Exposure to Extreme Heat Increases Preterm Birth Risk: Hypothetical Pathophysiological Mechanisms

Preterm birth (PTB), delivery before 37 weeks of gestation, is the leading cause of neonatal mortality globally, accounting for nearly half of all neonatal deaths. While numerous established risk factors for PTB have been identified, ongoing research continues to elucidate additional contributing factors. Epidemiological studies increasingly demonstrate that elevated ambient temperature is an environmental risk factor for PTB, with odds increasing 16% during heat waves and 5% per 1°C temperature rise. This is particularly concerning given escalating global warming trends. While maternal heat susceptibility during pregnancy may be linked to compromised thermoregulation from gestational adaptations, the exact pathophysiological mechanisms leading to heat-associated PTB remain unclear, hindering therapeutic development. This review proposes multitudes potential pathophysiologic mechanisms leading to PTB that can be induced by heat. They include but are not limited to metabolic derangement, mitochondria dysfunction, inflammation, endothelial dysfunction, oxidative stress, and change in cell fate. These mechanisms are derived from integrated knowledge of pregnancy physiology, parturition processes, and temperature effects on physiological pathways. We also outline future experimental approaches to test these hypotheses.