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Objective: Induction of labor (IOL) is one of the most widely used obstetric interventions. However, one-fifth of IOLs result in Cesarean section (CS). We aimed to assess maternal and fetal characteristics that influence the likelihood of CS following IOL, according to the indication for CS.Methods: This was a secondary analysis of pooled data from four randomized controlled trials, including women undergoing IOL at term who had a singleton pregnancy and an unfavorable cervix, intact membranes and the fetus in cephalic presentation. The main outcomes of this analysis were CS for failure to progress (FTP) and CS for suspected fetal compromise (SFC). Restricted cubic splines were used to determine whether continuous maternal and fetal characteristics had a non-linear relationship with outcome. Optimal cut-offs for those characteristics with a non-linear pattern were determined based on the maximum area under the receiver-operating-characteristics curve. Adjusted odds ratios (aOR) were computed, using multivariable logistic regression analysis, for the associations between optimally categorized characteristics and outcome.Results: Of a total of 2990 women undergoing IOL, 313 (10.5%) had CS for FTP and 227 (7.6%) had CS for SFC. The risk of CS for FTP was increased in women aged 31-35 years compared with younger women (aOR, 1.51 (95% CI, 1.15-1.99)), in nulliparous compared with parous women (aOR, 8.07 (95% CI, 5.34-12.18)) and in Sub-Saharan African compared with Caucasian women (aOR, 2.09 (95% CI, 1.33-3.28)). Higher body mass index (BMI) increased incrementally the risk of CS for FTP (aOR, 1.06 (95% CI, 1.04-1.08)). High birth-weight percentile was also associated with an increased risk of CS due to FTP (aOR, 2.66 (95% CI, 1.74-4.07) for birth weight between the 80.0th and 89.9th percentiles and aOR, 4.08 (95% CI, 2.75-6.05) for birth weight ≥ 90th percentile, as compared with birth weight between the 20.0th and 49.9th percentiles). For CS due to SFC, higher maternal age (aOR, 1.09 (95% CI, 1.05-1.12)) and BMI (aOR, 1.05 (95% CI, 1.03-1.08)) were associated with an incremental increase in risk. The risk of CS for SFC was increased in nulliparous compared with parous women (aOR, 5.91 (95% CI, 3.76-9.28)) and in South Asian compared with Caucasian women (aOR, 2.50 (95% CI, 1.23-5.10)). Birth weight < 10.0th percentile increased significantly the risk of CS due to SFC (aOR, 1.93 (95% CI, 1.22-3.05)), as compared with birth weight between the 20.0th and 49.9th percentiles. Bishop score did not demonstrate a significant association with the risk of CS for FTP or for SFC.Conclusions: In women undergoing IOL, maternal age, BMI, parity, ethnicity and birth-weight percentile are predictors of CS due to FTP and of CS due to SFC, but the direction and magnitude of the associations differ according to the indication for CS. These characteristics should be considered in combination with the Bishop score to stratify the risk of CS for different indications in women undergoing IOL. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins.Methods: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks' gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth < 37 weeks' gestation in a subsequent pregnancy.Results: Fourteen hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 572 had been allocated to induction of labor using a Foley catheter and 570 to induction of labor using prostaglandins. Of these, 162 (14%) were lost to follow-up. In total, 251 and 258 women had a known subsequent pregnancy > 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38-2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30-3.51).Conclusion: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation.Methods: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands.Results: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes.Conclusion: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the costs of labour induction with oral misoprostol versus Foley catheter.Design: Economic evaluation alongside a randomised controlled trial.Setting: Obstetric departments of six tertiary and 23 secondary care hospitals in the Netherlands.Population: Women with a viable term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix (Bishop score <6) without a previous caesarean section, were randomised for labour induction with oral misoprostol (n = 924) or Foley catheter (n = 921).Methods: We performed economic analysis from a hospital perspective. We estimated direct medical costs associated with healthcare utilisation from randomisation until discharge. The robustness of our findings was evaluated in sensitivity analyses.Main Outcome Measures: Mean costs and differences were calculated per women induced with oral misoprostol or Foley catheter.Results: Mean costs per woman in the oral misoprostol group and Foley catheter group were €4470 versus €4158, respectively [mean difference €312, 95% confidence interval (CI) -€508 to €1063]. Multiple sensitivity analyses did not change these conclusions. However, if cervical ripening for low-risk pregnancies in the Foley catheter group was carried out in an outpatient setting, with admittance to labour ward only at start of active labour, the difference would be €4470 versus €3489, respectively (mean difference €981, 95% CI €225-1817).Conclusions: Oral misoprostol and Foley catheter generate comparable costs. Cervical ripening outside labour ward with a Foley catheter could potentially save almost €1000 per woman.Tweetable Abstract: Oral misoprostol or Foley catheter for induction of labour generates comparable costs. [ABSTRACT FROM AUTHOR]

