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贝伐单抗注射治疗早产儿视网膜病变后的神经发育结局

Neurodevelopmental Outcomes Following Bevacizumab Injections for Retinopathy of Prematurity.

作者信息

Morin Julie, Luu Thuy Mai, Superstein Rosanne, Ospina Luis H, Lefebvre Francine, Simard Marie-Noëlle, Shah Vibhuti, Shah Prakesh S, Kelly Edmond N

机构信息

Department of Pediatrics and Ophthalmology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada;

School of Rehabilitation, University of Montreal, Montreal, Canada; and.

出版信息

Pediatrics. 2016 Apr;137(4). doi: 10.1542/peds.2015-3218. Epub 2016 Mar 17.

Abstract

BACKGROUND AND OBJECTIVE

Bevacizumab intravitreal injection, a vascular endothelial growth factor inhibitor, is used to treat retinopathy of prematurity (ROP). However, concerns have been raised regarding its systemic absorption and effect on developing tissues including brain. This study compared neurodevelopment at 18 months' corrected age in preterm infants of <29 weeks' gestation treated with bevacizumab versus laser ablation.

METHODS

Data from the Canadian Neonatal Network and the Canadian Neonatal Follow-Up Network databases were retrospectively reviewed. Infants born at <29 weeks' in 2010-2011 with treated ROP were studied. Neurodevelopmental outcome at 18 months was assessed by using neurologic examination and the Bayley Scales of Infant and Toddler Development Third Edition. Regression analyses were performed.

RESULTS

Of 125 treated infants, 27 received bevacizumab and 98 laser. The bevacizumab group, compared with laser, obtained a median Bayley Scales of Infant and Toddler Development Third Edition motor composite score of 81 (interquartile range, 70-91) versus 88 (79-97), a language composite score of 79 (65-97) versus 89 (74-97), and a cognitive score of 90 (80-100) versus 90 (85-100). Difference was detected on the motor score only (P = .02). Odds of severe neurodevelopmental disabilities (Bayley scores <70, severe cerebral palsy, hearing aids, or bilateral blindness) was 3.1 times higher (95% confidence interval: 1.2-8.4) in infants treated with bevacizumab versus laser after adjusting for gestational age, gender, maternal education, Score for Neonatal Acute Physiology-II score, bronchopulmonary dysplasia, sepsis, and severe brain injury.

CONCLUSIONS

Preterm infants treated with bevacizumab versus laser had higher odds of severe neurodevelopmental disabilities. Further investigation on the long-term safety of antivascular endothelial growth factor treatment of ROP is needed.

摘要

背景与目的

玻璃体内注射贝伐单抗,一种血管内皮生长因子抑制剂,用于治疗早产儿视网膜病变(ROP)。然而,人们对其全身吸收以及对包括大脑在内的发育中组织的影响表示担忧。本研究比较了接受贝伐单抗治疗与激光消融治疗的孕龄小于29周的早产儿在矫正年龄18个月时的神经发育情况。

方法

对加拿大新生儿网络和加拿大新生儿随访网络数据库的数据进行回顾性分析。研究对象为2010 - 2011年出生时孕龄小于29周且接受ROP治疗的婴儿。通过神经系统检查和贝利婴幼儿发展量表第三版评估18个月时的神经发育结局,并进行回归分析。

结果

在125例接受治疗的婴儿中,27例接受了贝伐单抗治疗,98例接受了激光治疗。与激光治疗组相比,贝伐单抗治疗组贝利婴幼儿发展量表第三版运动综合得分中位数为81(四分位间距,70 - 91),而激光治疗组为88(79 - 97);语言综合得分分别为79(65 - 97)和89(74 - 97);认知得分分别为90(80 - 100)和90(85 - 100)。仅在运动得分上检测到差异(P = 0.02)。在调整了孕龄、性别、母亲教育程度、新生儿急性生理学评分 - II、支气管肺发育不良、败血症和严重脑损伤等因素后,接受贝伐单抗治疗而非激光治疗的婴儿出现严重神经发育障碍(贝利评分<70、严重脑瘫、助听器或双侧失明)的几率高3.1倍(95%置信区间:1.2 - 8.4)。

结论

与激光治疗相比,接受贝伐单抗治疗的早产儿出现严重神经发育障碍的几率更高。需要进一步研究抗血管内皮生长因子治疗ROP的长期安全性。

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