöntemleri obstetrik 18. Cheung VY, Bocking AD, Dasilva OP. Preterm discordant komplikasyonlar ve perinatal mortalite. Jinekoloji Obstetrik twins: what birth weight difference is significant? Am J Obs- Dergisi 2004; 18: 135-9. Perinatal Journal • Vol: 13, Issue: 4/December 2005 191

Umbilical Artery Acid-Base Status and Lactate Levels in Term and Preterm Healthy Newborns: Relation to Delivery Mode

Ener Ça¤r› Dinleyici1, Neslihan Tekin2, Mehmet Arif Akflit2, Baflar Tekin3, Ömer Çolak4

1Department of Pediatrics, 2Department of Neonatology, 3Department of Gynecology and Obstetrics, 4Department of Biochemistry, Faculty of Medicine, Osmangazi University, Eskiflehir

Abstract Objective: Measurements of umbilical cord acid-base status are routinely carried-out in many perinatology centers. Umbilical cord gas measurements and complementary, provide the clinician with information of patient assessment, therapeutic decision making and prognostication in NICU. The aim of this prospective study was to establish the normal range of umbilical artery gas parameters, acid-base status and lactate levels in term and preterm healthy newborns and their relationship between deliv- ery mode. Methods: Umbilical artery gas parameters from 108 healthy newborns (85 term, 23 preterm; 48 vaginal deliveries and 60 cae- sarean sections) which were followed-up in Neonatology Unit, were evaluated. Results: Umbilical artery mean lactate levels were higher in preterm newborns than term newborns (29.4 ± 2.75, 21.0 ± 1.0 mg/dl, p<0.01). Umbilical artery mean pO2, sodium, chloride and osmolarity levels were lower in vaginal deliveries than cae- sarean section (p<0.05, p<0.001, p<0.01, p<0.01 respectively). Umbilical artery lactate levels were higher in vaginal deliveries (28.95 ± 1.65 mg/dl) than caesarean section (18.06 ± 0.99 mg/dl) (p<0.001). Umbilical artery p02, ct02 and s02 levels were positively correlated with F02Hb, FCOHb levels and negatively correlated with FHHb and FmetHb levels. Umbilical artery P02, ct02 and s02 levels were positively correlated with pH levels and negatively correlated with pC02 levels. Conclusion: Umbilical artery blood gase parameters must be evaluated with the clinical and laboratory findings of the newborns. Keywords: Umbilical artery, blood gase, delivery type, lactate, term, preterm.

Sa¤l›kl› term ve preterm yenido¤anlarda umbilikal arter asit-baz durumu ve laktat düzeyleri ve do¤um fleklinin iliflkisinin de¤erlendirilmesi Amaç: Umbilikal kord kan gaz› analizi birçok perinatoloji merkezinde rutin olarak yap›lmaktad›r. Umbilikal kord kan gaz› para- metrelerinin yorumlanmas›, yenido¤an yo¤un bak›m ünitelerinde takip edilen bebeklerin klinik durumunun, tedavi plan›n›n ve prognozunun belirlenmesinde önemli göstergelerden biridir. Bu çal›flmada; sa¤l›kl› term ve preterm yenido¤anlar›n umbilikal ar- ter kan gaz› parametreleri ile asit-baz dengesinin ve laktat düzeylerinin belirlenmesi ve bu parametreler ile do¤um flekli aras›nda- ki muhtemel iliflkinin de¤erlendirilmesi planlanm›flt›r. Yöntem: Çal›flmaya Neonatoloji ünitesinde takip edilen 108 yenido¤anda (85 term, 23 preterm; 48 vajinal yol ile do¤an, 60 se- zaryen ile do¤an) umbilikal arter kan gaz› parametreleri de¤erlendirildi. Bulgular: Preterm bebeklerde umbilikal arter laktat düzeyleri term bebeklere göre yüksek olarak saptand› (29.4 ± 2.75, 21.0 ± 1.0 mg/dl, p<0.01). Umbilikal arter ortalama pO2, Na, Cl ve osmolarite de¤erleri vajinal yol ile do¤anlarda sezaryen ile do¤an- lara göre daha düflük olarak saptand› (s›ras›yla p<0.05, p<0.001, p<0.01, p<0.01). Vajinal yol ile do¤an bebeklerde umbilikal ar- ter ortalama laktat düzeyleri (28.95 ± 1.65 mg/dl) sezaryen ile do¤an bebeklerin ortalama laktat düzeylerine (18.06 ± 0.99 mg/dl) göre yüksek olarak saptand› (p<0.001). Umbilikal arter p02, ct02 ve s02 düzeyleri ile F02Hb ve FCOHb düzeyleri ile po- zitif, FHHb ve FmetHb düzeyleri ile negatif korelasyon saptand›. Umbilikal arter P02, ct02 ve s02 düzeyleri ile umbilikal arter pH düzeyi aras›nda pozitif, pC02 düzeyi aras›nda ise negatif korelasyon saptand›. Sonuç: Sa¤l›kl› yenido¤anlardan elde edilen kan gaz› parametrelerinin hastan›n klinik bilgileri ile bütünlük içerisinde de¤erlendi- rilmesi gerekmektedir. Anahtar Sözcükler: Umbilikal arter, kan gaz›, do¤um flekli, laktat, term, preterm.

Correspondence: Dr. Ener Ça¤r› Dinleyici, Osmangazi Üniversitesi T›p Fakültesi, Çocuk Sa¤l›¤› ve Hastal›klar› Anabilim Dal›, Eskiflehir e-mail: [email protected] 192 Dinleyici EÇ et al., Umbilical Artery Acid-Base Status and Lactate Levels in Term and Preterm Healthy Newborns:

Introduction in our clinic for the reason that the blood gas para- Blood pressure parameters and the evaluation meters in the context of evaluation increased and to evaluate the possible relationship between these of these parameters is one of the most important parameters and type of birth. indicators for determining the clinical condition of the patient, treatment plan and prognosis.1-4 While the evaluation of blood gas parameters is an Methods important investigation of all the patients in inten- Newborns monitored in neonatology service sive care units, the fact that the physiology is dif- with the 5th minute Apgar score above 6, and hav- ferent in the newborn period and changes quickly ing neonatal period without problems are includ- and using a small amount of blood increases the ed in the study. 2 cc arterial bloods were taken value of the investigation.5 Only the pH, carbon from all the newborns after the cordon was dioxide and acid-base and oxygen partial pres- clamped by an injector washed with heparin. sures were evaluated but today many blood gas Samples were reached to the laboratory in ten parameters are evaluated together in order to eval- minutes in accordance with the cold chain. All the uate oxygenation and acid-base balance.1-5 Blood umbilical artery blood samples are investigated gases are the most important tools to determine using the parameters in table 1 in our unit bio- oxygenation, carbon dioxide homeostasis, acid- chemistry laboratory with ABL Radiometer device. base balance and pulmonary functions efficiency.5 Cut-off value for the umbilical artery value for Blood gases are also an important diagnosis tool healthy newborns were determined 7.20 in previ- for leading oxygen and ventilator cure for respira- ous studies, 108 newborns whose umbilical artery tory distress of newborns and also for the illnesses pH value is above that value were included in the relating with cardiac, renal and central nervous study. Work group is grouped according to their system. Betterments in the values of blood gases gestation week and birth type. can be seen as an efficiency of the treatment.1-5 All the statistical evaluation is done using SPSS Taking and evaluating the umbilical artery for Windows 10.0 (IL, Chicago, USA). Umbilical blood gases in the birth room has become a rou- artery blood gas parameters are given as average ± SEM. In order to compare the data between the tine implementation for a quality newborn care.1,2,4 groups, t test is used for independent groups, Especially evaluation of the new born in the first Pearson correlation analysis is used for correla- hours, joint evaluation of traditional Apgar scoring tions. p<0.05 value is considered significant statis- and umbilical artery and blood gas parameters tically. became important for early diagnosis approaches. Especially of the newborn with high risk and bad general condition, in cases such as shock, Results hypotension, peripheral vasoconstriction and acro- 85 terms, 23 preterm in total 108 newborns cyanosis, capillary and blood gas values reflect the were included in the study. 48 of the cases were real data.5 Notwithstanding, with the increase of born by vaginal delivery and 60 had cesarean sec- the parameters in the blood gas analysis, hypoxia tion. Characteristics of the term and preterm evaluation is not made by Apgar score and umbil- infants evaluated in the study are given in the ical artery pH value. Lactic acidaemia developed Table 2. The 1st and 5th minute average Apgar by hypoxia or compensated acid-base unbalances scores of the preterm infants were lower than term can be stated, ideas can be developed whether the infants (in order p<0.001 and p<0.001). hypoxia is acute or chronic, which mechanism Without separating pregnancy week and birth results the compensation. This study is done to week, average umbilical blood gas parameter val- determine the umbilical artery blood gas analysis ues of the 108 newborns are given in Table 3. In results for term and preterm healthy newborn born the evaluation due to the pregnancy week, umbil- Perinatal Journal • Vol: 13, Issue: 4/December 2005 193

Table 1. Values from blood gas device and umbilical artery analysis.

Blood gas values pH, p02,pC02 Oxmeter values CtHb1, Hctc, s022, F02Hb3, FC0Hb4, FHHb5, FmetHb6 Electrolytic values K, Na, Ca, Cl Metabolic values Glucose, lactate, bilirubin, mOsm Oxygen condition ct027, p50c8 1 1 1 1 Acid-base status cBaz cHC03- , ABE , SBE

1. CtHb: Is the total hemoglobin (Hb) concentration in blood. Total hemoglobin mainly includes all types pf hemoglobin; such as deoxy-, oxy, carboxy-, met- ve sulfhemoglobin. CtHb=c02Hb+cHHb+cC0Hb+cMetHb 2. s02: Oxygen saturation in the artery. s02=c02Hb/cHHb + c02Hb S02; Oxidized hemoglobin related with the oxygen carrying hemoglobin This parameter gives the best information when used realted with CtHb 3. F02Hb id defined as the ratio between (oxyhemoglobin n level _); 02Hb and ctHb (c02Hb/ctHb) concentrations .It is calculated as follows: F02Hb=c02Hb C02Hb+cHHb+cC0Hb+cMetHB 4. FC0Hb=Carboxy hemoglobin ratio FC0Hb=cC0Hb/ctHb 6. FmetHb=methemoglobin ratio 7. ct02 : oxygen concentration in blood, 8. p50 : Oxygen pressure in the half saturated blood. This parameter determines oxygen oscillation in the tissues and the position of the oxy- gen dissociation curve (ODC) which is essential.

ical artery sodium values (p<0.05) was found high- higher for the infants born by vaginal birth (28.95 er for term infants, potassium and calcium values ±1.65 mg/dl) than the average lactate levels of being in the normal border were found higher for cesarean section infants (p<0.001) (Table 4). preterm infants (in order p<0.01, p<0.05). Positive correlation was detected between oxy- Umbilical artery lactate levels were found higher genation parameters p02, ct02, s02 levels. Positive for preterm infants than term infants (29.4±2.75, for umbilical artery o02, ct02 and s02 levels and 21.0±1.0 mg/dl, p<0.01) (Table3). F02Hb and FCOHb levels, and negative correlation between FHHb and FmetHb levels were detected. For the infants born by vaginal delivery (n=48), Between umbilical artery Po0, ct02 and S02 levels umbilical artery average pO2, Na, Cl and osmolar- and umbilical artery pH level a positive, and ity values were lower than the cesarean section between pC02 level and negative correction was infants (n=60) (in order p<0.05, p<0.001, p<0.01, seen. F02Hb was positively correlated with pH and p<0.01). Umbilical Artery average Hct, K, Ca, glu- negatively correlated with pC02. FHHb was nega- cose levels were found higher for the infants born tively correlated with pH and positively correlated by vaginal birth than the cesarean section infants with pC02. There was negative correlation (in order p<0.05, p<0.05, p<0.01, p<0.01). between FmetHb and pH, p50c value showed neg- Umbilical artery average lactate levels were found ative correlation with pH (Table 4). There was no

Table 2. Charecteristic of 108 infants who’s umbilical artery blood gas was analyzed.*

Pregnancy week Birth weight Apgar score at Apgar score at (week) (g) 1st minute 5th minute

All the newborns (n=108) 37.9 ± 0.2 3053.5 ± 68.0 8.28 ± 0.2 9.54 ± 0.1 Term (n=85) 38.9 ± 0.1 3315.4 ± 80.4 8.65 ± 0.1** 9.74 ± 0.01** Preterm (23) 33.6 ± 0.4 2041.4 ± 112.4 6.90 ± 0.6 8.61 ± 0.4

Delivery type Vaginal (n=48) 37.5 ± 0.4 2926.6 ± 110.9 8.52 ± 0.2 9.65 ± 0.1 Cesarean (n=60) 38.2 ± 0.3 3152.8 ± 83.1 8.10 ± 0.2 9.38 ± 0.2

* Values are given mean± standard deviation. ** p<0.001, term and preterm infants. 194 Dinleyici EÇ et al., Umbilical Artery Acid-Base Status and Lactate Levels in Term and Preterm Healthy Newborns:

Table 3. Umbilical artery blood gas parameters due to age and delivery type for all the work group.

All newborns Newborns Term Preterm Vaginal Cesarean (n=108) (n=108) newborns newborns delivery section min-max (n=85) (n=23) (n=48) (n=60)

PH 7.30 ± 0.01 7.211 7.472 7.30 ± 0.01 7.30 ± 0.01 7.31± 0.01 7.29 ± 0.01 P02 (mmHg) 19.1 ± 0.7 6 47 18.7 ± 0.7 20.8 ± 1.6 17.62 ± 0.89c 20.35 ± 0.99 PC02 (mmHg) 43.0 ± 0.7 28.5 65 43.7 ± 0.8 40.7 ± 1.5 42.3 ± 1.0 43.6 ± 1.1 CtHb g/dl 14.6 ± 0.2 8.1 19.8 14.4 ± 0.2 15.1 ± 0.6 15.2 ± 0.3 c 14.1 ± 0.3 Hctc (%) 44.6 ± 0.8 25.3 60.4 44.1 ± 0.8 46.2 ± 1.8 46.7 ± 1.0 c 42.8 ± 1.1 S02 (%) 37.6 ± 1.9 9.2 96.8 36.5 ± 2.1 41.7 ± 3.7 35.5 ± 2.9 39.2 ± 2.4 F02Hb (%) 38.7 ± 1.9 9.6 94.7 37.2 ± 2.1 44.1 ± 4.2 35.8 ± 2.9 40.8 ± 2.5 FC0Hb (%) 1.02 ± 0.01 0 6.4 1.00 ± 0.1 1.08 ± 0.1 0.95 ± 0.1 1.06 ± 0.1 FHHb (%) 58.8 ± 2.0 3.1 89.6 59.9 ± 2.3 54.9 ± 3.7 61.4 ± 2.9 56.8 ± 2.7 FmetHb (%) 0.93 ± 0.01 0.2 2.5 0.94 ± 0.01 0.9 ± 0.01 0.91 ± 0.01 0.94 ± 0.01 Ck (mEq/L) 2.9 ± 0.01 1.4 3.93 2.83 ± 0.01a 3.15 ± 0.01 3.01 ± 0.01 c 2.80 ± 0.01 Cna (mEq/L) 146.9 ± 1.1 123 183 147.9 ± 1.3 b 143.1 ± 1.25 142.6 ± 1.4 d 150.2 ± 1.5 Cca (mg/dl) 1.82 ± 0.01 0.2 3.88 1.73 ± 0.01 b 2.15 ± 0.17 2.12 ± 0.11 e 1.58 ± 0.11 CCl (mEq/L) 111.6 ± 0.6 92 127 111.9 ± 0.7 a 110.3 ± 1.0 109.8 ± 0.8 e 112.9 ± 0.9 C glucose (mg/dl) 64.6 ± 2.7 23 163 62.8 ±2.8 71.6 ± 7.3 74.1 ± 4.8 e 57.4 ± 2.6 Laktat (mg/dl) 22.8 ± 1.05 7 56 21.0 ± 1.0 29.4 ± 2.75 28.9 ± 1.6 d 18.0 ± 0.9 Bilirubin (mg/dl) 0.77 ± 0.01 0 2.3 0.75 ± 0.01 0.81 ± 0.01 0.8 ± 0.01 0.7 ± 0.01 Mosm (mmol/kg) 295 ± 2.0 253 367 296 ± 2.5 290.7 ± 2.6 288.5 ± 2.6 e 300.1 ± 2.9 Ct02 (Vol%) 8.02 ± 0.4 1.9 19.9 7.80 ± 0.4 8.90 ± 0.9 8.0 ± 0.6 8.0 ± 0.5 P50c (mmHg) 22.6 ± 0.3 17.5 32.1 22.8 ± 0.3 21.9 ± 0.4 22.7 ± 0.5 22.6 ± 0.3 Cbaz (mmol/L) -4.98 ± 0.3 -12.9 7.9 -4.6 ± 0.4 -6.4 ± 0.6 -5.3 ± 0.4 -4.7 ± 0.5 HC03 (mmol/L) 19.1 ± 0.3 13.7 28 19.3 ± 0.3 18.5 ± 0.4 18.7 ± 0.3 19.5 ± 0.4 ABEC (mmol/L) -5.2 ± 0.4 -12.8 6 -4.9 ± 0.4 -5.9 ± 0.6 -5.3 ± 0.4 -5.1 ± 0.5 SBEC (mmol/L) -4.86 ± 0.3 -12.6 7.9 -4.6 ± 0.4 -5.8 ± 0.6 -5.1 ± 0.4 -4.6 ± 0.5

* Values are given mean± standard deviation. a. When p<0.001 term-preterm infants are compared, b. When p<0.05 term-preterm infants are compared, c. p<0.05 When vaginal deliveries and cesarean sections are compared, d. p<0.001 When vaginal deliveries and cesarean sections are compared, e. p<0.01 When vaginal deliveries and cesarean sections are compared.

correlation between oxygenation parameters and Negative correlation of electrolyte values of Na parameters showing the acid-base status except of and Cl with cbase, HCO3, ABEC, SBEC and lactate the positive correlation between umbilical artery and positive correlation of K and Ca with these s02 level and cbase level. values were detected (Table 4).

