{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:09:11Z","timestamp":1792638551407,"version":"4.5.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>High-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking.<\/jats:p><\/jats:sec>Objective<\/jats:title>To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks\u2019 gestation.<\/jats:p><\/jats:sec>Data Sources<\/jats:title>PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions.<\/jats:p><\/jats:sec>Study Selection<\/jats:title>Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg\/kg\/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death.<\/jats:p><\/jats:sec>Data Extraction and Synthesis<\/jats:title>Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks\u2019 postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death.<\/jats:p><\/jats:sec>Results<\/jats:title>Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n\u2009=\u20092186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P<\/jats:italic>\u2009=\u2009.53; I<\/jats:italic>2<\/jats:sup>\u2009=\u200972%) nor BPD or death (4 studies [n\u2009=\u20092299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P<\/jats:italic>\u2009=\u2009.59; I<\/jats:italic>2<\/jats:sup>\u2009=\u200961%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n\u2009=\u20091686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P<\/jats:italic>\u2009=\u2009.04; I<\/jats:italic>2<\/jats:sup>\u2009=\u200948%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n\u2009=\u20091892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P<\/jats:italic>\u2009=\u2009.008; I<\/jats:italic>2<\/jats:sup>\u2009=\u20090%).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Results of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.3934","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T15:02:03Z","timestamp":1679410923000},"page":"e233934","source":"Crossref","is-referenced-by-count":23,"title":["Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants"],"prefix":"10.1001","volume":"6","author":[{"given":"Isabelle","family":"Marc","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Centre Hospitalier Universitaire de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Boutin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centre Hospitalier Universitaire de 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