http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–4 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.942629
ORIGINAL ARTICLE
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Induction of labor in twin pregnancies with oral misoprostol versus vaginal dinoprostone – is it effective and safe? Georgine Huber, Heike Schu¨tz, and Birgit Seelbach-Go¨bel Department of Obstetrics and Gynecology, University Regensburg, St. Hedwig Hospital, Regensburg, Germany
Abstract
Keywords
Objective: To compare the effectiveness and safety of oral misoprostol versus vaginal dinoprostone for the induction of labor in twin pregnancies. Methods: All twin pregnancies 34 weeks 0 days that were induced with either misoprostol or dinoprostone in St. Hedwig Hospital between 2002 and 2013 were included in this retrospective study. Length of induction, mode of delivery, maternal and neonatal outcomes were compared between the two groups. Results: After identifying 186 twin mothers matching the inclusion criteria, 154 women were induced with misoprostol (group A) and 32 with dinoprostone (group B). There were no differences in demographic data between the groups. Rates of successful vaginal delivery (53.9% versus 56.3%) and length of induction to delivery (30.2 h versus 26.9 h) were also similar. There were slightly higher rates of postpartum hemorrhage in group B (16.6% versus 10.8%), but without reaching statistical significance. Neonatal outcomes regarding umbilical artery pH 57.20 and one minute Apgar also were without significant differences. Conclusions: Study data indicate that oral misoprostol and vaginal dinoprostone are similarly effective and safe for the induction of labor in twin gestations. Further trials with larger series are needed to confirm these results.
Dinoprostone, labor induction, misoprostol, time of delivery, twin gestation
Introduction In singleton gestations, induction of labor is a routine procedure in obstetrical care. In twin pregnancies, the best possible obstetric management and timing for induction of labor versus expectant management is a subject of controversial discussion. The evidence for standard protocols is limited and rarely based on large study numbers. The National Institute for Health and Clinical Excellence (Clinical Guidelines) recommends elective induction of labor from 36 weeks 0 days in monochorionic twin pregnancies and elective birth from 37 weeks 0 days in dichorionic twin gestations. This recommendation is based on the fact of increased risk of fetal death in ongoing pregnancies beyond 38 weeks 0 days [1–3]. The American College of Obstetricians and Gynecologists recommends delivery of uncomplicated dichorionic twins at 38 weeks 0 days to 38 weeks 6 days and uncomplicated monochorionic twins at 34 weeks 0 days to 37 weeks 6 days of gestation [4]. These suggestions are in line with a consensus opinion from a workshop held by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Address for correspondence: Dr. med. Georgine Huber, Frauenklinik St. Hedwig, Steinmetzstrabe 1-3, 93049 Regensburg, Germany. Tel: 0941-369-5204. Fax: 0941-369-5205. E-mail: georgine.huber@ barmherzige-regensburg.de
History Received 7 May 2014 Revised 15 June 2014 Accepted 4 July 2014 Published online 28 July 2014
Society for Maternal-Fetal Medicine [5]. Previous studies have indicated that induction of labor does neither increase adverse maternal or neonatal outcome nor the number of cesarean births [6–9]. While a Bishop Score 6 predicts successful induction with oxytocin, only a very limited number of studies have assessed the use of different prostaglandins for induction of labor in twin gestations. The authors of three reports have demonstrated the safety and efficacy of vaginal or oral misoprostol. In these protocols, misoprostol was either followed by the administration of oxytocin with progress of labor or misoprostol alone was compared with an oxytocin-only protocol [10–12]. Misoprostol is not licensed for the use of labor induction, and administration may be declined by some patients. Therefore, our question of interest was to compare misoprostol with an alternative, licensed prostaglandin (dinoprostone E2 vaginal tablet) and to explore potential differences in safety and effectiveness for induction of labor in twin gestations.
