The Implausibility of Neonatal Opioid Toxicity from Breastfeeding

The belief that newborns can develop opioid toxicity from breastfeeding is widely held but supported by very little data. Based largely on a single, highly publicized case report (the "Toronto case"), major health agencies worldwide now caution against codeine use by nursing mothers. As a result, "stronger" opioids with greater abuse liability are increasingly prescribed in its place, potentially to the detriment of maternal health. We re-examine aspects of this case report to demonstrate why such an occurrence is highly implausible. The Toronto case involved the death of a 13-day-old infant from opioid toxicity. The child's mother, who took codeine while breastfeeding, was found to have a duplication of CYP2D6*2, consistent with ultrarapid metabolizer status. This led to the conclusion that the child died from opioid toxicity due to enhanced maternal conversion of codeine to morphine, with the subsequent passage of large amounts of morphine into breast milk. We argue that this explanation is implausible based upon several factors: (1) the exceedingly small amount of opioids passed into breastmilk irrespective of maternal CYP genotype, (2) the observation that significant neonatal opioid accumulation can only occur in the setting of severely impaired renal function, and (3) the previously unreported finding of a markedly elevated codeine concentration in postmortem blood. Finally, a review of the literature identifies a paucity of convincing reports of neonatal opioid toxicity during breastfeeding, with no other confirmed cases of neonatal death despite the use of these drugs by millions of nursing mothers over the past 2 decades.