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Maternal and fetal risk factors for bladder exstrophy: A nationwide Swedish case-control study.

INTRODUCTION: Bladder exstrophy is a rare, congenital, complex malformation where the underlying cause is largely unknown. Both environmental and genetic mechanisms are thought to be involved. There are divergent results concerning the prevalence, birth descriptive data, and potential maternal risk factors for bladder exstrophy. Few previous studies have reflected nationwide populations, population registers, or spanned a longer period of time.

OBJECTIVE: To describe and assess bladder exstrophy and the potential maternal risk factors, for a time period of four decades, by conducting a nationwide register study of bladder exstrophy in Sweden.

METHODS: A matched-design, case-control, linkage-analysis study nested within the entire pool of live births in Sweden between 1973 and 2011 was performed. Cases with bladder exstrophy were identified using nationwide population-based birth and health registers. Inclusion criteria were people born in Sweden with the classification of bladder exstrophy according to the ICD coding system. Cases were matched with five controls per patient, based on birth year and sex. Prevalence was assessed and birth descriptive data were compiled. Potential maternal risk factors were obtained from medical birth registers of cases and assessed using conditional and multivariate logistic regression models to obtain odds ratios as a measure of the relative risk. Classification of the diagnosis in the registers constituted a possible limitation for determining the correct study population, which demanded strict validation and inclusion criteria. All data were collected prospectively, thereby avoiding potential recall bias.

RESULTS: The prevalence was calculated to be approximately 3 per 100,000 live births, with a male-to-female ratio of 1.14:1. In 92.5% of the cases, bladder exstrophy was an isolated malformation without associated major malformations. However, 41% had had surgery for congenital inguinal hernia and 11% of the male subjects had been operated on for cryptorchidism. A significantly higher proportion of cases had a birth weight <1500 g compared with controls, but other characteristics were comparable with controls. High maternal age was the only significant potential associated maternal risk factor.

CONCLUSIONS: One hundred and twenty children born with bladder exstrophy in Sweden during the last four decades were identified; this resulted in prevalence in Sweden of 3 per 100,000. The prevalence was stable over time and the sex ratio was equal. Birth characteristics were comparable to controls, and bladder exstrophy generally occurred as an isolated malformation without major associated malformations. Advanced maternal age was the only significant potential maternal risk factor.

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