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BMJ Open. 2018 Feb 24;8(2):e014972. doi: 10.1136/bmjopen-2016-014972.

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

Author information

1
Pharmacoepidemiology and Pharmacoeconomics, University of Groningen, Groningen, The Netherlands.
2
Division of Reproduction, Poznan University of Medical Sciences, Poznan, Poland.
3
Paediatric Department, Hospital Lillebaelt, Kolding, Denmark.
4
Obstetrician & Gynaecologist, Singleton Hospital, Swansea, UK.
5
School of Nursing, Ulster University, Northern Ireland, UK.
6
Queen Mary University of London, London, UK.
7
Faculty of Medical Science, University Medical Centre Groningen, Groningen, The Netherlands.
8
Department of Health Information and Research, Ministry of Health, Valletta, Malta.
9
School of Nursing, Swansea University, Swansea, UK.
10
Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
11
Provinciaal Instituut voor Hygiene, Antwerp, Belgium.
12
Birth Registry Mainz Model, Children's Hospital, University Medical Center of Mainz, Mainz, Germany.
13
Ulster University, Northern Ireland, UK.

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.

KEYWORDS:

diabetes in pregnancy; epidemiology; maternal medicine

PMID:
29478010
PMCID:
PMC5855464
DOI:
10.1136/bmjopen-2016-014972
[Indexed for MEDLINE]
Free PMC Article

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