Morphometric assessment of collagen accumulation in germinal matrix vessels of premature human neonates

Germinal matrix haemorrhage in premature neonates is commonly attributed to vascular immaturity, possibly related to an abbreviated process of angiogenesis. Terminal steps in the progression of angiogenesis are the formation of a subendothelial basal lamina containing collagen IV and an extracellular matrix containing collagens I and III. Immature vessels would predictably be deficient in these collagen subtypes. We analysed germinal matrix (GM), cortical, and white matter (WM) vessels with antibodies specific for collagens I, III and IV to test the hypothesis that GM vessels are immature. Brains were collected during post-mortem from prematurely born human neonates ranging in age from 17 weeks to 36 weeks postconception. All GM vessels were immunoreactive for collagen subtypes I, III and IV. Using digital image analysis, collagen IV immunoperoxidase-labelling was measured in vessels in GM, cortex and WM. Intensity values in GM and WM were normalized relative to cortical intensity within the same subject. At week 17 of gestation, GM vessels exhibited a higher concentration of collagen IV than did WM or cortical vessels. Regression analysis demonstrated that collagen intensity in GM was greater than that in cortex and WM at all stages. We conclude that GM vessels in even the youngest, prematurely born, viable neonates do not exhibit evidence of structural immaturity. The high incidence of GM haemorrhage in premature neonates may be related to factors other than a deficiency in accumulated collagen.