Using certain opioids in pregnancy increases risk for neonatal opioid withdrawal syndrome

More infants who were exposed to strong agonists and opioids with long half-lives developed neonatal opioid withdrawal syndrome compared with those not exposed, recent findings showed.

According to the study, which was published in JAMA Network Open, the prevalence of neonatal opioid withdrawal syndrome (NOWS) in the United States increased from 1.2 to 8.8 per 1,000 hospital births between 2000 and 2016. However, “most studies of the association between opioids and perinatal adverse outcomes assessed opioids as a class,” Daina B. Esposito, MPH, PhD, who was a PhD student at Boston University at the time of the study, and colleagues wrote.

“In this study, we aimed to compare the risk of NOWS across common types of opioids (as defined by agonist strength, half-life and active ingredient) when prescribed as monotherapy during the last 3 months of pregnancy,” they wrote.

Characterizing the cohort

Esposito and colleagues analyzed administrative billing data for 48,202 Medicaid-enrolled mothers and their live-born neonates in 46 states and Washington, D.C., available from Jan. 1, 2000, to Dec. 31, 2014. At least two opioid prescriptions of the same type were dispensed to all mothers within 90 days prior to delivery.

The researchers excluded mothers who had received naltrexone, naloxone or buprenorphine; who received methadone as opioid maintenance therapy for dependence; and who were diagnosed with opioid use disorder or opioid overdose within 270 days before delivery.

Esposito and colleagues compared opioids by agonist strength and half-life to determine the risk for NOWS within 30 days of delivery.

In total, 25,710 neonates were exposed to hydrocodone, 16,202 were exposed to codeine, 4,540 were exposed to oxycodone, 1,244 were exposed to tramadol, 260 were exposed to methadone, 93 were exposed to meperidine, 90 were exposed to hydromorphone and 63 were exposed to morphine. Of these, 1,069 (2.2%) neonates had a NOWS diagnosis and 559 (1.2%) had severe NOWS.

Risk for NOWS

Compared with exposure to hydrocodone, exposure to codeine had a lower risk for NOWS (adjusted RR = 0.57; 95% CI, 0.46-0.7). On the other hand, the risk for NOWS was higher with exposure to oxycodone (aRR = 1.87; 95% CI, 1.66-2.11), hydromorphone (aRR = 2.03; 95% CI, 1.09-3.78), morphine (aRR = 2.84; 95% CI, 1.3-6.22) and methadone (aRR = 3.02; 95% CI, 2.45-3.73) compared with hydrocodone. The risk for NOWS was similar with exposure to tramadol compared with hydrocodone (aRR = 1.06; 0.73-1.56). The researchers called the confidence interval estimates “too wide” for meaningful interpretation when comparing meperidine with hydrocodone (aRR = 1.22; 95% CI, 0.17-8.67).

Analyses by agonist strength revealed that exposure to strong agonists nearly doubled the risk for NOWS compared with weak agonist exposure (aRR = 1.97; 1.78-2.17).

The risk for NOWS was 33% higher with exposure to opioids with a long half-life vs. a short half-life (aRR = 1.33; 95% CI, 1.12-1.56). Neonates exposed to opioids with a medium half-life had a similar risk for NOWS vs. those exposed to opioids with a short half-life (aRR = 0.95; 0.85-1.06).

Esposito and colleagues proposed that prescribers can use these findings to determine which opioids should be prescribed for pain management during pregnancy to limit the risk for NOWS.