Medication-assisted treatment vs. detoxification for women who misuse opioids in pregnancy: Associations with dropout, relapse, neonatal opioid withdrawal syndrome (NOWS), and childhood sexual abuse

Macfie, Jenny; Towers, Craig V.; Fortner, Kimberly B.; Stuart, Gregory L.; Zvara, Bharathi J.; Kurdziel-Adams, Gretchen; Kors, Stephanie; Noose, Samantha K.; Gorrondona, Andrea M.; Cohen, Chloe

doi:10.1016/j.abrep.2020.100315

Cited by 5 publications

(15 citation statements)

References 41 publications

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“…These datasets are highly novel in that they directly compare three commonly used exposure protocols, i.e., in utero only (PND1), post-natal only (PND 14), and a combination of the two (3-Tri). Recently, there have been attempts to use translationally relevant models of NOWS both in terms of drug(s) of choice and duration of exposure, and although human exposure generally encompasses all 3 trimesters, there are increased attempts to detoxify pregnant patients in place of opioid agonist therapy ( Macfie et al, 2020 ). Thus, knowing the extent of gene expression changes at various times throughout pregnancy is important.…”

Section: Discussionmentioning

confidence: 99%

Molecular and long-term behavioral consequences of neonatal opioid exposure and withdrawal in mice

Dunn

Robinson

Nwokafor

et al. 2023

Front. Behav. Neurosci.

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IntroductionInfants exposed to opioids in utero are at high risk of exhibiting Neonatal Opioid Withdrawal Syndrome (NOWS), a combination of somatic withdrawal symptoms including high pitched crying, sleeplessness, irritability, gastrointestinal distress, and in the worst cases, seizures. The heterogeneity of in utero opioid exposure, particularly exposure to polypharmacy, makes it difficult to investigate the underlying molecular mechanisms that could inform early diagnosis and treatment of NOWS, and challenging to investigate consequences later in life.MethodsTo address these issues, we developed a mouse model of NOWS that includes gestational and post-natal morphine exposure that encompasses the developmental equivalent of all three human trimesters and assessed both behavior and transcriptome alterations.ResultsOpioid exposure throughout all three human equivalent trimesters delayed developmental milestones and produced acute withdrawal phenotypes in mice reminiscent of those observed in infants. We also uncovered different patterns of gene expression depending on the duration and timing of opioid exposure (3-trimesters, in utero only, or the last trimester equivalent only). Opioid exposure and subsequent withdrawal affected social behavior and sleep in adulthood in a sex-dependent manner but did not affect adult behaviors related to anxiety, depression, or opioid response.DiscussionDespite marked withdrawal and delays in development, long-term deficits in behaviors typically associated with substance use disorders were modest. Remarkably, transcriptomic analysis revealed an enrichment for genes with altered expression in published datasets for Autism Spectrum Disorders, which correlate well with the deficits in social affiliation seen in our model. The number of differentially expressed genes between the NOWS and saline groups varied markedly based on exposure protocol and sex, but common pathways included synapse development, the GABAergic and myelin systems, and mitochondrial function.

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Section: Discussionmentioning

confidence: 99%

Molecular and long-term behavioral consequences of neonatal opioid exposure and withdrawal in mice

Dunn

Robinson

Nwokafor

et al. 2023

Front. Behav. Neurosci.

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“…With respect to the development of 3D organoid models of POE, progress has primarily centered around studying the neurodevelopmental impact of opioid-based pharmacotherapies clinically recommended for the Medication-Assisted Treatment (MAT) of maternal OUD ( Substance Abuse and Mental Health Services Administration, 2016 ; The American College of Obstetricians and Gynecologists, 2017 ) ( Table 2 ). This is due to the rising rates of pregnant women seeking treatment for OUD ( Martin et al, 2015 ; Krans et al, 2019 ), motivated by the need to improve their own health and prevent neonatal opioid withdrawal ( Cleveland and Bonugli, 2014 ; Frazer et al, 2019 ; Macfie et al, 2020 ).…”

Section: Brain Organoid Models Of Prenatal Opioid Exposurementioning

confidence: 99%

Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology

Dwivedi,

Haddad

2024

Front. Cell. Neurosci.

