Knochenmineralmangel bei Frühgeborenen: Prävention mittels Urinmonitoring von Kalzium und Phosphat

Zusammenfassung

Hintergrund:

Ursächlich für den Knochenmineralmangel bei Frühgeborenen (KMMbF) ist eine mangelnde, gleichzeitige Verfügbarkeit von Kalzium (Ca) und Phosphat (P) bei rasch wachsendem Knochen.

Methode:

Literaturrecherche (PubMed) zur Prävention von KMMbF unter Berücksichtigung von Fallstricken des Therapiemonitorings durch Bestimmung von Ca und P im Urin.

Ergebnisse:

Intrauterine Einlagerungsraten von Ca und P können bei Frühgeborenen (FG) erzielt werden, wenn im Urin eine geringe Überschussversorgung mit Ca und P kontinuierlich nachgewiesen werden kann. Eine individuell gesteuerte Supplementierung mit Ca und P scheint sinnvoll, weil große Unterschiede der enteralen Ca-Resorption und der Wachstumsgeschwindigkeit den Ca- und P-Bedarf bestimmen. Wenn eine ausreichende Substitution anhand der Urinkonzentrationen von Ca und P festgestellt werden soll, ist die differenzialdiagnostische Abwägung ernährungsunabhängiger Gründe für eine Kalziurie und/oder Phosphaturie wichtig. Insbesondere müssen Medikamentennebenwirkungen auf die Ca-Ausscheidung und eine Einschränkung der renal-tubulären Phosphatrückresorption bei FG beachtet werden. Die Knochenmineralisation konnte in mehreren Studien auch durch gezielte physische Aktivität der Kinder verbessert werden.

Schlussfolgerungen:

Eine präventive, individuell gesteuerte Ca- und P-Supplementierung von FG nach dem Prinzip der Supplementierung in geringem Überschuss ist zur Vorbeugung eines KMMbF geeignet. Das Urinmonitoring einer adäquaten Ca- und P-Supplementierung von FG erfordert die Beachtung zusätzlicher Faktoren, die die Ca- und P-Ausscheidung im Urin beeinflussen. Darüber hinaus scheint der Einsatz gezielter physischer Aktivität zur Prävention eines KMMbF sinnvoll.

Abstract

Background:

Bone mineral deficiency of prematurity (BMDoP) is caused by the lack of simultaneous availability of calcium (Ca) and anorganic phosphate (P) during rapid skeletal growth.

Methods:

Review of the literature on the prevention of BMDoP, with specific attention to the limitations of the monitoring of urinary calcium and phosphate concentrations.

Results:

Intrauterine bone mineral accretion (BMA) can be achieved in preterm infants if urinary concentrations of Ca and P continuously show that the supplementation with these ions slightly exceeds the actual need. An individually adjusted supplementation with Ca and P appears rational because both growth velocity and enteral Ca absorption are highly variable and determine the need for enteral Ca and P administration. If, however, urinary concentrations of Ca and P are used to determine whether Ca and P supplementation is adequate, mechanisms affecting the urinary excretion of these ions other than nutrition have to be taken into account. Specifically, methylxanthines and diuretics increase the renal Ca losses, and the renal P threshold may be lowered in premature infants. A positive effect of physical activity on BMA has been shown in several studies.

Conclusions:

An individualized Ca and P supplementation in preterm infants aiming for supplementation in a slight excess of the actual need and guided by urinary Ca and P concentrations appears able to prevent BMDoP. Monitoring of urinary Ca and P concentrations needs to take into account non-nutritional factors affecting these concentrations. BMA may further be improved by physical activity.

