Growth Factors, Inflammatory Cytokines and Postnatal Bone Strength in Preterm Infants

Aim: To assess the relationships between growth factors, inflammatory cytokines and postnatal bone development in preterm infants. Methods: Fifty premature infants (24-32 weeks gestational age, mean birth weight: 1,024 ± 50 g) participated in the study. Bone strength was determined weekly by quantitative ultrasound measurements of bone speed of sound (SOS). Blood serum measurements of growth factors included circulating IGF-I and GH binding protein. Measurements of circulating cytokines included the pro-inflammatory mediator interleukin (IL)-6, and the anti-inflammatory mediator IL-1 receptor antagonist. Samples were collected when the preterm infants were stabilized and prior to discharge. Results: Despite a significant increase in body weight (from 1,024 ± 50 to 2,420 ± 59 g, p <0.001) and body length (from 35.4 ± 0.6 to 44.6 ± 0.4 cm, p <0.001) there was a significant decrease in bone SOS during the follow-up period. There was a significant increase in growth factors and a decrease in inflammatory cytokines during the follow-up. Participants were divided into preterm infants who increased bone SOS (bone gainers, n = 16, from 2,867 ± 38 to 2,910 ± 41 m/sec), or decreased bone SOS (bone losers, n = 34, from 2,967 ± 33 to 2,818 ± 28 m/sec) during follow-up. Baseline bone SOS was significantly lower in the bone gainers. Baseline circulating growth factors were higher and inflammatory cytokines lower in the bone gainers; however, only the difference in IL-6 reached statistical significance (6.4 ± 1.6 versus 10.5 ± 1.2 pg/ml, in bone gainers and losers, respectively; p <0.05). Conclusions: Preterm infants with lower bone SOS at birth tend to 'catch-up' during early postnatal weeks. Increases in bone strength in preterm infants were associated with reduced inflammatory state as suggested by lower levels of circulating IL-6.