Association between umbilical cord glucocorticoids and blood pressure at age 3 years

Among 286 newborns in Project Viva, a prospective pre-birth cohort study based in eastern Massachusetts, we measured cortisol (F) and cortisone (E) in venous cord blood and used the ratio of F/E as a marker for placental 11β-HSD2 activity. We measured blood pressure (BP) when the offspring reached age 3 years. Using mixed effects regression models to control for BP measurement conditions, maternal and child characteristics, we examined the association between the F/E ratio and child BP.At age 3 years, each unit increase in the F/E ratio was associated with a 1.6 mm Hg increase in systolic BP (95% CI 0.0 to 3.1). The F/E ratio was not associated with diastolic blood pressure or birth weight for gestational age z-score.A higher F/E ratio in umbilical venous cord blood, likely reflecting reduced placental 11β-HSD2 activity, was associated with higher systolic blood pressure at age 3 years. Our data suggest that increased fetal exposure to active maternal glucocorticoids may program later systolic blood pressure.Many observational studies have demonstrated an inverse association between birth weight and blood pressure (BP), raising the intriguing possibility that lifelong hypertension might be programmed in utero [1]. The mechanisms underlying this association remain unclear.One plausible hypothesis, based on animal data, proposes that a low protein diet during pregnancy leads to increased fetal glucocorticoid exposure, permanently programming both lower birth weight and elevated BP in offspring [2]. Studies in humans have not found a consistent association between maternal protein intake and offspring blood pressure [3-6], but few studies have examined whether fetal glucocorticoid exposure might program offspring BP.Experiments in rats have shown that maternal treatment during pregnancy with the synthetic glucocorticoid dexamethasone, which freely crosses the placenta, is associated with lower birth weight and raised BP in the offspring [7]. Protection from exposure to