澳大利亚墨尔本皇家妇科医院Peter G. Davis团队比较了微创表面活性物质治疗与假对照治疗对呼吸窘迫综合征早产儿死亡或支气管肺发育不良的影响。相关论文于2021年12月13日发表于《美国医学会杂志》上。

对于患有呼吸窘迫综合征的早产儿，通过细导管（微创表面活性剂疗法[MIST]）给予表面活性剂的益处尚不确定。

为了探讨低吸氧阈值下选择性应用MIST对无支气管肺发育不良（BPD）早产儿生存率的影响，研究组进行了一项随机临床试验，招募了485名胎龄为25至28周的早产儿，他们接受持续气道正压通气（CPAP）支持，并且在出生后6小时内需要吸入分数为0.30或更高的氧。该试验在全世界33个三级新生儿重症监护病房进行，临床医生和结果评估员均不知情。入组时间为2011年12月16日至2020年3月26日；随访于2020年12月2日完成。

将婴儿随机分为两组，其中MIST组 241例，通过细导管接受外源性表面活性剂治疗；对照组244例，接受假（对照）治疗。此后两组均继续CPAP，除非符合规定的插管标准。主要结局是校正胎龄36周死亡或生理性BPD的综合结局。主要结局的组成部分（校正胎龄36周前死亡和BPD）也被单独考虑。

485名随机分组婴儿的中位胎龄为27.3周，241名（49.7%）为女婴，均完成随访。MIST组中有105名婴儿（43.6%）在校正胎龄36周发生死亡或BPD，对照组有121名婴儿（49.6%），组间差异不显著。

MIST组中有24名（10.0%）婴儿在校正胎龄36周前死亡，对照组中有19名（7.8%），组间差异不显著。MIST组校正胎龄36周后存活者中有81名（37.3%）发生BPD，显著低于对照组的102名（45.3%）。MIST组和对照组分别有10.3%和11.1%的婴儿发生严重不良事件。

研究结果表明，在接受CPAP支持的患有呼吸窘迫综合征的早产儿中，与假手术（对照组）治疗相比，微创表面活性物质治疗并未显著降低校正胎龄36周后死亡或支气管肺发育不良综合结局的风险。

附：英文原文

Title: Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial

Author: Peter A. Dargaville, C. Omar F. Kamlin, Francesca Orsini, Xiaofang Wang, Antonio G. De Paoli, H. Gozde Kanmaz Kutman, Merih Cetinkaya, Lilijana Kornhauser-Cerar, Matthew Derrick, Hilal zkan, Christian V. Hulzebos, Georg M. Schmlzer, Ajit Aiyappan, Brigitte Lemyre, Sheree Kuo, Victor S. Rajadurai, Joyce O’Shea, Manoj Biniwale, Rangasamy Ramanathan, Alla Kushnir, David Bader, Mark R. Thomas, Mallinath Chakraborty, Mariam J. Buksh, Risha Bhatia, Carol L. Sullivan, Eric S. Shinwell, Amanda Dyson, David P. Barker, Amir Kugelman, Tim J. Donovan, Markus K. Tauscher, Vadivelam Murthy, Sanoj K. M. Ali, Pete Yossuck, Howard W. Clark, Roger F. Soll, John B. Carlin, Peter G. Davis, OPTIMIST-A Trial Investigators, Brian A Darlow, Michael Dunn, Amy Salter, Karen Butterley, Nicky Stephens, Lizzy Reid, Ross Dunn, Luke Stephens, Tammy Matzolic, Brenda Argus, Emily Twitchell, Joanna Barrotta, Elizabeth Noble, Kenneth Tan, Emma Yeomans, Melissa Lai, Pieter Koorts, Margaret Broom, Brenda Law, Po-Yin Cheung, Sylvia Van Os, Caroline Fray, Nicole Huneault-Purney, Melissa Faulkner, Chantal Horth, Rebecca Grimwood, A Riskin, Tatiana Kalinina, C Tsafrir, S Afuta, Fanny Timstut, Sabine Huth, Frances McCaffrey

Issue&Volume: 2021-12-13

Abstract:

Importance  The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain.

Objective  To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD).

Design, Setting, and Participants  Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020.

Interventions  Infants were randomized to the MIST group (n=241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n=244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met.

Main Outcomes and Measures  The primary outcome was the composite of death or physiological BPD assessed at 36 weeks’ postmenstrual age. The components of the primary outcome (death prior to 36 weeks’ postmenstrual age and BPD at 36 weeks’ postmenstrual age) also were considered separately.

Results  Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], 6.3% [95% CI, 14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P=.10). Incidence of death before 36 weeks’ postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, 3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P=.51), but incidence of BPD in survivors to 36 weeks’ postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, 7.8% [95% CI, 14.9% to 0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P=.03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group.

Conclusions and Relevance  Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks’ postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded.

DOI: 10.1001/jama.2021.21892

Source: https://jamanetwork.com/journals/jama/article-abstract/2787253