The use of opioid drugs in women of childbearing age has become a pressing public health concern.  It is clear that opiate use during pregnancy puts the mother and child at risk; opiate use during pregnancy has been associated with increased risk for oral clefts, neural tube defects, congenital heart defects, and ophthalmic problems.  In addition, obstetrical complications are more common in women using opioids during pregnancy and include maternal cardiac arrest, intrauterine growth restriction, placental abruption, preterm labor, and stillbirth.  While there has been a push to limit use of opiates during pregnancy, our information regarding the reproductive safety of some of the medications used to treat opiate addiction, including buprenorphine and naltrexone, is limited.

A recent study carried out in Western Australia has compared outcomes in neonates exposed to naltrexone (n=68), methadone (n=199) or buprenorphine (n=124) during pregnancy and a non-exposed control group (n=569).

Infants exposed prenatally to either buprenorphine or naltrexone had better outcomes than those exposed to methadone.  Rates of neonatal mortality and congenital abnormalities in naltrexone- and buprenorphine-exposed neonates did not differ significantly from the control group.  However, compared to non-exposed controls, neonates with naltrexone exposure were significantly smaller (3137.1 vs. 3378.0 g), spent more time in the hospital following birth (5.5 vs. 4.3 days) and had higher rates of neonatal abstinence syndrome (7.5 vs. 0.2%).  Compared to non-exposed controls, neonates with buprenorphine exposure spent more time in the hospital following birth (8.0 vs. 4.3 days) and had higher rates of neonatal abstinence syndrome (41.8% vs. 0.2%).

Neonates exposed prenatally to methadone had a higher 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. Methadone-exposed children also had longer hospital length of stay (11.3 days) and higher rates of neonatal abstinence syndrome (51.5%).

While the abuse of opiates during pregnancy carries significant risks, this study indicates that there are also some risks associated with the pharmacologic interventions used to manage opioid dependence.  Reassuringly, this study shows lower rates of congenital malformations and neonatal mortality in children exposed to naltrexone and buprenorphine than observed in women with opiate abuse or dependence.

Other research studies have demonstrated that substance abuse assessment and treatment integrated with prenatal care can improve both maternal and neonatal outcomes among women at high risk for substance abuse.  Although this type of program may seem costly, such programs can be cost-effective in that they reduce potentially costly negative outcomes.  The American College of Obstetrics and Gynecology states that treatment is more effective and less expensive than restrictive policies.  Without integrated programs, women identified with substance abuse problems are typically counseled to stop using and are referred to treaters outside the obstetrics department but they generally donot follow up with substance abuse treatment.  The availability of an expert who specializes in the treatment of substance abuse during pregnancy within the obstetrics clinic helps to remove many of the barriers that can hamper substance abuse treatment and may help to improve outcomes in both the mother and child.

Ruta Nonacs, MD PhD

 

Kelty E, Hulse G.  A Retrospective Cohort Study of Birth Outcomes in Neonates Exposed to Naltrexone in Utero: A Comparison with Methadone-, Buprenorphine- and Non-opioid-Exposed Neonates.  Drugs. 2017 Jul;77(11):1211-1219.

 

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