Effects of prenatal bacterial infection on cognitive performance in early childhood

Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up.

We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection.

We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models.

ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters.

We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring.