Neonatal Abstinence Syndrome Severity Index Predicts 18-Month Neurodevelopmental Outcome in Neonates Randomized to Morphine or Methadone

Flannery, Tess; Davis, Jonathan M.; Czynski, Adam J.; Dansereau, Lynne M.; Oliveira, Érica L.; Camardo, Samantha A.; Lester, Barry M.

doi:10.1016/j.jpeds.2020.08.034

Cited by 18 publications

(10 citation statements)

References 44 publications

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“…10,[52][53][54][55][56] While profiles are cohort-dependent and require statistical analysis, examining patterns of readily available summary scores can allow clinicians rapid,JAMA Network Open | PediatricsNeonatal Neurobehavior and Developmental Outcomes Among Preterm Infants bedside approximations of at-risk behavior, thus facilitating the neurobehavioral jump start for a variety of clinical scenarios.…”

mentioning

confidence: 99%

Analysis of Neonatal Neurobehavior and Developmental Outcomes Among Preterm Infants

et al. 2022

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confidence: 99%

Analysis of Neonatal Neurobehavior and Developmental Outcomes Among Preterm Infants

et al. 2022

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“…Indeed, the current study confirmed that there were improvements in neonatal neurobehavior following pharmacologic treatment for NAS. Given that atypical NNNS profiles have been linked to abnormal long-term developmental outcomes, our findings suggest that neonates who show positive changes in NNNS post-treatment may also have better long-term outcomes [25,27].…”

Section: Discussionmentioning

confidence: 80%

“…Neonatal neurobehavior has been extensively studied in relation to prenatal opioid exposure, with studies documenting differences in NNNS summary scores based on opioid exposure and type and dose of maternal opioid (e.g., methadone versus buprenorphine) [10,11,16,17]. More recently, NNNS scores have been shown to differentiate neonates with highand low-severity of NAS [25]. Neonates with severe NAS were more likely to have a neurobehavioral profile characterized by poor regulation, high arousal, hypertonicity, and physiological signs of stress and abstinence.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Treatment for Neonatal Abstinence Syndrome is Associated with Altered DNA Methylation and Neurobehavior

Camerota¹,

Davis²,

Dansereau³

et al. 2021

Preprint

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Objective: To determine whether pharmacological treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior.Study Design: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted and DNAm was examined at four CpG sites within the OPRM1 gene. The NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx – DNAmpre-tx) and NNNS summary scores (NNNSpost-tx – NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. Results: DNAm significantly decreased from pre- to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pre- to post-treatment. Increased length of treatment and higher morphine doses were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS.Conclusions: Pharmacological treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.

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“…Furthermore, a randomized control trial that examined the safety and efficacy of methadone vs. morphine reported a median length of treatment of 15 and 11.5 days (Davis et al, 2018 ). However, treatments that reduce the need for neurotoxic opioids are a high priority in this vulnerable population (Flannery et al, 2020 ). The NEOPAIN trial, a large multicenter randomized study of 898 infants demonstrated that although morphine is effective in decreasing clinical signs of pain, it can cause significant acute adverse effects such as changes in the heart and respiratory rate, hypotension, nasogastric feeds, and need for intravenous supplemental nutrition (Anand et al, 2004 ; Attarian et al, 2014 ).…”

Section: Developing An Alternative To Opioid Replacement Therapymentioning

confidence: 99%

“…Additionally, these pharmacotherapies themselves produce harmful side effects. Administering morphine during early neurodevelopment, specifically during a critical perinatal period, may cause neuronal apoptosis, white matter injury, decreased myelin maturation, and oxidative stress, leading to long-term developmental consequences (Rao et al, 2007 ; Attarian et al, 2014 ; Steinhorn et al, 2015 ; Flannery et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Transcutaneous Auricular Neurostimulation (tAN): A Novel Adjuvant Treatment in Neonatal Opioid Withdrawal Syndrome

Jenkins

Khodaparast

O’Leary

et al. 2021

Front. Hum. Neurosci.

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Maternal opioid use during pregnancy is a growing national problem and can lead to newborns developing neonatal opioid withdrawal syndrome (NOWS) soon after birth. Recent data demonstrates that nearly every 15 min a baby is born in the United States suffering from NOWS. The primary treatment for NOWS is opioid replacement therapy, commonly oral morphine, which has neurotoxic effects on the developing brain. There is an urgent need for non-opioid treatments for NOWS. Transcutaneous auricular neurostimulation (tAN), a novel and non-invasive form of electrostimulation, may serve as a promising alternative to morphine. tAN is delivered via a multichannel earpiece electrode worn on and around the left ear, targeting two cranial nerves—the vagus and trigeminal nerves. Prior research suggests that auricular neurostimulation exerts an anxiolytic effect on the body by releasing endogenous opioids and reduces withdrawal symptoms in adults actively withdrawing from opioids. In this first-in-human prospective, open-label trial, we investigated tAN as an adjuvant to morphine therapy in eight infants >33 weeks gestational age suffering from NOWS and receiving oral morphine treatment. Infants received tAN for 30 min 1 h before receiving a morphine dose. tAN was delivered at 0.1 mA below perception intensity at two different nerve targets on the ear: Region 1, the auricular branch of the vagus nerve; and Region 2, the auriculotemporal nerve. tAN was delivered up to four times daily for a maximum of 12 days. The primary outcome measures were safety [heart rate monitoring, Neonatal Infant Pain Scale (NIPS), and skin irritation] and morphine length of treatment (LOT). tAN was well-tolerated and resulted in no unanticipated adverse events. Comparing to the national average of 23 days, the average oral morphine LOT was 13.3 days (median 9 days) and the average LOT after tAN initiation was 7 days (median 6 days). These preliminary data suggest that tAN is safe and may serve as a promising alternative adjuvant for treating NOWS and reducing the amount of time an infant receives oral morphine.

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Neonatal Abstinence Syndrome Severity Index Predicts 18-Month Neurodevelopmental Outcome in Neonates Randomized to Morphine or Methadone

Cited by 18 publications

References 44 publications

Analysis of Neonatal Neurobehavior and Developmental Outcomes Among Preterm Infants

Analysis of Neonatal Neurobehavior and Developmental Outcomes Among Preterm Infants

Pharmacological Treatment for Neonatal Abstinence Syndrome is Associated with Altered DNA Methylation and Neurobehavior

Transcutaneous Auricular Neurostimulation (tAN): A Novel Adjuvant Treatment in Neonatal Opioid Withdrawal Syndrome

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