Schlüsselwörter

Frühgeborene - Knochenmineralmangel bei Frühgeborenen - Osteopenie - Osteopathie - Osteomalazie - Monitoring

Key words

infant premature - osteopenia - bone mineral deficiency of prematurity - osteomalacia - metabolic bone disease - osteopathy

• Literatur

• 1 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: 85-91
• 2 Altuncu E, Akman I, Yurdakul Z et al. Quantitative ultrasound and biochemical parameters for the assessment of osteopenia in preterm infants. J Matern Fetal Neonatal Med 2007; 20: 401-405
• 3 Atkinson SA, Shah JK, McGee C et al. Mineral excretion in premature infants receiving various diuretic therapies. J Pediatr 1988; 113: 540-545
• 4 Atkinson SA, Tsang RC. Calcium, Magnesium, Phosphorus and Vitamin D. In: Tsang RC, Uauy R, Koletzko B, Zlotkin SH. ed. Nutrition of the Preterm Infant Scientific Basis and Practical Guidelines. Cincinnati, Ohio: Digital Educational Publishing, Inc; 2005: 245-276
• 5 Backstrom MC, Maki R, Kuusela AL et al. Randomised controlled trial of vitamin D supplementation on bone density and biochemical indices in preterm infants. Arch Dis Child Fetal Neonatal Ed 1999; 80: F161-F166
• 6 Barltrop D, Oppe TE. Absorption of fat and calcium by low birthweight infants from milks containing butterfat and olive oil. Arch Dis Child 1973; 48: 496-501
• 7 Barltrop D, Oppe TE. Dietary factors in neonatal calcium homoeostasis. Lancet 1970; 2: 1333-1335
• 8 Bert S, Gouyon JB, Semama DS. Calcium, sodium and potassium urinary excretion during the first five days of life in very preterm infants. Biol Neonate 2004; 85: 37-41
• 9 Cameron JR, Mazess RB, Sorenson JA. Precision and accuracy of bone mineral determination by direct photon absorptiometry. Invest Radiol 1968; 3: 141-150
• 10 Campfield T, Braden G, Flynn-Valone P et al. Effect of diuretics on urinary oxalate, calcium, and sodium excretion in very low birth weight infants. Pediatrics 1997; 99: 814-818
• 11 Carroll DM, Doria AS, Paul BS. Clinical-radiological features of fractures in premature infants – a review. J Perinat Med 2007; 35: 366-375
• 12 Carroll WF, Fabres J, Nagy TR et al. Results of Extremely-low-birth-weight Infants Randomized to Receive Extra Enteral Calcium Supply. J Ped Gastroenterol Nutr 2011; 53: 339-345
• 13 Chesney RW, Hamstra AJ, DeLuca HF. Rickets of prematurity. Supranormal levels of serum 1,25-dihydroxyvitamin D. Am J Dis Child 1981; 135: 34-37
• 14 Congdon PJ, Horsman A, Ryan SW et al. Spontaneous resolution of bone mineral depletion in preterm infants. Arch Dis Child 1990; 65: 1038-1042
• 15 Dabezies EJ, Warren PD. Fractures in very low birth weight infants with rickets. Clin Orthop Relat Res 1997; 233-239
• 16 Day GM, Chance GW, Radde IC et al. Growth and mineral metabolism in very low birth weight infants. II. Effects of calcium supplementation on growth and divalent cations. Pediatr Res 1975; 9: 568-575
• 17 De Curtis M, Pieltain C, Studzinski F et al. Evaluation of weight gain composition during the first 2 months of life in breast- and formula-fed term infants using dual energy X-ray absorptiometry. Eur J Pediatr 2001; 160: 319-320
• 18 Fee BA, Weil Jr. WB. Body Composition of Infants of Diabetic Mothers by Direct Analysis. Ann N Y Acad Sci 1963; 110: 869-897
• 19 Fewtrell MS, Williams JE, Singhal A et al. Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm. Bone 2009; 45: 142-149
• 20 Gefter WB, Epstein DM, Anday EK et al. Rickets presenting as multiple fractures in premature infants on hyperalimentation. Radiology 1982; 142: 371-374