Methods Between January 2002 and December 2013, an overall of 1099 mothers of twins 24 weeks and 0 days of gestation were delivered in St. Hedwig Hospital, 443 mothers gave birth vaginally. Data for the study were collected retrospectively from the obstetric database, including all twin
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pregnancies undergoing induction of labor at a gestational age 34 weeks 0 days (n ¼ 186). All patients eligible for induction gave written informed consent. Two groups of patients were defined: group A consisted of 154 patients with misoprostol (prostaglandin E1, PGE1) for induction of labor, group B included 32 patients preferring dinoprostone (prostaglandin E2, PGE2). The patient sample included 98 nulliparae and 88 multiparous patients, 141 pregnancies were dichorionic and 45 gestations were monochorionic twin pregnancies. In order to avoid very small sample sizes, we did not divide into subgroups with regard to parity or chorionicity, since there was no statistically significant difference within the groups of patients. Inclusion criteria for induction of labor were: 37 weeks 0 days of gestation, presenting fetus in vertex position, premature rupture of membranes, oligohydramnios in one or both twins, intrauterine growth restriction 5 percentile, arrest of growth in one or both twins, non-reassuring fetal heart rate tracing, maternal conditions such as preeclampsia and patient’s choice. The PGE1-protocol for induction of labor consisted of a first dose of 50 mg oral misoprostol, followed by 100 mg after four hours. Maximum daily dose of misoprostol was 300 mg, administered for a maximum of three consecutive days. The PGE2-protocol also was applied for a maximum of three days, the 3 mg tablet administered vaginally every 6 h, not exceeding two tablets within 24 h. All patients received cardiotocography monitoring for a minimum of 60 min after application of the respective prostaglandin to rule out fetal distress and uterine hyperstimulation. The two groups were compared with regard to demographic data such as maternal age, parity, body mass index (BMI, kg per m2) and chorionicity of the twin gestation. The analysis of the obstetric outcome investigated the mode of delivery (vaginal, including vacuum extractions, versus cesarean delivery), length of induction to delivery of the first twin (hours, mean values) and postpartum hemorrhage (PPH, as defined by WHO4500 ml). Comparison of neonatal outcomes included mean values of umbilical artery pH, umbilical artery pH57.20 and mean values of Apgar scores at one minute in either twin. All data were processed using the Microsoft ExcelÕ program 2010 (Microsoft Corporation, Redmond, WA). Statistical analysis included the Student’s t-test and Fisher test, with p50.05 considered statistically significant. This study was approved by the Institutional Review Board of the St. Hedwig Hospital.
Results As listed in Table 1, demographic data like maternal age, BMI and parity were similar in both groups; also, there was no statistically significant difference regarding the number of dichorionic and monochorionic pregnancies. Table 2 presents the obstetric outcomes. In group A, 83 patients (53.9%) had a vaginal twin birth. Vacuum extraction had to be performed in seven deliveries (8.4%) because of fetal distress in the second twin. Indications for cesarean section (71 deliveries, 46.1%) were as follows: failed induction in 6 patients (8.5%), arrest disorders of the active phase in 46 patients (64.8%) and non-reassuring
J Matern Fetal Neonatal Med, Early Online: 1–4
Table 1. Maternal demographic data for induction of labor in twin gestations.
Maternal age (years) Body mass index (kg/m2) Paritity Primiparous Multiparous Chorionicity Dichorionic diamniotic Monochorionic diamniotic
Group A (n ¼ 154): misoprostol
Group B (n ¼ 32): dinoprostone
p values
33.1 (±5.2) 25.9 (±5.0)
32.7 (±4.9) 26.7 (±5.3)
NS NS
81 (52.6%) 73 (47.4%)
17 (53.1%) 15 (46.8%)
NS NS
116 (75.3%) 38 (24.6%)
25 (78.1%) 7 (21.8%)
NS NS
All values are expressed as n (%) or mean ± standard deviation; NS ¼ not significant.
Table 2. Obstetric outcome for induction of labor in twin gestations. Group A (n ¼ 154): misoprostol Vaginal deliveries 83 Non-assisted vaginal 76 Vacuum extraction 7 Cesarean section 71 Indications for cesarean section Failure of induction 6 Failure to progress 46 Non-reassuring fetal 19 heart rate monitoring
Group B (n ¼ 32): dinoprostone
p values
(53.9%) (91.6%) (8.4%) (46.1%)
18 16 2 14
(56.3%) (88.9%) (11.1%) (43.7%)
NS NS NS NS
(8.5%) (64.8%) (26.8%)
2 (14.3%) 10 (71.4%) 2 (14.3%)
NS NS NS
All values are expressed as n (%); NS, not significant.
Table 3. Length of induction and postpartum hemorrhage in twin deliveries. Group A (n ¼ 154): misoprostol Length of induction-delivery 30.2 (±7.9) (hours) Postpartum hemorrhage (4500 ml) Vaginal delivery 9 (10.8%) Cesarean section 6 (8.5%)
Group B (n ¼ 32): dinoprostone
p values
26.9 (±9.9)
NS
3 (16.6%) 2 (14.2%)
NS NS
All values are expressed as n (%) or mean ± standard deviation; NS, not significant.
fetal heart rate monitoring in one or both fetuses in 19 cases (26.8%). Group B consisted of 18 patients (56.3%) with a successful vaginal delivery, two vacuum extractions (11.1%) were performed. Fourteen cesarean sections (43.7%) had to be indicated: 2 cases of failed induction (14.3%), 10 patients failed to progress in the second stage of labor (71.4%) and fetal distress (14.3%) occurred during two deliveries. The data reported in Table 2 does not show statistically significant differences between PGE1 and PGE2 with regard to the number of successful vaginal deliveries in twins. Table 3 summarizes the length of induction to delivery and the rates of PPH in both groups: after induction of labor with misoprostol, mean duration was 30.2 (±7.9) h until the first twin was delivered vaginally, versus 26.9 (±9.9) h in
Labor induction twins
DOI: 10.3109/14767058.2014.942629
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Table 4. Neonatal outcome for induction of labor in twin gestations.
