Research article

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

Susanna Y Huh¹ , Ruth Andrew² , Janet W Rich-Edwards^3,4,6 , Ken P Kleinman³ , Jonathan R Seckl² and Matthew W Gillman^3,5

¹Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, MA, USA

²Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK

³Department of Ambulatory Care and Prevention, Harvard Medical School/Harvard Pilgrim Health Care, Boston, MA, USA

⁴Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, MA, USA

⁵Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

⁶Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

author email corresponding author email

BMC Medicine 2008, 6:25doi:10.1186/1741-7015-6-25

Published:	28 August 2008

Abstract

Background

Animal data show that decreased activity of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11β-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 11β-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 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.

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 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.