Crowther Caroline A, Haslam Ross R, Hiller Janet E, Doyle Lex W, Robinson Jeffrey S
Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, South Australia 5006, Australia.
Lancet. 2006 Jun 10;367(9526):1913-9. doi: 10.1016/S0140-6736(06)68846-6.
The efficacy and safety of repeat doses of prenatal corticosteroids remains uncertain. Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm.
In this hospital-based study, 982 women who remained at risk of preterm birth at less than 32 weeks' gestation, 7 or more days after receiving a first course of prenatal corticosteroids, were randomly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone (as Celestone Chronodose), or saline placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks' gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome, use and duration of oxygen and mechanical ventilation, and weight, length, and head circumference at birth and hospital discharge. Statistical analyses were on an intention to treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN48656428.
Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome (33%vs 41%; relative risk 0.82, 95% CI 0.71-0.95, p=0.01) and fewer had severe lung disease (12%vs 20%; relative risk 0.60, 95% CI 0.46-0.79, p=0.0003) than those in the placebo group. In keeping with these benefits, babies exposed to repeat corticosteroids needed less oxygen therapy (p=0.03), and shorter duration of mechanical ventilation (p=0.01). Mean weight, length, and head circumference at birth and hospital discharge did not differ between treatment groups. Z-scores for weight (p=0.04) and head circumference (p=0.03) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups (p=0.29 for weight, p=0.48 for head circumference).
Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course.
重复剂量的产前皮质类固醇的疗效和安全性仍不确定。我们的目的是确定给予有早产风险的妇女重复剂量的产前皮质类固醇是否能在无害的情况下降低新生儿发病率。
在这项基于医院的研究中，982名在妊娠小于32周时仍有早产风险、在接受第一疗程产前皮质类固醇7天或更长时间后，被随机分配接受重复肌肉注射11.4毫克倍他米松（商品名：Celestone Chronodose）或生理盐水安慰剂。在妊娠小于32周且妇女未分娩且有早产风险的情况下，每周重复一次。主要结局是新生儿呼吸窘迫综合征的发生和严重程度、氧气和机械通气的使用及持续时间，以及出生时和出院时的体重、身长和头围。统计分析采用意向性分析。本研究已注册为国际标准随机对照试验，注册号为ISRCTN48656428。
与安慰剂组相比，接受重复皮质类固醇治疗的婴儿患呼吸窘迫综合征的较少（33%对41%；相对危险度0.82，95%可信区间0.71 - 0.95，p = 0.01），患严重肺部疾病的也较少（12%对20%；相对危险度0.60，95%可信区间0.46 - 0.79，p = 0.0003）。与这些益处相符的是，接受重复皮质类固醇治疗的婴儿需要的氧疗较少（p = 0.03），机械通气时间较短（p = 0.01）。治疗组之间出生时和出院时的平均体重、身长和头围没有差异。接受重复皮质类固醇治疗的婴儿出生时体重（p = 0.04）和头围（p = 0.03）的Z评分较低，尽管出院时治疗组之间Z评分没有差异（体重p = 0.29，头围p = 0.48）。
暴露于重复剂量的产前皮质类固醇可降低新生儿发病率。在长期结局结果出来之前，我们研究中婴儿的短期益处支持对在初始疗程7天或更长时间后仍有极早产风险的妇女使用重复剂量的皮质类固醇。
