The Implausibility of Neonatal Opioid Toxicity from Breastfeeding

Abstract

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.

Opioid Use in Breastfeeding Mothers and Neonatal Risks

“…One death associated with codeine in the United States has led to advisories discouraging its use in breastfeeding women. However, recent reviews have successfully documented the implausibility of this case report 6 . Hydrocodone has been the primary opioid used postnatally in the United States for decades, with good outcomes.…”

“…However, recent reviews have successfully documented the implausibility of this case report. 6 Hydrocodone has been the primary opioid used postnatally in the United States for decades, with good outcomes.…”

“…A recent article by Zipursky and Juurlink make a strong argument against breastmilk as the sole source of this overdose. 6 Without doubt, millions of breastfeeding mothers have used codeine over the last 50 years. Interestingly, the use of codeine is now rebounding with the restrictions placed on hydrocodone, which was the most prevalent opioid used as little as 6 years ago.…”

“…Did the levels arise from maternal rapid metabolism and infant accumulation, or from some other external source? A recent article by Zipursky and Juurlink make a strong argument against breastmilk as the sole source of this overdose 6 …”

Risks of maternal codeine intake in breast-fed infants: A Joint Statement of Retraction from the Canadian Pharmacists Journal and Canadian Family Physician

“…Jonathan Zipursky and David Juurlink from the University of Toronto published a paper in the journal Clinical Pharmacology and Therapeutics calling into question that newborns can develop opioid toxicity from breastfeeding. 5 In the paper they re-examined aspects of this case report and strongly argued why such an occurrence is highly implausible. 5 They concluded that: .…”