+It is known that child neurodevelopment and cognitive outcomes are linked to maternal prenatal infections. It is thought that low grade inflammation from maternal infection activates a systemic immune response that is associated with negative effects on fetal brain development and function. Fetal neurodevelopment is stage dependent, with brain myelination beginning during the second trimester, and further growth into the third trimester. Thus it has been hypothesized that inflammation during specific gestation periods may have effects on the fetal growth process. Previous studies have found that maternal prenatal bacterial infections are linked with lower IQ scores at the age of 7, and viral infections are linked with decreased IQ scores and learning disabilities. Limited studies however have been done on the timing of these infections and cognitive outcomes. This prospective cohort study analyzed the effects of infection during each trimester of pregnancy on verbal, performance, and total IQ scores in children at 18 months, 4 years and 8 years. This study found that infections in the third trimester of pregnancy were significantly associated with decreased verbal IQ at age 4, as well as decreased verbal IQ, performance IQ and total IQ at age 8, suggesting that the timing of maternal infection is associated with child cognitive development. Future studies could examine the mechanisms which mediate these effects, as well as ways to moderate these effects.
+The final study comprised of 7,410 mother-child participants from a large, nationally representative sample of parents and children from the UK. Prenatal infection data from the first, second and third trimesters were collected in weeks 18 and 32 of gestation, as well as 8 weeks post-partum. The following infections were asked about: urinary tract infection, influenza, rubella, thrush, genital herpes or other infections. Responses on the timing of these infections were also collected and categorized into first, second or third trimester. The Griffiths Mental Development Scales (GDMS) was administered at 18 months, the Wechsler Preschool and Primary Scale of Intelligence-Revised UK edition (WPPSI-RUK) was administered at 4 years, and the Wechsler Intelligence Scale for Children 3rd edition (WISC-III) was administered at 8 years. Other perinatal and social factors associated with prenatal infections and/or children’s cognitive outcomes were gathered such as child sex, gestational age, birth weight, maternal age at birth, maternal education, maternal smoking history, maternal psychiatric history and deprivation indices. These factors were identified as potential confounders (maternal age, maternal education, deprivation indices, infection in other two trimesters) and covariates (maternal smoking, maternal psychiatric history, gestation, birth weight, and child sex) for the study. Linear regression models were used to examine the relationship between infections at each trimester and cognitive scores at 18 months, 4 years, and 8 years. Three models were used including an unadjusted model, a model that adjusted for confounders and a model that adjusted for confounders and additional covariates. It was found that the occurrence of prenatal infections was 54.6%, with most infections occurring during the second trimester. In the unadjusted model, third trimester infections were found to be significantly associated with decreased verbal scores at age 4 (β= − 0.076, p = .031), as well as decreased verbal IQ scores (β= − 0.036, p = .008), performance IQ scores (β= − 0.036, p = .009) and total IQ scores (β= − 0.040, p = .003) at age 8 . After confounders were adjusted for, significant associations were still found between third-trimester infections and performance IQ scores (β= − 0.039, p = .007) and total IQ scores (β= − 0.033, p = .020) at 8 years. Finally, the fully adjusted model that adjusted for confounders and covariates, showed that third trimester infections were significantly associated with lower performance IQ scores at age 8 (β= − 0.033, p = .032). Lower maternal education and higher deprivation were also found to be associated with lower cognitive scores across all trimesters. This study was limited in severity and cause of infection and was unable to include all cofounders and covariates. Additionally, the effects of maternal infection beyond the age of 8 years were not assessed. Overall, this study found that the timing of prenatal infection is associated with varied childhood cognitive outcomes, with third trimester infection being associated with lower IQ scores, with more significant effects as cognitive load increases over time.