NIRS Monitoring in Premature Infants

Introduction and specific aims:

Germinal matrix-intraventricular hemorrhage (GM-IVH) occurs in 45% of extremely low birth
weight (ELBW) premature infants, often leading to long-term neurodevelopmental impairments
(NDI). Post-hemorrhagic hydrocephalus (PHH) is a common complication of GM-IVH and increases
the risk of major NDI to 75-90%. Currently, the only bedside tool to assess for hemorrhage
and monitor for secondary hydrocephalus is ultrasound. Although increasing ventricular size
is currently used to determine need for intervention, measures based on cerebral physiology
are needed to better determine the impact of the expanding ventricles on individual cerebral
metabolism.

Our group has developed advanced FDNIRS-DCS technology for monitoring cerebral oxygen
metabolism (CMRO2) in newborns at the bedside. We hypothesize that baseline and evoked
cerebral metabolic dysfunctions are better biomarkers for GM-IVH and PHH severity and
response to PHH treatment. To test our hypotheses, we will address the following specific
aims:

Aim 1: Determine post-natal cerebral hemodynamics and oxygen metabolism trajectories in
GM-IVH and PHH neonates with respect to normal controls and differences between PHH infants
and infants affected by hydrocephalus due to other pathologies.

We hypothesize that:

1. Infants with GM-IVH have lower CBF and CMRO2 than healthy controls and the decrease is
in proportion to the severity of GM-IVH. (GM-IVH vs HC)

2. Infants with PHH have lower CBF and CMRO2 than healthy controls. (PHH vs HC)

3. For infants who developed PHH, the decrease of CBF and CMRO2 is affected by both
hemorrhages and the severity of hydrocephalus. (PHH vs VC)

Aim 2: Test the efficacy of cerebral hemodynamics and metabolism in detecting hydrocephalus
treatment response in both PHH and VC groups.

We hypothesize that CBF and CMRO2 increase in response to treatment-associated improvements
in hydrocephalus but remain depressed when response to treatment is inadequate.

Aim 3: Test the sensitivity of FDNIRS-DCS measured cerebral hemodynamics and oxygen
metabolism in predicting developmental outcomes in infants with GM-IVH and PHH. We will
assess neurodevelopmental outcomes in all enrolled infants at 5-7, 10-12, and 22-24 months
corrected age and correlate with FDNIRS-DCS measurements of CBF and CMRO2, and related
quantities with neurodevelopmental outcomes at approximately 5-7, 10-12, and 22-24 months
corrected age.

1. GM-IVH group:

Inclusion criteria for GM-IVH group: born at gestational age (GA) 24-32 weeks; < 3
months old corrected-GA (cGA) at first measure or eligible for measurement within 12
weeks after the infant reaches 40 weeks post-menstrual age (PMA). Grade I-III IVH
diagnosed by clinical cranial ultrasound or magnetic resonance imaging (MRI).

Exclusion criteria for GM-IVH group: chromosomal abnormalities known at the time of
enrollment; known or suspected metabolic disorder or neoplasm; critical congenital
heart disease; congenital hydrocephalus; brain lesions that affect cerebral brain
metabolism, other than GMH-IVH; central nervous system (CNS) infection.

2. PHH group:

Inclusion criteria for PHH group: born at gestational age (GA) 24-37 weeks < 3 months
old cGA at first measure or eligible for measurement within 12 weeks after the infant
reaches 40 weeks age (PMA). PHH diagnosed by clinical cranial ultrasound or MRI.

Exclusion criteria for PHH group: chromosomal abnormalities known at the time of
enrollment; known or suspected metabolic disorder or neoplasm; critical congenital
heart disease; congenital hydrocephalus; brain lesions that affect cerebral brain
metabolism, other than IVH-PHH; CNS infection. Implanted devices or other devices that
preclude the use of MRI.

3. HC group:

Inclusion criteria for HC group: born at gestational age (GA) 24-32 weeks; < 3 months
old cGA at first measure or eligible for measurement within 12 weeks after the infant
reaches 40 weeks age (PMA); Apgar >7 at 5 min.

Exclusion criteria for HC group: any clinical indication of brain injury or congenital
brain malformation; chromosomal abnormality known at the time of enrollment; known or
suspected metabolic disorder or neoplasm; critical congenital heart disease; CNS
infection.

4. VC group:

Inclusion criteria for VC group: < 12 months old cGA at first measure or eligible for
measurement within 1 year after the infant reaches 40 weeks age (PMA). Symptomatic
hydrocephalus of any etiology or at high risk of developing hydrocephalus of any etiology,
except post-hemorrhagic etiology; characterized by abnormal rate of head growth and full
anterior fontanelle. Ventricular enlargement diagnosed by ultrasonography or MRI; no signs
of IVH.

Exclusion criteria for VC group: known or suspected metabolic disorder or neoplasm;
critical congenital heart disease; CNS infection. Implanted devices or other devices that
preclude the use of MRI.