Objective Some clinicians advise prophylactic administration of antenatal steroids for fetal lung maturation in women with a triplet pregnancy. However, the effect of corticosteroids is limited to 10 to 14 days after administration. The aim of this study was to assess the natural course of triplet pregnancies to allow a better anticipation for administration of corticosteroids. Study Design We collected data on all triplet pregnancies in the Netherlands from 1999 to 2007 from the Netherlands Perinatal Registration. We calculated time to delivery, the risk of delivery in 2-week intervals at different gestational ages, and the time frame between hospital admission and delivery of the first child. Results Median gestational age at delivery of 494 women with a triplet pregnancy was 33+4 weeks (interquartile range of 31-35+1 weeks). Twenty-one women (4.3%) delivered between 22 and 24 weeks and 146 women (29.6%) delivered before 32 weeks. At a gestational age of 24 weeks, the chance to deliver within the next week was 0.6%. For 26, 28, 30, 31, and 32 weeks, these risks were 2.4, 2.5, 8.1, 7, and 16.7%, respectively. Conclusion Before 32 weeks of gestation, prophylactic administration of steroids is not indicated as the risk to deliver within 7 days is < 10%. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Increasingly, maternal administration of 17-[alpha]-hydroxyprogesterone caproate (17-OHPC) is utilized to prevent preterm birth, but the fetal safety of 17-OHPC is still a matter of concern. This study aimed to assess whether exposure to 17-OHPC during the second and third trimesters of pregnancy affects fetal biometry in twin gestations. METHODS: This study included a subset of women with a twin pregnancy who had been previously included in a randomized clinical trial comparing the effectiveness of 17-OHPC and placebo on neonatal outcomes and preterm birth rates in multiple pregnancy. In the present study, the individual growth patterns of femur length, head circumference and abdominal circumference were compared between fetuses of women who had been randomized to receive weekly injections of either 17-OHPC (n = 52) or placebo (n = 58) at between 16-20 and 36 weeks' gestation. RESULTS: The three biometric variables assessed developed similarly in fetuses in both the group exposed to 17-OHPC and the placebo group during the second half of pregnancy. Birth weight adjusted for parity and fetal sex was also comparable between groups. CONCLUSION: The use of 17-OHPC has no adverse effects on fetal biometry and birth weight in twins. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Please cite this paper as: van Dillen J, Mesman J, Zwart J, Bloemenkamp K, van Roosmalen J. Introducing maternal morbidity audit in the Netherlands. BJOG 2010;117:416–421. Objective To describe the panel audit process and to identify substandard care in selected women from a nationwide prospective cohort study into severe acute maternal morbidity (SAMM) in the Netherlands. Design Prospective audit of selected women with SAMM. Setting Eight audit meetings held throughout the Netherlands. Population All pregnant women in the Netherlands. Methods Before each meeting, SAMM details of selected women were sent to all panel members for individual assessment by completing an audit form. During a subsequent plenary meeting, findings were discussed and substandard care factors as judged by the majority of assessors were scored. Main outcome measures Incidence of substandard care and recommendations for improving the quality of care. Results Substandard care was identified in 53 of 67 women (79%). Specific recommendations were formulated concerning the procedure of audit and concerning local as well as national management guidelines. Conclusion Our findings reflect SAMM in the Netherlands and substandard care is present in four out of five women. Ongoing audit of women with SAMM is promoted both at local and national level. [ABSTRACT FROM AUTHOR]

Objective To assess incidence of uterine rupture in scarred and unscarred uteri and its maternal and fetal complications in a nationwide design. Design Population-based cohort study. Setting All 98 maternity units in the Netherlands. Population All women delivering in the Netherlands between August 2004 and August 2006 ( n = 371 021). Methods Women with uterine rupture were prospectively collected using a web-based notification system. Data from all pregnant women in the Netherlands during the study period were obtained from Dutch population-based registers. Results were stratified by uterine scar. Main outcome measures Population-based incidences, severe maternal and neonatal morbidity and mortality, relative and absolute risk estimates. Results There were 210 cases of uterine rupture (5.9 per 10 000 pregnancies). Of these women, 183 (87.1%) had a uterine scar, incidences being 5.1 and 0.8 per 10 000 in women with and without uterine scar. No maternal deaths and 18 cases of perinatal death (8.7%) occurred. The overall absolute risk of uterine rupture was 1 in 1709. In univariate analysis, women with a prior caesarean, epidural anaesthesia, induction of labour (irrespective of agents used), pre- or post-term pregnancy, overweight, non-Western ethnic background and advanced age had an elevated risk of uterine rupture. The overall relative risk of induction of labour was 3.6 (95% confidence interval 2.7–4.8). Conclusion The population-based incidence of uterine rupture in the Netherlands is comparable with other Western countries. Although much attention is paid to scar rupture associated with uterotonic agents, 13% of ruptures occurred in unscarred uteri and 72% occurred during spontaneous labour. [ABSTRACT FROM AUTHOR]

