Buprenorphine pharmacotherapy for the management of neonatal abstinence syndrome in methadone-exposed neonates.

We aimed to compare the outcomes of pharmacotherapy with either buprenorphine or methadone in infants treated for neonatal abstinence syndrome (NAS) secondary to intrauterine exposure to methadone. This is a multi-center, retrospective cohort study to assess length of treatment (LOT), hospital length of stay (LOS), and cumulative opioid exposure between infants treated with either methadone or buprenorphine for NAS secondary to in utero exposure to methadone. Infants delivered at a gestational age ≥35 weeks and a maternal history of opioid-use disorder and/or urine drug screen positive for methadone, and postnatal pharmacotherapy for NAS with either buprenorphine or methadone as first-line opioid replacement therapy, were eligible. Median LOT, LOS, and cumulative opioid exposure were compared between buprenorphine- and methadone-treated infants. A total of 156 infants (48 treated with buprenorphine and 108 with methadone) were identified. The median LOT and LOS for buprenorphine-treated infants was 8 and 13 days compared with 15 and 20 days for methadone-treated infants, respectively, P < .001 for both outcomes. Median cumulative opioid dose in morphine equivalents was 0.6 mg/kg for buprenorphine-treated infants vs 1.05 mg/kg for methadone-treated infants, P < .001. No adverse effects were noted among either group. Of infants treated with buprenorphine, 34 (71%) required the addition of adjunctive pharmacotherapy during the NICU stay, compared with 31 (32%) in the methadone-treated group, P = .0008. However, significantly fewer infants treated with buprenorphine required continuation of therapy beyond discharge as compared with those treated with methadone. The difference is most likely a reflection of the protocols used by the sites. In infants that required pharmacotherapy for NAS secondary to intrauterine exposure to methadone, treatment with buprenorphine, compared with methadone therapy, was associated with better outcomes. If confirmed with prospective data, buprenorphine could be considered first-line therapy for the two medication-assisted treatment regimens recommended by the American College of Obstetricians and Gynecologists.

Early Prediction Tool to Identify the Need for Pharmacotherapy in Infants at Risk of Neonatal Abstinence Syndrome.

OBJECTIVE: To develop a tool to predict the need for pharmacologic treatment of neonatal abstinence syndrome (NAS) within 36 hours from birth in infants at risk for opioid withdrawal. STUDY DESIGN: Retrospective study of infants born at gestation of ≥34 weeks with in utero exposure to opioids during two time periods from January 2013 through October 2016. Period 1 was used to develop a predictive tool for validation during period 2. Birth weight, gestational age, four categories of opioid exposure, and individual scores for 21 withdrawal symptoms from the Modified Finnegan Score at 36 hours of life were recorded. During period 1, a best subsets multiple regression analysis was performed on factors that were associated with pharmacotherapy on univariate analysis. Two tools were designed: one based on three highly predictive symptoms associated with need for pharmacotherapy for NAS and the other incorporating opioid exposure. Sensitivity, specificity, and positive and negative predictive values for the tools were calculated during period 2. RESULTS: The study included 264 infants (period 1, n=143; period 2, n=121). Polysubstance exposure and three withdrawal symptoms present at 36 hours of life that were significantly associated with pharmacotherapy for NAS comprised the tools. The "symptoms only tool" was able to predict that infants with a score <1 would not receive pharmacotherapy, and infants with scores of ≥4 would receive pharmacotherapy with positive predictive values of 90% and 100%, respectively. When opioid exposure was included, the "symptoms + exposure tool" was able to predict that infants with a score of ≤1 would not receive pharmacotherapy and infants with scores of ≥5 would receive pharmacotherapy with positive predictive values of 94% and 86%, respectively. CONCLUSION: An NAS prediction tool combining three clinical signs with and without category of opioid exposure had high positive predictive values for requiring and for not requiring pharmacotherapy. This tool may expedite pharmacotherapy decisions and optimize management for infants at risk for NAS.

A Cohort Comparison of Buprenorphine versus Methadone Treatment for Neonatal Abstinence Syndrome.

OBJECTIVES: To compare the duration of opioid treatment and length of stay among infants treated for neonatal abstinence syndrome (NAS) by using a pilot buprenorphine vs conventional methadone treatment protocol. STUDY DESIGN: This retrospective cohort analysis evaluated infants who received pharmacotherapy for NAS at 6 hospitals in Southwest Ohio from January 2012 through August 2014. A single neonatology provider group used a standardized methadone protocol across all 6 hospitals. However, at one of the sites, infants were managed with a buprenorphine protocol unless they had experienced chronic in utero exposure to methadone. Linear mixed models were used to calculate adjusted mean duration of opioid treatment and length of inpatient hospitalization with 95% CIs in infants treated with oral methadone compared with sublingual buprenorphine. The use of adjunct therapy was examined as a secondary outcome. RESULTS: A total of 201 infants with NAS were treated with either buprenorphine (n = 38) or methadone (n = 163) after intrauterine exposure to short-acting opioids or buprenorphine. Buprenorphine therapy was associated with a shorter course of opioid treatment of 9.4 (CI 7.1-11.7) vs 14.0 (12.6-15.4) days (P < .001) and decreased hospital stay of 16.3 (13.7-18.9) vs 20.7 (19.1-22.2) days (P < .001) compared with methadone therapy. No difference was detected in the use of adjunct therapy (23.7% vs 25.8%, P = .79) between treatment groups. CONCLUSION: The choice of pharmacotherapeutic agent is an important determinant of hospital outcomes in infants with NAS. Sublingual buprenorphine may be superior to methadone for management of NAS in infants with select intrauterine opioid exposures.