Liggins Institute, The University of Auckland, Auckland, New Zealand; School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
Lancet Child Adolesc Health. 2019 Nov;3(11):769-780. doi: 10.1016/S2352-4642(19)30292-5. Epub 2019 Sep 12.
Antenatal corticosteroids given to women before preterm birth improve infant survival and health. However, whether dexamethasone or betamethasone have better maternal, neonatal, and childhood health outcomes remains unclear. We therefore aimed to assess whether administration of antenatal dexamethasone to women at risk of preterm birth reduced the risk of death or neurosensory disability in their children at age 2 years compared with betamethasone. We also aimed to assess whether dexamethasone reduced neonatal morbidity, had benefits for the mother, or affected childhood body size, blood pressure, behaviour, or general health compared with betamethasone.
In this multicentre, double-blind, randomised controlled trial, we recruited pregnant women from 14 maternity hospitals in Australia and New Zealand that could provide care to preterm babies. Women were eligible for study inclusion if they were at risk of preterm birth before 34 weeks of gestation, had a singleton or twin pregnancy, and had no contraindications to antenatal corticosteroids. We randomly assigned women (1:1) to receive two intramuscular injections of either 12 mg dexamethasone (dexamethasone sodium phosphate) or 11·4 mg betamethasone (Celestone Chronodose), 24 h apart. The randomisation schedule used balanced, variable blocks that were stratified by hospital, gestational age, and number of fetuses (singleton or twins). We masked all participants, staff, and assessors to treatment groups. Analyses were by intention to treat. The primary outcome was death or neurosensory disability at age 2 years (corrected for prematurity). This study is registered with ANZCTR, ACTRN12608000631303.
Between Jan 28, 2009, and Feb 1, 2013, we randomly assigned 1346 (78%) women who were pregnant with 1509 fetuses to groups: 679 (50%) women were assigned to receive dexamethasone and 667 (50%) women were assigned to receive betamethasone. 27 (4%) fetuses, infants, or children in the dexamethasone group and 28 (4%) fetuses, infants, or children in the betamethasone group died before age 2 years. The primary outcome of death or neurosensory disability at age 2 years was determined for 603 (79%) of 763 fetuses whose mothers received dexamethasone and 591 (79%) of 746 fetuses whose mothers received betamethasone. We found a similar incidence of death or neurosensory disability in the dexamethasone (198 [33%] of 603 infants) and betamethasone groups (192 [32%] of 591 infants; adjusted relative risk [adjRR] 0·97, 95% CI 0·83 to 1·13; p=0·66). 18 (3%) of 679 women in the dexamethasone group and 28 of 667 (4%) women in the betamethasone group reported side-effects. Discomfort at the injection site, the most frequent side-effect, was less likely in the dexamethasone group than in the betamethasone group (six [1%] women vs 17 [3%] women; p=0·02).
The incidence of survival without neurosensory disability at age 2 years did not differ between dexamethasone and betamethasone treatment. Our findings indicate that either antenatal corticosteroid can be given to women before preterm birth to improve infant and child health.
National Health and Medical Research Council (Australia).
在早产前给妇女使用产前皮质类固醇可改善婴儿的生存和健康。然而，地塞米松和倍他米松在母亲、新生儿和儿童健康方面的效果更好仍不清楚。因此，我们旨在评估在有早产风险的妇女中使用产前地塞米松是否能降低其子女在 2 岁时死亡或神经发育障碍的风险，与使用倍他米松相比。我们还旨在评估与倍他米松相比，地塞米松是否能降低新生儿发病率，对母亲有好处，或影响儿童的体型、血压、行为或整体健康。
在这项多中心、双盲、随机对照试验中，我们从澳大利亚和新西兰的 14 家产科医院招募了孕妇，这些医院能够为早产儿提供护理。如果孕妇有在 34 周前早产的风险，怀有单胎或双胞胎妊娠，且无产前皮质类固醇的禁忌证，则有资格入组本研究。我们将妇女（1:1）随机分配接受两次肌内注射，剂量分别为 12 毫克地塞米松（地塞米松磷酸钠）或 11.4 毫克倍他米松（倍他米松 Celestone Chronodose），间隔 24 小时。随机分组方案使用平衡、可变的分组，按医院、胎龄和胎儿数量（单胎或双胞胎）分层。我们对所有参与者、工作人员和评估者均进行了分组处理。分析采用意向治疗。主要结局是 2 岁时死亡或神经发育障碍（校正早产）。本研究在澳大利亚新西兰临床试验注册中心（ANZCTR）注册，注册号为 ACTRN12608000631303。
在 2009 年 1 月 28 日至 2013 年 2 月 1 日期间，我们随机分配了 1346 名（78%）怀孕的妇女，这些妇女怀有 1509 个胎儿，分为两组：679 名（50%）妇女接受地塞米松治疗，667 名（50%）妇女接受倍他米松治疗。在接受地塞米松治疗的 679 名（79%）孕妇中，有 27 名（4%）胎儿、婴儿或儿童死亡，在接受倍他米松治疗的 667 名（79%）孕妇中，有 28 名（4%）胎儿、婴儿或儿童死亡。在 2 岁时死亡或神经发育障碍的主要结局中，有 603 名（79%）接受地塞米松治疗的孕妇的 763 名胎儿和 591 名（79%）接受倍他米松治疗的孕妇的 746 名胎儿得到了确定。我们发现，地塞米松（603 名婴儿中有 198 名[33%]）和倍他米松（591 名婴儿中有 192 名[32%]）组的死亡率或神经发育障碍发生率相似，调整后的相对风险（adjRR）为 0.97，95%CI 为 0.83 至 1.13；p=0.66）。在接受地塞米松治疗的 679 名妇女中，有 18 名（3%）和接受倍他米松治疗的 667 名妇女中，有 28 名（4%）报告了副作用。地塞米松组较常见的注射部位不适等副作用的发生率较低（6 名[1%]妇女 vs 17 名[3%]妇女；p=0.02）。
2 岁时无神经发育障碍的生存率在接受地塞米松和倍他米松治疗的妇女之间没有差异。我们的研究结果表明，无论是产前皮质类固醇都可以在早产前给妇女使用，以改善婴儿和儿童的健康。
澳大利亚国家卫生与医学研究理事会。
