Abstract：
OBJECTIVE: The objective of this meta-analysis was to determine whether maternal exposure to folate antagonists is associated with increased rates of congenital heart disease in offspring.
METHODS: A comprehensive search for articles in the MEDLINE (PubMed) and EMBASE databases published up to 21 August 2023 was performed. The search strategy was not limited by study design but only for articles in the English language.
RESULTS: Analysis of 6 cohort studies and 5 cross-sectional studies, published between 1976 and 2020, showed significant increase in rate of congenital heart disease (odds ratio 1.55, 95% confidence interval, 1.28-1.87) when exposed to folate antagonists compared with the control. Further subgroup analysis showed the increased rate for exposure to both dihydrofolate reductase inhibitors and antiepileptic drugs separately. No differences were observed when analyses were stratified by timing of study.
CONCLUSIONS: Administration of folate antagonists within the 12-week period preceding conception and throughout the second and third months of gestation exhibited a statistically significant elevation in the susceptibility to congenital heart diseases. Notably, the protective effect of folic acid supplementation was reported in cases of congenital heart disease linked to dihydrofolate reductase inhibitors but not that associated with antiepileptic drugs.
METHODS: A comprehensive search for articles in the MEDLINE (PubMed) and EMBASE databases published up to 21 August 2023 was performed. The search strategy was not limited by study design but only for articles in the English language.
RESULTS: Analysis of 6 cohort studies and 5 cross-sectional studies, published between 1976 and 2020, showed significant increase in rate of congenital heart disease (odds ratio 1.55, 95% confidence interval, 1.28-1.87) when exposed to folate antagonists compared with the control. Further subgroup analysis showed the increased rate for exposure to both dihydrofolate reductase inhibitors and antiepileptic drugs separately. No differences were observed when analyses were stratified by timing of study.
CONCLUSIONS: Administration of folate antagonists within the 12-week period preceding conception and throughout the second and third months of gestation exhibited a statistically significant elevation in the susceptibility to congenital heart diseases. Notably, the protective effect of folic acid supplementation was reported in cases of congenital heart disease linked to dihydrofolate reductase inhibitors but not that associated with antiepileptic drugs.
摘要：
目的：本荟萃分析的目的是确定母体暴露于叶酸拮抗剂是否与后代先天性心脏病发病率增加有关。
方法：对截至2023年8月21日的MEDLINE（PubMed）和EMBASE数据库中的文章进行了全面搜索。搜索策略不受研究设计的限制，而仅针对英语文章。
结果：对6项队列研究和5项横断面研究的分析，发表于1976年至2020年，显示先天性心脏病发病率显著增加(比值比1.55，95%置信区间，1.28-1.87）与对照组相比，暴露于叶酸拮抗剂时。进一步的亚组分析显示，暴露于二氢叶酸还原酶抑制剂和抗癫痫药物的比率分别增加。当按研究时间分层分析时，没有观察到差异。
结论：在受孕前12周以及妊娠第二个月和第三个月服用叶酸拮抗剂后，先天性心脏病的易感性有统计学意义的升高。值得注意的是,据报道,补充叶酸对先天性心脏病的保护作用与二氢叶酸还原酶抑制剂有关,但与抗癫痫药物无关.
方法：对截至2023年8月21日的MEDLINE（PubMed）和EMBASE数据库中的文章进行了全面搜索。搜索策略不受研究设计的限制，而仅针对英语文章。
结果：对6项队列研究和5项横断面研究的分析，发表于1976年至2020年，显示先天性心脏病发病率显著增加(比值比1.55，95%置信区间，1.28-1.87）与对照组相比，暴露于叶酸拮抗剂时。进一步的亚组分析显示，暴露于二氢叶酸还原酶抑制剂和抗癫痫药物的比率分别增加。当按研究时间分层分析时，没有观察到差异。
结论：在受孕前12周以及妊娠第二个月和第三个月服用叶酸拮抗剂后，先天性心脏病的易感性有统计学意义的升高。值得注意的是,据报道,补充叶酸对先天性心脏病的保护作用与二氢叶酸还原酶抑制剂有关,但与抗癫痫药物无关.
