The association between maternal immune activation and brain structure and function in human offspring: a systematic review
Anna Suleri1,2, Anna-Sophie Rommel3, Olga Dmitrichenko1,3
1Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Insights
Maternal immune activation during pregnancy from severe infections like HIV and Zika virus is linked to infant brain lesions. Less severe infections and inflammation show inconsistent effects on child neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Maternal immune activation (MIA) from infections or inflammation during pregnancy is increasingly linked to adverse child neurodevelopment.
- Research has primarily focused on preterm infants, necessitating a broader review of MIA effects on neurodevelopment.
Purpose of the Study:
- To systematically review neuroimaging studies examining the association between prenatal MIA and child structural/functional brain development.
- To synthesize findings across various MIA types, including inflammatory biomarkers, chorioamnionitis, other infections, HIV, and Zika virus.
Main Methods:
- Systematic review of 111 neuroimaging studies.
- Categorization of studies based on five MIA areas: inflammatory biomarkers, chorioamnionitis, other infections, HIV, and Zika virus.
- Analysis of study designs, sample sizes, and neurodevelopmental outcomes up to one year postpartum.
Main Results:
- Severe infections (HIV, Zika virus) consistently associated with cerebral lesions (microcephaly, atrophy, periventricular leukomalacia).
- Less severe infections and chronic inflammation showed inconsistent findings, primarily affecting white matter structure/function.
- Most studies focused on infant brain development, with a median sample size of 53 participants.
Conclusions:
- Prenatal exposure to severe infections significantly impacts infant brain structure.
- The effect of less severe infections and chronic inflammation on child neurodevelopment remains unclear due to inconsistent findings.
- Future research should explore long-term neurodevelopmental effects and investigate the persistence of observed brain alterations.
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.
