Markers of Type I and III Collagen Turnover as Indicators of Growth Velocity in Very Low Birth Weight Infants

Monitoring postnatal growth in very low birth weight (VLBW) infants is complicated by the difficulty of obtaining reliable measurements. A need thus exists for safe and reliable indicators of such infants' short-term growth velocity. We set out to study whether markers of type I collagen synthesis [amino-terminal propeptide of type I procollagen (PINP)] or degradation [via the matrix metalloproteinase pathway, carboxyl-terminal telopeptide of type I collagen (ICTP)] or of type III collagen synthesis [amino-terminal propeptide of type III procollagen (PIIINP)] could serve as such indicators. PINP, ICTP, and PIIINP were measured for 48 VLBW infants (mean birth weight, 923 g; range, 540-1485 g; mean gestational age, 27.6 wk; range, 23.7-32.7 wk) at the age of 1, 2, 4, and 8 wk. At each time point, these were compared with concurrent growth velocity rigorously assessed by frequent lower leg (knemometry) and weight measurements. PINP showed a significant positive correlation with lower leg growth velocity at 1, 2, and 4 wk and with weight growth velocity at 2, 4, and 8 wk. PIIINP showed a significant positive correlation with lower leg growth at 1, 2, and 8 wk and with weight growth at 2 and 8 wk. The ICTP/PINP ratio, reflecting type I collagen degradation in relation to its synthesis, showed close negative correlations with lower leg growth at 1 wk (r = -0.46; P = 0.003), 2 wk (r = -0.51; P = 0.002), and 4 wk (r = -0.56; P = 0.001) and with weight growth at 2 wk (r = -0.39; P = 0.018), 4 wk (r = -0.59; P = 0.0003), and 8 wk (r = -0.53; P = 0.005). A high ICTP/PINP ratio was an accurate predictor of impaired growth; a high ICTP/PINP ratio was a more rapid and at least as sensitive and specific indicator of slow growth as weight gain. We conclude that PINP, PIIINP, and the ICTP/PINP ratio all reflect postnatal growth velocity in VLBW infants. The most robust of these indicators is the ICTP/PINP ratio, which may thus serve as a clinical tool in assessing short-term growth of these infants.