Neonatal Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Robert Debré Children's Hospital, Paris, France2Université Paris Diderot, Sorbonne Paris-Cité, Inserm U1141, Paris, France.
Neonatal Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Robert Debré Children's Hospital, Paris, France.
JAMA. 2017 Apr 4;317(13):1329-1337. doi: 10.1001/jama.2017.2692.
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.
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.
After birth, patients were randomly assigned to receive placebo or hydrocortisone (0.5 mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days).
The prespecified exploratory secondary outcome of neurodevelopmental impairment was based on a standardized neurological examination and the revised Brunet-Lézine 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.
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.
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.
clinicaltrials.gov Identifier: NCT00623740.
地塞米松预防极早产儿支气管肺发育不良与不良神经发育事件有关。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，但关于其神经发育安全性仍有待评估。
评估极早产儿早期使用氢化可的松治疗是否与 2 岁时的神经发育障碍有关。
设计、设置和参与者：对 2008 年至 2014 年在法国 21 个新生儿重症监护病房进行的 PREMILOC（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生存）随机临床试验进行的探索性二次分析。随机化按胎龄组分层。神经发育评估于 2010 年至 2016 年进行。
出生后，患者被随机分配接受安慰剂或氢化可的松（0.5mg/kg，每日 2 次，共 7 天，然后每日 0.5mg/kg，共 3 天）。
预先设定的探索性次要结局为神经发育障碍，基于标准化神经系统检查和修订后的 Brunet-Lézine 量表（总体发育商评分和子评分；平均正常，100[标准差，15]）。全球发育商的最小临床重要差异为 5 分。
在筛查的 1072 名新生儿中，523 名被分配至氢化可的松组（n=256）或安慰剂组（n=267），406 名存活至 2 岁。共有 379 名患者（93%；46%为女性）接受了评估（氢化可的松组 194 名，安慰剂组 185 名），中位校正年龄为 22 个月（四分位距，21-23 个月）。无神经发育障碍的患者（氢化可的松组 73%，安慰剂组 70%）、轻度神经发育障碍的患者（氢化可的松组 20%，安慰剂组 18%）或中度至重度神经发育障碍的患者（氢化可的松组 7%，安慰剂组 11%）在两组间的分布无统计学差异（P=0.33）。两组间的总体发育商评分无统计学差异（氢化可的松组 91.7，安慰剂组 91.4；组间差异，0.3[95%CI，-2.7 至 3.4]；P=0.83）。两组间脑瘫或其他主要神经损伤的发生率无显著差异。
在这项对极早产儿随机临床试验的次要结局的探索性分析中，早期低剂量氢化可的松治疗与 2 岁时的神经发育无统计学显著差异相关。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。
clinicaltrials.gov 标识符：NCT00623740。
