Sex-specific alterations in placental 11β-hydroxysteroid dehydrogenase 2 activity and early postnatal clinical course following antenatal betamethasone

Abstract

Placental 11β-hydroxysteroid dehydrogenase-2 (11βHSD2) limits fetal glucocorticoid exposure and is associated with physiological stability in the premature newborn infant. Antenatal betamethasone alters 11βHSD2 activity and confers sex-specific advantages in neonatal outcome. We investigated the influence of betamethasone and sex on 11βHSD2 activity, neonatal adrenal function and clinical course in 24- to 36-wk gestation neonates from birth to day 5 of life. Univariate analyses demonstrated an interaction between timing of betamethasone exposure and sex for 11βHSD2 activity rate ( P = 0.02) and umbilical arterial cortisol ( P = 0.01). For infants born < 72 h following antenatal betamethasone, females had higher 11βHSD2 activity ( P < 0.01) and umbilical arterial cortisol ( P = 0.01) than males. Females born < 72 h of betamethasone exposure had higher day 1 urinary cortisol, if exposed to perinatal stress, than males ( P < 0.01). For infants born < 72 h after betamethasone exposure, 11βHSD2 activity was negatively correlated with Clinical Illness Severity Score score ( r = −0.79 P = 0.01) and positively correlated with mean arterial blood pressure ( r = 0.8 P = 0.01) only in females. Sex-specific placental 11BHSD2 autoregulation following antenatal betamethasone exposure may limit adrenal suppression in females influencing physiological stability following preterm birth. A lack of adjustment in 11βHSD2 and adrenal response may contribute to the increased incidence of poor outcome observed in preterm males.