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

Abstract

AbstractBackgroundThe 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.MethodsWe 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).ResultsAt 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).ConclusionsWe observed a significant impact of high maternal ACE history onwaFAV, a proxy for fetal adrenal development, but only in males. Our observation that thewaFAV in males of mothers with a high ACE history did not differ from thewaFAV 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.