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Record W3023705814 · doi:10.1002/cpt.1882

The Implausibility of Neonatal Opioid Toxicity from Breastfeeding

2020· review· en· W3023705814 on OpenAlexaffabout
Jonathan S. Zipursky, David N. Juurlink

Bibliographic record

VenueClinical Pharmacology & Therapeutics · 2020
Typereview
Languageen
FieldMedicine
TopicPrenatal Substance Exposure Effects
Canadian institutionsHealth Sciences CentreSunnybrook HospitalUniversity of TorontoInstitute for Clinical Evaluative SciencesSunnybrook Health Science Centre
Fundersnot available
KeywordsBreastfeedingOpioidToxicityMedicinePediatricsInternal medicineReceptor

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.990
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.120
GPT teacher head0.461
Teacher spread0.340 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designOther design
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations36
Published2020
Admission routes2
Has abstractyes

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