美国新墨西哥大学健康科学中心Kristi L. Watterberg团队研究了氢化可的松改善极早产儿无支气管肺发育不良的生存率。相关论文于2022年3月23日发表在《新英格兰医学杂志》上。

支气管肺发育不良是极端早产后的一种常见并发症。机械通气引起的炎症可能加剧了病情进展。在出生后第二周进行氢化可的松治疗是否能改善生存率，且无支气管肺发育不良和不良神经发育影响尚不明确。

研究组进行了一项试验，招募胎龄小于30周的婴儿，在14 - 28天插管至少7天。将这些婴儿随机分配，分别接受氢化可的松（4毫克/日/公斤体重）或安慰剂治疗。规定了强制拔管阈值。主要疗效结局为胎龄36周时无中重度支气管肺发育不良的生存率，主要安全结局为校正后22至26个月无中重度神经发育障碍的生存率。

研究组共纳入了800名婴儿，平均出生体重为715g，平均胎龄24.9周。氢化可的松组398名婴儿中有66名（16.6%）在36周时无中重度支气管肺发育不良存活，安慰剂组402名婴儿中有53名（13.2%），校正比率为1.27。

91.0%的婴儿有随访两年的结果。氢化可的松组358名婴儿中有132名（36.9%）存活，安慰剂组359名婴儿中有134名（37.3%）存活，且无中度或重度神经发育障碍，校正比率为0.98。氢化可的松组的高血压发生率为4.3%，显著高于安慰剂组的1.0%。两组的其他不良事件相似。

研究结果表明，在这项涉及早产儿的试验中，与安慰剂相比，从出生后第14天到第28天开始的氢化可的松治疗没有显著提高无中重度支气管肺发育不良的存活率。且两组间无中重度神经发育障碍的存活率亦无显著差异。

附：英文原文

Title: Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia

Author: Kristi L. Watterberg, M.D.,, Michele C. Walsh, M.D.,, Lei Li, Ph.D.,, Sanjay Chawla, M.D.,, Carl T. D’Angio, M.D.,, Ronald N. Goldberg, M.D.,, Susan R. Hintz, M.D., M.S.Epi.,, Matthew M. Laughon, M.D., M.P.H.,, Bradley A. Yoder, M.D.,, Kathleen A. Kennedy, M.D., M.P.H.,, Georgia E. McDavid, R.N.,, Conra Backstrom-Lacy, R.N.,, Abhik Das, Ph.D.,, Margaret M. Crawford, B.S., C.C.R.P.,, Martin Keszler, M.D.,, Gregory M. Sokol, M.D.,, Brenda B. Poindexter, M.D.,, Namasivayam Ambalavanan, M.D.,, Anna Maria Hibbs, M.D., M.S.C.E.,, William E. Truog, M.D.,, Barbara Schmidt, M.D.,, Myra H. Wyckoff, M.D.,, Amir M. Khan, M.D.,, Meena Garg, M.D.,, Patricia R. Chess, M.D.,, Anne M. Reynolds, M.D.,, Mohannad Moallem, M.D.,, Edward F. Bell, M.D.,, Lauritz R. Meyer, M.D.,, Ravi M. Patel, M.D.,, Krisa P. Van Meurs, M.D.,, C. Michael Cotten, M.D., M.H.S.,, Elisabeth C. McGowan, M.D.,, Abbey C. Hines, Psy.D., H.S.P.P.,, Stephanie Merhar, M.D.,, Myriam Peralta-Carcelen, M.D., M.P.H.,, Deanne E. Wilson-Costello, M.D.,, Howard W. Kilbride, M.D.,, Sara B. DeMauro, M.D., M.S.C.E.,, Roy J. Heyne, M.D.,, Ricardo A. Mosquera, M.D.,, Girija Natarajan, M.D.,, Isabell B. Purdy, Ph.D., C.P.N.P.,, Jean R. Lowe, Ph.D.,, Nathalie L. Maitre, M.D., Ph.D.,, Heidi M. Harmon, M.D.,, Laurie A. Hogden, M.D.,, Ira Adams-Chapman, M.D.,, Sarah Winter, M.D.,, William F. Malcolm, M.D.,, and Rosemary D. Higgins, M.D.

Issue&Volume: 2022-03-23

Abstract:

Background

Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.

Methods

We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age.

Results

We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups.

Conclusions

In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups.

DOI: 10.1056/NEJMoa2114897

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2114897