Background: Emerging research suggests that maternal immune activation (MIA) may be associated with an increased risk of adverse neurodevelopmental and mental health outcomes in offspring. Using data from the Raine Study, we investigated whether MIA during pregnancy was associated with increased behavioral and emotional problems in offspring longitudinally across development.
Methods: Mothers (Generation 1; N = 1905) were classified into the following categories: AAAE (Asthma/Allergy/Atopy/Eczema; N = 1267); infection (during pregnancy; N = 1082); no AAAE or infection (N = 301). The Child Behavior Checklist (CBCL) was administered for offspring at ages 5, 8, 10, 14, and 17. Generalized estimating equations were used to investigate the effect of maternal immune status on CBCL scores.
Results: AAAE conditions were associated with significant increases in CBCL Total (β 2.49; CI 1.98-3.00), Externalizing (β 1.54; CI 1.05-2.03), and Internalizing (β 2.28; CI 1.80-2.76) scores. Infection conditions were also associated with increased Total (β 1.27; CI 0.77-1.78), Externalizing (β 1.18; CI 0.70-1.66), and Internalizing (β 0.76; CI 0.28-1.24) scores. Exposure to more than one AAAE and/or infection condition was associated with a greater elevation in CBCL scores than single exposures in males and females. Females showed greater increases on the Internalizing scale from MIA, while males showed similar increases on both Internalizing and Externalizing scales.
Conclusions: MIA was associated with increased behavioral and emotional problems in offspring throughout childhood and adolescence. This highlights the need to understand the relationship between MIA, fetal development, and long-term outcomes, with the potential to advance early identification and intervention strategies.
Keywords: ADHD; anxiety; autism; depression; inflammation; neurodevelopment.