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Pregnancy Hormones and Offspring Psychiatric Problems: Testing Associations Between Placental Corticotropin-Releasing

Alexandra D W Sullivan, Emily S Barrett, Alexis Sullivan

Biopsychosocial Science and Medicine

|April 1, 2026

Insights

Maternal placental corticotropin-releasing hormone (pCRH) levels during pregnancy were not linked to offspring internalizing problems in middle childhood. This study found no evidence supporting pCRH as a mediator for intergenerational stress transmission effects.

Area of Science:

Neuroendocrinology
Developmental Psychology
Maternal-Fetal Medicine

Background:

Placental corticotropin-releasing hormone (pCRH) is crucial for fetal development and birth timing.
Prenatal programming theories suggest maternal pCRH mediates intergenerational stress transmission.
Empirical evidence for this link, especially in middle childhood, is limited.

Purpose of the Study:

To investigate associations between maternal pCRH and offspring internalizing psychopathology in middle childhood.
To examine pCRH's role as a neuroendocrine mediator in the intergenerational transmission of stress.
To explore the influence of fetal sex on these associations.

Main Methods:

Prospective study of 838 mother-child dyads from the CANDLE sample.
Maternal pCRH levels and rate of rise estimated from 2nd and 3rd trimester plasma.
Child internalizing psychopathology assessed at age eight via maternal/child reports and threat sensitivity tasks.

Main Results:

No significant associations were found between pCRH (rate of rise or cumulative exposure) and any of the six tested child outcomes.
These outcomes included child-reported depression/anxiety, maternal-reported internalizing problems, and threat sensitivity.
Fetal sex did not moderate the observed associations.

Conclusions:

Findings do not support pCRH as a maternal neuroendocrine mediator for intergenerational stress effects on offspring internalizing psychopathology in middle childhood.
This contrasts with theories and findings from smaller samples or younger age groups.
Further research is warranted to explore potential waning associations or alternative mechanisms.

Read full analysis

Abstract

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 second and third trimester blood plasma. We operationalized child internalizing psychopathology and related behavioral phenotypes at age 8 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 was associated with any of the 6 multi-method, multi-informant child outcomes tested (eg, child-reported depression and anxiety symptoms, maternal-reported internalizing problems, task-based indicators of threat sensitivity) ( p s 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.

Keywords:

anxiety depression intergenerational transmission internalizing psychopathology placental corticotropin-releasing hormone (pCRH)prenatal programming

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