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

Background: Animal data show that decreased activity of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2), which potently inactivates glucocorticoids (e. g. cortisol) to inert forms (cortisone), allows increased access of maternal glucocorticoids to the fetus and 'programs' hypertension. Data in humans are limited. We examined in humans the association between venous umbilical cord blood glucocorticoids, a potential marker for placental 11 beta-HSD2 enzyme activity, and blood pressure at age 3 years. Methods: 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 11 beta-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. Results: 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. Conclusion: A higher F/E ratio in umbilical venous cord blood, likely reflecting reduced placental 11 beta-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.