Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Department of Pediatrics, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan.
JAMA Netw Open. 2023 Dec 1;6(12):e2349942. doi: 10.1001/jamanetworkopen.2023.49942.
Kawasaki disease is an acute systemic vasculitis that primarily affects infants and young children. No reproducible risk factors have yet been identified, but a possible association between maternal folic acid supplementation and Kawasaki disease has been reported previously.
To investigate the associations of exposure to maternal serum folic acid levels and maternal folic acid supplementation with onset of Kawasaki disease during infancy among offspring.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Japan Environment and Children's Study, a nationwide birth cohort, which has enrolled children since 2011. This study used the data set released in October 2019, and analysis was performed in January 2023.
Maternal serum folic acid levels (≥10 ng/mL classified as exposed) during the second and third trimesters and the frequency of maternal folic acid supplementation during the first trimester and during the second and third trimesters of pregnancy (once a week or more was classified as exposed).
The primary outcome was onset of Kawasaki disease in offspring up to age 12 months. Odds ratios (ORs) for each exposure were estimated, and propensity score-adjusted logistic regression was conducted on the basis of the sets of variables.
The study population comprised 87 702 children who were followed-up for 12 months. Of these, 336 children developed Kawasaki disease. Mothers who took folic acid supplements (31 275 mothers [35.7%]; mean [SD] age, 32 [5] years) had higher serum folic acid levels than those who did not take supplements. Higher maternal serum folic acid levels were associated with a significantly lower risk of Kawasaki disease in offspring than lower levels (folic acid ≥10 vs <10 ng/mL, 56 of 20 698 children [0.27%] vs 267 of 64 468 children [0.41%]; OR, 0.68; 95% CI, 0.50-0.92). Children whose mothers took folic acid supplementation during the first trimester had a lower prevalence of Kawasaki disease than children whose mothers did not take folic acid (131 of 39 098 children [0.34%] vs 203 of 48 053 children [0.42%]), although the difference was not statistically significant (OR, 0.83; 95% CI, 0.66-1.04). Supplementation during the second and third trimesters was associated with a significantly lower risk of Kawasaki disease compared with no supplementation (94 of 31 275 children [0.30%] vs 242 of 56 427 children [0.43%]; OR, 0.73; 95% CI, 0.57-0.94).
In this cohort study, higher serum folic acid levels (≥10 ng/mL) and maternal folic acid supplementation more than once a week during the second and third trimesters were associated with reduced risk of Kawasaki disease in offspring during infancy.
川崎病是一种主要影响婴儿和幼儿的急性全身性血管炎。尚未确定可重复的危险因素，但之前有报道称，母体叶酸补充剂与川崎病之间可能存在关联。
研究母体血清叶酸水平和母体叶酸补充剂暴露与婴儿川崎病发病的相关性。
设计、地点和参与者：本队列研究使用了日本环境与儿童研究的数据，这是一项全国性的出生队列研究，自 2011 年以来一直在招募儿童。本研究使用了 2019 年 10 月发布的数据集，并于 2023 年 1 月进行了分析。
妊娠第二和第三个三个月的母体血清叶酸水平（≥10ng/mL 为暴露）和妊娠第一、第二和第三个三个月的母体叶酸补充剂的频率（每周一次或更多为暴露）。
主要结局是婴儿在 12 个月内川崎病的发病情况。对每个暴露因素的比值比（OR）进行了估计，并根据变量集进行了倾向评分调整的逻辑回归分析。
研究人群包括 87702 名随访 12 个月的儿童。其中 336 名儿童患上了川崎病。服用叶酸补充剂的母亲（31275 名母亲[35.7%]；平均[标准差]年龄 32[5]岁）的血清叶酸水平高于未服用补充剂的母亲。与较低水平相比，母体血清叶酸水平较高与川崎病发病风险显著降低相关（叶酸≥10 与<10ng/mL，20698 名儿童中有 56 名[0.27%]与 64468 名儿童中有 267 名[0.41%]；OR，0.68；95%置信区间，0.50-0.92）。与未服用叶酸的母亲相比，服用叶酸补充剂的母亲的孩子川崎病患病率较低（39098 名儿童中有 131 名[0.34%]与 48053 名儿童中有 203 名[0.42%]），尽管差异无统计学意义（OR，0.83；95%置信区间，0.66-1.04）。与不补充相比，妊娠第二和第三个三个月补充叶酸与川崎病发病风险显著降低相关（31275 名儿童中有 94 名[0.30%]与 56427 名儿童中有 242 名[0.43%]；OR，0.73；95%置信区间，0.57-0.94）。
在本队列研究中，较高的血清叶酸水平（≥10ng/mL）和妊娠第二和第三个三个月每周一次以上的母体叶酸补充剂与婴儿在婴儿期川崎病发病风险降低相关。
