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Erschienen in: European Journal of Pediatrics 2/2009

01.02.2009 | Review

Vitamin K, an update for the paediatrician

verfasst von: Myriam Van Winckel, Ruth De Bruyne, Saskia Van De Velde, Stephanie Van Biervliet

Erschienen in: European Journal of Pediatrics | Ausgabe 2/2009

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Abstract

Introduction

This review summarizes current knowledge on vitamin K for the paediatrician. Vitamin K is a fat-soluble vitamin, present in plants as phylloquinone and produced by bacteria as menaquinone. It is acting as a co-factor for γ-glutamyl carboxylase. This enzyme is responsible for post-translational modification of some glutamate side chains to γ-carboxyglutamate. The majority of γ-carboxylated proteins function in blood coagulation; others play a role in calcium homeostasis.

Data

Newborn babies are at particular risk of vitamin K deficiency, as placental transfer is limited and human milk is a poor source. Vitamin K prophylaxis at birth effectively prevents vitamin K deficiency bleeding (VKDB), formerly known as “haemorrhagic disease of the newborn”. Recent epidemiological studies provide data on the effectiveness of different administration routes and dosing schemes. Infants of mothers taking drugs that inhibit vitamin K are at risk of early VKDB and should receive 1 mg intramuscular (IM) as soon as possible after birth. Classic VKDB is prevented by intramuscular as well as by oral administration of 1 mg vitamin K. In exclusively breast-fed infants, single IM administration at birth is also effectively preventing (rare) late VKDB but single oral administration is not. If given orally, prophylaxis should be continued by either weekly administration of 1 mg till 12 weeks or repeating 2 mg at weeks 1 and 4. Daily administration of 25 μg offers insufficient protection. The only infants not fully protected in this way are those with yet unrecognised liver disease.

