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.

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

Infants enrolled into the study were exposed to opiates in-utero for at least one month of gestation. All infants enrolled meet the eligibility criteria listed above.