Substrates and Clearance Products of Fetal Adrenal Glucocorticoid Synthesis in Full-Term Human Umbilical Circulation

Abstract

Abstract In full-term elective caesarian sections, fetal flow of adrenal substrate steroids to products differs by sex, with males (M) in molar equilibrium whereas females (F) add net molarity and synthesize more cortisol. Using the same sampling design, paired, full-term, arterial, and venous umbilical cord samples and intrapartum chart records were obtained at the time of vaginal delivery (N = 167, 85 male) or emergency C-section (N = 38, 22 male). Eight steroids were quantified by liquid chromatography coupled to tandem mass spectrometry (adrenal glucocorticoids [cortisol, corticosterone], sequential cortisol precursor steroids [17-hydroxyprogesterone, 11-deoxycortisol], cortisol and corticosterone metabolites [cortisone and 11-dehydrocorticosterone], and gonadal steroids [androstenedione, testosterone]). Fetal sex was not significant in any analytic models. Going through both phase 1 and phase 2 labor increased fetal adrenal steroidogenesis and decreased male testosterone relative to emergency C-sections that do not reach stage 2 of labor (ie, head compressions) and elective C-sections with no labor. Sum adrenal steroid molarity arriving in venous serum was almost double the equivalent metric for deliveries without labor. No effects of operative vaginal delivery were noted. Maternal regional anesthetic suppressed venous concentrations, and fetal synthesis replaced that steroid. Approximate molar equivalence between substrate pool depletion and net glucocorticoid synthesis was seen. Paired venous and arterial umbilical cord serum has the potential to identify sex differences that underlie antenatal programming of hypothalamic-pituitary-adrenal axis function in later life. However, stage 2 labor before the collection of serum, and regional anesthetic for the mother, mask those sex differences.