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

Abstract

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.

Keywords: buprenorphine; methadone; neonatal abstinence syndrome; opioids; withdrawal.

Figure 1

Patient flow: treatment arm, need for adjunct therapy, and need for therapy at discharge

Figure 2

Length of stay and length of treatment for methadone‐ and buprenorphine‐treated Infants *P < .001

Figure 3

Cumulative opioid exposure for methadone‐ and buprenorphine‐treated Infants *P < .001. Methadone: median = 1.05 mg/kg (MME), IQR = 0.5‐3.94 mg/kg (MME). Buprenorphine: Median = 0.6 mg/kg (MME), IQR = 0.4‐1 mg/kg (MME)