Association of abnormal placental perfusion with the risk of male hypospadias: a hospital-based retrospective cohort study

Abstract

Background: The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly.

Methods: A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP.

Results: Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09-5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P < 0.001). A path analysis indicated that 28.18-46.61% of the risk of hypospadias may be attributed to the effect of APP.

Conclusions: Male hypospadias risk was associated with APP and increased with APP severity, as measured in the second trimester. APP had an important role in the development of the anomaly.

Keywords: Abnormal placental perfusion; Hypospadias; Preeclampsia; Retrospective cohort study; Uterine artery.

Fig. 1

Cumulative risk of male hypospadias across the groups by the number of placental perfusion insufficiency markers and the situation of left uterine artery resistance index (RI) and early diastolic notching (EDN). ^* P values for the log rank (Mantel-Cox) method compared with the cumulative risk of male hypospadias in the reference group