• 21 Geggel RL, Pereira GR, Spackman TJ. Fractured ribs: unusual presentation of rickets in premature infants. J Pediatr 1978; 93: 680-682
• 22 Giapros VI, Papaloukas AL, Andronikou SK. Urinary mineral excretion in preterm neonates during the first month of life. Neonatology 2007; 91: 180-185
• 23 Gimpel C, Krause A, Franck P et al. Exposure to furosemide as the strongest risk factor for nephrocalcinosis in preterm infants. Pediatr Int 2010; 52: 51-56
• 24 Glorieux FH, Salle BL, Delvin EE et al. Vitamin D metabolism in preterm infants: serum calcitriol values during the first five days of life. J Pediatr 1981; 99: 640-643
• 25 Grahnen H, Sjolin S, Stenstrom A. Mineralization defects of primary teeth in children born pre-term. Scand J Dent Res 1974; 82: 396-400
• 26 Greer FR, Lane J, Weiner S et al. An accurate and reproducible absorptiometric technique for determining bone mineral content in newborn infants. Pediatr Res 1983; 17: 259-262
• 27 Hallberg L. Does calcium interfere with iron absorption?. Am J Clin Nutr 1998; 68: 3-4
• 28 Hamilton B. The calcium and phosphorus metabolism of prematurely born infants. Acta Paediatr Scand 1922; 2: 1-84
• 29 Harrison CM, Johnson K, McKechnie E. Osteopenia of prematurity: a national survey and review of practice. Acta Paediatr 2008; 97: 407-413
• 30 Hellstern G, Poschl J, Linderkamp O. Renal phosphate handling of premature infants of 23-25 weeks gestational age. Pediatr Nephrol 2003; 18: 756-758
• 31 Hoff N, Haddad J, Teitelbaum S et al. Serum concentrations of 25-hydroxyvitamin D in rickets of extremely premature infants. J Pediatr 1979; 94: 460-466
• 32 Hoffmann WS, Parmelee AH, Grossman A. Electrolyte balance studies on premature infants on a diet of evaporated milk. Am J Dis Child 1949; 77: 49-60
• 33 Horsman A, Ryan SW, Congdon PJ et al. Bone mineral content and body size 65 to 100 weeks’ postconception in preterm and full term infants. Arch Dis Child 1989; 64: 1579-1586
• 34 Jain A, Agarwal R, Sankar MJ et al. Hypocalcemia in the newborn. Indian J Pediatr 2010; 77: 1123-1128
• 35 Kasper W, Hoevels O, Thilenius OG. Studies on calcium and phosphate metabolism in premature infants. V. Studies on the vitamin D requirement of premature infants. Z Kinderheilkd 1963; 87: 472-489
• 36 Keipert JA. Rickets with multiple fractured ribs in a premature infant. Med J Aust 1970; 1: 672-675
• 37 Kelly HJ, Sloan RE, Hoffman W et al. Accumulation of nitrogen and six minerals in the human fetus during gestation. Hum Biol 1951; 23: 61-74
• 38 Kislal FM, Dilmen U. Effect of different doses of vitamin D on osteocalcin and deoxypyridinoline in preterm infants. Pediatr Int 2008; 50: 204-207
• 39 Koletzko B, Goulet O, Hunt J et al. 1. Guidelines on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), Supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005; 41 (Suppl. 02) S1-S87
• 40 Koo WW, Krug-Wispe S, Neylan M et al. Effect of three levels of vitamin D intake in preterm infants receiving high mineral-containing milk. J Pediatr Gastroenterol Nutr 1995; 21: 182-189
• 41 Kruse K. Perinatal calcium metabolism. Physiology and Pathophysiology. Monatsschr Kinderheilkd 1992; 140: S1-S7
• 42 Kuschel CA, Harding JE. Calcium and phosphorus supplementation of human milk for preterm infants. Cochrane Database Syst Rev 2001; CD003310
• 43 Levine BS, Walling MW, Coburn JW. Intestinal absorption of calcium: Its assessment, normal physiology, and alterations in various disease states. In: Bronner F. ed. Disorders of Mineral Metabolism. New York: Academic Press; 1982: 103-188
