# Study protocol for the Bio-HEAT study: Investigating the Biological pathways from HEAT exposure to preterm birth and other adverse maternal and child health outcomes in South Africa

## TL;DR

This study investigates how heat exposure affects pregnant women and their babies in Johannesburg, focusing on biological pathways leading to preterm birth and other health issues.

## Contribution

The study introduces a transdisciplinary approach to explore biological and social mechanisms linking heat exposure to adverse maternal and child health outcomes.

## Key findings

- Heat exposure is linked to maternal inflammation and preterm birth through epigenetic and inflammatory pathways.
- The study will assess how heat affects breastmilk composition and volume using isotope techniques.
- Graphical causal models will be developed to identify protective mechanisms against heat-related health risks.

## Abstract

Epidemiological evidence linking heat exposure to adverse maternal and child health outcomes is compelling. However, the biological and social mechanisms underlying these associations remain poorly understood. Understanding the pathways explaining these associations is important given rising global temperatures, and the urgent need for developing and testing adaptive interventions.

This transdisciplinary study in Johannesburg, South Africa, will monitor a cohort of 200 women from their second trimester until one-year postpartum, alongside their infants. Heat exposure and environmental factors will be tracked using personal, community and facility-level temperature monitors and geospatial data. Data will be collected on social conditions, medical and obstetric history, heat stress and adaptation, hydration, mental wellbeing, and sleep quality. Clinical data includes physical measurements, ultrasound, cardiotocography, and biological specimens (blood, urine, saliva) analysed for inflammatory markers, RNA, metabolic indicators, renal function and hormonal levels. Placental and cord blood analyses will assess foetal stress. Infant data will include medical history, hospital visits, neurodevelopment, anthropometric measurements, vital signs, and urine analysis. Three nested sub-studies (20–50 participants) will explore specific aspects: Sub-study 1 will use wearable devices to monitor sleep, activity, and heart rate in high-risk women; Sub-study 2 will involve qualitative interviews; and Sub-study 3 will assess breastmilk composition and volume.

Our primary aim is to document linkages between heat exposure and inflammatory pathways that precede preterm birth. The hypothesis that heat exposure triggers maternal inflammation will be tested by analysing epigenetic changes associated with inflammatory cytokine protein and gene expression. We will investigate thermoregulation and hydration during labour. Using isotope techniques, we assess whether heat exposure alters breastmilk composition and volume. Conceptual frameworks and graphical causal models will be developed to delineate pathways of vulnerability and protective mechanisms.

Climate change is causing global temperatures to rise, leading to more frequent and intense heatwaves. This extreme heat can have health risks for pregnant women and their babies such as preterm birth and low birth weight. However, we do not yet fully understand how pregnant women’s body’s respond to heat, or why these health risks occur. Gaining this knowledge will help us to protect mothers and babies as the world gets warmer.

The Bio-HEAT study will follow 200 pregnant women from an underserved urban community in Johannesburg, South Africa. Heat exposure in the area is worsened by the Urban Heat Island effect where buildings, road and industry trap heat. Many people in this community don’t have access to cooling systems like air conditioning, and some use solid fuels like wood and coal for cooking, which makes their homes hotter. These conditions make them especially vulnerable to heat.

Our main goal is to understand how heat exposure might trigger inflammation and other changes in the body and lead to preterm birth. Women will be followed from their second trimester through to one year postpartum, along with their infants. Researchers will collect information through questionnaires, biological samples (like blood, urine and saliva), ultrasound scans, and wearable devices that measure heat exposure. Placenta and cord blood will be assessed for the effects of heat on babies before birth. The babies growth and health will also be monitored.

The study includes three smaller sub-studies: one to monitor activity, sleep and heart rate; another to gather personal experiences, and a third to explore how heat affects breastfeeding.

The findings from the study will help to inform strategies to reduce heat-related health risks for pregnant women and babies in similar urban settings globally.