MicroRNA Biomarkers for Neonatal Opioid Withdrawal Syndrome

Study Overview
=================
Brief Summary
-----------------
Infants with neonatal abstinence syndrome (NAS) experience prolonged hospital stays and poor neurodevelopmental outcomes, in-part because of the lack of accurate, individualized, biologic assessments available to manage this increasingly common medical condition. The proposed study will define the molecular mechanisms that regulate the response to opioid withdrawal in the developing brain by focusing on three candidate microRNAs (let-7a, miR-146a, miR-192) that have been shown to respond to opioid exposure in animal models and adults, and are impacted in both my preliminary study of infants with NAS, and my human neural progenitor cell (NPC) design of opioid withdrawal. By determining the mechanism through which microRNAs impact NPC differentiation in opioid withdrawal, and determining whether exosomal salivary microRNA levels predict treatment dose and neurodevelopmental outcomes in infants with NAS, this study will enhance our knowledge of NAS-related biology and identify potential biomarkers that could improve medical care for this important medical condition.

Official Title
-----------------
Understanding the microRNA Response to Opioid Withdrawal and Their Uses as Potential Biomarkers for Neonatal Abstinence Syndrome

Conditions
-----------------
Neonatal Opioid Withdrawal Syndrome, Neonatal Abstinence Syndrome

Intervention / Treatment
-----------------
* Genetic: Buccal swab saliva for further genetic testing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newborns ≥35weeks gestation with chronic in-utero opioid exposure (>1month of gestation exposure). Maternal exposure will be determined by evaluating the medical records for maternal medication use, maternal urine toxicology and neonatal meconium toxicology results per standard clinical care Neonates born at Penn State Hershey Medical Center or transferred at <48 hours after birth Mothers with chronic in-utero opioid use during pregnancy ( ≥1month of gestation) Exclusion Criteria: <35 week gestation Infant required mechanical ventilation or non-invasive mechanical support Infant exposure to magnesium sulfate Opioid-exposed neonates who are actively receiving dextrose infusion for persistent neonatal hypoglycemia at the time of enrollment (<48hours after birth). Infant with major congenital anomalies Parent or guardian unable to provide consent Mothers and neonates without history of opioid exposure/dependence

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 5 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Infants exposed to in utero opiates<br>Infants that meet IRB-approved inclusion/exclusion criteria. | Genetic: Buccal swab saliva for further genetic testing<br>* Genetic testing. Whole saliva RNA will be isolated for downstream microRNA quantification.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopmental outcome scores | Measured by Ages and Stages Questionnaire-3, score scale 0-60 | 6 months of age | 
| Maximum concentration of morphine required for withdrawal symptom control | Measured in mg/kg/ml | Measured at 24 hours of life | 
| Salivary microRNA level let-7a | Relative fluorescence (Cq) measured by qPCR using established housekeeping gene | Buccal swab collected at 24 hrs of life and at discharge | 
| Salivary level of microRNA-146a | Relative fluorescence (Cq) measured by qPCR using established housekeeping gene | Buccal swab collected at 24 hrs of life and at discharge | 
| Salivary level of microRNA-192 | Relative fluorescence (Cq) measured by qPCR using established housekeeping gene | Buccal swab collected at 24 hrs of life and at discharge | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
microRNA, saliva, neurodevelopmental, exosomes, infant