肠内高剂量二十二碳六烯酸与极早产儿的神经发育：一项系统评价和荟萃分析
Enteral High-Dose Docosahexaenoic Acid and Neurodevelopment in Extremely Preterm Infants: A Systematic Review and Meta-analysis.
作者信息
Shepherd Emily, Ikeda Naho, Sullivan Thomas R, Marc Isabelle, Guillot Mireille, McPhee Andrew J, Gibson Robert A, Makrides Maria, Gould Jacqueline F
机构信息
Women and Kids Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
出版信息
Curr Dev Nutr. 2025 Jul 24;9(9):107510. doi: 10.1016/j.cdnut.2025.107510. eCollection 2025 Sep.
BACKGROUND
Enteral high-dose docosahexaenoic acid (DHA) may be required for neurodevelopment, including cognition, of extremely preterm infants. High-level summative evidence is lacking.
OBJECTIVES
This study aims to examine associations between enteral high-dose DHA during the neonatal period and neurodevelopment in infants born ≤29 wk of gestation.
METHODS
The following databases were searched (from inception to 11 April, 2024): CINAHL, Cochrane Library, Embase, Medline, Scopus, and Web of Science. Eligible randomized controlled trials (RCTs) in infants born ≤29 wk, assessing direct enteral administration ≥ 40 mg/kg/d DHA, or breast milk/formula with DHA ≥ 0.60% total fatty acids, reporting neurodevelopmental outcomes. Two reviewers independently screened articles, extracted data, and assessed quality using the Cochrane Handbook guidance. Data were pooled using fixed or random-effect meta-analyses. The primary outcome was global cognitive scores from a standardized test.
RESULTS
We screened 1978 articles and included 3 high-quality RCTs (2028 infants born ≤29 wk). Enteral high-dose DHA was not associated with overall differences in global cognition scores at a corrected age (CA) of 18-36 mo [3 RCTs, 638 children, mean difference (MD) 0.67; 95% confidence interval (CI): -1.80, 3.15; = 0.59; = 0%] or CA of 5-7 y (2 RCTs, 852 children; MD: 2.22; 95% CI: -0.14, 4.57; = 0.06; = 33%); however, benefit was observed in the largest RCT with a direct enteral emulsion (656 children, CA of 5 y, MD 3.45; 95% CI: 0.38, 6.52; = 0.03). Associations with most secondary outcomes were not seen; however, high-dose DHA was associated with reduced mild motor (3 RCTs, CA of 18-36 mo) and cognitive (2 RCTs, CA of 5-7 y) impairment. No negative impacts were observed.
CONCLUSIONS
Enteral high-dose DHA in extremely preterm infants was not associated with differences in global cognition scores on meta-analysis; however, higher scores were observed with the use of a direct emulsion. Results support contemporary recommendations.This trial was registered at PROSPERO as CRD42022382744 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382744).
背景
极早产儿的神经发育（包括认知）可能需要肠内高剂量二十二碳六烯酸（DHA）。目前缺乏高水平的总结性证据。
目的
本研究旨在探讨新生儿期肠内高剂量DHA与孕周≤29周出生婴儿神经发育之间的关联。
方法
检索了以下数据库（从建库至2024年4月11日）：护理学与健康领域数据库（CINAHL）、考科蓝图书馆、荷兰医学文摘数据库（Embase）、医学文献数据库（Medline）、Scopus数据库和科学引文索引数据库（Web of Science）。纳入孕周≤29周婴儿的合格随机对照试验（RCT），评估直接肠内给予≥40mg/kg/d DHA，或母乳/配方奶中DHA≥总脂肪酸的0.60%，并报告神经发育结局。两名研究者独立筛选文章、提取数据，并根据考科蓝手册指南评估质量。使用固定效应或随机效应荟萃分析合并数据。主要结局是标准化测试的总体认知得分。
结果
我们筛选了1978篇文章，纳入3项高质量RCT（2028名孕周≤29周出生的婴儿）。肠内高剂量DHA与校正年龄（CA）为18 - 36个月时的总体认知得分总体差异无关[3项RCT，638名儿童，平均差（MD）0.67；95%置信区间（CI）：-1.80，3.15；I² = 0.５９；tau² = 0%]，或CA为5 - 7岁时也无关（2项RCT，852名儿童；MD：2.22；95% CI：-0.14，4.57；I² = 0.06；tau² = 33%）；然而，在最大的一项使用直接肠内乳剂的RCT中观察到有益效果（656名儿童，CA为5岁，MD 3.45；95% CI：0.38，6.52；P = 0.03）。未观察到与大多数次要结局的关联；然而，高剂量DHA与轻度运动障碍（3项RCT，CA为18 - 36个月）和认知障碍（2项RCT，CA为5 - 7岁）减少有关。未观察到负面影响。
结论
荟萃分析显示，极早产儿肠内高剂量DHA与总体认知得分差异无关；然而，使用直接乳剂时观察到得分更高。结果支持当代建议。本试验在国际前瞻性注册系统（PROSPERO）注册为CRD42022382744（https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382744）。
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