Physical activity programs for promoting bone mineralization and growth in preterm infants

Lack of physical stimulation may contribute to metabolic bone disease of preterm infants resulting in poor bone mineralization and growth. Physical activity programs in the presence of adequate nutrition might help to promote bone mineralization and growth.

The primary objective of this review was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fractures.

Following the standard search strategy of the Cochrane Neonatal Review Group, a search was conducted in September 2006 including PubMed, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2006), cross-references and handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine. No language restrictions were applied.

Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises for several minutes a day several days per week for at least two weeks) to no organized physical activity programs in preterm infants. Eligible studies included those that provided physical activity for the experimental group, with or without massage and/or tactile stimulation for both experimental and control groups, as well as information on at least one outcome of interest.

Two review authors independently performed searches and extracted data. All three review authors were involved in selection and assessment of quality of studies. The statistical methods included relative risk (RR), risk difference (RD) and number needed to treat (NNT) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, reported with 95% confidence intervals (CI). Heterogeneity was estimated by the I(2) statistic. A fixed effect model was used to pool data for meta-analyses.

Six trials enrolling 169 preterm infants (gestational age 26 to 34 weeks) were included in this review. All were small (N = 20 - 49) single center studies evaluating daily physical activity for 3.5 to 4 weeks during initial hospitalization. The methodological quality and reporting of all trials was poor. None of them stated the methods of concealment of patient allocation, the method of randomization or attempted blinding of the intervention. Only two trials attempted blinding of outcome assessors for outcomes relevant to this review. Two trials (N = 55) demonstrated moderate short-term benefits of physical activity on bone mineralization at completion of the physical activity program. Data was not pooled for meta-analyses due to methodological differences. The only trial (N = 20) 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 (N = 78) demonstrated an effect of physical activity on daily weight gain (WMD 2.77 g/kg/d, 95% CI 1.62, 3.92). Data from two trials (N = 58) showed no effect on linear growth (WMD -0.04 cm/week, 95% CI -0.19, 0.11) or head growth (WMD -0.03 cm/week, 95% CI -0.14, 0.09) during the study period. The I(2) statistic suggested heterogeneity on the analysis of linear growth (p = 0.006, I(2) = 86.9%). None of the trials assessed fractures or other outcomes relevant to this review. Data was insufficient for subgroup analyses based on birth weight and calcium/phosphorus intake.

There is weak evidence from six small randomized trials of poor methodological and reporting quality that physical activity programs might promote moderate short-term weight gain and bone mineralization in preterm infants. The clinical importance of these findings is questionable given the small effect size and low baseline risk of poor bone mineralization and growth in study participants. Data is inadequate to assess harm or long term effects. Current evidence does not justify the standard use of physical activity programs in preterm infants. Further evaluation of this intervention in well designed trials incorporating extremely low birth weight infants who are at high risk of osteopenia is required. Future trials should report on adverse events and long term outcomes including fractures, growth, bone mineralization, skeletal deformities and neurodevelopmental impairment. These trials should address the possibility that nutritional intake (calories, protein, calcium, phosphorus) might modify the effects of physical activity.