Vaginal delivery Umbilical artery pH Umbilical artery pH 57.20 1-min-APGAR Cesarean section Umbilical artery pH Umbilical artery pH 57.20 1-min-APGAR
Group A (n ¼ 154): misoprostol
Group B (n ¼ 32): dinoprostone
Twin 1 7.29 (±0.04) 7 (8.4%) 9
Twin 2 7.26 (±0.05) 9 (10.8%) 8
Twin 1 7.26 (±0.02) 2 (11.1%) 9
Twin 2 7.23 (±0.04) 2 (11.1%) 8
NS NS NS
7.31 (±0.05) 3 (3.6%) 9
7.32 (±0.04) 4 (4.8%) 8
7.30 (±0.04) 1 (5.6%) 8
7.33 (±0.05) 1 (5.6%) 8
NS NS NS
p values
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All values are expressed as n (%) or mean ± standard deviation; NS, not significant.
the dinoprostone group. We have observed slightly higher rates of PPH in group B patients (16.6%; n ¼ 3 after vaginal delivery and 14.2%; n ¼ 2 after cesarean section) compared with patients of group A (10.8%; n ¼ 9 after vaginal birth and 8.5%; n ¼ 6 after cesarean section). These results showed no statistically significant difference. The fetal outcome variables are given in Table 4. After vaginal birth, we found similar mean values of umbilical artery pH (group A, twin 1: 7.29; group B, twin 1: 7.26; group A, twin 2: 7.26; and group B, twin 2: 7.23) and comparable rates of umbilical artery pH 57.20 (group A, twin 1: 8.5%; group B, twin 1: 11.1%; group A, twin 2: 10.8%; and group B, twin 2: 11.1%) in both groups and in both twins. After cesarean section, there also were no statistically significant differences between the misoprostol group and the dinoprostone group regarding umbilical artery pH values. Mean values of Apgar scores at one minute did neither differ significantly between group A and B, nor between both twins, nor between the modes of delivery.
Discussion The data of our study indicate that oral misoprostol and vaginal dinoprostone are similarly effective and safe for the induction of labor in twin gestations. Both methods for cervical ripening do not differ significantly with regard to rates of vaginal deliveries, length of birth and maternal/ neonatal outcome. Contrary to the studies of Simo˜es et al. and Bush et al., who showed vaginal delivery rates of 77% and of 69%, respectively, only 54% of our patients induced with misoprostol gave birth vaginally [10,12]. After induction of labor with dinoprostone, 56% of our study group had a successful vaginal delivery. Since indications for cesarean section were similar, different definitions of arrest of labor in the first or second stage of delivery might explain the diverging results. Leftwich et al. have demonstrated that progression of active phase labor is slower in twin deliveries, independent of parity [13]. Our results are in line with data from Barrett et al., who also showed a frequency of more than 40% cesarean sections in vaginally intended twin births [8]. However, the authors describe the way of labor induction as using ‘‘standard protocols’’ without closer specification. Previous research has indicated that a maternal BMI 30 kg/m2 is an important predictor for successful induction in twin gestations [14]. Our own patient population showed BMI values below 30 kg/m2, but we still did not achieve higher rates of vaginal births.
