Methyltetrahydrofolate and folic acid supplementation in methylenetetrahydrofolate reductase polymorphisms: a randomized controlled trial
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摘要:
目的比较叶酸和活性叶酸补充对亚甲基四氢叶酸还原酶基因多态性人群妊娠结局影响。 方法采用前瞻性随机实验收集我院 30~40 岁有既往流产史或畸形胎儿史女性并记录实验对象体质量指数。从中筛选 MTHFR677 1298 基因突变的高风险人群 80 名，随机分为实验组 40 名，对照组 40 名。实验组给予活性三代叶酸 800 μg/d，对照组给予叶酸 800 μg/d。每周电话回访记录流产、妊娠并发症及妊娠结局例数。 结果对照组、实验组年龄、流产次数、基因突变风险等级及服药时长无显著性差异。 经过平均 40 周的电话回访跟踪，对照组孕妇妊娠结局：足月正常胎儿 32 例、早产儿 4 例、早孕期流产 2 例、晚期流产 1 例；实验组 1 例中途退出，足月正常胎儿 30 例、早产儿 1 例、早孕期流产 5 例、晚期流产 2 例。两组娩出活胎均无神经管畸形胎儿及其他结构畸形胎儿。两组妊娠结局经 Mann-Whitney U 检验，P＞0.05 无统计学差异。 结论对于 MTHFRC677T、A1298C 基因突变高风险人群给予甲基四氢叶酸无明显益处。建议高龄、有不良妊娠结局史女性叶酸每日补充量可由 400 μg/d 提高至 800 μg/d。 -
关键词:
- 亚甲基四氢叶酸还原酶基因多态性 /
- 高风险人群 /
- 甲基四氢叶酸 /
- 妊娠结局
Abstract:ObjectiveMethylenetetrahydrofolate reductase C677T and A1298 Cpolymorphismsreduce the ability of synthesis methyltetrahydrofolate. So the methyltetrahydrofolate supplement pregnancy outcome was compared tothe folic acid supplement in methylenete trahydrofolate reductase polymorphisms. MethodsThe 80 participants were women with recurrent abortion, aged 35 to 40 years, methy lenetetrahy drofolate reductase C677T and A1298 Cpolymorphisms. The cases were randomly assigned to receive either folic acid or methyltetrahydrofolateaccording to the stratified blocked randomization by age, the number of previous abortions and methylenetetrahydrofolate reductasepolymorphisms. Participants took daily 800 μg methylentetrahydrofolate or 800 μg folic acid from at least 12 weeks before conception to the 24 th week of the pregnancy. Pregnancy complications and preganacy outcome of two groups were followed-up. ResultsAfter an average of 40 weeks of tracking, 32 cases of pregnant women in the folic acid group delivered their babies full term, 4 cases premature delivery, 2 cases early miscarria ge and 1 case late abortion. In the methylenetetrahydrofolate group, a case was dropped, 30 cases of pregnant women delivered their babies full term, 5 cases premature delivery, 2 cases early miscarriage, 1 case late abortion. There was no significant difference in preganacy outcome between two groups. ConclusionThe results don't support any beneficial effect of 5-MTHF and folate supplementation inwomen with recurrent abortion with any MTHFR C677T and/or A1298C polymorphism. -
表 1 实验组对照组计量因素比较（n=40）
因素 叶酸组 MTHF组 年龄(岁） 35.6±4.5 35.6±5.0 BMI(kg/m2) 25.8±3.5 26.1±4.1 既往流产（次） 2.1±0.7 2.1±0.5 服药时长（周） 27.3±1.2 27.4±0.8 
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表 2 实验组对照组基因多态性因素比较（n=40）
MTHFR基因 叶酸组 MTHF组 C/C 20 19 MTHFR677CT C/T 16 17 T/T 4 4 Mann-Whitney U P=0.818 A/A 26 26 MTHFR1298AC A/C 9 10 C/C 5 4 Mann-Whitney U P=0.699
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表 3 实验组对照组妊娠结局
妊娠结局 叶酸组（n=40） MTHF组（n=39） 足月正常胎儿 32 30 早产儿 4 5 早期流产 2 2 晚期流产 1 1 Mann-Whitney U P=0.751
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