Center for Biobehavioral Health, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
Department of Pediatrics, College of Medicine, The Ohio State University, Columbus.
JAMA Pediatr. 2018 Dec 1;172(12):1126-1134. doi: 10.1001/jamapediatrics.2018.3082.
Intake of dietary docosahexaenoic acid (DHA) among toddlers is low. Supplementation may benefit developmental outcomes of toddlers who were born preterm.
To determine whether 6 months of daily DHA supplementation improves developmental outcomes of toddlers who were born preterm.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, fully masked, placebo-controlled trial was conducted from April 26, 2012, to March 24, 2017, at a large US pediatric academic center with 9 neonatal intensive care units. Children born at less than 35 weeks' gestation who were 10 to 16 months corrected age underwent 6 months of intervention. Of 2363 children assessed, 982 were eligible, 605 declined, and 377 enrolled and were randomized. Analyses were according to intent to treat.
One-to-one allocation to receive daily microencapsulated DHA, 200 mg, and arachidonic acid (AA), 200 mg (DHA+AA), or microencapsulated corn oil (placebo).
The primary outcome specified a priori was Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive composite score at 16 to 22 months corrected age. Secondary outcomes were Bayley-III language and motor composite scores and Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire effortful control and activity level scores. Subgroup analyses defined a priori were by income, sex, and birth weight.
Among 377 children randomized and included in the analysis (182 girls and 195 boys; median corrected age, 15.7 months), 338 children (89.7%) had complete data on the primary outcome. Bayley-III cognitive scores did not differ between the DHA+AA and placebo groups (difference in change, 0.5 [95% CI, -1.8 to 2.8]; effect size, 0.05; P = .66). Assignment to the DHA+AA group had a small to medium negative effect on Bayley-III language scores among children with lower birth weights (eg, a child with a birth weight of 1000 g assigned to receive DHA+AA experienced a 4.1-point relative decrease, while a child assigned to placebo did not; P = .03 for interaction). Supplementation had a similar negative effect on effortful control scores among children with annual household incomes greater than $35 000 (difference in change, -0.3 [95% CI, -0.4 to -0.1]; effect size, -0.37; P = .01). Bayley-III motor scores and activity level scores were unaffected.
Daily supplementation with 200 mg of DHA and 200 mg of AA for 6 months resulted in no improvement in cognitive development and early measures of executive function vs placebo, and may have resulted in negative effects on language development and effortful control in certain subgroups of children. These findings do not support DHA supplementation in the second year of life for children who are born preterm.
ClinicalTrials.gov Identifier: NCT01576783.
幼儿摄入的二十二碳六烯酸（DHA）含量较低。补充 DHA 可能有益于早产儿幼儿的发育结果。
确定六个月每日 DHA 补充是否能改善早产儿幼儿的发育结果。
设计、地点和参与者：一项随机、完全屏蔽、安慰剂对照试验于 2012 年 4 月 26 日至 2017 年 3 月 24 日在美国一家大型儿科学术中心进行，该中心设有 9 个新生儿重症监护病房。胎龄小于 35 周、校正年龄为 10 至 16 个月的儿童接受了 6 个月的干预。在评估的 2363 名儿童中，有 982 名符合条件，605 名拒绝，377 名登记并随机分组。分析根据意向治疗进行。
一对一分配接受每日微胶囊化 DHA（200mg）和花生四烯酸（AA）（200mg）（DHA+AA）或微胶囊化玉米油（安慰剂）。
预先指定的主要结果是贝利婴幼儿发育量表，第三版（Bayley-III），16 至 22 个月校正年龄的认知综合评分。次要结果是 Bayley-III 语言和运动综合评分以及婴儿行为问卷修订版和幼儿行为问卷努力控制和活动水平评分。预先定义的亚组分析是按收入、性别和出生体重进行的。
在随机分组并纳入分析的 377 名儿童中（182 名女孩和 195 名男孩；中位数校正年龄为 15.7 个月），有 338 名儿童（89.7%）在主要结局方面有完整的数据。DHA+AA 组和安慰剂组之间的 Bayley-III 认知评分没有差异（差异变化，0.5[95%CI，-1.8 至 2.8]；效应量，0.05；P=0.66）。在出生体重较低的儿童中，补充 DHA+AA 对 Bayley-III 语言评分有较小到中等的负面影响（例如，出生体重为 1000g 的儿童接受 DHA+AA 治疗，相对减少了 4.1 分，而接受安慰剂治疗的儿童没有；交互作用的 P=0.03）。补充 DHA+AA 对年收入超过 35000 美元的儿童的努力控制评分也有类似的负面影响（差异变化，-0.3[95%CI，-0.4 至-0.1]；效应量，-0.37；P=0.01）。Bayley-III 运动评分和活动水平评分不受影响。
每日补充 200mgDHA 和 200mgAA 6 个月，与安慰剂相比，对认知发育和早期执行功能没有改善，并且可能对某些亚组儿童的语言发育和努力控制产生负面影响。这些发现不支持在早产儿幼儿生命的第二年补充 DHA。
ClinicalTrials.gov 标识符：NCT01576783。
