Dalziel Stuart R, Walker Natalie K, Parag Varsha, Mantell Colin, Rea Harold H, Rodgers Anthony, Harding Jane E
Clinical Trials Research Unit, University of Auckland, Auckland, New Zealand.
Lancet. 2005;365(9474):1856-62. doi: 10.1016/S0140-6736(05)66617-2.
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.
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.
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.
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.
产前使用倍他米松治疗广泛用于预防早产儿的新生儿呼吸窘迫综合征，并能大幅降低新生儿死亡率和发病率。胎儿暴露于过量糖皮质激素被认为是成人疾病胎儿起源假说的核心机制之一。我们评估了产前使用倍他米松预防新生儿呼吸窘迫综合征是否会影响30岁时的心血管危险因素。
我们对534名个体进行了30岁时的随访，这些个体的母亲参与了一项关于产前使用倍他米松预防新生儿呼吸窘迫综合征的双盲、安慰剂对照随机试验。母亲们接受了两剂倍他米松或安慰剂，间隔24小时肌肉注射。随访评估包括人体测量；血压、血脂（空腹过夜后）和清晨皮质醇水平的测量；以及75克口服葡萄糖耐量试验。
暴露于倍他米松和安慰剂的个体在体型大小、血脂、血压、血浆皮质醇、糖尿病患病率或心血管疾病史方面没有差异。在75克口服葡萄糖耐量试验后，暴露于倍他米松的参与者在30分钟时血浆胰岛素浓度更高（60.5对52.0 mIU/L；几何均数比1.16 [95% CI 1.03至1.31]，p = 0.02），在120分钟时血糖浓度更低（4.8对5.1 mmol/L；差值 -0.26 mmol/L [-0.53至0.00]，p = 0.05），而暴露于安慰剂的参与者则不然。
产前暴露于倍他米松可能会导致成年后代出现胰岛素抵抗，但对30岁时的心血管危险因素没有临床影响。因此，产科医生应继续使用单疗程产前倍他米松来预防新生儿呼吸窘迫综合征。