• 44 Markestad T. Plasma concentrations of vitamin D metabolites in unsupplemented breast-fed infants. Eur J Pediatr 1983; 141: 77-80
• 45 Masel JP, Tudehope D, Cartwright D et al. Osteopenia and rickets in the extremely low birth weight infant – a survey of the incidence and a radiological classification. Australas Radiol 1982; 26: 83-96
• 46 Mazkereth R, Laufer J, Jordan S et al. Effects of theophylline on renal function in premature infants. Am J Perinatol 1997; 14: 45-49
• 47 McDevitt H, Tomlinson C, White MP et al. Changes in quantitative ultrasound in infants born at less than 32 weeks’ gestation over the first 2 years of life: influence of clinical and biochemical changes. Calcif Tissue Int 2007; 81: 263-269
• 48 McDevitt H, Tomlinson C, White MP et al. Quantitative ultrasound assessment of bone in preterm and term neonates. Arch Dis Child Fetal Neonatal Ed 2005; 90: F341-F342
• 49 McIntosh N, Livesey A, Brooke OG. Plasma 25-hydroxyvitamin D and rickets in infants of extremely low birthweight. Arch Dis Child 1982; 57: 848-850
• 50 Mihatsch WA, Muche R, Pohlandt F. The renal phosphate threshold decreases with increasing postmenstrual age in very low birth weight infants. Pediatr Res 1996; 40: 300-303
• 51 Mihatsch WA, Trotter A, Pohlandt F. Calcium and phosphor intake in preterm infants: sensitivity and specifity of 6-hour urine samples to detect deficiency.. Klin Padiatr. 2012 224. 61-65
• 52 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
• 53 Moyer-Mileur LJ, Ball SD, Brunstetter VL et al. Maternal-administered physical activity enhances bone mineral acquisition in premature very low birth weight infants. J Perinatol 2008; 28: 432-437
• 54 Moyer-Mileur LJ, Brunstetter V, McNaught TP et al. Daily physical activity program increases bone mineralization and growth in preterm very low birth weight infants. Pediatrics 2000; 106: 1088-1092
• 55 Nemet D, Dolfin T, Wolach B et al. Quantitative ultrasound measurements of bone speed of sound in premature infants. Eur J Pediatr 2001; 160: 736-740
• 56 Oppenheimer SJ, Snodgrass GJ. Neonatal rickets. Histopathology and quantitative bone changes. Arch Dis Child 1980; 55: 945-949
• 57 Pimlott JF, Howley TP, Nikiforuk G et al. Enamel defects in prematurely born, low birth-weight infants. Pediatr Dent 1985; 7: 218-223
• 58 Pohlandt F. Bone mineral deficiency as the main factor of dolichocephalic head flattening in very-low-birth-weight infants. Pediatr Res 1994; 35: 701-703
• 59 Pohlandt F. Hypothesis: myopia of prematurity is caused by postnatal bone mineral deficiency. Eur J Pediatr 1994; 153: 234-236
• 60 Pohlandt F. Prevention of postnatal bone demineralization in very low-birth-weight infants by individually monitored supplementation with calcium and phosphorus. Pediatr Res 1994; 35: 125-129
• 61 Pohlandt F. A radiological sign of bone demineralization in preterm infants. Klin Padiatr 1985; 197: 155-156
• 62 Pohlandt F, Gortner LPB. Severe bone demineralization in preterm infants due to decreased tubular phosphate reabsorption (DTPR). Pediatr Res 1988; 24: 275A
• 63 Pohlandt F, Mathers N. Bone mineral content of appropriate and light for gestational age preterm and term newborn infants. Acta Paediatr Scand 1989; 78: 835-839
• 64 Posner AS. Crystal chemistry of bone mineral. Physiol Rev 1969; 49: 760-792
• 65 Quinlan PT, Lockton S, Irwin J et al. The relationship between stool hardness and stool composition in breast- and formula-fed infants. J Pediatr Gastroenterol Nutr 1995; 20: 81-90
