Association Between Early Low-Dose Hydrocortisone Therapy in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years of Age
Association Between Early Low-Dose Hydrocortisone Therapy in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years of Age
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DOI：
10.1001/jama.2017.2692
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发表时间：
2017-04-04
影响因子：
120.7
通讯作者：
Alberti, Corinne
中科院分区：
文献类型：
--
作者：
Baud, Olivier;Trousson, Clemence;Alberti, Corinne
地塞米松预防极早产儿支气管肺发育不良的重要性与不良神经发育事件相关。早期低剂量氢化可的松治疗已被报道可改善无支气管肺发育不良的生存率，但其在神经发育方面的安全性仍有待评估。目的评估极早产儿早期应用氢化可的松治疗是否与2岁时神经发育障碍相关。一项对主要研究对象的探索性次要分析早期低剂量氢化可的松改善极早产儿无支气管肺发育不良的存活率2008年至2014年在21个法国新生儿重症监护病房进行的随机临床试验。随机化按胎龄组分层。2010年至2016年完成了神经发育评估。干预出生后，患者被随机分配接受安慰剂或氢化可的松治疗（0.5mg/kg，每天两次，持续7天，随后每天0.5 mg/kg，持续3天）。主要结果和指标预先指定的神经发育障碍探索性次要结果是基于标准化神经系统检查和修订后的Brunet-Lezine量表（总体发育商数评分和分项评分;平均标准，100 [SD，15]）。在1072名新生儿筛选中，523名被分配到氢化可的松组（n = 256）或安慰剂组（n = 267），406名存活至2岁。共评估了379例患者（93%; 46%为女性）（氢化可的松组194例，安慰剂组185例），校正年龄中位数为22个月（四分位距，21-23个月）。无神经发育障碍患者的分布（氢化可的松组为73%，安慰剂组为70%），有轻度神经发育障碍（氢化可的松组20%，安慰剂组18%），或患有中度至重度神经发育障碍（氢化可的松组为7%，安慰剂组为11%），两组之间无统计学显著差异（P = 0.33）。两组之间的平均整体发育商评分没有统计学显著差异（氢化可的松组为91.7，安慰剂组为91.4;组间差异为0.3 [95%CI，-2.7至3.4]; P = 0.83）。脑性瘫痪或其他主要神经功能障碍的发病率并没有显着不同groups.CONCLUSIONS和RELEVANCE在这一探索性分析的随机临床试验的极早产儿的次要结果，早期低剂量氢化可的松是不相关的神经发育在2岁的统计学显着差异。需要进一步的随机研究来提供氢化可的松在极早产儿中神经发育安全性的明确评估。
IMPORTANCE Dexamethasone to prevent bronchopulmonary dysplasia in very preterm neonates was associated with adverse neurodevelopmental events. Early low-dose hydrocortisone treatment has been reported to improve survival without bronchopulmonary dysplasia but its safety with regard to neurodevelopment remains to be assessed. OBJECTIVE To assess whether early hydrocortisone therapy in extremely preterm infants is associated with neurodevelopmental impairment at 2 years of age.DESIGN, SETTING, AND PARTICIPANTS An exploratory secondary analysis of the PREMILOC (Early Low-Dose Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia in Extremely Preterm Infants) randomized clinical trial conducted between 2008 and 2014 in 21 French neonatal intensive care units. Randomization was stratified by gestational age groups. Neurodevelopmental assessments were completed from 2010 to 2016.INTERVENTIONS After birth, patients were randomly assigned to receive placebo or hydrocortisone (0.5mg/kg twice per day for 7 days, followed by 0.5mg/kg per day for 3 days).MAIN OUTCOMES AND MEASURES The prespecified exploratory secondary outcome of neurodevelopmental impairment was based on a standardized neurological examination and the revised Brunet-Lezine scale (global developmental quotient score and subscores; mean norm, 100 [SD, 15]). The minimal clinically important difference on the global developmental quotient was 5 points.RESULTS Of 1072 neonates screened, 523 were assigned to hydrocortisone (n = 256) or placebo (n = 267) and 406 survived to 2 years of age. A total of 379 patients (93%; 46% female) were evaluated (194 in the hydrocortisone group and 185 in the placebo group) at a median corrected age of 22 months (interquartile range, 21-23 months). The distribution of patients without neurodevelopmental impairment (73% in the hydrocortisone group vs 70% in the placebo group), with mild neurodevelopmental impairment (20% in the hydrocortisone group vs 18% in the placebo group), or with moderate to severe neurodevelopmental impairment (7% in the hydrocortisone group vs 11% in the placebo group) was not statistically significantly different between groups (P = .33). The mean global developmental quotient score was not statistically significantly different between groups (91.7 in the hydrocortisone group vs 91.4 in the placebo group; between-group difference, 0.3 [95% CI, -2.7 to 3.4]; P = .83). The incidence of cerebral palsy or other major neurological impairments was not significantly different between groups.CONCLUSIONS AND RELEVANCE In this exploratory analysis of secondary outcomes of a randomized clinical trial of extremely preterm infants, early low-dose hydrocortisone was not associated with a statistically significant difference in neurodevelopment at 2 years of age. Further randomized studies are needed to provide definitive assessment of the neurodevelopmental safety of hydrocortisone in extremely preterm infants.