Objective To assess incidence, case fatality rate, risk factors and substandard care in severe maternal morbidity in the Netherlands. Design Prospective population-based cohort study. Setting All 98 maternity units in the Netherlands. Population All pregnant women in the Netherlands. Methods Cases of severe maternal morbidity were collected during a 2-year period. All pregnant women in the Netherlands in the same period acted as reference cohort ( n = 371 021). As immigrant women are disproportionately represented in Dutch maternal mortality statistics, special attention was paid to the ethnic background. In a subset of 2.5% of women, substandard care was assessed through clinical audit. Main outcome measures Incidence, case fatality rates, possible risk factors and substandard care. Results Severe maternal morbidity was reported in 2552 women, giving an overall incidence of 7.1 per 1000 deliveries. Intensive care unit admission was reported in 847 women (incidence 2.4 per 1000), uterine rupture in 218 women (incidence 6.1/10 000), eclampsia in 222 women (incidence 6.2/10 000) and major obstetric haemorrhage in 1606 women (incidence 4.5 per 1000). Non-Western immigrant women had a 1.3-fold increased risk of severe maternal morbidity (95% CI 1.2–1.5) when compared with Western women. Overall case fatality rate was 1 in 53. Substandard care was found in 39 of a subset of 63 women (62%) through clinical audit. Conclusions Severe maternal morbidity complicates at least 0.71% of all pregnancies in the Netherlands, immigrant women experiencing an increased risk. Since substandard care was found in the majority of assessed cases, reduction of severe maternal morbidity seems a mandatory challenge. [ABSTRACT FROM AUTHOR]

Velamentous cord insertion and vasa previa occur more frequently in monochorionic twin pregnancies than in singleton pregnancies. Both have been linked with poor perinatal outcome due to the increased risk of rupture of the velamentous vessels. We present a case of acute fetal distress in 2 fetuses in a monochorionic twin pregnancy caused by ruptured vasa previa that was not detected antenatally. Both infants were severely anemic at birth. Acute blood loss in twin 1 through the ruptured vessels, led to an acute feto-fetal transfusion from the co-twin through the placental vascular anastomoses. In monochorionic twins, ruptured vasa previa and acute hemorrhage in one fetus can lead to acute feto-fetal transfusion and result in severe hypovolemic shock and acute anemia in both fetuses. Increased awareness for vasa previa and the characteristic placental angioarchitecture in monochorionic twinning is of paramount importance. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain.Methods: We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation.Results: A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events.Conclusions: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.). [ABSTRACT FROM AUTHOR]

Objective: To estimate the incidence of uterine rupture in the Netherlands and evaluate risk indicators prelabour and during labor of women with adverse maternal and/or perinatal outcome., Methods: This is a population-based nationwide study using the Netherlands Obstetrics Surveillance System (NethOSS). We performed a two-year registration of pregnant women with uterine rupture. The first year of registration included both women with complete uterine rupture and women with incomplete (peritoneum intact) uterine rupture. The second year of registration included women with uterine rupture with adverse maternal and/or perinatal outcome. We collected maternal and obstetric characteristics, clinical signs, and symptoms during labor and CTG abnormalities. The main outcome measures were incidence of complete uterine rupture and uterine rupture with adverse outcome and adverse outcome defined as major obstetric hemorrhage, hysterectomy, embolization, perinatal asphyxia and/or (neonatal) intensive care unit admission., Results: We registered 41 women with a complete uterine rupture (incidence: 2.5 per 10,000 births) and 35 women with uterine rupture with adverse outcome (incidence: 0.9 per 10,000 births). No adverse outcomes were found among women with incomplete uterine rupture. Risk indicators for adverse outcome included previous cesarean section, higher maternal age, gestational age <37 weeks, augmentation of labor, migration background from Sub-Saharan Africa or Asia. Compared to women with uterine rupture without adverse outcomes, women with adverse outcome more often expressed warning symptoms during labor such as abdominal pain (OR 3.34, 95%CI 1.26-8.90) and CTG abnormalities (OR 9.94, 95%CI 2.17-45.65). These symptoms were present most often 20 to 60 min prior to birth., Conclusion: Uterine rupture is a rare condition for which several risk indicators were identified. Maternal symptoms and CTG abnormalities are associated with adverse outcomes and time dependent. Further analysis could provide guidance to expedite delivery.

Objectives: To explore how specific measures of antenatal care utilization are associated with outcomes in pregnancies complicated by preeclampsia and eclampsia in Ghana., Study Design: Participants were adult pregnant women with preeclampsia or eclampsia at a tertiary hospital in Ghana. Antenatal care utilization measures included timing of first visit, total visits, facility and provider type, and referral status. Antenatal visits were characterized by former and current World Health Organization recommendations, and by gestational age-based adequacy., Main Outcome Measures: Composites of maternal complications and poor neonatal outcomes. Multivariate logistic regressions identified associations with antenatal care factors., Results: Among 1176 participants, median number of antenatal visits was 5.0 (IQR 3.0-7.0), with 72.9% attending ≥4 visits, 19.4% attending ≥8 visits, and 54.9% attending adequate visits adjusted for gestational age. Care was most frequently provided in a government polyclinic (n = 522, 47.2%) and by a midwife (n = 704, 65.1%). Odds of the composite maternal complications were lower in women receiving antenatal care at a tertiary hospital (aOR 0.47, p = 0.01). Odds of poor neonatal outcomes were lower in women receiving antenatal care at a tertiary hospital (aOR 0.56, p < 0.001), by a specialist Obstetrician/Gynecologist (aOR 0.58, p < 0.001), and who attended ≥8 visits (aOR 0.67, p = 0.04). Referred women had twice the odds of a maternal complication (aOR 2.12, p = 0.007) and poor neonatal outcome (aOR 1.68, p = 0.002)., Conclusions: Fewer complications are seen after receiving antenatal care at tertiary facilities. Attending ≥8 visits reduced poor neonatal outcomes, but didn't impact maternal complications. Quality, not just quantity, of antenatal care is essential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 International Society for the Study of Hypertension in Pregnancy. All rights reserved.)

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta that is associated with poor reproductive outcomes. The intervillous infiltrate consists mostly of maternal mononuclear cells and fibrin depositions, which are both indicators for the severity of the intervillous infiltrate. The severity of the intervillous infiltrate as well as the clinical outcomes of pregnancy differ between cases. Our objective is to determine the relation between the severity of the intervillous infiltrate and the clinical outcomes of CHI., Methods: Cases of CHI were semi-quantitatively graded based on histopathological severity scores. Hereto, CD68 positive mononuclear cells were quantified, fibrin depositions visualized by both a PTAH stain and an immuohistochemical staining, and placental dysfunction was assessed via thrombomodulin staining., Results: This study included 36 women with CHI. A higher CD68 score was significantly associated with a lower birthweight. Loss of placental thrombomodulin was associated with lower gestational age, lower birthweight, and a lower placenta weight. The combined severity score based on CD68 and PTAH was significantly associated with fetal growth restriction, and the joint score of CD68 and fibrin was associated with birthweight and placental weight., Discussion: More severe intervillous infiltrates in CHI placentas is associated with a lower birth weight and placental weight. Furthermore, this study proposes thrombomodulin as a possible new severity marker of placental damage. More research is needed to better understand the pathophysiology of CHI., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Currently, there is no consensus on the optimal management to prevent postpartum hemorrhage (PPH) in hemophilia carriers. We aimed to evaluate peripartum management strategies in relation to maternal and neonatal bleeding outcomes by performing an extensive database search up to August 2020. Seventeen case-reports/series and 11 cohort studies were identified of overall 'poor' quality describing 502 deliveries. The PPH incidence in the individual patient data was 63%; 44% for those women receiving prophylaxis to correct coagulation and 77% for those without (OR 0.23, CI 0.09-0.58) and in cohort data 20.3% (26.8% (11/41) vs. 19.4% (55/284) (OR: 1.53, 95% CI: 0.72-3.24), respectively. Peripartum management strategies mostly consisted of clotting factor concentrates, rarely of desmopressin or plasma. Tranexamic acid appears promising in preventing secondary PPH, but was not used consistently. Neonatal bleeding was described in 6 affected male neonates, mostly after instrumental delivery or emergency CS, but insufficient information was provided to reliably investigate neonatal outcome in relation to management. The high PPH risk seems apparent, at most mildly attenuated by prophylactic treatment. Prospective cohort studies are needed to determine the optimal perinatal management in hemophilia., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins., Methods: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks' gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth < 37 weeks' gestation in a subsequent pregnancy., Results: Fourteen hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 572 had been allocated to induction of labor using a Foley catheter and 570 to induction of labor using prostaglandins. Of these, 