Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Ultrasound for the assessment of bone quality in preterm and term infants

Abstract

Objective:

As 80% of intrauterine bone mineralization takes place during the last trimester of pregnancy, preterm infants should be supplemented postnatally with optimal doses of calcium, phosphate and vitamin D. Calcium and phosphate excretion in the urine may be used to monitor individual mineral requirements, but are sometimes difficult to interpret. The objective of this study was to assess the value of quantitative ultrasound (QUS) for the analysis of bone status in neonates.

Study Design:

All admissions to three independent tertiary neonatal intensive care units were studied. In 172 preterm and term infants with a gestational age between 23 and 42 weeks (mean 33.8±5.0) and a birth weight from 405 to 5130 g (mean 2132±1091 g) bone status was evaluated prospectively by quantitative ultrasound velocity using a standardized protocol. Infants were followed in regular intervals up to their first discharge home. While measurements were conducted in weekly intervals initially (n=55), 2-week intervals were regarded as sufficient thereafter due to limited changes in QUS values within the shorter period. Infants with a birth weight below 1500 g were followed during outpatient visits until up to 17 months of age.

Result:

The intra-individual day-to-day reproducibility was 0.62%. QUS-values from the first week of life correlated significantly with gestational age and birth weight (r=0.5 and r=0.6; P<0.001). Small-for-gestational-age infants showed lower values for QUS than appropriate-for-gestational-age infants allowing for their gestational age. Follow-up measurements correlated positively with age and weight during the week of measurement (r=0.2 and r=0.4; P=0.001). Comparing bone quality at 40 weeks of age in infants born at term versus infants born at 24 to 28 weeks, preterm infants showed significantly lower QUS than term infants (P<.0001).There was a significant correlation of QUS with serum alkaline phosphatase (P=0.003), the supplementation with calcium, phosphate and vitamin D (P< 0.001 each), as well as risk factors for a reduced bone mineralization. No correlation was found between QUS and calcium or phosphate concentration in serum or urine.

Conclusion:

QUS is a highly reproducible, easily applicable and radiation-free technique that can be used to monitor bone quality in individual newborns. Further prospective randomized-trials are necessary to evaluate, if therapeutic interventions based on QUS are able to prevent osteopenia of prematurity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Rauch F, Schoenau E . Skeletal development in premature infants: a review of bone physiology beyond nutritional aspects. Arch Dis Child Fetal Neonatal Ed 2002; 86: F82–F85.

    Article  CAS  Google Scholar 

  2. Sargent JD, Stukel TA, Kresel J, Klein RZ . Normal values for random urinary calcium to creatinine ratios in infancy. J Pediatr 1993; 123: 393–397.

    Article  CAS  Google Scholar 

  3. Tsang RC . Nutritional needs of the preterm infant: scientific basis and practical guidelines. 2nd edition. Digital Education Publishing, Inc.: Cincinnati, OH, 2005.

    Google Scholar 

  4. Gilsanz V . Bone density in children: a review of the available techniques and indications. Eur J Radiol 1998; 26: 177–182.

    Article  CAS  Google Scholar 

  5. Bouxsein ML, Radloff SE . Quantitative ultrasound of the calcaneus reflects the mechanical properties of calcaneal trabecular bone. J Bone Miner Res 1997; 12: 839–846.

    Article  CAS  Google Scholar 

  6. Fricke O, Tutlewski B, Schwahn B, Schoenau E . Speed of sound: relation to geometric characteristics of bone in children, adolescents, and adults. J Pediatr 2005; 146: 764–768.

    Article  Google Scholar 

  7. Sakata S, Barkmann R, Lochmuller EM, Heller M, Gluer CC . Assessing bone status beyond BMD: evaluation of bone geometry and porosity by quantitative ultrasound of human finger phalanges. J Bone Miner Res 2004; 19: 924–930.

    Article  Google Scholar 

  8. Gluer CC, Eastell R, Reid DM, Felsenberg D, Roux C, Barkmann R et al. Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study. J Bone Miner Res 2004; 19: 782–793.

    Article  Google Scholar 

  9. Rubinacci A, Moro GE, Boehm G, de Terlizzi F, Moro GL, Cadossi R . Quantitative ultrasound for the assessment of osteopenia in preterm infants. Eur J Endocrinol 2003; 149: 307–315.

