Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Department of Pediatrics, University of British Columbia, BC Children's Hospital Research Institute, Vancouver, BC, Canada.
Pediatr Res. 2023 Aug;94(2):738-746. doi: 10.1038/s41390-023-02536-y. Epub 2023 Mar 1.
We assessed variability of analgesic use across three tertiary neonatal intensive care units (NICUs) accounting for early-life pain, quantified as number of invasive procedures. We also determined whether analgesia exposure modifies associations between early-life pain and neurodevelopment.
Multicenter prospective study of 276 very preterm infants (born <24-32 weeks' gestational age [GA]). Detailed data of number of invasive procedures and duration of analgesia exposure were collected in initial weeks after birth. Eighteen-month neurodevelopmental assessments were completed in 215 children with Bayley Scales for Infant Development-Third edition.
Multivariable linear regressions revealed significant differences in morphine use across sites, for a given exposure to early-life pain (interaction p < 0.001). Associations between early-life pain and motor scores differed by duration of morphine exposure (interaction p = 0.01); greater early-life pain was associated with poorer motor scores in infants with no or long (>7 days) exposure, but not short exposure (≤7 days).
Striking cross-site differences in morphine exposure in very preterm infants are observed even when accounting for early-life pain. Negative associations between greater early-life pain and adverse motor outcomes were attenuated in infants with short morphine exposure. These findings emphasize the need for further studies of optimal analgesic approaches in preterm infants.
In very preterm neonates, both early-life exposure to pain and analgesia are associated with adverse neurodevelopment and altered brain maturation, with no clear guidelines for neonatal pain management in this population. We found significant cross-site variability in morphine use across three tertiary neonatal intensive care units in Canada. Morphine use modified associations between early-life pain and motor outcomes. In infants with no or long durations of morphine exposure, greater early-life pain was associated with lower motor scores, this relationship was attenuated in those with short morphine exposure. Further trials of optimal treatment approaches with morphine in preterm infants are warranted.
我们评估了三个三级新生儿重症监护病房（NICU）在考虑到早期生命疼痛（以侵入性程序的数量衡量）的情况下使用镇痛药的差异，并确定了镇痛暴露是否改变了早期生命疼痛与神经发育之间的关联。
这是一项对 276 名极早产儿（出生时<24-32 周胎龄[GA]）的多中心前瞻性研究。在出生后的最初几周内收集了详细的侵入性程序数量和镇痛暴露持续时间的数据。在 215 名接受贝利婴幼儿发展量表第三版测试的儿童中完成了 18 个月的神经发育评估。
多变量线性回归显示，在给定的早期生命疼痛暴露情况下，不同地点的吗啡使用存在显著差异（交互作用 p<0.001）。早期生命疼痛与运动评分之间的关联因吗啡暴露时间的不同而不同（交互作用 p=0.01）；在无或长（>7 天）暴露的婴儿中，早期生命疼痛与运动评分较差相关，但在短暴露（≤7 天）的婴儿中则没有。
即使考虑到早期生命疼痛，在极早产儿中也观察到吗啡暴露的明显跨站点差异。在吗啡短暴露的婴儿中，早期生命疼痛与不良运动结局之间的负相关关系减弱。这些发现强调了需要进一步研究早产儿的最佳镇痛方法。
在极早产儿中，早期生命暴露于疼痛和镇痛都与不良的神经发育和改变的大脑成熟有关，而对于该人群的新生儿疼痛管理没有明确的指南。我们发现加拿大三个三级新生儿重症监护病房之间在吗啡使用方面存在显著的跨站点差异。吗啡的使用改变了早期生命疼痛与运动结果之间的关联。在无或吗啡暴露时间较长的婴儿中，早期生命疼痛与较低的运动评分相关，而在吗啡暴露时间较短的婴儿中，这种关系减弱。需要进一步研究在早产儿中使用吗啡的最佳治疗方法。
