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

Abstract

Abstract 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 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 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, compared to low ACE males, high ACE males (b=-0.08; z=-1.58; p = .114) and low ACE females (b=-0.09; z=-1.92; p = .055) had marginally smaller waFAV. Perceived stress did not differ between maternal ACE groups at baseline (t=-0.58; df = 142.18; p = .562), ultrasound 1 (t =-1.46; df = 141.05; p = .148), or ultrasound 2 (t=-0.67; df = 140.55; p = .504). 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.