Table 4. Correlation analysis results of the data of oxygenation.

p02 S02 ct02 F02Hb FC0Hb FHHb FmetHb

p02 r=0.89 r=0.73 r=0.86 r=0.33 r=-0.81 r=-0.51 p<0.01 p<0.01 p<0.01 p<0.01 p<0.01 p<0.01

S02 r=0.764 r=0.96 r=0.42 r=-0.84 r=-0.48 p<0.001 p<0.01 p<0.01 p<0.01 p<0.01

ct02 r=0.79 r=0.47 r=-0.8 r=-0.55 p<0.01 p<0.01 p<0.01 p<0.01

F02Hb r=0.39 r=-0.86 r=-0.53 p<0.01 p<0.01 p<0.01

FC0Hb r=-0.43 r=-0.33 p<0.01 p<0.01

FHHb r=0.55 p<0.01 Perinatal Journal • Vol: 13, Issue: 4/December 2005 195

Discussion et al,8 in their study on 16,060 newborns, average While Apgar scoring is taken as the major cri- umbilical artery pH was 7.26, pCO2 was 52 mmHg, teria in order to evaluate the condition of the new- ABE was -4, PO2 was 177 mmHg. They showed born and to define the affective newborn classical- that there was no relationship between delivery ly, it is suggested that it is not efficient to evaluate type and gestational week in this patient. Sener et 9 the perinatal asphyxia defined as hypoxemia and al found average umbilical pH value of 7.26±0.083 metabolic acidosis only by Apgar scoring, and in their study on 188 newborns born with sponta- blood gas analysis should be taken into consider- neous vaginal delivery. In our study, cases having ation for a more objective evaluation.6 Umbilical pH value above 7.20 was taken, average pO2 was artery gives a better idea than umbilical vein for 19.1 mmHg (6-47 mmHg), BE average value was - evaluation of fetal metabolic condition. Even 4.97 (-12.9- 7.9). though venous pH is normal, arterial acidaemia PaO2 is the most important determiner of sO2 can be detected. Umbilical artery can give an idea but it is not the only determiner. Factors affecting for fetal acid-base balance and also maternal acid- oxygen dissociation, curve at a certain pO2 are base balance and the effect of placental function.1- temperature, pH and pCO2. As it can be seen in 3 It will be appropriate that the reference values our study, there are positive correlation between due to gestation week and birth type being deter- sO2 and pH and a negative correlation with pCO2. mined and all the parameters being evaluated pO2 is the impulsive force for the oxygen mole- totally. For instance; pO2, ct02 and p50 are the res- cules to enter into erythrocyte and bind to hemo- piratory and homothetic section to maintain oxy- globin chemically, the higher pO2 and the higher gen for the tissue and they are the key parameters sO2 will be. ct02 is a parameter showing the total for using the useable oxygen in the artery. There number of oxygen molecules directly (bind to is a complex relationship between these parame- hemoglobin or not) different than PaO2 or SaO2, ters; a change in one of the parameters can be and it is directly related with hemoglobin content 5 compensated by the other two parameters. For different from the other two variable. It is calculate instance, a patient with hypoxemia, if Hb concen- by the part of the ctO2 bound to hemoglobin tration when pO2 become 56 mmGh and sO2 (HbX1.34XSaO2) and the dissolved part become 79%, patient will reach the useable of nor- (.003XPaO2): mal artery oxygen. On the other hand, if Hb con- ct02= Hb (g/dl) X1.34 ml O2/g Hb X SaO2 + centration is low or there is dyshemoglobinemia PaO2 X (.003 ml O2/ Hg/dl).5 for a patient with 56 mmGh pO2 and 79% sO2, oxygen usage will be low. For this reason, oxygen For this reason, it is an expected finding that taking, carrying and release must be evaluated these parameters (pO2, ctO2 and SO2 and FO2Hb, together for the appropriate diagnosis and treat- FHHHb and FmetHb) can show correlation with ment. In our study pO2 was lower but Hct was each other as seen in our study. higher for the vaginal births and there was com- It is important to determine the reason of low pensation. Apgar sore for premature infants and cord blood In the studies about umbilical artery blood gas acid-base status for these infants.10 Ramin et al10 it is thought that there can be affects of some fac- detected a difference of umbilical artery pH, pCO2, tors such as delivery type, gestation week and PO2, HCO3 and BE values between preterm and some other factors in addition to the differences term infants. Arikan et al11 stated that the average between the countries and clinics.7 Dudenhausen pH values can be high for the preterm and low for et al7 found the lowest umbilical cord pH value post terms. But, researchers showed that there is 7.04 and percentile value 7.21 in their studies on no relationship between umbilical cord oxygen 681 newborn. 10th percentile BE value was 7.21, saturation and gestation and they are distributed in 90th percentile pCO2 value was 62 mmHg. Helwig a wide range. We did not detected a difference 196 Dinleyici EÇ et al., Umbilical Artery Acid-Base Status and Lactate Levels in Term and Preterm Healthy Newborns:

between the values of umbilical artery pH, pCO2, monitoring. Kruger et al18 showed that there is cor- PO2, HCO3 and BE values in our study. In a study relation between the lactate levels of fetal head in our country Benian et al12 detected a difference skin blood and cordon blood. Cut-off value of fetal between term and preterm newborns similarly and scalp lactate level for fetal asphyxia is told as 4.8 stated that there no impact of pregnancy age for mmol/L. In the same study, serum lactate levels the cases without uteroplacental deficiency. showed decrease wit the postnatal age; upper Another factor that can be effective on umbili- level was 3.8 mmol/l for the one less than 48 cal artery blood gas is the birth action and the hours, 2.4 mmol/L of the ones between 49-96 delivery type. It is shown that even the duration hours, 1.5 mmol/L for the ones more than 96 19 between the cesarean is decided and exercised hours. Shirley et al stated that the lactate levels have importance on blood gas parameters.13 was more than 7 mmol/L for less than 2.5 % of the Nickelsen et al14 detected low acidosis or mixed normal birth but no correlation between cord lac- respiratory / metabolic acidosis in the newborns tate levels and oxygen and carbon-dioxide partial 16 born in the 2nd phase of the birth between 10-30th pressure was seen. Shah et al stated that the lac- minute. It was shown that oxytoxin and birth tate levels were higher for newborns with hypoxic induction have no effect on the cord blood gas ischemic encephalopathy and returning to normal analysis. It was shown that vacuum extractions and duration was longer. In our study, umbilical artery low forceps implementations are related with low lactate levels for preterm infants were determined 17 pH and high CO2 levels but it was thought to be higher than term infants. Westgren et al found related with the diagnosis reasoned for this type of higher lactate levels for instrumental delivery and birth and not related with vacuum or forceps. cesarean sections than the vaginal births. Lactate Difference between artery and vein parameters levels had positive correlation with fetal pH, were seen generally for the healthy newborns, it hemoglobin, base gap, pCO2 and HCO3 and had was seen to be low difference between artery and negative correlation with morbidity and mortality. vein parameters for depressed infants. In our In our study, umbilical average lactate levels was study, umbilical artery average pO2, Na, Cl and found higher for infants born by vaginal delivery osmolarity values were lower for newborns born than the average lactate levels for infants born by by vaginal delivery than the newborns born by cesarean section. cesarean section. Umbilical artery average Hct, K, On the other hand, lactate can accumulate Ca, glucose levels were higher for newborns born resulting from other reasons than hypoxia. Liver by vaginal birth than the newborns born by cesare- disease and some medicine and toxins can an section Christian et al15 compared the infants increase the blood lactate level in adults. In addi- born breech vaginal position and cephalic presen- tion, raise in the blood pyruvate can also increase tation, and found that cord blood pH values were the lactate level. For this reason, it is a more prop- low and pCO2 values were high for the infants er approach to accept the lactic acidosis as a non- born by vaginal position. specific determiner of hypoxia. Some studies show In recent years, in addition to traditional blood that there is a weak correlation between the oxy- gas parameters, umbilical artery and lactate levels gen accession to the tissue and lactic acid levels. It have been added to the evaluation. Lactic acid will was emphasized that lactic acidosis is not a sensi- accumulate because the cell transformed into tive determiner for hypoxia. This insensitivity can anaerobic metabolism from aerobic metabolism in result from the fact that there is no linear relation- the tissue hypoxia. Metabolic acidosis resulting ship with lactic acid while the progressive hypox- from lactic acid accumulation in the blood is a rea- ia. Raised levels can be temporary because lactic 17,18,20 son for hypoxia.16 Westgren et al17 stated that lac- acid is metabolized by the liver. tate of fetal head skin is successful as much as pH The main reason why the electrolytes does not to determine perinatal prognoses and suggested exist in the blood gas analysis is for the calculation that it can take the place of pH for intra partum of anion gap (anion gap=AG).5 Lorenz et al21 inves- Perinatal Journal • Vol: 13, Issue: 4/December 2005 197

tigated that anion gap when there is not metabol- 8. Helwig JT, Parer JT, Kilpatrick SJ, Laros RK Jr. Umbilical ic acidosis for the critically ill newborns and cord blood acide-bas state: what is normal. Am J Obstet whether the metabolic acidosis is lactic acidosis of Gynecol 1996; 174: 1807-12. hypertrophic acidosis by anion gap. In the study 9. fiener T, Yalç›n ÖT, Hassa H, Özalp S, Çevrio¤lu AS, DEmirüstü C. Komplikasyonsuz gebeliklerde umbilikal by measuring lactic acid levels, 16 mmol/L or more kord kan gaz› de¤erleri ve apgar skorar›n›n yenido¤an mor- anion gap was seen determiner for lactic acidosis, biditesinin belirlenmesindeki tan›sal de¤eri. Perinatoloji lower than 8 was seen determiner for no lactic aci- Dergisi 1996; 4: 141-4. dosis, and values between 8-16 mmol/L was seen 10. Ramin SM, Gilstrap LC3rd, Leveno KJ, Burris J, Little BB. that it was useless to distinguish the diagnosis. In Umbilical artery acid-base status in the preterm infant. Obs- our study, electrolyte values of Na and Cl had neg- tet Gynecol 1989; 74: 256-8. ative correlation with cbase, HC03, ABEC, SBEC 11. Ar›kan GM, Scholz HS, Petru E, Haeusler MC, Haas J, Weiss and lactate, and K and Ca had positive correlation PA. Cord blood oxygen saturation in vigorous infants at with these values. In our study, pH and base birth: what is normal. BJOG 2000; 107: 987-94. deficit had no correlation with pCO2, had negative 12. Benian A, Uluda¤ S, At›fl A, Gök M, Madazl› R. Do¤umda correlation with Na, Cl and positive correlation bak›lan umbilikal kordon kan gaz› de¤erlerinin önemi. Cer- rahpafla T›p Dergisi 2002; 33: 236-244. with K and glucose. 13. Holcroft CJ, Graham EM, Aina-Mumuney A, Rai KK, Hen- In conclusion, umbilical artery blood gases can derson JL, Penning DH. Cord gas analysis, decision-to- give objective results to evaluate oxygenation, and delivery interval, and the 30-minute rule for emergency acid-base status and to define perinatal asphyxia. cesareans. J Perinatol 2005; 25: 229-35. Data must be evaluated with the results from 14. Nickelsen C, Weber T. Acid-base evaluation of umbilical healthy newborns and change levels taken as base. cord blood: relation to delivery mode and Apgar scores. Evaluating every component systemically in evalu- Eur J Obstet Gynecol Reprod Biol 1987; 24: 153-65. ating and monitoring umbilical blood gases by 15. Christian SS, Brady K. Cord blood acid-base values in knowing the interaction between them will be breech-presenting infants born vaginally. Obstet Gynecol guiding. 1991; 78: 778-81. 16. Shah S, Tracy M, Smyth J. Postnatal lactate as an early References predictor of short-term outcome after intrapartum asphyxia. J Perinataol 2004; 24: 16-20. 1. Thorp JA, Rushing RS. Umbilical cord blood gas analysis. Obstet Gynecol Clin North Am 1999; 26: 695-709. 17. Westgren M, Divon M, Horal M, Ingemarsson I, Kublickas 2. Thorp JA, Dildy GA, Yeomans ER, Meyer BA, Parisi VM. M, Shimojo N, Nordstrom L. Routine measurements of um- Umbilical cord blood gas analysis at delivery. Am J Obstet bilical artery lactate levels in the prediction of perinatal out- Gynecol 1996; 175: 517-22. come. Am J Obstet Gynecol 1995; 173: 1416-22. 3. Westgate JA, Garibaldi JM, Grene KR. Umbilical cord blood 18. Kruger K, Kublickas M, Westgren M. Lactate in scalp and gas analysis at delivery: a time for quality data. BJOG 1994; cord blood from fetuses with ominous fetal heart rate pat- 101: 1054-1063. terns. Obstet Gynecol 1998; 92: 918-22. 4. Aksin DF. Interpretation of neonatal blood gases, part II: disorders of acid-base balance. Neonatal Network 1997; 16: 19. Shirey T, St Pierre J, Winkelman J. Cord lactate, pH, and 23-9. blood gases from healthy neonates. Gynecol Obstet Invest 5. Brouillette RT, Waxman DH. Evaluation of the newborns 1996; 41: 15-9. blood gas status. Clin Chem 1997; 43: 215-21. 20. Chanrachakul B, Chua S, Nordstrom L, Yam J, Arulkumaran 6. Martin GC, Green RS, Holzman IR. Acidosis in newborns S. Umbilical artery blood lactate in healthy newborns. J Med with nuchal cords and normal apgar scores. J Perinatol Assoc Thai 1999; 82: 388-93. 2005; 25: 162-5. 7. Dudenhausen JW, Luhr C, Dimer JS. Umbilical artery blood 21. Lorenz JM, Kleinman LI, Markarian K, Oliver M, Fernandez J. gases in healthy term newborn infants. Int J Gynaecol Obs- Serum anion gap in the differential diagnosis of metabolic tet 1997; 57: 251-8. acidosis in critically ill newborns. J Pediatr 1999; 135: 751-5. 198 Perinatal Journal • Vol: 13, Issue: 4/December 2005

Relationship Between Umbilical Artery Doppler Investigations and Perinatal Outcome in Patients with HELLP Syndrome

Mekin Sezik1, Mehmet Okan Özkaya1, Hülya Toyran Sezik2, Elif Gül Yapar3, Hakan Kaya2

1Department of Gynecology and Obstetrics, Faculty of Medicine, Süleyman Demirel University, Isparta 2Clinics of Gynecology and Obstetrics , Isparta Maternity Hospital, Isparta 3Zekai Tahir Burak Maternity and Children’s Hospital, Ankara

Abstract Objective: To investigate the association between umbilical artery Doppler studies and subsequent perinatal mortality in preg- nancies with HELLP syndrome. Methods: Seventy-seven women with HELLP syndrome were retrospectively evaluated regarding systole/diastole (S/D) ratios and presence of absent or reverse end-diastolic flow (AREDF) on umbilical artery Doppler velocimetry. Sensitivity, specificity, pos- itive predictive value (PPV), and negative predictive value (NPV) of S/D ≥5 and AREDF during umbilical artery doppler investiga- tions for the prediction of perinatal mortality were calculated. Results: Cesarean section rate was 76% (n=57). Indications for cesarean delivery were obstetric causes in 6 women (10.5%) and or HELLP syndrome in the remaining patients. Prenatal loss rate was 18% (n=14). There were 4 (6.3%) neona- tal deaths out of 63 live-born infants. Sensitivity, specificity, PPV, and NPV of S/D ratio ≥5 on umbilical artery doppler velocime- try for predicting subsequent perinatal mortality was 85.7%, 66.7%, 36.3%, and 95.5%, respectively. Sensitivity, specificity, PPV, and NPV of the presence of AREDV on umbilical artery Doppler velocimetry for predicting subsequent perinatal mortality was 71.4%, 82.5%, 47.6%, and 92.8%, respectively. Conclusions: Umbilical artery Doppler investigations might be essential for evaluating the risk of perinatal mortality and timing of delivery in patients with HELLP syndrome. Normal umbilical blood flow in HELLP syndrome may demonstrate a low risk for perinatal mortality. Keywords: HELLP syndrome, umbilical artery, Doppler investigations, perinatal mortality.

HELLP sendromlu hastalarda umbilikal arter Doppler incelemesinin perinatal sonuçlarla iliflkisi Amaç: HELLP sendromlu hastalarda umbilikal arter Doppler inceleme sonuçlar›n›n, perinatal ve postnatal dönem fetal iyilik hali göstergeleri ile olan iliflkisini belirlemektir. Yöntem: Yetmifl yedi HELLP sendromlu hasta retrospektif olarak incelendi. Doppler incelemesinde Sistol/Diastol (S/D) oran› ile diastolik ak›m yoklu¤u (DAY) ve ters ak›m (TA) varl›¤› durumlar› araflt›r›ld›. Umbilikal arter Doppler incelemesinde S/D ≥5 ve DAY- TA olmas› durumunun perinatal mortaliteyi belirleyebilmesindeki sensitivite, spesifisite, pozitif prediktif de¤er (PPD) ve negatif prediktif de¤eri (NPD) hesapland›. Bulgular: Sezaryen oran› %74 (57) idi. Sezaryen ile do¤urtulanlardan 6 (%10.5)’s› obstetrik endikasyonlarla sezaryen olurken, geri kalanlarda endikasyonu fetal distress ve HELLP sendromuna ba¤l› maternal patolojiler oluflturmaktayd›. Toplam 77 hastan›n 14’ünde (%18) takip s›ras›nda prenatal kay›p gerçekleflti. Canl› do¤an 63 bebekten 4 (%6.3)’ü postpartum dönemde kaybedil- di. Umbilikal arter Doppler (UAD) S/D ≥5 olmas›n›n perinatal mortalite riskini belirlemedeki sensitivitesi %85.7, spesivitesi %66.7, PPD’i %36.3 ve NPD’i %95.5, UAD incelemesinde DAYTA olmas› durumunda ise sensitivite %71.4, spesifisite %82.5, PPD %47.6 ve NPD %92.8 olarak saptand›. Sonuç: HELLP sendromunun anne ve fetus aç›s›ndan tafl›d›¤› riskler göz önüne al›nd›¤›nda, bu gebelerde umbilikal arter Doppler incelemesi hem perinatal mortalite riskinin belirlenmesi, hem de do¤um zaman›n planlanmas› için önemlidir. Normal umbilikal arter Doppler ak›m› olmas› perinatal mortalitenin daha az olmas›n›n göstergesi olabilir. Anahtar Sözcükler: HELLP sendromu, umbilikal arter, Doppler inceleme, perinatal mortalite.

Correspondence: Dr. Mekin Sezik, Süleyman Demirel Üniversitesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Isparta e-mail: [email protected] Perinatal Journal • Vol: 13, Issue: 4/December 2005 199

Introduction tions, complete urine analysis, hemogram, hemat- Preeclampsia is one of the most important com- ocrit, thrombosis count examinations. UAD exami- plications of the pregnancy. Increase in the blood nations were practiced by the same ultrasonogra- pressure and in the preeclampsia is a phy devices (Medison Sonace 8800 and Kretz rule.1 HELLP syndrome is a multi system illness Technic Combison 420) for the patients diagnosed with hemolysis, raised liver enzyme level and low HELLP syndrome or developed HELLP syndrome thrombocyte count.2 HELLP syndrome is generally while their monitoring. In the Doppler examina- followed by preeclampsia and sometimes spo- tion, Sistol/Diastol (S/D) ratio and absent of dias- radic. Although define etiopathogenesis is not tolic flow (ADF) or reverse flow (RF) were known, genetic closure, abnormal placentation, searched. It was examined whether there was immunological pathologies and mother vascular chronic hypertension or diabetes in anamnesis, endothelium dysfunction can play a role.3,4 It is abortion history and chronic illness in family his- known that HELLP syndrome has a relationship tory. Patients were closely monitored beginning between raised perinatal mortality and fetal growth from the time hospitalized to the time they were retardation (FBG).5 discharged from hospital after birth. Non-stress test (NST) results, intrauterine fetal loss and post par- It is shown that in the examination of umbilical tum fetal loss ratios, convulsion ratios were deter- artery Doppler (UAD), in the case of the absent or mined while the monitoring. reverse end-diastolic flow (AREDF) , some unde- sired consequences can happen such as intrauter- In UAD investigation, sensitivity, specificity, ine growth retardation or perinatal mortality.6,7 But positive predictive value (PPD) and negative pre- there is not acidosis in all of the fetuses that dictive value (NPD) according to perinatal mortal- AREDF is detected.8 Today, evaluation of umbili- ity of detected S/D ≥5 and AREDF were calculated. cal blood stream plays an important role for the In addition, sensitivity, specificity, PPD and NPD in detection of feto-placental deficiency.9 Although determining the probability of non-reactive NST there are some studies evaluating umbilical blood for being S/D ≥5 in UAD investigation were calcu- changes for pregnant with FBG and preeclampsia, lated. Sensitivity, specificity, PPD and NPD for NST this parameter is not studied efficiently for the to determine perinatal mortality were determined. patients with HELLP syndrome. Student’s t-test was used for statistical analysis. The objective of our study is to investigate the association between UAD investigation results and Results determinants of perinatal and postnatal period fetal Average age of the patients included in the well being. study was 28.0≥ 6.5 years, gravida was 2.4≥1.8 and parity was 1.1 ≥1.4. Demographical characterizes Methods of the patients and laboratory and Doppler results 77 patients with HELLP syndrome who hospi- are shown in the Table 1. talized and cured in Department of Gynecology For 14 of the total 77 patients (18%), intrauter- and Obstetrics of Isparta Süleyman Demirel ine fetal loss was seen while monitoring. 38 of the University and Clinics Gynecology and Obstetrics patients (49.3%) of the patients had female fetus, of Maternity Hospital Isparta, and Ankara Zekai 39 of the (50.3%) of the patients had male fetus. 7 Tahir Burak Maternity and Children’s Hospital patients (9%) were diagnosed eclampsia. When were investigated retrospectively. Some of the anamneses were examined, 10 of the patients patients were affected by HELLP syndrome while (13%) had abortion history, 4 of the patients (5.2%) they were monitored for preeclampsia or hyper- had chronic hypertension and 9 of the patients tension reasoning from pregnancy and some other (11.7%) had hypertension history in the family. 50 patients were diagnosed as HELLP syndrome in patients (65%) in total were cured with antihyper- their first time (AST≥ 70 U/L, thrombotic count < tensive treatment and magnesium sulfate treat- 150000/≥ and LHD > 150 U/L). All of the patients ment. 20 of the patients (26%) had vaginal delivery had the routine physical examination and obstetric and the other had cesarean section. 6 of the ultrasonography, routine bio chemistry examina- patients (10.5%) having cesarean section reasoned 200 Sezik M et al., Doppler investigations and perinatal outcome in patients with HELLP syndrome

Table 1. Demographical characteristics, laboratory and Doppler results of the patients.

Age (years) 28.0 ± 6.5 Thrombosis (/µL) 141.2 ± 65.9 Gravida 2.4 ± 1.8 Sodium (mmol/dl) 138.4 ± 4.0 Parite 1.1 ± 1.4 Potassium (mmol/dl) 4.35 ± 0.5 Estimated fetal weight by the ultrasonography (g) 1606 ± 699 Calcium (mmol/dl) 8.45 ± 0.8 Systolic blood pressure (mmHg) 151.5 ± 15.3 Prothrombin Time (sec) 11.9 ± 1.04 Diastolic blood pressure (mmHg) 97.9 ± 10.0 Activity partial thromboplastin time (Sec) 34.2 ± 4.7 Hemoglobin (g/dl) 13.0 ± 2.02 Urine protein for 24 hours (g) 341 ± 193 Hemotocric (%) 39.0 ± 6.3 24 saatlik idrar protein (g) 2.85 ± 1.7 Fibrinojen (g/L) 455 ± 120.5 Serum protein (g/dl) 6.08 ± 0.8 AST (U/L) 102.5 ± 131.6 Serum albumin (g/dl) 2.98 ± 0.5 ALT (U/L) 75.6 ± 93.1 Serum creatinine (mg/dl) 0.92 ± 0.4 Serum bilirubin (mg/dl) 0.7 ± 0.5

Table 2. Values for determining perinatal mortality in the Table 3. Values to determine non-reactive NST for being study. S/D ≥5 umbilical artery Doppler.

