上海交通大学医学院秦国友课题组在研究中取得进展。他们对妊娠期糖尿病和后代心血管疾病早期发作的关联性进行了分析，并随访40年。这一研究成果于2019年12月4日发表在国际顶尖学术期刊《英国医学杂志》上。

研究组在丹麦国家健康登记处进行了一项基于人群的队列研究。1977-2016年间，对丹麦2432000名没有先天性心脏病的婴儿进行随访，一直持续到首次确诊心血管疾病（CVD）、死亡、移民，截至2016年12月31日。

在40年的随访中，1153名糖尿病母亲和91311名无糖尿病母亲的后代确诊CVD。糖尿病母亲的后代有29%早发CVD，非糖尿病母亲的后代在40岁时的累积发病率为13.07%。孕前糖尿病和妊娠期糖尿病均与后代CVD发病率呈正相关。

研究组还发现特异性早发CVD的发病率增加，尤其是心力衰竭、高血压、深静脉血栓形成和肺栓塞。从儿童期至成年再到40岁，不同年龄组的CVD发病率均有所增加。有糖尿病并发症母亲的后代发病率增加更为明显。糖尿病和合并CVD的母亲后代早发CVD的风险较高。

综上，糖尿病母亲，特别是有CVD史或糖尿病并发症的母亲，其后代从儿童期到成年早期，早发CVD发病率增加。对育龄妇女糖尿病的预防、筛查和治疗有助于降低下一代CVD风险。

附：英文原文

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

Author: Yongfu Yu, Onyebuchi A Arah, Zeyan Liew, Sven Cnattingius, Jrn Olsen, Henrik Toft Srensen, Guoyou Qin, Jiong Li

Issue&Volume: 2019/12/04

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.

DOI: 10.1136/bmj.l6398

Source: https://www.bmj.com/content/367/bmj.l6398