Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality: a nationwide combined clinical and register-based cohort study (The EPICOM study)

Diabetologia. 2018 May;61(5):1071-1080. doi: 10.1007/s00125-018-4575-5. Epub 2018 Feb 24.


Aims/hypothesis: The aims of this study were to examine long-term mortality and morbidity rates in mothers with type 1 diabetes, both overall and according to the level of albuminuria prior to pregnancy, the presence of hypertension, pre-eclampsia and periconceptional HbA1c.

Methods: This study was a part of the EPICOM (Environmental Versus Genetic and Epigenetic Influences on Growth, Metabolism and Cognitive Function in Offspring of Mothers with Type 1 Diabetes) study, which is a prospective follow-up study focusing on pregnancies complicated by maternal type 1 diabetes. We carried out a nationwide combined clinical and register-based cohort study of mortality rates and hospital admissions in mothers with diabetes (n = 986) who gave birth between 1992 and 2000. Control mothers (n = 91,441) were women from the background population, matched according to age and year of childbirth. Age at follow-up was 32-66 years.

Results: Mortality rate was increased threefold in mothers with diabetes compared with control mothers (HR 3.41 [95% CI 2.42, 4.81]; p < 0.0001), and was also increased with pre-gestational kidney dysfunction (normoalbuminuria, HR 2.17 [95% CI 1.28, 3.68]; microalbuminuria, HR 3.36 [95% CI 0.82, 13.8]; macroalbuminuria, HR 12.9 [95% CI 5.45, 30.7]). Moreover, the presence of hypertension prior to or at any time during pregnancy and of pre-eclampsia also increased mortality rate (hypertension, HR 4.34 [95% CI 2.13, 8.84]; pre-eclampsia, HR 5.55 [95% CI 2.71, 11.4]). Mortality rate also increased with higher levels of HbA1c in early pregnancy (HbA1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA1c <64 mmol/mol (<8%) in the first trimester and normal pre-gestational urinary albumin excretion rate (n = 517), mortality rate was comparable with that of control mothers. Among mothers with diabetes, mortality rate was associated with HbA1c level: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.52 (95% CI 1.19, 1.94; p = 0.001). In mothers with diabetes, the overall incidence of hospital admissions was more than double (incidence rate ratio [IRR] 2.69 [95% CI 2.59, 2.80]; p < 0.0001) that of control mothers, as were admissions with various diagnoses from 14 out of 19 ICD-10 chapters. Among mothers with diabetes, the IRR for hospital admissions increased with the level of HbA1c: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.07 (95% CI 1.04, 1.10; p < 0.0001).

Conclusions/interpretation: Overall, mothers with type 1 diabetes have a two- to threefold increase in mortality and morbidity rates. HbA1c levels, level of albuminuria around the time of conception, and the presence of hypertension and pre-eclampsia are important risk factors for mortality/morbidity in this cohort. However, it is reassuring that mothers with type 1 diabetes without kidney complications and with HbA1c <64 mmol/mol (<8%) in early pregnancy have a similar survival potential during the period where they are raising their children to that of control mothers from the background population.

Keywords: Albuminuria; HbA1c; Hypertension; Maternal; Morbidity; Mortality; Pre-eclampsia; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albuminuria / complications
  • Case-Control Studies
  • Cognition
  • Cohort Studies
  • Denmark
  • Diabetes Mellitus, Type 1 / mortality*
  • Diabetes Mellitus, Type 1 / therapy*
  • Epigenesis, Genetic
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / metabolism
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Mothers
  • Patient Admission
  • Pregnancy
  • Pregnancy in Diabetics / mortality*
  • Pregnancy in Diabetics / therapy*
  • Registries
  • United States


  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human