Steroid hormones in early pregnancy and adverse birth outcomes: a Chinese birth cohort

Background: Adverse birth outcomes (ABOs) are major public health concerns. While maternal steroid hormones are essential for fetal development, their individual and combined effects on ABO remain unclear. Methods: This prospective cohort study included 364 pregnant women (30.7 ± 4.0 years) in Guangzhou, China. Nineteen steroid hormones were measured by LC-MS/MS. Regression and Qgcomp models were used to assess individual and combined associations with ABO, including low birth weight, macrosomia, small for gestational age (SGA), large for gestational age, and preterm birth. Results: Pregnant women with ABO had higher levels of androstenedione (A4) and testosterone (T) and lower levels of 11-deoxycortisol (11-DOF) and estriol (E3). In linear regression models, each 1-SD increase in cortisol (F) was associated with increases of 0.18 cm (95% CI: 0.02, 0.34) in birth length and 0.24 cm (95% CI: 0.04, 0.44) in head circumference, whereas estrone (E1) was inversely associated with gestational age (-0.20 weeks, 95% CI: -0.36, -0.05). In logistic regression analyses, each 1-SD increase in A4 (OR = 1.36, 95% CI: 1.07, 1.72), T (OR = 1.37, 95% CI: 1.08, 1.73), and dihydrotestosterone (DHT) (OR = 1.32, 95% CI: 1.03, 1.69) was associated with higher odds of ABO, whereas 11-DOF was inversely associated with ABO (OR = 0.70, 95% CI: 0.50, 0.98). For SGA, each 1-SD increase in A4 (OR = 1.40, 95% CI: 1.01, 1.94) and T (OR = 1.47, 95% CI: 1.08, 1.99) was associated with increased risk, whereas F (OR = 0.84, 95% CI: 0.72, 0.97) and 11-DOF (OR = 0.58, 95% CI: 0.35, 0.95) were inversely associated. In Qgcomp analyses, the androgen mixture was associated with ABO (OR = 1.40, 95% CI: 1.00, 1.97) and SGA (OR = 1.77, 95% CI: 1.04, 3.01), with A4 and T contributing the largest weights. Consistent directional patterns were observed for androgen-related hormones across outcomes and analytical approaches. Conclusions: Maternal hormonal milieu in early pregnancy may be associated with fetal growth and ABO risk, with consistent patterns for androgen-related hormones. These findings are exploratory and require validation in larger cohorts.