Published online September 1, 2004
PEDIATRICS Vol. 114 No. 3 September 2004, pp. 899-900 (doi:10.1542/peds.2004-0752)
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Reduced Bone Mineralization in Infants Fed Palm Olein-Containing Formula: A Randomized, Double-Blinded, Prospective Trial

Michael T. Clandinin, PhD
Agricultural, Food, and Nutritional Sciences,
University of Alberta,
Edmonton, AB, Canada T6G 2H1

Bodil Larsen, BSc, RD
Neonatal and Pediatric Intensive Care,
Stollery Children’s Hospital,
Edmonton, AB, Canada T6G 2B7

John Van Aerde, MD, PhD, FAAP, FRCPC
Departments of Pediatrics and Neonatology,
Stollery Children’s Hospital,
Edmonton, AB, Canada T6G 2B7

To the Editor.—

Koo et al1 studied the effects of a palm olein formula versus a formula without palm olein on bone mineral content (BMC) and bone mineral density (BMD) in term infants. They suggest that matching the fatty acid profile of human milk by using palm olein in infant formulas may result in an unintended depression of bone mass accretion and may potentially be detrimental to optimum bone health. The article does not mention that infants fed human milk and other currently marketed formulas have BMC and BMD values well below either of the 2 study formulas and all are well within published normative values at both 3 and 6 months of age (see Table 1).


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  		TABLE 1. BMC of Study Milks (Bone Calcification Measurement)

 
It is important to provide the reader with a human milk control group, the comparative gold standard to which infant formulas are compared. Equally important is the large variation in published normative data for BMC and BMD of both human-milk–fed and formula-fed infants. The study by Koo et al neglects to point out that the BMC and BMD values after feeding the palm olein-containing formula are well within published normative range.

The authors go on to state that it is not known whether the differences in BMC and BMD between infants fed formulas with or without palm olein would present beyond 6 months, because there is no literature available. However, it is well published that the bone health of mother’s milk feeders is lower than formula feeders and does not correct itself until the toddler years. 2

Similar studies on bone health have been conducted on both formula- and human-milk–fed infants.2–8 These studies have the same time intervals for testing as Koo et al, ie, baseline, 3 months, and 6 months. The clinical significance of the Koo et al article is not established, because there is no evidence that bone mineral accretion higher than that found in breastfed infants is beneficial.9

REFERENCES

  1. Koo WW, Hammami M, Margeson D, Nwaesei C, Montalto M, Lasekan J. Reduced bone mineralization in infants fed palm olein-containing formula: a randomized, double-blinded, prospective trial. Pediatrics. 2003;111(5 pt 1) :1017 –1023
  2. Butte NF, Wong WW, Hopkinson JM, Smith O, Ellis KJ. Infant feeding mode affects early growth and body composition. Pediatrics. 2000;106 :1355 –1366[Abstract/Free Full Text]
  3. Avila-Diaz M, Flores-Huerta S, Martinez-Muniz I, Amato D. Increments in whole body mineral content associated with weight and length in pre-term and full-term infants during the first six months of life. Arch Med Res. 2001;32 :288 –292[CrossRef][Web of Science][Medline]
  4. Faerk J, Petersen S, Peitersen B, Michaelsen KF. Diet and bone mineral content at term in premature infants. Pediatr Res. 2000;47 :148 –156[Web of Science][Medline]
  5. Rigo J, Nyamugabo K, Picard TC, Gerard P, Pieltain C, DeCurtis M. Reference values of body composition obtained by dual energy x-ray absorptiometry in preterm and term neonates. J Pediatr Gastroenterol Nutr. 1998;27 :184 –190[CrossRef][Web of Science][Medline]
  6. Koo WW, Walters J, Bush A, Chesney RW, Carlson SE. Dual energy x-ray absorptiometry studies of bone mineral status in newborn infants. J Bone Miner Res. 1996;11 :997 –1002[Web of Science][Medline]
  7. Specker BL, Beck A, Kalkwarf H, Ho M. Randomized trial of varying mineral intake on total body bone mineral accretion during the first year of life. Pediatrics. 1997;99(6) . Available at: www.pediatrics.org/cgi/content/full/99/6/e12
  8. Kennedy K, Fewtrell M, Morley R, et al. Double-blind, randomized trial of a synthetic triacylglycerol in formula-fed term infants: effects on stool biochemistry, stool characteristics, and bone mineralization. Am J Clin Nutr. 1999;70 :920 –927[Abstract/Free Full Text]
  9. Schanler RJ, Burns PA, Abrams SA, Garza C. Bone mineralization outcomes in human milk-fed preterm infants. Pediatr Res. 1992;31 :583 –586[Web of Science][Medline]
 
