Marc Isabelle, Lavoie Pascal M, Sullivan Thomas R, Pronovost Etienne, Boutin Amélie, Beltempo Marc, Guillot Mireille, Gould Jacqueline F, Simonyan David, McPhee Andrew J, Mohamed Ibrahim, Moore Lynne, Makrides Maria
Department of Pediatrics, CHU de Québec-Université Laval, Québec city, Quebec, Canada.
Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Am J Clin Nutr. 2025 Apr;121(4):826-834. doi: 10.1016/j.ajcnut.2025.01.004. Epub 2025 Feb 24.
Neonatal supplementation with high-dose docosahexaenoic acid (DHA) omega-3 may benefit neurodevelopment in very preterm infants, but concerns remain regarding a potential increased risk and severity of bronchopulmonary dysplasia (BPD). However, the interpretation of evidence on the effect of DHA on severe BPD is challenging because of the heterogeneity in the BPD definitions used across trials.
This study aims to determine whether, compared with placebo, neonatal enteral supplementation with high-dose DHA, mimicking placental transfer, is associated with severe BPD in very preterm infants using an individual participant data meta-analysis of randomized controlled trials (RCTs).
RCTs were eligible if recently conducted in infants born with gestational age (GA) <29 wk and compared enteral supplementation with high-dose DHA alone with a placebo. Using a harmonized data set, the primary outcome of severe BPD was defined as the need for "high-flow" nasal cannula >2 L/min, noninvasive positive airway pressure, or invasive mechanical ventilation at 36 wk postmenstrual age. Secondary outcomes (N = 15) included death, "death or severe BPD," ordinal BPD severity grade, and common neonatal morbidities. Associations between high-dose DHA and outcomes were estimated using a one-stage meta-analysis approach.
Two RCTs were identified in a systematic review (searched up to August 1, 2022; N = 2304) that met inclusion criteria (N = 1801; 904 DHA and 897 placebo; GA 26.7 ± 1.5 wk). Severe BPD in survivors occurred in 290/843 (34.4%) infants in the DHA group and 268/841 (31.9%) infants in the placebo group {relative risk [RR], 1.06 [95% confidence interval (CI): 0.93, 1.21]; P = 0.36}. DHA was not associated with "death or severe BPD" [RR, 1.05 (95% CI: 0.94, 1.17); P = 0.41], the ordinal severity grade [odds ratio for a more severe grade, 1.20 (95% CI: 0.998, 1.45); P = 0.053], or other neonatal outcomes. There was limited evidence of heterogeneity for BPD-related outcomes.
Neonatal enteral supplementation with high-dose DHA was not significantly associated with severe BPD in very preterm infants.
This study was registered at clinicaltrials.gov as NCT05915806, https://clinicaltrials.gov/study/NCT05915806.
META-ANALYSIS REGISTRY NUMBER AND WEBSITE: PROSPERO, CRD42023431063, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=431063.
新生儿补充高剂量ω-3二十二碳六烯酸（DHA）可能有益于极早产儿的神经发育，但对于支气管肺发育不良（BPD）潜在的风险增加和严重程度仍存在担忧。然而，由于各试验中BPD定义存在异质性，对DHA对重度BPD影响的证据解读具有挑战性。
本研究旨在通过对随机对照试验（RCT）进行个体参与者数据荟萃分析，确定与安慰剂相比，模拟胎盘转运的新生儿高剂量DHA肠内补充剂是否与极早产儿的重度BPD相关。
如果最近在孕周（GA）<29周出生的婴儿中进行的RCT，并且将单独高剂量DHA肠内补充剂与安慰剂进行比较，则该RCT符合纳入标准。使用统一数据集，重度BPD的主要结局定义为在月经龄36周时需要“高流量”鼻导管>2L/分钟、无创正压通气或有创机械通气。次要结局（N = 15）包括死亡、“死亡或重度BPD”、BPD严重程度分级以及常见的新生儿疾病。使用单阶段荟萃分析方法估计高剂量DHA与结局之间的关联。
在一项系统评价（检索至2022年8月1日；N = 2304）中确定了两项符合纳入标准的RCT（N = 1801；904例DHA组和897例安慰剂组；GA 26.7±1.5周）。DHA组843例存活婴儿中有290例（34.4%）发生重度BPD，安慰剂组841例婴儿中有268例（31.9%）发生重度BPD{相对风险[RR]，1.06[95%置信区间（CI）：0.93，1.21]；P = 0.36}。DHA与“死亡或重度BPD”[RR，1.05（95%CI：0.94，1.17）；P = 0.41]、序贯严重程度分级[更严重分级的优势比，1.20（95%CI：0.998，1.45）；P = 0.053]或其他新生儿结局无关。BPD相关结局的异质性证据有限。
新生儿高剂量DHA肠内补充剂与极早产儿的重度BPD无显著相关性。
本研究在clinicaltrials.gov注册为NCT05915806，https://clinicaltrials.gov/study/NCT05915806。
PROSPERO，CRD42023431063，https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=431063。
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