Background: Preterm birth (PTB), <37 weeks’ gestation, is a leading cause of perinatal mortality and morbidity. Wildfire smoke fine particulate matter (PM2.5) and extreme heat are each associated with increased PTB risk, and co-occurring wildfire-heat events are increasing in California. Yet their joint effects remain understudied.

Methods: In a birth cohort of live singleton births in California conceived between January 1, 2006–December 31, 2020 (N = 4,536,046), we assigned exposures based on maternal residence at birth. Wildfire PM2.5 was estimated using spatiotemporal models; smoke days were defined as ≥5 µg/m³ (2021 air quality guideline for annual PM2.5 by the World Health Organization) with alternative thresholds considered. Extreme heat was defined as days exceeding tract-specific 95th percentile maximum (daytime) or minimum (nighttime) temperatures, calibrated to the warm season to account for regional acclimatization. Smoke and heat waves were defined as 2–4+ consecutive exposure days and assessed individually and jointly. Multivariable logistic regression estimated ORs for PTB, with exposures expressed as percentage of pregnancy days to account for varying gestational length. Interaction was assessed on additive and multiplicative scales. Cox proportional hazards models examined critical exposure windows.

Results: Wildfire smoke days (≥5 µg/m³) were associated with increased PTB risk (OR = 1.02, 95% CI: 1.019, 1.022). Daytime heat showed a slightly stronger association (OR = 1.04, 95% CI: 1.040, 1.042) than nighttime heat (OR = 1.02, 95% CI: 1.023, 1.025). Interaction estimates for joint smoke and heat exposure were positive on both additive and multiplicative scales, indicating synergistic effects of PTB risk.

Conclusion: Wildfire smoke and extreme heat were independently and jointly associated with increased PTB risk. As co-occurring exposures intensify with climate change, mitigating combined exposures during pregnancy is a public health priority.