Importance Children born at less than 29 weeks' gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain. Objective To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks' gestation. Design, Setting and Participants This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks' gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years' corrected age. Interventions Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Main Outcomes and Measures The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child's behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention. Results Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, -0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health. Conclusions and Relevance In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks' gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation. Trial Registration Australian New Zealand Clinical Trial Registry: ACTRN12612000503820.

中文翻译：

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高剂量二十二碳六烯酸对妊娠 29 周以下新生儿和 5 岁时行为的影响：随机临床试验的随访。


重要性 妊娠不足 29 周出生的儿童有出现行为困难的风险。这可能部分是由于缺乏二十二碳六烯酸（DHA）经胎盘的供应，二十二碳六烯酸（DHA）是一种在大脑中具有结构和功能作用的关键脂肪酸。目的 确定通过补充满足新生儿 DHA 需求是否与妊娠 29 周以下出生儿童的行为功能改善相关。设计、设置和参与者 这是一项多中心、盲法、平行组随机临床试验，对 2012 年 6 月至 2015 年 9 月期间出生的妊娠 29 周以下婴儿进行，对来自 10 个澳大利亚参与中心的儿童进行了随访，不包括额外补充脂肪酸或患有严重先天性或染色体异常的人。随访时间为2018年8月至2021年5月。未退出最初试验的幸存儿童的父母被邀请在孩子年满5岁时填写问卷。干预措施 婴儿从肠内喂养的前 3 天内随机接受每天提供 60 毫克/公斤/天 DHA 的肠乳剂或豆油乳剂（不含 DHA），直至月经后 36 周或出院回家，以发生的情况为准第一的。主要结果和措施 这次随访的主要结果是家长评价的行为和情绪功能，如优势和困难问卷的总困难分数所示。家长还完成了有关孩子执行功能行为表现以及一系列健康结果的调查问卷，以评估 DHA 干预的潜在长期副作用。 结果 731 名儿童获得了主要结果数据（占 958 名幸存合格儿童的 76%；干预组 361 名，对​​照组 370 名）。在这 731 名患者中，452 名 (47%) 为女性，随访时的平均 (SD) 校正年龄为 5.4 (0.5) 岁。对缺失数据进行插补后，两组的平均总难度分数相同（干预组，n = 465；平均值 [SD]，11.8 [6.3]；对照组，n = 493；平均值 [SD]，11.8 [6.0] ]；根据性别、孕龄阶层和医院进行调整后的平均差异，0.01；95% CI，-0.87 至 0.89）。没有证据表明各组之间在行为、执行功能或健康等任何次要结果方面存在差异。结论和相关性 在这项随机临床试验的随访中，对于妊娠 29 周以下出生的婴儿，肠内补充 DHA（相当于子宫内估计剂量）并没有改善 5 岁时的行为功能。没有迹象表明补充 DHA 会产生不良反应。试验注册澳大利亚新西兰临床试验注册处：ACTRN12612000503820。