, et al
Phenobarbital and clonidine as secondary medications for neonatal opioid withdrawal syndrome
; doi.

Investigators from multiple institutions conducted a retrospective cohort study comparing outcomes in infants with neonatal opioid withdrawal syndrome (NOWS) treated with either phenobarbital or clonidine as an adjunct to morphine treatment. Study participants were enrolled in the Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Current Experience study, an observational cross-sectional study of infants with NOWS from 30 US hospitals between July 2016 and June 2017. For the current study, only those infants who were born at ≥36 weeks’ gestation, initiated NOWS scoring using the Finnegan or modified Finnegan scoring system in the first 120 hours of life, had documented prenatal opioid exposure, and had first-line treatment with morphine were included. Study participants were grouped into 2 cohorts: those treated with morphine and phenobarbital (M+P) and those treated with morphine and clonidine (M+C). The primary study outcomes were length of morphine treatment, length of hospital stay (LOS), and peak morphine dose. These outcomes were compared between cohorts using ANOVA or chi square tests. Multivariate linear regression was used to assess the independent effect of the different treatment regimens after adjusting for confounding variables. An additional linear mixed model was conducted to account for infants nested within a site.

Among 563 infants included in the study, 180 (32%) received either phenobarbital or clonidine in addition to morphine, with 72 (40%) in the M+P cohort and 108 (60%) receiving M+C. In the bivariate analyses, mean LOS was significantly shorter among those in the M+P cohort than in those receiving M+C (26.4 ±12.4 and 36.5 ±12.6 days, respectively; P <0.0001), and mean length of morphine treatment also was shorter among infants in the M+P cohort (20.8 ±11.4 days vs 28.1 ±11.3 days for those in the M+C cohort; P <0.0001), but peak morphine dose was significantly higher in those treated with M+P (P = 0.01). In the main multivariate analysis, compared to those in the M+C cohort, mean LOS for infants in the M+P cohort was 10.26 days shorter (95% confidence interval [CI], 7.31, 13.21) and mean length of morphine treatment 7.51 days shorter (95% CI, 4.75, 10.27), with no significant difference between groups in peak morphine dose. In the linear mixed model, the difference in LOS remained significantly shorter in the M+P group (P = 0.036), with no statistically significant difference in length of morphine treatment or peak morphine dose between the 2 cohorts.

The authors conclude that among infants with NOWS treated with a secondary medication in addition to morphine, those treated with phenobarbital had a shorter LOS than those administered clonidine as an adjunct therapy without increases in length of morphine treatment or peak morphine dosage.

Dr Mintzer has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use...

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