Steinhorn Rachel, McPherson Christopher, Anderson Peter J, Neil Jeffrey, Doyle Lex W, Inder Terrie
Department of Pediatrics, Washington University in St. Louis, St. Louis, MO.
Department of Pharmacy, Brigham and Women's Hospital, Boston, MA; Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA.
J Pediatr. 2015 May;166(5):1200-1207.e4. doi: 10.1016/j.jpeds.2015.02.012.
To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood.
Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine.
At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphine infants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphine children, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed.
Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood.
探讨极早产儿吗啡暴露与从出生至童年中期脑容量及神经发育结局之间的关联。
对维多利亚婴儿脑研究队列中的极早产儿进行观察性研究。从皇家妇女医院新生儿重症监护病房的所有入院患儿中，共招募了230名孕周<30周或出生体重<1250克的婴儿。57名（25%）婴儿在新生儿重症监护病房住院期间，根据主治医生的判断接受了吗啡镇痛。主要结局指标为足月时和7岁时的脑区体积；足月时的神经行为表现；以及2岁和7岁时的认知、运动、情感、行为、沟通和执行功能评分。采用线性回归比较接受和未接受吗啡治疗的参与者的结局。
足月时，接受吗啡治疗的早产儿与未接受吗啡治疗的婴儿灰质损伤发生率相似，但眶额区（左侧P = 0.002，右侧P = 0.01）和膝下区（左侧P = 0.01）的皮质体积有变小的趋势。7岁时，两组之间的皮质体积没有差异。2岁时，暴露于吗啡的儿童比未暴露于吗啡的儿童更易出现行为失调（P = 0.007），但7岁时未观察到吗啡对神经行为结局有不利影响。
新生儿重症监护期间接受的低剂量吗啡镇痛与脑结构的早期改变及短期神经行为问题有关，但这些问题在儿童期并未持续存在。
