Induction of labour at 41 weeks versus expectant management until 42 weeks (INDEX): multicentre, randomised non-inferiority trial

Abstract

Objective To compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk women. Design Open label, randomised controlled non-inferiority trial. Setting 123 primary care midwifery practices and 45 hospitals (secondary care) in the Netherlands, 2012-16. Participants 1801 low risk women with an uncomplicated singleton pregnancy: randomised to induction (n=900) or to expectant management until 42 weeks (n=901). Interventions Induction at 41 weeks or expectant management until 42 weeks with induction if necessary. Primary outcome measures Primary outcome was a composite of perinatal mortality and neonatal morbidity (Apgar score <7 at five minutes, arterial pH <7.05, meconium aspiration syndrome, plexus brachialis injury, intracranial haemorrhage, and admission to a neonatal intensive care unit (NICU). Secondary outcomes included maternal outcomes and mode of delivery. The null hypothesis that expectant management is inferior to induction was tested with a non-inferiority margin of 2%. Results Median gestational age at delivery was 41 weeks+0 days (interquartile range 41 weeks+0 days-41 weeks+1 day) for the induction group and 41 weeks+2 days (41 weeks+0 days-41 weeks+5 days) for the expectant management group. The primary outcome was analysed for both the intention-to-treat population and the per protocol population. In the induction group, 15/900 (1.7%) women had an adverse perinatal outcome versus 28/901 (3.1%) in the expectant management group (absolute risk difference −1.4%, 95% confidence interval −2.9% to 0.0%, P=0.22 for non-inferiority). 11 (1.2%) infants in the induction group and 23 (2.6%) in the expectant management group had an Apgar score <7 at five minutes (relative risk (RR) 0.48, 95% CI 0.23 to 0.98). No infants in the induction group and three (0.3%) in the expectant management group had an Apgar score <4 at five minutes. One fetal death (0.1%) occurred in the induction group and two (0.2%) in the expectant management group. No neonatal deaths occurred. 3 (0.3%) neonates in the induction group versus 8 (0.9%) in the expectant management group were admitted to an NICU (RR 0.38, 95% CI 0.10 to 1.41). No significant difference was found in composite adverse maternal outcomes (induction n=122 (13.6%) v expectant management n=102 (11.3%)) or in caesarean section rate (both groups n=97 (10.8%)). Conclusions This study could not show non-inferiority of expectant management compared with induction of labour in women with uncomplicated pregnancies at 41 weeks; instead a significant difference of 1.4% was found for risk of adverse perinatal outcomes in favour of induction, although the chances of a good perinatal outcome were high with both strategies and the incidence of perinatal mortality, Apgar score <4 at five minutes, and NICU admission low. Trial registration Netherlands Trial Register NTR3431.

Routine induction in late-term pregnancies: follow-up of a Danish induction of labour paradigm

“…One cohort study of 51 473 women found an increase in labour dystocia after induction of labour was performed at 41 GW (RR=1.29, 95% CI 1.22 to 1.37)35 while a randomised trial of 508 women found no difference (RR 0.55, 95% CI 0.20 to 1.45) 36. Conflicting results have been published regarding induction of labour and risk of CS 2 37 38. In this study, no change in the CS trend was found, despite the substantial increase in induction of labour.…”

A systematic scoping review of clinical indications for induction of labour

“…This review identified four RCTs relevant to these timeframes and concluded that there was insufficient evidence to support IOL at 41 weeks instead of 42 weeks. A recent RCT not included in these systematic reviews compared IOL at 41 weeks with EM until 42 weeks found that IOL was associated with reduced adverse perinatal outcomes (1.7% vs 3.1%, absolute risk difference, -1.4%, 95% CI -2.9 to 0.0), however, this study was underpowered to demonstrate superiority of IOL at 41 weeks [35].…”

“…There were 15 studies related to IOL for post-term pregnancy (> 40 weeks). These included a Cochrane review [6], a systematic review [34], an RCT [35], a prospective cohort study [36], nine retrospective cohort studies [37][38][39][40][41][42][43][44][45], and two secondary analyses of cohort studies [46,47]. The Cochrane review assessed the effects of a policy of IOL at or beyond term compared with a policy of awaiting spontaneous labour (or until planned birth is deemed necessary) on maternal and neonatal outcomes [6].…”

When to induce late term pregnancies

“…Two previous trials have made the same comparisons as SWEPIS; the first, from Turkey, recorded one death, in the expectant management group 4. The second, the INDEX (INDuction of labour at 41 weeks with a policy of EXpectant management until 42 weeks) trial, found a reduced risk of adverse perinatal outcomes in favour of induction, and the study recorded one perinatal death in the induction group compared with two in the expectant management group 5…”