Prescriptions for insulin and insulin analogues in children with and without major congenital anomalies: a data linkage cohort study across six European regions

Joanne Given, Joan K Morris, Ester Garne, Elisa Ballardini,, Laia Barrachina-Bonet, Clara Cavero-Carbonell, Mika Gissler, Francesca Gorini, Anna Heino, Sue Jordan, Amanda J. Neville, Anna Pierini, Ieuan Scanlon, Joachim Tan, Stine Kjaer Urhoj, Maria Loane

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Abstract

Are children with major congenital anomalies more likely to develop diabetes requiring insulin therapy, as indicated by prescriptions for insulin, than children without congenital anomalies? The aim of this study is to evaluate prescription rates of insulin/insulin analogues in children aged 0–9 years with and without major congenital anomalies. A EUROlinkCAT data linkage cohort study, involving six population-based congenital anomaly registries in five countries. Data on children with major congenital anomalies (60,662) and children without congenital anomalies (1,722,912), the reference group, were linked to prescription records. Birth cohort and gestational age were examined. The mean follow-up for all children was 6.2 years. In children with congenital anomalies aged 0–3 years, 0.04 per 100 child-years (95% CIs 0.01–0.07) had > 1 prescription for insulin/insulin analogues compared with 0.03 (95% CIs 0.01–0.06) in reference children, increasing ten-fold by age 8–9 years. The risk of > 1 prescription for insulin/insulin analogues aged 0–9 years in children with non-chromosomal anomalies (RR 0.92, 95% CI 0.84–1.00) was similar to that of reference children. However, children with chromosomal anomalies (RR 2.37, 95% CI 1.91–2.96), and specifically children with Down syndrome (RR 3.44, 95% CIs 2.70–4.37), Down syndrome with congenital heart defects (RR 3.86, 95% CIs 2.88–5.16) and Down syndrome without congenital heart defects (RR 2.78, 95% CIs 1.82–4.27), had a significantly increased risk of > 1 prescription for insulin/insulin analogues aged 0–9 years compared to reference children. Female children had a reduced risk of > 1 prescription aged 0–9 years compared with male children (RR 0.76, 95% CI 0.64–0.90 for children with congenital anomalies and RR 0.90, 95% CI 0.87–0.93 for reference children). Children without congenital anomalies born preterm (< 37 weeks) were more likely to have > 1 insulin/insulin analogue prescription compared to term births (RR 1.28, 95% CIs 1.20–1.36). Conclusion: This is the first population-based study using a standardised methodology across multiple countries. Males, children without congenital anomalies born preterm and those with chromosomal anomalies had an increased risk of being prescribed insulin/insulin analogues. These results will help clinicians to identify which congenital anomalies are associated with an increased risk of developing diabetes requiring insulin therapy and allow them to reassure families of children who have non-chromosomal anomalies that their risk is similar to that of the general population.
Original languageEnglish
Pages (from-to)2235-2244
Number of pages10
JournalEuropean Journal of Pediatrics
Volume182
Issue number5
Early online date4 Mar 2023
DOIs
Publication statusPublished (in print/issue) - 31 May 2023

Bibliographical note

Funding Information:
This work was supported by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No 733001, from 1 January 2017 to 31 May 2022. The views presented here are those of the authors only, and the European Commission is not responsible for any use that may be made of the information presented here.

Publisher Copyright:
© 2023, Crown.

Keywords

  • Diabetes
  • Insulin
  • Data linkage
  • population based
  • Cohort Studies
  • Congenital Abnormalities
  • drug utilisation
  • childhood
  • Down syndrome
  • pharmacoepidemiology
  • Cohort study
  • Congenital anomalies
  • Diabetes Mellitus requiring insulin

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