White Matter Injury and Structural Anomalies in Infants with Prenatal Opioid Exposue

Merhar, Stephanie L.; Parikh, Nehal A.; Braimah, Adebayo; Poindexter, Brenda B.; Tkach, Jean A.; Kline‐Fath, Beth M.

doi:10.3174/ajnr.a6282

Cited by 31 publications

(25 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic oxy exposure altered the white matter of the rats via deformation of axonal tracks, reduced size of axonal fascicles, loss of myelin basic protein, and accumulation of the amyloid precursor protein (Fan et al, 2018 ). Importantly, human studies of infants prenatally-exposed to opioids have shown alterations in the white matter, such as punctate white matter lesions or white matter signal abnormalities on structural MR imaging (Walhovd et al, 2012 ; Merhar et al, 2019 ). The results from our RNA-seq analysis align with these previous observations from both animal models and human studies.…”

Section: Discussionmentioning

confidence: 99%

A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior

Odegaard

Schaal

Clark

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes.Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (1H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood.Results:1H-MRS studies revealed significant changes in key brain metabolites in the exposed offspring that were corroborated with changes in synaptic currents. Transcriptomic analysis employing RNA-sequencing identified alterations in the expression of pivotal genes associated with synaptic transmission, neurodevelopment, mood disorders, and addiction in the treatment groups. Furthermore, Von Frey analysis revealed lower pain thresholds in both exposed groups.Conclusions: Given the increased use of opiates, understanding the persistent developmental effects of these drugs on children will delineate potential risks associated with opiate use beyond the direct effects in pregnant women.

show abstract

Section: Discussionmentioning

confidence: 99%

A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior

Odegaard

Schaal

Clark

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Interestingly, a higher percentage (45% vs. 20% in control offspring) of male offspring from morphine-exposed dams were classified as having higher and more severe global behavioral scores during adulthood. Merhar et al . (2019) reported that 40% of opioid-exposed newborns exhibit significant brain alterations, suggesting that the disruption of key processes during the development of the nervous system might increase vulnerability to behavioral deficits later in life.…”

Section: Discussionmentioning

confidence: 99%

In utero exposure to morphine leads to sex-specific behavioral alterations that persist into adulthood in cross-fostered mice

Fleites

Markwalter²,

Johnson³

et al. 2022

Preprint

View full text Add to dashboard Cite

Introduction: The opioid epidemic has seen an increase in drug use among women of reproductive age. It is well established that Opioid Use Disorder (OUD) can have many negative consequences for the health of mothers and their babies, both during pregnancy and after delivery, but our understanding of the impact of fetal opioid exposure on behavior during adolescence and adulthood is less understood. Preclinical studies have unveiled some of the long-term effects of in utero morphine exposure primarily using injections as the route of drug delivery. Our study utilized a model for oral, voluntary morphine self-administration to investigate neonate, adolescent, and adult offspring behavioral phenotypes and subsequent ethanol misuse liability. Methods: We first validated a paradigm for maternal oral intake of morphine, where female mice became morphine dependent pre-pregnancy, and continued to voluntarily consume morphine in the continuous two-bottle choice (C2BC) paradigm during pregnancy and up to offspring postnatal day 7 (PND 7). Offspring were cross-fostered to a drug-naive dam at PND 7, to model first and second trimester in utero exposure in humans and to mimic the stress associated with NOWS. Bodyweight and ultrasonic vocalizations were assessed to determine alterations in the neonates. Offspring from control and morphine-exposed dams were then tested during adolescence and adulthood in a battery of behavioral tests to assess baseline behavioral phenotypes. We also computed a global behavioral score (GBS) to integrate offspring multiple behavioral outcomes into a composite score that could be used to identify potential vulnerable and resilient populations in offspring exposed prenatally to morphine. Offspring that were tested during adolescence were also evaluated during adulthood in the ethanol intermittent 2BC to assess ethanol misuse risk. Results: Using an oral maternal morphine C2BC protocol, we demonstrated that morphine dams display signs of dependence, measured by somatic signs during withdrawal, and voluntarily drink morphine throughout gestation. Neonate cross-fostered offspring display changes in spontaneous activity, body weight, and ultrasonic vocalization parameters. During adolescence, offspring display both increased baseline anxiety-like/compulsive-like behavior, while in adulthood they display increased anxiety-like behavior. No changes were found for baseline physical signs, locomotion, and depressive-like behavior during adolescence or adulthood. In addition, a greater percentage of adult male offspring exposed to maternal morphine fell into moderate and high GBS classifications, signaling a more severe behavioral phenotype, compared to male control offspring. These effects were not observed in adult female offspring exposed to morphine in utero. Additionally, male adult offspring exposed to maternal morphine reduced their 2-hour ethanol intake in the intermittent two-bottle choice (I2BC) paradigm, although no changes in 24-hour ethanol intake and preference were found. No changes were observed in female offspring of morphine-exposed dams. Conclusion: Overall, maternal morphine exposure leads to sex-specific changes in neonate, adolescent, and adult behavior, including ethanol intake.

