Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Nov 1;144(5):725-732.
doi: 10.1097/AOG.0000000000005722. Epub 2024 Sep 5.

Glycemic Control and Risk of Congenital Malformations in Women With Type 1 Diabetes

Ida Holte Thorius  1 , Janne Petersen, Lise Lotte N Husemoen, Amra C Alibegovic, Mari-Anne Gall, Peter Damm, Elisabeth R Mathiesen
Affiliations
Observational Study

Glycemic Control and Risk of Congenital Malformations in Women With Type 1 Diabetes

Ida Holte Thorius et al. Obstet Gynecol. .

Abstract

Objective: To investigate the association between maternal glycemic control and the risk of congenital malformations in offspring of women with type 1 diabetes and to examine whether there is a hemoglobin A 1C (Hb A 1C ) threshold value at which the risk for malformations increases significantly.

Methods: Analyses were performed on data from a multinational, observational cohort of 1,908 liveborn offspring of women with type 1 diabetes recruited in early pregnancy from 17 countries between 2013 and 2018. Offspring with malformations were identified according to European Surveillance of Congenital Anomalies version 1.4 and categorized as having one or more major malformations or minor malformations exclusively. The association between first-trimester Hb A 1C levels and the risk of congenital malformations was investigated with splines in crude and adjusted logistic regression models.

Results: In total, 11.9% of the offspring (n=227) of women with type 1 diabetes had congenital malformations, including 2.1% (n=40) with at least one severe malformation. Women giving birth to offspring with malformations had a higher prevalence of psychiatric disorders (13.2% vs 7.2%, P <.01), thyroid disorders (33.0% vs 26.7%, P <.05), and folic acid supplementation (87.1% vs 77.7%, P <.01). The Hb A 1C levels in the first trimester were similar (median 6.8% [interquartile range 6.3-7.6%] vs 6.7% [6.2-7.6%], P =.13) compared with women giving birth to offspring without malformations. The spline analysis illustrated a curvilinear association between Hb A 1C levels and the risk of malformations with no clear threshold values. Higher first-trimester Hb A 1C levels were associated with an increased risk of malformations (crude odds ratio [OR] 1.13, 95% CI, 1.01-1.27, adjusted odds ratio [aOR] 1.29, 95% CI, 1.10-1.51) and major malformations (crude OR 1.49, 95% CI, 1.23-1.81, aOR 1.57, 95% CI, 1.15-2.09).

Conclusion: An increased risk for congenital malformations was curvilinearly associated with higher Hb A 1C levels in early pregnancy among women with type 1 diabetes without any threshold values identified.

Clinical trial registration: ClinicalTrials.gov , NCT01892319.

PubMed Disclaimer

Conflict of interest statement

Financial Disclosure Ida Holte Thorius is an industrial PhD student, funded by Novo Nordisk and holds shares in Novo Nordisk. Lise Lotte N. Husemoen, Amra C. Alibegovic, and Mari-Anne Gall are employees of and hold shares in Novo Nordisk. Elisabeth R. Mathiesen has received speakers' fees from Novo Nordisk and has participated in steering committee tasks and guidance involving writing protocols for Novo Nordisk. Elisabeth R. Mathiesen and Peter Damm have participated in several multinational clinical studies on the use of insulin in pregnant women with pre-existing diabetes, in collaboration with Novo Nordisk. Janne Petersen did not report any potential conflicts of interest.

References

    1. Glinianaia SV, Morris JK, Best KE, Santoro M, Coi A, Armaroli A, et al. Long-term survival of children born with congenital anomalies: a systematic review and meta-analysis of population-based studies. PLoS Med 2020;17:e1003356. doi: 10.1371/journal.pmed.1003356 - DOI
    1. Feig DS, Hwee J, Shah BR, Booth GL, Bierman AS, Lipscombe LL. Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: a large, population-based study in Ontario, Canada, 1996–2010. Diabetes Care 2014;37:1590–6. doi: 10.2337/dc13-2717 - DOI
    1. Ludvigsson JF, Neovius M, Söderling J, Gudbjörnsdottir S, Svensson A-M, Franzén S, et al. Periconception glycaemic control in women with type 1 diabetes and risk of major birth defects: population based cohort study in Sweden. BMJ 2018;362:k2638. doi: 10.1136/bmj.k2638 - DOI
    1. Evers IM, de Valk HW, Visser GHA. Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ 2004;328:915. doi: 10.1136/bmj.38043.583160.EE - DOI
    1. Murphy HR, Howgate C, O'Keefe J, Myers J, Morgan M, Coleman MA, et al. Characteristics and outcomes of pregnant women with type 1 or type 2 diabetes: a 5-year national population-based cohort study. Lancet Diabetes Endocrinol 2021;9:153–64. doi: 10.1016/S2213-8587(20)30406-X - DOI

Publication types

Substances

Associated data