Neonatal Abstinence Syndrome After Methadone or Buprenorphine Exposure

The recommended treatment for opioid dependence in pregnant women is methadone, a full mu-opioid agonist. However, in utero exposure to methadone is associated with neonatal abstinence syndrome (NAS) that is characterized by hyperirritability of the central nervous system and a dysfunctional autonomic nervous system. Management of NAS often requires prolonged hospitalization and pharmacologic intervention. A partial mu-opioid agonist, buprenorphine, has been investigated as an alternative treatment for opioid dependence but relatively few studies of this drug have been conducted in pregnant women. Some prospective open-label and controlled studies suggest that NAS occurring in neonates treated prenatally with buprenorphine was less likely to require treatment than NAS in neonates exposed to prenatal methadone. However, the results of these studies have been inconsistent.This double-blind, randomized, controlled study compared the use of buprenorphine and methadone for management of pregnant women with opioid dependency. The study subjects were 175 pregnant opioid-dependent women enrolled at 8 international sites. A total of 131 of these women completed the trial; 58 (44%) were patients receiving buprenorphine and 73 (56%) were women treated with methadone. The 5 primary neonatal outcomes included the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, length of hospital stay, and head circumference. The P values for all group comparisons were calculated according to prespecified thresholds for significance.More women receiving prenatal buprenorphine (28/86, 33%) discontinued treatment as compared with those receiving prenatal methadone (16/89, 18%). In comparison with methadone, neonates of women treated with prenatal buprenorphine required significantly less morphine (mean dose, 1.1 vs. 10.4 mg; P < 0.009), had a 43% decrease in the hospital stay (10.0 vs. 17.5 days, P < 0.009), and spent 58% less time in the hospital receiving medication for NAS (4.1 vs. 9.9 days, P < 0.003). No significant differences were found between groups for other primary or secondary outcomes, including the number of neonates requiring NAS treatment, the peak NAS score, head circumference, or any other adverse neonatal or maternal outcome.These findings suggest that buprenorphine is an acceptable alternative to methadone for treatment for opioid dependency during pregnancy and with further studies, may actually be