ArticleUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology2025
Maternal stress and fetoplacental cortisol regulation in small-for-gestational-age newborns.
Article in Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Stressed, Stained, and Stored: The Impact of Maternal Distress and Smoking on Amniotic Biomarkers-A Scoping Review.International journal of molecular sciences · 2026Article
- Mid-pregnancy psychosocial distress and the risk of third-trimester small-for-gestational-age fetuses: a prospective cohort study in coastal Indonesia.Frontiers in psychiatry · 2026Article
- Effects of occupational stress on the distribution of circulating T lymphocyte subsets and psychological health of young anaesthesiologists.BMC psychology · 2025Article
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12 authors.
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Abstract
objectivePrevious research has identified an association between maternal stress, fetal growth and the expression of glucocorticoid-related genes in the placenta, particularly 11-beta hydroxysteroid dehydrogenase-2 (HSD11β2). However, to date, no studies have simultaneously explored the relationships between maternal stress, placental expression and methylation of HSD11β2, and fetal cortisol metabolites according to fetal growth. The aim of the present study was to evaluate the association between perceived antenatal maternal stress, the expression and methylation of the placental HSD11β2 gene, fetal cortisol metabolites in amniotic fluid and birth weight.
methodsThis nested case-control study, which was part of a large prospective cohort study, was conducted at two maternofetal medicine units in Barcelona, Spain (BCNatal: Hospitals Clinic and Sant Joan de Déu). We enrolled singleton pregnancies and classified neonates as small-for-gestational age (SGA) if their birth weight was below the 10
resultsMedian maternal perceived stress (PSS, 23 (interquartile range (IQR), 17-28) vs 20 (IQR, 15-26); P < 0.001) and median anxiety state (STAI-state, 19.0 (IQR, 14.0-29.0) vs 16.0 (IQR, 11.0-24.0); P < 0.001) scores were significantly higher in the SGA group compared with the control group. SGA cases showed lower median placental HSD11β2 RNA expression (Δ Ct, 50.5 (IQR, 21.6-106.0) vs 92.7 (IQR, 62.3-118.0); P = 0.013) with similar DNA methylation levels (mean ± SD, 10.7 ± 3.0% vs 11.0 ± 2.8%; P = 0.648) compared with AGA controls. Analysis of amniotic fluid revealed altered cortisol metabolism in SGA fetuses, with increased median 5α-tetrahydrocortisol concentration (SGA, 0.09% (IQR, 0.06-0.15%) vs controls, 0.07% (IQR, 0.05-0.11%); P = 0.020) and activity of its related enzyme (5α-reductase activity in SGA, 0.19% (IQR, 0.14-0.31%) vs controls, 0.17% (IQR, 0.12-0.22%); P = 0.007), together with a decrease in median 6-hydroxycortisol concentration (SGA, 0.09% (IQR, 0.06-0.11%) vs controls, 0.11% (IQR, 0.08-0.12%); P < 0.001) and activity of its related enzyme (CYP3A7 activity in SGA, 0.19% (IQR, 0.11-0.25%) vs controls, 0.24% (IQR, 0.17-0.33%); P < 0.001).
conclusionsSGA pregnancy is associated with high perceived maternal stress and dysregulated fetoplacental cortisol metabolism. These results deepen our understanding of the pathophysiology of SGA and highlight the potential benefit of intervention to mitigate maternal stress. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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