BACKGROUND AND PURPOSE:

• Pregnant women with pregestational diabetes (DM type 1 or 2) will often be treated with insulin analogues, which appear to provide better control and outcomes compared to human insulin
• However, there have been very limited data as to whether there are any associations between birth defects and use of insulin analogues in the first trimester
• Wang et al. (BMJ Open 2018) compared the heart anomalies in fetuses exposed to either insulin analogues or human insulin in mothers with gestational diabetes mellitus

METHODS:

• Population-based retrospective cohort study
  • Based on the EUROCAT database
• Participants: Women with pregestational diabetes who were referred to hospitals in the region of study and were delivered between 1996 and 2012
• Exposure (in first trimester) definition
  • Human insulin only (reference)
  • Insulin analogue only
  • Both human insulin and insulin analogue
• Primary outcome: Risk of non-chromosomal major congenital anomaly fetus and infant
• Secondary outcome: Congenital heart defects

RESULTS:

• Final study cohort included 1634 pregnancies
• During the first trimester:
  • 870 fetuses (52.4%) were exposed to human insulin only
  • 397 fetuses (23.9%) to insulin analogues only
  • 394 fetuses (23.7%) to both human insulin and insulin analogues
• Mean HbA1c value in the first trimester were higher in human insulin group and less likely to be in the 44-53 mmol/mol (6.2% – 7.0%) range (P<0.001)
• The risk of major congenital anomaly in fetuses exposed to insulin analogues only was lower than those exposed to human insulin only
  • Human insulin only: 70 (8.0%) fetuses
  • Insulin analogue: 15 (3.8%) fetuses
  • Both human and analogue: 19 (4.8%) fetuses
• The relative risk for overall birth defects adjusted for glycemic control and region was 0.56 (95% CI 0.29 to 1.06) and not significant
• However, exposure to insulin analogues only was associated with reduced risk for congenital heart defects
  • Adjusted relative risk 0.14 (95% CI 0.03 to 0.62)

CONCLUSION:

• Exposure to insulin analogues in the first trimester did not increase the risk of major congenital anomaly compared with exposure to human insulin
• There is possibly a lower risk of congenital heart defects among fetuses exposed to insulin analogues

Learn More – Primary Sources:

Insulin analogues use in pregnancy among women with pregestational diabetes mellitus and risk of congenital anomaly: a retrospective population-based cohort study

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