title: Maternal risk factors involved in specific congenital anomalies of the kidney and urinary tract: A case-control study.
abstract: BACKGROUND
  Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a heterogeneous group of birth defects with a variety of genetic and nongenetic factors suspected of involvement in the etiology. However, little is known about risk factors in specific CAKUT phenotypes. Therefore, we studied potential maternal risk factors in individual phenotypes within the CAKUT spectrum.
  
  
  METHODS
  Questionnaire data were collected from parents of 562 children with CAKUT and 2139 healthy controls within the AGORA data- and biobank. Potential maternal risk factors investigated included folic acid use, overweight and obesity, smoking, alcohol consumption, subfertility, and diabetes mellitus. We performed logistic regression analyses to assess associations between these potential risk factors and CAKUT phenotypes.
  
  
  RESULTS
  Increased risks of CAKUT were observed for folic acid use and maternal obesity, while fertility treatment by in vitro fertilization or intrauterine insemination and diabetes diagnosed during pregnancy also seem to be associated with CAKUT. Use of multivitamins reduced the risk (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.2-1.0) as opposed to use of folic acid supplements only (OR, 1.3; 95% CI, 1.0-1.8). Folic acid use was associated with duplex collecting systems (OR, 1.8; 95% CI, 1.0-3.4) and vesicoureteral reflux (OR, 1.8; 95% CI, 1.1-2.9) in particular. A relatively strong association was observed between diabetes during pregnancy and posterior urethral valves (OR, 2.6; 95% CI, 1.1-5.9).
  
  
  CONCLUSIONS
  Use of folic acid only seems to be counterproductive for prevention of CAKUT, in contrast to multivitamin use. Furthermore, we observed differences in risk factor patterns among CAKUT phenotypes, which stress the importance of separate analyses for each phenotype. Birth Defects Research (Part A) 106:596-603, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Groen In 't Woud
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kirsten Y
authors.initials: KY
authors.lastname: Renkema
authors.affiliation: Department of Pediatrics, Radboudumc Amalia Children's Hospital, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Michiel F
authors.initials: MF
authors.lastname: Schreuder
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Charlotte H W
authors.initials: CH
authors.lastname: Wijers
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Loes F M
authors.initials: LF
authors.lastname: van der Zanden
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
authors.affiliation: Department of Urology/Pediatric Urology, Radboudumc Amalia Children's Hospital, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Wout F J
authors.initials: WF
authors.lastname: Feitz
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Ernie M H F
authors.initials: EM
authors.lastname: Bongers
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.|Department of Pediatrics, Radboudumc Amalia Children's Hospital, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Iris A L M
authors.initials: IA
authors.lastname: van Rooij
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects*; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D009765:Obesity / Q000150:complications / Q000453:epidemiology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000453:epidemiology*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
chemical_list: D005492:Folic Acid
keywords: CAKUT; assisted reproduction; congenital malformations; folic acid; kidney; multivitamins; obesity; risk factors