Prenatal Maternal Stress and Weak Handedness in Early Childhood: The Iowa Flood Study.

Weak handedness is frequently observed in individuals with neurodevelopmental and psychiatric disorders. Although birth-related stressors, such as prematurity, have been shown to contribute to this association, the influence of early prenatal maternal stress (PNMS) remains under-explored. This study examined the trimester-specific effects of disaster-related PNMS on handedness development using rare longitudinal data from the 2008 Iowa Flood Study. Pregnant women exposed to major flooding were assessed for objective (hardship severity) and subjective (psychological distress) PNMS and postnatal maternal depression, and their children's handedness was reported at 60 months (n = 217, 45.6% female). Path analyses revealed distinct trimester-dependent associations between PNMS and offspring handedness. When stress exposure occurred during the first trimester, weak handedness in offspring was predicted by the child's sex, with male sex being associated with higher weak handedness (β = -0.29) only. In contrast, for third trimester exposure, higher objective PNMS was associated with higher weak handedness (β = -0.34), while the child's sex was no longer a significant predictor (β = 0.11). These findings suggest that PNMS influences the ontogenesis of handedness through trimester-specific mechanisms, potentially mediated by epigenetic modifications. Potential neurobiological mechanisms underlying these associations and their clinical implications for neurodevelopmental outcomes are discussed.