Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study

Abstract

OBJECTIVE To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes. RESEARCH DESIGN AND METHODS Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins. RESULTS Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI −0.01, 0.04]; adjusted risk difference −0.003 [95% CI −0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064, 0.000]) and after (−0.036 [95% CI –0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference −0.181 [95% CI −0.300, −0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; −0.139 [95% CI −0.232, −0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference −0.030 [95% CI −0.058, −0.002]), preeclampsia (6.4% vs. 10.0%; −0.036 [95% CI −0.064, −0.007]), and stillbirth (0.4% vs. 1.8%; −0.013 [95% CI −0.024, −0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment. CONCLUSIONS Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

Comparison of treatment with insulin Detemir and NPH in women with gestational diabetes mellitus: glycemic control and pregnancy outcomes

“…[21,22] This was further corroborated by the EVOLVE study, where insulin detemir was compared to other basal insulins (mainly glargine and NPH). [17] Information about insulin detemir in GDM is scarce and originates mainly from studies with both pregestational and gestational diabetes. [15,16,18,24, 26] Herrera et al and Ji et al in their randomized controlled trials comparing insulin detemir versus NPH included both women with GDM and pregestational T2DM who also received short-acting insulin before meals as needed.…”

“…Our results are consistent with the ndings reported by most previous studies. [9,15,16,17,21,24] Only the recent randomized study by Bartal et al reported lower rates of adverse neonatal outcomes but with a higher rate of LGA in the detemir group. [21] To the best of our knowledge this is the largest retrospective study investigating exclusively insulin detemir versus NPH, either of these administered in a single dose at night, in pregnancies with GDM only.…”

“…[16] In a recent multinational prospective cohort study "The Real World EVOLVE Study" in pregnant women with pre-existing diabetes, insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth. [17] Further, a meta-analysis of RCTs comparing insulin detemir versus NPH in 1450 pregnant women with gestational or pregestational diabetes showed signi cant results in favor of insulin detemir concerning maternal hypoglycemic events and gestational age at delivery. [18] Notably, real life data concerning the use of insulin detemir alone in GDM is limited.…”

Major congenital malformations in offspring of women with chronic diseases—impact of the disease or the treatment?

“…However, this may only represent a minority of the cases with major congenital malformations, as observed in women with diabetes mellitus. 38 These factors limit the possibility for solid conclusions. It was a pragmatic choice to only search for cohort studies in the PubMed database published in the last 12 years.…”

Complex Management of Nephrotic Syndrome and Kidney Failure during Pregnancy in a Type 1 Diabetes Patient: A Challenging Case

“…On the mother’s side, this includes a higher risk of kidney disease progression in the presence of full diabetic nephropathy. On the offspring’s side, these include a higher risk of malformations, particularly related to poor maternal glycemic control in the preconception and early pregnancy periods, and of both intrauterine and neonatal death [ 12 , 13 , 14 , 15 ]. Fetal growth may be differently affected by diabetes.…”