MicroRNA Biomarkers for Neonatal Opioid Withdrawal Syndrome

Milton S. Hershey Medical Center50 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Neonatal Opioid Withdrawal Syndrome Neonatal Abstinence Syndrome

Interventions

Eligibility

Sex: ALLMin age: 1 DayMax age: 5 Days

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Neurodevelopmental outcome scores

Measured by Ages and Stages Questionnaire-3, score scale 0-60

Time frame: 6 months of age

Maximum concentration of morphine required for withdrawal symptom control

Measured in mg/kg/ml

Time frame: Measured during the course of hospital stay

Salivary microRNA level let-7a

Relative fluorescence (Cq) measured by qPCR using established housekeeping gene

Time frame: Buccal swab collected within 96 hrs of life and at discharge

Salivary level of microRNA-146a

Relative fluorescence (Cq) measured by qPCR using established housekeeping gene

Time frame: Buccal swab collected within 96 hrs of life and at discharge

Salivary level of microRNA-192

Relative fluorescence (Cq) measured by qPCR using established housekeeping gene

Time frame: Buccal swab collected within 96 hrs of life and at discharge

Salivary level of microRNA-149-3p

Relative fluorescence (Cq) measured by qPCR using established housekeeping gene

Time frame: Buccal swab collected within 96 hrs of life and at discharge

MicroRNA Biomarkers for Neonatal Opioid Withdrawal Syndrome

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Central Contacts