Neurobehavior of preterm infants at 36 weeks postconception as a function of morphine analgesia

This study evaluated early neurobehavioral outcomes in ventilated preterm infants randomized to receive morphine analgesia or placebo in the Neurological Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial. Eight hundred and ninety-eight infants between 23 and 32 weeks of gestation were randomized to receive preemptive morphine analgesia (morphine) or placebo. Infants also received additional analgesia (AA) with open-label morphine. The Neurobehavioral Assessment of the Preterm Infant (NAPI) was used to evaluate 572 of 793 survivors (72.1%) at 36 weeks of postconceptual age. The Neonatal Medical Index (NMI) was used to evaluate the severity of medical complications. Regression analyses were used to determine the effect of covariates. Infants were equally distributed in morphine and placebo groups with similar neonatal and demographic characteristics. Infants assessed with the NAPI were more likely to have sepsis (p = 0.03), bronchopulmonary dysplasia (p = 0.02), and longer length of stay (p = 0.008). Infants randomized to the morphine group had higher NMI scores (odds ratio [OR]; 95% confidence interval [CI]: 1.75; 1.23 to 2.50; p = 0.002). Use of AA was associated with higher NMI scores (OR; 95% CI: 4.5; 2.9 to 5.9; p < 0.001). Of the NAPI subscales, the (mean ± standard deviation [SD]) popliteal angle cluster scores were significantly higher in the morphine group compared with placebo (51.2 ± 33.2 versus 45.0 ± 33.5; p = 0.03). AA use was associated with lower (mean ± SD) motor scores in the morphine group (48.2 ± 16.1 versus 52.7 ± 19.1; p = 0.03) and with lower popliteal angle cluster scores in both the morphine group (41.5 ± 34.0 versus 59.5 ± 30.1; p < 0.0001) and the placebo group (40.8 ± 36.8 versus 49.4 ± 28.0; p = 0.004). No differences were noted in the other NAPI subscales cluster scores in either subgroup. We conclude that morphine analgesia may result in subtle neurobehavioral differences in premature infants.