The double-blind trial of Surbek et al. demonstrated superior effectiveness for vaginal misoprostol compared with dinoprostone regarding induction to delivery time in singleton pregnancies [15]. In contrast to these results, we observed slightly longer induction to delivery intervals for the misoprostol group (30.2 h versus 26.9 h for the dinoprostone group) in twin labor induction. Although not statistically significant, the number of cesarean sections due to non-reassuring fetal heart rate tracing in one or both twins differed clearly between our two groups (28.8% after induction with misoprostol versus 14.3% after induction with dinoprostone). These findings vary from those obtained by Faucett et al. and Aghideh et al., who could not detect higher rates of fetal distress after induction of labor with misoprostol versus dinoprostone in singleton pregnancies [16,17]. Our data are in accordance with the observation in literature that misoprostol more often leads to cardiotocographic abnormalities than dinoprostone. Higher doses of misoprostol (50 mg and 100 mg as administered in our study) seem more likely to cause cardiotocographic changes such as early decelerations [18–20]. In singleton pregnancies, obstetricians can easily prove the unborn’s well-being by performing fetal blood sampling during labor. Thus, high rates of cesarean sections caused by non-reassuring fetal heart rate can be avoided. In twin pregnancies, not only do we lack the chance of fetal blood sampling in the second twin but also our risk tolerance might be lower regarding when to perform a cesarean section in case of non-reassuring fetal heart rate monitoring. Potential side-effects of misoprostol are uterine hyperstimulation and uterine rupture. The results of our study compare favorably with those reported in literature, confirming the safe administration of PGE1 for induction of labor in twin pregnancies: there was no case of uterine rupture [10,12]. Suzuki et al. examined the safety of PGE2 with oral application, no maternal side-effects were observed after administration to twin mothers [21]. In an article investigating risk factors for PPH after vaginal delivery of twins, the authors cited rates of 24% PPH, the induction of labor being one of the main risk factors [22]. Our findings show lower risks for PPH, especially in the misoprostol group: 11% of our patients suffered from PPH versus 17% in the dinoprostone group. It is difficult to compare our findings of neonatal outcome to previous studies because there is only limited research work available. We did not find severe adverse neonatal outcomes in both of our induction groups. Bush et al. showed a rate of umbilical artery pH 57.20 in 3.5% of neonates
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after misoprostol induction, whereas we found umbilical artery pH 57.20 in 8.5% for the first twin and in 10.8% for the second twin, respectively [12]. To the best of our knowledge, this is the first study discussing the use of two prostaglandins, oral misoprostol and vaginal dinoprostone, for the induction of labor in twin gestations. Compared with previous works, our study provides quite a large number of misoprostol induced twin gestations. A limitation of our analysis is the small sample size of the dinoprostone group, which increases the risk of not identifying statistical differences in outcome between the two groups. The low number originates from the patients’ clear preference for the oral induction agent misoprostol. Similar findings were reported by Dodd et al., comparing oral misoprostol with vaginal dinoprostone gel for induction of labor in singleton pregnancies. Oral treatment was preferred by almost 60% of women [23]. However, we acknowledge the fact that further trials with larger series are needed to confirm our results.
Declaration of interest The authors report no declarations of interest.
References 1. NICE Clinical Guidelines No 129, Sept. 2011 RCOG. Available from: http://www.nice.org.uk/nicemedia/live/13571/56422/56422. pdf [last accessed 5 May 2014]. 2. Hartley RS, Emanuel I, Hitti J. Perinatal mortality and neonatal morbidity rates among twin pairs at different gestational ages: optimal delivery timing at 37 to 38 weeks’ gestation. Am J Obstet Gynecol 2001;184:451–8. 3. Kahn B, Lumey LH, Zybert PA, et al. Prospective risk of fetal death in singleton, twin, and triplet gestations: implications for practice. Obstet Gynecol 2003;102:685–92. 4. American College of Obstetricians and Gynecologists. Medically indicated late-preterm and early-term deliveries. Committee Opinion No.560. Obstet Gynecol 2013;121:908–10. 5. Spong CY, Mercer BM, D’Alton M, et al. Timing of indicated latepreterm and early-term birth. Obstet Gynecol 2011;118:323–33. 6. Dodd JM, Crowther CA, Haslam RR, Robinson JS; Twins Timing of Birth Trial Group. Elective birth at 37 weeks of gestation versus standard care for women with an uncomplicated twin pregnancy at term: the Twins Timing of Birth Randomised Trial. BJOG 2012; 119:964–73. 7. Harle T, Brun JL, Leng JJ. Induction of labor in twin pregnancy after 36 weeks does not increase maternal-fetal morbidity. Int J Gynaecol Obstet 2002;77:15–21.
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8. Barrett JF, Hannah ME, Hutton EK, et al; Twin Birth Study Collaborative Group. A randomized trial of planned cesarean or vaginal delivery twin pregnancy. N Engl J Med 2013;360: 1295–305. 9. Taylor M, Rebarber A, Saltzman DH, et al. Induction of labor in twin compared with singleton pregnancies. Obstet Gynecol 2012; 120:297–301. 10. Simo˜es T, Condec¸o P, Dias E, et al. Induction of labor with oral misoprostol in nulliparous mothers of twins. J Perinat Med 2006; 34:111–14. 11. Wolfe MD, de la Torre L, Moore LE, et al. Is the protocol for induction of labor in singletons applicable to twin gestations? J Reprod Med 2013;58:137–42. 12. Bush MC, Csaba A, Eddleman KA, Saphier CJ. Is misoprostol safe for labor induction in twin gestations? J Matern Fetal Neonatal Med 2006;19:35–8. 13. Leftwich HK, Zaki MN, Wilkins I, Hibbard JU. Labor patterns in twin gestations. Am J Obstet Gynecol 2013;209: 254.e1–5. 14. Park KH, Hong JS, Kang WS, et al. Body mass index, Bishop score, and sonographic measurement of the cervical length as predictors of successful labor induction in twin gestations. J Perinat Med 2009;37:519–23. 15. Surbek DV, Boesinger H, Hoesli I, et al. A double-blind comparison of the safety and efficacy of intravaginal misoprostol and prostaglandin E2 to induce labor. Am J Obstet Gynecol 1997;177: 1018–23. 16. Faucett AM, Daniels K, Lee HC, et al. Oral misoprostol versus vaginal dinoprostone for labor induction in nulliparous women at term. J Perinatol 2014;34:95–9. 17. Aghideh FK, Mullin PM, Ingles S, et al. A comparison of obstetrical outcomes with labor induction agents used at term. J Matern Fetal Neonatal Med 2014;27:592–6. 18. Loto OM, Ikuomola AA, Ayuba II, Onwudiegwu U. Comparative study of the outcome of induction of labor using 25mg and 50mg of vaginal misoprostol. J Matern Fetal Neonatal Med 2012;25: 2359–62. 19. Pevzner L, Alfirevic Z, Powers BL, Wing DA. Cardiotocographic abnormalities associated with misoprostol and dinoprostone cervical ripening and labor induction. Eur J Obstet Gynecol Reprod Biol 2011;156:144–8. 20. Ozkan S, Caliskan E, Doger E, et al. Comparative efficacy and safety of vaginal misoprostol versus dinoprostone vaginal insert in labor induction at term: a randomized trial. Arch Gynecol Obstet 2009;280:19–24. 21. Suzuki S, Otsubo Y, Sawa R, et al. Clinical trial of induction of labor versus expectant management in twin pregnancy. Gynecol Obstet Invest 2000;49:24–7. 22. Suzuki S, Kikuchi F, Ouchi N, et al. Risk factors for postpartum hemorrhage after vaginal delivery of twins. J Nippon Med Sch 2007;74:414–17. 23. Dodd JM, Crowther CA, Robinson JS. Oral misoprostol for induction of labour at term: randomized controlled trial. BMJ 2006;332:509–13.
ORIGINAL ARTICLE
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Oregon Health Sciences University on 03/26/15 For personal use only.
Induction of labor in twin pregnancies with oral misoprostol versus vaginal dinoprostone – is it effective and safe? Georgine Huber, Heike Schu¨tz, and Birgit Seelbach-Go¨bel Department of Obstetrics and Gynecology, University Regensburg, St. Hedwig Hospital, Regensburg, Germany
Abstract
Keywords
Objective: To compare the effectiveness and safety of oral misoprostol versus vaginal dinoprostone for the induction of labor in twin pregnancies. Methods: All twin pregnancies 34 weeks 0 days that were induced with either misoprostol or dinoprostone in St. Hedwig Hospital between 2002 and 2013 were included in this retrospective study. Length of induction, mode of delivery, maternal and neonatal outcomes were compared between the two groups. Results: After identifying 186 twin mothers matching the inclusion criteria, 154 women were induced with misoprostol (group A) and 32 with dinoprostone (group B). There were no differences in demographic data between the groups. Rates of successful vaginal delivery (53.9% versus 56.3%) and length of induction to delivery (30.2 h versus 26.9 h) were also similar. There were slightly higher rates of postpartum hemorrhage in group B (16.6% versus 10.8%), but without reaching statistical significance. Neonatal outcomes regarding umbilical artery pH 57.20 and one minute Apgar also were without significant differences. Conclusions: Study data indicate that oral misoprostol and vaginal dinoprostone are similarly effective and safe for the induction of labor in twin gestations. Further trials with larger series are needed to confirm these results.