    Article  CAS  Google Scholar 

  10. Ritschl E, Wehmeijer K, de Terlizzi F, Wipfler E, Cadossi R, Douma D et al. Assessment of skeletal development in preterm and term infants by quantitative ultrasound. Pediatr Res 2005; 58: 341–346.

    Article  Google Scholar 

  11. Pereda L, Ashmeade T, Zaritt J, Carver JD . The use of quantitative ultrasound in assessing bone status in newborn preterm infants. J Perinatol 2003; 23: 655–659.

    Article  Google Scholar 

  12. Litmanovitz I, Dolfin T, Friedland O, Arnon S, Regev R, Shainkin-Kestenbaum R et al. Early physical activity intervention prevents decrease of bone strength in very low birth weight infants. Pediatrics 2003; 112: 15–19.

    Article  Google Scholar 

  13. Gonnelli S, Montagnani A, Gennari L, Martini S, Merlotti D, Cepollaro C et al. Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status. Osteoporos Int 2004; 15: 541–546.

    Article  CAS  Google Scholar 

  14. Nemet D, Dolfin T, Wolach B, Eliakim A . Quantitative ultrasound measurements of bone speed of sound in premature infants. Eur J Pediatr 2001; 160: 736–740.

    Article  CAS  Google Scholar 

  15. Tomlinson C, McDevitt H, Ahmed SF, White MP . Longitudinal changes in bone health as assessed by the speed of sound in very low birth weight preterm infants. J Pediatr 2006; 148: 450–455.

    Article  CAS  Google Scholar 

  16. McDevitt H, Tomlinson C, White MP, Ahmed SF . Quantitative ultrasound assessment of bone in preterm and term neonates. Arch Dis Child Fetal Neonatal Ed 2005; 90: F341–F342.

    Article  CAS  Google Scholar 

  17. Littner Y, Mandel D, Mimouni FB, Dollberg S . Bone ultrasound velocity of infants born small for gestational age. J Pediatr Endocrinol Metab 2005; 18: 793–797.

    Article  Google Scholar 

  18. 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: E12.

    Article  CAS  Google Scholar 

  19. Bauer DC, Gluer CC, Cauley JA, Vogt TM, Ensrud KE, Genant HK et al. Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 1997; 157: 629–634.

    Article  CAS  Google Scholar 

  20. Schonau E, Radermacher A, Wentzlik U, Klein K, Michalk D . The determination of ultrasound velocity in the os calcis, thumb and patella during childhood. Eur J Pediatr 1994; 153: 252–256.

    Article  CAS  Google Scholar 

  21. Shaw JC . Evidence for defective skeletal mineralization in low-birthweight infants: the absorption of calcium and fat. Pediatrics 1976; 57: 16–25.

    CAS  PubMed  Google Scholar 

  22. Wright LL, Glade MJ, Gopal J . The use of transmission ultrasonics to assess bone status in the human newborn. Pediatr Res 1987; 22: 541–544.

    Article  CAS  Google Scholar 

  23. Koo WW, Walters J, Bush AJ, Chesney RW, Carlson SE . Dual-energy X-ray absorptiometry studies of bone mineral status in newborn infants. J Bone Miner Res 1996; 11: 997–102.

    Article  CAS  Google Scholar 

  24. Salle BL, Braillon P, Glorieux FH, Brunet J, Cavero E, Meunier PJ . Lumbar bone mineral content measured by dual energy X-ray absorptiometry in newborns and infants. Acta Paediatr 1992; 81: 953–958.

    Article  CAS  Google Scholar 

  25. Avila-Diaz M, Flores-Huerta S, Martinez-Muniz I, Amato D . Increments in whole body bone mineral content associated with weight and length in pre-term and full-term infants during the first 6 months of life. Arch Med Res 2001; 32: 288–292.

    Article  CAS  Google Scholar 

  26. Chan GM, Armstrong C, Moyer-Mileur L, Hoff C . Growth and bone mineralization in children born prematurely. J Perinatol 2008; 28: 619–623.

    Article  CAS  Google Scholar 

  27. Littner Y, Mandel D, Mimouni FB, Dollberg S . Decreased bone ultrasound velocity in large-for-gestational-age infants. J Perinatol 2004; 24: 21–23.

    Article  Google Scholar 

  28. Littner Y, Mandel D, Mimouni FB, Dollberg S . Bone ultrasound velocity curves of newly born term and preterm infants. J Pediatr Endocrinol Metab 2003; 16: 43–47.

    Article  Google Scholar 

  29. Zadik Z, Price D, Diamond G . Pediatric reference curves for multi-site quantitative ultrasound and its modulators. Osteoporos Int 2003; 14: 857–862.

    Article  Google Scholar 

  30. Sundberg M, Gardsell P, Johnell O, Ornstein E, Sernbo I . Comparison of quantitative ultrasound measurements in calcaneus with DXA and SXA at other skeletal sites: a population-based study on 280 children aged 11 to 16 years. Osteoporos Int 1998; 8: 410–417.

    Article  CAS  Google Scholar 

  31. Baroncelli GI, Federico G, Bertelloni S, de Terlizzi F, Cadossi R, Saggese G . Bone quality assessment by quantitative ultrasound of proximal phalanxes of the hand in healthy subjects aged 3--21 years. Pediatr Res 2001; 49: 713–718.

    Article  CAS  Google Scholar 

  32. Lequin MH, van Rijn RR, Robben SG, Hop WC, van Kuijk C . Normal values for tibial quantitative ultrasonometry in caucasian children and adolescents (aged 6 to 19 years). Calcif Tissue Int 2000; 67: 101–105.

    Article  CAS  Google Scholar 

  33. Minton SD, Steichen JJ, Tsang RC . Bone mineral content in term and preterm appropriate-for-gestational-age infants. J Pediatr 1979; 95: 1037–1042.

    Article  CAS  Google Scholar 

  34. Mercy J, Dillon B, Morris J, Emmerson AJ, Mughal MZ . Relationship of tibial speed of sound and lower limb length to nutrient intake in preterm infants. Arch Dis Child Fetal Neonatal Ed 2007; 92: F381–F385.

    Article  CAS  Google Scholar 

  35. Ahmad I, Nemet D, Eliakim A, Koeppel R, Grochow D, Coussens M et al. Body composition and its components in preterm and term newborns: a cross-sectional, multimodal investigation. Am J Hum Biol 2010; 22: 69–75.

    Article  Google Scholar 

  36. Namgung R, Tsang RC, Sierra RI, Ho ML . Normal serum indices of bone collagen biosynthesis and degradation in small for gestational age infants. J Pediatr Gastroenterol Nutr 1996; 23: 224–228.

    Article  CAS  Google Scholar 

  37. Namgung R, Tsang RC . Factors affecting newborn bone mineral content: in utero effects on newborn bone mineralization. Proc Nutr Soc 2000; 59: 55–63.

    Article  CAS  Google Scholar 

  38. Beltrand J, Alison M, Nicolescu R, Verkauskiene R, Deghmoun S, Sibony O et al. Bone mineral content at birth is determined both by birth weight and fetal growth pattern. Pediatr Res 2008; 64: 86–90.

    Article  Google Scholar 

  39. Zanardo V, Dani C, Trevisanuto D, Meneghetti S, Guglielmi A, Zacchello G et al. Methylxanthines increase renal calcium excretion in preterm infants. Biol Neonate 1995; 68: 169–174.

    Article  CAS  Google Scholar 

  40. Backstrom MC, Kouri T, Kuusela AL, Sievänen H, Koivisto AM, Ikonen RS et al. Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity. Acta Paediatr 2000; 89: 867–873.

    Article  CAS  Google Scholar 

  41. Altuncu E, Akman I, Yurdakul Z, Ozdoğan T, Solakoğlu M, Selim N et al. Quantitative ultrasound and biochemical parameters for the assessment of osteopenia in preterm infants. J Matern Fetal Neonatal Med 2007; 20: 401–405.

    Article  CAS  Google Scholar 

  42. Shrivastava A, Lyon A, Mcintosh N . The effect of dexamethasone on growth, mineral balance and bone mineralisation in preterm infants with chronic lung disease. Eur J Pediatr 2000; 159: 380–384.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to all infants and their parents who took part in this study, to all nurses and doctors for their assistance, and to Heidi Weitmann Coleman for her editorial support. The prototype Osteoson K IV was kindly provided by Minhorst, Meudt, Germany

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B Rack.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rack, B., Lochmüller, EM., Janni, W. et al. Ultrasound for the assessment of bone quality in preterm and term infants. J Perinatol 32, 218–226 (2012). https://doi.org/10.1038/jp.2011.82

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2011.82

Keywords

This article is cited by

Search

Quick links