Maternal Methadone Destabilizes Neonatal Breathing and Desensitizes Neonates to Opioid-Induced Respiratory Frequency Depression
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Date
2021-02-26
Authors
Hocker, Austin D.
Morrison, Nina R.
Selby, Matthew L.
Huxtable, Adrianne G.
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers in Physiology
Abstract
Pregnant women and developing infants are understudied populations in the opioid
crisis, despite the rise in opioid use during pregnancy. Maternal opioid use results
in diverse negative outcomes for the fetus/newborn, including death; however, the
effects of perinatal (maternal and neonatal) opioids on developing respiratory circuitry
are not well understood. Given the profound depressive effects of opioids on central
respiratory networks controlling breathing, we tested the hypothesis that perinatal
opioid exposure impairs respiratory neural circuitry, creating breathing instability. Our
data demonstrate maternal opioids increase apneas and destabilize neonatal breathing.
Maternal opioids also blunted opioid-induced respiratory frequency depression acutely
in neonates; a unique finding since adult respiratory circuity does not desensitize to
opioids. This desensitization normalized rapidly between postnatal days 1 and 2 (P1
and P2), the same age quantal slowing emerged in respiratory rhythm. These data
suggest significant reorganization of respiratory rhythm generating circuits at P1–2, the
same time as the preBötzinger Complex (key site of respiratory rhythm generation)
becomes the dominant respiratory rhythm generator. Thus, these studies provide
critical insight relevant to the normal developmental trajectory of respiratory circuits
and suggest changes to mutual coupling between respiratory oscillators, while also
highlighting how maternal opioids alter these developing circuits. In conclusion, the
results presented demonstrate neurorespiratory disruption by maternal opioids and
blunted opioid-induced respiratory frequency depression with neonatal opioids, which
will be important for understanding and treating the increasing population of neonates
exposed to gestational opioids.
Description
16 pages
Keywords
Opioids, Maternal insults, Neonatal, Breathing, Chemosensitivity, Opioid-induced respiratory frequency depression, Quantal slowing
Citation
Hocker AD, Morrison NR, Selby ML and Huxtable AG (2021) Maternal Methadone Destabilizes Neonatal Breathing and Desensitizes Neonates to Opioid-Induced Respiratory Frequency Depression. Front. Physiol. 12:604593. doi: 10.3389/fphys.2021.604593