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Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia

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Janne Tidselbak Larsen, Research Assistant, National Centre of Register-based Research, Aarhus University

We published a paper in Schizophrenia Research showing that children, who had their blood sample taken for the Danish Neonatal Screening Biobank (DNSB) taken at day 10 after birth or later, had an increased risk of schizophrenia later in life. This strange finding persisted even after control for a long range of possible confounding factors such as socioeconomic status, family history of mental illness or child admission to somatic department right after birth. It indicates that delayed neonatal blood sampling is associated with some hitherto unexplained risk factors for schizophrenia, related to conditions in the child or the parents associated with late blood sampling.

The paper was based on dry blood spots from the DNSB. 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. 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. We applied a case-control design. 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.

Both early and late blood sampling was associated with increased risk for schizophrenia. Compared to blood sampling at day 5, sampling at day 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, sampling at day 6 to 9 and at day 10 to 53 was 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 0-4 day was associated with an IRR of 1.27 (95% CI 0.94-1.71), 6-9 days 1.31 (95% CI 0.94-1.84) and 10+ days 3.52 (95% CI 1.50 to 8.24).

After adjusting risk estimates for well known risk factors and 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.

The article "Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia" was published in Schizophrenia Research 2014 Jan 24 [Epub ahead of print].

Facts about the studies

  • A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register and one control was selected for each case, matched on sex and exact date of birth
  • After controlling for confounders such as early hospitalisation of children, family history of mental disorders, maternal and paternal age, education and income, delayed blood sampling was still associated with increased risk of schizophrenia

Further information

Janne Tidselbak Larsen, Research Assistant, National Centre of Register-based Research, Aarhus University, phone: +45 871 66062, Email: jtl@econ.au.dk 

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