title: Parental age and the risk of isolated cleft lip: a registry-based study.
abstract: OBJECTIVE
  An increasing number of children in high-income countries have older parents. Several studies have suggested that pregnancy outcomes including cleft lip (CL) are associated with high parental age. CL is a relatively common birth defect, and the prevalence is higher in Norway than in most high-income countries.
  
  
  METHODS
  We studied the association of parental age with the risk of isolated CL (with or without cleft palate) in 2,449,218 births from the population-based Medical Birth Registry of Norway in the period from 1967 until 2010. Individuals who had other birth defects or died before the age of three were excluded. Generalized additive models were used to estimate associations across the continuum of parent's age. A baseline risk was calculated, for births in the interquartile range for maternal age (24-31 years) and paternal age (26-34 years).
  
  
  RESULTS
  The baseline risk of isolated CL was 1.15 per 1000. Several analyses were conducted for mother's and father's age. The risk increased with the age of both parents, with risk estimates of 1.27 per 1000 and higher for children of parents at an advanced age. In an interaction analysis, the risk was increased only when the age of both parents was high.
  
  
  CONCLUSIONS
  Our analyses suggest that the risk of fathering an infant with CL increases with advancing age. Additional analyses showed, however, that the risk was increased only when the age of both parents was high.
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. Electronic address: Erik.Berg@igs.uib.no.
authors.forename: Erik
authors.initials: E
authors.lastname: Berg
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Health Registries, Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Rolv T
authors.initials: RT
authors.lastname: Lie
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Plastic Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: Åse
authors.initials: Å
authors.lastname: Sivertsen
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øystein A
authors.initials: ØA
authors.lastname: Haaland
mesh_terms: D000328:Adult; D000367:Age Factors; D002971:Cleft Lip / Q000453:epidemiology*; D002972:Cleft Palate / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D010290:Parents; D011247:Pregnancy; D015995:Prevalence; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
keywords: Birth defect; Cleft lip; Maternal age; Orofacial cleft; Parental age; Paternal age