Placental 11β-HSD2 and Cardiometabolic Health Indicators in Infancy.

Abstract

Fetal excessive exposure to glucocorticoids may program cardiometabolic risk. Placental 11 β-hydroxysteroid dehydrogenase 2 (11β-HSD2) serves as a barrier to prevent fetal overexposure to maternal glucocorticoids. It has not been explored whether placental 11β-HSD2 levels are associated with cardiometabolic health in postnatal life. In a prospective birth cohort study of 246 mother-infant pairs, we measured placental 11β-HSD2 expression and maternal (32-35 weeks of gestation) and cord plasma cortisol concentrations. The primary outcomes were HOMA of insulin resistance (IR) and blood pressure (BP) in infants at age 1 year. Other outcomes included fasting insulin, HOMA β-cell function, carotid intima-media thickness, weight <i>z</i> score, and skinfold thickness (triceps and subscapular) at age 1 year. Placental 11β-HSD2 expression was negatively correlated with HOMA-IR (<i>r</i> = -0.17, <i>P</i> = 0.021) and fasting insulin (<i>r</i> = -0.18, <i>P</i> = 0.017) and marginally negatively correlated with systolic BP (<i>r</i> = -0.16, <i>P</i> = 0.057) but was not correlated with HOMA of β-cell function, diastolic BP, carotid intima-media thickness, and skinfold thickness (all <i>P</i> > 0.1) in infants at age 1 year. Cord plasma cortisol was negatively correlated to skinfold thickness (<i>r</i> = -0.20, <i>P</i> = 0007) but was not correlated with other outcomes at age 1 year. Maternal plasma cortisol was positively correlated with maximal carotid intima-media thickness (<i>r</i> = 0.20, <i>P</i> = 0.03) but was not correlated with other outcomes. Adjusting for maternal and infant characteristics, the associations were similar. The study is the first to show that higher placental 11β-HSD2 expression is associated with lower IR in infancy. Independent cohort studies are required to confirm this novel finding.