Dinoprostone, labor induction, misoprostol, time of delivery, twin gestation
Introduction In singleton gestations, induction of labor is a routine procedure in obstetrical care. In twin pregnancies, the best possible obstetric management and timing for induction of labor versus expectant management is a subject of controversial discussion. The evidence for standard protocols is limited and rarely based on large study numbers. The National Institute for Health and Clinical Excellence (Clinical Guidelines) recommends elective induction of labor from 36 weeks 0 days in monochorionic twin pregnancies and elective birth from 37 weeks 0 days in dichorionic twin gestations. This recommendation is based on the fact of increased risk of fetal death in ongoing pregnancies beyond 38 weeks 0 days [1–3]. The American College of Obstetricians and Gynecologists recommends delivery of uncomplicated dichorionic twins at 38 weeks 0 days to 38 weeks 6 days and uncomplicated monochorionic twins at 34 weeks 0 days to 37 weeks 6 days of gestation [4]. These suggestions are in line with a consensus opinion from a workshop held by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Address for correspondence: Dr. med. Georgine Huber, Frauenklinik St. Hedwig, Steinmetzstrabe 1-3, 93049 Regensburg, Germany. Tel: 0941-369-5204. Fax: 0941-369-5205. E-mail: georgine.huber@ barmherzige-regensburg.de
History Received 7 May 2014 Revised 15 June 2014 Accepted 4 July 2014 Published online 28 July 2014
Society for Maternal-Fetal Medicine [5]. Previous studies have indicated that induction of labor does neither increase adverse maternal or neonatal outcome nor the number of cesarean births [6–9]. While a Bishop Score 6 predicts successful induction with oxytocin, only a very limited number of studies have assessed the use of different prostaglandins for induction of labor in twin gestations. The authors of three reports have demonstrated the safety and efficacy of vaginal or oral misoprostol. In these protocols, misoprostol was either followed by the administration of oxytocin with progress of labor or misoprostol alone was compared with an oxytocin-only protocol [10–12]. Misoprostol is not licensed for the use of labor induction, and administration may be declined by some patients. Therefore, our question of interest was to compare misoprostol with an alternative, licensed prostaglandin (dinoprostone E2 vaginal tablet) and to explore potential differences in safety and effectiveness for induction of labor in twin gestations.
Methods Between January 2002 and December 2013, an overall of 1099 mothers of twins 24 weeks and 0 days of gestation were delivered in St. Hedwig Hospital, 443 mothers gave birth vaginally. Data for the study were collected retrospectively from the obstetric database, including all twin
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Oregon Health Sciences University on 03/26/15 For personal use only.
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G. Huber et al.
pregnancies undergoing induction of labor at a gestational age 34 weeks 0 days (n ¼ 186). All patients eligible for induction gave written informed consent. Two groups of patients were defined: group A consisted of 154 patients with misoprostol (prostaglandin E1, PGE1) for induction of labor, group B included 32 patients preferring dinoprostone (prostaglandin E2, PGE2). The patient sample included 98 nulliparae and 88 multiparous patients, 141 pregnancies were dichorionic and 45 gestations were monochorionic twin pregnancies. In order to avoid very small sample sizes, we did not divide into subgroups with regard to parity or chorionicity, since there was no statistically significant difference within the groups of patients. Inclusion criteria for induction of labor were: 37 weeks 0 days of gestation, presenting fetus in vertex position, premature rupture of membranes, oligohydramnios in one or both twins, intrauterine growth restriction 5 percentile, arrest of growth in one or both twins, non-reassuring fetal heart rate tracing, maternal conditions such as preeclampsia and patient’s choice. The PGE1-protocol for induction of labor consisted of a first dose of 50 mg oral misoprostol, followed by 100 mg after four hours. Maximum daily dose of misoprostol was 300 mg, administered for a maximum of three consecutive days. The PGE2-protocol also was applied for a maximum of three days, the 3 mg tablet administered vaginally every 6 h, not exceeding two tablets within 24 h. All patients received cardiotocography monitoring for a minimum of 60 min after application of the respective prostaglandin to rule out fetal distress and uterine hyperstimulation. The two groups were compared with regard to demographic data such as maternal age, parity, body mass index (BMI, kg per m2) and chorionicity of the twin gestation. The analysis of the obstetric outcome investigated the mode of delivery (vaginal, including vacuum extractions, versus cesarean delivery), length of induction to delivery of the first twin (hours, mean values) and postpartum hemorrhage (PPH, as defined by WHO4500 ml). Comparison of neonatal outcomes included mean values of umbilical artery pH, umbilical artery pH57.20 and mean values of Apgar scores at one minute in either twin. All data were processed using the Microsoft ExcelÕ program 2010 (Microsoft Corporation, Redmond, WA). Statistical analysis included the Student’s t-test and Fisher test, with p50.05 considered statistically significant. This study was approved by the Institutional Review Board of the St. Hedwig Hospital.
Results As listed in Table 1, demographic data like maternal age, BMI and parity were similar in both groups; also, there was no statistically significant difference regarding the number of dichorionic and monochorionic pregnancies. Table 2 presents the obstetric outcomes. In group A, 83 patients (53.9%) had a vaginal twin birth. Vacuum extraction had to be performed in seven deliveries (8.4%) because of fetal distress in the second twin. Indications for cesarean section (71 deliveries, 46.1%) were as follows: failed induction in 6 patients (8.5%), arrest disorders of the active phase in 46 patients (64.8%) and non-reassuring
J Matern Fetal Neonatal Med, Early Online: 1–4
Table 1. Maternal demographic data for induction of labor in twin gestations.
