Risk for Fetal Loss Early in Pregnancy Not Greater With Noninsulin vs Insulin Therapy

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Compared with women with type 1 diabetes, women with type 2 diabetes had a higher risk for miscarriages but a lower prevalence of malformations.
Compared with women with type 1 diabetes, women with type 2 diabetes had a higher risk for miscarriages but a lower prevalence of malformations.

Women diagnosed with diabetes treated with noninsulin antidiabetic agents early in pregnancy compared with women treated with insulin may not be at a higher risk for fetal loss or major congenital malformations, according to a study published in Diabetes, Obesity, and Metabolism. 

Researchers conducted a nested cohort study and recruited 1194 women from within The Health Improvement Network (THIN) to evaluate the association between the use of noninsulin antidiabetic medications vs insulin in the first trimester of pregnancy, as well as the risk for miscarriages, stillbirths, and major structural malformations in these two groups.

A total of 311 women studied were on noninsulin antidiabetic agents and 883 were on insulin therapy.

Study results found the number of miscarriages and stillbirths to be higher in pregnant women with diabetes compared with women without diabetes (15.9% and 1.5% vs 10.5% and 0.4%, respectively). In addition, the frequency of malformations was higher in women with diabetes compared with women without diabetes (7.4% vs 2.8%, respectively), with cardiac malformations being the most common malformation observed (3.2% vs 0.8%, respectively), followed by genital anomalies (1.1% vs 0.3%, respectively). 

Women with type 1 diabetes (T1D) were less likely to have a miscarriage compared with women with type 2 diabetes (T2D) (12.8% vs 20.5%, respectively), however women with T1D more commonly had children with major malformations compared with women with T2D (9.2% vs 4.0%, respectively) with odds ratio [OR] after adjustment of 3.16 (95% CI, 2.29-4.35) and 0.96 (95% CI, 0.52-1.77), respectively. 

When the frequency of malformations studied was compared to pre-pregnancy glycated hemoglobin (HbA1c) levels, it was found that women with levels >7% had a frequency of 12.8%, while women with levels <7% had a frequency of 2.7%.  Women with poor glycemic control compared with women with good pre-pregnancy glycemic control were found to have a risk for malformation (OR 4.29; 95% CI, 1.23-14.91). 

Women placed on noninsulin antidiabetic medications, with or without insulin, during their first trimester were found to have a significantly higher risk for miscarriage compared with women only on insulin (21.9% vs 13.3%, respectively); however, these results decreased significantly after adjustment for diabetes and pre-pregnancy glycemic control (OR 1.19; 95% CI, 0.75-1.89).  Further, a lower prevalence of births with major malformations was observed in women treated with noninsulin antidiabetic agents with or without insulin (2.6%), compared with women treated with insulin alone (9.6%) (adjusted OR 0.25%; 95% CI, 0.08-0.88). 

Researchers concluded that women with pre-gestational diabetes compared with women without diabetes had a 60% higher risk for having a miscarriage, 3 times higher risk for having a stillbirth, and 2 times higher risk for having a child with a major malformation. Women on noninsulin antidiabetic medications compared with women on insulin alone had similar rates of miscarriage and stillbirths; however, women on noninsulin antidiabetic medications had a lower risk for malformations. Finally, malformation rates were higher in women with poor glycemic control compared with women with good preconception glycemic control.  Researchers also noted that adverse pregnancy outcomes can vary in women with pre-gestational T1D and T2D.  When prescribing noninsulin antidiabetic medications and insulin to women who are pregnant or planning to become pregnant, clinicians should consider the adverse outcomes associated with these medications, and provide appropriate education to women regarding the overall risks to the fetus and pregnancy while they are receiving these medications or treatments.

Reference

Cea-Soriano L, García-Rodríguez LA, Brodovicz KG, Gonzalez EM, Bartels DB, Hernández-Díaz S.  Safety of non-insulin glucose-lowering drugs in pregnant women with pre-gestational diabetes: A cohort study [published online March 2, 2018].  Diabetes Obes Metab. doi:10.1111/dom.13275

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