Davis JM, et al. - In this randomized, double-blind, intention-to-treat trial, the researchers compared the safety and efficacy of methadone and morphine in neonatal abstinence syndrome (NAS). They found that short-term outcomes were better in infants receiving methadone compared with morphine with use of weight- and sign-based treatment for NAS.

Methods

• This investigation was conducted on term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy.
• From February 9, 2014, to March 6, 2017, 117 infants were randomized to receive methadone or morphine.
• Mothers who declined randomization could consent to data collection and standard institutional treatment.
• For this analysis, infants were evaluated 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 and 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.
• Length of hospital stay (LOS) was the primary end point.
• LOS attributable to NAS and length of drug treatment (LOT) were the secondary end points.

Results

• An aggregate of 183 mothers consented to have their infants in the study; 117 infants needed treatment.
• 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) because 1 parent withdrew consent.
• In infants who received methadone, demographic variables and risk factors were similar except for more prenatal cigarette exposure.
• Adjusting for study site and maternal opioid type, methadone was correlated with reduced mean number of days for LOS by 14% (relative number of days, 0.86; 95% CI, 0.74-1.00; P=.046), corresponding to a difference of 2.9 days; 14% reduction in LOS attributable to NAS (relative number of days, 0.86; 95% CI, 0.77-0.96; P=.01), corresponding to a difference of 2.7 days; and 16% reduction in LOT (relative number of days, 0.84; 95% CI, 0.73-0.97; P=.02), corresponding to a difference of 2.3 days.
• In addition, methadone was correlated with decreased median LOS (16 vs 20 days, P=.005), LOS attributable to NAS (16 vs 19 days, P=.005), and LOT (11.5 vs 15 days, P=.009).
• As compared to 170 nonrandomized infants treated with morphine per standard institutional protocols, study infants had better short-term outcomes.