Maternal age (years) Body mass index (kg/m2) Paritity Primiparous Multiparous Chorionicity Dichorionic diamniotic Monochorionic diamniotic
Group A (n ¼ 154): misoprostol
Group B (n ¼ 32): dinoprostone
p values
33.1 (±5.2) 25.9 (±5.0)
32.7 (±4.9) 26.7 (±5.3)
NS NS
81 (52.6%) 73 (47.4%)
17 (53.1%) 15 (46.8%)
NS NS
116 (75.3%) 38 (24.6%)
25 (78.1%) 7 (21.8%)
NS NS
All values are expressed as n (%) or mean ± standard deviation; NS ¼ not significant.
Table 2. Obstetric outcome for induction of labor in twin gestations. Group A (n ¼ 154): misoprostol Vaginal deliveries 83 Non-assisted vaginal 76 Vacuum extraction 7 Cesarean section 71 Indications for cesarean section Failure of induction 6 Failure to progress 46 Non-reassuring fetal 19 heart rate monitoring
Group B (n ¼ 32): dinoprostone
p values
(53.9%) (91.6%) (8.4%) (46.1%)
18 16 2 14
(56.3%) (88.9%) (11.1%) (43.7%)
NS NS NS NS
(8.5%) (64.8%) (26.8%)
2 (14.3%) 10 (71.4%) 2 (14.3%)
NS NS NS
All values are expressed as n (%); NS, not significant.
Table 3. Length of induction and postpartum hemorrhage in twin deliveries. Group A (n ¼ 154): misoprostol Length of induction-delivery 30.2 (±7.9) (hours) Postpartum hemorrhage (4500 ml) Vaginal delivery 9 (10.8%) Cesarean section 6 (8.5%)
Group B (n ¼ 32): dinoprostone
p values
26.9 (±9.9)
NS
3 (16.6%) 2 (14.2%)
NS NS
All values are expressed as n (%) or mean ± standard deviation; NS, not significant.
fetal heart rate monitoring in one or both fetuses in 19 cases (26.8%). Group B consisted of 18 patients (56.3%) with a successful vaginal delivery, two vacuum extractions (11.1%) were performed. Fourteen cesarean sections (43.7%) had to be indicated: 2 cases of failed induction (14.3%), 10 patients failed to progress in the second stage of labor (71.4%) and fetal distress (14.3%) occurred during two deliveries. The data reported in Table 2 does not show statistically significant differences between PGE1 and PGE2 with regard to the number of successful vaginal deliveries in twins. Table 3 summarizes the length of induction to delivery and the rates of PPH in both groups: after induction of labor with misoprostol, mean duration was 30.2 (±7.9) h until the first twin was delivered vaginally, versus 26.9 (±9.9) h in
Labor induction twins
DOI: 10.3109/14767058.2014.942629
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Table 4. Neonatal outcome for induction of labor in twin gestations.
Vaginal delivery Umbilical artery pH Umbilical artery pH 57.20 1-min-APGAR Cesarean section Umbilical artery pH Umbilical artery pH 57.20 1-min-APGAR
Group A (n ¼ 154): misoprostol
Group B (n ¼ 32): dinoprostone
Twin 1 7.29 (±0.04) 7 (8.4%) 9
Twin 2 7.26 (±0.05) 9 (10.8%) 8
Twin 1 7.26 (±0.02) 2 (11.1%) 9
Twin 2 7.23 (±0.04) 2 (11.1%) 8
NS NS NS
7.31 (±0.05) 3 (3.6%) 9
7.32 (±0.04) 4 (4.8%) 8
7.30 (±0.04) 1 (5.6%) 8
7.33 (±0.05) 1 (5.6%) 8
NS NS NS
p values
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All values are expressed as n (%) or mean ± standard deviation; NS, not significant.
the dinoprostone group. We have observed slightly higher rates of PPH in group B patients (16.6%; n ¼ 3 after vaginal delivery and 14.2%; n ¼ 2 after cesarean section) compared with patients of group A (10.8%; n ¼ 9 after vaginal birth and 8.5%; n ¼ 6 after cesarean section). These results showed no statistically significant difference. The fetal outcome variables are given in Table 4. After vaginal birth, we found similar mean values of umbilical artery pH (group A, twin 1: 7.29; group B, twin 1: 7.26; group A, twin 2: 7.26; and group B, twin 2: 7.23) and comparable rates of umbilical artery pH 57.20 (group A, twin 1: 8.5%; group B, twin 1: 11.1%; group A, twin 2: 10.8%; and group B, twin 2: 11.1%) in both groups and in both twins. After cesarean section, there also were no statistically significant differences between the misoprostol group and the dinoprostone group regarding umbilical artery pH values. Mean values of Apgar scores at one minute did neither differ significantly between group A and B, nor between both twins, nor between the modes of delivery.
