Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial.
BACKGROUND
Antenatal betamethasone treatment is widely used for the prevention of neonatal respiratory distress syndrome in preterm infants and substantially reduces neonatal mortality and morbidity. Fetal exposure to excess glucocorticoids has been proposed as one of the core mechanisms of the fetal origins of adult disease hypothesis. We assessed whether antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome affects cardiovascular risk factors at 30 years of age.


METHODS
We followed up at age 30 years 534 individuals whose mothers participated in a double-blind, placebo-controlled, randomised trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Mothers received two doses of betamethasone or placebo given by intramuscular injection 24 h apart. Follow-up assessments included anthropometry; measurement of blood pressure, blood lipids (after overnight fasting), and early morning cortisol levels; and a 75 g oral glucose tolerance test.


RESULTS
There were no differences between those exposed to betamethasone and to placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease. After a 75 g oral glucose tolerance test, participants exposed to betamethasone had higher plasma insulin concentrations at 30 min (60.5 vs 52.0 mIU/L; ratio of geometric means 1.16 [95% CI 1.03 to 1.31], p=0.02) and lower glucose concentrations at 120 min (4.8 vs 5.1 mmol/L; difference -0.26 mmol/L [-0.53 to 0.00], p=0.05) than did those exposed to placebo.


CONCLUSIONS
Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no clinical effect on cardiovascular risk factors at 30 years of age. Thus, obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.
Dalziel
Stuart R
SR
Clinical Trials Research Unit, University of Auckland, Auckland, New Zealand.
Walker
Natalie K
NK
Parag
Varsha
V
Mantell
Colin
C
Rea
Harold H
HH
Rodgers
Anthony
A
Harding
Jane E
JE
D000328:Adult; D001623:Betamethasone / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure; D049628:Body Size; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
D005938:Glucocorticoids; D007328:Insulin; D008055:Lipids; D001623:Betamethasone; D006854:Hydrocortisone