show abstract

“…Several human studies have evaluated the effect of opioids exposure during pregnancy on later periods of children life. Merhar and Parikh (2019) demonstrated that term infants (at 4–8 weeks of age) with a prenatal opioid (methadone, buprenorphine, and street drugs) exposure had punctate white matter lesions or white matter signal abnormality on structural MR imaging, and two of the opioid‐exposed infants had a septopreoptic fusion anomaly (Merhar & Parikh, 2019).…”

Section: Discussionmentioning

confidence: 99%

Brain‐derived neurotrophic factor and nerve growth factor concentrations in maternal and umbilical cord blood of opium‐addicted mothers

Fanaei

Riki

Khayat

et al. 2020

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Background It is reported that opium consumption during pregnancy is associated with adverse pregnancy outcomes and neurodevelopmental defects in infants. BDNF and NGF alterations during pregnancy cause neurobehavioral deficits in the offspring. The aim of this study was to investigate the effect of opium addiction of pregnant women on BDNF and NGF levels in maternal and umbilical cord blood as well as pregnancy outcome. Materials and methods The present research was a cross‐sectional study. Thirty‐five addicted pregnant women and 35 healthy pregnant women were included in the study. Blood samples were taken immediately after delivery from the maternal vein and umbilical cord. Then, BDNF and NGF concentrations in serum were measured by ELISA kits. The outcomes of pregnancy were determined by a checklist. Descriptive, t test, Mann–Whitney, and Chi‐squared test were used to analyze the data. SPSS version 21 software was used for the analyses. A p‐value <.05 was considered significant. Results BDNF levels were significantly lower in maternal and umbilical cord blood in the opium‐addicted group (917.2 31 ± 316.5 and 784.6 ± 242.9 pg/ml, respectively) compared to the control group (1351 ± 375 and 1063 ± 341 pg/ml, respectively) (p < .0001 and p < .0002, respectively). Similarly, NGF level was significantly lower in maternal and umbilical cord blood in the opium‐addicted group (302.7 ± 35.50 and 226.6 ± 45.43 pg/ml, respectively) compared to the control group (345.7 ± 43.16 and 251.2 ± 37.72 pg/ml, respectively) (p < .0001 and p = .0165, respectively). Adverse pregnancy outcomes such as NICU admissions, congenital anomalies, neonatal deaths, meconium contaminated amniotic fluid, respiratory problems, neonatal resuscitation, and low Apgar score were significantly higher in the opium‐addicted group than in the control group. Conclusion The results of this study revealed that opium consumption during pregnancy reduces BDNF and NGF levels in maternal and umbilical cord blood, which may cause neurodevelopmental disorders in later periods of infants' life.

show abstract

White Matter Injury and Structural Anomalies in Infants with Prenatal Opioid Exposue

Cited by 31 publications

References 40 publications

A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior

A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior

In utero exposure to morphine leads to sex-specific behavioral alterations that persist into adulthood in cross-fostered mice

Brain‐derived neurotrophic factor and nerve growth factor concentrations in maternal and umbilical cord blood of opium‐addicted mothers

Contact Info

Product

Resources

About