• 纳入丹麦国家数据库243万新生儿数据,随访40年,母亲糖尿病组(DM)包括孕前诊断糖尿病和孕期糖尿病;
  • 总体上看,DM组后代发生心血管疾病(CVD)的风险增高1.29倍,其中心力衰竭1.45倍,高血压疾病1.78倍,深静脉血栓1.82倍,肺栓塞1.91倍;
  • 非DM组40年累积患病率为13.07%,比DM组低4.72%;
  • 孕前诊断糖尿病、孕期糖尿病分别使后代CVD风险提高1.34、1.19倍;
  • 母亲DM同时伴有并发症或者CVD的对后代的影响更大。

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



2019-12-04, Article

Abstract & Authors:展开

Objective : To evaluate the associations between maternal diabetes diagnosed before or during pregnancy and early onset cardiovascular disease (CVD) in offspring during their frst 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.

First Authors:
Yongfu Yu

Correspondence Authors:
Guoyou Qin

All Authors:
Yongfu Yu,Onyebuchi A Arah,Zeyan Liew,Sven Cnattingius,Jørn Olsen,Henrik Tof Sørensen,Guoyou Qin,Jiong Li