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BMJ. 2019 Dec 4;367:l6398. doi: 10.1136/bmj.l6398.

Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up.

Author information

1
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
2
Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), CA, USA.
3
Department of Statistics, College of Letters and Science, University of California, Los Angeles (UCLA), CA, USA.
4
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
5
Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA.
6
Division of Epidemiology, Department of Medicine Solna 17176, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
7
Department of Biostatistics, School of Public Health, and The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai 200032, China gyqin@fudan.edu.cn.
8
Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

OBJECTIVE:

To evaluate the associations between maternal diabetes diagnosed before or during pregnancy and early onset cardiovascular disease (CVD) in offspring during their first four decades of life.

DESIGN:

Population based cohort study.

SETTING:

Danish national health registries.

PARTICIPANTS:

All 2 432 000 liveborn children without congenital heart disease in Denmark during 1977-2016. Follow-up began at birth and continued until first time diagnosis of CVD, death, emigration, or 31 December 2016, whichever came first.

EXPOSURES FOR OBSERVATIONAL STUDIES:

Pregestational diabetes, including type 1 diabetes (n=22 055) and type 2 diabetes (n=6537), and gestational diabetes (n=26 272).

MAIN OUTCOME MEASURES:

The primary outcome was early onset CVD (excluding congenital heart diseases) defined by hospital diagnosis. Associations between maternal diabetes and risks of early onset CVD in offspring were studied. Cox regression was used to assess whether a maternal history of CVD or maternal diabetic complications affected these associations. Adjustments were made for calendar year, sex, singleton status, maternal factors (parity, age, smoking, education, cohabitation, residence at childbirth, history of CVD before childbirth), and paternal history of CVD before childbirth. The cumulative incidence was averaged across all individuals, and factors were adjusted while treating deaths from causes other than CVD as competing events.

RESULTS:

During up to 40 years of follow-up, 1153 offspring of mothers with diabetes and 91 311 offspring of mothers who did not have diabetes were diagnosed with CVD. Offspring of mothers with diabetes had a 29% increased overall rate of early onset CVD (hazard ratio 1.29 (95% confidence interval 1.21 to 1.37); cumulative incidence among offspring unexposed to maternal diabetes at 40 years of age 13.07% (12.92% to 13.21%), difference in cumulative incidence between exposed and unexposed offspring 4.72% (2.37% to 7.06%)). The sibship design yielded results similar to those of the unpaired design based on the whole cohort. Both pregestational diabetes (1.34 (1.25 to 1.43)) and gestational diabetes (1.19 (1.07 to 1.32)) were associated with increased rates of CVD in offspring. We also observed varied increased rates of specific early onset CVDs, particularly heart failure (1.45 (0.89 to 2.35)), hypertensive disease (1.78 (1.50 to 2.11)), deep vein thrombosis (1.82 (1.38 to 2.41)), and pulmonary embolism (1.91 (1.31 to 2.80)). Increased rates of CVD were seen in different age groups from childhood to early adulthood until age 40 years. The increased rates were more pronounced among offspring of mothers with diabetic complications (1.60 (1.25 to 2.05)). A higher incidence of early onset CVD in offspring of mothers with diabetes and comorbid CVD (1.73 (1.36 to 2.20)) was associated with the added influence of comorbid CVD but not due to the interaction between diabetes and CVD on the multiplicative scale (P value for interaction 0.94).

CONCLUSIONS:

Children of mothers with diabetes, especially those mothers with a history of CVD or diabetic complications, have increased rates of early onset CVD from childhood to early adulthood. If maternal diabetes does have a causal association with increased CVD rate in offspring, the prevention, screening, and treatment of diabetes in women of childbearing age could help to reduce the risk of CVD in the next generation.

PMID:
31801789
PMCID:
PMC6891797
DOI:
10.1136/bmj.l6398
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Lundbeck Foundation, the Danish Council for Independent Research and Independent Research Fund Denmark, the Nordic Cancer Union, the Karen Elise Jensens Fond, Novo Nordisk Foundation, the Danish Centre for Strategic Research in Type 2 Diabetes Project (DD2) and the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation, the National Natural Science Foundation of China, NIH grant from the National Center for Advancing Translational Science, the Eunice Kennedy Shriver National Institute of Child Health and Human Development for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

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