Conclusions

Further work is needed before firm recommendations can be made regarding dose in preterm infants and in patients with fat malabsorption/cholestasis or regarding the role of vitamin K in the prevention of osteoporosis.
Literatur
1.
Zurück zum Zitat American Academy of Pediatrics, Committee on Nutrition (1961) Vitamin K compounds and their water soluble analogues: use in therapy and prophylaxis in pediatrics. Pediatrics 28:501–507 American Academy of Pediatrics, Committee on Nutrition (1961) Vitamin K compounds and their water soluble analogues: use in therapy and prophylaxis in pediatrics. Pediatrics 28:501–507
2.
Zurück zum Zitat American Academy of Pediatrics, Committee on Nutrition (2003) Controversies concerning vitamin K and the newborn. Pediatrics 112:191–192CrossRef American Academy of Pediatrics, Committee on Nutrition (2003) Controversies concerning vitamin K and the newborn. Pediatrics 112:191–192CrossRef
3.
Zurück zum Zitat American Academy of Pediatrics, Committee on Nutrition (1998) Nutritional needs of preterm infants. In: Pediatric Nutrition Handbook, fifth edn. American Academy of Pediatrics, Elk Grove Village IL, p 278 American Academy of Pediatrics, Committee on Nutrition (1998) Nutritional needs of preterm infants. In: Pediatric Nutrition Handbook, fifth edn. American Academy of Pediatrics, Elk Grove Village IL, p 278
4.
5.
Zurück zum Zitat Bangh SA, Hughes KA, Roberts DJ, Kovarik SM (2005) Neonatal Ergot Poisoning: a persistent iatrogenic illness. Am J Perinatol 22:239–243PubMedCrossRef Bangh SA, Hughes KA, Roberts DJ, Kovarik SM (2005) Neonatal Ergot Poisoning: a persistent iatrogenic illness. Am J Perinatol 22:239–243PubMedCrossRef
6.
Zurück zum Zitat Booth SL, Suttie JW (1998) Dietary intake and adequacy of vitamin K1. J Nutr 128:785–788PubMed Booth SL, Suttie JW (1998) Dietary intake and adequacy of vitamin K1. J Nutr 128:785–788PubMed
7.
Zurück zum Zitat Busfield A, McNinch A, Tripp J (2007) Neonatal vitamin K prophylaxis in Great Britain and Ireland: the impact of perceived risk and product licensing on effectiveness. Arch Dis Child 92:754–758PubMedCrossRef Busfield A, McNinch A, Tripp J (2007) Neonatal vitamin K prophylaxis in Great Britain and Ireland: the impact of perceived risk and product licensing on effectiveness. Arch Dis Child 92:754–758PubMedCrossRef
8.
Zurück zum Zitat Cashman K (2005) Vitamin K status may be an important determinant of childhood bone health. Nutr Rev 63:284–289PubMedCrossRef Cashman K (2005) Vitamin K status may be an important determinant of childhood bone health. Nutr Rev 63:284–289PubMedCrossRef
9.
Zurück zum Zitat Clarke P, Mitchell S (2003) Vitamin K prophylaxis in preterm infants: current practices. J Thromb Haemost 1:384–386PubMedCrossRef Clarke P, Mitchell S (2003) Vitamin K prophylaxis in preterm infants: current practices. J Thromb Haemost 1:384–386PubMedCrossRef
10.
Zurück zum Zitat Clarke P, Mitchell S, Wynn R, Sundaram S, Speed V, Gardener E, Roeves D, Shearer M (2006) Vitamin K prophylaxis for preterm infants: a randomized, controlled trial of 3 regimens. Pediatrics 118:e1657–1666PubMedCrossRef Clarke P, Mitchell S, Wynn R, Sundaram S, Speed V, Gardener E, Roeves D, Shearer M (2006) Vitamin K prophylaxis for preterm infants: a randomized, controlled trial of 3 regimens. Pediatrics 118:e1657–1666PubMedCrossRef
11.
Zurück zum Zitat Conway S, Wolfe S, Brownlee K, White H, Oldroyd B, Truscott J, Harvey J, Shearer M (2005) Vitamin K status among children with cystic fibrosis and its relationship to bone mineral density and bone turnover. Pediatrics 115:1325–1331PubMedCrossRef Conway S, Wolfe S, Brownlee K, White H, Oldroyd B, Truscott J, Harvey J, Shearer M (2005) Vitamin K status among children with cystic fibrosis and its relationship to bone mineral density and bone turnover. Pediatrics 115:1325–1331PubMedCrossRef
12.
Zurück zum Zitat Cornelissen M, Von Kries R, Loughnan P, Schubiger G (1997) Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K. Eur J Pediatr 156:126–130PubMedCrossRef Cornelissen M, Von Kries R, Loughnan P, Schubiger G (1997) Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K. Eur J Pediatr 156:126–130PubMedCrossRef
13.
