Enteral High-Dose Docosahexaenoic Acid and Neurodevelopment in Extremely Preterm Infants: A Systematic Review and Meta-analysis

IF 3.2 Q2 NUTRITION & DIETETICS

Current Developments in Nutrition Pub Date : 2025-07-24 DOI:10.1016/j.cdnut.2025.107510

Emily Shepherd , Naho Ikeda , Thomas R. Sullivan , Isabelle Marc , Mireille Guillot , Andrew J McPhee , Robert A Gibson , Maria Makrides , Jacqueline F Gould

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Abstract

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; P = 0.59; I² = 0%] or CA of 5–7 y (2 RCTs, 852 children; MD: 2.22; 95% CI: –0.14, 4.57; P = 0.06; I² = 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; P = 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).

查看原文本刊更多论文

肠内高剂量二十二碳六烯酸与极早产儿神经发育：一项系统综述和荟萃分析

背景：肠内高剂量二十二碳六烯酸（DHA）可能需要用于极早产儿的神经发育，包括认知。缺乏高层次的总结性证据。目的本研究旨在探讨新生儿期肠内高剂量DHA与妊娠≤29周婴儿神经发育的关系。方法检索自建库至2024年4月11日的数据库：CINAHL、Cochrane Library、Embase、Medline、Scopus和Web of Science。在出生≤29周的婴儿中，评估直接肠内给药≥40 mg/kg/d DHA，或DHA≥0.60%总脂肪酸的母乳/配方奶粉，报告神经发育结局的合格随机对照试验（RCTs）。两位审稿人独立筛选文章，提取数据，并使用Cochrane手册指导评估质量。采用固定效应或随机效应荟萃分析汇总数据。主要结果是标准化测试的整体认知得分。结果我们筛选了1978篇文章，包括3项高质量的随机对照试验（2028名出生≤29周的婴儿）。肠内高剂量DHA与校正年龄（CA） 18-36月龄时整体认知评分的总体差异无关[3项随机对照试验，638名儿童，平均差异（MD） 0.67；95%置信区间（CI）： -1.80, 3.15；P = 0.59；[I2 = 0%]或CA为5 - 7y(2个rct， 852名儿童；MD: 2.22; 95% CI: -0.14, 4.57; P = 0.06; I2 = 33%)；然而，直接肠内乳剂的最大RCT（656名儿童，CA为5岁，MD为3.45;95% CI: 0.38, 6.52; P = 0.03）观察到益处。与大多数次要结局没有关联；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个月）减少相关。没有观察到负面影响。结论经meta分析，极早产儿经肠注射高剂量DHA与整体认知评分差异无相关性；然而，使用直接乳液观察到更高的分数。结果支持当代的建议。该试验在普洛斯彼罗注册为CRD42022382744 （https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382744）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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