Associations Between Maternal Infection During Pregnancy, Childhood Infections, and the Risk of Subsequent Psychotic Disorder--A Swedish Cohort Study of Nearly 2 Million Individuals

Abstract

Objective: Recent studies question whether the risk for psychotic disorder associated with prenatal exposure to infection are due to infections per se, or to shared susceptibility of both infections and psychiatric disorders. Moreover, the potential link between prenatal infection and serious infections during childhood, another alleged risk factor for psychotic disorder, remains unknown. The aim of this study was to investigate the role of maternal infections during pregnancy in context of parental psychiatric disorders and subsequent childhood infections.

Method: All children born in Sweden 1978-1997 were linked to the National Patient Register. Hazard ratios of nonaffective psychosis were estimated in relation to maternal infection during pregnancy and odds ratios of childhood infection were calculated in relation to maternal infection during pregnancy. Relative excess risk due to interaction (RERI) estimated biological synergism between parental psychiatric disorder and maternal infection during pregnancy, and between maternal infection during pregnancy and childhood infection.

Results: Maternal infection during pregnancy was not statistically significantly associated with offspring psychosis (adjusted hazard ratio: 1.06, 95% CI 0.88-1.27). However, maternal infection during pregnancy and maternal psychiatric disorders acted synergistically in offspring psychosis development (RERI 1.33, 95% CI 0.27-2.38). Maternal infection during pregnancy increased the risk of offspring childhood infections (OR 1.50, 95% CI 1.45-1.54). These 2 factors also interacted in psychosis development (RERI 0.63, 95% CI 0.12-1.14).

Conclusions: Among mothers with a history of psychiatric disease, infection during pregnancy increases the risk of psychosis in offspring. Maternal infections during pregnancy appear to contribute to the risk of childhood infections, which together render the child more vulnerable to psychosis development.

Keywords: fetal; interaction; prenatal; psychosis; schizophrenia.

Fig. 1.

Risk of nonaffective psychoses (hazard ratio and 95% CI) among individuals with and without maternal infection during pregnancy, parental infection sometime in the 5 y before pregnancy, and parental psychiatric disorder. Fully adjusted for birth year, sex, urban birth, winter birth, parental age ≥ 35 y, small for gestational age, parent born outside Sweden, low socioeconomic status, any parent any inpatient care before or during pregnancy except for treatment of infection or psychiatric care. Circles represent the general population and diamonds the restricted model.

Fig. 2.

Risk of nonaffective psychoses (hazard ratio and 95% CI) following exposure to maternal infection during pregnancy (A) or before pregnancy (B), and childhood infection. Fully adjusted for birth year, sex, urban birth, winter birth, parental age ≥ 35 y, small for gestational age, parental history of psychiatric disorder, parent born outside Sweden, low socioeconomic status, any parent any inpatient care before or during pregnancy except for treatment of infection or psychiatric care, and for the child during childhood (0–13 y). Circles represent the general population and diamonds the restricted model.