Perinatal mortalite NST non -reactive

Sensitivity Specificity PPD NPD + – Total

Umbilical artery Doppler S/D ≥5 %85.7 %66.7 %36.3 %95.5 Umbilical Doppler S/D ≥5+26733 Umbilical artery DAYTA %71.4 %82.5 %47.6 %92.8 –103444 NST non-reactive %100 %71.4 %43.8 %100 Total 36 41 77

Sensitivity: %72.2, Specificity: %82.9, PPD: %78.8, NPD: %72.3 from obstetric inductions and the other from fetal intrauterine period.10 Abnormal Doppler results or distress and maternal factors of HELLP syndrome AREDF detection is related with bad perinatal (thrombocytopenia, increase of hepatic enzyme). 9 results.10 Perinatal mortality ratios reaching 80% of the patients (11.7%) gave the birth after the 36th was informed for AREDF developed cases.10 In the pregnancy week, other infants (88.3%) were Doppler investigation in intrauterine period, preterm delivery. 4 of the 63 live births (6.3%) besides umbilical artery, investigations of middle were lost after in the 2nd, 7th and cerebral artery and uterine artery can also be 15th days. made. In the studies of Lacin et al emphasized that Sensitivity, specificity, PPD and NPD to deter- UAD investigation results are better than middle mine perinatal mortality in cases of UAD S/D ≥5 cerebral artery in order to show perinatal results.11 and non-reactive NST is given in the table 2. Nevermore, it is stated that joint investigation of Sensitivity in determining the perinatal mortality bilateral uterine artery, middle cerebral artery and for being UAD S/D ≥5 is 87.5%, specificity is umbilical artery is better for the estimation of the 66.7%, PPD is 36.3% and NPD is 95.5 %, In case of results of perinatal.12 Joern et al investigated para- AREDF in UAD investigation, sensitivity is 71.4 %, meters of umbilical artery and bilateral uterine specificity is 82.5%, PPD is 47.6% and NPD is artery Doppler for FBG and/or preeclampsia or 92.8%. Sensitivity, specificity, PPD and NPD to HELLP syndrome patients in their studies.13 They determine probability of non-reactive NST is given detected that average birth week and birth weight in the Table 3. decrease significantly with a Doppler distortion in one of these veins. In the same study, in the cases Discussion of Doppler distortion of double side uterine artery, Doppler investigations are an important 90% problem can develop for risky pregnancies, method to evaluate fetal well being in the and this ratio is 72% for umbilical artery. Perinatal Journal • Vol: 13, Issue: 4/December 2005 201

Consequently, it is emphasized that investigation fetuses whose Doppler results is FBG to determine of bilateral uterine artery is an indispensable bad fetal condition is stated in the literature.17 method to determine fetal risk.13 In our study, fetal loss in intrauterine group In our study, UAD results, perinatal results and with AREDF is 47.6% (10 of the total 21 patients); NST were evaluated for the patients hospitalized neonatal mortality is 18.2% (2 fetuses from total 21 for HELPP syndrome or developed HELLP syn- patients). 12 of the fetuses in 32 patients with UAD drome while monitoring. We detected that AREDF S/D≥5 (37.5%) was lost in the intrauterine period, detection in the UAD investigation or S/D ≥5 have 3 of 20 live born fetuses (15%) was lost in the high sensitivity and specificity in order to deter- neonatal period. All of the 4 fetuses lost in the mine perinatal mortality. neonatal period were born in the 32nd pregnancy Spirilla et al searched umbilical artery S/D ratio week. Similar to our study as in our study, for and short term neonatal complications and neuro- patients with AREDF in UAD investigation, high logical developments for the first two years for 582 ratios of neonatal death was informed.16,18 In our monomer pregnancies (between 24-35 weeks). study, prematurity should be effective for neonatal 45.7% of the patients had also FBG diagnosis. In deaths, not the deficiency in Doppler examination. this group of patients, neonatal death or cerebral Indeed, AREDF detection in umbilical artery blood palsy (p: 0.001) was seen at the ratio of 3.4% when current may not have a separate effect on perina- S/D ratio is below 95 percent, 4.9% when it is 95 tal mortality after the chances such as FBG and percent and above and 17.3% when AREDF devel- premature is checked.19 The objective of the con- ops.7 In our study, 18% fetus of the mothers with servative approach to the cases with HELLP syn- HELLP syndrome is lost in intrauterine period. 10 drome is to decrease perinatal mortality by gaining of them (71.4%) had S/D ratio of ≥5.74% of the time with fetal maturation but in our study, 14 of patients had cesarean section, 89.5% of these had the fetuses (18%) were lost during the conserva- cesarean induction reasoned from fetal distress or tive treatment. The reason for that can be the low maternal problems from HELLP syndrome. pregnancy week of the cases and thus the insis- Venous Doppler investigations were done in tence for continuing conservative treatment. the literature. Ductus venosus is one of the most used veins for that. For 35 patients that AREDF In the literature, it is stated that UAD result are was detected in UAD, short term results of ductus not efficient to determine fetal well being and the venosus and effect to birth timing were investigat- seriousness of the preeclampsia (thrill, hyperten- ed. Short term results (such as artery pH, intra- sion level and other) but in the cases of deficient 20,21 ventricular bleeding, and mortality) showed that Doppler, ratio of FBG and cesarean increases. evaluation of ductus venosus Doppler pulsality HELLP syndrome is an important obstetric index is important. In the study, it is also impor- problem that can cause bad results both for the tant ductus venosus Doppler evaluation in order mother and the infant. Umbilical artery S/D ratio is to determine fetal results and pregnancy timing for ≥5 for approximately half of the pregnancies with the pregnancies with AREDF in umbilical artery HELLP syndrome. When umbilical artery S/D ratio current.14 is ≥5, high sensitivity and NPD ratios are detected In the literature generally patients with for the determination of perinatal mortality. When preeclampsia or FBG are studied in arterial AREDF is monitored in UAD examination, high Doppler investigations.15,16 UAD examinations are specificity and NPD ratios are detected for the not commonly used for the HELLP syndrome determination of perinatal mortality. Pregnancies cased in order to evaluate perinatal results. High with pathologic UAD examinations, pregnancies sensitivity (83%) and high specificity (80%) for the result earlier. 202 Sezik M et al., Doppler investigations and perinatal outcome in patients with HELLP syndrome

When the risks of HELLP syndrome are consid- or reversed end-diastolic flow velocity in Doppler umbilical ered for mother and infant, UAD investigation of artery waveforms. J Med Assoc Thai 1994; 77: 81-6. these pregnancies are important both for the 11. Laçin S, Demir N, Koyuncu F, Sayg›l› U, Göktay Y, Erten O. Predictivity of cerebral/umbilical artery Doppler ratio in determination of perinatal mortality risk and the severe preeclampsia. Gynecol Obstet Reprod Med 1998; 4: timing of birth. We believe that when not only the 17-20. evaluation of umbilical artery but also bilateral 12. Joern H, Funk A, Rath W. Doppler sonographic findings for uterine artery and middle cerebral Doppler evalu- hypertension in pregnancy and HELLP syndrome. J Perinat Med 1999; 27: 388-94. ation is made, perinatal and postnatal mortality 13. Joern H, Rath W. Comparison of Doppler sonographic and morbidity can be better determined. examinations of the umbilical and uterine arteries in high- risk pregnancies. Fetal Diagn Ther 1998; 13: 150-3. References 14. Muller T, Nanan R, Rehn M, Kristen P, Dietl J. Arterial and ductus venosus Doppler in fetuses with absent or reverse 1. Davey DA, MacGillivray I. The classification and definition end-diastolic flow in the umbilical artery: correlation with of the hypertensive disorders of pregnancy. Am J Obstet short-term perinatal outcome. Acta Obstet Gynecol Scand Gynecol 1988; 158: 892-8. 2002; 81: 860-6. 2. Martin JN Jr, Blake PG, Perry KG Jr, McCaul JF, HessLW, Martin RW. The natural history of HELLP syndrome: pat- 15. Baschat AA, Gembruch U, Reiss I, Gortner L, Weiner CP, terns of disease progression and regression. Am J Obstet Harman CR. Relationship between arterial and venous Gynecol 1991; 164: 1500-9. Doppler and perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol 2000; 16: 407-13. 3. Bussen S, Sutterlin M, Steck T. Plasma endothelin and big endothelin levels in women with severe preeclampsia or 16. Soregaroli M, Bonera R, Danti L, Dinolfo D, Taddei F, Val- HELLP-syndrome. Arch Gynecol Obstet 1999; 262: 113-9. camonico A, et al. Prognostic role of umbilical artery Dopp- ler velocimetry in growth-restricted fetuses. J Matern Fetal 4. Sezik M, Toyran H, Yapar EG. Distribution of ABO and Rh Neonatal Med 2002; 11: 199-203. blood groups in patients with HELLP syndrome. Arch Gyne- col Obstet 2002; 267: 33-6. 17. Ertan AK, Wagner S, Hendrik HJ, Tanriverdi HA, Schmidt 5. Sibai BM. The HELLP syndrome (hemolysis, elevated liver W. Clinical and biophysical aspects of HELLP-syndrome. J enzymes, and low platelets): much ado about nothing? Am Perinat Med 2002; 30: 483-9. J Obstet Gynecol 1990; 162: 311-6. 18. Karsdorp VH, van Vugt JM, van Geijn HP, Kostense PJ, Ar- 6. Kaya F, Özcan T, Kaya N, Do¤an MM, Dan›flman N, Gök- duini D, Montenegro N, et al. Clinical significance of absent men O. Yüksek riskli gebelikte umbilikal doppler analiz so- or reversed end diastolic velocity waveforms in umbilical nuçlar› ile perinatal prognoz iliflkisi. T Klin Jin Obstet 1998; artery. Lancet 1994; 344: 1664-8. 8: 122-5. 19. Sezik M, Tuncay G, Yapar EG. Prediction of adverse neona- 7. Spinillo A, Montanari L, Bergante C, Gaia G, Chiara A, Faz- tal outcomes in preeclampsia by absent or reversed end- zi E. Prognostic value of umbilical artery Doppler studies in diastolic flow velocity in the umbilical artery. Gynecol Obs- unselected preterm deliveries. Obstet Gynecol 2005; 105: tet Invest 2004; 57: 109-13. 613-20. 20. Todros T, Ronco G, Fianchino O, Rosso S, Gabrielli S, Val- 8. Nicolaides KH, Bilardo CM, Soothill PW, Campbell S. Ab- secchi L, et al. Accuracy of the umbilical arteries Doppler sence of end diastolic frequencies in umbilical artery: a sign flow velocity waveforms in detecting adverse perinatal out- of fetal hypoxia and acidosis. BMJ 1988; 297: 1026-7. comes in a high-risk population. Acta Obstet Gynecol Scand 9. Gagnon R, Van den Hof M; Diagnostic Imaging Committee, 1996; 75: 113-9. Executive and Council of the Society of Obstetricians and 21. Bush KD, O'brien JM, Barton JR. The utility of umbilical ar- Gynaecologists of Canada. The use of fetal Doppler in obs- tery Doppler investigation in women with the HELLP tetrics. J Obstet Gynaecol Can 2003; 25: 601-14. (hemolysis, elevated liver enzymes, and low platelets) syn- 10. Tannirandorn Y, Phaosavasdi S. Significance of an absent drome. Am J Obstet Gynecol 2001; 184: 1087-9. Perinatoloji Dergisi • Cilt: 13, Say›: 4/Aral›k 2005 203

Misoprostol for Second and Third-Trimester Labor Induction In Women with Previous Cesarean Delivery

Halil Aslan, Altan Cebeci, Yavuz Ceylan

Perinatology Unit, Bak›rköy Training and Research Hospital for Gynecology, Obstetrics and Pediatrics, ‹stanbul

Abstract Objective: To evaluate the use of misoprostol in second and third trimester labor induction in women with previous cesarean delivery. Methods: Women with previous cesarean delivery and normal controls seen for second and third trimester labor induction were randomly assigned to receive either misoprostol vaginally 50 µg or 100 µg every 6 hours until active phase of labor achieved. Primary outcome measures were uterine rupture, induction-delivey interval, vaginal delivery at 24 hours. Statistical analysis was performed with the ANOVA for continous variables and the chi square and Fisher exact test for categorical variables. P<0.05 was considered significant. Results: Three hundred and twenty three were randomised, with 67 with prior cesarean section and 256 controls. The two groups were comparable with respect to gestational age, birth weight, preinduction cervical length and total misoprostol dose. The mean induction-delivery interval was significantly longer for the prior cesarean group (61.9 ± 7.71 hours vs 26.3 ± 1.45 hours, p<0.001). Significantly more women in the control group were delivered within 24 hours (p<0.001). No uterine rupture was detected in the previous cesarean group. Conclusion: In second and third trimester labor induction, the use of misoprostol in women with previous cesarean delivery was not associated with an excess of complications, side effects and cesarean delivery rates. Keywords: Misoprostol, previous cesarean delivery, labor induction.

Eski sezaryenli kad›nlarda II. ve III. trimesterde misoprostolle do¤um indüksiyonu: prospektif kontrollü çal›flma Amaç: Eski sezaryenli olgularda ikinci ve üçüncü trimesterde do¤um indüksiyonu için misoprostol kullan›m›n› de¤erlendirmek. Yöntem: Do¤um indüksiyonu nedeniyle de¤erlendirilen eski sezaryenli ve uterin skar› bulunmayan kontrol grubu 50 ve 100 µg misoprostol dozlar› için randomize edildi. Do¤umun aktif faz›na kadar 6 saat arayla vagen arka forniksine 50 ya da 100 µg mi- soprostol tablet uyguland›. Olgular uterin rüptür, indüksiyon-do¤um aral›¤› ve 24 saatte vaginal do¤um gibi sonuçlar yönünden de¤erlendirildi. ‹statistik analiz SPSS 10.0 program› ile sürekli de¤iflkenler için ANOVA ve kategorik de¤iflkenler için ki kare ve Fis- her kesin olas›l›k testi ile yap›ld, p<0.05 anlaml› olarak kabul edildi. Bulgular: 67’si eski sezaryenli 256’s› kontrol olmak üzere 323 gebe iki ayr› misoprostol dozu için randomize edildi. Her iki grup gebelik haftas›, do¤um a¤›rl›¤›, indüksiyon öncesi servikal uzunluk ve toplam misoprostol dozu aç›s›ndan benzerdi. Ortalama in- düksiyon-do¤um aral›¤› eski sezaryenli olgularda belirgin olarak uzun bulundu (61.9 ± 7.71 saat; 26.3 ± 1.45 saat, p<0.001). 24 saat içinde do¤um oran› kontrol grubundaki gebeler de anlaml› flekilde daha fazlayd› (p<0.001). Eski sezaryenli grupta uterin rüptür görülmedi. Sonuç: ‹kinci ve üçüncü trimesterde eski sezaryenli olgularda misoprostol do¤um indüksiyonu komplikasyon, yan etki ve sezar- yen do¤um oranlar› yönünden kontrol grubuna göre farkl›l›k göstermemifltir. Ancak indüksiyon-do¤um aral›¤› eski sezaryenli ol- gularda belirgin flekilde uzun bulunmufltur. Anahtar Sözcükler: Misoprostol, eski sezaryen, do¤um indüksiyonu.

Correspondence Dr. Halil Aslan Bak›rköy Kad›n Do¤um ve Çocuk Hastal›klar› E¤itim ve Araflt›rma Hastanesi, Perinatoloji Ünitesi, ‹stanbul e-mail: [email protected] 204 Aslan H, Cebeci A, Ceylan Y. Misoprostol for Second and Third-Trimester Labor Induction In Women

Introduction groups as old cesarean section and control By increasing of prenatal ultrasonographic groups and they were randomized for 50 and 100 microgram vaginal misoprostol application. The diagnostic possibilities, determination of fetal induction was started with 50 microgram for the abnormalities before birth confront us the ending patients admitted to clinic on odd days of the of pregnancy in lethal or severe fetal abnormalities month and 100 microgram misoprostol for the as a serious choice.1 As similar, it is also necessary patients hospitalized on even days of the month. to ending the pregnancy in pregnancies compli- According to randomization divided tablets of 50 cated with intrauterine fetal death (IUFD). In or 100 microgram misoprostol tablets are placed recent years, cesarian section ratios were also to the posterior vaginal fornices every 6 hours. increased quickly in our country as in the world.2,3 Cervices length was measured by transvaginal We confront this as an increase in pregnancy ter- ultrasonography prior to this transaction and mination and delivery induction necessity in old Bishop scores were recorded by vaginal exami- cesarean section cases because of fetal abnormali- nation. Following misoprostol dose was not ty or IUFD. It is not clear that what is the most administered to patients that determined in active appropriate induction method in this type of cases. phase. Additional methods such as extra-amniot- Misoprostol is a synthetic prostaglandin E1 analog ic rivanol application by transcervical Foley and it is used widely in second trimester pregnan- catheter, oxytocin administration or increase in cy terminating and delivery induction.4,5 In the lit- the misoprostol dose is applied to the cases that erature, there is no sufficient study related to effi- birth was not occurred within 48 hours during the cacy and reliability of delivery induction in old whole study period. Parameters such as demo- cesarean section cases. For this reason, we per- graphic data related to cases, pregnancy week, formed a randomized prospective study to investi- baby birth weight, induction-birth interval, total gate the reliability and efficacy of misoprostol in misoprostol dose, induction indication, side old cesarean section cases in II. and III. trimesters effect, additional method usage, vaginal delivery in our unit in 24 hours and complications due to intervention (uterine rupture, causing Methods transfusion and placental retention) were record- ed. Statistical analyses with SPSS 10.0 was made This randomized controlled prospective study with using ANOVA for numeric variations and chi is performed between November 2001 and March square or Fisher accurate probability test for cat- 2005 dates at Perinatology Clinic. During the egorical variations. study pregnancy termination and delivery induc- tion is performed using 4 different misoprostol (Cytotec, Ali Raif, TR) doses in 62 pregnant Results because of fetal abnormality, IUFD and severe 67 cases (20.7%) accepted to study were old preeclampsia. Pregnancy termination decision cesarean section. 172 cases (53.3%) because of because of fetal abnormality is taken at a council fetal abnormality, 120 cases (37.2%) because of of branch specialists of obstetrics and gynecolo- IUFD and 31 cases because of severe preeclamp- gy, pediatric surgery and chiefly pediatric sia were administered delivery induction with Cardiology, developmental neurology, pediatric misoprostol or were taken indication of pregnancy nephrology and neonatology and also with the termination. There was not observed any differ- participtation of the family. Study is approved by ence about maternal age between old cesarean ethic committee and informed acknowledgement section cases that applied induction with miso- form is taken from all of the pregnants. 238 out of prostol and control groups. Despite this, it was 562 misoprostol induction used pregnants were observed that parity was significantly high in old excluded out of study because they were belong cesarean section group as expected (p<0.001) to 200 and 400 µg misoprostol protocol, and one when compared to control group. Pregnancy age pregnant was excluded because she had previous was calculated based upon the last menstruation birth by classic incisional cesarean section. date (LMD) and if LMD is not known it was calcu- Residual of 323 pregnants were divided into two lated based upon early prenancy ulrasonography. Perinatoloji Dergisi • Cilt: 13, Say›: 4/Aral›k 2005 205

Average pregnancy age was 24 weeks during birth cases, it is determined in 2 cases (2.9%) postpar- for both two groups. There was no significant dif- tum bleeding necessitating blood transfusion and ference between old cesarean sectio pregnants that in 2 cases (2.9%) placental retention. It is strange were administered misoprostol induction and con- that there exists one case (0.3%) of uterine rupture trol group about numerical variations such as birth due to delivery induction with misoprostol in con- weight, Bishop score, cervices length before trol group. Furthermore, there is 3 cases (1.1%) of induction and total misoprostol dose used. placental retention in control group. It is not found Although mean time from induction to birth was any significant difference about complications due significantly longer in cases with old ceaserean to misoprostol between two groups. sectio (61.9 ± 7.71 hours) than control group (26.3 ± 1.45 hours) (p<0.001). 319 (98.8%) of 323 preg- nants included in the study pregnancy ended with Discussion vaginal route. There was no difference about vagi- There is a marked acceleration in cesarean sec- nal deliveries after induction between two groups. tios today.2 Its one of natural reflections to the When the probability of vaginal delivery in first 24 obstetrical applications is increasing in require- hours after induction is examined it is observed ment of pregnancy termination and delivery induc- that 143 pregnant (44.3%) gave a birth after 24 tion in pregnants with old cesarean section. There hours. When the ratios of vaginal delivery in 24 are limited number of studies in literature con- hours is compared between two groups, it is found cerning efficacy and safety of delivery induction in that this ratio was significantly low in old cesarean old cesarean sectio cases.6-10 Misoprostol is a section when compared to control group prostaglandine E1 analogue and is started to be (p<0.001). When two different misoprostol doses (50 and 100 µg) administered to old cesarean sec- used in an increasing frequency with the aim of 4,5 tion and control group is examined, it is obvious delivery induction. Generally, it is mostly found that 100 µg misoprostol protocol was used signifi- studies related to termination of II. trimester preg- cantly more in control group (Table 1). nancies with misoprostol.6-9, 11 In our study, it is a While there is no side effect in 92.9% of cases salient characteristic that pregnancy week is due to misoprostol, in 17 cases (5.3%) nausea- greater than 28 weeks in 30% of cases. However vomitting, in 4 cases (1.2%) fever and in 2 cases vaginal delivery ratio of 98.8% we obtained is con- (0.6%) diarrhea are determined. There is no signif- sistent with the ratios reported in previous similar icant difference about side effects due to miso- studies (99.4% for II. trimester pregnancy termina- prostol usage between groups. Additional method tion; 86.9 % for delivery induction at term).7,12 One is used in 49 cases (15.2%) because birth didn’t of the results obtained from our study is induction- occur within 48 hours after induction. Additional birth interval and >24 hours vaginal delivery rates method is significantly more used in old cesarean are found significantly high in old cesarean section section cases according to control group cases induced with misoprostol. When looked at (p<0.001). When complications due to misoprostol myometrial contractility and cervical maturation; it induction are evaluated in old cesarean section is obvious that suggesting a mechanism explaining

Table 1. Results concerning nominal measurements.

