Circulating glucocorticoid bioactivity in the preterm newborn after antenatal betamethasone treatment
Circulating glucocorticoid bioactivity in the preterm newborn after antenatal betamethasone treatment
复制标题
DOI：
10.1210/jc.2004-0013
复制
发表时间：
2004-08-01
影响因子：
5.8
通讯作者：
Andersson, S
中科院分区：
文献类型：
--
作者：
Kajantie, E;Raivio, T;Andersson, S
对有早产风险的母亲进行产前糖皮质激素治疗在降低新生儿死亡率和发病率方面具有很高的成本效益。然而，关于到达胎儿的实际糖皮质激素生物活性（GBA）的信息有限。通过采用最近开发的重组细胞生物测定法，我们研究了暴露于标准产前倍他米松方案的早产新生儿的循环GBA（母亲12 mg倍他米松两次，间隔24小时;如果需要，在7 - 10天内重复）。对71名婴儿（平均胎龄28.9周，范围24.6 - 32周;平均出生体重1208 g，范围480-2010 g）的脐带血中的血浆GBA和皮质醇浓度进行了测定。从最后一次服用倍他米松到分娩的中位时间为2.0天。脐带GBA范围为小于15.6至170 nmol/L皮质醇当量。该水平高度依赖于最后一次倍他宁剂量和出生之间的时间，即在最后一次类固醇剂量后不久（< 12小时）出生的婴儿显示出比参考组平均高4倍的GBA（出生前最后一次倍他宁剂量后> 7天或未治疗的婴儿; 74与21 nmol/L皮质醇当量; P< 0.0001）。相反，如果最后一次类固醇剂量和分娩之间的时间超过72小时，则循环GBA强烈依赖于脐带皮质醇（r = 0.85; P < 0.0001; n = 30）。在校正了脐带皮质醇浓度和最后一次类固醇剂量后的时间的多元回归分析中，脐动脉阻力增加，严重胎儿窘迫的迹象，与较低的脐带GBA相关（P = 0.01）。总之，早产儿产前暴露于倍他米松会导致一个相当大的，但短暂的，超生理GBA的峰值，大约3天后，最后一次倍他米松剂量，循环GBA来自脐带皮质醇浓度。
Antenatal glucocorticoid treatment of mothers at risk of premature delivery is highly cost-effective in reducing neonatal mortality and morbidity. However, there is only limited information on the actual glucocorticoid bioactivity (GBA) reaching the fetus. By employing a recently developed recombinant cell bioassay, we studied circulating GBA in preterm newborns exposed to the standard antenatal betamethasone regimen ( 12 mg betamethasone twice, 24-h interval, for the mother; repeated in 7 - 10 d if required). Plasma GBA and cortisol concentrations were measured in cord blood of 71 infants ( mean gestational age, 28.9 wk; range, 24.6 - 32 wk; mean birth weight, 1208 g; range, 480-2010 g). The median time between the last administered betamethasone dose and birth was 2.0 d. Cord GBA ranged from less than 15.6 to 170 nmol/liter cortisol equivalents. The level was highly dependent on the time between the last betamethasone dose and birth, i.e. infants born shortly (< 12 h) after the last steroid dose displayed on average 4-fold higher GBA than that in the reference group ( infants with > 7 d since the last betamethasone dose before birth or without treatment; 74 vs. 21 nmol/liter cortisol equivalents; P< 0.0001). By contrast, if more than 72 h had elapsed between the last steroid dose and birth, circulating GBA was strongly dependent on cord cortisol ( r = 0.85; P < 0.0001; n = 30). In multiple regression analysis adjusted for cord cortisol concentration and the time since the last steroid dose, increased umbilical artery resistance, a sign of severe fetal distress, was associated with lower cord GBA ( P = 0.01). In conclusion, antenatal exposure of preterm fetuses to betamethasone causes a sizeable, but brief, peak of supraphysiological GBA, and approximately 3 d after the last betamethasone dose, circulating GBA derives from cord cortisol concentration.