Association of abnormal placental perfusion with the risk of male hypospadias: a hospital-based retrospective cohort stu
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RESEARCH ARTICLE
Open Access
Association of abnormal placental perfusion with the risk of male hypospadias: a hospital-based retrospective cohort study Chen Zhu1, Bin Zhang2, Ting Peng2, Ming-Qing Li3,4, Yun-Yun Ren1* and Jiang-Nan Wu5*
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: Hypospadias, Abnormal placental perfusion, Uterine artery, Preeclampsia, Retrospective cohort study
Background Hypospadias are one of the most common birth defects in infants and have a substantial impact on childhood renal survival and the quality of life of affected children [1–3]. For example, infants with hypospadias may suffer from complications later in life, including a higher risk of testicular cancer and subfertility [4, 5], despite corrective surgery treatment. Furthermore, the prevalence of the anomaly in * Correspondence: [email protected]; [email protected] 1 Department of Ultrasound, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China 5 Department of Clinical Epidemiology, Obstetrics and Gynecology Hospital, Fudan University, 566 Fangxie Road, Shanghai 200011, China Full list of author information is available at the end of the article
China is increasing [6]. According to the Report on the Prevention and Treatment of Birth Defects in China (2012), the prevalence of hypospadias has increased from 3.08 per 10,000 births in 1996 to 5.03 per 10,000 births in 2011 and ranks sixth among all birth defects in 2011 [7]. However, the causes of hypospadias are mostly unknown. Placental dysfunction was considered a plausible candidate cause of congenital anomalies, such as hypospadias and congenital heart defects, because placental dysfunction may cause inadequate fetal hCG provision and intrauterine growth restric
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