Full-term deliveries without antecedent labor reveal sex differences in umbilical cord glucocorticoid concentrations

Background Previous studies have shown that pregnant women have higher salivary cortisol levels when the fetus is female. These findings suggest a basis for the sex differences observed in many offspring outcomes after exposure to in utero stress, but it is not known if fetal adrenal glucocorticoid synthesis differs by sex. Methods Arterial and venous umbilical cord blood samples were collected immediately after scheduled cesarean delivery (n = 52, 25 female). Cortisol and corticosterone concentrations were quantified by liquid chromatography coupled to tandem mass spectrometry. Results Sex differences were observed for fetal arterial and venous cortisol and venous corticosterone, with higher levels present when the fetus was female. However, sex differences were not observed for fetal synthesis of cortisol, suggesting that the fetus does not control the differences observed in cord blood glucocorticoids. Conclusions The presence of sex differences in umbilical cord glucocorticoid concentrations in the absence of sex differences in glucocorticoid synthesis by the fetal adrenal gland suggests that these differences have a maternal or placental origin. Thus, the in utero glucocorticoids in circulation are sex-specific and may have developmental importance for sex differences in psychiatric and neurodevelopment disorders that display sex biases.