Infants exposed to opioids during pregnancy are at risk for neonatal opioid withdrawal syndrome (NOWS); however, according to a recent study, the risk is greater in infants exposed to certain opioids, including methadone.
The prevalence of neonatal opioid withdrawal syndrome (NOWS) in the United States increased from 1.2 to 8.8 per 1,000 births between 2000 and 2016. Most studies have looked at risk for withdrawal symptoms across the entire class of opioids; however, a recent study indicates that there are clear differences in risk for NOWS depending on the type of opioid used, seeing the greatest risk in infants exposed to stronger opioid agonists and those with a longer half-life. (Important Note: This study focused only on prescribed opioids and did not include illicit opioid use or the use of opioids to treat opioid use disorder.)
This cohort study analyzed administrative claims data of Medicaid-insured mothers and newborns in 46 states and Washington DC, including 48,202 opioid-exposed pregnancies with liveborn infants. Opioid exposure was defined as the dispensation of two or more opioid prescriptions during pregnancy, within 90 days of delivery.
Among opioid-exposed pregnancies with live newborns, a total of 1069 neonates (2.2%) had NOWS and 559 (1.2%) had severe NOWS. Relative to hydrocodone, opioid withdrawal syndrome was 2- to 3-fold more common in infants exposed to stronger agonists and opioids with a longer half-life: oxycodone (adjusted relative risk or aRR 1.87; 95% CI, 1.66-2.11), morphine (aRR 2.84; 95% CI, 1.30-6.22), and methadone (aRR 3.02; 95% CI, 2.45-3.73).
Implications for Mothers Receiving Medication Assisted Therapy for Opioid Use Disorder
While this study included only mothers using methadone for pain management and did not include infants born to mothers using methadone or buprenorphine for the treatment of opioid use disorder (OUD), the finding of significantly higher rates of NOWS in infants with prenatal exposure to methadone is relevant to the treatment of mothers with OUD.
Buprenorphine (not included in the current study) and methadone are both opioids and have both been shown to be safe and effective treatments for opioid use disorder during pregnancy. Patients must be informed that NOWS may still occur in babies whose mothers receive these medications. Although both medications may be associated with NOWS, the current research does not support stopping or reducing the dose of medication near the time of delivery in order to prevent NOWS, as this may lead to increased illicit drug use and greater risk to the fetus.
Because the postpartum period is a time of increased risk for relapse in women with substance use disorders (SUDs), it is important to continue to provide support and to engage women with opioid use disorders in consistent treatment after delivery. In addition, parenting a child with NOWS is a risk factor for opioid use relapse; thus, it is important to educate women receiving either buprenorphine or methadone that there is a risk of NOWS and to prepare them for this possibility. Similarly it is important to minimize stigma and to educate other health care providers, as well as family members, that NOWS in this setting is not a sign of illicit opioid use.
Ruta Nonacs, MD PhD
Esposito DB, Huybrechts KF, Werler MM, Straub L, Hernández-Díaz S, Mogun H, Bateman BT. Characteristics of Prescription Opioid Analgesics in Pregnancy and Risk of Neonatal Opioid Withdrawal Syndrome in Newborns. JAMA Netw Open. 2022 Aug 1;5(8):e2228588.