Interactive relations between maternal prenatal stress, fetal brain connectivity, and gestational age at delivery

Moriah E Thomason,Jasmine L Hect,Rebecca Waller,Paul Curtin

doi:10.1038/s41386-021-01066-7

Abstract

Studies reporting significant associations between maternal prenatal stress and child outcomes are frequently confounded by correlates of prenatal stress that influence the postnatal rearing environment. The major objective of this study is to identify whether maternal prenatal stress is associated with variation in human brain functional connectivity prior to birth. We utilized fetal fMRI in 118 fetuses [48 female; mean age 32.9 weeks (SD = 3.87)] to evaluate this association and further addressed whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Community detection was used to empirically define networks and enrichment was used to isolate differential within- or between-network connectivity effects. Significance for χ2 enrichment was determined by randomly permuting the subject pairing of fetal brain connectivity and maternal stress values 10,000 times. Mixtures modelling was used to test whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Increased maternal prenatal negative affect/stress was associated with alterations in fetal frontoparietal, striatal, and temporoparietal connectivity (β = 0.82, p < 0.001). Follow-up analysis demonstrated that these associations were stronger in women with better health behaviors, more positive interpersonal support, and lower overall stress (β = 0.16, p = 0.02). Additionally, magnitude of stress-related differences in neural connectivity was marginally correlated with younger gestational age at delivery (β = −0.18, p = 0.05). This is the first evidence that negative affect/stress during pregnancy is reflected in functional network differences in the human brain in utero, and also provides information about how positive interpersonal and health behaviors could mitigate prenatal brain programming.

Highlights

Children born to mothers who endure heightened psychological or physiological stress during pregnancy may experience negative consequences as a result of these early programming events
The present study addresses this gap by leveraging emergent functional magnetic resonance imaging techniques to evaluate, for the first time, whether and how variation in maternal stress relates to human fetal brain system organization
The primary objective of this study is to establish whether maternal prenatal stress relates to changes in the child’s brain before birth; the second is to determine whether psychosocial support and health behaviors affect this association; and the third is to test whether this neurobiological embedding of stress relates to how early a child will be born

Summary

Introduction

Children born to mothers who endure heightened psychological or physiological stress during pregnancy may experience negative consequences as a result of these early programming events. Postnatal studies in neonates and children corroborate these observations showing that stress alters newborn functional neural connectivity [27,28,29] and child structural brain development [30]. Differences in child brain structure have been shown to mediate, in part, the association between prenatal stress and affective problems in childhood [31]. While such findings suggest that prenatal stress alters the fetal brain, examining these outcomes postnatally represents a major limitation. Prospective evidence that the fetal brain is altered is needed to provide stronger evidence that maternal stress during pregnancy impacts the human brain in utero

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