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辅助生殖技术受孕的早产儿的神经发育结局。

Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology.

机构信息

Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.

Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.

出版信息

Am J Obstet Gynecol. 2021 Sep;225(3):276.e1-276.e9. doi: 10.1016/j.ajog.2021.03.027. Epub 2021 Mar 30.

Abstract

BACKGROUND

There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited.

OBJECTIVE

This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally.

STUDY DESIGN

This retrospective cohort study included inborn, nonanomalous infants, born at <29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment.

RESULTS

Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88).

CONCLUSION

Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at <29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

摘要

背景

人们对通过辅助生殖技术受孕的儿童的发育情况表示担忧。尽管有多项研究调查了辅助受孕的结果,但专门针对通过辅助生殖技术受孕并早产的婴儿的神经发育结果的数据却很有限。

目的

本研究旨在评估和比较通过辅助生殖技术受孕并在 29 周以下胎龄早产的婴儿在 18 至 24 个月纠正胎龄时的神经发育结果,以及通过自然受孕的婴儿的神经发育结果。

研究设计

本回顾性队列研究纳入了在 2010 年 1 月 1 日至 2016 年 12 月 31 日期间在加拿大新生儿随访网络的 10 个诊所中接受过 18 至 24 个月纠正胎龄神经发育评估的、出生时胎龄<29 周的、非畸形的、内在的婴儿。主要结局为 18 至 24 个月时的神经发育障碍,定义为存在以下任何一种情况:脑瘫;贝利 III 认知、运动或语言综合评分<85;感觉神经性或混合性听力损失;单侧或双侧视力障碍。次要结局包括死亡率、死亡率或神经发育障碍复合结局、显著神经发育障碍以及主要结局的各个组成部分。我们在调整后使用双变量和多变量分析比较了通过辅助生殖技术受孕的婴儿和通过自然受孕的婴儿的结局。

结果

在 4863 名合格的新生儿中,有 651 名(13.4%)是通过辅助生殖技术受孕的。辅助生殖组的母亲年龄、教育水平、糖尿病患病率、接受产前皮质激素治疗率和剖宫产率均高于自然受孕组。除了脑室周围出血率较低外(33%[546 例中的 181 例]与 39%[3318 例中的 1284 例];P=.01),两组新生儿发病率和死亡率相似。在 4176 例存活婴儿中,有 3386 例(81%)在 18 至 24 个月的纠正胎龄时进行了随访。在调整胎龄、产前类固醇、性别、小于胎龄、多胎妊娠、分娩方式、母亲年龄、母亲教育、妊娠高血压、母亲糖尿病和吸烟等因素后,多变量逻辑回归显示通过辅助生殖技术受孕与神经发育障碍的几率较低相关(调整后的优势比,0.67;95%置信区间,0.52-0.86),与死亡或神经发育障碍复合结局的几率较低相关(调整后的优势比,0.67;95%置信区间,0.54-0.84)。通过辅助生殖技术受孕与降低贝利 III 认知综合评分<85(调整后的优势比,0.68;95%置信区间,0.48-0.99)和综合语言评分<85(调整后的优势比,0.67;95%置信区间,0.50-0.88)的几率较低相关。

结论

与自然受孕相比,通过辅助生殖技术受孕与 29 周以下胎龄早产婴儿在 18 至 24 个月纠正胎龄时的不良神经发育结局(尤其是认知和语言结局)的几率较低相关。需要进行长期随访研究,以评估这些儿童在达到学龄时的学习障碍和复杂视觉空间及处理技能发展的风险。

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