Maternal homocysteine and folate levels and risk of recurrent spontaneous abortion: A meta‐analysis of observational studies

Abstract Aim The aim of the study was to review and summarize the epidemiologic evidence on the associations of homocysteine (HCY) and folate with the risk of recurrent spontaneous abortion (RSA). Methods This review was performed following Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines. PubMed, Google Scholar, Cochrane Libraries and Chinese databases were searched through May 2019 to identify studies that met prestated inclusion criteria. Either a fixed‐ or a random‐effects model was used to calculate the combined standardized mean difference (SMD) and 95% confidence intervals (CI). Results Twenty‐three studies involving 2052 RSA cases and 1476 healthy controls were included. Overall, women with RSA compared with those without RSA were at a significantly higher level of HCY both in plasma (SMD = 1.34; 95% CI: 0.76–1.93) and in serum (SMD = 1.46; 95% CI: 1.02–1.91), but lower level of folate both in serum (SMD = −1.63; 95% CI: −2.51 to −0.75) and in red blood cells (SMD = −1.30; 95% CI: −1.76 to −0.85). However, a statistically significant association between plasma folate and risk of RSA was not been observed (SMD = −0.82; 95% CI: −1.73 to 0.09). These findings have to be viewed with caution for the significant heterogeneity ( I 2 : from 88 to 98%). Conclusion High HCY levels in both plasma and serum as well as low folate levels in serum and red blood cells are significantly associated with risk of RSA, which indicates that measures to reduce HCY levels or folate supplementation may help to reduce the risk of RSA. However, prospective studies are needed to confirm our findings.