BACKGROUND Some earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC). METHODS AND FINDINGS This was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (<37 weeks 0 days) occurred in 7.9% of children born after ART and 4.8% in children born after SC, and 5.7% versus 3.3% had a low birth weight (<2,500 g). Mean (SD) follow-up time was 8.6 (6.2) years for children born after ART and 14.0 (8.6) years for children born after SC. In total, 135 (0.11%), 645 (0.65%), and 18 (0.01%) children born after ART were diagnosed with cardiovascular disease (ischemic heart disease, cardiomyopathy, heart failure, or cerebrovascular disease), obesity or type 2 diabetes, respectively. The corresponding values were 10,702 (0.14%), 30,308 (0.74%), and 2,919 (0.04%) for children born after SC. In the unadjusted analysis, children born after ART had a significantly higher risk of any cardiovascular disease (hazard ratio [HR] 1.24; 95% CI 1.04-1.48; p = 0.02), obesity (HR 1.13; 95% CI 1.05-1.23; p = 0.002), and type 2 diabetes (HR 1.71; 95% CI 1.08-2.73; p = 0.02). After adjustment, there was no significant difference between children born after ART and children born after SC for any cardiovascular disease (adjusted HR [aHR]1.02; 95% CI 0.86-1.22; p = 0.80) or type 2 diabetes (aHR 1.31; 95% CI 0.82-2.09; p = 0.25). For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. For obesity, there was a small but significant increased risk among children born after ART (aHR 1.14; 95% CI 1.06-1.23; p = 0.001). Important limitations of the study were the relatively short follow-up time, the limited number of events for some outcomes, and that the outcome obesity is often not considered as a disease and therefore not caught by registers, likely leading to an underestimation of obesity in both children born after ART and children born after SC. CONCLUSIONS In this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART. TRIAL REGISTRATION NUMBER ISRCTN11780826.

中文翻译：

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辅助生殖技术后出生的儿童的心血管疾病、肥胖和 2 型糖尿病：一项基于人群的队列研究。

背景 一些较早的研究已经发现辅助生殖技术 (ART) 后出生的儿童心脏代谢危险因素发生显着变化的迹象。大多数这些研究是基于具有高选择偏倚风险的小队列。在这项研究中，我们比较了 ART 后出生的单胎与自然受孕 (SC) 后出生的单胎儿童患心血管疾病、肥胖和 2 型糖尿病的风险。方法和结果 这是一项基于人群的大型队列研究，研究对象是 1984 年至 2015 年间出生在挪威、瑞典、芬兰和丹麦的个人。数据来自国家 ART 和医疗出生登记，并与来自国家患者登记和各自国家的其他基于人口的登记册。总共有 122,429 名儿童在 ART 后出生，7,574 名，包括 SC 后出生的 685 名儿童。ART 的平均 (SD) 母亲年龄为 33.9 (4.3) 岁，SC 的平均 (SD) 年龄为 29.7 (5.2) 岁，67.7% 与 41.8% 为初产妇，45.2% 与 32.1% 受过 12 年以上的教育。7.9% 的 ART 后出生的儿童和 4.8% 的 SC 后出生的儿童发生早产（<37 周 0 天），5.7% 与 3.3% 的出生体重较低（<2,500 g）。ART 后出生的儿童的平均 (SD) 随访时间为 8.6 (6.2) 年，SC 后出生的儿童为 14.0 (8.6) 年。总共有 135 (0.11%)、645 (0.65%) 和 18 (0.01%) 名在 ART 后出生的儿童被诊断出患有心血管疾病（缺血性心脏病、心肌病、心力衰竭或脑血管疾病）、肥胖或 2 型糖尿病， 分别。相应的值为 10,702 (0.14%)、30,308 (0.74%) 和 2,919 (0.14%)。04%) 对于 SC 后出生的儿童。在未经调整的分析中，ART 后出生的儿童患任何心血管疾病的风险显着更高（风险比 [HR] 1.24；95% CI 1.04-1.48；p = 0.02）、肥胖（HR 1.13；95% CI 1.05-1.23； p = 0.002）和 2 型糖尿病（HR 1.71；95% CI 1.08-2.73；p = 0.02）。调整后，ART 后出生的儿童和 SC 后出生的儿童在任何心血管疾病（调整后的 HR [aHR]1.02；95% CI 0.86-1.22；p = 0.80）或 2 型糖尿病（aHR 1.31；95 % CI 0.82-2.09；p = 0.25)。对于任何心血管疾病，95% CI 相当窄，排除了相当大的影响，而 2 型糖尿病的 95% CI 很宽，不排除有临床意义的影响。对于肥胖，ART 后出生的儿童风险虽小但显着增加（aHR 1.14；95% CI 1.06-1.23；p = 0.001）。该研究的重要局限性是随访时间相对较短，某些结果的事件数量有限，并且结果肥胖通常不被视为一种疾病，因此不会被登记册发现，这可能导致对肥胖的低估ART 后出生的孩子和 SC 后出生的孩子。结论 在本研究中，我们观察到 ART 后出生的儿童和 SC 后出生的儿童患心血管疾病或 2 型糖尿病的风险没有差异。对于肥胖，ART 后出生的儿童的风险虽小但显着增加。试用注册号 ISRCTN11780826。该研究的重要局限性是随访时间相对较短，某些结果的事件数量有限，并且结果肥胖通常不被视为一种疾病，因此不会被登记册发现，这可能导致对肥胖的低估ART 后出生的孩子和 SC 后出生的孩子。结论 在本研究中，我们观察到 ART 后出生的儿童和 SC 后出生的儿童患心血管疾病或 2 型糖尿病的风险没有差异。对于肥胖，ART 后出生的儿童的风险虽小但显着增加。试用注册号 ISRCTN11780826。该研究的重要局限性是随访时间相对较短，某些结果的事件数量有限，并且结果肥胖通常不被视为一种疾病，因此不会被登记册发现，这可能导致对肥胖的低估ART 后出生的孩子和 SC 后出生的孩子。结论 在本研究中，我们观察到 ART 后出生的儿童和 SC 后出生的儿童患心血管疾病或 2 型糖尿病的风险没有差异。对于肥胖，ART 后出生的儿童的风险虽小但显着增加。试用注册号 ISRCTN11780826。可能导致 ART 后出生的儿童和 SC 后出生的儿童对肥胖的低估。结论 在本研究中，我们观察到 ART 后出生的儿童和 SC 后出生的儿童患心血管疾病或 2 型糖尿病的风险没有差异。对于肥胖，ART 后出生的儿童的风险虽小但显着增加。试用注册号 ISRCTN11780826。可能导致 ART 后出生的儿童和 SC 后出生的儿童对肥胖的低估。结论 在本研究中，我们观察到 ART 后出生的儿童和 SC 后出生的儿童患心血管疾病或 2 型糖尿病的风险没有差异。对于肥胖，ART 后出生的儿童的风险虽小但显着增加。试用注册号 ISRCTN11780826。