De-Regil Luz Maria, Peña-Rosas Juan Pablo, Fernández-Gaxiola Ana C, Rayco-Solon Pura
Research and Evaluation, Micronutrient Initiative, 180 Elgin Street, Suite 1000, Ottawa, ON, Canada, K2P 2K3.
Cochrane Database Syst Rev. 2015 Dec 14;2015(12):CD007950. doi: 10.1002/14651858.CD007950.pub3.
It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear.
This review aims to examine whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies (including cleft palate) without causing adverse outcomes in mothers or babies. This is an update of a previously published Cochrane review on this topic.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015). Additionally, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 August 2015) and contacted relevant organisations to identify ongoing and unpublished studies.
We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity.
Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. We assessed the quality of the body of evidence using the GRADE approach.
Five trials involving 7391 women (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs) were included. Four comparisons were made: 1) supplementation with any folate versus no intervention, placebo or other micronutrients without folate (five trials); 2) supplementation with folic acid alone versus no treatment or placebo (one trial); 3) supplementation with folate plus other micronutrients versus other micronutrients without folate (four trials); and 4) supplementation with folate plus other micronutrients versus the same other micronutrients without folate (two trials). The risk of bias of the trials was variable. Only one trial was considered to be at low risk of bias. The remaining studies lacked clarity regarding the randomisation method or whether the allocation to the intervention was concealed. All the participants were blinded to the intervention, though blinding was unclear for outcome assessors in the five trials.The results of the first comparison involving 6708 births with information on NTDs and other infant outcomes, show a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58); five studies; 6708 births; high quality evidence). Only one study assessed the incidence of NTDs and showed no evidence of an effect (RR 0.07, 95% CI 0.00 to 1.32; 4862 births) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births). Subgroup analyses suggest that the positive effect of folic acid on NTD incidence and recurrence is not affected by the explored daily folic acid dosage (400 µg (0.4 mg) or higher) or whether folic acid is given alone or with other vitamins and minerals. These results are consistent across all four review comparisons.There is no evidence of any preventive or negative effects on cleft palate (RR 0.73, 95% CI 0.05 to 10.89; three studies; 5612 births; low quality evidence), cleft lip ((RR 0.79, 95% CI 0.14 to 4.36; three studies; 5612 births; low quality evidence), congenital cardiovascular defects (RR 0.57, 95% CI 0.24 to 1.33; three studies; 5612 births; low quality evidence), miscarriages (RR 1.10, 95% CI 0.94 to 1.28; five studies; 7391 pregnancies; moderate quality evidence) or any other birth defects (RR 0.94, 95% CI 0.53 to 1.66; three studies; 5612 births; low quality evidence). There were no included trials assessing the effects of this intervention on neonatal death, maternal blood folate or anaemia at term.
AUTHORS' CONCLUSIONS: Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.
据报道，孕前补充叶酸可预防神经管缺陷（NTD）。不同剂量、形式和方案的叶酸补充剂对预防其他出生缺陷以及母婴结局的影响尚不清楚。
本综述旨在研究孕前补充叶酸是否能降低神经管及其他先天性异常（包括腭裂）的风险，同时不导致母亲或婴儿出现不良结局。这是对先前发表的关于该主题的Cochrane综述的更新。
我们检索了Cochrane妊娠与分娩组试验注册库（2015年8月31日）。此外，我们检索了世界卫生组织（WHO）国际临床试验注册平台（ICTRP）（2015年8月31日），并联系了相关组织以识别正在进行和未发表的研究。
我们纳入了所有评估孕前单独补充叶酸，或与其他维生素和矿物质联合补充对不同年龄和胎次女性影响的随机或半随机试验。
两位综述作者独立根据纳入标准评估研究的合格性，从纳入研究中提取数据，检查数据录入的准确性，并评估纳入研究的偏倚风险。我们使用GRADE方法评估证据体的质量。
纳入了五项试验，涉及7391名女性（2033名有NTD妊娠史，5358名无NTD妊娠史）。进行了四项比较：1）补充任何叶酸与不干预、安慰剂或不含叶酸的其他微量营养素（五项试验）；2）单独补充叶酸与不治疗或安慰剂（一项试验）；3）补充叶酸加其他微量营养素与不含叶酸的其他微量营养素（四项试验）；4）补充叶酸加其他微量营养素与不含叶酸的相同其他微量营养素（两项试验）。试验的偏倚风险各不相同。只有一项试验被认为偏倚风险较低。其余研究在随机化方法或干预分配是否隐藏方面缺乏明确性。所有参与者对干预措施不知情，尽管五项试验中结局评估者的盲法情况不明确。第一项比较涉及6708例出生且有神经管缺陷和其他婴儿结局信息，结果显示，与不干预/安慰剂或不含叶酸的维生素和矿物质相比，每日补充叶酸（单独或与其他维生素和矿物质联合）对预防神经管缺陷有保护作用（风险比（RR）0.31，95%置信区间（CI）0.17至0.58）；五项研究；6708例出生；高质量证据）。只有一项研究评估了神经管缺陷的发生率，未显示出有影响的证据（RR 0.07，95% CI 0.00至1.32；4862例出生），尽管接受叶酸的组未发现任何病例。叶酸对复发有显著保护作用（RR 0.34，95% CI 0.
