Obesity Induces Further Autonomic Impairment in Sheep Exposed Antenatally to Betamethasone

Abstract

Glucocorticoids including betamethasone are routinely administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal betamethasone exposure (BMX) may lead to deleterious long term consequences. In a sheep model of fetal programming, BMX offspring exhibit elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate by 6 month of age. In this study we examined the hypothesis that adding obesity to BMX will have a negative effect on cardiovascular function in these sheep. To test this hypothesis, 19 female sheep at 1 year of age were divided into 4 groups. Lean control (LC, n=6), Lean Beta (LB, n=5), obese control (OC, n=4) and obese beta (OB, n=4). Obesity was induced by allowing the animals to eat ad libitum for 12 weeks and obesity was determined if the sheep showed a 40% weight gain compared to baseline weight. BMX impaired BRS measured as Seq ALL (13 ± 1 in LB vs 23 ± 4 ms/mmHg in LC, p<0.05) while BRS tended to be further impaired in OB (10 ± 1 ms/mmHg, p=0.07 vs LB). BMX reduced heart rate variability measured as rMSSD (47 ±5 in LB vs 84 ± 12 ms in LC). HRV tended to be reduced in the OC group (48 ± 13, p=0.08 vs LC) and in the OB group (39 ± 2 ms, p=0.18 vs LB). MAP was higher in LB vs LC and was further increased in both OC and OB. In human exposed in utero to betamethasone, weight gain exacerbates the risk of developing autonomic dysfunction and cardiovascular disease. Thus, body weight gain should be monitored in these subjects in early adulthood. Support: HD‐47584, GM‐064249