Maternal adverse childhood experiences impact fetal adrenal volume in a sex-specific manner

BACKGROUND: The mechanisms by which parental early life stress can be transmitted to the next generation, in some cases in a sex-specific manner, are unclear. Maternal preconception stress may increase susceptibility to suboptimal health outcomes via in utero programming of the fetal hypothalamic–pituitary–adrenal (HPA) axis. METHODS: We recruited healthy pregnant women (N = 147), dichotomized into low (0 or 1) and high (2+) adverse childhood experience (ACE) groups based on the ACE Questionnaire, to test the hypothesis that maternal ACE history influences fetal adrenal development in a sex-specific manner. At a mean (standard deviation) of 21.5 (1.4) and 29.5 (1.4) weeks gestation, participants underwent three-dimensional ultrasounds to measure fetal adrenal volume, adjusting for fetal body weight ((wa)FAV). RESULTS: At ultrasound 1, (wa)FAV was smaller in high versus low ACE males (b = − 0.17; z = − 3.75; p < .001), but females did not differ significantly by maternal ACE group (b = 0.09; z = 1.72; p = .086). Compared to low ACE males, (wa)FAV was smaller for low (b = − 0.20; z = − 4.10; p < .001) and high ACE females (b = − 0.11; z = 2.16; p = .031); however, high ACE males did not differ from low (b = 0.03; z = .57; p = .570) or high ACE females (b = − 0.06; z = − 1.29; p = .196). At ultrasound 2, (wa)FAV did not differ significantly between any maternal ACE/offspring sex subgroups (ps ≥ .055). Perceived stress did not differ between maternal ACE groups at baseline, ultrasound 1, or ultrasound 2 (ps ≥ .148). CONCLUSIONS: We observed a significant impact of high maternal ACE history on (wa)FAV, a proxy for fetal adrenal development, but only in males. Our observation that the (wa)FAV in males of mothers with a high ACE history did not differ from the (wa)FAV of females extends preclinical research demonstrating a dysmasculinizing effect of gestational stress on a range of offspring outcomes. Future studies investigating intergenerational transmission of stress should consider the influence of maternal preconception stress on offspring outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13293-023-00492-0.