Association of maternal antenatal distress with child amygdala-prefrontal cortex functional connectivity at 2–3 years in a South African birth cohort study

Abstract

Maternal antenatal psychological distress can negatively affect child development, particularly in low- and middle-income countries (LMICs) where women are at heightened risk for distress. This study examined the association between maternal antenatal distress and child amygdala-prefrontal cortex functional connectivity in a South African birth cohort using resting-state fMRI. Children aged 2-3 years who were either exposed to maternal distress in utero (n = 27) or unexposed (n = 85) were analyzed using region-of-interest analysis. Multivariate analysis of covariance assessed group differences, adjusting for confounders, and Pearson correlations examined associations with externalizing behaviors 6-18 months later across the whole sample (n = 111). Exposed children showed weaker amygdala-medial PFC and amygdala-lateral PFC connectivity than unexposed peers (medial PFC: mean=0.099 vs 0.164, p = 0.034; lateral PFC: mean=0.095 vs 0.132, p = 0.025). These differences were significant in boys only (medial PFC: p = 0.016; lateral PFC: p = 0.019). Additionally, hippocampus-PFC connectivity at ages 2-3 was negatively associated with later externalizing behaviors. Findings suggest exposure to maternal psychological distress in utero impacts amygdala-PFC connectivity in early childhood, while exploratory associations between hippocampus-PFC and externalizing behavior point to potential links with later behavioral outcomes. Understanding these neural correlates may inform early interventions to disrupt intergenerational transmission of psychological risk.