Maternal stress in pregnancy and pubertal timing in girls and boys: a cohort study

Objective: To investigate whether maternal stress in pregnancy is associated with pubertal timing in girls and boys and to explore potential mediation by childhood body mass index (BMI) and childhood psychosocial stress. Design: Cohort study. Setting: Not applicable. Patients: In total, 14,702 girls and boys from the Puberty Cohort, nested within the Danish National Birth Cohort. Intervention: Maternal stress was obtained from a computer-assisted telephone interview in gestational weeks 30–32 as maternal life stress and emotional distress in pregnancy using questions on the basis of validated screening tools. Maternal life stress and emotional distress in pregnancy were analyzed separately and in an interaction analysis. Main Outcome Measures: Pubertal timing was measured half-yearly from age 11 years and throughout pubertal development and assessed as Tanner stages 1–5 (breast and pubic hair development in girls and genital and pubic hair development in boys), menarche in girls, voice break and first ejaculation in boys, and occurrence of acne and axillary hair in both girls and boys. A combined estimate for overall pubertal timing was derived using Huber-White robust variance estimation. Mean differences in age at attaining the pubertal milestones according to prenatal exposure to no (reference), low-, moderate-, or high-maternal stress in pregnancy were estimated using a multivariable censored regression model. Potential mediation by childhood BMI and childhood psychosocial stress was investigated in separate models. Results: After adjustment for potential confounding factors, prenatal exposure to high-maternal life stress (combined estimate: −1.8 months 95% CI, −2.7 to −0.8 and −0.9 months 95% CI, −1.8 to 0.0), high maternal emotional distress (combined estimate: −1.5 months 95% CI, −2.5 to −0.5 and −1.7 months 95% CI, −2.8 to −0.7), and both high-maternal life stress and emotional distress (combined estimate: −2.8 months 95% CI, −4.2, to −1.4 and −1.7 months 95% CI, −3.1 to −0.2) were associated with earlier pubertal timing in girls and boys, respectively. The associations were not mediated by childhood BMI or childhood psychosocial stress. Conclusions: Prenatal exposure to maternal stress in pregnancy was associated with earlier pubertal timing in girls and boys in a dose-dependent manner. The associations were not mediated by childhood BMI or childhood psychosocial stress.