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 (_waFAV). Results: At ultrasound 1, _waFAV 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, _waFAV 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, _waFAV 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 _waFAV, a proxy for fetal adrenal development, but only in males. Our observation that the _waFAV in males of mothers with a high ACE history did not differ from the _waFAV 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.