Buprenorphine exposure in infants of opioid‐dependent mothers at birth

Abstract

Buprenorphine, a partial opioid agonist used in treating opioid dependence, is not approved in Australia for use in pregnancy. Nevertheless, many pregnant women choose to remain on the drug. To investigate cord/maternal transfer ratios for buprenorphine and norbuprenorphine in women at delivery. Maternal and cord serum samples were collected from 10 maternal-infant pairs at delivery. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Maternal and infant demographic information was collected. Linear regression was used to assess the relationship between maternal and cord measurements. Median (interquartile range) maternal age was 27 (23.8-32) years, with 90% of the women on buprenorphine before pregnancy. Median infant birthweight was 3148 (3088-3545) g and 60% of infants had neonatal abstinence requiring admission to a neonatal intensive care unit for a median of 8.5 (2.5-16.3) days. Median maternal buprenorphine daily dose was 8.5 mg (range 1-28 mg). Mean (95% confidence interval) cord serum concentrations of buprenorphine and norbuprenorphine were 0.4 (0.3-0.5) μg/L and 1.2 (0.9-1.4) μg/L, respectively. Mean maternal concentrations of buprenorphine and norbuprenorphine were 1.0 (0.6-1.4) μg/L and 1.2 (0.9-1.4) μg/L, respectively. Mean cord/maternal ratios were 0.43 (0.36-0.5) for buprenorphine and 0.53 (0.43-0.63) for norbuprenorphine. Maternal buprenorphine and norbuprenorphine concentrations and ratio of buprenorphine/norbuprenorphine explained 85.7, 69.6 and 94.4%, respectively, of variation in the corresponding cord concentrations. Usual therapeutic doses of buprenorphine administered to pregnant women resulted in low concentrations of buprenorphine and norbuprenorphine in maternal serum and a low transfer to the fetal circulation (cord plasma) at birth.