Association of plasma folic acid, vitamin-B12 and homocysteine with recurrent pregnancy loss. “A case control study”

OBJECTIVE: To investigate the relationship of serum homocysteine, folic acid, and vitamin-B12 levels with recurrent pregnancy loss (RPL). METHODS: A case-control study was conducted in the Department of Gynecology and Obstetrics, Dr. Ruth Pfau Civil Hospital, Karachi from July 2021 to June 2022. Total 124 participants were recruited from gynecology outpatient department after taking informed consent. The participants included 62 non-pregnant females with two or more consecutive unexplained RPLs and 62 healthy women having at least two successful deliveries without any pregnancy loss. Serum folic acid and vitamin-B12 levels were measured by chemiluminescent method and serum homocysteine was measured by enzyme-linked immunosorbent assay (ELISA). Comparison of quantitative variables with RPL cases and control was done by Mann-Whitney U-test (for non-normally distributed data) and independent sample t-test (for normally distributed data), while Pearson’s chi-square test was used for the association of qualitative variables with RPL cases and control. Correlation of homocysteine with vitamin-B12 and folic acid was assessed in RPL cases. RESULTS: The median age of the study population was 27 (IQR 25-32) years. The median body mass index (BMI) was 26.25 (IQR 22-29) kg/m(2). Cases had significantly lower serum folic acid (p-value=0.022), while vitamin-B12 was decreased in cases as compared to controls (p-value=0.295). Mean concentration of serum homocysteine was higher in RPL cases as compared to controls (p-value=0.094). There was significant association of serum vitamin B12 (p-value=0.001) and folic acid levels (p-value=0.004) with RPL. The homocysteine was not significantly correlated with vitamin-B12 (r=0.124, p=0.338) and folic acid (r=0.067, p=0.606) in the RPL group. CONCLUSION: Reduced level of serum folic acid and vitamin B12 was significantly associated with RPL cases, while homocysteine was marginally raised however the difference was not significant. Folic acid and vitamin B12 supplementation before next pregnancy in RPL patients is likely to be beneficial in improving pregnancy outcomes.