Old sectio Control OR 95% P value n (%) n (%) confidence interval

Multiparity 65 (100.0) 128 (49.8) 32.7 (7.85-136.6) <0.001 Active phase success in 12 hours 38 (56.7) 157 (61.0) 0.83 (0.48-1.43) 0.51 Misoprostol dose (100 µg) 36 (53.7) 208 (80.9) 0.27 (0.15-0.48) <0.001 Vaginal delivery (<24 saat) 23 (34.3) 158 (61.4) 0.32 (0.18-0.57) <0.001 Vaginal delivery (toplam) 65 (97.0) 255 (99.2) 3.92 (0.54-28.38) 0.19 Additional method requirement 20 (29.8) 29 (11.2) 3.34 (1.74-6.41) <0.001 206 Aslan H, Cebeci A, Ceylan Y. Misoprostol for Second and Third-Trimester Labor Induction In Women

the late response of scarred uterus to misoprostol induction in old cesarean sectio cases was that all induction is very hard. When we limited the analy- of the cases were <24 pregnancy week. Kayani et sis to evaluating the succession of entering to the al8 reported the uterine rupture risk related to active phase of delivery action in cases induced induction is between 1-5% and determined that with misoprostol in 12 hours because of that rea- risk of uterine rupture related to delivery induction son, the obtained result indicates that there is no in old cesarean section cases who had not vaginal difference between both groups. This makes us to delivery previously was higher. think that real prolongation in induction-birth interval occurs after entering the active phase in Conclusion old cesarean section cases. Using additional method in old cesarean section cases much more This study ensured the evaluation of delivery also supports this. It must don’t forget that imple- induction with misoprostol in old cesarean section menters may have a prejudice of choice as not cases in same center even so at different dates and administrating the next dose of misoprostol to the with different methodologies. In conclusion, com- old cesarean section group although pregnant has plication, side effect and vaginal birth rates are not entered to active phase with worry of rupture. similar to the control group in delivery induction But, the most important thing is significantly more with misoprostol in old cesarean section cases usage of 100 µg misoprostol protocol in control because of fetal abnormalities and IUFD in II. and group according to old cesarean section group. III. trimesters but, it is understood that induction- birth interval is longer in old cesarean section The most severe complication is uterine rupture in old cesarean section cases administered delivery cases. There is need for randomized controlled induction in second or III. trimester.13 There is prospective studies including sufficient number of found a few data in literature about results and cases in order to obtain reliable evidences about complications of medical pregnancy termination effect of delivery induction with misoprostol in old and delivery induction in old cesarean section cesarean section cases to the rate of uterine rup- cases. It is not known true incidences related to ture. complications such as uterine rupture or hysterec- tomy. It is reported that incidence of uterine rup- References ture following induction is 0.2% - 0.9% in litera- 1. Elsheikh A, Antsaklis A,Mesogitis S, Papantoniou N, Rodo- ture.14 However, heterogen structure of cases, dif- lakis A, Vogas E, et al. Use of misoprostol for the termina- ferences in rupture definition and classification, tion of the second trimester pregnancies. Arch Gynecol Obstet 2001; 265: 204-6. different induction methods and protocols are lim- 2. Koç I. Increased cesarean section rates in Turkey. Eur J iting the evaluation of uterine rupture incidence. Contracept Reprod Health Care 2003; 8: 1-10. 15 According to a study by Lydon-Rochelle et al to 3. Leitch CR, Walker JJ. The rise in cesarean section rate: the show the true increase in risk of uterine rupture same indication with a lower treshold. Br J Obstet Gynecol related to induction with prostaglandines, sample 1998; 105: 621-6. size of the study must be 10.000 women. 4. Kwon JS, Davies GAL, Mackenzie PV. A comparison of oral and vaginal misoprostol for induction of labor at term: a In our previous study that we evaluated miso- randomised trial. Br J Obstet Gyneacol 2001; 108: 23-6. prostol induction in old cesarean section cases, the 5. Has R, Batukan C, Ermifl H, Cevher E, Araman A, K›l›ç G, ‹b- uterine rupture incidence is reported as a high rahimo¤lu L. A comparison of 25 abd 50 µg vaginally ad- ratio of 9%.10 There was no uterine rupture in old ministered misoprostol for preinduction cervical ripening and cesarean section group in this study and it can be labor induction. Gynecol Obstet Reprod Med 2000; 6: 171-4. explained with factors such as high misoprostol 6. Dickinson JE. Misoprostol for second-trimester pregnancy dose used in previous study, greater pregnancy termination in women with a prior cesarean delivery. Obs- tet Gynecol 2005; 105: 352-6. week, oral misoprostol maintenance protocol, lack of experience concerning misoprostol induction. 7. Daskalakis GJ, Mesogitis SA, Papantoniou NE, Moulopoulos GG, Papapanagiotou AA, Antsaklis AJ. Misoprostol for sec- 7 Daskalakis et al showed that the main cause for ond trimester pregnancy termination in women with prior the low risk of rupture related to misoprostol cesarean section. BJOG 2005; 112: 97-9. Perinatoloji Dergisi • Cilt: 13, Say›: 4/Aral›k 2005 207

8. Kayani SI,Alfirevic Z. Uterine rupture after induction labor 12. Boulot P, Hoffet M, Bachelard B. Late vaginal abortion af- in women with previous cesarean section. BJOG 2005; 112: ter previous cesarean birth: potential for uterine rupture. 451-5. Gynecol Obstet Invest 1993; 36: 87-90. 9. Dodd J, Crowther C. Induction of labor for women with a 13. Wing DA, Lowett K, Paul RH. Disruption of prior uterine in- previous cesarean birth: A systematic review of the litera- cision following misoprostol for labor induction in women ture. Aust N Z J Obstet Gyneacol 2004; 44: 392-5. with previous cesarean delivery. Obstet Gynecol 1998; 91: 10. Aslan H, Unlu E, Agar M, Ceylan Y. Uterine rupture as- 828-30. sociated with misoprostol labor induction in women with 14. American College of Obstetricians and Gynecologists. previous cesarean delivery. Eur J Obstet Gynecol Reprod Vaginal birth after previous cesarean delivery. Washington: Biol 2004; 113: 45-8. The College, 1998: 1-8. ACOG Practice Patterns Bulletin 11. Bebbington MW, Kent N, Lim K, Gagnon A, Delisle MF, Tes- No. 2. sier F, Wilson D. A randomized controlled trial comparing 15. Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP. Risk two protocols for use of misoprostol in midtrimester preg- of uterine rupture during labor among with a prior cesare- nancy termination. Am J Obstet Gynecol 2002; 187: 853-7. an delivery. N Engl J Med 2001; 345: 3-8. 208 Perinatal Journal • Vol: 13, Issue: 4/December 2005

Vaginal Birth After Cesarean Section: Is It Safe?

Emre Sinan Güngör, Egemen Ertafl, Perran Moröy, fievki Çelen, Nuri Dan›flman, Leyla Mollamahmuto¤lu

Clinics of Gynecology of Obstetrics, Dr. Zekai Tahir Burak Gynecological Hospital, Ankara

Abstract Objective: Our goal was to analyse the effects of trial of labor on fetal and maternal outcomes among women with single pre- vious lower segment cesarean delivery. Methods: 124 patients following a single prior cesarean delivery were selected prospectively for trial of labor between 1.1.2002- 30.4.2004. The inclusion criterias were, single and alive fetuses with vertex presentation, estimated fetal weight lower than 4000 g and greater than 28 weeks pregnancies’ and whose cervical effacement was 80% and dilatations over 5 cm at first examination. The patients who had cephalopelvic disproportion or classic uterine incision and whose previous indication was cephalo-pelvic disproportion were excluded from the study. During trial of labor induction was not used and the labor was fol- lowed up by continuous external cardiotocography. Results: The mean age of the cases was 27.4 ± 4.47 years, the mean gestational week was 33 ± 4 weeks, and the mean fetal weight was 2312 ± 410 g. At admission the mean servical dilatation was 4.68 ± 1.3 cm. In one case complete and in two cases partial uterine rupture from previous scar tissues occurred and immediate laparatomy was performed. The overall rate of uter- ine rupture was in %2.4 of the cases. Perinatal morbidity was established to be 13%, without any perinatal mortality. Conclusion: In view of the fact that primary cesarean rates can be reduced if their actual indications are considered, vaginal birth after single cesarean may be considered as an amenable and acceptable method in tertiary clinics with adequate facilities for the mother and the newborn in carefully selected cases. Keywords: Vaginal birth, cesarean section, uterine rupture.

Sezaryen sonras› vajinal do¤um: güvenli midir? Amaç: Alt segment transvers uterin insizyon ile geçirilmifl tek sezaryen operasyonu olan olgularda, vaginal do¤umun, fetal ve maternal prognoz üzerine olan etkisinin araflt›r›lmas›. Yöntem: 1.1.2002-30.4.2004 tarihleri aras›nda geçirilmifl tek sezaryen tan›s›yla takip edilen olgulardan vaginal yoldan do¤um uy- gulanmak üzere seçilen 124 olgu üzerinde prospektif olarak yürütüldü. Çal›flmaya tek canl› bafl gelifli fetusu olan, tahmini fetal a¤›rl›¤›n 4000 g alt› olan, kemik pelvis darl›¤› olmayan, 28. gebelik haftas›ndan büyük ve ilk muayenelerinde servikal silinmesi %80, servikal dilatasyonlar› 5 cm üzerindeki olgular dahil edildi. Klasik uterin kesi operasyon kay›t notu olan ve ilk sezaryen en- dikasyonu bafl pelvis uygunsuzlu¤u olan olgular çal›flmaya dahil edilmedi. Do¤um eylemi eksternal olarak sürekli monitorize fle- kilde takip edildi ve oksitosin ile do¤um indüksiyonu uygulanmad›. Bulgular: Sezaryen sonras› vajinal do¤um (SSVD) yapt›r›lan hastalar›m›z›n yafl ortalamas› 27.4 ± 4.47, ortalama gebelik haftala- r› 33 ± 4 hafta, ortalama bebek a¤›rl›¤› 2312 ± 410 g olarak saptand›. Hastalar›n kabulü s›ras›nda pelvik muayenelerinde;ortala- ma servikal aç›kl›klar› 4.68 ±1.3 cm ve silinmeleri ise > %75 olarak gözlendi. Bir olguda alt segment eski uterin skar yerinde komp- let rüptür, 2 olguda ise parsiyel rüptür tespit edildi ve acil laparotomiye al›nd›. Post operatif takip sorunsuzdu. Tüm olgular›m›z- daki rüptür oran› %2.4 idi. 16 yenido¤an solunum s›k›nt›s› nedeniyle yenido¤an ünitemizce konsülte edildi. Perinatal morbidite %13 olarak saptand›. Perinatal mortalite gözlenmedi. Sonuç: Primer sezaryen oranlar›n›n gerçek endikasyonlar›n kullan›lmas› ile azalt›labilece¤i gerçe¤inden hareketle, ‘sezaryen son- ras› vajinal do¤um’; dikkatli seçilmifl olgularda, anne ve yenido¤an için yeterli donan›m ve bak›m koflullar›n›n oldu¤u tersiyer re- ferans kliniklerinde uygulanabilir ve kabul edilebilir bir yöntem olarak görülmektedir. Anahtar Sözcükler: Vajinal do¤um, sezaryen uterus rüptürü.

Correspondence: Dr. Emre Sinan Güngör, Dr. Zekai Tahir Burak Kad›n Hastanesi, Kad›n Hastal›klar› ve Do¤um, Ankara e-mail: [email protected] Perinatal Journal • Vol: 13, Issue: 4/December 2005 209

Introduction abnormal labor progress were excluded from the For the first time, Edwin B. Cragin declared that study. the cases having one time cesarean section should For the pregnancies older than 28th pregnancy have the cesarean section in their following preg- week, cases having cervical effacement of 80%, nancy.1 Although there have been developments in cervical dilatations above 5 cm are included in the obstetrical practice until that years, the ques- the study. Under 28th week, early phases of the tion that in which way a patient having a cesarean pregnancy is included in the study. Patients under section previously should delivery is not yet 26th pregnancy week are not included in the answered. study. In this type of cases, vaginal birth is tried firstly as it is stated in our hospital protocol. The Ratio of cesarean section was 2-5% in 1950’s; it entire patient and patient’s caregivers were increased to 25-30% in 1990’s. However, neonatal informed by the work group and written permis- mobility and mortality ratio did not significantly sion approval was taken. There were obstetrician, decrease.2 In recent decade, many researchers sup- neonatolog and anesthesiologist in the team all ported the trail of vaginal birth for selected cases the time. in order to decrease the number of unnecessary abdominal births and increase the number of vagi- Trial of labor was followed continuously for nal births after cesarean section.3,4 Wide multi-cen- fetal heart trace and spontaneous uterine contrac- tered studies showed that the vaginal birth after tions externally. Amniotomy was not exercised cesarean section can reach success ratios of 60- until effacement and partiation was completed in 90% by selecting the correct patient. This applica- membrane intact cases. Induction with oxytocin tion, at the same time, decreased the hospitaliza- or augmentation was not implemented during the tion duration and ratio of .2,4 vaginal birth monitoring. Intervened birth was But, there are two fundamental problems for the practiced for the cased by vacuum and/or forceps trial of the method and practice of vaginal birth if it was needed. after cesarean section. These are the unsuccessful- Perineum, vagina, collum and cavum uteri ness of the vaginal birth and uterine rupture.5 check was done for case having vaginal birth. Uterine rupture is a serious complication which Perinatal goodness was evaluated by birth can cause the rise of fetal mortality and mobility.6 weight, APGAR scores of first and 5th minutes and The objective of this study is to analyze the clinical examinations of the newborns. New born effects of trial of labor on fetal and maternal out- cases showing respiratory distress findings and in comes among women with single previous lower neonatal care unit were determined and moni- segment cesarean delivery. tored. All of the data belonging to the cases were Methods evaluated on computer. Statistical analysis were discussed using SPSS (11.05 version) as descrip- This study is carried on 124 patients following tive and frequency analysis. a single prior cesarean delivery previously select- ed prospectively for trial of labor between 1.1.2002- 30.4.2004. The criteria to be included to Results the study were, single and alive fetuses with ver- Average age of the patients having trial of labor tex presentation, fetal weight lower than 4000 after cesarean (C/S) was 27.4±4.47, average preg- gram estimated by ultrasonography and Leopold nancy weeks was 33±4 weeks and average new- maneuver. The patients who had classic or T uter- born weight was 2312±410 gram (Table 1). ine incision and whose first cesarean indication Presentation of patients according to their preg- was caused by cephalo-pelvic disproportion and nancy weeks are presented in Table 2. 210 Güngör ES et al, Vaginal Birth After Cesarean Section: Is It Safe?

Table 1. Demographical and clinical characteristics of the Three patients gave birth with the vacuum. In cases. the routine uterine cavity investigation after the Value interval Mean±standard deviation birth, uterus ruptures were detected in the 2.4% Age 21 - 40 years 27.4 ± 4.7 years (3/124) of the cases. In one 29 years old case hav- Pregnancy week 26 - 40 weeks 33 ± 4 weeks ing a 3820 gram baby, complete rupture was Newborn weight 960 - 3820 g 2312 ± 410 g Activity duration 30 min - 20 hours 6.5 ± 2.4 hours detected, in 2 cases 27 and 30 years old having Dilatation 1 cm - 10 cm 4.68 ± 2.25 cm 3150 and 3460 gram baby, partial rupture was Gravida 2 - 7 3.59 ± 1.23 detected in the scar place of the bottom segment Parity 1 - 4 2.27 ± 0.54 old utter. These three cases in the 37th and 38th week of pregnancy were urgently taken to laparo- tomy. C/S inductions of these cases in their first Table 2. Distribution of the cases to the weeks. births were fetal distress. Rupture place was pri- marily remedied. These paints were transfused 2 Case units of new blood to each because of their low Pregnancy week N=124 % hemogram values (7.5 g/dl, 7 g/dl and 6.9 g/dl). 38 - 40 week 30 24.2 34 - 37 week 54 43.5 There were no early complications concerning 30 - 33 week 32 25.8 anesthesia and complication in the port operative 26 - 29 week 8 6.5 period. They were discharged from hospital with- Total 124 100 out ant problems. When the cases are evaluated according to their pregnancy intervals, it is seen that period between It is seen that 43.5% of the cases was in the the pregnancies were shorter than 20 months in pregnancy weeks of 34-37 weeks. When the cases 17.74% of the cases (22/124). 2.4% (3/124) of the decided to make vaginal birth after a cesarean is cases that we detected uterus rupture was also evaluated according to their first C/S inductions; included in that group. In addition, when new 53.22% of the cases positive construction stress born weights of the first cesarean birth and this test, 40.32% of the cases primigravid breech pre- vaginal birth is compared, it is seen that the weight sentation, 4.03% of the cases hypertension, preeclampsia, intrauterine growth restriction of the new born was more in the cases that we [IUGR], 5.41% of the cases twin pregnancy detected uterus rupture (2540±426 g to 3466±354 (breech-vertex presentation) (Table 3). g) p< 0.05. In the pelvic examination made when the APGAR score of the one hundred eight patients were accepted to the perinatology unit, (87.09%) newborn in the1st minute, 7 of them in average cervical Bishop scores was observed as the 7th minute were above 9. APGAR scores of the 7±2, average dilatation was 4.68±1.3 cm and aver- 1st and 5th minutes of 16 newborn were in order age effacement was > 75%. 2-6 and 4-8 limit. 16 newborns were consulted

Table 3. Distribution of first cesarean inductions to weeks.

