Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease

后代 医学 孟德尔随机化 怀孕 亚甲基四氢叶酸还原酶 优势比 混淆 微量营养素 四分位间距 同型半胱氨酸 产科 生理学 内科学 基因型 生物 遗传学 病理 基因 遗传变异
作者
Hongyan Chen,Yi Zhang,Dingmei Wang,Xiaotian Chen,Mengru Li,Xiangyuan Huang,Yuan Jiang,Yalan Dou,Yin Wang,Xiaojing Ma,Wei Sheng,Bing Jia,Weili Yan,Guoying Huang,Guoying Huang,Weili Yan,Xiaojing Ma,Weifen Luo,Wei Sheng,Yi Zhang
出处
期刊:Annals of Internal Medicine [American College of Physicians]
卷期号:175 (9): 1212-1220 被引量:17
标识
DOI:10.7326/m22-0741
摘要

Background: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. Objective: To quantify the association between periconception maternal RBC folate and offspring CHD risk. Design: Prospective, nested, case–control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644) Setting: 29 maternity institutions in 12 districts of Greater Shanghai, China. Participants: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). Measurements: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. Results: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). Limitation: Potential confounding due to unmeasured covariates in the nested case–control study. Conclusion: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. Primary Funding Source: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.
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