Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage

We have created an innovative new method which uses frequency domain near-infrared spectroscopy (FDNIRS) in combination with diffuse correlation spectroscopy (DCS) to quantitatively measure cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) right at the infant’s bedside. We have previously found CBF and CMRO 2 are more sensitive indicators of cerebral pathophysiology than hemoglobin saturation (SO 2 ). Using FDNIRS-DCS, we had found extremely premature infants with germinal matrix hemorrhage (GMH) have lower cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) than gestational age-matched controls. For this study, we investigate whether GMH, along with age and hematocrit levels, affect evoked hemodynamic responses. The study protocol was reviewed and approved by the Institutional Review Board for Partners Healthcare. We enrolled eleven premature infants in the neonatal intensive care unit at Brigham and Women’s Hospital. Three of them had Grade I GMH diagnosed by head ultrasound on the first three days of life. We integrated continuous wave NIRS (CWNIRS) with DCS to measure dynamic changes of cerebral hemoglobin concentrations (HbO) and CBF in response to somatosensory stimuli. For each measurement, we measured differential path length factors and baseline cerebral hemoglobin concentrations with FDNIRS to quantify relative hemodynamic and metabolic changes (rHbO, rCBF and rCMRO 2 ) in response to tactile stimulation. We observed a faster response time to reach peak value in preterm infants with increasing postmenstrual age (PMA), demonstrating the response matures with age to become more adult-like (r=-0.513, p=0.007). In addition, infants measured at older PMA tend to have responses with a larger undershoot in HbO. However, the HbO undershoot did not translate into an undershoot in CMRO 2 . The HbO undershoot may therefore be a consequence of low hematocrit during the first two months of life which results in insufficient oxygen supply and leads to abnormally large oxygen extraction from the blood. We found the activation pattern of Grade I GMH infants did not differ from premature infants without hemorrhage. The study is ongoing and shows our method is suitable to measure cerebral maturation in neonates with hemorrhage.

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Alterations in Cerebral Blood Flow in Preterm Infants with Intraventricular Hemorrhage

PEDIATRICS ◽

10.1542/peds.68.6.763 ◽

1981 ◽

Vol 68 (6) ◽

pp. 763-769

Author(s):

Laura R. Ment ◽

Richard A. Ehrenkranz ◽

Robert C. Lange ◽

Peter T. Rothstein ◽

Charles C. Duncan

Keyword(s):

Computed Tomography ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Ct Scan ◽

Preterm Infants ◽

Intraventricular Hemorrhage ◽

Mean Value ◽

Germinal Matrix ◽

The Mean ◽

Xenon 133

Xenon-133 inhalation hemispheric cerebral blood flow (HCBF) determinations at one to two days and four to six days postnatally and at 37 weeks postconceptual age have been correlated with computed tomography (CT) scan and autopsy findings in 15 preterm infants weighing less than 1,250 gm at birth. Ten of these infants had germinal matrix hemorrhages (GMH) or intraventricular hemorrhages (IVH). Although HCBF obtained at one to two days showed no mean difference between the GMH/IVH group and the nonhemorrhage infants, hemispheric flow ratios showed significant discrepancies in the GMH/IVH group. In addition, in four of five patients in whom the hemorrhage appeared asymmetric on CT scan, the side of higher flow correlated with the hemorrhage. At four to six days HCBF showed a lower mean value in the GMH/IVH patients than in the nonhemorrhage patients and differences in the interhemispheric ratios in the GMH/IVH group persisted. There were no differences in the mean HCBF values or hemispheric ratios between the two groups of infants at 37 weeks postconceptual age.

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Indomethacin for Prevention of Neonatal Intraventricular Hemorrhage

DICP ◽

10.1177/106002809102501213 ◽

1991 ◽

Vol 25 (12) ◽

pp. 1344-1348 ◽

Cited By ~ 1

Author(s):

Dennis F. Thompson ◽

Marsha A. Raebel ◽

Kenneth C. Lamp ◽

Maryann S. Reynolds

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Vitamin E ◽

Intracerebral Hemorrhage ◽

Premature Infants ◽

Intraventricular Hemorrhage ◽

Low Grade ◽

Cerebral Vasoconstriction ◽

Pharmacologic Therapies

Up to 50 percent of premature infants develop an intracerebral hemorrhage. Intracerebral hemorrhage in neonates occurs most frequently in the periventricular or intraventricular areas. Intravascular, vascular, and extravascular factors influence the development of hemorrhage. Pharmacologic therapies, such as phenobarbital, vitamin K, pancuronium bromide, vitamin E, and indomethacin, have been used in an attempt to prevent intraventricular hemorrhage (IH). Indomethacin inhibits prostaglandin production, which results in cerebral vasoconstriction and reduced cerebral blood flow. Several clinical studies have evaluated the role of indomethacin for the prevention of IH in premature infants. No definitive recommendations can be made regarding indomethacin use for this purpose. However, the two largest studies conducted to date have shown indomethacin to be effective in preventing or limiting the progression of IH. The drug appears to be most effective in reducing low-grade IH. More extensive research is needed to determine the most effective dose, duration, and serum concentration of indomethacin.

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