Cerebral Physiology of NOWS

The investigators propose to use a novel optical-based device that combines two advanced NIRS techniques, frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS), to quantify regional cerebral oxygenation (SO2), cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) in neonates with similar ease of use as commercial NIRS devices, offering a more comprehensive metabolic profile of early brain function. Our technology has been validated in infant populations, demonstrating robust biomarkers of brain health and function in both healthy and at-risk infants. A pilot study at Riley Hospital for Children has already revealed differences in absolute cerebral oxygenation (SO2) as measured by quantitative FD-NIRS instrumentation in a small sample of neonates with POE and age-matched controls on the first 24 hours of life.

The investigators hypothesize that infants who develop severe NOWS will exhibit early measurable alterations in cerebral oxygenation, blood flow, and/or metabolism in the early postnatal period. Thus, the investigators propose to acquire FD-NIRS/DCS measurements in infants with prenatal opioid exposure (POE) in their first days of life.

Aim 1: Determine early trajectories of cerebral physiology in neonates with POE using a non-invasive FD-NIRS/DCS device.

Aim 2: Investigate early associations between FD-NIRS/DCS measurements and short-term clinical outcomes in neonates with POE.

Aim 3: Monitor changes in cerebral physiology during pharmacologic treatment in infants with severe NOWS.

Inclusion criteria

Infants with prenatal opioid exposure:

• Term born or near-term born (> 36w) infants
• Birth weight > 2 Kg
• History of prenatal opioid exposure

Control infants:

• Term born or near-term born (> 36w) infants
• Birth weight > 2 Kg

Mothers of infants with prenatal opioid exposure:

• greater or equal to 19 years of age
• Use of opioid substances during pregnancy - Defined as pregnant women who 1) are clinically diagnosed as having an opioid use disorder and are on methadone or buprenorphine maintenance program or 2) have a urine drug test positive for prescribed or illicit opioids

Mothers of control infants:

• greater than or equal to 19 years of age

Exclusion criteria

Infants with prenatal opioid exposure:

• APGAR score at 5 min < 7
• Any major congenital malformations or genetic syndromes
• Need for positive pressure ventilation in the delivery room

Control infants:

• APGAR score at 5 min < 7
• Any major congenital malformations or genetic syndromes
• Need for positive pressure ventilation in the delivery room
• Any history of prenatal opioid exposure

Mothers of infants with prenatal opioid exposure:

• Major maternal illness during pregnancy or delivery that could impact infant cerebral perfusion as deemed by the study investigators (e.g. uterine rupture or preeclampsia)

Mothers of control infants:

• Major maternal illness during pregnancy or delivery that could impact infant cerebral perfusion as deemed by the study investigators (e.g. uterine rupture or preeclampsia)
• Tobacco, SSRI or any opioid use during pregnancy