Abstract
Vitamin K has regained paediatric interest due to a recurrence of bleeding caused by deficiency of the vitamin in newborns and young infants. Increasing awareness of these clinical problems, the development of new methods for the detection of vitamin K deficiency and the direct measurement of vitamin K in tissues have stimulated research. Much new data obtained from these studies has proved helpful to the understanding of vitamin K deficiency in infancy. For example low concentrations of vitamin K have been found in fetal and neonatal livers. The implications of these findings with respect to manifest vitamin K deficiency and to new methods for detection of subclinical vitamin K deficiency are discussed. Breast-feeding is a major risk factor for classical haemorrhagic disease of the newborn and for late onset bleeding due to vitamin K deficiency in young infants. The interdependencies between breast-feeding and vitamin K deficiency are discussed on the basis of new data obtained from direct measurement of vitamin K in maternal milk. The review further focusses on pathophysiological concepts of bleeding due to vitamin K deficiency in infancy and current concepts of vitamin K prophylaxis.
This is a preview of subscription content, access via your institution.
Abbreviations
- HDN:
-
haemorrhagic disease of newborn
- LHDN:
-
late haemorrhagic disease of newborn
- PIVKA II:
-
Protein induced by vitamin K absence or inhibition for prothrombin (factor II)
- HPLC-UV:
-
high performance liquid chromatography with ultraviolet light absorption
References
Aballi AJ (1977) Vitamin K deficiency in the newborn (letter). Lancet II:559
Aballi AJ (1985) Vitamin K deficiency in infants (letter). J Pediatr 106:1059
Alpan A, Avital A, Peleg O, Dgani Y (1984) Late presentation of haemorrhagic disease of newborn. Arch Dis Child 59:482–483
Bechthold H, Andrassy K, Jähnchen E, Koderich J, Koderich H, Weilemann LS, Sonntag HG, Ritz E (1984) Evidence of impaired hepatic vitamin K 1 metabolism in patients treated with N-methylthiotetrazole cephalosporins. Thromb Haemostas 51:358–361
Behrmann BA, Chan WK, Finer NN (1985) Resurgence of hemorrhagic disease of the newborn: a report of three cases. Can Med Assoc J 133:884–885
Bhanchet P, Tuchinda S, Hathirat P, Visudhiphan P, Bhamarapharati N, Bukkavesa S (1977) A bleeding syndrome in infants due to acquired prothrombin complex deficiency. Clin Pediatr 16: 992–997
Blanchard RA, Furie BC, Barnet J, Peck C, Fave K, Jabobs M, DeFurio L, Furie B (1985) Vitamin K deficency in newborns and their mother. Thromb Haemostas 54:226 (abstr)
Bleyer WA, Skinner AL (1976) Fatal neonatal hemorrhage after maternal anticonculsant therapy. JAMA 235:626–627
Büller H, Peters M, Burger B, Nagelkerke N, Ten Cate JW, Breedervelt C, Heymans H (1986) Vitamin K status beyond the neonatal period: a prospective study in normal breast-fed and formula-fed infants. Eur J Pediatr 145:496–499
Caballero FM, Buchanan GR (1980) Abetalipoproteinemia presenting as as severe vitamin K deciency. Pediatrics 65:161–163
Chan-Lui WY, Stoebel BA, Young CY (1983) Hemorrhagic tendency as a complication of moxalactam therapy in bacterial meningitis. Brain Dev 5:417–420
Chaou WT, Chou ML, Eitzmann DV (1984) Intracranial hemorrhage and vitamin K deficiency in early infancy. J Pediatr 105: 880–884
Choonara IA, Park BK (1985) Plasma concentrations after oral or intramuscular vitamin K 1 in neonates (letter). Arch Dis Child 60:1203–1204
Committee on Nutrition, American Academy of Pediatrics (1961) Vitamin K compounds and the water-soluable analogues: use in therapy and prophylaxis in pediatrics. Pediatrics 28:501–506
Cooper NA, Lynch MA (1979) Delayed haemorrhagic disease of the newborn with extradural haematoma. Br Med J 279:164–165
O'Connor ME, Livingstone DS, Hannah J, Wilkins D (1983) Vitamin K deficiency and breastfeeding. Am J Dis Child 137:601–602
O'Connor ME, Addiego JE (1986) Use of oral vitamin K 1 to prevent hemorrhagic disease of the newborn infant. J Pediatr 108:616–619
Dam H, Clavind J, Larsen HE, Plum P (1942) Investigations into the cause of physiological hypoprothrombinemia in newborn children. IV. The vitamin K content of woman's milk and cow's milk. Acta Med Scand 112:210–208
Deblay MF, Vert P, Andre M, Marchal P (1982) Transplacental vitamin K prevents hemorrhagic disease of the infant of epileptic mothers. Lancet I:1247
Dunn PM (1982) Vitamin K for all newborn babiers. Lancet II: 770
Ernährungskommission der deutschen Gesellschaft für Kinderheikunde (1986) Zur Vitamin K Prophylaxe bei Neugeborenen. Dtsch Ärzteblatt 83:3380–3383
Forbes D (1983) Delayed presentation of haemorrhagic disease of the newborn. Med J Aust 2:136–138