162 (14%) were lost to follow-up. In total, 251 and 258 women had a known subsequent pregnancy > 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38-2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30-3.51)., Conclusion: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: Chronic intervillositis of unknown etiology (CIUE) is a histopathological lesion of the placenta that is frequently accompanied by unfavourable pregnancy outcomes, e.g. miscarriage, fetal growth restriction (FGR) and intrauterine fetal death. Earlier described case series and cohorts have been based on diverse diagnostic criteria of CIUE. To improve our understanding of clinical outcomes associated with CIUE, we report the obstetric and perinatal outcomes in a cohort based on the recently described diagnostic criteria., Methods: CIUE is defined as an infiltrate occupying 5% or more of the intervillous space with approximately 80% of mononuclear cells positive for CD68 in the absence of an infection. Thirty-eight cases were included. Also previous and subsequent pregnancies were described., Results: Pregnancies accompanied by CIUE frequently resulted in FGR (51.6%) and pre-term birth (55.3%). Twenty-nine out of 38 pregnancies (76.3%) with CIUE resulted in a living baby. Women with CIUE frequently have had a miscarriage (16/38; 42%). Four-teen subsequent pregnancies in 8 women resulted in 2 miscarriages, 2 terminations of pregnancy for FGR, 1 early neonatal death and 9 living babies (9/14; 64.3%). Histopathologically confirmed CIUE recurred in 5 out of 10 subsequent pregnancies. Two pregnancies with recurrent CIUE were terminated, one pregnancy ended in a late miscarriage and another resulted in term birth complicated by FGR. Recurrent CIUE can also be accompanied by an uncomplicated pregnancy (1/5; 20%)., Conclusion: This study provides additional insight into the clinical phenotype of CIUE and emphasises the need for further research to understand the pathophysiology behind different pregnancy outcomes in CIUE., (Copyright © 2020. Published by Elsevier Ltd.)

Women with Von Willebrand disease (VWD) have an increased risk of developing postpartum hemorrhage (PPH). Our aim is to evaluate peripartum management strategies in relation to maternal and neonatal bleeding complications in VWD. Electronic databases were searched up to January 2019. Seventy-one case-reports and -series and 16 cohort studies were selected, including 811 deliveries. Cohort studies reported primary PPH in 32% and secondary PPH in 13% of the women. The overall primary PPH incidence in the individual patient data was 34%, similar between women who received prophylactic treatment to prevent PPH and those who didn't. Neonatal bleeding events were reported in 4.6% of deliveries. Overall, the available evidence on peripartum management in women with VWD was of low quality. The ongoing high risk for PPH is evident, despite prophylactic treatment, as well as the need for higher quality evidence from larger prospective cohort studies to improve management strategies., Competing Interests: Disclosures MCP, MLW, EPM-B, LN, ABUM, MHED, JJD, JMM, KWMB, REGS, ATL, and KPMvG have no conflict of interest related to this review. MJHAK received unrestricted research grants from Pfizer and Innovatiefonds with no involvement in this review. JE received research funding from CSL Behring and honorarium for educational activity from Roche, not related to this review. MP received unrestricted grants from CSL Behring, Pfizer and Novo Nordisk, not related to this review., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A possible way of immunomodulation of the maternal immune system before pregnancy would be exposure to paternal antigens via seminal fluid to oral mucosa. We hypothesized that women with recurrent miscarriage have had less oral sex compared to women with uneventful pregnancy. In a matched case control study, 97 women with at least three unexplained consecutive miscarriages prior to the 20 th week of gestation with the same partner were included. Cases were younger than 36 years at time of the third miscarriage. The control group included 137 matched women with an uneventful pregnancy. The association between oral sex and recurrent miscarriage was assessed with conditional logistic regression, odds ratios (ORs) were estimated. Missing data were imputed using Imputation by Chained Equations. In the matched analysis, 41 out of 72 women with recurrent miscarriage had have oral sex, whereas 70 out of 96 matched controls answered positive to this question (56.9% vs. 72.9%, OR 0.50 95%CI 0.25-0.97, p = 0.04). After imputation of missing exposure data (51.7%), the association became weaker (OR 0.67, 95%CI 0.36-1.24, p = 0.21). In conclusion, this study suggests a possible protective role of oral sex in the occurrence of recurrent miscarriage in a proportion of the cases. Future studies in women with recurrent miscarriage explained by immune abnormalities should reveal whether oral exposure to seminal plasma indeed modifies the maternal immune system, resulting in more live births., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Postpartum hemorrhage is the leading cause of maternal mortality and severe morbidity. Despite efforts to improve maternal outcomes, management of postpartum hemorrhage still faces