Preoperative Illnesses in Children Do Not Increase the Risk of Complications After Hypospadias Repair.

BACKGROUND: Preoperative illnesses might induce immunosuppression and subsequently increase morbidity after surgery. Several studies have tried to identify risk factors for complications after hypospadias correction, but effects of illnesses in the weeks just before surgery are unknown. We aimed to determine the associations between preoperative illnesses not severe enough to postpone surgery and short-term complications after hypospadias repair in children. METHODS: In this retrospective cohort study, data were collected from 681 children with anterior or middle type hypospadias that had initial 1-stage repair in the period 1983-2012 in the Radboudumc, The Netherlands. The associations between common illnesses, such as common cold, fever and ear infection, within 2 weeks before repair, and postoperative complications, such as urethrocutaneous fistula, wound dehiscence and stenosis, within 2 months and 1 year after surgery, were analyzed using multivariable logistic regression analyses. RESULTS: Of the 681 boys, 22% had preoperative illnesses, most often common cold, and 14% had postoperative complications. Children with preoperative illnesses had fewer postoperative complications within 2 months (n = 13, 9%) than children without preoperative illnesses (n = 79, 16%), resulting in a 50% risk reduction (odds ratio: 0.49; 95% confidence interval: 0.26-0.93). Preoperative infections (common cold, fever and ear infection), in particular, reduced the risk of postoperative infections (wound and urinary tract infections; odds ratio: 0.37; 95% confidence interval: 0.14-0.98). Results were similar for complications within 1 year. CONCLUSIONS: Common preoperative illnesses not severe enough to postpone surgery did not increase the postoperative complication risk and even seemed to have a protective effect, especially for postoperative infections. Consequently, there is no reason to alter preoperative screening.

AGORA, a data- and biobank for birth defects and childhood cancer.

BACKGROUND: Research regarding the etiology of birth defects and childhood cancer is essential to develop preventive measures, but often requires large study populations. Therefore, we established the AGORA data- and biobank in the Netherlands. In this study, we describe its rationale, design, and ongoing data collection. METHODS: Children diagnosed with and/or treated for a structural birth defect or childhood cancer and their parents are invited to participate in the AGORA data- and biobank. Controls are recruited through random sampling from municipal registries. The parents receive questionnaires about demographics, family and pregnancy history, health status, prescribed medication, lifestyle, and occupational exposures before and during the index pregnancy. In addition, blood or saliva is collected from children and parents, while medical records are reviewed for diagnostic information. RESULTS: So far, we have collected data from over 6,860 families (3,747 birth defects, 905 childhood cancers, and 2,208 controls). The types of birth defects vary widely and comprise malformations of the digestive, respiratory, and urogenital tracts as well as facial, cardiovascular, kidney, skeletal, and central nervous system anomalies. The most frequently occurring childhood cancer types are acute lymphatic leukemia, Hodgkin and non-Hodgkin lymphoma, Wilms' tumor, and brain and spinal cord tumors. Our genetic and/or epidemiologic studies have been focused on hypospadias, anorectal malformations, congenital anomalies of the kidney and urinary tract (CAKUT), and orofacial clefts. CONCLUSION: The large AGORA data- and biobank offers great opportunities for investigating genetic and nongenetic risk factors for disorders in children and is open to collaborative initiatives. Birth Defects Research (Part A) 106:675-684, 2016. © 2016 Wiley Periodicals, Inc.

Interaction between MTHFR 677C>T and periconceptional folic acid supplementation in the risk of Hypospadias.

BACKGROUND: Hypospadias is a congenital malformation with both environmental factors and genetic predisposition involved in the pathogenesis. The role of maternal periconceptional folic acid supplement use in the development of hypospadias is unclear. As folate levels may also be influenced by the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, we hypothesize that a gene-environment interaction between this polymorphism and folic acid use is involved in the etiology of hypospadias. METHODS: We conducted a case-control study among 855 hypospadias cases and 713 population-based controls from the AGORA data- and biobank. Folic acid supplement use was derived from maternal questionnaires and infant and maternal DNA was used to determine the MTHFR C677T polymorphism using Taqman assays. We performed separate analyses for different hypospadias phenotypes (anterior/middle/posterior). RESULTS: Hypospadias was neither associated with folic acid use or the MTHFR C677T polymorphism, nor with their interaction. However, we did find an association with middle hypospadias when no supplements were used (odds ratio = 1.6; 95% confidence interval, 1.1-2.4), especially in infants carrying the CT/TT genotype (odds ratio = 2.5; 95% confidence interval, 1.4-4.7). In addition, more infants with these genotypes seemed to have posterior hypospadias, regardless of folic acid use. CONCLUSION: Our study does not suggest a major role for folic acid supplements or the MTHFR C677T polymorphism in the etiology of hypospadias in general, but not using folic acid and/or carrying the MTHFR C677T polymorphism may be associated with middle and posterior hypospadias. Therefore, we stress the importance of studying gene-environment interactions preferably in stratified analyses for different hypospadias phenotypes.