Brustad Nicklas, Vahman Nilo, Ralfkiaer Ulrik, Mikkelsen Marianne, Brandt Sarah, Kyvsgaard Julie Nyholm, Vinding Rebecca, Stokholm Jakob, Chawes Bo, Bønnelykke Klaus
Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Gentofte, Denmark
Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Gentofte, Denmark.
BMJ Open. 2024 Dec 31;14(12):e092902. doi: 10.1136/bmjopen-2024-092902.
Previous randomised controlled trials (RCTs) have indicated a protective role of pregnancy supplementation with fish oil and high-dose vitamin D, respectively, on offspring asthma, infections and several other disorders in early childhood. However, current evidence is not considered sufficient for recommending these supplements in pregnancy. In two RCTs, we aim to investigate whether these protective effects can be confirmed in larger trials with the goal of changing clinical practice and improving child health.
Randomisation of 4000 pregnant women to either (1) (n=2000) the fish oil trial of 2.4 g/day (55% eicosapentaenoic acid (EPA) and 37% docosahexaenoic acid (DHA)) in triacylglycerol form versus placebo or (2) (n=2000) the vitamin D trial of high-dose (3200 IU/day) vitamin D versus placebo on top of the recommended 400 IU/day. Supplementation begins in gestational week 24 (22-26) until 1 week after delivery. Allocation to the trials will be determined based on the preinterventional maternal blood levels of EPA+DHA with a dried blood screening test. Women with low levels (below 4.7% of total fatty acids) will be assigned to the fish oil RCT, and women with high levels will be assigned to the vitamin D RCT. Maternal blood will be used for genetic, metabolomic and proteomic profiling. A 3-year follow-up of the children with longitudinal registration of parent-reported symptoms, diagnoses, medication use and hospitalisations will be performed. The primary outcome is persistent wheeze or asthma until age 3 years, with predefined analyses of effect modification by maternal genotypes. Secondary outcomes are lower respiratory tract infections, gastrointestinal infections, croup, troublesome lung symptoms, eczema, allergy, bone fractures, developmental milestones, mental health, cognition and growth until age 3 years. A follow-up on both primary and secondary outcomes is planned after unblinding, from age 3-6 years.
The RCTs are approved by the Danish local ethics committee (H-23055833). The studies are registered at ClinicalTrials.gov (NCT06560255 and NCT06570889). Study results will be communicated to the medical community, including publications in peer-reviewed journals. All results will be published and available on www.copsac.com.
NCT06560255 and NCT06570889.
先前的随机对照试验（RCT）分别表明，孕期补充鱼油和高剂量维生素D对后代哮喘、感染及其他几种幼儿期疾病具有保护作用。然而，目前的证据被认为不足以推荐在孕期使用这些补充剂。在两项RCT中，我们旨在研究这些保护作用能否在更大规模的试验中得到证实，以期改变临床实践并改善儿童健康。
将4000名孕妇随机分为两组：（1）（n = 2000）鱼油试验组，每日服用2.4克（三酰甘油形式，其中55%为二十碳五烯酸（EPA），37%为二十二碳六烯酸（DHA）），与安慰剂组对比；（2）（n = 2000）维生素D试验组，在推荐的每日400国际单位基础上，额外服用高剂量（每日3200国际单位）维生素D，与安慰剂组对比。补充剂从妊娠第24周（22 - 26周）开始服用，直至分娩后1周。根据干预前通过干血筛查检测的孕妇血液中EPA + DHA水平来确定试验分组。水平较低（低于总脂肪酸的4.7%）的女性将被分配到鱼油RCT组，水平较高的女性将被分配到维生素D RCT组。孕妇血液将用于基因、代谢组学和蛋白质组学分析。对儿童进行3年随访，纵向记录家长报告症状、诊断、用药情况和住院情况。主要结局是3岁前持续喘息或哮喘，并对母体基因型的效应修饰进行预定义分析。次要结局包括3岁前的下呼吸道感染、胃肠道感染、哮吼、令人烦恼的肺部症状、湿疹、过敏、骨折、发育里程碑、心理健康、认知和生长情况。揭盲后计划对3至6岁的主要和次要结局进行随访。
这些RCT已获得丹麦当地伦理委员会（H-23055833）批准。研究已在ClinicalTrials.gov注册（NCT06560255和NCT06570889）。研究结果将传达给医学界，包括在同行评审期刊上发表。所有结果将在www.copsac.com上发布并可供查阅。
NCT06560255和NCT06570889。
