Background Current evidence on prenatal exposure to heat stress and childhood neurodevelopment is sparse. Cerebral palsy (CP) is the most common neuromotor disorder in childhood and there are growing concerns that environmental factors may play an etiological role. Our aim was to investigate whether prenatal exposure to high ambient temperature was associated with CP risk in the offspring.

Methods We conducted a nested case-control study in California that included all CP cases identified from a statewide service system on developmental disabilities and randomly selected 20% of all live births without CP as controls during 2005-2015. Gestational weekly average temperatures were calculated from high resolution (1 km) daily mean temperature data based on maternal residential address. Extreme heat was defined as weekly averages above the 90th percentile of the local temperature distribution. We implemented a distributed lag model within a logistic regression framework to estimate the associations between ambient temperatures increase, extreme heat and CP risk, across gestational week 0 to 31 covering early- and mid-pregnancy, and in the final seven weeks preceding birth capturing the late pregnancy. We also examined possible heterogeneity across maternal socio-demographic characteristics. Finally, we performed a sibling analysis to consider the influence of uncontrolled confounding.

Findings The study population included 5,938 CP cases and 1,092,313 controls. There was an associated 2% increased odds of CP (95% credible interval: 1% to 5%) per 5 °C increase in ambient temperature in gestational week 0 to 3, and higher odds of 1.03 to 1.05 for extreme heat. A similar susceptible window in early pregnancy was observed in sibling analysis. We also observed a tendency of more pronounced associations for neighborhoods with higher social vulnerability and a cumulative association with higher temperature in the final seven weeks preceding births.

Interpretation Early-pregnancy exposure to high ambient temperatures were associated with increased risk of childhood CP. While the estimated magnitude was small, our findings suggest that CP risk should be monitored in the population within the context of climate change.

Funding Yale Planetary Solutions, National Institutes of Environmental Health Sciences

The authors have declared no competing interest.

This study was funded by Yale Planetary Solutions and National Institutes of Environmental Health Sciences (NIEHS)

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The study protocol was approved by the official institutional review board at Yale University (IRB no. 2000028297) and the California Committee for the Protection of Human Subjects (project no. 12-10-0861) and was exempted from the informed consent requirement because there was no contact with human subjects. The study was reported by following the Strengthening and Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

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The data that support findings from this study are from the California Department of Public Health and Department of Developmental Services. The authors have no rights to share the data.