Ohls Robin K, Cannon Daniel C, Phillips John, Caprihan Arvind, Patel Shrena, Winter Sarah, Steffen Michael, Yeo Ronald A, Campbell Richard, Wiedmeier Susan, Baker Shawna, Gonzales Sean, Lowe Jean
Departments of Pediatrics,
Internal Medicine.
Pediatrics. 2016 Mar;137(3):e20153859. doi: 10.1542/peds.2015-3859. Epub 2016 Feb 15.
We previously reported improved neurodevelopmental outcomes at 2 years among infants treated with the erythropoiesis-stimulating agents (ESAs) darbepoetin alfa (darbepoetin) or erythropoietin. Here we characterize 4-year outcomes.
Former preterm infants randomly assigned to receive darbepoetin (10 μg/kg, once per week), erythropoietin (400 U/kg, 3 times/week), or placebo through 35 weeks' postconceptual age were evaluated at 3.5 to 4 years of age. For comparison, healthy children formerly delivered full term (term controls [TCs]) were also recruited. All participants were assessed by using measures of full-scale IQ (FSIQ) and general language from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, and an overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory. Rates of neurodevelopmental impairment were compared across groups.
Multivariate analysis of variance compared children randomly assigned to ESAs (n = 39), placebo (n =14), and TCs (n = 24). FSIQ and performance IQ were significantly higher in the ESA group than in the placebo group (FSIQ: 91.1 ± 17.5 vs 79.2 ± 18.5, P = .036; performance IQ: 93.0 ± 17.0 vs 79.5 ± 19.5, P = .018). Follow-up analyses revealed that the children receiving ESAs performed better than those who received placebo on executive function tasks. The ESA group's performance was below that of TCs, but the results did not reach significance on executive function. The incidence of neurodevelopmental impairment was greater in the placebo group than in the ESA group.
ESA-treated infants had better cognitive outcomes and less developmental impairment at 3.5 to 4 years of age compared with placebo-treated infants. ESAs show promise in improving long-term cognitive outcomes of infants born prematurely.
我们之前报道过,接受促红细胞生成素(ESA)治疗的婴儿在2岁时神经发育结局有所改善,其中促红细胞生成素包括α-达贝泊汀(darbepoetin)或促红细胞生成素。在此,我们对4岁时的结局进行了描述。
将曾是早产儿且被随机分配接受达贝泊汀(10μg/kg,每周1次)、促红细胞生成素(400U/kg,每周3次)或安慰剂治疗直至孕龄35周的婴儿在3.5至4岁时进行评估。为作比较,还招募了曾足月出生的健康儿童(足月对照[TC])。所有参与者均使用韦氏学前及初小儿童智力量表第三版中的全量表智商(FSIQ)和语言综合量表进行评估,并基于评估抑制控制和空间工作记忆的测试对执行功能进行整体测量。比较各组神经发育障碍的发生率。
方差多变量分析对随机分配至促红细胞生成素组(n = 39)、安慰剂组(n = 14)和足月对照组(n = 24)的儿童进行了比较。促红细胞生成素组的FSIQ和操作智商显著高于安慰剂组(FSIQ:91.1±17.5对79.2±18.5,P = 0.036;操作智商:93.0±17.0对79.5±19.5,P = 0.018)。后续分析显示,接受促红细胞生成素治疗的儿童在执行功能任务上的表现优于接受安慰剂治疗的儿童。促红细胞生成素组的表现低于足月对照组,但在执行功能方面结果未达到显著差异。安慰剂组神经发育障碍的发生率高于促红细胞生成素组。
与接受安慰剂治疗的婴儿相比,接受促红细胞生成素治疗的婴儿在3.5至4岁时具有更好的认知结局和更少的发育障碍。促红细胞生成素在改善早产婴儿的长期认知结局方面显示出前景。