Biological impacts of rising temperatures on maternal, fetal and newborn health: protocol for a cohort study (BIRTH-Cohort).

INTRODUCTION: Climate change has led to extreme heat events, disproportionately affecting vulnerable populations. Heat stress during pregnancy is linked to adverse health outcomes, yet the biological mechanisms remain poorly understood. This research study aims to investigate the effect of environmental heat on maternal, fetal and infant health and examine the biological pathways linking heat stress to adverse pregnancy outcomes. METHODS AND ANALYSIS: This prospective cohort study will recruit 6000 pregnant women from three districts in Sindh, Pakistan. Eligible participants ≥18 years old, will have a minimum of five scheduled visits from <14 weeks' gestation and will be followed up to 12 months postpartum. Primary outcomes include low birth weight and small vulnerable newborns (SVN); secondary outcomes include preterm birth, small for gestational age (SGA), miscarriage, stillbirth, and composite maternal and neonatal morbidity and mortality. Fetal ultrasound scans with Doppler assessments will be performed at each visit to measure fetal growth, uteroplacental and fetoplacental circulation. Each woman's heat exposure will be measured using wearable sensors and heat strain biomarkers. In a subset of 1000 women, maternal heart rate, skin temperature sleep patterns and physical activity will be monitored throughout pregnancy using wearable devices. Time-varying, distributed lag and non-linear models will examine associations between heat stress indices and pregnancy outcomes. ETHICS AND DISSEMINATION: The study has received ethical approval from the Aga Khan University (AKU) (Ref: 26249) and the Pakistan National Bioethics Committee (Ref: 1065/23/1736). Written informed consent will be obtained from all participants before enrolment. Referral pathways to healthcare facilities will be established to ensure timely management of pregnancy complications. Findings will be disseminated through peer-reviewed publications, scientific conferences, and engagement with policymakers and public health stakeholders to inform climate-resilient maternal health strategies. Results will also be shared with participants and communities through meetings and informal sessions to raise awareness and support evidence-based heat adaptation. TRIAL REGISTRATION NUMBER: NCT01234567.