Departments of Medical Epidemiology and Biostatistics and.
Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Pediatrics. 2021 Jul;148(1). doi: 10.1542/peds.2020-033183. Epub 2021 Jun 25.
To examine the long-term impact of assisted reproductive techniques (ART) on offspring neurodevelopment, accounting for parental factors and the role of infertility.
Linkage of national registers allowed follow-up of >2.4 million children born in Sweden 1986-2012. Information on ART was retrieved from fertility clinics, medical records, and maternal self-report. Attention-deficit/hyperactivity disorder (ADHD) was identified from specialist diagnosis and/or use of medication through 2018. School performance was assessed from records of ninth year final grade averages (0-20) and eligibility for upper secondary school through 2017.
Children conceived with ART had lower risk of ADHD (hazard ratio 0.83; 95% confidence interval [CI]: 0.80 to 0.87) and did better in school (grade mean difference 1.15; 95% CI: 1.09 to 1.21 and eligibility odds ratio 1.53; 95% CI: 1.45 to 1.63) compared with all other children. Differences in parental characteristics explained and even reversed associations, whereas no disadvantage was seen when the comparison was restricted to children of couples with known infertility (adjusted hazard ratio 0.95; 95% CI: 0.90 to 1.00, adjusted mean difference 0.05; 95% CI: -0.01 to 0.11, and adjusted odds ratio 1.03; 95% CI: 0.96 to 1.10). Among children conceived with ART, there was furthermore no indication that intracytoplasmic sperm injection (compared with standard in vitro fertilization) or frozen (compared with fresh) embryo transfer had any adverse influence.
With this nationwide, long-term follow-up, we provide additional reassurance concerning offspring neurodevelopment after use of ART, finding no indication for concern about risk of ADHD or school performance in adolescence.
探讨辅助生殖技术(ART)对后代神经发育的长期影响,同时考虑到父母因素和不孕因素的作用。
通过国家登记册的关联,对 1986 年至 2012 年在瑞典出生的超过 240 万名儿童进行了随访。ART 信息从生育诊所、医疗记录和母亲自我报告中获取。通过 2018 年的专科诊断和/或药物使用情况,确定注意力缺陷多动障碍(ADHD)。通过 2017 年的第九年级期末成绩平均值(0-20)和高中入学资格,评估学校表现。
与其他所有儿童相比,通过 ART 受孕的儿童患 ADHD 的风险较低(风险比 0.83;95%置信区间[CI]:0.80 至 0.87),在学校表现更好(年级平均差异 1.15;95%CI:1.09 至 1.21 和入学资格优势比 1.53;95%CI:1.45 至 1.63)。父母特征的差异解释甚至逆转了关联,而当比较仅限于夫妇中已知不孕的儿童时,没有发现劣势(调整后的风险比 0.95;95%CI:0.90 至 1.00,调整后的平均差异 0.05;95%CI:-0.01 至 0.11,调整后的优势比 1.03;95%CI:0.96 至 1.10)。在通过 ART 受孕的儿童中,也没有迹象表明胞浆内精子注射(与标准体外受精相比)或冷冻(与新鲜相比)胚胎移植有任何不良影响。
通过这项全国性的长期随访,我们对使用 ART 后后代神经发育提供了额外的保证,没有发现 ADHD 风险或青春期学校表现的担忧迹象。