title: Associations between inherited thrombophilias, gestational age, and cerebral palsy.
abstract: OBJECTIVE
  This study was undertaken to investigate associations between inherited thrombophilic polymorphisms and cerebral palsy (CP) in a large case-control study.
  
  
  METHODS
  This is a population-based case-control study. Genomic DNA from newborn screening cards of 443 white CP cases and 883 white controls was tested for factor V Leiden (FVL, G1691A), prothrombin gene mutation (PGM, G20210A), and methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C.
  
  
  RESULTS
  MTHFR C677T was associated with an increased risk of developing any CP (32-36 weeks' gestation, homozygous odds ratio [OR] 2.55, 95% CI 1.12-5.74; heterozygous OR 1.91, 95% CI 1.01-3.66). MTHFR C677T was also associated with diplegia at both less than 32 weeks' gestation (homozygous OR 2.76, 95% CI 1.21-6.12) and all gestations (heterozygous OR 1.58 95%, CI 1.02-2.45). For children less than 32 weeks, FVL homozygosity may be associated with an increase in the risk of developing quadriplegia (OR 9.12, 95% CI 0.86-53.71). MTHFR A1298C (heterozygous) was associated with a reduced risk of diplegia developing at 32 to 36 weeks' gestation (OR 0.16, 95% CI 0.02-0.70). There were no associations between any type of CP and thrombophilia for children born 37 weeks or greater. Heterozygous PGM and homozygous MTHFR C677T combined were associated with quadriplegia at all gestational ages (OR 5.33, 95% CI 1.06-23.25).
  
  
  CONCLUSIONS
  MTHFR C677T approximately doubles the risk of CP in preterm infants. A combination of homozygous MTHFR C677T and heterozygous PGM increases the risk of quadriplegia 5-fold at all gestational ages.
authors.affiliation: Department of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, South Australia. gibsonc@mail.wch.sa.gov.au
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Gibson
authors.forename: Alastair H
authors.initials: AH
authors.lastname: MacLennan
authors.forename: William M
authors.initials: WM
authors.lastname: Hague
authors.forename: Eric A
authors.initials: EA
authors.lastname: Haan
authors.forename: Kevin
authors.initials: K
authors.lastname: Priest
authors.forename: Annabelle
authors.initials: A
authors.lastname: Chan
authors.forename: Gustaaf A
authors.initials: GA
authors.lastname: Dekker
mesh_terms: D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000097:blood / Q000209:etiology*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000097:blood / Q000209:etiology*; D019851:Thrombophilia / Q000097:blood / Q000150:complications* / Q000235:genetics*