Cohort Profile for the Heat in Pregnancy- India (HiP-India) Study.

BACKGROUND: Extreme heat exposure - defined as sustained ambient temperatures exceeding local thresholds - has been associated with several adverse pregnancy outcomes, including preterm birth, stillbirth, gestational diabetes and small for gestational age. However, the mechanisms linking environmental heat to these outcomes, and the biological markers that signify individual vulnerability, are not well understood. We present the protocol for a prospective cohort study within the Heat in Pregnancy-India consortium (HiP-India). This study aims to characterise the physiological and pathophysiological responses of the mother, placenta, and fetus to varying levels of temperature, humidity, and air pollution exposure, and to identify the critical windows and mechanisms of heat-related risk during pregnancy.

METHODS: 600 women with singleton pregnancies, with confirmed gestational age by ultrasound between 11-14 weeks, will be recruited prospectively from three distinct climate zones in India: Gurugram, Delhi NCR 'semi-arid'; Bilaspur, Chhattisgarh 'humid sub-tropical and tropical wet and dry'; and Puducherry 'tropical wet and dry'. Each participant will have their level of exposure to heat, humidity and air pollution measured for 24 hours each trimester in their home and/or workplace using individual and area monitoring devices. Perceived heat stress will be captured using a modified HOTHAPS questionnaire, while physiological heat strain will be measured through urinary specific gravity, core body temperature, heart rate and blood pressure. Within 48 hours of environmental monitoring, maternal haemodynamic parameters will be assessed non-invasively. Fetal ultrasound will be performed to evaluate growth and fetal-placental blood flow, and maternal blood samples collected to evaluate circulating biomarkers of placental function and stress. Cardiotocography will be conducted in the third trimester only. Delivery outcomes for both mothers and neonates will be extracted from hospital records and interviews. In a subset of 100 women, markers of lactation physiology will be recorded during the first 2 weeks after delivery.

ETHICS AND DISSEMINATION OF RESULTS: All necessary ethical approvals from relevant committees at participating institutions have been obtained. Written informed consent will be obtained from all participants. The findings from this study are expected to inform climate adaptation strategies and emergency response policies to protect pregnant populations from the impacts of extreme heat, both within India and in other similarly affected regions globally. Results are aimed for journal publication, communicate findings to participants in plain language, disseminating information at conferences and events of similar nature.