The opioid neonatal abstinence syndrome (NAS) is a condition of withdrawal symptoms after utero exposure to opioids. Sublingual buprenorphine shows promise as a new treatment in NAS. This trial will investigate the safety and tolerability of sublingual buprenorphine in infants exposed to both opioids and benzodiazepines in utero or with exposure of opioids in those who are breastfeeding.

Infants with in utero exposure to opioids often require therapy with morphine for an extended period. In a clinical trial, sublingual buprenorphine reduced this treatment period by ~30%. However, infants with both opioid and benzodiazepine exposure were not included in the trial. This study will test the safety and tolerability of sublingual buprenorphine in infants with in utero exposure to benzodiazepines or who are breastfeeding.

Inclusion Criteria:

1. ≥ 37 weeks gestation
2. Exposure to opioids in utero
3. Demonstration of signs and symptoms of neonatal abstinence syndrome requiring treatment
4. Exposure to benzodiazepines in utero and/or receiving breast milk. Benzodiazepine use is defined as maternal use in the past 30 days, and/or receipt of benzodiazepines by prescription (as determined by self-report or intake urine) by the mother 30 days prior to birth.

Exclusion Criteria:

1. Major congenital malformations and/or intrauterine growth retardation defined as birth weight <2200 gm
2. Medical illness requiring intensification of medical therapy. This includes, but is not limited to suspected sepsis requiring antibiotic therapy.
3. Hypoglycemia requiring treatment with intravenous dextrose
4. Bilirubin >20 mg/dL (The need for phototherapy is not exclusionary)
5. Seizure activity or other neurologic abnormality