Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Princess Amalia Department of Pediatrics, Department of Neonatology, Isala Clinics, Zwolle, The Netherlands Department of Pediatrics, VUMC, Amsterdam, The Netherlands Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA Departments of Medical Psychology and Psychotherapy, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Department of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Department of Medical Psychology, Isala Clinics, Zwolle, The Netherlands.
Pain. 2011 Jun;152(6):1391-1397. doi: 10.1016/j.pain.2011.02.017. Epub 2011 Mar 12.
Newborns on ventilatory support often receive morphine to induce analgesia. Animal experiments suggest that this may impair subsequent cognitive and behavioral development. There are sparse human data on long-term effects of neonatal morphine. We aimed to investigate the effects of continuous morphine administered in the neonatal period on the child's functioning. We conducted a follow-up study among 5-year-olds who, as mechanically ventilated neonates, had participated in a placebo-controlled trial on effects of morphine administration on pain and neurologic outcome. They were now tested on intelligence, visual motor integration, behavior, chronic pain, and health-related quality of life. Univariate analyses showed significantly lower overall intelligence quotient (IQ) scores for children who earlier had received morphine, that is, mean 94 (SD 14.5) versus 100 (SD 12.9) for those who received placebo (P = 0.049). Other between-group differences in outcomes were not found. The statistical difference disappeared after correction for treatment condition, open-label morphine consumption over the first 28 days, and a propensity score for clinically relevant co-variables in multiple regression analyses. However, scores on one IQ subtest, "visual analysis," were significantly negatively related to having received morphine and to open-label morphine consumption the first 28 days. The finding of a significant effect of morphine on the "visual analysis" IQ subtest calls for follow-up at a later age focusing on the higher-order neurocognitive functions. Morphine received in the neonatal period has negative effects on the child's cognitive functioning at the age of 5 years which warrants follow-up at a later age.
新生儿在接受通气支持时经常接受吗啡以诱导镇痛。动物实验表明，这可能会损害随后的认知和行为发育。关于新生儿吗啡的长期影响，人类数据很少。我们旨在研究新生儿期给予持续吗啡对儿童功能的影响。我们对 5 岁的儿童进行了随访研究，这些儿童作为机械通气的新生儿，参加了一项关于吗啡给药对疼痛和神经结局影响的安慰剂对照试验。现在对他们进行智力、视觉运动整合、行为、慢性疼痛和健康相关生活质量方面的测试。单变量分析显示，早期接受吗啡的儿童整体智商 (IQ) 得分明显较低，即接受吗啡的儿童平均为 94（标准差 14.5），而接受安慰剂的儿童为 100（标准差 12.9）（P = 0.049）。在其他结果方面，两组之间没有差异。在多元回归分析中，经治疗条件、头 28 天开放标签吗啡使用、以及临床相关协变量的倾向评分校正后，统计学差异消失。然而，在接受吗啡和头 28 天开放标签吗啡使用的情况下，一个 IQ 子测试“视觉分析”的得分明显呈负相关。吗啡对“视觉分析”IQ 子测试的显著影响表明需要在以后的年龄进行随访，重点关注更高阶的神经认知功能。新生儿期接受的吗啡对 5 岁儿童的认知功能有负面影响，需要在以后的年龄进行随访。
