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Reply to A Lapillonne and BL Salle

Department of Pediatrics HSC 3V42 McMaster University Hamilton, Ontario, Canada L8N 3Z5

Dear Sir:

Interpretation of measurements of bone mineral content (BMC) in prematurely born infants is difficult; confounding variables such as gestational age, body size, body composition, and dietary intake must all be considered. It is gratifying that Lapillonne and Salle share our concern about this difficulty. The issue of size-related artifacts in the analysis of bone mineral measures was addressed previously by Prentice et al (1) in adults and by Molgaard et al (2) in children. These authors share our view that measures of body size, other than total body mass [eg, lean mass or height-(length)-for-age], are important variables to consider when expressing the whole-body BMC of subjects for research purposes.

Lapillonne and Salle give the example that, in their study, preterm infants fed a preterm formula or enriched mother's milk had a mean difference in BMC of 18.6 g that was in part explained by a mean difference in body weight of 401 g (3). Our data (4), however, do not confirm the hypothesis of these authors that body weight is the best predictor of BMC in infants. For example, in our study (4), the preterm infants with the lowest body weight at full-term age (3.164 kg), who were fed mother's milk fortified with calcium glycerophosphate, had a BMC only 4.6 g less than that of the preterm infants with the highest body weight (3.462 kg) at full-term age, who were fed preterm formula. Thus, despite a mean difference in body weight of 398 g (similar to the difference in body weight between the diet groups in Lapillonne et al's study), whole-body BMC was not significantly different between the 2 groups. In addition, whereas BMC was lower in preterm infants than in infants born full term, albeit by only 13.9 g, the mean body weight of the preterm infants was actually greater (3.642 kg compared with 3.405 kg). In this example, differences in length and in the proportions of lean body mass and fat mass distinguished the preterm from the full-term infants. Thus, we predict that in such instances BMC is best expressed as a function of lean mass or body length.

The results of 2 recent studies that showed that lean mass may be the preferred basis on which to express BMC in preterm infants when body composition is variable between dietary treatment groups are summarized in Table 1. Differences in BMC of sometimes > 20 g between diet groups (breast-fed compared with formula-fed infants or standard formula compared with nutrient-enriched formula), when expressed as a function of corrected age, cannot be explained by differences in body weight. In both of the studies noted in Table 1, the percentage fat mass of the infants was significantly different between the diet groups at the ages noted: breast-fed infants had a higher fat mass than formula-fed infants (5) and infants fed the standard energy-enriched formula had a greater percentage body fat mass than infants fed the enriched formula (6). In these studies, when BMC was expressed as a function of the lean compartment rather than of whole body weight, the significant difference in BMC between the diet groups disappeared.

Although body weight appears to "correct" for differences in BMC if infant groups differ in body weight, we believe that it is more accurate to express BMC as a function of lean mass because body weight does not necessarily reflect body composition, as supported by the above-mentioned examples. If a difference in body composition is overlooked, diet may be seen as a major factor contributing to a lower BMC (eg, breast-feeding compared with formula-feeding); however, differences in body composition also contribute significantly to the differences in whole-body BMC.

Lapillonne et al's (3) observation that BMC in preterm infants at full-term age is lower than that of infants born at full term was not referenced in our paper (4) because it did not address our initial research question. Lapillonne et al's data (3) were difficult to compare with our data because of differences in the study population (their full-term infants had a BMC of only 62.4 g, which was similar to the BMC of our preterm infants at full-term age), in the study design (lack of randomization), and in dietary management. Both Lapillonne et al's study (3) and our recent study (5) showed that the infant's diet after discharge from the hospital appears to have more influence on BMC during the first year of life than does the infant's diet while in the hospital.

We agree that interpretation of BMC in preterm infants remains a complicated task. However, because it is possible to measure BMC, fat mass, and lean mass with DXA, it is our view that DXA-derived data should be compared on the basis of body composition rather than on the basis of weight alone because body-composition data provide a more realistic comparison between preterm infants receiving different dietary treatments.

1. Prentice A, Parsons TJ, Cole TJ. Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. Am J Clin Nutr 1994;60:837–42.
2. Molgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF. Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 1997;76:9–15.
3. Lapillonne AA, Glorieux FH, Salle B, et al. Mineral balance and whole body bone mineral content in very-low-birth-weight infants. Acta Paediatr Suppl 1994;405:117–22.
4. Wauben IP, Atkinson SA, Grad TL, et al. Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized controlled trial. Am J Clin Nutr 1998;67:465–72.
5. Wauben IPM, Atkinson SA, Shah JK, Paes B. Growth and body composition of preterm infants: influence of nutrient fortification of mother's milk in hospital and breastfeeding post-hospital discharge. Acta Paediatr 1998;87:780–5
6. Brunton JA, Saigal S, Atkinson SA. Growth and body composition in infants with bronchopulmonary dysplasia up to 3 months corrected age: a randomized trial of a high energy nutrient enriched formula fed after hospital discharge. J Pediatr 1998;133:340–5.

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