A Retrospective Cohort Study of Birth Outcomes in Neonates Exposed to Naltrexone in Utero: A Comparison with Methadone-, Buprenorphine- and Non-opioid-Exposed Neonates
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Naltrexone may provide a suitable alternative to methadone and buprenorphine in the treatment of pregnant opioid-dependent women; however, little is known about its effects on neonatal morbidity and mortality.
The aim was to evaluate the health of neonates exposed to naltrexone in utero, and compare it with outcomes in neonates exposed to methadone or buprenorphine and a non-exposed control group.
Sequential cohorts of Western Australian (WA) opioid-dependent women treated with implant naltrexone, oral methadone or sublingual buprenorphine were identified via records from a drug and alcohol clinic (Subiaco, WA) for naltrexone and state prescribing records for methadone and buprenorphine. A control cohort of non-opioid-dependent women was obtained from the WA electoral roll. Identifying information and treatment records for these women were linked against the Midwife Notification System records to identify exposed offspring born between 2001 and 2011. Birth characteristics, congenital anomalies and perinatal mortality for all neonates were extracted from state records.
The birth characteristics of naltrexone-exposed neonates (n = 68) were superior to methadone-exposed neonates (n = 199) in terms of birth size (birth weight, head circumference and length), hospital length of stay (5.5 vs. 11.3 days), and rates of neonatal abstinence syndrome (NAS) (7.5 vs. 51.5%). Naltrexone-exposed neonates were generally not significantly different to buprenorphine-exposed neonates (n = 124), with the exception of significantly lower rates of NAS (7.5 vs. 41.8%) and shorter hospital length of stay (5.5 vs. 8.0 days) in naltrexone-exposed neonates. Compared with the control group of neonates (n = 569), naltrexone-exposed neonates were not significantly different in terms of overall rates of congenital anomalies, stillbirths and neonatal mortality; however, they were significantly smaller (3137.1 vs. 3378.0 g), spent more time in hospital following birth (5.5 vs. 4.3 days) and had higher rates of NAS (7.5 vs. 0.2%). Exposure of neonates to prenatal methadone was associated with a high incidence of neonatal mortality (2.0 vs. 0.2 per 100 live births) and congenital anomalies (10.6 vs. 4.4 per 100 births) compared with the control group. Rates of neonatal mortality and congenital abnormalities in buprenorphine-exposed neonates were not significantly different to the control group.
The use of implant naltrexone during pregnancy was not associated with higher rates of negative birth outcomes compared with methadone- and buprenorphine-exposed neonates. Significantly, naltrexone and buprenorphine were not associated with the high rates of neonatal mortality or congenital anomalies seen in methadone-exposed neonates.
The research team would like to acknowledge the support of the Data Linkage Branch and the data custodians for linking the data, and the Western Australian Department of Health data custodians for providing the data.
Compliance with ethical standards
Conflict of interest
Erin Kelty has no interests to declare; Prof. Gary Hulse has no interests to declare.
Funding for this study was provided by the State Health Research Advisory Council (SHRAC) via a Research Translation Project Grant and a Telethon Institute for Child Health Research Grant.
- 1.Center for substance abuse treatment. Medication-assisted treatment for opioid addiction in in Opioid treatment programs. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2005, (Treatment Improvement Protocol (TIP) Series, No. 43). Medication-assisted treatment for Opioid addiction during pregnancy. https://www.ncbi.nlm.nih.gov/books/NBK64148/.
- 3.WHO. Guidelines for the identification and management of substance use and substance use disorders in pregnancy. Geneva: World Health Organisation; 2014.Google Scholar
- 4.Binder T, Vavrinkova B. Prospective randomised comparative study of the effect of buprenorphine, methadone and heroin on the course of pregnancy, birthweight of newborns, early postpartum adaptation and course of the neonatal abstinence syndrome (NAS) in women followed up in the outpatient department. Neuro Endocrinol Lett. 2008;29(1):80–6.PubMedGoogle Scholar
- 5.Patrick S, Schumacher R, Benneyworth B, Krans E, McAllister J, Davis M. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000–2009. JAMA. 2012;307(18):1934–40.Google Scholar
- 21.Bower C, et al., Report of the Western Australian register of developmental anomolies: 1980–2011. 2012. King Edward Memorial Hospital.Google Scholar
- 22.WHO, CDC, ICBDSR. Birth defects surveillance: a manual for programme managers. Geneva: World Health Organisation; 2014.Google Scholar
- 30.Zedler BK, et al. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction, 2016.Google Scholar