Despite advances in maternity care, stillbirth remains a major burden. It disproportionately affects black and Asian mothers, those with obesity and women over the age of 35 years. Induction of labour may benefit these women, but there is no clear evidence to guide recommendations on optimal timing of induction because of variations in the intervention and insufficient power in primary trials for rare outcomes such as stillbirth and perinatal mortality, or to assess whether effects differ by maternal characteristics. We will conduct an individual participant data (IPD) meta-analysis of randomised trials to assess the overall and differential effect of induction of labour, according to timing of induction and maternal characteristics, on adverse perinatal and maternal outcomes. We will also rank induction of labour timing strategies by their effectiveness to inform clinical and policy decision-making.
We will identify randomised trials on induction of labour by searching MEDLINE, CINAHL, EMBASE, BIOSIS, LILACS, Pascal, SCI, CDSR, ClinicalTrials.gov, ICTRP, ISRCTN registry, CENTRAL, DARE and Health Technology Assessment Database, without language restrictions, from inception to June 2025. Primary researchers of identified trials will be invited to join the OPTIMAL Collaboration and share the original trial data. Data integrity and trustworthiness assessment will be performed on all eligible trials. We will check each study’s IPD for consistency with the original authors before standardising and harmonising the data. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool. We will perform a series of one-and-two-stage random-effects meta-analyses to obtain the summary intervention effect on composite adverse perinatal outcome (stillbirth, neonatal death or severe morbidity requiring admission to neonatal unit) with 95% CIs and summary treatment–covariate interactions (maternal age, ethnicity, parity, socioeconomic status, body mass index and method of conception). Heterogeneity will be summarised using tau2, I2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Small study effects (potential publication bias) will be investigated using funnel plots.
The study is registered on PROSPERO (CRD420251066346) and ethics approval is not required. We will disseminate findings widely to women, healthcare professionals and policymakers through academic, professional bodies and social media channels, and in peer-reviewed journals to achieve impact.
CRD420251066346.
Black adults are generally exposed to more stressors over the life course and, due to the intersections of racism and economic and social resources, they tend to have more limited resources to cope with social stressors than white adults. This mismatch between stress exposures and resources may lead to dysregulated responses or reactivity to stressors and contribute to persistent racial disparities seen in adverse pregnancy outcomes (APOs). Prior studies examining stress exposures have been hampered by the challenge of capturing stress exposures comprehensively, given they are manifold, dynamic and accumulate over time. The Stress Reactivity and Maternal Health Study seeks to overcome this limitation by examining the impact of physiological and psychological stress reactivity to everyday stressors on APOs.
We are recruiting 700 nulliparous self-identified non-Hispanic black and white pregnant individuals from academic medical centres in the USA. We use ecological momentary assessments administered via smartphones to collect repeated measurements of exposure to everyday stressors throughout the day over the course of seven consecutive days at two different time points mid-pregnancy (14–22 weeks and 22–28 weeks). At the same time, we collect intensive measurements of heart rate variability, blood pressure, salivary cortisol and positive and negative affect. We will use mixed-effects models to estimate personalised indicators of cardiovascular, neuroendocrine and affective reactivity to everyday stressors. We will then use linear and logistic regression modelling to examine associations of these personalised indicators of stress reactivity with placental histological lesions and the occurrence of APOs. Finally, we will use the gap-closing estimand method to quantify the extent to which racial disparities in adverse placental and pregnancy outcomes are explained by differences in prenatal stress exposure and prenatal stress reactivity.
The Northwestern University institutional review board (IRB) approved this study and serves as the single IRB of record (STU00218683). All participants will sign an informed consent document prior to participation, and data will be treated confidentially. Findings will be disseminated in peer-reviewed scientific journals, briefs, infographics and presentations.