Sex-specific alterations in placental 11beta-hydroxysteroid dehydrogenase 2 activity and early postnatal clinical course following antenatal betamethasone.
Placental 11beta-hydroxysteroid dehydrogenase-2 (11betaHSD2) limits fetal glucocorticoid exposure and is associated with physiological stability in the premature newborn infant. Antenatal betamethasone alters 11betaHSD2 activity and confers sex-specific advantages in neonatal outcome. We investigated the influence of betamethasone and sex on 11betaHSD2 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 11betaHSD2 activity rate (P = 0.02) and umbilical arterial cortisol (P = 0.01). For infants born < 72 h following antenatal betamethasone, females had higher 11betaHSD2 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, 11betaHSD2 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 11betaHSD2 and adrenal response may contribute to the increased incidence of poor outcome observed in preterm males.
Stark
Michael J
MJ
Robinson Institute, Dept. of Paediatrics and Reproductive Health, Level 6 Medical School North, Univ. of Adelaide, SA, Australia 5005.
Wright
Ian M R
IM
Clifton
Vicki L
VL
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001034:Apgar Score; D001623:Betamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D001724:Birth Weight; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology*; D011247:Pregnancy; D047928:Premature Birth / Q000188:drug therapy; D012727:Sex Characteristics; D013312:Stress, Physiological / Q000502:physiology; D055815:Young Adult
D001623:Betamethasone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone