Vascular Endothelial Growth Factor in the Cerebrospinal Fluid of Infants Who Died of Sudden Infant Death Syndrome: Evidence for Antecedent Hypoxia

• Published in: Pediatrics (Evanston) Vol. 111; no. 2; pp. 358 - 363
• Main Authors: Jones, Kimberly L, Krous, Henry F, Nadeau, Julie, Blackbourne, Brian, Zielke, H. Ronald, Gozal, David
• Format: Journal Article
• Language: English
• Published: Elk Grove Village, IL Am Acad Pediatrics 01-02-2003; American Academy of Pediatrics
• Subjects: Analysis; Animals; Anoxia; Babies; Biological and medical sciences; Body fluids; Body Fluids - chemistry; Cause of Death; Cerebrospinal fluid; Disease Models, Animal; Endothelial Growth Factors - blood; Endothelial Growth Factors - cerebrospinal fluid; Endothelial Growth Factors - immunology; Endothelial Growth Factors - metabolism; Enzyme-Linked Immunosorbent Assay; Humans; Hypoxia; Hypoxia - blood; Hypoxia - cerebrospinal fluid; Hypoxia - complications; Infant; Infant, Newborn; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - cerebrospinal fluid; Intercellular Signaling Peptides and Proteins - immunology; Intercellular Signaling Peptides and Proteins - metabolism; Lymphokines - blood; Lymphokines - cerebrospinal fluid; Lymphokines - immunology; Lymphokines - metabolism; Male; Medical sciences; Oxygen - blood; Pediatrics; Physical growth; Physiological aspects; Pneumology; Rats; Rats, Sprague-Dawley; Respiratory system : syndromes and miscellaneous diseases; Risk factors; SIDS; Spine; Sudden Infant Death - blood; Sudden Infant Death - cerebrospinal fluid; Sudden Infant Death - etiology; Sudden infant death syndrome; Time Factors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vitreous Body - chemistry; United States; Human; Oxygen; Pathophysiology; Respiratory disease; Pathogenesis; Sudden death; Infant; Cerebrospinal fluid; Enzyme immunoassay; Syndrome; Vascular endothelium growth factor; Hypoxia; Antecedent
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.111.2.358

Recurrent hypoxemia has been proposed as an important pathophysiological mechanism underlying sudden infant death syndrome (SIDS). However, conflicting results emerged when xanthines were used as markers for hypoxia. The vascular endothelial growth factor (VEGF) gene is highly sensitive to changes in tissue partial oxygen tension, and changes in genomic and protein expression occur even after changes in oxygenation within the physiologic range.
For determining whether hypoxia precedes SIDS, VEGF levels were measured using an enzyme-linked immunosorbent assay in the cerebrospinal fluid (CSF) of 51 SIDS infants and in 33 additional control infants who died of an identifiable cause. In addition, 6 rats that had a chronically implanted catheter in the lateral ventricle were exposed to a short hypoxic challenge, and VEGF concentrations were measured in CSF at various time points for 24 hours. Another set of 6 rats were killed with a pentobarbital overdose, and VEGF CSF levels were obtained at different time points after death.
Mean VEGF concentrations in CSF were 308.2 +/- 299.1 pg/dL in the SIDS group and 85.1 +/- 82.9 pg/dL in those who died of known causes. Mean postmortem delay averaged 22 hours for both groups. In rat experiments, hypoxic exposures induced time-dependent increases in VEGF, peaking at 12 hours and returning to baseline at 24 hours. Postmortem duration in the animals was associated with gradual increases in VEGF that reached significance only at 36 hours.
We conclude that VEGF CSF concentrations are significantly higher in infants who die of SIDS. We postulate that hypoxia is a frequent event that precedes the sudden and unexpected death of these infants.