Maternal Prenatal Psychological Stress and Iron Levels in the Fetal Brain

Fetal iron status has long-lasting effects on neurodevelopmental outcomes and risk of psychopathology. Although prenatal exposure to maternal psychological stress has been linked to offspring peripheral iron status at birth, it is unknown whether maternal prenatal stress is related to fetal brain iron during gestation. We utilized 86 multi-echo functional magnetic resonance imaging (fMRI) scans from 52 fetuses (23 females; gestational age [GA] 24-38 weeks) to estimate R2* relaxometry as a proxy for fetal brain iron levels. Our results showed that greater maternal anxiety symptoms were associated with higher estimated fetal iron levels in the left cerebellar vermis after controlling for fetal sex and GA. Our finding suggests that fetal brain iron levels may be sensitive to exposure to maternal stress in utero. In a subset of participants with available infant outcome data (n = 31), no significant associations were found between fetal brain iron levels and later cognitive, language, and motor development during infancy. Overall, this study presents the first evidence of associations between maternal prenatal stress and fetal brain iron, which lays the groundwork for future investigations of biological embedding of prenatal maternal stress on the fetal brain and later neurodevelopment through prenatal iron accumulation as a potential mechanism.