Winston W. K. Koo, MB BS
Department of Pediatrics,
Wayne State University,
Detroit, MI 48201

In Reply.—

We appreciate the opportunity to respond to the views expressed by Clandinin et al regarding our recent publication comparing bone mineral content (BMC) in groups of infants randomized to receive 1 of 2 infant formulas.1 The premise that generally applicable, normative reference values for BMC already exist in infants is incorrect. Unlike the situation in adults, there are no established reference normative bone data from a large number of infants. Furthermore, the variability of the values and the differences in methodology used to obtain the cited values render the Clandinin et al synthesis of these studies of little value in creating a context for interpretation of our recently published study.

The data on BMC generated in infant populations have used many types of devices from multiple manufacturers. For example, single-photon absorptiometry and dual-energy x-ray absorptiometry (DXA) from several manufacturers have both been used in these studies. Single-photon absorptiometry measured BMC from a small segment of the forearm, whereas DXA measures total body BMC. Some of these systems are better validated than others for use in infants. There are also software complexities even with the use of a single device in a study. Some studies have directly assessed total body BMC, and others have used extrapolations from regional measurements. The populations studied have also differed from the standpoints of geographical location, ethnic background, body size, and gestational and postnatal ages of the subjects. No synthesis of this literature can lead to meaningful normative values.

To date, our BMC data represent the most valid and realistic bone data in infants, because 80% of our data were collected on the most recent generation of a DXA device with the highly efficient fan-beam scan. The remainder was collected by using pencil-beam DXA, still the most used DXA technique worldwide. BMC data collected on both instruments in our laboratory have been validated and verified with chemically analyzed whole-body calcium and ash content (the accepted true measures of BMC) of piglets.2,3 Most available data on BMC in growing subjects lack this validation, and pencil-beam DXA underestimated the true BMC.4–6 Our pencil-beam DXA data were appropriately cross calibrated7 and converted to the fan-beam values. The data presented in our article1 are closer to the true BMC than the historical data cited by Clandinin et al.

Because of the limitations of the existing methods and studies, comparisons of absolute BMC among feeding groups is best done within a study. Even within a study, the exclusivity of breastfeeding varies with increasing age,8,9 and the use of several versions of software9,10 can adversely affect the validity of DXA measurements.11,12

Studies8,13 have demonstrated that exclusively breastfed infants have BMC similar to those fed milk-based formula without palm olein (PO) but higher than those fed PO milk-based formula when evaluated in the same study. One of these studies8 evaluated BMC in normal infants fed either a PO-containing formula or a PO-free formula, with a breastfed reference group. At 1 month of age, the breastfed group (when 28 of 31 infants were exclusively breastfed) had significantly higher BMC than those in the PO group. However, as the infants in the breastfed group became older, they consumed increasing amounts of PO-containing formula and averaged 16 oz/day at 3 months and 23 oz/day at 6 months. As the breastfed infants were given increasing amounts of the PO formula, their bone mass accretion resembled that of infants who consumed the PO formula exclusively. Consequently, their bone mass was significantly lower than the infants fed formula without PO at 3 and 6 months of age.

It was not the purpose of our article to compare the formulas evaluated with breastfed infants. Such a comparison, especially with exclusively breastfed infants, would be of potential interest and, at this point, of unknown significance. The high prevalence of clinical complications of osteoporosis is related to insufficient bone mass,14 and even the association of childhood fractures with low bone mass15 or calcium intake16 indicate higher rather than lower BMC to be of likely clinical benefit. To this end, life-cycle strategies to encourage initial accretion and later maintenance of higher BMC are becoming an important nutrition goal of primary practice.14 Infancy is a period of extremely rapid skeletal growth with a gain of ~25 to 30 cm in length17 and tripling of the bone mass.18 The data from our randomized, double-blind, controlled clinical trial indicate that avoidance of PO-oil–dominant formulas in infancy can contribute to achieving this goal of optimize bone mass accretion.

