To assess whether umbilical cord concentrations of methadone, buprenorphine, and their metabolites were associated with maternal medication dose and neonatal opioid withdrawal syndrome (NOWS) severity.
Approach:
Design and participants: Prospective, multisite cohort analysis of 92 pregnancies (94 neonates) involving continuous methadone or buprenorphine treatment for at least 30 days before delivery.
Measurements: Mass spectrometry quantified medications and metabolites in umbilical cord tissue. Severe NOWS was defined by pharmacologic treatment or specified clinical assessment criteria.
Analysis: Researchers examined correlations among maternal dose, cord concentrations, and NOWS severity, and used adjusted logistic regression to compare severe NOWS by medication type.
Key Findings:
Severe NOWS occurred in 43.6% of neonates and was more frequent with methadone than buprenorphine exposure (55.6% vs 27.5%; P = .01). Adjusted odds of severe NOWS were higher with methadone exposure (adjusted OR, 3.42; 95% CI, 1.17-9.96; P = .02).
Cord methadone and EDDP concentrations correlated positively with maternal methadone dose; maternal buprenorphine dose was not significantly associated with cord buprenorphine or norbuprenorphine concentrations.
Cord drug concentrations and maternal doses were comparable between severe and nonsevere NOWS groups. Peak Finnegan scores were not correlated with maternal dose or cord concentrations.
Sensitivity analyses restricted to pharmacologically treated severe NOWS cases produced consistent findings.
Interpretation:
Cord tissue concentrations reflected maternal methadone dose, but neither maternal dose nor measured cord opioid concentrations was associated with NOWS severity. The authors state that medication-related differences in NOWS may involve factors beyond absolute exposure.
Limitations:
The modest sample size limited causal analysis, and medication selection was not randomized.
Limited racial and ethnic diversity may restrict generalizability.
NOWS assessment protocols differed across sites, although results were consistent across definitions.
Conclusion:
In this cohort, methadone exposure was associated with higher odds of severe NOWS than buprenorphine exposure, but dose and cord concentrations did not explain severity. The authors report that the findings do not support reducing medication doses to prevent severe NOWS and reinforce individualized dosing based on maternal clinical stability.
