Maternal bacterial infections during pregnancy are associated with an elevated risk for offspring psychotic disorders, and this association varies by the severity of the infection and the sex of the offspring, according to study results published in the American Journal of Psychiatry.

Because previous studies have suggested that immune challenges before birth may elevate schizophrenia risk and the risk for related psychoses, the study authors investigated the hypothesis that maternal bacterial infections during pregnancy increase the offspring’s risk of developing psychotic disorders in adulthood. They analyzed prospectively collected data on 15,421 pregnancies in women enrolled in the Collaborative Perinatal Project between 1959 and 1966. This sample included 116 offspring who developed confirmed psychotic disorders. Associations between maternal bacterial infection and risk for psychosis over the subsequent years were estimated (with follow-up between 1997 and 2003), stratified by the sex of the offspring and the presence of parental mental illness, with adjustments made for covariates.

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Of the 15,421 pregnancies in the cohort, 23% (n=3499) had bacterial infections during pregnancy, which was strongly associated with offspring psychosis risk (adjusted odds ratio (aOR) 1.8; 95% CI, 1.2-2.7) and varied by infection severity and sex of offspring. The effect of multisystemic bacterial infection (aOR 2.9; 95% CI, 1.3-5.9) was more strongly associated with psychosis risk than localized bacterial infections (aOR 1.6; 95% CI, 1.1-2.3). Male offspring were significantly more likely to develop psychosis after maternal exposure to bacterial infection during pregnancy (aOR 2.6; 95% CI, 1.6-4.2) whereas female offspring showed no difference in risk by exposure status (aOR 1; 95% CI, 0.5-1.9; P =.018). Similarly, male offspring were more than 2 times as likely to develop psychosis after maternal exposure to a localized bacterial infection compared with female offspring (male offspring aOR 2.1; 95% CI, 1.2-3.4 and female offspring aOR 1; 95% CI, 0.5-1.9; P =.084). Only one female offspring was exposed to multisystemic maternal bacterial infection; however, male offspring who were exposed to maternal multisystemic infection during pregnancy had 5 times the odds of developing psychosis relative to unexposed male offspring (aOR 5; 95% CI, 2-10.7).

Study limitations included enrolling the most severe cases of psychotic disorders, an overrepresentation of participants with residential stability and independence in follow-up, potential misclassification of exposure, and the presence of potential confounding factors.

Study investigators concluded, “These findings could be an important first step to motivating large-scale national register-based investigation of this type of research question. Larger samples would provide opportunities to address some of the crucial components on the etiologic pathway from prenatal bacterial infection to psychosis, such as gestational timing of exposure, sex-specific transmission of psychotic illness, specific subtypes of psychosis, and finer categorization of infectious exposure. If replicated, our findings would also call for public health and clinical efforts that focus on preventing and managing bacterial infection in pregnant women.”

Disclosure: Several study authors declared an affiliation with the pharmaceutical industry. Please see the original reference for details.

Reference

Lee YH, Cherkerzian S, Seidman LJ, et al. Maternal bacterial infection during pregnancy and offspring risk of psychotic disorders: Variation by severity of infection and offspring sex [published online October 4, 2019]. Am J Psychiatry. doi:10.1176/appi.ajp.2019.18101206