Department of Pediatrics, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Québec, Canada.
Library, Université Laval, Québec, Québec, Canada.
JAMA Netw Open. 2023 Mar 1;6(3):e233934. doi: 10.1001/jamanetworkopen.2023.3934.
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.
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' gestation.
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.
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.
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.
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' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death.
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 = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%).
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.
高剂量二十二碳六烯酸（DHA），一种长链多不饱和脂肪酸，可能会影响支气管肺发育不良（BPD）的风险。然而，缺乏支持非常早产儿中这种临床关联的高级别总结性证据。
研究新生儿期肠内补充高剂量 DHA 与 29 周以下胎龄早产儿 BPD 风险之间的关系。
从成立到 2022 年 8 月 1 日，在 PubMed、Embase、Web of Science、Cochrane 对照试验中心注册库、medRxiv 和 ClinicalTrials.gov 上搜索合格文章，无语言限制。
符合条件的随机临床试验（RCT）入选标准为（1）其干预措施包括直接给予至少 40mg/kg/d 的 DHA 补充剂，或母乳喂养或配方奶喂养至少占总脂肪酸的 0.4%，（2）如果他们报告了 BPD、死亡、BPD 严重程度或 BPD 和死亡的联合结局的数据。
两名调查员独立完成了标题和摘要、全文筛选、数据提取和使用 Cochrane 风险偏倚 2.0 进行质量评估。使用随机效应荟萃分析汇总了风险比（RR）和 95%置信区间（CI）。
主要结局是使用试验特异性定义的 BPD，进一步根据 36 周校正胎龄时系统脉搏血氧测定评估的更严格 BPD 定义对 RCT 进行分层。其他结局是 BPD、死亡、BPD 严重程度或 BPD 和死亡的联合结局。
在筛选的 2760 项研究中，纳入了 4 项 RCT，涉及 2304 名婴儿（1223 名男孩[53.1%]；平均[SD]胎龄，26.5[1.6]周）。肠内补充高剂量 DHA与 BPD（4 项研究[n=2186 名婴儿]；RR，1.07[95%CI，0.86-1.34]；P=0.53；I2=72%）或 BPD 或死亡（4 项研究[n=2299 名婴儿]；RR，1.04[95%CI，0.91-1.18]；P=0.59；I2=61%）均无关。然而，在使用更严格 BPD 定义的 RCT 中发现与 BPD 呈负相关（2 项研究[n=1686 名婴儿]；RR，1.20[95%CI，1.01-1.42]；P=0.04；I2=48%）。此外，DHA 与中重度 BPD 呈负相关（3 项研究[n=1892 名婴儿]；RR，1.16[95%CI，1.04-1.29]；P=0.008；I2=0%）。
本研究结果表明，新生儿期肠内补充高剂量 DHA 总体上与 BPD 无关，但在使用更严格 BPD 定义的纳入 RCT 中发现了负相关。这些发现表明，不建议在非常早产儿中补充高剂量 DHA 以预防 BPD。