First cesarean induction Pregnancy Fetal Breech Hypertension, Twin week distress presentation preeclampsia, IUGR pregnancy

N% N % N % N%

Weeks 38-40 12 9.73 10 8.06 5 4.1 3 2.4 Weeks 34-37 27 21.7 21 6.9 4 3.2 2 1.6 Weeks 30-33 13 10.4 11 8.8 4 3.2 4 3.2 Weeks 26-29 3 2.4 2 1.6 3 2.4 – – Perinatal Journal • Vol: 13, Issue: 4/December 2005 211

under newborn unit because of respiratory prob- Bujold et al stated that the rupture risks is 2-3 times lems. All of the cases were discharged from new- more for the cases whose interval between the two born unit postpartum 3rd day in good health. pregnancies is shorter than 24 months.12 In this Perinatal morbidity was detected as 13%. There study, both two cases developing ruptures had was no perinatal mortality observed. intervals between two pregnancies less than 20 months. To summarize, risk factors for uterine rup- Discussion tures are; cesareans practiced by cephalo-pelvic Vaginal birth after cesarean is a practicable disproportion inductions, lower vertical cesarean process for the available selected cases that the scar, macrocosmic fetus, advanced maternal age risk evaluation is done. Nevertheless, it is still dis- and probably the most important one the short 7 cusses that which birth type is safe for the new- interval between two pregnancies. Correlation born and whether the vaginal birth after cesarean between the increase in the birth weight and rup- (SSVD) is an acceptable risk. ture frequency is parallel to the literature. In our study complete rupture was in a case practicing As a result of recently studies, the dramatically 3820 g SSVD. It is stated that mother’s age being increase in the ratio of cesarean sections states that over 30 is concerned with the increase of uterus it is not a right strategy to make elective second rupture risk by 2.7 times.16 Ages of the patients in cesarean for every case. Flamm et al states that the our working group were between 21 and 40. But maternal mortality is lower in the cases of vaginal birth after cesarean.15 In addition, maternal compli- we did not detect this kind of complications for the cations resulting from surgery such as infection, cases over 30 years old. This consequence is simi- 17 hemorrhage, injury to internal organs, transfusion lar to the studies of Çal›flkan et al. needs will be less frequently met and the period of Developments in trial of labor should be close- hospital stay will shorten.4 ly followed and evaluated besides estimated fetal It is noted that in the first cesarean induction; weight by ultrasonography in our birth medicine when SSVD is tried in the cases having cephalo- practice. In addition, uterine scar ultrasonography pelvic disproportion and/or abnormal labor is a helpful method in order to determine the uter- progress in the event of induction apply, the ine rupture before the birth. Rozenberg et al stat- chance of success decreases.7 On the other hand, ed that the risk of uterine rupture and scar parti- Zelop et al state that the chance of success for tion is low if the bottom segments are thick. vaginal birth after cesarean increases if the esti- Negative predictive value of the uterine bottom mated fetal weight is below 4000 g.8 segment thickness determined less than 3.5 mm by ultrasonographically detection is denoted as The most important catastrophic consequence 13 of the SSVD is uterine rupture and the perinatal 99.3%. and maternal mortality and mortality resulting from If deletion or divergence stops during the dis- that. The ratio of perinatal morality is declared as sertation following for 2 hours or more, with the 3.5% and the ratio of perinatal morbidity is cesarean sections of these cases, cesarean ratios declared as 12% in the literature.9 In our study, increase by 7.9%, and the development of uterine perinatal mobility is not seen, and perinatal mor- rupture frequency decreases by 42.1%.14 bidity is 13% compatible with the literature. There are two applicable examination tools to In some studies of the literature, rupture ratios estimate the success probability of the vaginal birth are stated between 0.8% and 1.5%.10,11 In our serial, after cesarean. There are; the scoring system devel- rupture ratio is 2.4% being higher than the litera- oped by Flamm et al including the parameters of ture ratio.4,7 There are many studies evaluating the age, previous vaginal birth history, first cesarean factors increasing the rupture risk in the literature, induction, cervical partiality and deletion rates and 212 Güngör ES et al, Vaginal Birth After Cesarean Section: Is It Safe?

scoring system developed by Troyer including sim- labor after cesarean. Obstet Gynecol 2001; 97: 381-4. ilar parameters.8,15 7. Mohammed A, Mary S, Erika S, Jeffrey F, George M. The ef- fect of birth weight on vaginal birth after cesarean delivery As a consequence of this study, starting from success rates. Am J Obstet Gynecol 2003; 188: 824-30. the reality that primary cesarean ratios can be 8. Zelop CM, Shipp TD, Repke JT, Cohen A, Liebermen E. decreased by using real inductions, vaginal birth Outcomes of trial of labor following previous cesarean delivery among women with fetuses weighing >4000 g. Am after cesarean is an applicable and acceptable J Obstet Gynecol 2001; 185: 903-5. method for carefully selected cases in tertiary ref- 9. Cowan RK, Kinch RA, Ellis B, Anderson R. Trial of labor fol- erence clinics having adequate supplies and care lowing cesarean delivery. Obstet Gynecol 1994; 83: 933-6. conditions for the mother and newborn by taking 10. Caughey AB, Shipp TD, Repke JT, Zelop CM, Cohen A, Lieberman E. Rate of uterine rupture during a trial of labor the acceptance of the family. in women with one or two prior cesarean deliveries. Am J Obstet Gynecol 1999; 181: 872-6. References 11. Sims EJ, Newman RB, Hulsey TC. Vaginal birth after cesare- 1. Hashima JN, Eden KB, Osterweil P, Nygren P, Guise JM. an: To induce or not to induce. Am J Obstet Gynecol 2001; Predicting vaginal birth after cesarean delivery: a review of 184: 1122-4. prognostic factors and screening tools. Am J Obstet Gynecol 12. Bujold E, Menta SH, Bujold C, Gauthier RJ. Interdelivery in- 2004; 190: 547-55. terval and uterine rupture. Am J Obstet Gynecol 2002; 187: 2. Carroll CS, Magann EF, Chauhan SP, Klauser CK, Morrison 1199-202. JC. Vaginal birth after cesarean section versus elective repe- 13. Bretelle F, Cravello L, Shojai R, Roger V, D’ercole C, Blanc at cesarean delivery: Weight-based outcomes. Am J Obstet B. Vaginal birth following two previous cesarean sections. Gynecol 2003; 188: 1516-22. Eur J Obstet Gynecol 2001; 94: 23-6. 3. American College of Obstetricians and Gynecologists. Clini- 14. Hamilton EF, Bujold E, McNamara H, Gauthier R, Platt RW. cal management guidelines for obstetrics and gynecology Dystocia among women with symptomatic uterine rupture. vaginal birth after cesarean section. Washington (DC): The Am J Obstet Gynecol 2001; 184: 620-4. College; 1999. Practice bulletin No. 5. 15. Flamm BL, Geiger AM. Vaginal birth after cesarean delivery: 4. Kobelin CG. Intrapartum management of vaginal birth after cesarean section. Clin Obstet Gynecol 2001; 44: 588-93. an admission scoring system. Obstet Gynecol 1997; 90: 907-10. 5. Chauhan S, Martin JN, Henrichs CE, Morrison JC, Magann 16. Shipp TD, Zelop C, Repke JT, Cohen A, Caughey AB, EF. Maternal and perinatal complications with uterine rup- Lieberman E. The association of maternal age and sympto- ture in 142.075 patients who attempted vaginal birth after matic uterine rupture during a trial of labor after prior cesarean delivery: A review of the literature. Am J Obstet cesarean delivery. Obstet Gynecol 2002; 99: 585-8. Gynecol 2003; 189: 408-17. 17. Cal›skan E, Ozturk N, Gelisen O, Dilbaz S, Dilbaz B, 6. Laura G, Thomas DS, Amy C, Carolyn MZ, John TR, Ellice Haberal A. Vaginal birth after previous cesarean delivery L. Oxytocin dose and the risk of uterine rupture in trial of with unknown uterine incision. Artemis 2002; 3: 47-50. Perinatal Journal • Vol: 13, Issue: 4/December 2005 213

Retrospective Analysis of Multiple Pregnancies

Mahmut Erdemo¤lu1, Ahmet Kale1, Nurten Akdeniz1, Ahmet Yal›nkaya1, Y›lmaz Özcan1, Murat Yayla2

1Department of Gynecology and Obstetrics, Faculty of Medicine, Dicle University, Diyarbak›r 2Clinics of Gynecology and Obstetrics, Haseki Hospital, Istanbul

Abstract Objective: To evalute the multiple pregnancies who had delivered in our clinics retrospectively. Methods: Two hundred eighty three multiple pregnancies delivered were evaluated retrospectively between January 1999 and December 2004 at Obstetrics Department. The demographic characteristics, maternal age, parity, chorionicity, gestational weeks at delivery, presentation modes of fetuses, delivery modes, neonatal weight, fetal anomaly rate, cesarean rates and indi- cations, perinatal morbidity and mortality rates were evaluated .Statatistical analysis were evaluated with SPSS 10.0 S program. Results: 7674 deliveries occured in our clinic. 261 (3.4%) twin pregnancy and, 22 (0.29%) triplet pregnancy were found. Dichorionicity was 69.3% and monochorionicity was 30.7% in twin pregnancies. Cesarean section rate was 62.1% in twin and 68.2% in triplet pregnancies. Preterm labour was 23% and preeclampsia was 15.7% in twin pregnancies. Preterm labour was 30%, preeclampsia was 8% in triplet pregnancies. Fetal anomaly rate was 3.6%. Conclusion: The prevalence of multiple pregnancies has increased because of ovulation induction and assisted reproductive tech- nologies. Professionals should prevent multiple pregnancies due to increased maternal and fetal mortality and morbidity. Keywords: Multiple pregnancy, chorionicity.

Ço¤ul gebeliklerin retrospektif analizi

Amaç: Klini¤imizde do¤umu gerçekleflen ço¤ul gebelik olgular›n›n retrospektif analizini yapmakt›r. Yöntem: Klini¤imizde Ocak 1999 ile Aral›k 2004 y›llar› aras›nda do¤umu gerçekleflen toplam 283 ço¤ul gebelik olgusu retros- pektif olarak incelendi. Olgular›n yafl›, paritesi ve koryonisite durumlar›, do¤um an›ndaki gebelik haftalar›, fetuslar›n prezantas- yon flekilleri, do¤um flekilleri, do¤um a¤›rl›klar› belirlendi. Olgularda konjenital anomali oran›, sezaryen endikasyonlar›, perinatal morbidite ve mortalite oranlar› incelendi. ‹statistiksel de¤erlendirme SSPS 10.0 S paket program› ile yap›ld›. Bulgular: Klini¤imizde 7674 do¤um gerçekleflmifltir. Tüm do¤umlar içerisinden 261 (%3.4) ikiz ve 22 (%0.29) üçüz ço¤ul gebe- lik olgusu saptand›. Ço¤ul gebeliklerin 261’ini (%92.2) ikiz gebeliklerin oluflturdu¤u saptand›. ‹kiz olgular›n›n%69.3’ü dikoryo- nik,%30.7’sinin monokoryonik oldu¤u saptand›. ‹kiz gebeliklerin%62.1’si ve üçüz gebeliklerin%68.2’si sezaryen ile do¤um yap- m›flt›r. ‹kiz gebeliklerin%23’ünde erken do¤um eylemi,%15.7‘sinde preeklampsi üçüz gebeliklerde ise%30’unda erken do¤um eylemi,%8’inde preeklampsi saptand›. Konjenital anomali oran›%3.6 olarak saptand›. Sonuç: Son y›llarda yard›mc› üreme tekniklerinin yayg›nlaflmas› ile birlikte artan ço¤ul gebelikler beraberinde maternal ve fetal morbidite ve mortaliteye neden olmaktad›r. Bu nedenle yard›mc› üreme teknikleri ile u¤raflan profesyoneller ço¤ul gebelikleri en- gellemelidirler. Anahtar Sözcükler: Ço¤ul gebelik, koryonisite.

Correspondence: Dr. Ahmet Kale, Dicle Üniversitesi T›p Fakültesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, 21280 Diyarbak›r e-mail: [email protected] 214 Erdemo¤lu M et al., Retrospective Analysis of Multiple Pregnancies

Introduction ovulation induction because of infertility or in vitro There has been a significant increase in the fertilization and embryo transfer (IVF-ET). Ratios of incidence of multifetal pregnancies with wide- twin and triple pregnancies are found as 261 spread usage of ovulation induction assisted repro- (3.4%) and 22 (0.29%) consecutively among total deliveries in our clinic. ductive techniques and rate of multifetal pregnan- cies reached to 3% in recent years.1 Followings and Average pregnancy weeks at the moment of management of these pregnancies become impor- delivery is determined as 33±0.2 weeks in twin and tant because multifetal pregnancies are related to 32±0.7 weeks in triple pregnancies. It is deter- increased maternal and perinatal morbidity and mined that in 85.9% of twin cases birth occurred mortality.2 Most frequent causes of high perinatal before 37. week and most frequently between 33- morbidity and mortality in multifetal pregnancies 36 weeks and in 90.90% of triple pregnancies gave are difficult labour caused by presentation abnor- birth before 37 week and most frequently between malities, respiratory distress syndrome caused by 33-36 weeks. low birth weight and prematurity.3 Widespread It is determined that 69.3% of twin cases were usage of electronic fetal monitorization, obstetrical dichorionic, 30.7% were mono chorionic. It is ultrasonography and improvement of neonatal determined that presentation of twin pregnancies units ensured progresses in reducing of neonatal at birth was 38% vertex-vertex, 26.8% vertex-non- morbidity.4,5 vertex, 14.9% nonvertex-vertex, 20.3% nonvertex- Aim of this study is to make retrospective nonvertex (Table 1). analysis of multifetal pregnancies delivered in our clinic. Table 1. Presentation forms of twin pregnancies at delivery.

Methods Presentation n % A sum of 283 (3.69%) multifetal pregnancy Vertex-vertex 99 38.0 cases including 261 twin (3.4%) and 22 triple Vertex-nonvertex 70 26.8 Nonvertex-vertex 39 14.9 (0.29%) births among a total of 7674 births Nonvertex-nonvertex 53 20.3 occurred in our clinic from January 1999 to Total 261 100.0 December 2004 were investigated retrospectively. Ages, parity and chorionicity, pregnancy weeks at the moment of delivery, presentation form of fetus, According to the mood of delivery 62.1% of delivery moods, birth weights, congenital anomaly twin pregnancies were given birth by cesarean sec- rate, indication of cesarean section, perinatal mor- tion and 37.9% by vaginally. The most frequent bidity and mortality rates of the cases were exam- cesarean section indication of twin pregnancies ined. It is stated that chorionicity of cases is deter- were buttock presentation of before coming fetus mined by examination with prepartum ultrasonog- (27.8%) and transvers presentation (16%). It is raphy and examination of placenta macroscopical- determined that 68.2% of triple pregnancies were ly after birth. Being more than 15% weight differ- given birth by cesarean section and 31.8% by vagi- ence among fetuses is described as discordance. nally. It is determined that 45.5% of triple preg- SSPS 10.0 S package program is used for statistical nancies were the pregnancies resulted from infer- evaluation. tility treatment. The most frequent cesarean section indication of triple pregnancies was also elective (Table 2). Results It is determined that average weight of first 261 (92.2%) of multifetal pregnancies were newborn was 2065±02 g and second newborn was twin. It is found average ages of cases as 28.54 (16- 1972±64 g in twin pregnancies; 1660±45 g, 47), gravidas 3.30, parities 2.00. 187 (66.07%) of 1648±64 g, 1643±63 g consecutively in triple preg- multifetal pregnancy cases were multipares. It is nancies. Furthermore, 63.3% premature birth and determined that 10.25% of multifetal pregnancy 10.6% stillbirth is determined in multifetal preg- cases were constituted of pregnants conceived by nancies (Table 3). Perinatal Journal • Vol: 13, Issue: 4/December 2005 215

Table 2. Cesarean section indications in twin pregnancies. Table 4. Obstetrical problems in multifetal pregnancies.

Indications n % Obstetrical problems n %

Breech presentation 45 27.8 Preterm birth 69 41.1 Transvers presentation 26 16.0 Premature membrane rupture 24 14.3 Elective 24 14.8 Polyhydramniosis 10 6.0 Repeated cesarean sectio 22 13.6 Preeclampsia 41 24.4 Fetal distress 15 9.2 Eclampsia 5 2.9 Entanglement of umbilical cord 7 4.3 HELLP syndrome 5 2.9 Arrest of labour 6 3.7 Placental detachment 3 1.8 Foodling breech presentation 5 3.1 3 1.8 Placenta previa 3 1.9 Heart disease 2 1.2 Arm prolapse 3 1.9 Placenta previa 4 2.4 Advanced maternal age 3 1.9 Postpartum atonic bleeding 1 0.6 Face presentation 1 0.6 Postpartum pulmonary 1 0.6 Detachment 1 0.6 Conjoined twin 1 0.6

Discussion Multifetal pregnancy rates showed an increase Table 3. Fetal problems determined in multifetal pregnan- cies. parallel to the widespread usage of assisted repro- ductive techniques in recent years. In western Fetal problems n % communities multifetal pregnancies constitutes 3% Premature birth 119 63.3 of pregnancies.6 It is understood that ratios are Stillbirth 20 10.6 7-8 Intrauterine dead fetus 6 3.2 approaching these values also in our country. It Twin-to-twin transfusion syndrome 6 3.2 is found that twin rates reached to 25-30%, triple Intrauterine development retardness 17 9.1 rates to 5% and pregnancies with more fetus are to Congenital anomaly 20 10.6 0.5-1%.9 In our study, it is determined twin preg- nancy rate was 3.4%, triple pregnancy was 0.24% and 10.25% of multifetal pregnancies were treat- It is determined preterm delivery in 23%, pre- ment pregnancies. mature membrane rupture in 8.8%, placenta inser- tion anomaly in 1.9%, preeclampsia in 15.7%, As fetus number increases pregnancy period HELLP syndrome in 1.9%, intrauterine fetal death gets shorter. Approximately half of twins deliveries th in 2.3%, polyhydramniosis in 3.4%, gestational dia- at 36 week or earlier. Average birth week of triple betes in 0.8% and heart disease in 0.8% of the twin pregnancies was 33.5 week and 90% of them deliv- th nd pregnancies. It is determined preterm delivery in ers before 37 week, 24% before 32 and 8% th 10 30%, preeclampsia in 8%, eclampsia in 1%, early before 28 week. In our study, it is determined th membrane rupture in 11% of triple pregnancies 85.9% of twin cases are given birth before 37 (Table 4). pregnancy week. It is determined also 90.9% of th Congenital anomaly rate is determined as 3.6% triple cases are given birth before 37 and 45.5% nd (n=21). Among these congenital anomalies; 28.6% before 32 week. Most of our cases did not take hydrops (n=6), 23.8% neural system anomaly antenatal care and admitted to hospital in late (n=5), 23.8% genitourinary tract anomaly (n=5), stage of birth. Because of these reasons and also 14.2% extremity anomaly (n=3), 4.8% teratoma with presence of cases requiring delivery induction (n=1), 4.8% conjoined twins (n=1) were deter- like preeclampsia, eclampsia and HELLP syndrome mined. in high proportion, it caused our ratios got higher. It is determined that discordance ratio was 25% Vertex-vertex presentation is most seen in in twin pregnancies and 54% in triple pregnancies. twins.11 Usual approach in vertex-vertex presenta- Perinatal mortality rate is determined as 23% (9.2% tion cases is birth via normal vaginal tract and in twins, 24% in triples) in multifetal pregnancies cesarean section indications are like in single preg- and 12.6% of them were intrauterine mort fetal. nancies.12 In our cases vertex-vertex presentation 216 Erdemo¤lu M et al., Retrospective Analysis of Multiple Pregnancies

rate is determined as 58.6% and also it is deter- perinatal mortality with pregnancy week and low mined 50.5% of them is given birth via normal birth weight (p<0.001). vaginal tract and 49.5% of them with cesarean sec- Major malformations occur in 2% and minor tion. It is specified that birth with cesarean section malformations occur in 4% of twins.17 In our study, is safer in nonvertex-vertex, nonvertex-nonvertex congenital anomaly ratio is determined as 3.6% presentation cases. It is known that fetal mortality and it is compatible with the literature. is high in locked twin cases.13 It is determined that Furthermore, it is not different from our clinic’s before coming fetus was nonvertex in 35.2% of our general congenital anomaly ratio of 3.06%.18 cases and 93.5% of these cases were given birth by Incidence of transfusion syndrome from twin to cesarean section. It is preferred birth has to be per- twin is not definite but, one fourth of monochori- formed with cesarean section in nonvertex presen- onic twins shows some characteristics of that syn- 19 tation of before coming fetus in multifetal preg- drome. Twin to twin transfusion syndrome is nancies in our clinic. Cesarean section rate is determined in six of our cases and perinatal mor- tality is determined in these cases except two reported as 16-44% in twins.14 In our study, fetuses. Tan and his friends20 reported the con- cesarean section ratio of twin cases was 62.1% and joined twin ratio as 1/60.000. In our study, con- it is higher than literature. It grows out of because joined twin is determined in one of our case of our high ratio of nonvertex presentation of (1/7674) and both of fetuses that delivered by before coming fetus, our high ratio of complicated cesarean section became ex at postoperative 36th pregnants and preference of elective cesarean sec- hour. tion in treatment pregnancies. Discordance among birth weights in triple In the study of Buyru et al4, they found peri- pregnancies is three times higher than in twin natal mortality rate in newborn given birth by pregnancies and is a criteria of worst prognose.21 cesarean section lower than given birth via vaginal In our study, discordance among birth weights of tract and emphasized that presentation form does fetuses is determined 25% in twins and 54% in not effect mortality directly. In our study, it is triples. determined that in 8 cases (5%) of births by cesare- In multifetal pregnancies; it is seen an increase an section and in 17 cases (17.2%), babies with 0- in obstetric complications such as premature birth, 0 Apgar score were given birth. It is determined early membrane rupture, pregnancy anemia, preg- 60.2% of 118 cases that mortality seen in one week nancy toxicosis, congenital anomalies, abortus, early perinatal period is given birth by vaginal tract antepartum, intrapartum and postpartum bleed- and 39.8% by cesarean section. We assessed the ings.22 The most frequently seen obstetric problems higher fetal mortality rate in group given birth by in our cases are determined as preterm birth vaginal tract to intrauterine dead fetuses, fetuses 41.1%, early membrane rupture 14.3%, pregnancy with congenital anomalies and immature fetuses toxicosis (preeclampsia, eclampsia, HELLP) 30.2% are given birth mostly by vaginal tract. and other complications 14.4%. Coonrad et al23 Perinatal mortality is found 4 times higher in reported that preeclampsia is seen four times high- twin pregnancies compared to single pregnancies15 er in twin pregnancies compared to single preg- but, there are also studies suggesting there is no nancies. Mastrobatista et al24 reported that severe difference. Kilpatrick and his friends found the preeclampsia is seen as 23% in triple pregnancies perinatal mortality rates in single pregnancies as and 5% in twin pregnancies. In our study, 0.25% and in twin pregnancies as 0.11% which has preeclampsia ratio is determined 15.7% in twin a gestation age above 30 weeks.16 In our study, pregnancies as it is determined 9.09% in triple perinatal mortality in multifetal pregnancies is pregnancies. determined as 0.16%. Average birth weights of Increasing in the multifetal pregnancies, as a babies constituting perinatal mortality was 1085 result of becoming of assisted reproductive tech- grams in twins, 1031 grams in triples; average niques widespread, is causing preterm birth, pre- pregnancy weeks was 28 weeks in twins, 27 weeks maturity, early membrane rupture, low birth in triples. There is statistical significancy between weight, intrauterine development retardation and Perinatal Journal • Vol: 13, Issue: 4/December 2005 217

