title: Epidemiological survey of 214 families with bladder exstrophy-epispadias complex.
abstract: OBJECTIVE
  We sought to identify causative nongenetic and genetic risk factors for the bladder exstrophy-epispadias complex.
  
  
  METHODS
  A total of 237 families with the bladder exstrophy-epispadias complex were invited to participate in the study, and information was obtained from 214 families, mainly from European countries.
  
  
  RESULTS
  Two families showed familial occurrence. Male predominance was found among all subgroups comprising epispadias, classic bladder exstrophy and cloacal exstrophy, with male-to-female ratios of 1.4:1, 2.8:1 and 2.0:1, respectively (p = 0.001). No association with parental age, maternal reproductive history or periconceptional maternal exposure to alcohol, drugs, chemical noxae, radiation or infections was found. However, periconceptional maternal exposure to smoking was significantly more common in patients with cloacal exstrophy than in the combined group of patients with epispadias/classic bladder exstrophy (p = 0.009). Only 16.8% of mothers followed the current recommendations of periconceptional folic acid supplementation, and 17.6% had started supplementation before 10 weeks of gestation. Interestingly, in the latter group mothers of patients with cloacal exstrophy were more compliant with folic acid supplementation than were mothers of the combined group of patients with epispadias/classic bladder exstrophy (p = 0.037). Furthermore, mothers of children with cloacal exstrophy knew significantly more often prenatally that their child would have a congenital malformation than did mothers of children with epispadias/classic bladder exstrophy (p <0.0001).
  
  
  CONCLUSIONS
  Our study corroborates the hypothesis that epispadias, classic bladder exstrophy and cloacal exstrophy are causally related, representing a spectrum of the same developmental defect, with a small risk of recurrence within families. Embryonic exposure to maternal smoking appears to enforce the severity, whereas periconceptional folic acid supplementation does not seem to alleviate it. There is a disproportional prenatal ultrasound detection rate between severe and mild phenotypes, possibly due to the neglect of imaging of full bladders with a focus on neural tube defects.
authors.affiliation: Department of Clinical Biochemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Gambhir
authors.forename: T
authors.initials: T
authors.lastname: Höller
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: G
authors.initials: G
authors.lastname: Schott
authors.forename: H
authors.initials: H
authors.lastname: Vogt
authors.forename: B
authors.initials: B
authors.lastname: Detlefsen
authors.forename: A-K
authors.initials: AK
authors.lastname: Ebert
authors.forename: M
authors.initials: M
authors.lastname: Fisch
authors.forename: S
authors.initials: S
authors.lastname: Beaudoin
authors.forename: R
authors.initials: R
authors.lastname: Stein
authors.forename: S A
authors.initials: SA
authors.lastname: Boyadjiev
authors.forename: J P
authors.initials: JP
authors.lastname: Gearhart
authors.forename: W
authors.initials: W
authors.lastname: Rösch
authors.forename: B
authors.initials: B
authors.lastname: Utsch
authors.forename: T M
authors.initials: TM
authors.lastname: Boemers
authors.forename: H
authors.initials: H
authors.lastname: Reutter
authors.forename: M
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D000328:Adult; D001746:Bladder Exstrophy / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D004842:Epispadias / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D012307:Risk Factors; D013577:Syndrome