BackgroundLack of physical stimulation may contribute to metabolic bone disease of preterm infants resulting in poor bone mineralization and growth. Physical activity programs combined with adequate nutrition might help to promote bone mineralization and growth.ObjectivesTo determine the effect of physical activity programs on bone mineralization, the risk of fractures and growth in preterm infants.Search strategyThe standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. The search included the CENTRAL (The Cochrane Library, Issue 3, 2009), MEDLINE, EMBASE, CINAHL (1966 to September 2009), cross-references and handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine.Selection criteriaRandomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises) to no organized physical activity programs in preterm infants.Data collection and analysisData collection, study selection, and data analysis were performed according to the methods of the CNRG.Main resultsEight trials enrolling 214 preterm infants (gestational age 26 to 34 weeks) were included in this review. All were small (N = 16 to 49) single center studies evaluating daily physical activity for 3.5 to 8 weeks during initial hospitalization. The methodological quality and reporting of all trials was limited.Three trials demonstrated moderate short-term benefits of physical activity on bone mineralization at completion of the physical activity program. The only trial assessing long-term effects on bone mineralization showed no effect of physical activity administered during initial hospitalization on bone mineralization at 12 months corrected age. Meta-analysis from three trials demonstrated a positive effect of physical activity on daily weight gain (Weighted Mean Difference (WMD) 2.77 g/kg/d, 95% CI 1.62, 3.92). Data from three trials showed a positive effect on linear growth (WMD 0.14 cm/week, 95% CI 0.02, 0.26) but not on head growth (WMD -0.03 cm/week, 95% CI -0.14, 0.09) during the study period. None of the trials assessed fractures or other outcomes relevant to this review.Authors' conclusionsThere is some evidence that physical activity programs might promote short-term weight gain and bone mineralization in preterm infants. Data is inadequate to assess harm or long-term effects. Current evidence does not support the routine use of physical activity programs in preterm infants. Further trials incorporating infants with a high baseline risk of osteopenia are required. These trials should address adverse events, long-term outcomes, and the effects of nutritional intake (calories, protein, calcium, phosphorus).