title: A pilot study of preemptive morphine analgesia in preterm neonates: effects on head circumference, social behavior, and response latencies in early childhood.
abstract: Use of preemptive analgesia in Neonatal Intensive Care Units is recommended for severe and/or invasive procedures. However, the potential long-term consequences of such analgesia, which may be prolonged, are only beginning to be studied. In this pilot study, a subset of subjects previously enrolled in the Neurological Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial was assessed at early childhood. These ex-preterm infants (born at 23-32 weeks of gestational age) required intubation within 72 h postpartum and were randomized to receive either preemptive morphine analgesia (maximum of 14 days) or placebo within 8h post-intubation. At 5-7 years of age, neuropsychological outcomes, morphometrics, adaptive behavior, parent-rated behavior, motivation, and short-term memory were measured. Although overall IQ and academic achievement did not differ between the morphine treated (n=14) and placebo (n=5) groups, preemptive morphine analgesia was associated with distinct differences in other outcome variables. Head circumference of morphine treated children was approximately 7% smaller (Cohen'sd: 2.83, effect size large) and body weight was approximately 4% less (Cohen'sd: 0.81, effect size large); however, height did not differ. In the short-term memory task (delayed matching to sample), morphine treated children exhibited significantly longer choice response latencies than placebo children (3.86±0.33 and 2.71±0.24 s, respectively) (p<0.03) and completed approximately 27% less of the task than placebo children (Cohen'sd: 0.96, effect size large). Parents described morphine treated children as having more social problems, an effect specific to creating and maintaining friendships (Cohen'sd: -0.83, effect size large). Despite the small sample size and the preliminary nature of this study, these results are strongly suggestive of long-lasting effects of preemptive morphine analgesia. A larger investigation with more comprehensive assessments of some of these key features will enable a more complete understanding of the relationship between preemptive morphine treatment and long-term neurocognitive, behavioral, and adaptive outcomes.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR, United States; Department of Pediatrics, Arkansas Children's Hospital, Little Rock, AR 72079, USA. Sherry.Ferguson@fda.hhs.gov
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Ferguson
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Ward
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: R Whit
authors.initials: RW
authors.lastname: Hall
authors.forename: K J S
authors.initials: KJ
authors.lastname: Anand
mesh_terms: D000293:Adolescent; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006257:Head / Q000033:anatomy & histology / Q000254:growth & development*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development*; D008137:Longitudinal Studies; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D059408:Pain Management; D010865:Pilot Projects; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D012919:Social Behavior
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine