OC02.02: Maternal stress and fetoplacental cortisol regulation in small‐for‐gestational‐age newborns

Previous research suggests an association between maternal stress, fetal growth, and the expression of placental glucocorticoid-related genes. This study evaluated the association between perceived maternal stress, expression, and methylation of the 11-Beta Hydroxysteroid Dehydrogenase 2 (HSD11β2) gene in the placenta, fetal cortisol metabolites in amniotic fluid, and birthweight. This nested case-control study within a large cohort assessed stress in singleton gestation mothers using the PSS and STAI. Mothers who delivered SGA neonates (birthweight < 10th centile, n = 343) were compared to those with adequate fetal growth (n = 399). We also examined placental HSD11B2 RNA expression and DNA methylation at this gene locus and analysed fetal cortisol, cortisone, and enzyme activity in amniotic fluid via liquid chromatography-tandem mass spectrometry. In SGA pregnancies, median PSS (23 [17–28] vs. 20 [15–26], p < 0.001) and STAI scores (1.95 [1.70–2.30] vs. 1.8 [1.5–2.2], p < 0.001) were significantly higher than controls. Placental HSD11B2 RNA was lower in SGA (50.5 [21.6–105] vs. 92.7 [62–117], p = 0.013), with no DNA methylation difference (p = 0.642). Amniotic fluid showed altered cortisol metabolism in SGA, with increased 5a-tetrahydrocortisol (0.09% vs. 0.07%, p = 0.005) and decreased 6 hydroxycortisol (0.09% vs. 0.11%, p < 0.001). SGA pregnancies show increased maternal stress and altered fetoplacental cortisol metabolism, offering insights into SGA's pathophysiology and underscoring the need for strategies to lower maternal stress. AGA (N = 399) SGA (N = 343)