RTI International, Evidence-based Practice Center, University of North Carolina at Chapel Hill2RTI International, Research Triangle Park, North Carolina.
RTI International, Evidence-based Practice Center, University of North Carolina at Chapel Hill.
JAMA. 2017 Jan 10;317(2):190-203. doi: 10.1001/jama.2016.19193.
Neural tube defects are among the most common congenital anomalies in the United States. Periconceptional folic acid supplementation is a primary care-relevant preventive intervention.
To review the evidence on folic acid supplementation for preventing neural tube defects to inform the US Preventive Services Task Force for an updated Recommendation Statement.
MEDLINE, Cochrane Library, EMBASE, and trial registries through January 28, 2016, with ongoing surveillance through November 11, 2016; references; experts.
English-language studies of folic acid supplementation in women. Excluded were poor-quality studies; studies of prepubertal girls, men, women without the potential for childbearing, and neural tube defect recurrence; and studies conducted in developing countries.
Two investigators independently reviewed abstracts, full-text articles, and risk of bias of included studies. One investigator extracted data and a second checked accuracy. Because of heterogeneity, data were not pooled.
Neural tube defects, harms of treatment (twinning, respiratory outcomes).
A total of 24 studies (N > 58 860) were included. In 1 randomized clinical trial from Hungary initiated in 1984, incidence of neural tube defects for folic acid supplementation compared with trace element supplementation was 0% vs 0.25% (Peto odds ratio [OR], 0.13 [95% CI, 0.03-0.65]; n = 4862). Odds ratios from cohort studies recruiting participants between 1984 and 1996 demonstrated beneficial associations and ranged from 0.11 to 0.27 (n = 19 982). Three of 4 case-control studies with data from 1976 through 1998 reported ORs ranging from 0.6 to 0.7 (n > 7121). Evidence of benefit led to food fortification in the United States beginning in 1998, after which no new prospective studies have been conducted. More recent case-control studies drawing from data collected after 1998 have not demonstrated a protective association consistently with folic acid supplementation, with ORs ranging from 0.93 to 1.4 and confidence intervals spanning the null (n > 13 990). Regarding harms, 1 trial (OR, 1.40 [95% CI, 0.89-2.21]; n = 4767) and 1 cohort study (OR, 1.04 [95% CI, 0.91-1.18]; n = 2620) found no statistically significant increased risk of twinning. Three systematic reviews found no consistent evidence of increased risk of asthma (OR, 1.06 [95% CI, 0.99-1.14]; n = 14 438), wheezing, or allergy.
In studies conducted before the initiation of food fortification in the United States in 1998, folic acid supplementation provided protection against neural tube defects. Newer postfortification studies have not demonstrated a protective association but have the potential for misclassification and recall bias, which can attenuate the measured association of folic acid supplementation with neural tube defects.
神经管缺陷是美国最常见的先天畸形之一。围孕期叶酸补充是初级保健相关的预防干预措施。
回顾叶酸补充预防神经管缺陷的证据，为美国预防服务工作组更新推荐声明提供信息。
MEDLINE、Cochrane 图书馆、EMBASE 和试验登记处，截至 2016 年 1 月 28 日，通过 2016 年 11 月 11 日的持续监测；参考文献；专家。
女性中叶酸补充的英文研究。排除了低质量的研究；青春期前女孩、男性、无生育能力的女性以及神经管缺陷复发的研究；以及在发展中国家进行的研究。
两名调查员独立审查了摘要、全文文章和纳入研究的偏倚风险。一名调查员提取了数据，另一名调查员检查了准确性。由于存在异质性，因此未对数据进行汇总。
神经管缺陷，治疗的危害（双胞胎，呼吸结果）。
共纳入 24 项研究（N>58860）。在 1984 年匈牙利发起的一项随机临床试验中，与微量元素补充相比，叶酸补充的神经管缺陷发生率为 0%比 0.25%（Peto 优势比[OR]，0.13 [95%CI，0.03-0.65]；n=4862）。1984 年至 1996 年期间招募参与者的队列研究的 OR 从 0.11 到 0.27（n=19982）。3 项病例对照研究（1976 年至 1998 年的数据）报告的 OR 范围为 0.6 至 0.7（n>7121）。证据表明，从 1998 年开始，美国开始进行食品强化，在此之后，没有新的前瞻性研究进行。更近期的病例对照研究，从 1998 年后收集的数据中进行，并没有一致显示叶酸补充与神经管缺陷之间存在保护关联，OR 范围为 0.93 至 1.4，置信区间跨越零（n>13990）。关于危害，1 项试验（OR，1.40 [95%CI，0.89-2.21]；n=4767）和 1 项队列研究（OR，1.04 [95%CI，0.91-1.18]；n=2620）发现双胞胎的风险没有统计学显著增加。3 项系统评价发现哮喘（OR，1.06 [95%CI，0.99-1.14]；n=14438）、喘息或过敏的风险没有一致的增加证据。
在美国于 1998 年开始进行食品强化之前进行的研究中，叶酸补充可预防神经管缺陷。更新后的强化后研究并未显示出保护关联，但存在分类和回忆偏倚的可能性，这可能会削弱叶酸补充与神经管缺陷之间的关联。
