title: Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study.
abstract: BACKGROUND
  Congenital anomalies are a leading cause of infant death and disability and their incidence varies between ethnic groups in the UK. Rates of infant death are highest in children of Pakistani origin, and congenital anomalies are the most common cause of death in children younger than 12 in this ethnic group. We investigated the incidence of congenital anomalies in a large multiethnic birth cohort to identify the causes of the excess of congenital anomalies in this community.
  
  
  METHODS
  We obtained questionnaire data from the mothers of children with one or more anomalies from the Born in Bradford study, a prospective birth cohort study of 13,776 babies and their families in which recruitment was undertaken between 2007 and 2011. Details of anomalies were prospectively reported to the study and we cross checked these details against medical records. We linked data for anomalies to maternal questionnaire and clinical data gathered as part of the Born in Bradford study. We calculated univariate and multivariate risk ratios (RRs) with 95% CIs for various maternal risk factors.
  
  
  RESULTS
  Of 11,396 babies for whom questionnaire data were available, 386 (3%) had a congenital anomaly. Rates for congenital anomaly were 305·74 per 10,000 livebirths, compared with a national rate of 165·90 per 10,000. The risk was greater for mothers of Pakistani origin than for those of white British origin (univariate RR 1·96, 95% CI 1·56-2·46). Overall, 2013 (18%) babies were the offspring of first-cousin unions. These babies were mainly of Pakistani origin--1922 (37%) of 5127 babies of Pakistani origin had parents in first-cousin unions. Consanguinity was associated with a doubling of risk for congenital anomaly (multivariate RR 2·19, 95% CI 1·67-2·85); we noted no association with increasing deprivation. 31% of all anomalies in children of Pakistani origin could be attributed to consanguinity. We noted a similar increase in risk for mothers of white British origin older than 34 years (multivariate RR 1·83, 95% CI 1·14-3·00). Maternal education to degree level was protective (0·53, 95% CI 0·38-0·75), irrespective of ethnic origin.
  
  
  CONCLUSIONS
  Consanguinity is a major risk factor for congenital anomaly. The risk remains even after adjustment for deprivation, and accounts for almost a third of anomalies in babies of Pakistani origin. High levels of educational attainment are associated with reduced risk in all ethnic groups. Our findings will be valuable in health promotion and public health, and to those commissioning antenatal, paediatric, and clinical genetic services. Sensitive advice about the risks should be provided to communities at increased risk, and to couples in consanguineous unions, to assist in reproductive decision making.
  
  
  BACKGROUND
  National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care programme.
authors.affiliation: Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK; Department of Genetics, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK. Electronic address: medesh@leeds.ac.uk.
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Neil
authors.initials: N
authors.lastname: Small
authors.forename: Peter C
authors.initials: PC
authors.lastname: Corry
authors.forename: Sam
authors.initials: S
authors.lastname: Oddie
authors.forename: Catherine
authors.initials: C
authors.lastname: Whibley
authors.forename: Emily S
authors.initials: ES
authors.lastname: Petherick
authors.forename: Teena
authors.initials: T
authors.lastname: Malik
authors.forename: Nicole
authors.initials: N
authors.lastname: Pawson
authors.forename: Patricia A
authors.initials: PA
authors.lastname: McKinney
authors.forename: Roger C
authors.initials: RC
authors.lastname: Parslow
mesh_terms: D000328:Adult; D002947:Cities / Q000208:ethnology; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000208:ethnology*; D003241:Consanguinity; D004522:Educational Status; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D010154:Pakistan / Q000208:ethnology; D011446:Prospective Studies; D012307:Risk Factors; D012959:Socioeconomic Factors; D014504:Urban Health; D044465:White People / Q000208:ethnology