Zurück zum Zitat Costakos D, Greer F, Lover L, Dahlen L, Suttie J (2003) Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg. Am J Perinatol 20:485–90PubMedCrossRef Costakos D, Greer F, Lover L, Dahlen L, Suttie J (2003) Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg. Am J Perinatol 20:485–90PubMedCrossRef
14.
Zurück zum Zitat Crowther CA, Henderson-Smart DJ (2001) Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage (review). The Cochrane Database Syst Rev 2001 Issue1 Crowther CA, Henderson-Smart DJ (2001) Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage (review). The Cochrane Database Syst Rev 2001 Issue1
15.
Zurück zum Zitat Dam H (1929) Cholesterinstoffwechsel in Hühnereiern und Hühnchen. Biochem Zeitschr 215:475–81 Dam H (1929) Cholesterinstoffwechsel in Hühnereiern und Hühnchen. Biochem Zeitschr 215:475–81
16.
Zurück zum Zitat Dam H (1935) The antihaemorrhagic vitamin of the chick. Biochem J 29:1273–85PubMed Dam H (1935) The antihaemorrhagic vitamin of the chick. Biochem J 29:1273–85PubMed
17.
Zurück zum Zitat Fear NT, Roman E, Ansell P, Simpson J, Day N, Eden OB, United Kingdom Childhood Cancer Study (2003) Vitamin K and childhood cancer: a report from the United Kingdom Childhood Cancer Study. Br J Cancer 89:1228–1231PubMedCrossRef Fear NT, Roman E, Ansell P, Simpson J, Day N, Eden OB, United Kingdom Childhood Cancer Study (2003) Vitamin K and childhood cancer: a report from the United Kingdom Childhood Cancer Study. Br J Cancer 89:1228–1231PubMedCrossRef
18.
Zurück zum Zitat Furie B, Bouchard B, Furie BC (1999) Vitamin K-dependent biosynthesis of γ-carboxyglutamic acid. Blood 93:1798–1808PubMed Furie B, Bouchard B, Furie BC (1999) Vitamin K-dependent biosynthesis of γ-carboxyglutamic acid. Blood 93:1798–1808PubMed
19.
Zurück zum Zitat Golding J, Paterson M, Kinlen LJ (1990) Factors associated with childhood cancer in a national cohort study. Br J Cancer 62:304–308PubMed Golding J, Paterson M, Kinlen LJ (1990) Factors associated with childhood cancer in a national cohort study. Br J Cancer 62:304–308PubMed
20.
Zurück zum Zitat Greer FR, Marshall SP, Foley AS, Suttie JW (1997) Improving the vitamin K status of breastfeeding infants with maternal vitamin K supplements. Pediatrics 99:88–92PubMedCrossRef Greer FR, Marshall SP, Foley AS, Suttie JW (1997) Improving the vitamin K status of breastfeeding infants with maternal vitamin K supplements. Pediatrics 99:88–92PubMedCrossRef
21.
Zurück zum Zitat Hansen KN, Minousis M, Ebbesen F (2003) Weekly oral vitamin K prohylaxis in Denmark. Acta Paediatr 92:802–805PubMedCrossRef Hansen KN, Minousis M, Ebbesen F (2003) Weekly oral vitamin K prohylaxis in Denmark. Acta Paediatr 92:802–805PubMedCrossRef
22.
24.
Zurück zum Zitat Ijland M, Rodrigues Pereira R, Cornelissen EAM (2008) Incidence of late vitamin K deficiency bleeding in newborns in the Netherlands in 2005: evaluation of the current guideline. Eur J Pediatr 167:165–169PubMedCrossRef Ijland M, Rodrigues Pereira R, Cornelissen EAM (2008) Incidence of late vitamin K deficiency bleeding in newborns in the Netherlands in 2005: evaluation of the current guideline. Eur J Pediatr 167:165–169PubMedCrossRef
25.
Zurück zum Zitat Kumar D, Greer F, Super D, Suttie J, Moore J (2001) Vitamin K status of premature infants: implications for current recommendations. Pediatrics 108:1117–1122PubMedCrossRef Kumar D, Greer F, Super D, Suttie J, Moore J (2001) Vitamin K status of premature infants: implications for current recommendations. Pediatrics 108:1117–1122PubMedCrossRef
26.
Zurück zum Zitat Mager DR, McGee PL, Furuya KN, Roberts EA (2006) Prevalence of vitamin K deficiency in children with mild to moderate chronic liver disease. J Pediatr Gastroenterol Nutr 42:71–76PubMedCrossRef Mager DR, McGee PL, Furuya KN, Roberts EA (2006) Prevalence of vitamin K deficiency in children with mild to moderate chronic liver disease. J Pediatr Gastroenterol Nutr 42:71–76PubMedCrossRef
27.
Zurück zum Zitat Mayer TC, Angus J (1956) The effect of large doses of “Synkavit” in the newborn. Arch Dis Child 31:212–215 Mayer TC, Angus J (1956) The effect of large doses of “Synkavit” in the newborn. Arch Dis Child 31:212–215
28.
