Potential Biochemical Growth Markers in Premature Infants

Abstract
Identification of a biochemical marker of growth in low birth weight (LBW) infants would be of benefit to rapidly assess the effects of illness and/or therapeutic intervention. The aims of the present study were (1) to measure serially the C-terminal fragment of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) in LBW infants during the first 6 weeks of life; (2) to correlate the changes in PICP, BSAP, and OC with the changes in weight; and (3) to evaluate PICP levels as a marker for bronchopulmonary dysplasia (BPD). Premature neonates (≤ 36 weeks of gestation) had cord blood and then weekly blood samples taken from up to 6 weeks after birth. Daily changes in weight were recorded. Measurements of serum PICP, BSAP, and OC were done in duplicate by immunoassay. In a subset population (25-30 weeks), PICP levels in the first 4 weeks of life were evaluated as a marker for subsequent development of BPD. A total of 77 infants had serum PICP and BSAP measured. The mean (±SEM) gestational ages of all the infants were 30.4 (± 0.3) weeks and birth weights 1477 (±55) g. Fifteen infants also had measurements of OC done. In these 15 infants, change in weight was correlated significantly with PICP (p < 0.0001), but not with either BSAP (p = 0.8) or OC measurements (p = 0.9). In appropriate for gestational age (AGA) infants (n = 66), the PICP values decreased from the cord blood values to the week 1 measurement, coinciding with the fall in weight over the same time period. BSAP values, on the other hand, continued to increase from birth onwards. Over the first 6 weeks of postnatal life in these infants, change in weight had a stronger positive correlation with PICP (R 2 = 0.43, p < 0.0001) than BSAP (R 2 = 0.03, p < 0.01). In the subset population, PICP levels at week 4 were significantly lower (p < 0.04) in those infants who subsequently developed BPD. PICP measurements are correlated with somatic growth in premature infants and could be used as a biochemical marker in infants who develop BPD.