fetal anomalies and also increase in number of 10. Berkowitz RL, Lynch L, Stone J, Alvarez M. The current sta- individuals with anomalies in further life. tus of multifetal pregnancy reduction. Am J Obstet Gynecol 1996; 174: 1265-72. Considerable financial sources are spent for new- 11. Jakobovits AA. The abnormilities of the presentation in the born care as a consequent of multifetal pregnan- twin pregnancy and perinatal mortality. Eur J Obstet cies. We consider that preferring single pregnan- Gynecol Reprod Biol 1993; 52: 181-5. cies instead of multifetal pregnancies will be an 12. Chervenak FA, Johnson RE, Youcha S, Hobbins JC, Ber- appropriate choice to reduce the maternal and kowitz RL. Intrapartum management of twin gestation. Obs- fetal morbidity and mortality caused by multifetal tet Gynecol 1985; 65: 119-24. pregnancies and also to prevent the financial loss- 13. Hogle KL, Hutton EK, McBrien KA, Barrett JF, Hannah ME: es. Cesarean delivery for twins: A systematic review and metaanlysis. Am J Obstet Gynecol 2003; 188: 220. 14. Thompson SA, Lyons TL, Makowski EL. Outcomes of twin References gestations at the University of Colorado Health Sciences 1. Venture SJ, Martin JA, Curtin SC, Mathews TJ. Report of fi- Center, 1973-1983. J Reprod Med 1987; 32: 328-39. nal natality statistics, 1996. Monthly vital statistics report; 15. Mc Carthy B.J,Sachs B. P,Layde P.M . The epidemiology of vol 46, no. 11 (suppl) Hyaattsville, Maryland: National Cen- neonatal death in twins. Am J Obstet Gynecol 1981; 141: ter for Healt Statistics, 1998. 252-6. 2. Evans MI, Berkowitz RL, Wapner RJ Carpenter RJ, Goldberg 16. Kilpatrick SJ, Jackson R, Croughan-Minihane M. Perinatal JD, Ayoub MA, et al. ‹mrovement in outcomes of multifetal pregnancy reduktion with increased experience. Am J Obs- motrality in twins and singletons matched for gestational tet Gynecol 2001; 184: 97-103. age at 30 weeks. Am J Obstet Gynecol 1996; 174: 66-71. 3. ‹maizumi Y. A comparative study of twinning and triplet ra- 17. Cameron AH, Edwards JH, Derom R, Theiry M, Boelaert R: tes in 17 countries 1992-96. Acta Genet Med Gemello 1998; The value of twin surveys in the study of malformation. Eur 47: 10-4. J Obstet Gynecol Reprod Biol 1983; 14: 347-56. 4. Buyru F, Yüksel A, Demirören T, Kovanc› E, Mutafo¤lu T, 18. Yayla M, Gül T, Gürmüfl H, Nazaro¤lu H, Erden AC. Dicle Bengisu E: ‹kiz gebeliklerde perinatal mortalite. Kad›n Do- üniversitesindeki do¤umlarda konjenital anomali prevalan- ¤um Derg 1996; 12: 12-6. s›: 6 y›ll›k seri. Zeynep Kamil T›p Bülteni 1997; 29: 177-82. 5. Baldwin VJ. Anomalous development of twins . In Baldwin 19. Galea P, Skot JM, Goel KM. Feto- fetal transfusion syn- VJ, ed. Pathology of Multiple Pregnancy. New York: Sprin- drome. Arch Dis Child 1982; 57: 781-3. gier- Verlag, 1994: 169-97. 20. Tan KL, Goon SM, Salmon Y, Wee JH. Conjoined twins. Ac- 6. American College of Obstetricans and Gynecologists: Spe- ta Obstet Gynecol Scand 1971; 50: 373-80 cial problems of multiple gestation. Education Bulletin No: 21. Blickstein I Jacquez DL, Keith LG, A novel approach to in- 253, 1998. tertriplet birth weight discordance. Am J Obstet Gynecol 7. Kamac› M, Zetero¤lu fi, fiahin G, fiengül M, Gülümser S, 2003; 188: 1026-30. Bolluk G. Ço¤ul Gebeliklerde do¤um yöntemleri obstetrik komplikasyonlar› ve perinatal mortalite. Jinekoloji ve Obs- 22. Cruz AC. ‹kiz gebelik. Zuspan FB (ed). Current Therapy in tetrik Dergisi 2004; 18: 135-9. Obstetrics and Gynecology. 4th edt. (çev. ed Güner H). An- kara: Atlas Tic. Afi, 391-7, 1995. 8. Karl›k ‹, Kesim M Çal›flkan K, Koç G, ‹nan F. Klini¤imizde do¤um yapan ço¤ul gebeliklerin de¤erlendirilmesi. Perina- 23. Coonrad DV, Hickok DE, Zhu K, Easterling TR, Daling JR. toloji Dergisi 1996; 4: 83-7. Risk faktors for preeklampsia in twin pregnancies; A popu- lation-based chort stady. Obstet Gynecol 1995; 85; 645-50. 9. American Fertility Society, Society for Assisted Reproducti- ve Technology. Assisted reproductive technology in the 24. Mastrobattista JM, Skupski DW, Monga M, Blanco JD, United States and Canada: 1992 results generated from the August P. The rate of severe preeclampsia is increased in American Fertility Society/Society for Assisted Reproductive triplet as compared to twin gestations. Am J Perinatol 1997; Technologj Registry. Fertil Steril 1994; 62: 1121-8. 14: 263-5. 218 Perinatal Journal • Vol: 13, Issue: 4/December 2005

The Predictive Value of Middle Cerebral Artery Peak Systolic Velocity in Repeated Intrauterine Transfusion: A Case Report

Yeflim Bülbül Baytur, Ümit Sungurtekin ‹nceboz, Tayfun Özçak›r, Y›ld›z Uyar, Hüsnü Ça¤lar

Department of Gynecology and Obstetrics, Faculty of Medicine, Celal Bayar University Manisa

Abstract Objective: Middle cerebral artery peak systolic velocity has been used for predicting fetal anemia and timing for first and sec- ond cordocentesis. However, predicting value of middle cerebral artery peak systolic velocity after multiple intrauterine transfu- sions is unknown. Case: Thirty-one-year-old woman, gravida 5, para 4, with Rh-isoimmunization who were presented with fetal hydrops at her 24th week’s of gestation was undergone intrauterine transfusion four times between 24 and 31 weeks of gestation. Doppler exam- ination of middle cerebral artery peak systolic velocity was performed before and after cordocentesis during each procedure. There was an inverse correlation between fetal hemoglobin values and Doppler measurements of middle cerebral artery. Result: The timing of intrauterine transfusion is traditionally determined by fetal hemoglobin measurement from cord blood of the fetus. Middle cerebral artery peak systolic velocity has been found useful for determining fetal hemoglobin level in the severely anemic fetuses after first and second transfusion. It may also be an appropriate non-invasive alternative in repeated transfusions for the timing of transfusion. Keywords: Rh-isoimmunization, middle cerebral artery, peak systolic velocity, intrauterine transfusion, severe anemia.

Tekrarlayan intrauterin transfüzyonlarda orta beyin arter tepe sistolik h›z›n›n de¤eri: Bir olgu sunumu

Amaç: Orta beyin arter tepe sistolik h›z›, fetal anemi tahmininde ve ilk ve ikinci kordosentezlerin zamanlamas›nda kullan›lmakta- d›r. Ancak, tekrarlayan çoklu intrauterin transfüzyonlar sonras›nda, orta beyin arter tepe sistolik h›z›n›n belirleyici de¤eri bilinme- mektedir. Olgu: 31 yafl›nda, G5P4, 24. gebelik haftas›nda fetusta hidrops ile baflvuran, Rh izoimmünizasyonlu gebeye 24-31. gebelik haf- talar› aras›nda dört kez intrauterine transfüzyon uyguland›. Her ifllem s›ras›nda, kordosentez ile fetal hemoglobin tayininden ön- ce ve sonra, Doppler ultrason ile orta beyin arter tepe sistolik h›z› bak›ld›. Fetal hemoglobin de¤erleri ile orta beyin arter tepe sis- tolik h›z› aras›nda ters yönde bir iliflki vard›. Sonuç: Tekrarlayan intrauterine transfüzyonlarda, transfüzyonun zamanlamas› invaziv bir giriflim olan kordosentez ile fetal he- moglobin tayini yap›larak belirlenmektedir. Daha önce transfüzyon yap›lmam›fl ya da tek transfüzyon yap›lm›fl olgularda, fetal anemi tayininde faydal› bulunan orta beyin arter tepe sistolik h›z›, çoklu transfüzyonlarda intrauterin transfüzyonun zamanlan- mas›nda invaziv olmayan uygun bir alternatif olabilir. Anahtar kelimeler: Rh-izoimmünizasyon, orta beyin arteri, tepe sistolik h›z›, intrauterin transfüzyon, a¤›r anemi.

Correspondence: Dr. Yeflim Bülbül Baytur, Celal Bayar Üniversitesi T›p Fakültesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Manisa e-mail: [email protected] Perinatal Journal • Vol: 13, Issue: 4/December 2005 219

Background sions on the OBA-TH measurement is not precise- The Doppler ultrasound and middle cerebral ly known. artery peak systolic velocity (OBA-TH) are used in Our objective with this case report is to empha- the diagnosis of the fetal anemia ancillary to Rh- size the association and significance of OBA-TH isoimmunization as a non-invasive diagnosis measurements with fetal hemoglobin values in a method. It has been shown that if according to hydropic fetus treated with repeated intrauterine week of gestation 1.5 folds above the median transfusions. OBA-TH measurement (1.5 MoM) is used as the threshold value, anemic fetuses at medium or Case heavy degree can be detected correctly.1 The method traditionally used to predict which fetus is Thirty-one-year old woman, G5, P4, who was anemic enough to require transfusion is the cor- referred to Celal Bayar University Department of docentesis and hemoglobin measurement in fetal Obstetrics and Gynecology, Perinatology on her th blood.2,3 However, this method has a 1-2% percent 24 week of gestation upon the detection of ascite risk of fetal loss and at the same time increases the and hydrops in the abdomen of the fetus in the risk of sensitization.4 In cases which it is necessary ultrasonography. Epidemic ascite was detected in to repeat the intrauterine transfusion, the timing of the abdomen and was detected on the the subsequent transfusion is done according to scalp and abdominal walls in the ultrasonography the hematocrit value derived after the transfusion. (Figure 1). The patient with an obstetric history of OBA-TH has been found useful in determining the gestational loss and fetal mortality due to three degree of fetal anemia and consequently the trans- Rh-isoimmunizations was found to be negative in fusion requirement in fetuses which were never the indirect coombs test applied one week prior transfused before or were only transfused once.5 to contact despite being monitored with the indi- However, adult red cells which change place with rect coombs test since the 13th week of gestation. fetal red cells differ in terms of their capacity to The patient with the repeated indirect coombs test carry oxygen, aggregation characteristics and was notified that the test result is positive and that vicosities.5 As a result, the effect of fetal blood the antibody titre is too high for titration. characteristics that change after repeated transfu- Cordocentesis was done one the 24th week of ges-

Resim 1. Fetusta asit ve hidrops. 220 Baytur YB ve ark., Tekrarlayan ‹ntrauterin Transfüzyonlarda Orta Beyin Arter Tepe Sistolik H›z›n›n De¤eri

Resim 2. OBA-TH’n›n Doppler ultrasonografi ile ölçümü. tation of the patient for whom intrauterine trans- taken before and after the transfusion are all fusion was decided. Upon hemoglobin (Hb) val- shown in Table 1. On the 2nd transfusion, the deci- ues being 3.5 g/dL, hematocrit (Htc) 13%, the 80% sion as to when the transfusion would be repeat- hematocrit, 0 Rh (-), serologic infection tests ed was taken due to the continuation of fetal being negative, the amount of blood which is ascite, and according to post transfusion fetal Hb necessary to be given in the previously defined and Htc values in the following transfusions.1 The form, through the transperitoneal and intravascu- fetus was observed between transfusions a couple lar method was calculated with the formula and of times per week with ultrasonography, and in transfused with the plan to increase hematocrit to addition, weekly with the non-stress test after the 30%.4 Blood was taken after the transfusion 28th week of gestation. Fetal ascite disappeared process for the Hb and Htc values, however, after the 2nd transfusion (Figure 3). While fetal these value could not be reviewed due to the Hb and Htc values increased after the transfu- technical failure in the laboratory. The fetal blood sions, the measured OBA-TH decreased (Table 1). type 0 Rh (+) was positive with the direct Coombs There was an inverse correlation between the test. Pre and post transfusion OBA-TH was mea- fetal Hb, Htc values and the OBA-TH. sured from the peak waveform in way to enable Upon the development of acute persistent the angle between the Doppler ultrasound and bradicardia during the final transfusion performed artery to be near 0, in the form previously on the 31st week of gestation, a 1900 gr live baby described with the Doppler ultrasonography girl was delivered with an emergency caesarean (Figure 2). The patient had undergone three more section. The Hb and Htc value after delivery was st intravascular transfusions up to the 31 week of 11 g/dL and 34%, relatively. her gestation. Fetal Hb and Htc values and also OBA-TH measurements were taken before and after every transfusion. The weeks of transfusion, Discussion the time between transfusions, the volume of The measurement of OBA-TH with the Doppler blood given, the Hb, Htc, OBA-TH measurements ultrasound is a valuable tool in the assay of the Perinatal Journal • Vol: 13, Issue: 4/December 2005 221

Tablo 1. Hemoglobin, hematokrit ve OBA-TH’nin transfüzyonlar öncesi ve sonras›ndaki de¤erleri.

GebelikHemoglobin Hematokrit (%) Verilen OBA-TH (cm/s) Transfüzyon haftas› kan miktar› No (Aral›k) Önce Sonra Önce Sonra (ml) Önce Sonra

1 24. hafta (10 gün) 3.5 – 11.5 – 40 52 34 (1.7 MoM) (1-1.3 MoM)

2 25. hafta (16 gün) 1.5 8.9 3 27 75 80 39 (>2 MoM) (1-1.3 MoM)

3 27. hafta (21 gün) 5.9 10.2 17.8 29.4 55 50 27 (1.3-1.5 MoM) (<1 MoM)

4 31. hafta 5.7 11 17 34 60 0.63 (1.5 MoM) *

*Acil sezaryen ihtiyac› nedeniyle ölçülemedi. fetal hemoglobin value in fetuses carrying the risk is considered that the fetus has severe or medium of anemia. It has been found to be useful in the degree of anemia.1 However, OBA-TH values may assay of fetal hemoglobin value and the prediction show variation since the characteristics of fetal of the time of transfusion in anemic fetuses with blood change in fetuses that have previously severe or medium degree anemic fetuses even if undergone transfusion due to the adult blood the value of prediction is not too high in lightly given. Thus, when 100% sensitivity is taken in the anemic or non-anemic fetuses.6 In fetal anemia detection of severe, medium degree and light ane- related to Rh-isoimmunization, cardiac “output” mia with studied OBA-TH measurements in the increases in response to hematocrit decrease and prediction of the 2nd transfusion time for cases fetal cerebral arteries increase blood flow with which have undergone transfusion for one time, quick response to hypoxia. If OBA-TH values are the wrong positive rate has been found to be 6%, above 1.5 MoM according to week of gestation, it 37% and 70%, respectively.5 Researchers have

Resim 3. Transfüzyon sonras› azalan asit. 222 Baytur YB ve ark., Tekrarlayan ‹ntrauterin Transfüzyonlarda Orta Beyin Arter Tepe Sistolik H›z›n›n De¤eri

reported the OBA-TH threshold value for severe In our case, post transfusion fetal Hb and Htk anemia in the same study as 1.69 MoM. This value values dropped quicker than expected. The cause is higher than the threshold value for cases that of this may be high maternal antibody titre or the have not undergone any transfusion before (1.5 intraperitoneal application of a section of the first MoM). The low capacity to carry oxygen and low transfusion. It is suggested that red cells given viscosity of the “new” blood has been indicated as intraperitoneal are absorbed later in hydropic the cause of this. There is no study in relation to fetuses and consequently, intravascular transfusion the OBA-TH value in determining the fetal anemia is preferred.4 On the other hand, some authorities in intrauterine transfusions repeated more than recommend the intravascular and intraperitoneal once. Furthermore, it is suggested that the mea- method in combination, and suggest that red cells surement of OBA-TH with the Doppler ultrasound that are to be left for the peritoneal will form a particularly in hydropic fetuses could be an ancil- reservoir.8 For this reason, in the first transfusion lary method in determining the fetal hemoglobin we preferred to combine the intraperitoneal value with cordocentesis and amniocentesis, how- method with the intravascular one. As a result, 7 ever that it cannot substitute these methods. OBA-TH which is found to be useful in the assay In our case, the OBA-TH measured before the of fetal anemia in cases that have not undergone first transfusion when the fetus was in the hydrop- any transfusion before or that have undergone a ic state was over the 1.69 threshold value. The single transfusion, may be a suitable non-invasive OBA-TH value which dropped below 1.5 MoM alternative in the timing of the intrauterine transfu- after the transfusion increased again over 2 MoM in sion in multiple transfusions. There is need for 10 days after the first transfusion. These values prospective studies on this subject. were inversely proportioned with the fetal Hb and Htk values measured with cordocentesis. However, References despite the OBA-TH values measured after the 2nd transfusion being below the threshold value neces- 1. Mari G, Deter RL, Carpenter RL, Rahman F, Zimmermann R, Moise KJ Jr, et al. Noninvasive diagnosis by Doppler ult- sary for transfusion, the Hb and Htc values rasonography of fetal anemia due to maternal red-cell al- observed with cordocentesis were at the border loimmunization. Collaborative Group for Doppler Assess- requiring transfusion (Table 1). These values indi- ment of the Blood Velocity in Anemic Fetuses. N Engl J Med cate that it may be necessary to use different 2000; 342: 9-14. threshold values from fetuses that have not under- 2. Öndero¤lu L, Öncüo¤lu C. Rh disease: Intrauterine intravas- gone transfusion before or that have undergone cular fetal blood transfusion by cordocentesis. Turkish Jour- transfusion once only for OBA-TH measurement nal of Pediatrics 1999; 41: 61-5. and fetal hemoglobin assay in transfusions repeat- 3. Kimya Y, Cengiz C, Karabay A. Rh izoimmünizasyonuna ba¤l› a¤›r fetal hemolitik hastal›¤›n intrauterin tedavisi. ed more than once in hydropic fetuses. However, Medical Network Klinik Bilimler ve Doktor 2000; 6(3): 383-7. since it will not be possible to reach a conclusion 4. Rauk PN, Daftary A. Erythroblastosis fetalis.In Clinical with a single case, new prospective studies are Maternal Fetal Medicine. Edd Winn HN, Hobbins JC. Part- necessary to predict the OBA-TH value and thresh- henon Publishing, London. 2000: 609-29. old values in fetal hemoglobin assay in repeated 5. Detti L, Oz U, Guney I, Ferguson JE, Bahado-Singh RO, transfusions. The objective of this case report is not Mari G. Collaborative Group for Doppler Assessment of the to reach a conclusion on this subject, but to Blood Velocity in Anemic Fetuses. Doppler ultrasound velocimetry for timing the second intrauterine transfusion emphasize this requirement. in fetuses with anemia from red cell alloimmunization. Am A majority of the cases with Rh-isoimmunization J Obstet Gynecol 2001; 185: 1048-51. are non-anemic or are lightly anemic. In their 6. Mari G, Detti L, Oz U, Zimmerman R, Dueric P, Stefos T. study, Detti et al. report the ratio of non-anemic or Accurate prediction of fetal hemoglobin by Doppler ult- light anemic fetuses as 72%, medium degree ane- rasonografi. Obstet Gynecol 2002; 99: 589-93. mic fetuses as 11%, and severely anemic ones as 7. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol 2002; 100: 600-11. 17%. The low proportion of pregnant women who are severely anemic and far from their term makes 8. Ulreich S, Gruslin A, Nodell CG, Pretorius DH. Fetal Hydrops and Ascites .In Diagnostic Imaging of Fetal it difficult to reach the sufficient number of cases in Anomalies.Edd Nyberg DA, McGahan JP, Pretorius DH, Pilu a prospective study on the subject. G. Lippincott Williams&Wilkins, Philadelphia, 2003: 713-44. Perinatal Journal • Vol: 13, Issue: 4/December 2005 223

Death of One Fetus in Twin Pregnancy: Report of Four Cases

Semih Mun, Tolga M›zrak, Cüneyt Eftal Taner, Gülflen Derin, Cem Büyüktosun

SSK Ege Maternity Hospital, ‹zmir

Abstract Objectives: Twin pregnancies are the pregnacies that intrauterine and perinatal morbidity and mortaliy is higher when compared to monozygotic pregnancies. Cases: 10% of all perinatal deaths are related with dizygotic twins. In this study we reported four twin pregnancies that had intrauterine death of one twin at 20 th week or later. We analyzed the cases according to maternal age, ultrasonographic find- ings, results of biochemical tests, birth weeks and perinatal outcomes. One case was monochorionic - monoamniotic and the other three were dichorionic - diamniotic. In two cases other twins died at 9 th and 13 th days after the diagnosis. The other two that were dichorionic - diamniotic reached term without any complications. Conclusion: In case of monofetal death of twin pregnancies, the type of placenta should be analyzed and then follow up and treatment modalities of these cases should be choosen. Keywords: Twin pregnancy, single fetal death.

