The association between maternal immune activation and brain structure and function in human offspring: a systematic review

Abstract

Maternal immune activation (MIA) during pregnancy, as a result of infectious or inflammatory stimuli, has gained increasing attention for its potential role in adverse child neurodevelopment, with studies focusing on associations in children born preterm. This systematic review summarizes research on the link between several types of prenatal MIA and subsequent child structural and/or functional brain development outcomes. We identified 111 neuroimaging studies in five MIA areas: inflammatory biomarkers (n = 13), chorioamnionitis (n = 18), other types of infections (n = 18), human immunodeficiency virus (HIV) (n = 42), and Zika virus (n = 20). Overall, there was large heterogeneity in the type of MIA exposure examined and in study methodology. Most studies had a prospective single cohort design and mainly focused on potential effects on the brain up to one year after birth. The median sample size was 53 participants. Severe infections, i.e., HIV and Zika virus, were associated with various types of cerebral lesions (e.g., microcephaly, atrophy, or periventricular leukomalacia) that were consistently identified across studies. For less severe infections and chronic inflammation, findings were generally inconsistent and mostly included deviations in white matter structure/function. Current findings have been mainly observed in the infants’ brain, presenting an opportunity for future studies to investigate whether these associations persist throughout development. Additionally, the inconsistent findings, encompassing both regions of interest and null results, call into question whether prenatal exposure to less severe infections and chronic inflammation exerts a small effect or no effect on child brain development.