title: Parental risk factors and anorectal malformations: systematic review and meta-analysis.
abstract: BACKGROUND
  Anorectal malformations (ARM) are rare forms of congenital uro-rectal anomalies with largely unknown causes. Besides genetic factors, prenatal exposures of the parents to nicotine, alcohol, caffeine, illicit drugs, occupational hazards, overweight/obesity and diabetes mellitus are suspected as environmental risk factors.
  
  
  METHODS
  Relevant studies published until August 2010 were identified through systematic search in PubMed, EMBASE, ISI Web of Knowledge and the Cochrane Library databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal and paternal smoking, maternal alcohol consumption, underweight (body mass index [BMI] < 18.5), overweight (BMI 25-29.9), obesity (BMI ≥30) and maternal diabetes mellitus with ARM using meta-analyses.
  
  
  RESULTS
  22 studies that reported on the association between prenatal environmental risk factors and infants born with ARM were included in this review. These were conducted in the United States of America (n = 12), Spain (n = 2), Sweden (n = 2), the Netherlands (n = 2), Japan (n = 1), France (n = 1), Germany (n = 1) and Hungary (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, control types and adjustment for covariates. Consistently increased risks were observed for paternal smoking and maternal overweight, obesity and diabetes, but not for maternal smoking and alcohol consumption. In meta-analyses, pooled odds ratios (95% confidence intervals) for paternal smoking, maternal overweight, obesity, pre-gestational and gestational diabetes were 1.53 (1.04-2.26), 1.25 (1.07-1.47), 1.64 (1.35-2.00), 4.51 (2.55-7.97) and 1.81 (1.23-2.65), respectively.
  
  
  CONCLUSIONS
  Evidence on risk factors for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate paternal smoking and maternal overweight, obesity and diabetes to be associated with increased risks. Further, ideally large-scale multicentre and register-based studies are needed to clarify the role of key risk factors for the development of ARM.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Zwink
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Jenetzky
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000071056:Anorectal Malformations; D001006:Anus, Imperforate / Q000209:etiology* / Q000235:genetics*; D005260:Female; D015386:Hazardous Substances / Q000633:toxicity; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors
chemical_list: D015386:Hazardous Substances