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.
In spite of numerous recent outcome studies of extremely low birth weight (ELBW) infants, no data exist on their development prior to term. In this study we traced and compared the neurobehavioral development of 251 ELBW (< 1,000 g) and 240 low birth weight (LBW; 1,000 g–2,500 g) preterms born between 1995 and 2004 from 32 to 37 weeks postconceptional age (PCA), using the Neurobehavioral Assessment of the Preterm Infant (NAPI Korner & Thom, 1990). Compared to the original NAPI cohort of 521 infants (born 1983–1989), the ELBW and LBW infants were at higher medical risk, displayed weaker motor development, a tighter scarf sign and popliteal angle at all or most PCAs, and a weaker cry at older PCAs; they did not differ in irritability and percent asleep ratings. Few differences were noted between the ELBW and LBW groups. Research is now needed to determine whether the 1995 to 2004 NAPI values of ELBW and LBW infants at 32 to 37 weeks PCA are predictive of later outcome of high‐risk preterms.
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