Zurück zum Zitat Nantel G, Tontisirin K eds. (2002) Human vitamin and mineral requirements. Report of a joint FAO-WHO expert consultation. chapter 10. Vitamin K. pp.133–150 Nantel G, Tontisirin K eds. (2002) Human vitamin and mineral requirements. Report of a joint FAO-WHO expert consultation. chapter 10. Vitamin K. pp.133–150
29.
Zurück zum Zitat National Academy of Sciences. Institute of Medicine. Food and Nutrition board (2001) Recommended dietary intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium and zinc. Chapter 5, pp. 162–196 National Academy of Sciences. Institute of Medicine. Food and Nutrition board (2001) Recommended dietary intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium and zinc. Chapter 5, pp. 162–196
30.
Zurück zum Zitat Nicolaidou P, Stavrinadis I, Loukou I, Papadopoulou A, Georgouli H, Douros K, Priftis K, Gourgiotis D, Matsinos Y, Doudounakis S (2006) The effect of vitamin K supplementation on biochemical markers of bone formation in children and adoslescents wiht cystic fibrosis. Eur J Pediatr 165:540–545PubMedCrossRef Nicolaidou P, Stavrinadis I, Loukou I, Papadopoulou A, Georgouli H, Douros K, Priftis K, Gourgiotis D, Matsinos Y, Doudounakis S (2006) The effect of vitamin K supplementation on biochemical markers of bone formation in children and adoslescents wiht cystic fibrosis. Eur J Pediatr 165:540–545PubMedCrossRef
31.
Zurück zum Zitat Oldenburg J, Marinova M, Müller-Reible C, Watzka M (2008) The vitamin K cycle. Vitam Horm 78:35–62PubMedCrossRef Oldenburg J, Marinova M, Müller-Reible C, Watzka M (2008) The vitamin K cycle. Vitam Horm 78:35–62PubMedCrossRef
32.
Zurück zum Zitat Pereira SP, Shearer MJ, Williams R, Mieli-Vergani G (2003) Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding. Arch Dis Child Fetal Neonatal Ed 88:F113–118PubMedCrossRef Pereira SP, Shearer MJ, Williams R, Mieli-Vergani G (2003) Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding. Arch Dis Child Fetal Neonatal Ed 88:F113–118PubMedCrossRef
33.
Zurück zum Zitat Pettifor JM, Benson R (1975) Congenital malformations associated with the administration of oral anticoagulants during pregnancy. J Pediatr 86:459–462PubMedCrossRef Pettifor JM, Benson R (1975) Congenital malformations associated with the administration of oral anticoagulants during pregnancy. J Pediatr 86:459–462PubMedCrossRef
34.
Zurück zum Zitat Puckett RM, Offringa M (2000) Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev, issue 4 Puckett RM, Offringa M (2000) Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev, issue 4
35.
Zurück zum Zitat Roman E, Fear NT, Ansell P, Bull D, Draper G, Mc Kinney P, Michaelis J, Passmore S, Von Kries R (2002) Vitamin K and childhood cancer: analysis of individual patient data form six different case-control studies. Br J Cancer 86:63–69PubMedCrossRef Roman E, Fear NT, Ansell P, Bull D, Draper G, Mc Kinney P, Michaelis J, Passmore S, Von Kries R (2002) Vitamin K and childhood cancer: analysis of individual patient data form six different case-control studies. Br J Cancer 86:63–69PubMedCrossRef
36.
Zurück zum Zitat Schubiger G, Grüter J, Schearer M (1997) Plasma vitamin K1 and PIVKAII after oral administration of mixed-micellar or Cremophor EL-solubilized preparations of vitamin K1 to normal breast-fed newborns. J Pediatr Gastroenterol Nutr 24:280–284PubMedCrossRef Schubiger G, Grüter J, Schearer M (1997) Plasma vitamin K1 and PIVKAII after oral administration of mixed-micellar or Cremophor EL-solubilized preparations of vitamin K1 to normal breast-fed newborns. J Pediatr Gastroenterol Nutr 24:280–284PubMedCrossRef
37.
Zurück zum Zitat Schubiger G, Stocker C, Bänziger O, Laubscher B, Zimmerman H (1999) Oral vitamin K1 prophylaxis for newborns with a new mixed-micellar preparation of phylloquinone: 3 years experience in Switzerland. Eur J Pediatr 158:599–602PubMedCrossRef Schubiger G, Stocker C, Bänziger O, Laubscher B, Zimmerman H (1999) Oral vitamin K1 prophylaxis for newborns with a new mixed-micellar preparation of phylloquinone: 3 years experience in Switzerland. Eur J Pediatr 158:599–602PubMedCrossRef
39.
Zurück zum Zitat Suchy JS, Sokol RJ, Balistreri WF (2007) Liver disease in children, 3rd edn. Cambridge University Press, Cambridge, pp 214–215 Suchy JS, Sokol RJ, Balistreri WF (2007) Liver disease in children, 3rd edn. Cambridge University Press, Cambridge, pp 214–215
40.
Zurück zum Zitat Sutor AH, von Kries R, Cornelissen MEA, Mc Ninch A, Andrew M (1999) Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/perinatal subcommittee. International Society on Thrombosis and Haemostasis. Thromb Haemost 81:456–461PubMed Sutor AH, von Kries R, Cornelissen MEA, Mc Ninch A, Andrew M (1999) Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/perinatal subcommittee. International Society on Thrombosis and Haemostasis. Thromb Haemost 81:456–461PubMed
41.
Zurück zum Zitat Suttie JW (1995) The importance of menaquinones in human nutrition. Annu Rev Nutr 15:399–417PubMedCrossRef Suttie JW (1995) The importance of menaquinones in human nutrition. Annu Rev Nutr 15:399–417PubMedCrossRef
42.
Zurück zum Zitat Townsend CW (1894) The haemorrhagic disease of the newborn. Arch Paediatr 11:559–565 Townsend CW (1894) The haemorrhagic disease of the newborn. Arch Paediatr 11:559–565
43.
Zurück zum Zitat USDA National Nutrient Database for Standard Reference, release 20 (2008) Vitamin K (phylloquinone) (μg) content of selected foods USDA National Nutrient Database for Standard Reference, release 20 (2008) Vitamin K (phylloquinone) (μg) content of selected foods
44.
Zurück zum Zitat Van Hasselt P, de Koning TJ, Kvist N, De Vries E, Rydahl Lundin C, Berger R, Kimpen J, Houwen R, Horby Jorgensen M, Verkade HJ, Netherlands Study Group for Biliary Atresia Registry (2008) Prevention of Vitamin K deficiency bleeding in breastfed infants: lessons from the Dutch and Danish Biliary Atresia Registries. Pediatrics 121:e857–e863PubMedCrossRef Van Hasselt P, de Koning TJ, Kvist N, De Vries E, Rydahl Lundin C, Berger R, Kimpen J, Houwen R, Horby Jorgensen M, Verkade HJ, Netherlands Study Group for Biliary Atresia Registry (2008) Prevention of Vitamin K deficiency bleeding in breastfed infants: lessons from the Dutch and Danish Biliary Atresia Registries. Pediatrics 121:e857–e863PubMedCrossRef
45.
Zurück zum Zitat Van Summeren M, Braam L, Noirt F, Kuis W, Vermeer C (2007) Pronounced elevation of undercarboxylated osteocalcin in healthy children. Pediatr Res 61:366–70PubMedCrossRef Van Summeren M, Braam L, Noirt F, Kuis W, Vermeer C (2007) Pronounced elevation of undercarboxylated osteocalcin in healthy children. Pediatr Res 61:366–70PubMedCrossRef
46.
Zurück zum Zitat Von Kries R (1992) Vitamin K prophylaxis—a useful public health measure? Paediatr Perinat Epidemiol 6:7–13CrossRef Von Kries R (1992) Vitamin K prophylaxis—a useful public health measure? Paediatr Perinat Epidemiol 6:7–13CrossRef
47.
Zurück zum Zitat Von Kries R, Hachmeister A, Göbel U (2003) Oral mixed micellar vitamin K for prevention of late vitamin K deficiency bleeding. Arch Dis Child Fetal Neonatal Ed 88:F109–112CrossRef Von Kries R, Hachmeister A, Göbel U (2003) Oral mixed micellar vitamin K for prevention of late vitamin K deficiency bleeding. Arch Dis Child Fetal Neonatal Ed 88:F109–112CrossRef
48.
Zurück zum Zitat Von Kries R, Shearer M, McCarthy P, Haug M, Harzer G, Göbel U (1987) Vitamin K1 content of maternal milk: influence of the stage of lactation, lipid composition and vitamin K1 supplements given to the mother. Pediatr Res 22:513–517CrossRef Von Kries R, Shearer M, McCarthy P, Haug M, Harzer G, Göbel U (1987) Vitamin K1 content of maternal milk: influence of the stage of lactation, lipid composition and vitamin K1 supplements given to the mother. Pediatr Res 22:513–517CrossRef
49.
Zurück zum Zitat Widdershoven J, van Munster P, de Abreu R, Bosman H, van Lith T, van der Putten-van Meyel M, Motohara K, Matsuda I (1987) Four methods compared for measuring des-carboxy-prothrombin (PIVKA-II). Clin Chem 33:2074–2078PubMed Widdershoven J, van Munster P, de Abreu R, Bosman H, van Lith T, van der Putten-van Meyel M, Motohara K, Matsuda I (1987) Four methods compared for measuring des-carboxy-prothrombin (PIVKA-II). Clin Chem 33:2074–2078PubMed
Metadaten
Titel
Vitamin K, an update for the paediatrician
verfasst von
Myriam Van Winckel
Ruth De Bruyne
Saskia Van De Velde
Stephanie Van Biervliet
Publikationsdatum
01.02.2009
Verlag
Springer-Verlag
Erschienen in
European Journal of Pediatrics / Ausgabe 2/2009
Print ISSN: 0340-6199
Elektronische ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-008-0856-1

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