title: Phenotype severity in the bladder exstrophy-epispadias complex: analysis of genetic and nongenetic contributing factors in 441 families from North America and Europe.
abstract: OBJECTIVE
  To identify genetic and nongenetic risk factors that contribute to the severity of the bladder exstrophy-epispadias complex (BEEC).
  
  
  METHODS
  Patients with BEEC from North America (n = 167) and Europe (n = 274) were included. The following data were collected: associated anomalies, parental age at conception, mode of conception, periconceptional folic acid supplementation, maternal risk factors during pregnancy, and environmental risk factors. The patients were divided into 3 subgroups according to phenotype severity: (i) mild, epispadias (n = 43); (ii) intermediate, classic bladder exstrophy (n = 366); and (iii) severe, cloacal exstrophy (n = 31). These subgroups then were compared with identify factors that contribute to phenotype severity.
  
  
  RESULTS
  Males were overrepresented in all subgroups. A relatively high prevalence of cleft lip, with or without cleft palate, was observed. Maternal smoking and medical radiation during the first trimester were associated with the severe cloacal exstrophy phenotype. Compliance with periconceptional folic acid supplementation was associated with the mildest phenotype (epispadias).
  
  
  CONCLUSIONS
  Periconceptional folic acid supplementation appears to prevent the development of the severe phenotype of BEEC.
authors.affiliation: Institute of Human Genetics, Children's Hospital, University of Bonn, Bonn, Germany. reutter@uni-bonn.de
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
authors.forename: Lisa
authors.initials: L
authors.lastname: Gambhir
authors.forename: Anne-Karoline
authors.initials: AK
authors.lastname: Ebert
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Rösch
authors.forename: Raimund
authors.initials: R
authors.lastname: Stein
authors.forename: Annette
authors.initials: A
authors.lastname: Schröder
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Boemers
authors.forename: Enrika
authors.initials: E
authors.lastname: Bartels
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogt
authors.forename: Boris
authors.initials: B
authors.lastname: Utsch
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.forename: Birte
authors.initials: B
authors.lastname: Detlefsen
authors.forename: Nadine
authors.initials: N
authors.lastname: Zwink
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rogenhofer
authors.forename: Rita
authors.initials: R
authors.lastname: Gobet
authors.forename: Goedele M A
authors.initials: GM
authors.lastname: Beckers
authors.forename: Arend
authors.initials: A
authors.lastname: Bökenkamp
authors.forename: Abdol-Mohammad
authors.initials: AM
authors.lastname: Kajbafzadeh
authors.forename: Enrique
authors.initials: E
authors.lastname: Jaureguizar
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
authors.forename: Yegappan
authors.initials: Y
authors.lastname: Lakshmanan
authors.forename: John P
authors.initials: JP
authors.lastname: Gearhart
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Jenetzky
mesh_terms: D000328:Adult; D000863:Antacids / Q000627:therapeutic use; D001746:Bladder Exstrophy / Q000453:epidemiology*; D002971:Cleft Lip / Q000453:epidemiology; D002972:Cleft Palate / Q000453:epidemiology; D004842:Epispadias / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005307:Fertilization in Vitro / Q000706:statistics & numerical data; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D010331:Paternal Age; D010641:Phenotype; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011295:Prenatal Care; D011859:Radiography / Q000706:statistics & numerical data; D012307:Risk Factors; D012720:Severity of Illness Index; D017678:Sex Distribution; D012907:Smoking / Q000453:epidemiology; D020554:Sperm Injections, Intracytoplasmic / Q000706:statistics & numerical data; D011795:Surveys and Questionnaires; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000863:Antacids; D014803:Vitamin B Complex; D005492:Folic Acid