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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. Highlights: Three-dimensional ultrasound serves as a non-invasive way to measure fetal adrenal volume as a proxy for development of the fetal hypothalamic–pituitary–adrenal axis. Weight-adjusted fetal adrenal volume (waFAV) differed between subgroups based on offspring sex and the mother's history of adverse childhood experiences (ACEs). In males of mothers with a high ACE history, waFAV was significantly smaller than in males of mothers with a low ACE history but indistinguishable from the waFAV of females from either maternal ACE group; however, males of mothers with a low ACE history had larger waFAV than females from either maternal ACE group. These findings suggest male vulnerability to dysmasculinization of waFAV in response to maternal preconception stress in line with previous animal studies showing a dysmasculinizing effect of gestational stress on a range of offspring outcomes. [ABSTRACT FROM AUTHOR]

Background: Depression during pregnancy affects 5%-8% of women. While the percentage of women in the US taking serotonin reuptake inhibitors during pregnancy has risen over the last decade, pregnant women continue to report that they prefer non-pharmacologic interventions. Objective: We review the literature regarding neuromodulation techniques for major depressive disorder during pregnancy. The rationale for their use in this population, new developments, and future directions are discussed. Methods: A literature search was conducted in PubMed Plus, Ovid Medline, and Embase to collect all articles on neuromodulation for the treatment of depression during pregnancy. Key search words included electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation, transcranial direct current stimulation, neuromodulation, depression, and pregnancy. Given the sparse literature, all articles from 1960 to 2014 that addressed the use of neuromodulation in pregnancy were included. Conclusion: The data support the use of electroconvulsive therapy in all trimesters of pregnancy for major depressive disorder. New data are emerging for the use of transcranial magnetic stimulation in pregnancy, which is likely safe, but more data are needed before it can be recommended as a primary treatment modality during pregnancy. Other neuromodulation techniques have not been well studied in this population. [ABSTRACT FROM AUTHOR]