Methadone exposure in utero was shown to increase the risk for neonatal abstinence syndrome compared with buprenorphine exposure in a study recently published in Epidemiology.
Live-born infants who had been exposed to methadone (n=407) or buprenorphine (n=309) in utero were included in this single-site study. Exposure status and the outcome of neonatal abstinence syndrome were determined using pharmacy billing claims. The relationship between treatment exposure in utero and outcome status was evaluated.
To control for severity of addiction, which was unmeasured in the original cohort, a validation study evaluated indicators of addiction severity using medical chart data for methadone (n=100) and buprenorphine exposure (n=100).
Methadone exposure in utero was associated with an increased risk for neonatal abstinence syndrome compared with buprenorphine exposure (relative risk [RR], 1.3; 95% CI, 1.2-1.5). After adjustment for parity, maternal race, and smoking, among other factors, similar results were reported (adjusted RR, 1.3; 95% CI, 1.1-1.5).
In the validation cohort, the researchers reported that severe addiction was more common for methadone- vs buprenorphine exposure (77% vs 32%). After adjustment for severe addiction, methadone was still associated with an increased risk for neonatal abstinence syndrome (RR, 1.2).
The study authors concluded that, “the results from the probabilistic bias analysis suggest that unmeasured confounding by severity of addiction only slightly biased the conventional results away from the null.” They noted that these results, “suggest that the previous findings that buprenorphine is associated with lower risk of neonatal abstinence syndrome compared with methadone in infants exposed in utero are subject to minimal bias from unmeasured confounding.”
Lemon LS, Caritis SN, Venkataramanan R, Platt RW, Bodnar LM. Methadone versus buprenorphine for opioid use dependence and risk of neonatal abstinence syndrome [published online November 6, 2017]. Epidemiology. doi: 10.1097/EDE.0000000000000780