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Insulin analogues use in pregnancy among women with pregestational diabetes mellitus and risk of congenital anomaly: a retrospective population-based cohort study
  1. Hao Wang1,
  2. Ewa Wender-Ozegowska2,
  3. Ester Garne3,
  4. Margery Morgan4,
  5. Maria Loane5,
  6. Joan K Morris6,
  7. Marian K Bakker7,
  8. Miriam Gatt8,
  9. Hermien de Walle7,
  10. Susan Jordan9,
  11. Anna Materna-Kiryluk10,
  12. Vera Nelen11,
  13. Guy Thys11,
  14. Awi Wiesel12,
  15. Helen Dolk13,
  16. Lolkje T W de Jong-van den Berg1
  1. 1 Pharmacoepidemiology and Pharmacoeconomics, University of Groningen, Groningen, The Netherlands
  2. 2 Division of Reproduction, Poznan University of Medical Sciences, Poznan, Poland
  3. 3 Paediatric Department, Hospital Lillebaelt, Kolding, Denmark
  4. 4 Obstetrician & Gynaecologist, Singleton Hospital, Swansea, UK
  5. 5 School of Nursing, Ulster University, Northern Ireland, UK
  6. 6 Queen Mary University of London, London, UK
  7. 7 Faculty of Medical Science, University Medical Centre Groningen, Groningen, The Netherlands
  8. 8 Department of Health Information and Research, Ministry of Health, Valletta, Malta
  9. 9 School of Nursing, Swansea University, Swansea, UK
  10. 10 Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland
  11. 11 Provinciaal Instituut voor Hygiene, Antwerp, Belgium
  12. 12 Birth Registry Mainz Model, Children’s Hospital, University Medical Center of Mainz, Mainz, Germany
  13. 13 Ulster University, Northern Ireland, UK
  1. Correspondence to Dr Hao Wang; hao.wang{at}rug.nl

Abstract

Objectives To evaluate the risk of major congenital anomaly associated with first-trimester exposure to insulin analogues compared with human insulin in offspring of women with pregestational diabetes.

Design and setting A population-based cohort of women with pregestational diabetes (n=1661) who delivered between 1996 and 2012 was established retrospectively from seven European regions covered bythe European Surveillance of Congenital Anomalies (EUROCAT) congenital anomaly registries.

Primary outcome measures The risk of non-chromosomal major congenital anomaly in live births, fetal deaths and terminations for a fetal anomaly exposed to insulin analogues in the first trimester of pregnancy was compared with the risk in those exposed to human insulin only.

Results During the first trimester, 870 fetuses (52.4%) were exposed to human insulin only, 397 fetuses (23.9%) to insulin analogues only and 394 fetuses (23.7%) to both human insulin and insulin analogues. The risk of major congenital anomaly in fetuses exposed to insulin analogues only was lower than those exposed to human insulin only; the relative risk adjusted for glycaemic control and region was 0.56 (95% CI 0.29 to 1.06). The significantly lower risk related to exposure of insulin analogues only was observed in congenital heart defects: adjusted relative risk 0.14 (95% CI 0.03 to 0.62).

Conclusions In this retrospective population-based cohort study across Europe, first-trimester exposure to insulin analogues did not increase the risk of major congenital anomaly compared with exposure to human insulin. A possible lower risk of congenital heart defects among fetuses exposed to insulin analogues only deserves further investigation.

  • diabetes in pregnancy
  • epidemiology
  • maternal medicine

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Footnotes

  • Contributors HW: drafting/revising the manuscript for content; study concept or design; analysis or interpretation of data; acquisition of data; statistical analysis; study supervision or coordination. EW-O: drafting/revising the manuscript for content; analysis or interpretation of data; study supervision or coordination; obtaining funding only for meetings attending. EG: reviewed all drafts of the manuscript for content; study concept or design; analysis or interpretation of data; acquisition of data; study supervision or coordination as Steering Group member; obtaining funding; attended all meetings. MM: drafting/revising the manuscript for content; study concept or design; analysis or interpretation of data; acquisition of data. ML: drafting/revising the manuscript for content; analysis of interpretation of data; acquisition of data; study supervision or coordination. JKM: drafting/revising the manuscript for content; analysis or interpretation of data; statistical analysis. MKB: drafting/revising the manuscript for content; analysis or interpretation of data; acquisition of data. MG: drafting/revising the manuscript for content; acquisition of data. HW: drafting/revising the manuscript for content; acquisition of data. SJ: drafting/revising the manuscript for content; study concept or design; analysis or interpretation of data; acquisition of data; study supervision or coordination; obtaining funding. AM-K: acquisition of data. VN and GT: drafting/revising the manuscript for content; acquisition of data. AW: drafting/revising the manuscript for content; study concept or design; analysis or interpretation of data; acquisition of data; statistical analysis; study supervision or coordination. HD: drafting/revising the manuscript for content; study concept or design; analysis of interpretation of data; statistical analysis; study supervision or coordination; obtaining funding. LTWJ-B: drafting/revising the manuscript for content; study concept or design; analysis or interpretation of data; acquisition of data; study supervision or coordination; obtaining funding; attended all meetings of EUROmediCAT.

  • Funding This study was part of the EUROmediCAT research project (www.euromedicat.eu) which has been supported by the European Commission under the Seventh Framework Programme Grant agreement no 260598.

  • Competing interests EW-O is a member of Polish Novo Nordisk advisory board, she gives lectures and leads workshops organised by Eli Lilly and Novo Nordisk in Poland.

  • Patient consent Not required.

  • Ethics approval Approval was received from an ethical standards committee in each country.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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