REFERENCES

  1. Koo WWK, Hammami M, Margeson DP, Nwaesei C, Montalto MB, Lasekan JB. Reduced bone mineralization in infants fed palm olein containing formula: a randomized, double-blinded, prospective trial. Pediatrics. 2003;111 :1017 –1023[Abstract/Free Full Text]
  2. Koo WWK, Hammami M, Hockman EM. Use of fan beam dual energy x-ray absorptiometry to measure body composition of piglets. J Nutr. 2002;132 :1380 –1383[Abstract/Free Full Text]
  3. Koo WW, Hammami M, Hockman EM. Validation of bone mass and body composition measurements in small subjects with pencil beam DXA. J Am Coll Nutr. 2004;23 :79 –84[Abstract/Free Full Text]
  4. Koo WWK, Massom LR, Walters J. Validation of accuracy and precision of dual energy x-ray absorptiometry for infants. J Bone Miner Res. 1995;10 :1111 –1115[Web of Science][Medline]
  5. Picaud JC, Rigo J, Nyamugabo K, Milet J, Senterre J. Evaluation of dual-energy x-ray absorptiometry for body composition assessment in piglets and term human neonates. Am J Clin Nutr. 1996;63 :157 –163[Abstract/Free Full Text]
  6. Fusch C, Slotboom J, Fuehrer U, et al. Neonatal body composition: dual energy x-ray absorptiometry, magnetic resonance imaging, and three-dimensional chemical shift imaging versus chemical analysis in piglets. Pediatr Res. 1999;46 :465 –473[Web of Science][Medline]
  7. Koo WWK, Hammami M, Hockman EM. Interchangeability of pencil- and fan- beam dual-energy x-ray absorptiometry measurements in small subjects. Am J Clin Nutr. 2003;78 :236 –240[Abstract/Free Full Text]
  8. Specker BL, Beck A, Kalkwarf H, Ho M. Randomized trial of varying mineral intake on total body bone mineral accretion during the first year of life. Pediatrics. 1997;99(6) . Available at www.pediat=rics.org/cgi/content/full/99/6/e12
  9. Butte NF, Wong WW, Hopkinson JM, Smith EO, Ellis KJ. Infant feeding mode affects early growth and body composition. Pediatrics. 2000;106 :1355 –1366
  10. Butte NF, Hopkinson JM, Wong WW, Smith EO, Ellis KJ. Body composition during the first 2 years of life: an updated reference. Pediatr Res. 2000;47 :578 –585[Web of Science][Medline]
  11. Koo WWK, Walters J, Bush AJ. Technical considerations of dual-energy x-ray absorptiometry-based bone mineral measurements for pediatric studies. J Bone Miner Res. 1995;10 :1998 –2004[Web of Science][Medline]
  12. Koo WWK, Hockman EM, Hammami M. Dual energy x-ray absorptiometry measurements in small subjects: conditions affecting clinical measurements. J Am Coll Nutr. 2004;23 :212 –219[Abstract/Free Full Text]
  13. Kennedy K, Fewtrell MS, Morley R, et al. Double-blind, randomized trial of a synthetic triacylglycerol in formula-fed term infants: effects on stool biochemistry, stool characteristics, and bone mineralization. Am J Clin Nutr. 1999;70 :920 –927
  14. National Institutes of Health. Osteoporosis Prevention, Diagnosis, and Therapy. National Institutes of Health Consensus Statement 17:1. Bethesda, MD: National Institutes of Health; 2000
  15. Jones IE, Taylor RW, Williams SM, Manning PJ, Goulding A. Four-year gain in bone mineral in girls with and without past forearm fractures: a DXA study. J Bone Miner Res. 2002;17 :1065 –1072[CrossRef][Web of Science][Medline]
  16. Goulding A, Rockell JE, Black RE, Grant AM, Jones IE, Williams SM. Children who avoid drinking cow’s milk are at increased risk for prepubertal bone fractures. J Am Diet Assoc. 2004;104 :250 –253[CrossRef][Web of Science][Medline]
  17. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC Growth Charts: United States. Advance Data From Vital and Health Statistics, No. 314. Hyattsville, MD: National Center for Health Statistics; 2000
  18. Koo WWK, Bush AJ, Walters J, Calson SE. Postnatal development of bone mineral status during infancy. J Am Coll Nutr. 1998;17 :65 –70[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics

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