Use of naltrexone in treating opioid use disorder in pregnancy.

The mainstay of the management of opioid use disorder in pregnancy is with methadone or buprenorphine medication-assisted treatment. Methadone and buprenorphine are opioid agonist drugs. Naltrexone, an opioid antagonist, is also a medication-assisted treatment option; however, to date, only a few retrospective studies have reported its use in pregnancy. Our study objective was to evaluate prospectively obstetric and newborn outcomes and the maternal/fetal effects of the use of naltrexone as a medication-assisted treatment in pregnant patients with opioid use disorder. We performed a prospective cohort study collecting data on all pregnant women who were treated with naltrexone medication-assisted treatment compared with pregnant women who were treated with methadone or buprenorphine medication-assisted treatment. Based on a sample size calculation, it was determined that for a power of 90, a minimum of 160 study participants (80 in each group) was needed with an alpha of .01 and an expected 60% rate of newborn infants who were treated for neonatal abstinence syndrome in the methadone or buprenorphine medication-assisted treatment group compared with a 30% rate in the naltrexone medication-assisted treatment group. In a random subset of 20 maternal/newborn dyads, blood levels for naltrexone and 6-beta-naltrexol (an active metabolite) were analyzed at delivery. A total of 230 patients were studied: 121 patients with naltrexone medication-assisted treatment compared with 109 patients with methadone or buprenorphine medication-assisted treatment. No differences between groups were seen regarding demographics, the use of comedications/drugs, or obstetric outcomes. For newborn outcomes, the rate of neonatal abstinence syndrome in neonates >34 weeks gestation was significantly lower in the naltrexone medication-assisted treatment group (10/119 [8.4%] vs 79/105 [75.2%]; P<.0001). Multivariate analysis demonstrated that the only significant factor for the rate of neonatal abstinence syndrome was the form of medication-assisted treatment. Of 87 patients who received naltrexone up to delivery, no neonates experienced symptoms of neonatal abstinence syndrome. No maternal relapses occurred in the 7-day no-treatment window before the initiation of naltrexone therapy. No cases of spontaneous abortion or stillbirth occurred in either group. In 64 patients who started naltrexone therapy at ≥24 weeks gestation, no changes were seen in the fetal heart monitor tracing with drug initiation. The incidence of birth anomalies was no different between the groups. Umbilical cord blood and maternal levels for naltrexone and 6-beta-naltrexol matched; no levels were elevated, and values were undetected if naltrexone was discontinued >60 hours before delivery. These study data demonstrate that, in pregnant women who choose to completely detoxify off opioid drugs during gestation, naltrexone, as a continued form of medication-assisted treatment, is a viable option for some pregnant patients who experience opioid use disorder. Naltrexone crosses the placenta, and maternal and fetal levels are concordant. Because naltrexone clears quickly from the maternal circulation, this rapid clearance needs to be addressed with patients. This is important because maternal relapse could occur in a short time-period if the oral drug is discontinued without the knowledge of their healthcare providers. Nonetheless, the drug is well-tolerated by both mother and fetus, and newborn infants do not experience symptoms of neonatal abstinence syndrome if naltrexone medication-assisted treatment is maintained to delivery.

Towers CV ，Katz E ，Weitz B ，Visconti K ... -  《-》

Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women.

Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. Outside of pregnancy, buprenorphine is used in combination with naloxone to reduce opioid abuse and diversion. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Both methadone and buprenorphine are widely used to treat opioid use disorder; however, compared with methadone, buprenorphine is associated with shorter treatment duration, less medication needed to treat neonatal abstinence syndrome (NAS) symptoms, and shorter hospitalizations for neonates. Despite being the standard of care, medication-assisted treatment with methadone or buprenorphine is still underused, making it apparent that more options are necessary. Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies.

Tran TH ，Griffin BL ，Stone RH ，Vest KM ，Todd TJ ... -  《-》

A Retrospective Cohort Study of Birth Outcomes in Neonates Exposed to Naltrexone in Utero: A Comparison with Methadone-, Buprenorphine- and Non-opioid-Exposed Neonates.

Kelty E ，Hulse G 《-》

Neonatal outcomes after fetal exposure to methadone and buprenorphine: national registry studies from the Czech Republic and Norway.

Opioid maintenance treatment (OMT) is recommended to opioid-dependent females during pregnancy. However, it is not clear which medication should be preferred. We aimed to compare neonatal outcomes after prenatal exposure to methadone (M) and buprenorphine (B) in two European countries. Nation-wide register-based cohort study using personalized IDs assigned to all citizens for data linkage. The Czech Republic (2000-14) and Norway (2004-13). [Correction added after online publication on 26 April 2018: The Czech Republic (2000-04) corrected to (2000-14).] PARTICIPANTS: Opioid-dependent pregnant Czech (n = 333) and Norwegian (n = 235) women in OMT who received either B or M during pregnancy and their newborns. We linked data from health registries to identify the neonatal outcomes: gestational age, preterm birth, birth weight, length and head circumference, small for gestational age, miscarriages and stillbirth, neonatal abstinence syndrome (NAS) and Apgar score. We performed multivariate linear regression and binary logistic regression to explore the associations between M and B exposure and outcomes. Regression coefficient (β) and odds ratio (OR) were computed. Most neonatal outcomes were more favourable after exposure to B compared with M, but none of the differences was statistically significant. For instance, in the multivariate analysis, birth weight was β = 111.6 g [95% confidence interval (CI) = -10.5 to 233.6 and β = 83.1 g, 95% CI = -100.8 to 267.0] higher after B exposure in the Czech Republic and Norway, respectively. Adjusted OR of NAS for B compared with M was 0.94 (95% CI = 0.46-1.92) in the Norwegian cohort. Two national cohorts of women receiving opioid maintenance treatment during pregnancy showed small but not statistically significant differences in neonatal outcomes in favour of buprenorphine compared with methadone.

Nechanská B ，Mravčík V ，Skurtveit S ，Lund IO ，Gabrhelík R ，Engeland A ，Handal M ... -  《-》

Comparison of neonatal outcomes in pregnant women undergoing medication-assisted treatment of opioid use disorder with methadone or buprenorphine/naloxone.

Petrich M ，Battin M ，Walker E ，Brown M ，Abdelwahab M ，Ma'ayeh M ，Rood KM ... -  《-》