• 66 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
• 67 Rigo J, Nyamugabo K, Picaud JC et al. 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
• 68 Rigo J, Pieltain C, Salle B et al. Enteral calcium, phosphate and vitamin D requirements and bone mineralization in preterm infants. Acta Paediatr 2007; 96: 969-974
• 69 Rigo J, Senterre J. Nutritional needs of premature infants: current issues. J Pediatr 2006; 149: S80-S88
• 70 Rodriguez-Soriano J, Aguirre M, Oliveros R et al. Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol 2005; 20: 579-584
• 71 Salle BL, Delvin EE, Lapillonne A et al. Perinatal metabolism of vitamin D. Am J Clin Nutr 2000; 71: 1317 S-1324 S
• 72 Salle BL, Glorieux FH, Delvin EE et al. Vitamin D metabolism in preterm infants. Serial serum calcitriol values during the first four days of life. Acta Paediatr Scand 1983; 72: 203-206
• 73 Schilling R, Haschke F, Kovarik J et al. Untersuchungen zum Phosphor- und Kalzium-Stoffwechsel Frühgeborener bei Ernährung mit Frauenmilch und mit adaptierter Milch. Padiatr Padol 1982; 17: 667-674
• 74 Schilling R, Haschke F, Kovarik J et al. Phosphatverarmung kleiner Frühgeborener bei Ernährung mit Frauenmilch. Klin Padiatr 1982; 194: 400-404
• 75 Schulzke SM, Trachsel D, Patole SK. Physical activity programs for promoting bone mineralization and growth in preterm infants. Cochrane Database Syst Rev 2007; CD005387
• 76 Senterre J, Putet G, Salle B et al. Effects of vitamin D and phosphorus supplementation on calcium retention in preterm infants fed banked human milk. J Pediatr 1983; 103: 305-307
• 77 Shaw JC. Evidence for defective skeletal mineralization in low-birthweight infants: the absorption of calcium and fat. Pediatrics 1976; 57: 16-25
• 78 Shenai JP, Reynolds JW, Babson SG. Nutritional balance studies in very-low-birth-weight infants: enhanced nutrient retention rates by an experimental formula. Pediatrics 1980; 66: 233-238
• 79 Skalova S, Kowad M, Kutilek S. Three Different causes of Hypercalciurie. Klin Padiatr 2011; 223: 287-289
• 80 Specker BL, Beck A, Kalkwarf H et al. Randomized trial of varying mineral intake on total body bone mineral accretion during the first year of life. Pediatrics 1997; 99: E12
• 81 Specker BL, Mulligan L, Ho M. Longitudinal study of calcium intake, physical activity, and bone mineral content in infants 6–18 months of age. J Bone Miner Res 1999; 14: 569-576
• 82 Sutton A, Barltrop D. Absorption, accretion and endogenous faecal excretion of calcium by the newborn infant. Nature 1973; 242: 265
• 83 Thomas PS, Glasgow JF. The “mandibular mantle” – a sign of rickets in very low birth weight infants. Br J Radiol 1978; 51: 93-98
• 84 Tomlinson C, McDevitt H, Ahmed SF et al. 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
• 85 Trotter A, Maier L, Pohlandt F. Calcium and phosphorus balance of extremely preterm infants with estradiol and progesterone replacement. Am J Perinatol 2002; 19: 23-29
• 86 Trotter A, Pohlandt F. Calcium and phosphorus retention in extremely preterm infants supplemented individually. Acta Paediatr 2002; 91: 680-683
• 87 Widdowson EM, Spray CM. Chemical development in utero. Arch Dis Child 1951; 26: 205-214
• 88 Williams ML, Rose CS, Morrow 3rd G et al. Calcium and fat absorption in neonatal period. Am J Clin Nutr 1970; 23: 1322-1330
• 89 Zanardo V, Dani C, Trevisanuto D et al. Methylxanthines increase renal calcium excretion in preterm infants. Biol Neonate 1995; 68: 169-174