OPtimal Timing of Induction of labour to improve Maternal and perinatAL outcomes (OPTIMAL): An individual participant data meta-analysis and qualitative evaluation.

RESEARCH QUESTION What is the optimal timing of labour induction to reduce adverse perinatal outcomes, are there differential effects by maternal and intervention factors, and is early induction acceptable? BACKGROUND Despite advances in maternity care, stillbirth remains a major burden. Stillbirths disproportionately affects Black and Asian mothers, those with obesity and older women.

There is no clear evidence to make recommendations on optimal timing of induction for these women, due to insufficient power and variations in the intervention in primary trials. Our individual participant data (IPD) meta-analysis and mixed-methods study can address these limitations.

AIM Our overall aim is to reduce adverse perinatal outcomes through optimal timing of induction of labour in mothers considered to have uncomplicated term pregnancies, through personalised, woman-centred care, that is acceptable to women and their families.

OBJECTIVES Primary Determine using IPD meta-analysis of randomised trials, the overall, and differential effect of induction of labour according to maternal characteristics (age, ethnicity, parity, socioeconomic status, BMI, and assisted conception) on composite adverse perinatal outcome (stillbirth, neonatal death, and neonatal morbidity requiring admission to neonatal unit).

Secondary Assess the effect of induction of labour on critically important individual maternal and perinatal outcomes.

Determine whether the effect of induction of labour varies by gestational age, and rank order of induction of labour by timing using NMA. Estimate the association between gestational age at induction and maternal and neonatal outcomes.

Obtain the views of women, birth-partners, healthcare professionals, and key stakeholders on the acceptability and implementability of induction of labour strategies using mixed-methods research. Involve and engage women and their support networks.

METHODS Our project has three interlinked work packages (WP) WP1 (20m)–IPD meta-analysis on differential effects of induction of labour We will update our search to identify relevant induction of labour trials, and invite investigators to join the OPTIMAL Collaboration and share the original trial data.

So far, we have agreement to share data from >70% of participants (12,013 women), providing us sufficient power to detect any interactions between subgroups for a 40% reduction in composite perinatal outcome with induction of labour vs expectant management for subgroups.

We will perform one-and-two-stage random-effects meta-analyses to obtain pooled intervention effect for primary and secondary outcomes.

We will examine whether the maternal characteristics modify intervention effect by extending the meta-analysis framework to summarise treatment-covariate interaction terms, whilst avoiding ecological bias and study-level confounding.

WP2 (18m)–Mixed-methods study to identify barriers and facilitators of induction of labour from diverse groups of women and birth-partners, and for healthcare professionals to deliver care.

WP3 (24m)–Promote involvement and engage with women and their support networks to maximise patient and public involvement and engagement.

TIMELINE 24 months ANTICIPATED IMPACT AND DISSEMINATION We expect to provide robust evidence on optimal timing of induction for women based on their individual risk profile. Findings can be rapidly incorporated into national guidelines. This could reduce avoidable perinatal deaths and address inequalities.

We will disseminate findings widely to women, healthcare professionals, and policymakers through academic, and social media channels to achieve impact.