The association and diagnostic value of maternal serum placental biomarkers for fetal hypospadias and cryptorchidism.

Abstract

Background: Clinically, the diagnosis of hypospadias and cryptorchidism presents a certain degree of complexity due to the variability in anatomical presentation and potential comorbid conditions. This study aimed to evaluate the diagnostic value of maternal serum placental biomarkers [first-trimester (FT) gestation: 10-13⁺⁶ weeks; second-trimester (ST) gestation: 15-20⁺⁶ weeks] to predict hypospadias and cryptorchidism.

Methods: We performed a retrospective case-control study, and participants were divided into three groups: a hypospadias group (222 cases), a cryptorchidism group (120 cases), and a control group (311 cases). Receiver operating characteristic (ROC) curve, area under the curve (AUC), sensitivity, and specificity analyses were used to evaluate the performance of the different predictive models constructed with maternal serum pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), and ST free beta human chorionic gonadotropin (ST-free β-hCG) individually or in combination for hypospadias and cryptorchidism.

Results: Maternal serum PAPP-A and uE3 multiple of median (MoM) levels in the hypospadias group were lower than these in the control group [0.70 (0.10-2.41) vs. 1.03 (0.33-2.69) MoM; 0.80 (0.25-1.71) vs. 1.01 (0.63-1.56) MoM], while AFP and ST-free β-hCG MoM levels in the hypospadias group were higher than these in the control group [1.40 (0.34-8.27) vs. 1.02 (0.33-3.29) MoM; 1.25 (0.66-3.56) vs. 1.02 (0.52-1.90) MoM]. Meanwhile, maternal serum PAPP-A, AFP, and uE3 MoM levels in the cryptorchidism group were all lower than these in the control group [0.92 (0.31-3.01) vs. 1.03 (0.33-2.69) MoM; 1.00 (0.57-1.98) vs. 1.02 (0.52-1.90) MoM; 0.94 (0.69-1.49) vs. 1.01 (0.63-1.56) MoM], but ST-free β-hCG MoM level in the cryptorchidism group was higher than that in the control group [1.04 (0.28-3.51) vs. 1.02 (0.33-3.29) MoM] (all P<0.001). The best models in the screening protocol were the combined screening of multiple markers (PAPP-A + AFP + uE3) to predict hypospadias (AUC =0.795, P<0.001, sensitivity =0.800, specificity =0.788), and the screening model (PAPP-A + uE3) to predict cryptorchidism (AUC =0.658, P=0.03, sensitivity =0.778, specificity =0.614). Overall accuracy of predictive models was not sufficient.

Conclusions: The combined risk model of maternal serum PAPP-A, AFP and uE3 had a relatively better diagnostic value for hypospadias and cryptorchidism than the models constructed with other placental biomarkers individually or in combination.