Buprenorphine-Naloxone for Pregnant Patients With Opioid Use Disorder

In pregnant patients with opioid use disorder, is buprenorphinenaloxone as safe and effective as buprenorphine?

Buprenorphine-naloxone can be used to treat opioid use disorder in pregnant patients. It has an obstetric safety profile similar to those of alternative treatments for this disorder and is associated with a lower rate of neonatal opioid withdrawal syndrome (NOWS). (Strength of Recommendation: B, consistent meta-analyses not limited to randomized controlled trials [RCTs].)

A 2020 systematic review and meta-analysis identified five retrospective cohort trials with 1,875 pregnant patients receiving various therapies, including buprenorphine-naloxone, for opioid use disorder in pregnancy.¹ Alternative treatments included buprenorphine, methadone, and long-acting opioids.

Compared with other treatment groups, the buprenorphinenaloxone groups had similar rates of full-term delivery (three trials; n = 729; odds ratio [OR] = 1.04; 95% CI, 0.64–1.7), vaginal delivery (three trials; n = 405; OR = 0.87; 95% CI, 0.56–1.34), and neonatal intensive care unit admission (three trials; n = 405; OR = 1.04; 95% CI, 0.68–1.60). Newborns of patients in the buprenorphine-naloxone groups had lower rates of NOWS compared with newborns of patients prescribed other opioid agonist medications (four trials; n = 634; OR = 0.52; 95% CI, 0.36–0.75). Researchers noted that three of the studies had a high risk of bias. This review did not directly compare buprenorphine-naloxone with buprenorphine.

A 2022 systematic review and meta-analysis identified 20 trials (including four RCTs and 16 cohort studies) that evaluated 7,251 pregnant patients with opioid use disorder; the patients were prescribed buprenorphine or methadone as opioid substitution therapy.² Maternal outcomes included treatment adverse effects, maintenance on treatment, illicit drug use, mode of delivery, and death. Neonatal outcomes included stillbirth, birth weight, growth (ie, body length and head circumference at birth, small-for-gestational-age status), gestational age at delivery (ie, prematurity), and opioid withdrawal treatment.

Limited to only RCT data, compared with methadone, buprenorphine was associated with greater birth weight (two trials; n = 149; mean difference = 353 g; 95% CI, 40–645 g), longer body length (two trials; n = 149; weighted mean difference = 2.28 cm; 95% CI, 1.06–3.49 cm), and lower risk of prematurity (risk ratio [RR] = 0.41; 95% CI, 0.18–0.93). In addition, fewer cases of NOWS developed in neonates born to patients treated with buprenorphine compared with methadone (three trials; n = 164; RR = 0.84; 95% CI, 0.45–0.83). Other clinical outcomes were comparable for the methadone and buprenorphine groups. Buprenorphine-naloxone was not evaluated.

A 2022 single-center, retrospective cohort study compared use of buprenorphine-naloxone vs buprenorphine for opioid use disorder in 106 pregnant patients and their newborns.³ Mean age was 30 years. Pregnant patients received treatment with buprenorphine-naloxone (n = 33) or buprenorphine (n = 73) and prenatal care via a single, high-acuity obstetrics program. Patients who transitioned to methadone were excluded.

Researchers gave patients in the intervention group a mean of 12 mg/day of buprenorphine-naloxone at initiation, increasing to 15 mg/day at delivery. The comparison group received a mean of 13 mg/day of buprenorphine at initiation, increasing to 16 mg/day at delivery. Researchers identified return to opioid use during pregnancy with routine urine drug testing. The difference in rate of return to opioid use between the buprenorphine-naloxone and buprenorphine groups was not statistically different (adjusted OR = 1.93; 95% CI, 0.78–4.76), nor was the rate of pharmacologic treatment of NOWS among newborns (adjusted OR = 0.65; 95% CI, 0.27–1.54). The study may have been underpowered to identify a difference, and about one-third of patients in the final buprenorphine-naloxone group transitioned from buprenorphine earlier in pregnancy.