Gürdeniz Gözde, Kim Min, Brustad Nicklas, Ernst Madeleine, Russo Francesco, Stokholm Jakob, Bønnelykke Klaus, Hougaard David, Rasmussen Morten, Cohen Arieh, Chawes Bo
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.
Section of Chemometrics and Analytical Technologies, Department of Food Science, University of Copenhagen, Frederiksberg C, Denmark.
Allergy. 2023 Feb;78(2):429-438. doi: 10.1111/all.15554. Epub 2022 Oct 27.
Intake of fish-oil and fatty fish during pregnancy has been shown to reduce the risk of childhood asthma but biomarkers of such intake are lacking.
To establish biomarkers of prenatal fish-oil exposure from newborn dry blood spot metabolomics profiles and assess their relevance for childhood asthma risk stratification.
The Danish COPSAC mother-child cohort was utilized to investigate the effect of a double-blinded randomized controlled trial of fish-oil supplementation during pregnancy on dry blood spot liquid-chromatography mass spectrometry-based metabolomics profiles of 677 newborns. We thereafter investigated the association between fish-oil associated biomarkers in the newborn and development of asthma-related outcomes. Replication was sought in the independent observational COPSAC cohort with 387 newborn metabolomics profiles.
The newborn metabolomics profiles differed between children in the fish-oil vs. placebo group in COPSAC (area under the receiver operator curve = 0.94 ± 0.03, p < .001). The fish-oil metabolomics profile and the top biomarker, 3-carboxy-4-methyl-5-propyl-2-furan propanoic acid (CMPF) were both associated with a decreased risk of asthma by age 6 years (HR = 0.89, p = .002 and HR = 0.67, p = .005, respectively). In COPSAC , newborn CMPF level was also inversely associated with asthma risk by age 6 years (HR = 0.69, p = .01). Troublesome lung symptoms and common infections in the first 3 years were also inversely associated with newborn CMPF levels in both cohorts.
Newborn children's blood levels of the furan fatty acid metabolite CMPF reflect fish-oil and fatty fish intake during pregnancy and are associated with a lower risk of asthma across two cohorts, which could aid newborn screening for childhood asthma.
孕期摄入鱼油和富含脂肪的鱼类已被证明可降低儿童患哮喘的风险,但缺乏此类摄入的生物标志物。
从新生儿干血斑代谢组学谱中建立产前鱼油暴露的生物标志物,并评估其与儿童哮喘风险分层的相关性。
利用丹麦COPSAC母婴队列研究孕期补充鱼油的双盲随机对照试验对677名新生儿基于干血斑液相色谱质谱的代谢组学谱的影响。此后,我们研究了新生儿中与鱼油相关的生物标志物与哮喘相关结局发生之间的关联。在独立的观察性COPSAC队列中对387份新生儿代谢组学谱进行了重复研究。
COPSAC队列中,鱼油组与安慰剂组儿童的新生儿代谢组学谱存在差异(受试者工作特征曲线下面积 = 0.94 ± 0.03,p <.001)。鱼油代谢组学谱和顶级生物标志物3-羧基-4-甲基-5-丙基-2-呋喃丙酸(CMPF)均与6岁时哮喘风险降低相关(HR = 0.89,p =.002;HR = 0.67,p =.005)。在COPSAC队列中,新生儿CMPF水平也与6岁时哮喘风险呈负相关(HR = 0.69,p =.01)。两个队列中,前3年出现的令人烦恼的肺部症状和常见感染也与新生儿CMPF水平呈负相关。
新生儿血液中呋喃脂肪酸代谢物CMPF的水平反映了孕期鱼油和富含脂肪鱼类的摄入量,并且与两个队列中较低的哮喘风险相关,这有助于新生儿期筛查儿童哮喘。