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Abstract Objective To evaluate maternal urinary CA19-9 as a potential marker for diagnosing severe antenatal hydronephrosis (ANH) during pregnancy and to compare the values with those in normal pregnancies as controls. Materials & Methods A total of 20 women in their third pregnancy trimester were enrolled. An anteroposterior diameter (APD) of ≥15 was considered as severe ANH. Case group consisted of 10 women with a diagnosis of severe ANH. Ten women with similar age, gestational age (GA), fetal sex, normal ultrasonography, and no history of any congenital anomalies were chosen as controls. Urine samples were collected and maternal urinary CA19-9 was measured. The levels in case and control groups were compared using Mann-Whitney U test. Results Each group consisted of 9 mothers with male fetuses and one with female fetus. The APD in the ANH group ranged from 17 to 40 mm. Five of 10 children in the ANH group also had contralateral APD of ≥4 mm (bilateral ANH). Mean age and GA of pregnant women in two groups were comparable. Mean maternal CA19-9 was significantly higher in ANH group compared to controls (mean 134.5 U/ml vs. 22.2 U/ml, P<0.001). Conclusions To our best knowledge, this is the first time that maternal urinary CA19-9 has been used as a marker for ANH. Based on these pilot data, CA19-9 levels are significantly higher in the urine of pregnant women carrying fetuses with severe ANH and it may have the potential to serve as a noninvasive and useful biomarker for diagnosing ANH.