Prenatal heat and air pollution exposure alter progesterone and child behavior: A longitudinal study

Prenatal heat exposure may be linked to childhood behavioral difficulties, but the underlying endocrine mechanisms and moderating effects of air pollution remain poorly understood. This study examined potential interactions between prenatal heat and air pollution in relation to child behavior through alterations in progesterone levels. Data from a birth cohort (Stress in Pregnancy Study, 2009-2014) included 256 children with predominantly racial/ethnic minority backgrounds, recruited from two New York City prenatal clinics. Heat exposure was determined by trimester-specific exposure to summer months, with air pollution (NO₂, PM_2.5) assessed by residence location during pregnancy. Primary outcomes included hair progesterone levels at age 3 and behaviors at ages 4-5. Prenatal exposure to heat and air pollution showed significant interactions on progesterone levels. In only high-pollution areas, later trimester heat exposure was associated with progressive progesterone reduction in a dose-response pattern. Multi-group structural equation modeling revealed that only in high-pollution areas, first-trimester heat exposure was associated with elevated progesterone (β ∼ .20, P < .01), which was subsequently associated with increased internalizing (β ∼ .59, P < .01) and externalizing difficulties (β ∼ .54, P < .05) at age 5. These effects were not observed in less polluted areas. This is the first study to suggest progesterone as a key biological mediator potentially linking environmental exposures to behavioral outcomes, suggesting that heat-behavior associations may be amplified by air pollution. Within a Developmental Origin of Health and Disease (DOHaD) framework, findings suggest how early environmental exposures may program biological systems with lasting effects, highlighting intervention opportunities in vulnerable communities.