RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center.
RTI International, Research Triangle Park, North Carolina.
JAMA. 2023 Aug 1;330(5):460-466. doi: 10.1001/jama.2023.9864.
Neural tube defects are among the most common birth defects in the US.
To review new evidence on the benefits and harms of folic acid supplementation for the prevention of neural tube defects to inform the US Preventive Services Task Force.
Sources included PubMed, Cochrane Library, Embase, and trial registries from July 1, 2015, through July 2, 2021; references; and experts, with surveillance through February 10, 2023. Two investigators independently reviewed English-language randomized studies and nonrandomized cohort studies in very highly developed countries that focused on the use of folic acid supplementation for the prevention of neural tube defect-affected pregnancies; methodological quality was dually and independently assessed.
Twelve observational studies (reported in 13 publications) were eligible for this limited update (N = 1 244 072). Of these, 3 studies (n = 990 372) reported on the effect of folic acid supplementation on neural tube defects. For harms, 9 studies were eligible: 1 randomized clinical trial (n = 431) reported on variations in twin delivery, 7 observational studies (n = 761 125) reported on the incidence of autism spectrum disorder, and 1 observational study (n = 429 004) reported on maternal cancer. Two cohort studies and 1 case-control study newly identified in this update reported on the association between folic acid supplementation and neural tube defects (n = 990 372). One cohort study reported a statistically significant reduced risk of neural tube defects associated with folic acid supplementation taken before pregnancy (adjusted relative risk [aRR], 0.54 [95% CI, 0.31-0.91]), during pregnancy (aRR, 0.62 [95% CI, 0.39-0.97]), and before and during pregnancy (aRR, 0.49 [95% CI, 0.29-0.83]), but this association occurred for only the later of 2 periods studied (2006-2013 and not 1999-2005). No other statistically significant benefits were reported overall. No study reported statistically significant harms (multiple gestation, autism, and maternal cancer) associated with pregnancy-related folic acid exposure.
New evidence from observational studies provided additional evidence of the benefit of folic acid supplementation for preventing neural tube defects and no evidence of harms related to multiple gestation, autism, or maternal cancer. The new evidence was consistent with previously reviewed evidence on benefits and harms.
神经管缺陷是美国最常见的出生缺陷之一。
回顾叶酸补充剂预防神经管缺陷的益处和危害的新证据，为美国预防服务工作组提供信息。
来源包括 2015 年 7 月 1 日至 2021 年 7 月 2 日的 PubMed、Cochrane 图书馆、Embase 和试验登记处；参考文献；以及专家，监测至 2023 年 2 月 10 日。两名调查员独立审查了在高度发达的国家进行的以叶酸补充剂预防神经管缺陷相关妊娠为重点的随机研究和非随机队列研究；方法学质量进行了双重独立评估。
本次有限更新有 12 项观察性研究（在 13 项研究中报道）符合条件（N=1244072）。其中，3 项研究（n=990372）报告了叶酸补充剂对神经管缺陷的影响。关于危害，有 9 项研究符合条件：1 项随机临床试验（n=431）报告了双胞胎分娩的变化，7 项观察性研究（n=761125）报告了自闭症谱系障碍的发病率，1 项观察性研究（n=429004）报告了母亲的癌症。本次更新中新发现的两项队列研究和一项病例对照研究报告了叶酸补充剂与神经管缺陷之间的关联（n=990372）。一项队列研究报告称，与怀孕前（调整后的相对风险[ARR]，0.54 [95%CI，0.31-0.91]）、怀孕期间（ARR，0.62 [95%CI，0.39-0.97]）以及怀孕前和怀孕期间（ARR，0.49 [95%CI，0.29-0.83]）服用叶酸补充剂相关的神经管缺陷风险显著降低，但这种关联仅出现在研究的后期（2006-2013 年，而非 1999-2005 年）。总体而言，没有报告其他具有统计学意义的益处。没有研究报告与妊娠相关的叶酸暴露相关的多胎妊娠、自闭症或母亲癌症的统计学意义上的危害。
来自观察性研究的新证据提供了叶酸补充剂预防神经管缺陷的额外益处证据，并且没有与多胎妊娠、自闭症或母亲癌症相关的危害证据。新证据与之前关于益处和危害的审查证据一致。
