Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (−0.5 SD [95% CI: −0.7, −0.2]), lighter (−0.6 SD [−0.9, −0.3]) and have lower skinfold thicknesses (e.g. −14% [−24%, −3%] suprailiac), and blood pressure (−3 mmHg [−6, −0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.

辅助生殖技术 (ART) 的使用越来越多，但人们对 ART 受孕后代的长期健康状况知之甚少。比较组的选择不力和机制描述不明确阻碍了当前的理解。在一项前瞻性队列（新加坡成长走向健康结果；GUSTO；临床试验 ID：NCT01174875）中，包括 83 名 ART 受孕和 1095 名自然受孕的单身人士，我们评估了 ART 对人体测量、血压、血清代谢生物标志物和脐带血的影响。通过模拟基于机器学习的估计器支持的实用试验来实现组织 DNA 甲基化。我们发现 ART 受孕的孩子个子矮 (−0.5 SD [95% CI: −0.7, −0.2])，体重轻 (−0.6 SD [−0.9, −0.3])，皮褶厚度也较低（例如 −14% [ -24%, -3%] 上血压）和 6-6.5 岁时的血压（-3 mmHg [-6, -0.5] 收缩压），代谢生物标志物没有明显差异。差异不能用父母人体测量或合并症、多基因风险评分、母乳喂养或疾病来解释。我们的模拟表明 ART 与较低的NECAB3 DNA 甲基化密切相关，阴性对照分析表明这些估计是无偏的。然而，甲基化变化似乎并不介导观察到的儿童表型差异。