Sine Knorr1,2, Svend Juul3, Birgitte Bytoft4,5, Zuzana Lohse6, Tine D Clausen7, Rikke B Jensen5,8, Peter Damm4,5, Henning Beck-Nielsen6, Elisabeth R Mathiesen5,9, Dorte M Jensen6, Claus H Gravholt10,11. 1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark. sine.knorr@clin.au.dk. 2. Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. sine.knorr@clin.au.dk. 3. Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. 4. Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark. 5. Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Department of Endocrinology, Odense University Hospital, Odense, Denmark. 7. Department of Gynaecology and Obstetrics, Nordsjællands Hospital, Hillerød, Denmark. 8. Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. 9. Center for Pregnant Women with Diabetes, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark. 10. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark. 11. Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Abstract
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.
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.
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