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Maternal prenatal stress is associated with altered placental microstructure in low-risk pregnancies and pregnancies with Congenital Heart Disease

Bonthrone, A. F.; Cromb, D.; Ahmad Javed, S.; Aviles Verdera, J.; Pushparajah, K.; Rutherford, M.; Hutter, J.; Counsell, S. J.

2026-03-03 obstetrics and gynecology
10.64898/2026.03.02.26347408 medRxiv
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ObjectivesTo assess if maternal stress is higher in pregnancies with congenital heart disease (CHD) compared to low-risk pregnancies and if maternal stress is associated with placental microstructure and function. To explore if CHD alters the relationship between maternal stress and placental measures. MethodsIn this prospective observational study, 27 participants carrying a fetus with CHD and 42 participants with typical low-risk pregnancies underwent 1-2 combined diffusion{square}T2* relaxation placental MRIs from 20 weeks gestation (GA) and completed the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory [43 male fetuses, median (IQR) GA at assessment 30.86 weeks (27.43-34.00), interval between assessments 6.00 weeks (4.86-7.14)]. 98 complete placental MRI and maternal stress datasets were available. Generalized Estimating Equations were used for analyses. ResultsHigher trait anxiety was associated with higher placental apparent diffusion coefficient (p=0.023) adjusting for CHD, sex, GA at assessment, GA at assessment2, state anxiety, depressive symptoms and previous mental health treatment. Maternal state anxiety (p=0.005) and depressive symptoms (p=0.046) were higher in pregnancies with CHD adjusting for GA at assessment and previous mental health treatment. CHD did not alter these relationships (p>0.119). ConclusionsMaternal proneness to anxiety, measured with the trait anxiety inventory, is associated with increased diffusivity in the placenta, which may reflect altered microstructural maturation. Mothers with fetal CHD show more depressive symptoms and feelings of anxiety and may benefit from screening for elevated maternal stress. The findings contribute to a growing body of research regarding the influence of prenatal stress on placental development. HighlightsO_LIMaternal stress and placental MRI data acquired in pregnancies with and without CHD C_LIO_LIMaternal trait anxiety is associated with increased placental diffusivity C_LIO_LIMaternal state anxiety and depressive symptoms are higher in fetal CHD C_LIO_LIState anxiety and depressive symptoms not associated with placental MRI measures C_LIO_LICHD did not moderate relationships between placental MRI measures and stress C_LI

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