Pregnancy Hormones and Offspring Psychiatric Problems: Testing Associations Between Placental Corticotropin Releasing Hormone and Children’s Age 8 Internalizing Outcomes

OBJECTIVE: Placental corticotropin-releasing hormone (pCRH) is a peptide essential for fetal development and birth timing. Prenatal programming frameworks position maternal pCRH as a primary neuroendocrine mediator underlying the intergenerational transmission of stress, but empirical evidence is sparse. Using rigorous methodology, we conducted the first investigation of associations between pCRH and multi-informant indicators of offspring internalizing psychopathology during middle childhood. METHODS: This study used the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) sample of socioeconomically diverse mother-child dyads (n=838) followed prospectively from pregnancy. We estimated pCRH rate of rise and level at delivery using maternal 2nd and 3rd trimester blood plasma. We operationalized child internalizing psychopathology and related behavioral phenotypes at age eight with maternal report of internalizing problems, child report of depression and anxiety, and task-based indicators of threat sensitivity. Covariate-adjusted regression models estimated associations between pCRH and offspring outcomes and whether fetal sex moderated associations. RESULTS: Neither rate of rise nor cumulative exposure were associated with any of the six multi-method, multi-informant child outcomes tested (e.g., child-reported depression and anxiety symptoms, maternal-reported internalizing problems, task-based indicators of threat sensitivity (ps range from .16-.83). Fetal sex did not moderate associations. CONCLUSIONS: Contrasting theory and findings in smaller samples at younger ages, evidence from this study did not support pCRH as a plausible maternal neuroendocrine mediator for the intergenerational transmission of stress effects on offspring internalizing psychopathology during middle childhood. Future research exploring potential for waning associations across early childhood or other potential mechanisms is warranted.