To study the clinical value of the levels of serum pregnancy-associated plasma protein A(PAPP-A) combined with inhibin-A of women during the second trimester of pregnancy for predicting their birth defects. Methods: The clinical data of the pregnant women who underwent regular prenatal checkups and gave birth from January 2021 to May 2024 were collected. Among them, 86 pregnant women with fetal structural abnormalities were in the study group and 90 pregnant women with normal newborns were in the control group. The levels of serum PAPP-A and inhibin-A of the women during the second trimester of pregnancy were compared between the two groups. Pearson analysis was applied to analyze the correlation between the serum PAPP-A level of the women in the study group and their inhibin-A level. Logistic analysis was applied to analyze the influencing factors of the birth defects of the offspring of the women. Receiver operator characteristic(ROC) curve was applied to analyze the clinical value of the combined serum PAPP-A and inhibin-A levels of the women for predicting the birth defects of their offspring. Results: The serum PAPP-A(7.33±1.48 ng/ml) of the women in the study group was significantly lower than that(9.56±1.74 ng/ml) of the women in the control group. The inhibin-A level(478.25±93.48 pg/ml) of the women in the study group was significantly higher than that(365.87±81.51 pg/ml) of the women in the control group(all P<0.05). The serum PAPP-A level of the women in the study group was negatively correlated with their inhibin - A level(r=0.340, P=0.001). The proportion of folic acid intake of the women in the study group was significantly lower than that of the women in the control group. The proportions of the respiratory infections during the first trimester of pregnancy, the anemia during pregnancy, the raising animals and the smoking of the women in the study group were significantly higher than those of the women in the control group(all P<0.05). The folic acid intake and the increased serum PAPP-A level of the women were the protective factors of the birth defects of their offspring, while the respiratory infections during the first trimester of pregnancy, the anemia during pregnancy, the raising animals the smoking, and the increased serum inhibin-A level of the women were the risk factors of the birth defects of their offspring(all P<0.05). The area under the curve(AUC), the sensitivity and the specificity of the serum PAPP-A level of the women for predicting the birth defects of their offspring were 0.802, 79.1% and 80.0%, respectively. The AUC, the sensitivity and the specificity of the serum inhibin-A level of the women for predicting the birth defects of their offspring were 0.803, 74.4% and 81.1%, respectively. The AUC, the sensitivity and the specificity of the serum PAPP-A level combined with inhibin-A level of the women for predicting the birth defects of their offspring were 0.874, 91.9% and 75.6%, respectively(P<0.05). Conclusion: The decrease of the serum PAPP-A level and the increase of the serum inhibin-A level of the pregnant women during the second trimester of pregnancy are not conducive to their fetal growth and development normally. The predictive value of the combined serum PAPP-A and Inhibin-A levels of the pregnant women during the second trimester of pregnancy for the birth defects of their offspring increases, and which may be used for clinical predicting the birth defects of the offspring of the pregnant women in the future.