Discussion The data of our study indicate that oral misoprostol and vaginal dinoprostone are similarly effective and safe for the induction of labor in twin gestations. Both methods for cervical ripening do not differ significantly with regard to rates of vaginal deliveries, length of birth and maternal/ neonatal outcome. Contrary to the studies of Simo˜es et al. and Bush et al., who showed vaginal delivery rates of 77% and of 69%, respectively, only 54% of our patients induced with misoprostol gave birth vaginally [10,12]. After induction of labor with dinoprostone, 56% of our study group had a successful vaginal delivery. Since indications for cesarean section were similar, different definitions of arrest of labor in the first or second stage of delivery might explain the diverging results. Leftwich et al. have demonstrated that progression of active phase labor is slower in twin deliveries, independent of parity [13]. Our results are in line with data from Barrett et al., who also showed a frequency of more than 40% cesarean sections in vaginally intended twin births [8]. However, the authors describe the way of labor induction as using ‘‘standard protocols’’ without closer specification. Previous research has indicated that a maternal BMI 30 kg/m2 is an important predictor for successful induction in twin gestations [14]. Our own patient population showed BMI values below 30 kg/m2, but we still did not achieve higher rates of vaginal births.
The double-blind trial of Surbek et al. demonstrated superior effectiveness for vaginal misoprostol compared with dinoprostone regarding induction to delivery time in singleton pregnancies [15]. In contrast to these results, we observed slightly longer induction to delivery intervals for the misoprostol group (30.2 h versus 26.9 h for the dinoprostone group) in twin labor induction. Although not statistically significant, the number of cesarean sections due to non-reassuring fetal heart rate tracing in one or both twins differed clearly between our two groups (28.8% after induction with misoprostol versus 14.3% after induction with dinoprostone). These findings vary from those obtained by Faucett et al. and Aghideh et al., who could not detect higher rates of fetal distress after induction of labor with misoprostol versus dinoprostone in singleton pregnancies [16,17]. Our data are in accordance with the observation in literature that misoprostol more often leads to cardiotocographic abnormalities than dinoprostone. Higher doses of misoprostol (50 mg and 100 mg as administered in our study) seem more likely to cause cardiotocographic changes such as early decelerations [18–20]. In singleton pregnancies, obstetricians can easily prove the unborn’s well-being by performing fetal blood sampling during labor. Thus, high rates of cesarean sections caused by non-reassuring fetal heart rate can be avoided. In twin pregnancies, not only do we lack the chance of fetal blood sampling in the second twin but also our risk tolerance might be lower regarding when to perform a cesarean section in case of non-reassuring fetal heart rate monitoring. Potential side-effects of misoprostol are uterine hyperstimulation and uterine rupture. The results of our study compare favorably with those reported in literature, confirming the safe administration of PGE1 for induction of labor in twin pregnancies: there was no case of uterine rupture [10,12]. Suzuki et al. examined the safety of PGE2 with oral application, no maternal side-effects were observed after administration to twin mothers [21]. In an article investigating risk factors for PPH after vaginal delivery of twins, the authors cited rates of 24% PPH, the induction of labor being one of the main risk factors [22]. Our findings show lower risks for PPH, especially in the misoprostol group: 11% of our patients suffered from PPH versus 17% in the dinoprostone group. It is difficult to compare our findings of neonatal outcome to previous studies because there is only limited research work available. We did not find severe adverse neonatal outcomes in both of our induction groups. Bush et al. showed a rate of umbilical artery pH 57.20 in 3.5% of neonates
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G. Huber et al.
after misoprostol induction, whereas we found umbilical artery pH 57.20 in 8.5% for the first twin and in 10.8% for the second twin, respectively [12]. To the best of our knowledge, this is the first study discussing the use of two prostaglandins, oral misoprostol and vaginal dinoprostone, for the induction of labor in twin gestations. Compared with previous works, our study provides quite a large number of misoprostol induced twin gestations. A limitation of our analysis is the small sample size of the dinoprostone group, which increases the risk of not identifying statistical differences in outcome between the two groups. The low number originates from the patients’ clear preference for the oral induction agent misoprostol. Similar findings were reported by Dodd et al., comparing oral misoprostol with vaginal dinoprostone gel for induction of labor in singleton pregnancies. Oral treatment was preferred by almost 60% of women [23]. However, we acknowledge the fact that further trials with larger series are needed to confirm our results.
Declaration of interest The authors report no declarations of interest.
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