Author's Response to Letter

Abstract

Authors' response: Thank you for the opportunity to respond to these comments regarding our study (1). The question of primary interest in our study was whether the type of feeding during the first 4 months of life affected bone mineralization at 4 years of age. We acknowledge that there are some differences reported in bone mineralization up to 1 year of age, but the bone accreted by 12 months contributes only 10% to 20% to the bone density achieved in young adulthood. This issue is highly relevant because dietary intake after 12 months has far greater impact on bone density than intake during infancy (2). So, Dr. Koo is right, in that we have not specifically isolated the effect of palm olein based formulas. Our study, however, found no difference in bone mineral content at 4 years of age regardless of what babies consume during the first 4 months of life. We believe our study was designed to adequately detect a clinically significant effect relevant to long-term outcomes. The articles cited by Dr. Koo as justification for why our study could not measure the persistence of a negative effect from palm olein oil predominant formulas all measured bone mineralization outcomes in infants up to 1year of age (3,4,5). Of these studies, the longest follow-up was 12 months of age in Specker et al. (3), and there were no differences in bone mass among the feeding groups studied. Therefore, not all of the above cited studies demonstrated feeding related changes in bone mineralization up to 1 year of age. It is because of this lack of consistent results up to 1 year of age that we felt a longer-term follow-up study in normal healthy children would help clarify the issue. In response to the statement of inappropriate sample size calculation, we agree that there are many factors that may influence bone mass at the age that we studied. As discussed in our article, factors such as solid food intake, heredity, etc., are difficult if not impossible to control in this type of long-term analysis. Dr. Koo suggests that a more appropriate approach to determining the sample size would be to base the calculation on the absolute difference of mean bone mineral content of 16.3 g at the end of formula feeding that was observed in his article (5). This, however, is not justified because there is no rationale given as to why this represents a clinically relevant difference in the 4-year-old age group nor in the age group (6 months) he studied. This 16.3 g difference would represent 2.9% of the average value found for the human milk group in our study, which is much smaller that the 7.3% difference between formula groups found by Koo. Our study was powered to detect a difference of 0.52 standard deviation units between feeding groups, which is similar to the rationale used to estimate sample size in Koo's article. It did not seem appropriate to us to design our study based on an absolute difference observed at 6 months that was statistically significant but not clinically relevant. The Methods section of our article describes the details regarding procedures that were performed to standardize the bone densitometry (DEXA) examination and ensure valid data. The analysis of the DEXA results used analysis of covariance, which controlled for study site, sex, and initial body weight/height parameters. We agree with Dr. Koo that evidence-based medicine is critical to providing the best possible recommendations for our patients regarding feeding options and their long-term effects. However, these recommendations should not be based on extrapolating information from infant studies to beyond 12 months of age. We believe that our study contributes positively to the body of scientific knowledge regarding the impact of infant feeding on bone health at 4 years of age. Rosemary J. Young, MS, RN Dean L. Antonson, MD University of Nebraska Medical Center Omaha, NE Paul W. Ferguson, PhD Mead Johnson Nutritionals Evansville, IN Nancy D. Murray, MS, RN The Center for Human Nutrition Omaha, NE Kim Merkel, RPh Mead Johnson Nutritionals Evansville, IN Timothy E. Moore, MD University of Nebraska Medical Center Omaha, NE