Objective: To explore the clinical value of serum folic acid, HCY and vitamin A in predicting pregnant women with birth defects. Methods: A total of 300 pregnant women were enrolled from September 2017 to May 2019 at the Third Affiliated Hospital of Zhengzhou university, including 100 cases with abnormal fetal structure but no chromosomal abnormalities found in prenatal diagnosis, and 200 normal cases who underwent prenatal examination. Serum folic acid, Hcy and vitamin A levels were measured to compare the predicting significance for birth defects. Results: The serum levels of folic acid, Hcy and vitamin A in the pregnant women with birth defects were significantly different compared with normal pregnant women (P<0.05). Folic acid and vitamin A were protective factors for birth defects, whereas HCY was a risk factor for birth defects. The area under the ROC curve (AUC) of the combined detection for birth defects was 0.747, and the specificity was 79.0%. Conclusion: Serum folic acid, Hcy, and vitamin A have higher clinical value for the combined prediction of birth defects, but the optimal prediction cut-off value needs to be supported by a study with larger sample size.