IMPORTANCE Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established. OBJECTIVE To compare the safety and efficacy of methadone and morphine in NAS. DESIGN, SETTING, AND PARTICIPANTS In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible. A total of 117 infants were randomized to receive methadone or morphine from February 9, 2014, to March 6, 2017. Mothers who declined randomization could consent to data collection and standard institutional treatment. INTERVENTIONS Infants were assessed with the Finnegan Neonatal Abstinence Scoring System every 4 hours and treated with methadone or placebo every 4 hours or morphine every 4 hours. Infants with persistently elevated Finnegan scores received dose increases. Infants who exceeded a predetermined opioid dose received phenobarbital. Dose reductions occurred every 12 to 48 hours when signs of NAS were controlled with therapy, stopping at 20% of the original dose. MAIN OUTCOMES AND MEASURES The primary end point was length of hospital stay (LOS). The secondary end points were LOS attributable to NAS and length of drug treatment (LOT). RESULTS A total of 183 mothers consented to have their infants in the study; 117 infants required treatment. Because 1 parent withdrew consent, data were analyzed on 116 infants (mean [SD] gestational age, 39.1 [1.1] weeks; mean [SD] birth weight, 3157 [486] g; 58 [50%] male). Demographic variables and risk factors were similar except for more prenatal cigarette exposure in infants who received methadone. Adjusting for study site and maternal opioid type, methadone was associated with decreased mean number of days for LOS by 14%

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The effect of allopurinol to inhibit purine metabolism via the xanthine oxidase pathway in neonates with severe, progressive hypoxemia during rescue and reperfusion with extracorporeal membrane oxygenation (ECMO) was examined. Twenty-five term infants meeting ECMO criteria were randomized in a double-blinded, placebo-controlled trial. Fourteen did not receive allopurinol, whereas 11 were treated with 10 mg/kg after meeting criteria and before cannulation, in addition to a 20-mg/kg priming dose to the ECMO circuit. Infant plasma samples before cannulation, and at 15, 30, 60, and 90 min, and 3, 6, 9, and 12 h on bypass were analyzed (HPLC) for allopurinol, oxypurinol, hypoxanthine, xanthine, and uric acid concentrations. Urine samples were similarly evaluated for purine excretion. Hypoxanthine concentrations in isolated blood-primed ECMO circuits were separately measured. Hypoxanthine, xanthine, and uric acid levels were similar in both groups before ECMO. Hypoxanthine was higher in allopurinol-treated infants during the time of bypass studied (p = 0.022). Xanthine was also elevated (p < 0.001), and uric acid was decreased (p = 0.005) in infants receiving allopurinol. Similarly, urinary elimination of xanthine increased (p < 0.001), and of uric acid decreased (p = 0.04) in treated infants. No allopurinol toxicity was observed. Hypoxanthine concentrations were significantly higher in isolated ECMO circuits and increased over time during bypass (p < 0.001). This study demonstrates that allopurinol given before cannulation for and during ECMO significantly inhibits purine degradation and uric acid production, and may reduce the production of oxygen free radicals during reoxygenation and reperfusion of hypoxic neonates recovered on bypass.