at least four challenges, discussed in this review. First, current definitions for severe postpartum hemorrhage hamper early identification of women with a high risk of adverse outcomes. Adaptations to the definitions and the use of clinical tools such as shock index and early warning systems may facilitate this early identification. Second, surgical and radiological interventions to prevent hysterectomy are not always successful. More knowledge on the influence of patient and bleeding characteristics on the success rates of these interventions is necessary. Scarce data suggest that early timing of intrauterine balloon tamponade may improve maternal outcomes, whereas early timing of arterial embolization seems to be unrelated to maternal outcomes. Third, fluid resuscitation with crystalloids and colloids is unavoidable in the early phases of postpartum hemorrhage but may result in dilutional coagulopathy. Effects of different volumes of clear fluids on the occurrence of dilutional coagulopathy and maternal outcomes is unknown. Fourth, a better understanding of diagnosis and correction of coagulopathy during postpartum hemorrhage is needed. Low plasma fibrinogen levels at the start of postpartum hemorrhage predict progression to severe hemorrhage, but standard coagulation screens are time consuming. A solution may be point-of-care coagulation testing; however, clinical usefulness during postpartum hemorrhage has not been demonstrated. To date, early administration of tranexamic acid is the only hemostatic intervention that was proven to improve outcomes in women with postpartum hemorrhage., (© 2018 International Society on Thrombosis and Haemostasis.)

HLA-G expressed by trophoblasts at the fetal-maternal interface and its soluble form have immunomodulatory effects. HLA-G expression depends on the combination of DNA polymorphisms. We hypothesized that combinations of specific single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of HLA-G play a role in unexplained recurrent miscarriage. In a case control design, 100 cases with at least three unexplained consecutive miscarriages prior to the 20th week of gestation were included. Cases were at time of the third miscarriage younger than 36 years, and they conceived all their pregnancies from the same partner. The control group included 89 women with an uneventful pregnancy. The association of HLA-G 3'UTR SNPs and specific HLA-G haplotype with recurrent miscarriage was studied with logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) were reported. Individual SNPs were not significantly associated with recurrent miscarriage after correction for multiple comparisons. However, the presence of the UTR-4 haplotype, which included +3003C, was significantly lower in women with recurrent miscarriage (OR 0.4, 95% CI 0.2-0.8, p = 0.015). In conclusion, this is the first study to perform a comprehensive analysis of HLA-G SNPs and HLA-G haplotypes in a well-defined group of women with recurrent miscarriage and women with uneventful pregnancy. The UTR-4 haplotype was less frequently observed in women with recurrent miscarriage, suggesting an immunoregulatory role of this haplotype for continuation of the pregnancy without complications. Thus, association of HLA-G with recurrent miscarriage is not related to single polymorphisms in the 3'UTR, but is rather dependent on haplotypes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: A history of recurrent miscarriage is associated with future cardiovascular disease. The aim of this study was to determine novel cardiovascular biomarkers in women with a history of recurrent miscarriage as this might lead to a better understanding of the association., Study Design: Women who visited the recurrent miscarriage clinic at Leiden University Medical Centre (between 2000 and 2010), and had three consecutive miscarriages ≤30 years were invited to participate in this follow-up study (between 2012 and 2014). The reference group consisted of women with at least one uncomplicated pregnancy and a history of no miscarriage, matched on zip code, age, and date of pregnancy., Main Outcome Measures: Cardiovascular biomarkers were determined, classified into; inflammation (HsCRP, lipoprotein-associated phospholipase A2), thrombosis (homocysteine, folate, anti-cardiolipin antibodies and anti-ß-2-glycoprotein antibodies), lipid metabolism (lipoprotein(a)), renal function (creatinine, microalbuminuria), myocardial damage (N-terminal pro-brain natriuretic peptide, high sensitive TroponineT) and multiple mechanisms (albumin, vitamin D)., Results: In both groups, 36 women were included. Women with recurrent miscarriage had a significantly higher median HsCRP (1.49 mg/L) compared to women with no miscarriage (1.01 mg/L, p = 0.03) and a significantly lower mean albumin (46.0 vs 47.6g/L, p = 0.004) and vitamin D (55.6 vs 75.4nmol/L, p = 0.007), respectively. Differences remained after adjustments for classic cardiovascular risk factors (BMI, smoking, diabetes mellitus, and hypertension)., Conclusions: Our findings suggest a proinflammatory state in women with a history of recurrent miscarriage, which suggests a less optimal health, compared to women with no miscarriage. More research (observational and intervention) is warranted to investigate the association with vitamin D., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Chronic intervillositis of unknown etiology (CIUE) is a poorly understood, relatively rare condition characterized histologically by the intervillous infiltration of mononuclear cells in the placenta. Clinically, CIUE is associated with poor pregnancy outcome (e.g., impaired fetal growth, preterm birth, fetal death) and high risk of recurrence in subsequent pregnancies. Because CIUE is not defined consistently, it is essential to clearly define this condition. We therefore review the published definitions of CIUE. In addition, we provide an overview of the reviewed histopathological and maternal characteristics, obstetric features, and pregnancy outcomes. Medical publication databases were searched for articles published through February 2017. Eighteen studies were included in our systematic review. The sole inclusion criterion used in all studies was the presence of intervillous infiltrates. Overall, CIUE was characterized by adverse pregnancy outcome. Miscarriage occurred in 24% of cases, with approximately half of these miscarriages defined as late. Impaired growth was commonly observed, 32.4% of pregnancies reached term, and the live birth rate was 54.9%. The high recurrence rate (25.1%) of the intervillous infiltrates in subsequent pregnancies underscores the clinical relevance of CIUE, the need for increased awareness among pathologists and clinicians, and the need for further research. Criteria for the diagnosis of CIUE are proposed and a Delphi study could be used to resolve any controversy regarding these criteria. Future studies should be designed to characterize the full clinical spectrum of CIUE., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

HLA-C is the only polymorphic classical HLA I antigen expressed on trophoblast cells. It is known that higher incidence of C4d deposition on trophoblast cells is present in women with recurrent miscarriage. C4d is a footprint of antibody-mediated classical complement activation. Therefore, this study hypothesize that antibodies against HLA-C may play a role in the occurrence of unexplained consecutive recurrent miscarriage. Present case control study compared the incidence of HLA-C specific antibodies in 95 women with at least three consecutive miscarriages and 105 women with uneventful pregnancy. In the first trimester of the next pregnancy, presence and specificity of HLA antibodies were determined and their complement fixing ability. The incidence of HLA antibodies was compared with uni- and multivariate logistic regression models adjusting for possible confounders. Although in general a higher incidence of HLA antibodies was found in women with recurrent miscarriage 31.6% vs. in control subjects 9.5% (adjusted OR 4.3, 95% CI 2.0-9.5), the contribution of antibodies against HLA-C was significantly higher in women with recurrent miscarriage (9.5%) compared to women with uneventful pregnancy (1%) (adjusted OR 11.0, 95% CI 1.3-89.0). In contrast to the control group, HLA-C antibodies in the recurrent miscarriage group were more often able to bind complement. The higher incidence of antibodies specific for HLA-C in women with recurrent miscarriage suggests that HLA-C antibodies may be involved in the aetiology of unexplained consecutive recurrent miscarriage., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: The ProTWIN Trial (NTR1858) showed that, in women with a multiple pregnancy and a cervical length < 25(th) percentile (38 mm), prophylactic use of a cervical pessary reduced the risk of adverse perinatal outcome. We investigated whether other maternal or pregnancy characteristics collected at baseline can improve identification of women most likely to benefit from pessary placement., Methods: ProTWIN is a multicenter randomized trial in which 808 women with a multiple pregnancy were assigned to pessary or control. Using these data we developed a multivariable logistic model comprising treatment, cervical length, chorionicity, pregnancy history and number of fetuses, and the interaction of these variables with treatment as predictors of adverse perinatal outcome., Results: Short cervix, monochorionicity and nulliparity were predictive factors for a benefit from pessary insertion. History of previous preterm birth and triplet pregnancy were predictive factors of possible harm from pessary. The model identified 35% of women as benefiting (95% CI, 32-39%), which is 10% more than using cervical length only (25%) for pessary decisions. The model had acceptable calibration. We estimated that using the model to guide the choice of pessary placement would reduce the risk of adverse perinatal outcome significantly from 13.5% when no pessary is inserted to 8.1% (absolute risk reduction, 5.4% (95% CI, 2.1-8.6%))., Conclusions: We developed and internally validated a multivariable treatment selection model, with cervical length, chorionicity, pregnancy history and number of fetuses. If externally validated, it could be used to identify women with a twin pregnancy who would benefit from a pessary, and lead to a reduction in adverse perinatal outcomes in these women. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Thyroid peroxidase antibodies (TPO-Ab) in euthyroid women are associated with recurrent miscarriage (RM) and other pregnancy complications such as preterm birth. It is unclear if treatment with levothyroxine improves pregnancy outcome., Aim: The aim of this study is to determine the effect of levothyroxine administration on live birth rate in euthyroid TPO-Ab positive women with recurrent miscarriage., Methods/design: We will perform a multicenter, placebo controlled randomized trial in euthyroid women with recurrent miscarriage and TPO-Ab. Recurrent miscarriage is defined as two or more miscarriages before the 20th week of gestation. The primary outcome is live birth, defined as the birth of a living fetus beyond 24weeks of gestation. Secondary outcomes are ongoing pregnancy at 12weeks, miscarriage, preterm birth, (serious) adverse events, time to pregnancy and survival at 28days of neonatal life. The analysis will be performed according to the intention to treat principle. We need to randomize 240 women (120 per group) to demonstrate an improvement in live birth rate from 55% in the placebo group to 75% in the levothyroxine treatment group. This trial is a registered trial (NTR 3364, March 2012). Here we discuss the rationale and design of the T4-LIFE study, an international multicenter randomized, double blind placebo controlled, clinical trial aimed to assess the effectiveness of levothyroxine in women with recurrent miscarriage and TPO-Ab., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To compare incidences, characteristics, management and outcome of eclampsia in the Netherlands and the UK., Design: A comparative analysis of two population-based prospective cohort studies., Setting: All hospitals with consultant-led maternity units., Population: Women with eclampsia in the Netherlands (226) and the UK (264)., Methods: Comparison of individual level data from national studies in the Netherlands and the UK (LEMMoN 2004-06; UKOSS 2005/06)., Main Outcome Measures: Incidence, maternal complications and differences in management strategies., Results: Incidences of eclampsia differed significantly between both countries: the Netherlands 5.4/10,000 deliveries versus UK 2.7/10,000 (relative risk [RR] 1.94, 95% confidence intervals [95% CI] 1.6-2.4). The proportion of women with a preceding diagnosis of pre-eclampsia was comparable between both countries (the Netherlands 42%; UK 43%), as was the proportion who received magnesium sulphate prophylaxis. Women in the Netherlands had a significantly higher maximum diastolic blood pressure (111 mmHg versus 95 mmHg, P < 0.001); significantly fewer received anti-hypertensive medication (16% versus 71%; RR 0.2, 95% CI 0.1-0.3) and were treated less often with magnesium sulphate after their first fit (95% versus 99%; RR 0.96, 95% CI 0.92-0.99). Maternal death occurred in three cases in the Netherlands compared with zero in the UK., Conclusions: The incidence of eclampsia in the Netherlands was twice as high compared with the UK when using uniform definitions. Women with eclampsia in the Netherlands were not managed according to guidelines, particularly with respect to blood pressure management. Changes in management practice may reduce both incidence and poor outcomes., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: To investigate whether vaginal Group B Streptococcus (GBS) colonisation or other baseline characteristics of women with preterm premature rupture of membranes (PPROM) can help in identifying subgroups of women who would benefit from immediate delivery., Design: Secondary analysis of the PPROMEXIL trials., Setting: Sixty hospitals in the Netherlands., Population: Women with PPROM between 34 and 37 weeks of gestation., Methods: Random assignment of 723 women to immediate delivery or expectant management., Main Outcome Measures: Early onset neonatal sepsis., Results: Vaginal GBS colonisation status was the only marker which was significantly associated with the benefit of immediate delivery (P for interaction: 0.04). GBS colonisation was observed in 14% of women. The risk of early onset neonatal sepsis in GBS-positive women was high (15.2%) when they were managed expectantly but this risk was reduced to 1.8% with immediate delivery. The early onset neonatal sepsis risk was much lower in neonates of GBS-negative women: 2.6% after expectant management and 2.9% with immediate delivery. We estimated that by inducing labour only in GBS-positive women, there would be a 10.4% increase in term delivery rate, while keeping neonatal sepsis and caesarean delivery rates comparable to a strategy of labour induction for all., Conclusions: Our post hoc findings suggest that women with PROM between 34 and 37 weeks might benefit from immediate delivery if they have GBS vaginal colonisation, while in GBS-negative women labour induction could be delayed until 37 weeks., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage., Design: Randomised non-inferiority trial., Setting: Thirty-seven Dutch university and general hospitals., Population: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities., Methods: Women were allocated to RBC transfusion or non-intervention., Main Outcome Measures: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum., Results: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable., Conclusions: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified., (© 2014 Royal College of Obstetricians and Gynaecologists.)