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Over the past two decades, Opioid Use Disorder (OUD) among pregnant women has become a major global public health concern. OUD has been characterized as a problematic pattern of opioid use despite adverse physical, psychological, behavioral, and or social consequences. Due to the relapsing–remitting nature of this disorder, pregnant mothers are chronically exposed to exogenous opioids, resulting in adverse neurological and neuropsychiatric outcomes. Collateral fetal exposure to opioids also precipitates severe neurodevelopmental and neurocognitive sequelae. At present, much of what is known regarding the neurobiological consequences of OUD and prenatal opioid exposure (POE) has been derived from preclinical studies in animal models and postnatal or postmortem investigations in humans. However, species-specific differences in brain development, variations in subject age/health/background, and disparities in sample collection or storage have complicated the interpretation of findings produced by these explorations. The ethical or logistical inaccessibility of human fetal brain tissue has also limited direct examinations of prenatal drug effects. To circumvent these confounding factors, recent groups have begun employing induced pluripotent stem cell (iPSC)-derived brain organoid technology, which provides access to key aspects of cellular and molecular brain development, structure, and function in vitro. In this review, we endeavor to encapsulate the advancements in brain organoid culture that have enabled scientists to model and dissect the neural underpinnings and effects of OUD and POE. We hope not only to emphasize the utility of brain organoids for investigating these conditions, but also to highlight opportunities for further technical and conceptual progress. Although the application of brain organoids to this critical field of research is still in its nascent stages, understanding the neurobiology of OUD and POE via this modality will provide critical insights for improving maternal and fetal outcomes.

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“…Eight studies met our inclusion criteria (Table 1). These eight studies were published between 2003 and 2020 and were conducted in the United States of America (n = 5) [7][8][9][10][11], Norway (n = 2) [12,13], and the United Kingdom (n = 1) [14]. Studies used a variety of study designs consisting of retrospective (n = 6), prospective (n = 1), and mixed prospective/retrospective (n = 1) cohorts.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Studies used a variety of study designs consisting of retrospective (n = 6), prospective (n = 1), and mixed prospective/retrospective (n = 1) cohorts. Four studies utilized comparison groups which consisted of opioid maintenance groups (n = 3) [8,9,13] or non-using control groups (n = 1) [12].…”

Section: Study Characteristicsmentioning

confidence: 99%

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Opioid Medical Detoxification Compared to Opioid Agonist Treatment during Pregnancy: A Scoping Review

Ordean,

DeVuono

2024

Healthcare

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Opioid use disorder (OUD) is highly prevalent, affecting up to 1% of pregnancies. The current standard of care for the management of OUD during pregnancy has been maintained with opioid agonist treatment (OAT), using either methadone or buprenorphine. OAT use has been associated with a risk of neonatal abstinence syndrome (NAS), which requires a longer neonatal length of stay for monitoring and possible pharmacological treatment. As a result, opioid medical detoxification (OMD) was proposed as an alternative strategy to reduce the stigma associated with OAT and to eliminate the risk of NAS by detoxifying or tapering pregnant persons during their pregnancy before delivery; however, the safety and effectiveness of OMD during pregnancy have not been established. This scoping review aims to summarize recent evidence related to maternal, obstetrical, and neonatal outcomes of OMD in comparison to OAT maintenance. This review also provides recommendations for future research initiatives to fill gaps in managing this patient population.

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Medication-assisted treatment vs. detoxification for women who misuse opioids in pregnancy: Associations with dropout, relapse, neonatal opioid withdrawal syndrome (NOWS), and childhood sexual abuse

Cited by 5 publications

References 41 publications

Molecular and long-term behavioral consequences of neonatal opioid exposure and withdrawal in mice

Molecular and long-term behavioral consequences of neonatal opioid exposure and withdrawal in mice

Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology

Opioid Medical Detoxification Compared to Opioid Agonist Treatment during Pregnancy: A Scoping Review

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