Objective: To investigate the role of maternal serum alpha-fetoprotein (AFP)levels measured in the second trimester of pregnancy for Down Syndrome screening in predicting the outcome of pregnancy associated with gestational diabetes mellitus, low birth weight and preterm labor.,Materials and Methods: This study was conducted retrospectively in 412 pregnant women whom applied for Down Syndrome Screening Test. Maternal midtrimester AFP levels were obtained between 15th to 20th weeks of gestation on the basis of fetal biparietal measurement. AFP levels were defined as MoM. Pregnant women were considered negative (control) when their blood glucose level was < 140 mg/dL (n=348). Those with one hour postprandial plasma glucose concentration 3 140 mg/dL and a positive 100 g oral glucose tolerance test (OGTT) is defined gestational diabetes mellitus (n=19). Those with one hour postprandial plasma glucose concentration 3 140 mg/dL and a negative 100 g oral glucose tolerance test (OGTT) is defined glucose intolerant (n=45). Preterm labor is described as labor that occured prior to 37th weeks of gestation. Babies whose weight was lower than 2500 g is defined low birth weight, and birth weight higher than 4000 g is defined macrosomic.,Results: Maternal serum AFP levels of 27 preterm labored women were high as compared to 385 women labored in term [1.21 +/- 1.27 MoM vs 0.88 +/- 0.46 MoM] (P=0.000). Maternal serum AFP levels of babies with low birth weight (< 2500 g) (n=21) were higher than that of babies with normal birth weight (n=391) (> 2500 g), [1.34 +/- 1.38 MoM vs 0.88 +/- 0.45 MoM] and this difference was significant (P=0.000). The level of AFP in pregnant women with gestational diabetes mellitus and glucose intolerance without complication were 0.92, 0.76 and 0.81 MoM, respectively and this difference was not significant (P> 0.05).,Conclusion: We contemplate pregnancies with a high maternal serum AFP, which is measured during the second trimester for Down syndrome screening test, is a crucial marker in predicting the pregnancy outcome in respect to birth weight and preterm labor.