‹kiz eflinin intrauterin ölümü: dört olgu sunumu

Amaç: Ço¤ul gebelikler, intrauterin ve perinatal morbidite ve mortalitenin daha fazla görüldü¤ü gebeliklerdir. Tüm perinatal ölümlerin ortalama %10’unu ikiz gebelikler ile ilgilidir. Olgular: Bu çal›flmada ikiz eflinin 20. gebelik haftas›nda veya daha sonra intrauterin exitus oldu¤u saptanan 4 olgu sunularak ol- gular›n maternal yafl, gebelik say›lar›, ultrasonografik bulgular›, biyokimyasal testleri, do¤um haftalar› ve perinatal sonuçlar› ince- lendi. Bir olgu monokoryonik - monoamniyotik ve di¤er üç olgu ise dikoryonik - diamniotik idi. ‹ki olguda ikiz eflleri tan› konduk- tan 9 ve 13 gün sonra exitus oldu. Dikoryonik - diamniyotik olan 2 olgu terme kadar ulaflt› ve herhangi bir komplikasyon izlen- medi. Sonuç: Monofetal ölüm ile komplike olmufl ikiz gebeliklerde plasenta yap›lar› tespit edilmeli, tedavi ve takip seçene¤i ona göre belirlenmelidir. Anahtar Sözcükler: ‹kiz eflinin ölümü, gebelik.

Background is higher when compared to monozygotic preg- Twin pregnancies are the pregnancies that nancies.1 In multiple pregnancies, the frequency of intrauterine and perinatal morbidity and mortality complications including preterm birth, preeclamp-

Correspondence: Dr. Semih Mun, SSK Ege Do¤umevi, ‹zmir e-mail: [email protected] 224 Mun S et al., Death of One Fetus in Twin Pregnancy: Report of Four Cases

sia, intrauterine growth retardation, and twin-to- the first one. In other two cases that reach the twin transfusion syndrome is increased.2,3 10% of term, pregnancy week average was 37 weeks and all perinatal deaths are related with dizygotic 3 days (between 37-38th weeks). Prenatal ultra- twins. The rate of intrauterine fetal demise in mul- sonographic monitoring was consistent with the tiple pregnancies is higher three times of monozy- latest tests and biophysical profiles were normal. gotic pregnancies. Perinatal morbidity and mortal- In Doppler blood flow tests, umbilical artery, uter- ity are seen in dizygotic pregnancies frequently ine artery and middle cerebral artery flow patterns three times to monozygotic pregnancies.1 were in normal limits. Average values of the cur- The demise of one of the twins in first trimester rent blood analysis for 4 cases: fibrinogen; 224 is relatively seen in general and it doesn’t harm the (193248 mg/dl), prothrombin time; 13.4 second mother and the other fetus in following weeks and (12.114.8 second), thrombocyte counts; 166.000/ 3 3 doesn’t affect the maternal prognosis.4,5 However, mm (119.000209.000 trombosit/mm ), hemoglo- the demise of one of the twins may cause serious bin; 12.8 g/dl (14.2-11.6 g/l), leukocyte; 11.250/ 3 problems for both mother and the fetus in second mm , FDP (Fibrin decomposition products); 1.000 or third trimester.6 Major maternal and another fetal ng/dl. All four cases were monitored during their problems are intravenous coagulation, neurologi- hospitalization and two of them were monitored cal and nefrologic damage, premature birth. on monthly basis by ultrasonography and labora- tory tests. In two cases where the twin fetuses In this case study four twin pregnancies that were intrauterine demised and pregnancies termi- had intrauterine death of one twin at 20th week or nated by inducing by misoprostol abortion. These later are analyzed and discussed. Four twin fetus cases were discharged without any complication are diagnosed in 20th week or later intrauterine exi- on the first day of postpartum. In the other two tus. The cases were analyzed in regard the age, cases that reach the term, delivered by cesarean. In pregnancy, ultrasonic findings, biochemical tests, one case, a male fetus with 3000 g weight and 9 maternal weeks, and perinatal results. Apgar, and a male exitus fetus with 1400 g, in the second case a male fetus with 3000 g weight and Case 7 Apgar, and a male exitus fetus with 700 g weight Four twin fetuses which are monitored within were delivered. No neonatal morbidity has been Perinatology Unit of SSK Ege Maternity and diagnosed for both fetuses. Mothers were dis- Gynecology Training Hospital, are diagnosed in charged without any complication on the second 20th week or later intrauterine exitus. The cases day of postoperative period. Macroscopic placen- were analyzed in regard the age, pregnancy, ultra- ta examinations and ultrasonographic monitoring sonic findings, biochemical tests, maternal weeks, in postpartum period showed that one of the cases and perinatal results. was monochorionic monoamniotic and the other three were dichorionic diamniotic. As per fetal In four cases constituting research group, both mortality etiology, the ultrasonographic monitoring fetuses were alive, proven by the first trimester in the monochorionic monoamniotic case, as there ultrasonography. Average maternal age of four was in demised fetus, and poli- cases was 27 (between 23-31). Pregnancy week hydramnios, acid, hydrops findings in other case, average where one of the twin fetuses was Twin-to-Twin transfusion was planned, the exact demised 24 (between 20-28th weeks). Ultrasono- etiology couldn’t be clarified in other three diamni- graphic tests showed that one case was mono- otic dichorionic cases. chorionic monoamniotic and the other three cases are dichorionic diamniotic. The other fetus was demised 13 days later once monochorionic Discussion monoamniotic case twin was exitus. In another The mortality through the exitus of one twin, case, the other fetus was exitus 9 days later than and major morbidity rate was reported 46%.7 Perinatal Journal • Vol: 13, Issue: 4/December 2005 225

Though the etiology cannot be strictly detected in preferred.11 However, because the cerebral and numerous cases; twin-to-twin transfusion syn- nephrologic complications developed in living drome, preeclampsia, rhesus immunization, chro- fetus started once the other fetus demises, a close mosomal or congenital anomalies, single umbilical follow-up is suggested as a conservative treat- artery, placental and umbilical chord placement ment.6 But as there is no such a problem in diamni- anomalies, umbilical venous thrombosis and uter- otic dichorionic twin pregnancies, conservative ine malformations are major causes.7 As the etiolo- approach is preferred, and ultrasonographic fol- gy of fetal mortality in our cases, by the ultrasono- low-up of the fetus development and amnion fluid graphic monitoring in the monochorionic is suggested.12 Non stress test and Doppler ultra- monoamniotic case, as there was oligohydramnios sonography monitoring are important for detecting in demised fetus, and polihydramnios, ascites, fetal distress development, twice in a week.6 In the hydrops findings in other case, twin-to-twin trans- same time, the maternal coagulation system should fusion syndrome was deciced; the exact etiology be monitored by a series of lab test. Most impor- couldn’t be clarified in other three diamniotic tant factor to determine the mode of delivery is dichorionic cases. general obstetric situation of the mother. Twin Major factors determining the treatment and fol- pregnancy and the demise of one fetus cannot low-up approach in multiple pregnancies compli- constitute indication for the cesarean. When one of cated with intrauterine monofetal death are the the twins dies, the pregnancy is terminated by risks that mother and living fetus take. Most fre- cesarean because of the coagulopathy develop- quently used and suggested method is follow-up ment and this increases the prematurity related 9 of the maternal coagulation system by a series of morbidity. lab test. Pitchard et al8 proved that there is coag- In conclusion, in case of monofetal death of ulation disorder at various levels in mono preg- twin pregnancies, the amnion and placenta struc- nancies left in uterus after the exitus. When one of tures should be detected and then follow up and the twins dies, the pregnancy is terminated by treatment modalities of these cases should be cho- cesarean because of the coagulopathy develop- sen. If placenta and amnion are diamniotic dichori- ment and this increases the prematurity related onic, a conservative approach including close fol- morbidity.9 In our study, the lab test results for low-up may be adopted until the lung maturation coagulation system were within the normal limits. of the fetus is ensured. In cases that term or via- There are various studies that indicate that the bility limit are reached, emergency delivery is gen- living fetus is under high morbidity and mortality erally accepted. While determining the birth risk. After the first fetus demised, there is an modality, the obstetric indications should be con- sidered and the prematurity should be avoided. intrauterine mortality risk at 7.8 - 20% for living fetus.4,10 In addition, in 28-50% of live-born fetuses, central neural system damage at various levels References 5,10 1. Lumme R,Saarikoski S. Antepartum death of one twin. Int J occur. The amount of blood transfused to Gynaecol Obstet 1987; 5: 331-6. demised fetus from the living one, the type, the 2. D’Alton ME, Simpson LL. Syndromes in twins. Semin density and the placement of the anastomosis in Perinatol 1995,19: 375-86. monochorionic placenta, and this determines the 3. Newman RB, Ellings JM. Antepartum management of the multiple gestation: the case for specialized care. Semin anemia and organ damage in living fetus. No com- Perinatol 1997; 19: 387-403. plication has been developed in the living fetuses 4. Peterson IR, Nyholm HCJ. Multiple pregnancies with single intrauterine demise: description of twenty – eight pregnan- that complete the term. cies. Acta Ostet Gynecol Scand 1999; 78: 202-6. In monochorionic monoamniotic twin pregnan- 5. Axt R, Mink D, Hendrik J, Ertan K, Vonn Blohm M, Schmidt cies, in case where one of the fetuses demises in W. Maternal and neonatal outcome of twin pregnancies complicated by single fetal death. J Perinat Med 1999; 27: antenatal period, termination of the pregnancy is 221-7. 226 Mun S et al., Death of One Fetus in Twin Pregnancy: Report of Four Cases

6. Fusi L, Gordon H. Twin pregnancy complicated by single 10. Liu S, Benirschke K, Scioscia AL, Mannino FL. Intrauterine intrauterine death: Problems and outcome with conser- death in multiple gestation. Acta Genet Med Gemellol 1992; vative management. Br J Obstet Gynaecol 1990; 97: 511-6. 41(1): 5-26. 7. Baxi LV, Daftary A, Loucopoulos a. Single fetal demise in a twin gestation: umbilical vein thrombosis. Gynecol Obstet 11. Tawanattanacharoen S, Taylor MJO, Letsk EA, Cox PM, Invest 1998; 46(4): 266-7. Cowan FM, Fisk NM. Intrauterine rescue transfusion in 8. Cattanach SA, Wedel M, White S, Young M. Single int- monochorionic multiple pregnancies with recent single int- rauterine fetal death in a suspected monozygotic twin preg- rauterine death. Perinat Diagn 2001; 21: 274-8. nancy. Aust NZJ Obstet Gynaecol 1990; 30: 137-40. 12. Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC, Hauth 9. Wong DJ, Kirz DS. Outcome of twin gestations complicated by antepartum fetal demise. Am J Obstet Gynecol 1991; JC, Wenstrom KD (eds): Multifetal Pregnancy. In: Williams 164(SPO Abst.603): 411. Obstetrics. Mc Graw Hill 21st Edition 2001; 765-810. Perinatal Journal • Vol: 13, Issue: 4/December 2005 227

Impetigo Herpetiformis: A Case Report

‹ncim Bezircio¤lu1, Merve Biçer1, Levent Karc›1, Füsun Özder2, Ali Balo¤lu1

1First Clinic of Gynecology and Obstetrics, 2Clinics of Dermatology, Atatürk Training and Research Hospital, ‹zmir

Abstract Objective: Impetigo herpetiformis is a rare and potentially life-threatening pustular dermatosis affecting mainly pregnant women. We report here a case of impetigo herpetiformis which occured in twenty-ninth week of pregnancy. Case: A 32 year old gravida 2, para1 pregnant woman who was referred to our institution because of congestive heart failure, gestational diabetes mellitus and oligohidroamnios in 27th gestational age was hospitalized. Eruptive pustular lesions which appeared in 29th week of the gestation has spread her entire body. Her pustular cultures were negative. A punch skin biopsy from a pustule on the trunk made the diagnosis of impetigo herpetiformis. The patient who developed spontaneous uterine contractions was treated with betamethazone and tocolysis. The patient who did not respond to this treatment was taken to delivery at 30 weeks of gestation.The newborn showed no skin lesions after birth. The skin lesions of the mother improved in the second postpartum week. Conclusion: The rates of maternal mortality and fetal mortality and morbidity due to placental insufficiency are increased in impetigo herpetiformis. To reduce the mortality and morbidity rates the antenatal management of impetigo herpetiformis should be organized with a multidisciplinary approach. Keywords: Impetigo herpetiformis, generalized pustular .

Impetigo herpetiformis: Bir olgu sunumu Amaç: ‹mpetigo herpetiformis gebelerde görülen yaflam› riske edebilen nadir bir püstüler dermatozdur. Bu çal›flmada 29.gebe- lik haftas›nda ortaya ç›kan impetigo herpetiformis olgusu sunulmufltur. Olgu: 32 yafl›nda G2P1 27. gebelik haftas›nda konjestif kalp yetmezli¤i, gestasyonel diyabetes mellitus, oligohidramnios tan›lar›yla klini¤imize refere edilen olgu hospitalize edildi. ‹zlemde 29. gebelik haftas›nda ortaya ç›kan eritemli püstüler lezyonlar tüm vücuda yay›ld›. Püstüllerden al›nan örneklerde bakteriyolojik üreme olmad›, histolojik tan› impetigo herpetiformis olarak konuldu. Spontan uterin kontraksiyonlar› bafllayan olguya Betametazon ve tokoliz tedavisine baflland›. Tokolize yan›t vermeyen olgu 30.gebelik haftas›nda do¤urtuldu. Fetal impetigo görülmedi. Cilt lezyonlar› postpartum 2 hafta içerisinde h›zla iyileflti. Sonuç: ‹mpetigo herpetiformis olgular›nda maternal mortalite, ayr›ca fetoplasental yetmezlik nedeniyle fetal mortalite ve mor- bidite oranlar› artm›flt›r. Bu oranlar› azaltabilmek için antenatal izlem protokollerini multidisipliner bir yaklafl›mla düzenlemek gerekmektedir. Anahtar kelimeler: ‹mpetigo herpetiformis, jeneralize püstüler psoriazis.

Background hormonal disorder in pregnancy.1 It has various clinic and histological similarities to the general- Impetigo herpetiformis is a rare and potentially ized . Impetigo herpetiformis is life-threatening pustular dermatosis affecting main- considered as variant of pustular psoriasis that ly pregnant women. The disease was triggered by appears in pregnancy.2

Correspondence: Dr. ‹ncim Bezircio¤lu, ‹zmir Atatürk E¤itim ve Araflt›rma Hastanesi 1. Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹zmir e-mail: [email protected] 228 Bezircio¤lu ‹ et al., Impetigo Herpetiformis: A Case Report

In the literature more than 100 cases were cerebral artery were normal. The treatment described.1 Fetal mortality and morbidity risks are arranged by regular insulin, digoxin, diltizem, high because of maternal mortality and placental acetyl salicylic acid, low molecule weight heparin. 3 deficiency. This case report was presented in On 29th gestational week, skin lesions appeared order to highlight the importance of impetigo her- in the pubical zone, with itchy, eritematous (Figure petiformis in maternal and fetal, mortality and mor- 1). The periphery pustules were spread to all over bidity. Although it was seen among 6-33 age the body (Figure 2). Oral mucosa and soft palate group, it was also reported for menopause group.2 2-3 mm eritemous papules were developed. The hair with hair, plamar-plantar surfaces and finger- Case nails were intact 3 Mrs. AT is 32-year-old. In 27th gestational week, Laboratory results, leukocyte 14000/mm , ery- she was referred to our clinic with 2 para 1 con- throcyte sedimentation rate (ESR): 29 mm/h, serum gestive heart failure, oligohydramnios diagnosis. calcium: 7.3 mg/dl, serum phosphate: 2.5 mg/dl, She had diagnosed mitral stenosis, and tricuspid albumin: 2.41 gr/ml. Liver, kidney function tests failure and used digoxin. The patient delivered a and parathyroid hormone levels were normal. spontaneous vaginal unvivid birth 1 year earlier There was no bacteriologic reproduction in the when an in utero fetal loss has been developed in specimens acquired from pustule and in blood cul- her first pregnancy. She is hospitalized once she ture. The histological examination of biopsy mate- has atrial fibrillation and gestational diabetes on rial taken from the lesion displayed that multilocu- 27th week of current pregnancy. lar spngy intraepidermal pustules, acanthosis, In ultrasonographic monitoring, fetal biometry parakeratosis (Figure 3). was consistent with latest monitoring. In Doppler The case was diagnosed Impetifo herepiformis measurement, dicrotic notch was monitored in based on the clinical and histopathological fea- bilateral arteries, while umbilical artery and middle tures. As a result of the dermatological consulta-

Figure 1. Eritemous dermal lesions. Perinatoloji Dergisi • Cilt: 13, Say›: 4/Aral›k 2005 229

Figure 2. Pustular lesions. tion, local betamethazon administration, 3 times hypoparathyroid, infection, oral contraceptive and per day, (Betnovate cream, Glaxo Welcome stress are known to facilitate the development of Medical Industries A.fi, Istanbul, Turkey) has impetigo herpetiformis.5,6 begun. It appears in second and third trimesters but On 29th gestational week, in order to stimulate mostly occurs in third trimester. The frequency is lung maturation and contribute to the treatment of variable and the symptoms don’t completely ame- the lesions, betamethazon 12 mg/24 h (Celestone liorate. In following pregnancies, it tends to appear chronodose; Schering Plugh Medical Products AS, earlier and acute.7 In our study, lesions appeared Istanbul, Turkey). in third trimester. In 29th gestational week, the case that devel- It may be life-threatening for both mother and oped premature membrane rupture, delivered a fetus. The dermal lesions are intensified sepsis risk, male infant, 1450 g, 42 cm, 12 hours later by a while placental defect and decreasing intervillous vaginal modality. According to Lubchenco–LO circulation may cause fetal morbidity and mortali- maturation curve, the weight was 50 percantile, the ty.3,5 length 75 percantile.4 The skin lesions were ame- Lesions begin with symmetrical eritemous liorated within 2 weeks post partum. plaques in convolution of the skin. Sterile pustules appear in the periphery of the plaques. The pus- Discussion tules amalgamate and expand to the periphery Impetigo herpetiformis is a dermatosis charac- when the center opens and crust. Oral and phar- terized by sterile pustules that occur in pregnancy. ynx lesions may be developed. General situation The disease appears in pregnancy. Some indicates worsens and systemic symptoms including lassi- that it has an etiological relationship with the preg- tude, headache, fever, palpitation, nausea, diar- nancy.5 Even though there isn’t any strict patho- rhea, tetani as well as eruption.7 In our case, logical mechanism, the use hypocalcaemia, lesions started from pubical zone and expanded to 230 Bezircio¤lu ‹ et al., Impetigo Herpetiformis: A Case Report

Figure 3. Epidermis multiocular spongious intraepithelial pustular, acanthosis, parakeratosis structure.

