SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
School of Public Health, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
JAMA Netw Open. 2023 Jun 1;6(6):e2317870. doi: 10.1001/jamanetworkopen.2023.17870.
High-dose omega-3 docosahexaenoic acid (DHA) supplementation of children born at less than 29 weeks' gestation has been shown to improve IQ despite increasing the risk of bronchopulmonary dysplasia (BPD). Given that BPD is associated with poorer cognitive outcomes, it is unclear whether the increased risk of BPD with DHA supplementation is associated with decreased benefit to IQ.
To investigate whether the increased risk of BPD with DHA supplementation was associated with diminished IQ benefit.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data collected from a multicenter, blinded, randomized controlled trial of DHA supplementation in children born at less than 29 weeks' gestation. Participants were recruited from 2012 to 2015 and followed up until 5 years' corrected age. Data were analyzed from November 2022 to February 2023.
Enteral DHA emulsion (60 mg/kg/d, to match the estimated in-utero requirement) or a control emulsion from the first 3 days of enteral feeds until 36 weeks' postmenstrual age or discharge home.
Physiological BPD was assessed at 36 weeks' postmenstrual age. IQ was assessed at 5 years' corrected age using the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition; children from the 5 highest-recruiting Australian hospitals were assessed. The total effect of DHA supplementation on IQ was divided into direct and indirect effects using mediation analysis, with BPD as the presumed mediating variable.
Among 656 surviving children from hospitals involved in IQ follow-up (mean [SD] gestational age at birth, 26.8 [1.4] weeks; 346 males [52.7%]), there were 323 children with DHA supplementation and 333 children in the control group. Mean IQ was 3.45 points (95% CI, 0.38 to 6.53 points) higher in the DHA group than the control group, despite an increase in the risk of BPD (160 children [49.7%] vs 143 children [42.8%] with BPD). The indirect effect of DHA on IQ via BPD was not statistically significant (-0.17 points; 95% CI, -0.62 to 0.13 points), with most of the effect of DHA on IQ occurring independently of BPD (direct effect = 3.62 points; 95% CI, 0.55 to 6.81 points).
This study found that associations of DHA with BPD and IQ were largely independent. This finding suggests that if clinicians supplement children born preterm with high-dose DHA, any resulting increase in BPD risk would not be associated with meaningful reductions in the IQ benefit.
尽管补充高剂量的ω-3 二十二碳六烯酸（DHA）会增加支气管肺发育不良（BPD）的风险，但已证明补充这种物质可以提高胎龄小于 29 周出生的儿童的智商。鉴于 BPD 与认知结果较差有关，因此尚不清楚 DHA 补充剂增加 BPD 的风险是否与智商获益减少有关。
研究 DHA 补充剂增加 BPD 的风险是否与智商获益减少有关。
设计、地点和参与者：这是一项使用来自多中心、盲法、随机对照 DHA 补充剂试验的数据进行的队列研究，该试验纳入了胎龄小于 29 周的儿童。参与者于 2012 年至 2015 年招募，并随访至 5 年校正年龄。数据分析于 2022 年 11 月至 2023 年 2 月进行。
从开始肠内喂养的第 3 天开始，给患儿喂食 DHA 乳剂（60mg/kg/d，以匹配估计的宫内需求）或对照乳剂，持续到 36 周的校正胎龄或出院。
在 36 周的校正胎龄时评估生理性 BPD。在 5 年的校正年龄时使用韦氏学前和小学智力量表，第四版评估智商；来自澳大利亚 5 家招聘人数最多的医院的儿童进行了评估。使用中介分析将 DHA 补充剂对智商的总影响分为直接和间接影响，以 BPD 为假定的中介变量。
在参与智商随访的 656 名幸存儿童中（出生时的平均[标准差]胎龄，26.8[1.4]周；男性 346 名[52.7%]），DHA 组 323 名，对照组 333 名。DHA 组的平均智商比对照组高 3.45 分（95%CI，0.38 至 6.53 分），尽管 BPD 的风险增加（DHA 组 160 名[49.7%]儿童与对照组 143 名[42.8%]儿童患有 BPD）。DHA 通过 BPD 对 IQ 的间接影响无统计学意义（-0.17 分；95%CI，-0.62 至 0.13 分），DHA 对 IQ 的大部分影响独立于 BPD（直接效应=3.62 分；95%CI，0.55 至 6.81 分）。
这项研究发现，DHA 与 BPD 和智商的关联在很大程度上是独立的。这一发现表明，如果临床医生给早产儿补充高剂量的 DHA，由此导致的 BPD 风险增加不会与智商获益的显著减少有关。
