Background:

Cerebral palsy (CP) is the most common childhood movement disorder, and its incidence varies seasonally. Influenza, a common seasonally varying pathogen, has been associated with poor birth and neurodevelopmental outcomes. However, no studies have examined whether community influenza activity is associated with CP risk.

Methods:

A cohort of 4.47 million live births in California from 2007-2015 was linked to CP diagnostic records through 2021 from a statewide diagnostic system, yielding 4,679 cases. Weekly influenza-like illness (ILI) surveillance data were obtained from the California Department of Public Health and averaged for each pregnancy and trimester to estimate community influenza circulation. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for CP diagnosis based on community influenza activity, adjusted for maternal, neighborhood, and environmental factors. Temporal negative controls were used to evaluate uncontrolled confounding bias, and causal mediation analyses were conducted to identify potential causal pathways for the associations found.

Results:

Increased influenza activity during the first trimester was associated with CP diagnosis (OR 1.07 [95% CI 1.02-1.13]), especially for years dominated by the H1N1 viral subtype (OR = 1.18 [95% CI 1.11-1.26]). This relationship was robust to temporal negative controls that assessed community influenza activity before and after pregnancy. Mediating effects were noted for preterm birth and very preterm birth (mediated percentages 9.6% and 17.92%, respectively) but not for preeclampsia (mediated percentage <1%).

Conclusions:

Maternal exposure to increased community influenza during the first trimester of pregnancy is associated with increased CP risk, especially in years dominated by descendants of the 2009 novel H1N1 virus. Given continued emergence of novel respiratory pathogens, the potential implications of these findings merit further investigation.