Postpartum maternal codeine therapy and the risk of adverse neonatal outcomes: The devil is in the details

摘要

In 2007, the United States Food and Drag Administration issued a health advisory to warn the public that the use of codeine by some breastfeeding mothers may lead to life-threatening side effects in nursing infants. Health Canada issued a similar warning in 2008. These warnings were based solely on the death of a 13-day-old infant whose mother had been taking therapeutic doses of codeine for postpartum pain relief. The infant's postmortem blood contained a toxic concentration of morphine, and breast milk morphine concentrations from day 10 of the infant's life were the highest ever reported in the literature. It was subsequently discovered that the breastfeeding mother had genetic duplications in the cytochrome P450 2D6 (CYP2D6) gene. Codeine is converted into morphine in the body by CYP2D6, and it is morphine, which mediates the analgesic effects of codeine. Individuals with functional duplications of the CYP2D6 gene (such as the mother in this case) may produce up to 75% more morphine from codeine than the general population.