Maternal opioids age-dependently impair neonatal respiratory control networks
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Date
2023-03-16
Authors
Beyeler, Sarah A.
Naidoo, Robyn
Morrison, Nina R.
McDonald, Emilee A.
Albarrán, David
Huxtable, Adrianne G.
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers in Physiology
Abstract
Infants exposed to opioids in utero are an increasing clinical population and these
infants are often diagnosed with Neonatal Abstinence Syndrome (NAS). Infants
with NAS have diverse negative health consequences, including respiratory
distress. However, many factors contribute to NAS, confounding the ability to
understand how maternal opioids directly impact the neonatal respiratory system.
Breathing is controlled centrally by respiratory networks in the brainstem and
spinal cord, but the impact of maternal opioids on developing perinatal respiratory
networks has not been studied. Using progressively more isolated respiratory
network circuitry, we tested the hypothesis that maternal opioids directly impair
neonatal central respiratory control networks. Fictive respiratory-related motor
activity from isolated central respiratory networks was age-dependently impaired
in neonates after maternal opioids within more complete respiratory networks
(brainstem and spinal cords), but unaffected in more isolated networks (medullary
slices containing the preBötzinger Complex). These deficits were due, in part, to
lingering opioids within neonatal respiratory control networks immediately after
birth and involved lasting impairments to respiratory pattern. Since opioids are
routinely given to infants with NAS to curb withdrawal symptoms and our previous
work demonstrated acute blunting of opioid-induced respiratory depression in
neonatal breathing, we further tested the responses of isolated networks to
exogenous opioids. Isolated respiratory control networks also demonstrated
age-dependent blunted responses to exogenous opioids that correlated with
changes in opioid receptor expression within a primary respiratory rhythm
generating region, the preBötzinger Complex. Thus, maternal opioids agedependently
impair neonatal central respiratory control and responses to
exogenous opioids, suggesting central respiratory impairments contribute to
neonatal breathing destabilization after maternal opioids and likely contribute
to respiratory distress in infants with NAS. These studies represent a significant
advancement of our understanding of the complex effects of maternal opioids,
even late in gestation, contributing to neonatal breathing deficits, necessary first
steps in developing novel therapeutics to support breathing in infants with NAS.
Description
19 pages
Keywords
Maternal opioid use, Neonatal respiratory control, In vitro electrophysiology, Perinatal development, Neonatal abstinence syndrome
Citation
Beyeler SA, Naidoo R, Morrison NR, McDonald EA, Albarrán D and Huxtable AG (2023), Maternal opioids age-dependently impair neonatal respiratory control networks. Front. Physiol. 14:1109754. doi: 10.3389/fphys.2023.1109754