Background: Hydronephrosis is the most common problem in prenatal sonography, which early detection decreases its complication and increases the survival rate of infants. Increased carbohydrate antigen 19-9 (CA19-9) tumor marker has been observed in nonmalignant conditions including hydronephrosis secondary to ureteral stones. This study aimed to determine the relationship between urinary CA19-9 in mothers with hydronephrosis fetuses with prognosis, severity, and cause of neonatal renal insufficiency. Materials and Methods: The present study is a retrospective/prospective cohort study. The CA19-9 was measured in 63 pregnant women who had a fetus with hydronephrosis in the third trimester of pregnancy. The relationship between CA19-9 and the following parameters was evaluated: causes of hydronephrosis, need for hospitalization after birth, need for surgery, treatment status, and survival. Results: In the present study, high values of CA19-9 (more than 27.8%) were able to predict severe hydronephrosis in neonates with a sensitivity of 80.6% and a specificity of 59.6%. An increase in this marker also could determine the pathological cause of hydronephrosis such as posterior urethral valves, the need for hydronephrosis surgery (P < 0.001), the need for hospitalization (P < 0.001), and the need to assisted ventilation (P = 0.001). Conclusion: The level of CA19-9 biomarker in the urine of pregnant mothers with hydronephrosis fetuses can be predictive value. Even urinary CA19-9 of mothers during the pregnancy can predict the need for the neonatal intensive care unit after delivery. [ABSTRACT FROM AUTHOR]