Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials.

INTRODUCTION: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. MATERIAL AND METHODS: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). RESULTS: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94-1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83-1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65-5.90). CONCLUSIONS: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making.

The influence of various induction methods on adverse outcomes in small for gestational age neonates: A secondary analysis of the PROBAAT 1 and 2 trials.

OBJECTIVE: To evaluate the safety aspects of different induction methods in pregnancies with small-for-gestational-age neonates. STUDY DESIGN: This was a secondary analysis of two previously reported multicenter, randomized controlled trials conducted in the Netherlands. In the original trials, women were randomized to either a 30 cc Foley catheter, vaginal prostaglandin E2 (PROBAAT-1) or oral misoprostol (PROBAAT-2). A total of 425 patients with a term, singleton pregnancy in cephalic presentation with an indication for labor induction and a small-for-gestational-age neonate were included in this secondary analysis. Our primary outcome was a composed adverse neonatal outcome of Apgar score < 7 after 5 min and/or a pH in the umbilical artery < 7.05 and/or NICU admission. Secondary outcomes were mode of birth, operative birth for fetal distress and pH < 7.10 in the umbilical artery. For these outcome measures, multivariate as well as bivariate analyses were performed. RESULTS: An adverse neonatal outcome occurred in 4.7 % (10/214) induction with a Foley catheter, versus 12.8 % (19/149) after misoprostol (RR 0.36; 95 % CI 0.17-0.76) and 4.7 % (3/64) after Prostaglandin E2 (RR 0.98; 95 %CI 0.28-3.51). For individual components of the composed outcome of adverse events, a difference was found between a Foley catheter and misoprostol for Apgar score < 7 at 5 min (0.5 % versus 3.4; RR 0.14; 95 %CI 0.02-1.16) and NICU admission (1.9 % versus 6.1 %; RR 0.31; 0.10-0.97). No differences were found for mode of birth. CONCLUSIONS: For women who gave birth to a small-for-gestational-age neonate, a Foley catheter is probably a safer induction method compared to oral misoprostol.

Pregnant women's willingness to participate in a randomized trial comparing induction of labor at 39 weeks versus expectant management: A survey in the Netherlands.

INTRODUCTION: A randomized controlled trial (RCT) in the United States, the ARRIVE trial, has indicated that induction of labor (IOL) in low-risk nulliparous women with a gestational age (GA) of 39 weeks compared to expectant management (EM) resulted in a significant lower rate of cesarean deliveries. The Dutch maternity care system is different compared to the United States with, among other factors, an overall significantly lower percentage of caesarean sections (CS). To investigate whether IOL has a favorable outcome in the Dutch maternity care system, a new trial is advised. In this questionnaire-based study we aim to evaluate whether Dutch low-risk pregnant women would be willing to participate in an RCT comparing IOL at 39 weeks to EM. MATERIALS AND METHODS: We conducted an online survey in 2020 in the Netherlands. Respondent recruitment took place both in outpatient clinics at hospitals and midwife practices and via social media. Inclusion criteria were pregnant women with singleton gestation, GA ≤ 39 weeks, age 18 years or older and residency in the Netherlands. Exclusion criteria were multiple gestation, a history of a CS, planned IOL or CS in current pregnancy and GA > 39 weeks. A subgroup was formed of low risk (receiving primary care) nulliparous women with a gestational age between 34 and 39 weeks, comparable with the ARRIVE trial. RESULTS: Three hundred eighty respondents participated. Of all respondents (nulli- and multiparous), 47 (12.4%) would be willing to participate in the hypothetical RCT and 70 (18.4%) might be willing to participate. Amongst the 70 women in the subgroup 11 women (15.7%) would be willing to participate and 17 (24.3%) might be willing to participate. DISCUSSION AND CONCLUSION: Calculating sample size in a country with a low CS rate, in relation to 69.2% of women are not willing to participate in an RCT comparing IOL at 39 weeks with EM, would require >18.000 women to be counselled for participation. We believe such a study is a challenge in the Netherlands.

Changes in local protocols on inpatient cervical priming and introduction of outpatient priming: A nationwide survey in the Netherlands.

OBJECTIVE: The aims of this study are to assess (changes in) local procedures for inpatient cervical priming as part of induction of labor and to identify the implementation of outpatient cervical priming in the Netherlands. METHODS: This survey study was conducted from October 2019 until January 2020; obstetricians of all 72 hospitals with a maternity unit in the Netherlands received a questionnaire. The questionnaire consisted of three parts: basic hospital data, local protocol on methods of inpatient induction of labor (IPI), local protocol for outpatient induction of labor (OPI). RESULTS: A response was received from 66/72 hospitals, giving a response rate of 92%. For IPI the most preferred method was a Foley catheter (87.9%), 27.6% protocols switched to prostaglandins after day 1 if the cervix was not ripe yet. A prostaglandin gel or pessary was not the preferred method on day 1 but only used after 24 h in 5 hospitals (7.6%). OPI was offered in 53% (35/66 hospitals), all using a Foley catheter. CONCLUSION: In the Netherlands, local protocols for IPI have shifted towards the use of a Foley catheter. More than half of the hospitals offer OPI. As safety and efficacy data of OPI are lacking, research on this topic is urgently warranted.

Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus Surgery Without HIPEC for Goblet-Cell Carcinoids and Mixed Adenoneuroendocrine Carcinomas: Propensity Score-Matched Analysis of Centers in the Netherlands and Belgium.

BACKGROUND: The value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs. PATIENTS AND METHODS: Two cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018. RESULTS: After matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P < .001; GCC: 39 vs. 12 months, P = .017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P = .001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P = .038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings. CONCLUSION: CRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC.