Management of neonatal bone health
- Steven A Abrams, MD
Steven A Abrams, MD
- Section Editor — Neonatology
- Professor, Department of Pediatrics
- Dell Medical School at the University of Texas at Austin
- Section Editors
- Joseph A Garcia-Prats, MD
Joseph A Garcia-Prats, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
- Kathleen J Motil, MD, PhD
Kathleen J Motil, MD, PhD
- Section Editor — Pediatric Nutrition
- Professor of Pediatric Nutrition
- Baylor College of Medicine
Bone health is a critically important concern in the neonate, especially for premature infants who are at risk for rickets. Because of their rapid growth, all neonates when compared with older individuals have higher relative requirements of calcium (Ca) and phosphorus (P), which are critical components for bone structural integrity and growth. Preterm infants have even greater dietary requirements, as they need to compensate for the loss of accretion of these nutrients during the third trimester of pregnancy.
The management of bone health in neonates, including preterm infants, will be reviewed here.
Neonatal bone health is critical during this active period of growth. As a result, it is imperative that infants receive the necessary intake of the key nutrients calcium (Ca) and phosphorus (P) to ensure adequate mineralization for bone structural integrity and growth. The daily requirement of these nutrients is affected by the gestational age of the infant, and factors that affect intestinal absorption and urinary excretion.
Gestational age and placental transfer — During pregnancy, calcium and phosphorus are actively transferred from the mother to the fetus, reaching a peak accretion rate at 32 to 36 weeks gestation for calcium of 100 to 130 mg/kg of fetal weight per day, and for phosphorus, 60 to 70 mg/kg of fetal weight per day [1-4]. The third trimester is the period of most active growth and the increased accretion rate is in response to the higher fetal needs for the developing skeleton. As a result, requirements of Ca and P increase with decreasing gestational age to compensate for the loss of accretion of these minerals.
In particular, extremely low birth weight (ELBW) infants (birth weights below 1000 g) or those born before 27 weeks gestation are at high risk for rickets [3,5,6]. Unfortified human milk, parenteral nutrition, and formulas designed for term infants do not contain enough Ca and P to fully meet the needs for bone mineralization in preterm infants. As a result, the use of these diets without further supplementation would limit bone growth, resulting in rickets, and potentially increase the risk of bone fractures. (See 'Rickets in premature infants' below.)
- Widdowson EM. Importance of nutrition in development, with special reference to feeding low-birth-weight infants. In: Meeting Nutritional Goals for Low-Birth-Weight Infants, Sauls HS, Bachhuber WL, Lewis LA (Eds), Ross Laboratories, Columbus 1982. p.4.
- Ziegler EE, O'Donnell AM, Nelson SE, Fomon SJ. Body composition of the reference fetus. Growth 1976; 40:329.
- Abrams SA, Committee on Nutrition. Calcium and vitamin d requirements of enterally fed preterm infants. Pediatrics 2013; 131:e1676.
- Ellis KJ, Shypailo RJ, Schanler RJ. Body composition of the preterm infant. Ann Hum Biol 1994; 21:533.
- Backström MC, Kuusela AL, Mäki R. Metabolic bone disease of prematurity. Ann Med 1996; 28:275.
- Rigo J, De Curtis M, Pieltain C, et al. Bone mineral metabolism in the micropremie. Clin Perinatol 2000; 27:147.
- Bronner F, Salle BL, Putet G, et al. Net calcium absorption in premature infants: results of 103 metabolic balance studies. Am J Clin Nutr 1992; 56:1037.
- Schanler RJ, Rifka M. Calcium, phosphorus and magnesium needs for the low-birth-weight infant. Acta Paediatr Suppl 1994; 405:111.
- Abrams SA, Esteban NV, Vieira NE, Yergey AL. Dual tracer stable isotopic assessment of calcium absorption and endogenous fecal excretion in low birth weight infants. Pediatr Res 1991; 29:615.
- Hicks PD, Rogers SP, Hawthorne KM, et al. Calcium absorption in very low birth weight infants with and without bronchopulmonary dysplasia. J Pediatr 2011; 158:885.
- Rowe J, Rowe D, Horak E, et al. Hypophosphatemia and hypercalciuria in small premature infants fed human milk: evidence for inadequate dietary phosphorus. J Pediatr 1984; 104:112.
- Mize CE, Uauy R, Waidelich D, et al. Effect of phosphorus supply on mineral balance at high calcium intakes in very low birth weight infants. Am J Clin Nutr 1995; 62:385.
- Senterre J, Salle B. Renal aspects of calcium and phosphorus metabolism in preterm infants. Biol Neonate 1988; 53:220.
- Agostoni C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr 2010; 50:85.
- Nutritional care of preterm infants: Scientific basis and practical guidelines, Koletzko B, Poindexter B, Uauy R (Eds), Karger, Basel, Switzerland 2014.
- Rowe JC, Goetz CA, Carey DE, Horak E. Achievement of in utero retention of calcium and phosphorus accompanied by high calcium excretion in very low birth weight infants fed a fortified formula. J Pediatr 1987; 110:581.
- Nehra D, Carlson SJ, Fallon EM, et al. A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for metabolic bone disease. JPEN J Parenter Enteral Nutr 2013; 37:570.
- Fort P, Salas AA, Nicola T, et al. A Comparison of 3 Vitamin D Dosing Regimens in Extremely Preterm Infants: A Randomized Controlled Trial. J Pediatr 2016; 174:132.
- Natarajan CK, Sankar MJ, Agarwal R, et al. Trial of daily vitamin D supplementation in preterm infants. Pediatrics 2014; 133:e628.
- Ziegler EE, Biga RL, Fomon SJ. Nutritional requirements of the premature infant. In: Textbook of Pediatric Nutrition, Suskind RM (Ed), Raven Press, New York 1981. p.29.
- Schanler RJ, Oh W. Composition of breast milk obtained from mothers of premature infants as compared to breast milk obtained from donors. J Pediatr 1980; 96:679.
- Atkinson SA, Radde IC, Anderson GH. Macromineral balances in premature infants fed their own mothers' milk or formula. J Pediatr 1983; 102:99.
- Schanler RJ. Calcium and phosphorus absorption and retention in preterm infants. Exp Med 1991; 2:24.
- Butte NF, Garza C, Smith EO, Nichols BL. Human milk intake and growth in exclusively breast-fed infants. J Pediatr 1984; 104:187.
- Koo WW, Sherman R, Succop P, et al. Sequential bone mineral content in small preterm infants with and without fractures and rickets. J Bone Miner Res 1988; 3:193.
- Lucas A, Brooke OG, Baker BA, et al. High alkaline phosphatase activity and growth in preterm neonates. Arch Dis Child 1989; 64:902.
- Rowe JC, Wood DH, Rowe DW, Raisz LG. Nutritional hypophosphatemic rickets in a premature infant fed breast milk. N Engl J Med 1979; 300:293.
- Abrams SA, Schanler RJ, Tsang RC, Garza C. Bone mineralization in former very low birth weight infants fed either human milk or commercial formula: one-year follow-up observation. J Pediatr 1989; 114:1041.
- Abrams SA, Schanler RJ, Garza C. Bone mineralization in former very low birth weight infants fed either human milk or commercial formula. J Pediatr 1988; 112:956.
- Schanler RJ, Abrams SA. Postnatal attainment of intrauterine macromineral accretion rates in low birth weight infants fed fortified human milk. J Pediatr 1995; 126:441.
- Prestridge LL, Schanler RJ, Shulman RJ, et al. Effect of parenteral calcium and phosphorus therapy on mineral retention and bone mineral content in very low birth weight infants. J Pediatr 1993; 122:761.
- Schulzke SM, Kaempfen S, Trachsel D, Patole SK. Physical activity programs for promoting bone mineralization and growth in preterm infants. Cochrane Database Syst Rev 2014; :CD005387.
- Mitchell SM, Rogers SP, Hicks PD, et al. High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support. BMC Pediatr 2009; 9:47.
- Moreira A, Swischuk L, Malloy M, et al. Parathyroid hormone as a marker for metabolic bone disease of prematurity. J Perinatol 2014; 34:787.
- Cooke RJ, Embleton ND, Griffin IJ, et al. Feeding preterm infants after hospital discharge: growth and development at 18 months of age. Pediatr Res 2001; 49:719.
- Carver JD, Wu PY, Hall RT, et al. Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge. Pediatrics 2001; 107:683.
- Lucas A, Fewtrell MS, Morley R, et al. Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants. Pediatrics 2001; 108:703.
- Lyon AJ, McIntosh N, Wheeler K, Williams JE. Radiological rickets in extremely low birthweight infants. Pediatr Radiol 1987; 17:56.
- Lucas-Herald A, Butler S, Mactier H, et al. Prevalence and characteristics of rib fractures in ex-preterm infants. Pediatrics 2012; 130:1116.
- Abrams SA. Enteral feeding of the preterm infant: An update of recent findings. In: Baillieres Clinical Paediatrics: Nutritional Support, Ryan S (Ed), Bailliere Tindall, London 1997. p.305.
- Rigo J, Pieltain C, Salle B, Senterre J. Enteral calcium, phosphate and vitamin D requirements and bone mineralization in preterm infants. Acta Paediatr 2007; 96:969.
- Abrams SA, Griffin IJ, Davila PM. Calcium and zinc absorption from lactose-containing and lactose-free infant formulas. Am J Clin Nutr 2002; 76:442.
- 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.
- Abrams SA. Dietary guidelines for calcium and vitamin D: a new era. Pediatrics 2011; 127:566.
- Gestational age and placental transfer
- Intestinal absorption
- Renal excretion and absorption
- MANAGEMENT OF BONE HEALTH IN PRETERM INFANTS
- In-hospital management
- - Enteral nutrition
- Calcium and phosphorus
- Vitamin D
- Choice of dietary source: fortified human milk and preterm formula
- - Parenteral nutrition
- - Physical stimulation
- - Assessment and management
- Postdischarge management
- - Breastfed infants
- - Formula-fed infants
- RICKETS IN PREMATURE INFANTS
- Risk factors
- Clinical features
- MANAGEMENT OF BONE HEALTH IN TERM INFANTS
- Human milk
- - Vitamin D supplementation
- - Vitamin D
- SUMMARY AND RECOMMENDATIONS