Effect of Docosahexaenoic Add Supplementation vs Placebo on Developmental Outcomes of Toddlers Born Preterm A Randomized Clinical Trial
Effect of Docosahexaenoic Add Supplementation vs Placebo on Developmental Outcomes of Toddlers Born Preterm A Randomized Clinical Trial
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DOI：
10.1001/jamapediatrics.2018.3082
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发表时间：
2018-12-01
期刊：
影响因子：
26.1
通讯作者：
Sheppard, Kelly W.
中科院分区：
文献类型：
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作者：
Keim, Sarah A.;Boone, Kelly M.;Sheppard, Kelly W.
幼儿对膳食中二十二碳六烯酸(DHA)的摄入量很低。目的为了确定每日补充DHA是否能改善早产儿的发育结果，设计、设置和参与者从2012年4月26日到2017年3月24日，在美国一家大型儿科学术中心进行了一项随机、完全掩蔽的安慰剂对照试验，共有9个新生儿重症监护病房。10至16个月矫正年龄小于35周出生的儿童接受6个月的干预。在接受评估的2363名儿童中，982名符合条件，605名拒绝，377名登记并被随机分配。分析根据治疗意向。干预一对一分配，每天接受微囊化DHA，200 mg，花生四烯酸(AA)，200 mg(DHA+AA)，或微囊化玉米油(安慰剂)。主要结果和测量预先指定的主要结果是贝利婴幼儿发育量表，第三版(贝利-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、婴儿行为问卷修订版和儿童早期行为问卷、努力控制和活动水平评分。结果在随机抽取的377名儿童中(182名女孩和195名男孩；校正后的中位年龄为15.7个月)，338名儿童(89.7%)获得了关于主要结局的完整数据。在DHA+AA组和安慰剂组之间，Bayley-Ill认知评分没有差异(变化差异，0.5[95%CI，-1.8至2.8]；效应大小，0.05；P=.66)。在出生体重较低的儿童中，分配到DHA+AA组对Bayley-III语言得分有轻微到中等的负面影响(例如，被分配给DHA+AA组的出生体重为1000克的儿童经历了4.1分的相对下降，而被分配到安慰剂组的儿童没有；交互作用的P=0.03)。在家庭年收入超过35000美元的儿童中，补充剂对努力控制得分也有类似的负面影响(变化差异。-0.3[95%CI，-0.4至-0.1]；效应大小，-0.37；P=0.01)。结论每日补充200 mg DHA和200 mg AA与安慰剂相比，在认知发育和早期执行功能方面没有改善，并可能对某些儿童亚组的语言发育和努力控制产生负面影响。这些发现不支持在生命的第二年对早产儿补充DHA。
IMPORTANCE Intake of dietary docosahexaenoic acid (DHA) among toddlers is low. Supplementation may benefit developmental outcomes of toddlers who were born preterm.OBJECTIVE 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.INTERVENTIONS One-to-one allocation to receive daily microencapsulated DHA, 200 mg, and arachidonic acid (AA), 200 mg (DHA+AA), or microencapsulated corn oil (placebo).MAIN OUTCOMES AND MEASURES 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.RESULTS 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-Ill 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-Ill motor scores and activity level scores were unaffected.CONCLUSIONS AND RELEVANCE 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.