辅助生殖技术出生儿童的神经发育不良发生率：来自北欧辅助生殖技术与安全委员会的一项注册研究。

The neurodevelopmental morbidity of children born after assisted reproductive technology: a Nordic register study from the Committee of Nordic Assisted Reproductive Technology and Safety group.

机构信息

Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

出版信息

Fertil Steril. 2022 May;117(5):1026-1037. doi: 10.1016/j.fertnstert.2022.01.010. Epub 2022 Feb 23.

DOI:10.1016/j.fertnstert.2022.01.010

PMID:35216828

Abstract

OBJECTIVE

To assess the risk of neurodevelopmental disorders in singletons born after the use of assisted reproductive technology (ART) compared with singletons born without the use of ART.

DESIGN

Nordic register-based study.

SETTING

Cross-linked data from Medical Birth Registers and National ART and Patient Registers; liveborn singletons in 1995-2014 in Denmark and Finland, 2005-2015 in Norway, and 1995-2015 in Sweden with follow-up to 2014 (Denmark and Finland) or 2015 (Norway and Sweden).

PATIENTS

A total of 5,076,444 singletons: 116,909 (2.3%) born with and 4,959,535 (97.7%) born without the use of ART (non-ART).

INTERVENTIONS

In vitro fertilization, intracytoplasmic sperm injection, and fresh and frozen embryo transfer.

MAIN OUTCOME MEASURES

The primary outcomes (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes) were learning and motor functioning disorders (F80-F83), autism spectrum disorder (F84), attention-deficit/hyperactivity disorder and conduct disorders (F90-F92), and tic disorders (F95). Crude hazard ratios (HRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals were calculated.

RESULTS

Singletons in the ART cohort had a higher adjusted risk of learning and motor functioning disorders (HR, 1.01 [0.96-1.07]; aHR, 1.17 [1.11-1.24]) and a tendency toward a higher risk of autism spectrum disorder (HR, 1.12 [1.04-1.21]; aHR, 1.07 [0.98-1.16]) and attention-deficit/hyperactivity disorder and conduct disorders (HR, 0.82 [0.77-0.86]; aHR, 1.17 [0.99-1.12]) but not of tic disorders (HR, 1.21 [1.06-1.38]; aHR, 1.17 [0.96-1.27]). No differences in risk were found between children born after in vitro fertilization and intracytoplasmic sperm injection or after fresh and frozen embryo transfer.

CONCLUSIONS

Our findings of only small differences in neurodevelopment between ART and non-ART singletons are reassuring and in line with previous studies.

摘要

目的

评估使用辅助生殖技术（ART）后出生的单胎与未使用 ART 后出生的单胎发生神经发育障碍的风险。

设计

北欧基于登记的研究。

设置

来自丹麦和芬兰的医疗出生登记处和全国 ART 与患者登记处的 1995-2014 年、挪威的 2005-2015 年和瑞典的 1995-2015 年的活产单胎数据与随访至 2014 年（丹麦和芬兰）或 2015 年（挪威和瑞典）进行了交叉链接；共纳入 5076444 例单胎：116909 例（2.3%）为 ART 单胎，4959535 例（97.7%）为非-ART 单胎。

干预措施

体外受精、卵胞浆内单精子注射以及新鲜和冷冻胚胎移植。

主要结局测量指标

主要结局（国际疾病分类，第十版）为学习和运动功能障碍（F80-F83）、自闭症谱系障碍（F84）、注意缺陷多动障碍和品行障碍（F90-F92）和抽动障碍（F95）。计算了粗危害比（HRs）和调整后的危害比（aHRs）及其 95%置信区间。

结果

ART 队列中单胎发生学习和运动功能障碍的风险更高（HR，1.01 [0.96-1.07]；aHR，1.17 [1.11-1.24]），自闭症谱系障碍（HR，1.12 [1.04-1.21]；aHR，1.07 [0.98-1.16]）和注意缺陷多动障碍和品行障碍（HR，0.82 [0.77-0.86]；aHR，1.17 [0.99-1.12]）的风险有升高趋势，但抽动障碍（HR，1.21 [1.06-1.38]；aHR，1.17 [0.96-1.27]）无差异。体外受精与卵胞浆内单精子注射或新鲜与冷冻胚胎移植后出生的儿童之间，神经发育风险无差异。