title: Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia.
abstract: BACKGROUND
  The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia.
  
  
  METHODS
  A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case, matched on sex and exact date of birth.
  
  
  RESULTS
  Both early and late blood sampling was associated with increased risk for schizophrenia. Compared to blood sampling at day 5, sampling at days 0 to 4 after birth was associated with an incidence rate ratio (IRR) of 1.46 (95% CI 1.15-1.87) for development of schizophrenia, and sampling at days 6 to 9 and at days 10 to 53 was associated with an IRR of 1.5 (95% CI 1.13-1.98) and 3.00 (95% CI 1.59-5.67), respectively. After adjusting the estimates for place of birth, both parents' psychiatric illness, maternal and paternal age, parents' country of origin, child admission, and parental education and income, the estimates were slightly different. Thus, blood collection at 0-4days was associated with an IRR of 1.27 (95% CI 0.94-1.71), 6-9days 1.31 (95% CI 0.94-1.84) and 10+days 3.52 (95% CI 1.50 to 8.24).
  
  
  CONCLUSIONS
  After adjusting risk estimates for well-known risk factors, delay in sampling of blood for neonatal screening was associated with unexplained increased risk of schizophrenia. Thus, a key finding is that age at test is a proxy for unobserved risk factors for schizophrenia due to unexplained reasons for late blood sampling. Date of sampling will be included in future analyses of genetic and environmental risk factors.
authors: Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Denmark. Electronic address: mn@dadlnet.dk.
authors: Merete
authors: M
authors: Nordentoft
authors: iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Denmark; National Centre for Register-based Research, Aarhus University, Denmark.
authors: Janne Tidselbak
authors: JT
authors: Larsen
authors: iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Denmark; National Centre for Register-based Research, Aarhus University, Denmark.
authors: Carsten Bøcker
authors: CB
authors: Pedersen
authors: Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Denmark.
authors: Holger Jelling
authors: HJ
authors: Sørensen
authors: Danish Centre for Neonatal Screening, Statens Serum Institut, Denmark, Denmark.
authors: Mads Villiam
authors: MV
authors: Hollegaard
authors: Danish Centre for Neonatal Screening, Statens Serum Institut, Denmark, Denmark.
authors: David Michael
authors: DM
authors: Hougaard
authors: iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Denmark; National Centre for Register-based Research, Aarhus University, Denmark.
authors: Preben Bo
authors: PB
authors: Mortensen
authors: iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Denmark; National Centre for Register-based Research, Aarhus University, Denmark.
authors: Liselotte
authors: L
authors: Petersen
mesh_terms: D000367:Age Factors; D018070:Biological Specimen Banks; D001800:Blood Specimen Collection; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology*; D012959:Socioeconomic Factors; D013997:Time Factors
keywords: Schizophrenia genetic environmental epidemiology risk factors