Ten Hove Christine H, Vliegenthart Roseanne J, Te Pas Arjan B, Brouwer Emma, Rijken Monique, van Wassenaer-Leemhuis Aleid G, van Kaam Anton H, Onland Wes
Department of Neonatology, Emma Children's Hospital, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
Neonatology. 2016;110(1):21-6. doi: 10.1159/000444006. Epub 2016 Mar 12.
Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP).
To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established.
From a retrospective cohort of preterm infants with a gestational age (GA) <30 weeks and/or a birth weight <1,250 g, born between 2000 and 2010, infants treated with doxapram (n = 142) and a nontreated control group were selected (n = 284). Patient characteristics and clinical and neurodevelopmental outcome data at 24 months' corrected age were collected. Neurodevelopmental delay (ND) was defined as having a Mental or Psychomotor Developmental Index (MDI/PDI) <-1 standard deviation (SD), cerebral palsy, or a hearing or visual impairment. Odds ratios (OR) were calculated using multiple logistic regression analyses adjusting for potential confounders.
Infants treated with doxapram had a lower GA compared to controls. The number of infants with a MDI or PDI <-1 SD was not different between the groups. The risk of the combined outcome death or ND was significantly lower in the doxapram group after adjusting for confounding factors (OR = 0.54, 95% CI: 0.37, 0.78). Doxapram-treated infants had a higher risk of bronchopulmonary dysplasia and patent ductus arteriosus, but a lower risk of spontaneous intestinal perforation. All other morbidities were not different between the groups.
This study suggests that doxapram is not associated with an increased risk of ND. These findings need to be confirmed or refuted by a large, well-designed, placebo-controlled randomized trial.
多沙普仑已被提倡用于治疗早产儿持续性呼吸暂停（AOP）。
鉴于多沙普仑的安全性仍有待确定，评估其对早产儿长期神经发育结局的影响。
从2000年至2010年间出生的胎龄（GA）<30周和/或出生体重<1250g的早产儿回顾性队列中，选取接受多沙普仑治疗的婴儿（n = 142）和未治疗的对照组（n = 284）。收集矫正年龄24个月时的患者特征以及临床和神经发育结局数据。神经发育延迟（ND）定义为智力或精神运动发育指数（MDI/PDI）<-1个标准差（SD）、脑性瘫痪或听力或视力障碍。使用多因素逻辑回归分析计算比值比（OR），并对潜在混杂因素进行校正。
与对照组相比，接受多沙普仑治疗的婴儿GA较低。两组间MDI或PDI<-1 SD的婴儿数量无差异。校正混杂因素后，多沙普仑组死亡或ND联合结局的风险显著降低（OR = 0.54，95%CI：0.37，0.78）。接受多沙普仑治疗的婴儿患支气管肺发育不良和动脉导管未闭的风险较高，但患自发性肠穿孔的风险较低。两组间所有其他疾病无差异。
本研究表明多沙普仑与ND风险增加无关。这些发现需要通过大型、设计良好的安慰剂对照随机试验来证实或反驳。