the body. The lesions are seen in oral mucosa and gious zones, are characteristic, and they are soft palate tissue. In lesion samples, no bacterio- accepted similar to the spongioform pustules of logical reproduction has been observed. Further Kogoj specific to the psoriasis. Extension and systemic findings haven’t been diagnosed in our parakeratosis are frequently monitored.3 In our study. The lesions are ameliorated in postpartum case, prolongation in spongioform pustular papil- period, leaving a postinflammatory pigmentation, lary and parakeratosis have been diagnosed. in a couple of weeks.7 In our case study, the Most important complication of the disease is lesions were ameliorated within 2 weeks. placental defect, and intrauterine fetal mortality.6 In Leukocytosis, hypocalcaemia, hyperphospha- our case, while impetigo herpetiformis related pla- temia, hypoproteinemia, ESR increase are most cental defect develop as well as maternal heart fail- frequent laboratory findings. It is noted that ure related intrauterine maturation latency, gesta- hypoalbuminemia develops as a result of albumin tional diabetes ensured that intrauterine maturation loss from large exudative zones, and hypocal- develops in normal limits. caemia appears as a secondary effect of the For treatment in less severe cases, topical hypoalbuminemia.7 In the differential diagnosis of steroid applies, besides, in severe cases systemic the cases, subcorneal pustular dermatosis may be steroid is in use.5,8 For secondary infections, antibi- considered. But, the general situation doesn’t cor- otics, fluid, electrolyte and calcium replaced. In rupt in subcorneal pustular dermatosis.1 In our hyperparathyroidism cases, phosphate limitation, case, leukocytosis, hypocalcaemia, hypoalbumine- calciferol and dehydrocolecalciferol applications mia, ERT increases were diagnosed. Parathormone are suggested. For treatment resistant cases, levels were normal. cyclosporine and phototherapy treatments are in In impetigo herpetiformis cases, as a use.5 In our case, topical steroid wasn’t adminis- histopathological symptom in a lesion, polymor- trated since systemic symptoms haven’t been diag- phic leukocyte accumulation at epidermis spon- nosed. In addition, systemic parenteral corticos- Perinatoloji Dergisi • Cilt: 13, Say›: 4/Aral›k 2005 231

teroid was administrated in order to stimulate lung cal appearance. This rare entity is important for maturation. In post partum period, systemic corti- both maternal and fetus mortality and morbidity. costeroid administration wasn’t continued since a diminution was expected in lesions. Parenteral cal- References 1. Lawley TJ, Yancey KB. Skin Changes and Diseases in Preg- cium replacement was used. nancy. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Since it is similar in clinic and histopathological Goldsmith LA, Katz SI. (Eds) Fitzpatrick’s Dermatology in General Medicine. Sixth edition. New York, McGraw- regard, impetigo herpetiformis may be a variant of hill;2003; 1361-5. the generalized pustular psoriasis.3,8 Impetigo her- 2. Pustular Diseased. In: Braun-Falco O, Plewig G, Wolff HH, petiformis is seen in the persons that don’t have Burgdorf WHC. (Eds) Dermatology. Second edition. New York, Springer-Verlag; 2000; 697-708. psoriasis in their personal or family history, and it 3. Breier-Maly J, Ortel B, Breier F, Schmidt JB, Honigsmann H. is induced after the birth.5,9 It is known that it Generalized pustular psoriasis of pregnancy (impetigo her- repeats in successful gestations, more severe and petiformis). Dermatology 1999; 198: 61-4. 9 4. Can G, Çoban A, ‹nce Z. Bölüm 7: Yenido¤an ve hastal›k- earlier. In our case, it appears the first time in sec- lar›. Neyzi O. Ertu¤rul T. (Eds) Pediatri. Üçüncü bask›, ond gestation. The psoriasis wasn’t reported in Nobel t›p Kitapevleri 2002; p: 339. personal or family history. 5. Aslanpençe ‹, Dede FS, Gökçü M, Geliflen O. Impetigo her- petiformis unresponsive to therapy in a pregnant adoles- The symptoms of the psoriatic cases are cent. J pediatr Adolesc Gynecol 2003; 16: 129. reduced at 30-65% when the patients are con- 6. fiahin HG, fiahin HA, Metin A, Zetero¤lu fi, U¤rafl S. Rec- curent impetigo herpetiformis in a pregnant adolescent: ceived. The symptoms worsen only in 10-20% of case report. Eur J Obstet Gynecol Rep Biol 2002; 101(2): 201- the cases.9 The amelioration occurs generally in 203. first trimester. The gestational response remains 7. Errickson CV, Matus NR. Skin disorders of pregnancy. Am Fam Physic 1994; 49: 605-10. the same in following gestations. The amelioration 8. Do¤an G, Hazneci E, Kar›ncao¤lu Y, Özen S. ‹mpetigo her- in psoriasis table for the pregnant women is relat- petiformis: Olgu sunumu. 1999; 6: 162-5. ed to the immune system down regulation.10,11 9. Tauscher AE, Fleischer AB, Phelps KC, Feldman SR. Psoriasis and pregnancy. J Cutan Med Surg 2002; 6: 561-70. 87.7% of the cases are involved after the pregnan- 10. Siba P. Raychaudhuri, md, Teja Navare, md, Jeff Gross, ms, cy. In our case, lesions are rapidly induced after and Smriti K. Raychaudhuri, md Clinical course of psoriasis the gestation. Our case was diagnosed in clinic during pregnancy. Int J Dermat 2003; 42: 518. development as impetigo herpetiformis as it was 11. Boyd AS, Morris LF, PhillipsCM, et al. Psoriasis and preg- nancy: hormone and immune system interaction. Int J Der- similar in regard of morphologically and histologi- matol 1996; 35: 169. 232 Perinatal Journal • Vol: 13, Issue: 4/December 2005

Treatment of Viable Cesarean Scar Ectopic Pregnancy with Intraamniotic Methotrexate Injection

Orhan Ünal, Olufl Api, Bülent Kars, Salim Korucu, Çi¤dem Korucu, Sadullah Bulut

Kartal Dr. Lütfi K›rdar E¤itim ve Araflt›rma Hastanesi, Kad›n Do¤um Klini¤i, ‹stanbul

Abstract Objective: TPregnancy in previous cesarean scar is the rarest form of ectopic pregnancy. We aimed to present a case of cesare- an scar ectopic pregnancy that was successfully treated with intraamniotic methotrexate injection under ultrasonographic guid- ance. Case: A 41-year-old woman, gravida 4, para 2, abortus 1, with a history of two caesarean sections, presented at 5 weeks' ges- tation and requested pregnancy termination. Upon transvaginal ultrasonography, a hypoechogenic round-shaped mass image, 10x9 mm in diameter - similar to gestational sac - which was localized on Kerr incision, just upon the internal cervical os, was identified. Neither yolk sac nor fetal pole was identified. Serum beta-hCG was 7595 mIU/ml. The patient was re-examined a week later. Transvaginal ultrasonography revealed that the gestational sac diameter proceeded to 24x15 mm with a fetal pole with cardiac activity and beta-hCG was 14000 mIU/ml. Intraamniotic methotrexate (MTX) (10 mg) injection was applied under ultrasonographic guidance. The hemodynamically stable patient was followed on outpatient basis. Serum beta-hCG levels were 20252 mIU/ml and 19399 mIU/ml, with one week intervals. Gestational sac diameter decreased to 15x10 mm with loss of the fetal pole image. Due to the increasing levels of beta-hCG, intramniotic MTX injection was repeated at a dose of 20 mg, 2 weeks after the first injection. Thereafter, the patient was followed with serial ultrasonography and serum beta-hCG monitorization. Cesarean scar pregnancy was completely resorbed upon 9 weeks interval. Conclusion: Ultrasound-guided methotrexate injection is a successful alternative to terminate cesarean scar pregnancy. Keywords: Cesarean scar pregnancy, conservative treatment, intraamniotic methotrexate

Canl› sezaryen skar gebeli¤inde intraamniotik methotrexat enjeksiyonu ile baflar›l› tedavi Amaç: Nadir bir ektopik gebelik türü olan bir sezaryen skar gebelik olgusunun sunulmas› ile tan› ve tedavi modalitelerinin litera- tür ›fl›¤›nda tart›fl›lmas›. Olgu: K›rkbir yafl›nda G4P2A1 olan hastan›n 9 y›l ve 3 y›l önce 2 kez sezaryen seksiyo ile do¤um yapt›¤› ö¤renildi. Bir haftal›k adet rötar› bulunan hasta aile planlamas› iste¤i ile klini¤imize baflvurdu. Yap›lan transvajinal ultrasonografide (TVUSG) internal os’un hemen üstünde eksantrik yerleflimli, Kerr insizyon hatt›n›n üzerinde gestasyonel kese ile uyumlu hipoekojen halka fleklin- de ve 10x9 mm çap›nda yap› izlendi. ‹çinde yolk sac ve fetal pol izlenmedi. Hastan›n beta-hCG düzeyi 7595 mIU/ml olarak gel- di. Bir hafta sonra tekrarlanan TVUSG’de gestasyonel kesenin 24x15 mm çapa ulaflt›¤› ve içinde kalp at›m› izlenen fetal imge ol- du¤u gözlendi. Beta-hCG düzeyi 14000 mIU/ml olarak geldi. Hastaya sezaryen skar gebelik tan›s› ile TVUSG eflli¤inde gestasyo- nel kese içine, intraamniotik 10 mg methotrexate enjeksiyonu yap›ld›. Kanamas› olmayan hasta ayaktan takibe al›nd›. Yap›lan ta- kiplerde hastan›n beta-hCG düzeyi 1 hafta ara ile 20252 mIU/ml ve 19399 mIU/ml geldi , gestasyonel kese 15x10 mm’ye geri- leyerek fetal imge görüntüsü kayboldu. Beta-hCG düzeyinin düflmemesi-aksine artmas›-nedeniyle, birinci methotrexat enjeksiyo- nunu takiben 2 hafta sonra, yeniden TVUSG eflli¤inde ikinci intraamniotik methotrexat enjeksiyonu (20 mg) yap›ld›. Beta-hCG ta- kibine al›nan hastan›n haftal›k takiplerinde beta-hCG de¤erinin düfltü¤ü ve gestasyonel kese görüntüsünün rezorbe oldu¤u izlen- di. Sonuç: Son y›llarda sezaryen sectio ile yap›lan do¤umlar›n artmas› nedeniyle uterin skar gebelikler de daha s›k gözlenmeye bafl- lam›flt›r. Uterin skar gebeli¤in tedavisinde TVUSG eflli¤inde intraamniotik methotrexat enjeksiyonu etkin ve baflar›l› bir yöntemdir. Anahtar Sözcükler: Sezaryen skar gebelik, konservatif tedavi, intraamniotik methotrexat.

Correspondence: Dr. Orhan Ünal, Kartal Dr. Lütfi K›rdar E¤itim ve Araflt›rma Hastanesi, Kad›n Do¤um Klini¤i, ‹stanbul e-mail: [email protected] Perinatal Journal • Vol: 13, Issue: 4/December 2005 233

Background by ultrasonic monitoring is the most appropriate option.3 The pregnancy implanted in cesarean scar is the rarest form of the ectopic pregnancy, is a clin- We aimed to discuss the diagnosis, treatment, ic case containing life-threatening situation. Since it follow up approaches in light of the literature, to is so rare, there isn’t any agreed clinical adminis- emphasize the importance of transvaginal sonog- tration. The data in the literature is mostly formed raphy in early diagnosis and follow-up. of the case studies. In English literature, as from 2002, 66 cesarean scar pregnancy cases were Case 1 reported. This figure reflects increasing cesarean A 41-year-old woman, with a history of two births and the use of transvaginal ultrasonography caesarean sections, which one was 9 years ago and for diagnosing scar pregnancies. Former cesarean the other 3 years ago. The patient who has 1 week cases, the risk factors for scar pregnancy are dilata- menstrual latency, requested the hospitalization for tion, and curettage history, placental pathology, abortion. Upon transvaginal ultrasonography, a ectopic pregnancy history and in vitro fertilization hypoechogenic round-shaped mass image, 10x9 cycle.1,2 Among the treatment options, there are mm in diameter -similar to gestational sac- which direct methotrexate or potassium chloride injection was localized on Kerr incision, just upon the inter- and/or systemic methotrexate injection, vaginal nal cervical ostium, was identified. Neither yolk sonography, as well as embryo aspiration, spool- sac nor fetal pole was identified. Serum beta-hCG ing treatment, removing the gestational tissue was 7595 mIU/ml. The patient was re-examined a through laparotomy, dilatation and curettage, week later. Transvaginal ultrasonography revealed transarterial uterine artery embolization.2-6 that the gestational sac diameter proceeded to However, in the extent of the examined case 24x15 mm with a fetal pole with cardiac activity series, direct methotrexate injection, accompanied and beta-hCG was 14000 mI U/ml. The patient has

Figure 1. Ultrasonographic image of scar pregnancy. 234 Ünal O et al., Treatment of Viable Cesarean Scar Ectopic Pregnancy with Intraamniotic Methotrexate Injection

Figure 2. Ultrasonographic image of scar pregnancy.

undergone 10 mg methotrexate injection accom- and serum beta-hCG results. Consequently, cesare- panied by TVUSG directly into the uterus upon the an scar pregnancy was completely resorbed in the cesarean scar pregnancy diagnosis. The patient end of 9th week who hasn’t hemorrhage underwent an outpatient follow up. In the monitoring, beta-hCG level was Discussion measured 20252 mlU/ml and 19399 mlU/ml, gesta- Cesarean scar pregnancy was a contraindica- tional mass was reduced to 15 x 10 mm and fetal tion of the cesarean cases that are showing a sig- image was disappeared. Since Beta-hCG level aug- nificant increase in recent years. In a series of 12 ments, after first methotrexate injection, within 2 cases studied by Seow et al reported that, cesare- weeks, second intraamniotic methotrexate injec- an scar pregnancy frequency was estimated tion was made (20 mg). After 3 days of second 1/2226 and scar pregnancy rate was 6.1% for dose methotrexate injection, the patient flood dur- women that have at least one cesarean birth and 3 ing 10 days. 10th day of the vaginal bleeding, one ectopic pregnancy. The pregnancy age was transvaginal ultrasonography was repeated and 5-12 weeks on diagnosis, and the time between latest cesarean and scar pregnancy was found 6- showed that the diameter of the gestational sac 12 months. To 12 patients, direct methotrexate or was reduced to 5 x 5 mm and serum beta-hCG potassium chloride injection and/or systemic level was reduced to 1778 mlU/ml. Serum beta- methotrexate injection, vaginal sonography, as hCG was 3259 mIU/ml after one week. The vagi- well as embryo aspiration, spooling treatment, nal hemorrhage stopped and transvaginal USG removing the gestational tissue through laparoto- showed that the gestational sac was still 5 x 5 mm. my, dilatation and curettage methods were Weekly beta-hCG follow up indicated the values applied and 11 of 12 patients retained their repro- and the image of gestational sac disappeared. ductivity ability. And one patient who had under- Figure 1 and 2 show the weekly gestational sac gone dilatation and curettage had hysterectomy Perinatal Journal • Vol: 13, Issue: 4/December 2005 235

Weekly change of GS

30 1. MTX 25

20 2. MTX

15 GS

10 Gestational sac (mm) 5

0 123456789101112 Week

Figure 1. Weekly change in diameter of gestational sac (GS). because of excessive bleeding. However, in the scar pregnancy, ultrasonography of the patient was extent of the examined case series, direct repeated 1 week later and showed that the diame- methotrexate injection, accompanied by ultrasonic ter of gestational sac increased and fetal image monitoring is the most appropriate option and sur- appeared, beta-hCG was elevated. 10 mg MTX gical/invasive methods should be avoided because injected to the patient accompanied by transvagi- of the high morbidity. Our case is a with a history nal USG. During the 15 days follow up, despite the of two caesarean sections, which one was 9 years fetal image disappeared beta-hCG didn’t reduce, in ago and the other 3 years ago. The pregnancy age contrary elevated and through second USG 20 mg is weeks on the diagnosis. In order to be sure of MTX injection was applied. Following the second

Weekly hCG

25000 2. MTX

20000 1. MTX

15000 hCG hCG 10000

5000

0 1 23456789101112

Week

Figure 2. Weekly serum beta-hCG. 236 Ünal O et al., Treatment of Viable Cesarean Scar Ectopic Pregnancy with Intraamniotic Methotrexate Injection

treatment, the scar pregnancy begun to resorb treatment and prevents the surgical operation rapidly. Since the scar pregnancy is a rare form of requirements that may cause hysterectomy. the ectopic pregnancy, treatment schedule is dif- fernt according to the patient. The data in the lit- References erature is mostly formed of the case reports. Based 1. Maymon R, Halperin R, Mendlovic S, Schneider D, Herman on the presented case, transvaginal USG and A. Ectopic pregnancies in a Caesarean scar: review of the serum beta-hCG are important indicators in the fol- medical approach to an iatrogenic complication. Hum Rep- low up of the scar pregnancy treatment. Beta-hCG rod Update. Hum Reprod Update. 2004 Nov-Dec;10(6):515- values that don’t reduce or indifference of ultra- 23. Epub 2004 Sep 16. sonographic pregnancy image are related to the 2. Maymon R, Halperin R, Mendlovic S, Schneider D, Vaknin Z, Herman A, Pansky M. Ectopic pregnancies in Caesarean unsuccessful treatment or readministration of dose. section scars: the 8 year experience of one medical centre. On the other hand, resorbation of the scar preg- Hum Reprod 2004; 19(2): 278-84. nancy ultrasonographic image, administrated 3. Seow KM, Huang LW, Lin YH, Lin MY, Tsai YL, Hwang JL. intraamniotic MTX may last 2-12 months.3,7 Cesarean scar pregnancy: issues in management. Ult- Researching the literature, 54% of the ectopic preg- rasound Obstet Gynecol 2004; 23(3):247-53. nancy cases delivered 2 or more cesarean fetus 4. Doubilet PM, Benson CB, Frates MC, Ginsburg E. Sonog- and 30% had dilatation or curettage operation. For raphically guided minimally invasive treatment of unusual ectopic pregnancies. J Ultrasound Med 2004; 23(3): 359-70. the women with ectopic pregnancy, placental 5. Yang MJ, Jeng MH. Combination of transarterial em- pathology (placenta previa) history and the ones bolization of uterine arteries and conservative surgical treat- with 2 or more cesarean (in particular, because of ment for pregnancy in a cesarean section scar. A report of bottom-down presentation), the scar pregnancy 3 cases. J Reprod Med 2003; 48(3): 213-6. 1 development is more probable. 6. Arslan M, Pata O, Dilek TU, Aktas A, Aban M, Dilek S. In conclusion, cesarean scar pregnancies are Treatment of viable cesarean scar ectopic pregnancy with suction curettage. Int J Gynaecol Obstet 2005; 89(2): 163-6. frequently observed in recent years as cesarean 7. Haimov-Kochman R, Sciaky-Tamir Y, Yanai N, Yagel S. births are increased. Being aware of this possibili- Conservative management of two ectopic pregnancies imp- ty and using early transvaginal USG augment the lanted in previous uterine scars. Ultrasound Obstet Gynecol early diagnosis and the success of the conservative 2002; 19(6): 616-9. PER‹NATOLOJ‹ JOURNAL Volume 13 / Issue 4 / 2005

Contents

Viewpoint Delivery Methods in Multifetal Pregnancies 187 Mehmet Okan Özkaya, Mekin Sezik, Hakan Kaya Research Articles Umbilical Artery Acid-Base Status and Lactate Levels in 191 Term and Preterm Healthy Newborns: Relation to Delivery Mode Ener Ça¤r› Dinleyici, Neslihan Tekin, Mehmet Arif Akflit, Baflar Tekin, Ömer Çolak Relationship Between Umbilical Artery Doppler 198 Investigations and Perinatal Outcome in Patients with HELLP Syndrome Mekin Sezik, Mehmet Okan Özkaya, Hülya Toyran Sezik, Elif Gül Yapar, Hakan Kaya Misoprostol for Second and Third-Trimester Labor Induction in 203 Women with Previous Cesarean Delivery Halil Aslan, Altan Cebeci, Yavuz Ceylan Vaginal Birth After Cesarean Section: Is It Safe? 208 Emre Sinan Güngör, Egemen Ertafl, Perran Moröy, fievki Çelen, Nuri Dan›flman, Leyla Mollamahmuto¤lu Retrospective Analysis of Multiple Pregnancies 213 Mahmut Erdemo¤lu, Ahmet Kale, Nurten Akdeniz, Ahmet Yal›nkaya, Y›lmaz Özcan, Murat Yayla

Case Reports The Predictive Value of Middle Cerebral Artery Peak 218 Systolic Velocity in Repeated Intrauterine Transfusion: A Case Report Yeflim Bülbül Baytur, Ümit Sungurtekin ‹nceboz, Tayfun Özçak›r, Y›ld›z Uyar, Hüsnü Ça¤lar Death of One Fetus in Twin Pregnancy: 223 Report of Four Cases Semih Mun, Tolga M›zrak, Cüneyt Eftal Taner, Gülflen Derin, Cem Büyüktosun Impetigo Herpetiformis: A Case Report 227 ‹ncim Bezircio¤lu, Merve Biçer, Levent Karc›, Füsun Özder, Ali Balo¤lu Treatment of Viable Cesarean Scar Ectopic Pregnancy with Intraamniotic 232 Methotrexate Injection Orhan Ünal, Olufl Api, Bülent Kars, Salim Korucu, Çi¤dem Korucu, Sadullah Bulut Index Subject and Author Index 247