Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease: A Nationwide Cohort Study.
Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease: A Nationwide Cohort Study.
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DOI：
10.1161/circulationaha.115.017465
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发表时间：
2016-06-07
期刊：
影响因子：
37.8
通讯作者：
Melbye M
中科院分区：
文献类型：
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作者：
Øyen N;Diaz LJ;Leirgul E;Boyd HA;Priest J;Mathiesen ER;Quertermous T;Wohlfahrt J;Melbye M
母体糖尿病与后代先天性心脏病（CHD）风险增加有关;然而，因果机制知之甚少。我们在丹麦全国范围内的队列中进一步研究了这种关联。在一项全国性队列研究中，我们确定了1978年至2011年出生的2025727人;其中7296人（0.36%）暴露于母体妊娠前糖尿病。通过使用国家患者登记册和丹麦药房填写的所有处方的个人水平信息来确定妊娠前糖尿病。CHD患者（n= 16325）被分配到胚胎学相关的心脏表型。母亲患有妊娠前糖尿病的后代的CHD患病率为318/10000活产（n=232），而基线风险为80/10000; CHD的校正相对风险为4.00（95%置信区间，3.51-4.53）。这种关联不受出生年份、母亲糖尿病发病年龄或糖尿病病程的影响，与1型（胰岛素依赖型）和2型（胰岛素非依赖型）糖尿病相关的CHD风险无显著差异。有急性糖尿病并发症的母亲所生的人比无并发症的母亲所生的人有更高的CHD风险（相对风险，7.62; 95%置信区间，5.23-10.6，和相对风险，3.49; 95%置信区间，2.91-4.13，分别为P=0.0004）。所有特异性CHD表型均与母亲妊娠前糖尿病相关（相对危险度范围，2.74-13.8）。母亲妊娠前糖尿病导致的CHD风险显著增加既不随时间变化，也不因糖尿病亚型而不同。与急性妊娠前糖尿病并发症的相关性特别强，表明葡萄糖在因果通路中的作用。
Maternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort. In a national cohort study, we identified 2 025 727 persons born from 1978 to 2011; among them were 7296 (0.36%) persons exposed to maternal pregestational diabetes mellitus. Pregestational diabetes mellitus was identified by using the National Patient Register and individual-level information on all prescriptions filled in Danish pharmacies. Persons with CHD (n=16 325) were assigned to embryologically related cardiac phenotypes. The CHD prevalence in the offspring of mothers with pregestational diabetes mellitus was 318 per 10 000 live births (n=232) in comparison with a baseline risk of 80 per 10 000; the adjusted relative risk for CHD was 4.00 (95% confidence interval, 3.51–4.53). The association was not modified by year of birth, maternal age at diabetes onset, or diabetes duration, and CHD risks associated with type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes mellitus did not differ significantly. Persons born to women with previous acute diabetes complications had a higher CHD risk than those exposed to maternal diabetes mellitus without complications (relative risk, 7.62; 95% confidence interval, 5.23–10.6, and relative risk, 3.49; 95% confidence interval, 2.91–4.13, respectively; P=0.0004). All specific CHD phenotypes were associated with maternal pregestational diabetes mellitus (relative risk range, 2.74–13.8). The profoundly increased CHD risk conferred by maternal pregestational diabetes mellitus neither changed over time nor differed by diabetes subtype. The association with acute pregestational diabetes complications was particularly strong, suggesting a role for glucose in the causal pathway.