Forestier F, Daffos F, Rainaut M, Sole Y, Amiral J (1985) Vitamin K dependent proteins in fetal haemostasis at mid trimester pregnancy. Thromb Haemostas 53:401–403
Fujimura Y, Okubo Y, Sakai T, Sugimoto M, Takase T, Yoshioka A, Fukui H (1984) Precursor proteins PIVKA II, IX and X in the plasma of patients with ‘hemorrhagic disease of the newborn’. Haemostasis 14:211–217
Göbel U, Sonnenschein-Kosenow S, Petrich C, v. Voss H (1977) Vitamin K deficiency in the newborn (letter). Lancet II:187–188
Göbel U, v. Kries R, Bewersdorff S, Henninghausen B, Schmidt E (1986) Erniedrigte Prothrombin-Gerinnungsaktivitäten bei gestillten Kindern? Klin Pädiat 198:13–16
Harroon Y, Shearer MJ, Gunn SG, McEnery G, Barkhan P (1982) The content of phylloquinone (vitamin K 1) in human milk, cow's milk and infant formula determined by high-performance liquid chromatography. J Nutr 112:1105–1117
Hathaway WME, Lane PA (1985) Vitamin K deficiency in infants. J Pediatr 107:990
Hope PL, Hall MA, Millward-Sadler P (1982) Alpha 1-Antitrypsin deficiency presenting as a bleeding diathesis in the newborn. Arch Dis Child 57:68–72
Jenkins HR, Leonhard JV, Kay JDB, Pool RW, Sills JA, Isherwood DM (1982) Alpha 1 antitrypsin deficiency bleeding diathesis and intracranial haemorrhage. Arch Dis Child 57:722–723
Keenan WJ, Jewett T, Glueck HI (1971) Role of feeding and vitamin K in hypoprothrombinemia of the newborn. Am J Dis Child 121:524–533
Kries R von, Wahn V, Koletzko B, Göbel U (1984) Späte Manifestation eines Vitamin K Mangels bei gestillten Säuglingen. Monatsschr Kinderheilk 132:293–295
Kries R von, Zenses Ch, Göbel U (1985) Immunoelectrophoretic determination of PIVKA II in capillary plasma. Haemostasis 15:42–43 (abstr)
Kries R von, Reifenhäuser A, Göbel U, McCarthy PT, Shearer MJ, Barkhan P (1985) Late onset haemorrhagic disease of newborn with temporary malabsorption of vitamin K 1 (letter). Lancet I:1035
Kries R von, Göbel U, Shearer MJ, McCarthy PT (1985) Vitamin K deficiency in breastfed infants (letter). J Pediatr 107:650–651
Kries R von, Maase B, Becker A, Göbel U (1985) Latent vitamin K deficiency in healthy infants? (letter) Lancet II:1421–1422
Kries R von, Becker A, Göbel U (1987) Vitamin K in the newborn: influence of nutritional factors on acarboxyprothrombin detectability and factor II and VII clotting activity. Eur J Pediatr 146:123–127
Kries R von, Tangermann R, Shearer MJ, Göbel U (1987) Vitamin K deficiency in breastfed infants. In: A. Goldman (ed) Lactation. III. Impact of lactation on the recipient infant. Plenum Press, New York
Kries R von, Kreppel St, Becker A, Göbel U (1987) PIVKA II levels after prophylactic vitamin K. Arch Dis Child 62:938–940
Lane PA, Hathway WE (1985) Vitamin K in infancy. J Pediatr 106:351–58
Lane PA, Hathaway WE, Githens JH, Krugmann RD, Rosenberg DA (1983) Fatal intracranial haemorrhage in a normal infant secondary to vitamin K deficiency. Pediatr 72:562–564
Lorber J, Lilleyman JS, Peile EB (1979) Acute infantile thrombocytosis and vitamin K deficiency associated with intracranial haemorrhage. Arch Dis Child 54:471–472
McCarthy PT, Shearer MJ, Gau G, Crampton OE, Barkhan P, (1986) Vitamin K content in human liver at different ages. Haemostasis 16 [Suppl 5]: 83–84 (abstr)
McMillan CW, Roberts HR (1966) Congenital combined deficiency of coagulation factors II, VII, IX and X. N Engl J Med 274:1313–1316
McNinch AW, L'Orme R, Tripp JH (1983) Haemorrhagic disease of the newborn returns. Lancet I:1089–1090
McNinch AW, Upton C, Samuels M, Shearer MJ, McCarthy PT, Tripp JH, L'Orme R (1985) Plasma concentrations after oral or parenteral vitamin K 1 in neonates. Arch Dis Child 60:814–818
Minford AMB, Eden OB (1979) Haemorrhage responsive to vitamin K in a 6 week old infant. Arch Dis Child 54:310–311
Motohara K, Matskura M, Matsuda I, Iribe K, Ikeba T, Kondo Y, Yonekubo A, Yamamoto Y, Tsuchiya F (1984) Severe vitamin K deficiency in breastfed infants. J Pediatr 105:943–945
Motohara K, Kuroki Y, Kan H, Matsuda I (1985) Detection of vitamin K deficiency by the use of an enzymelinked immunosorbent assay for circulating abnormal prothrombin. Pediatr Res 19:354–357
Motohara K, Endo F, Matsuda I (1986) Vitamin K deficiency in breastfed infants at one month of age. J Pediatr Gastroenterol Nutr 5:931–933
Motohara K, Endo F, Matsuda I (1987) Screening for late neonatal vitamin K deficiency by acarboxy prothrombin in dried blood spots. Arch Dis Child 62:370–375
Moss M (1969) Hypoprothrombinemic bleeding in a young infant. Am J Dis Child 117:540–542
Nagao T, Ilzuka A (1982) Idiopathic vitamin K deficiency in infancy: its entity and its enigmas. Acta Haematol JPN 45:849–859
Nakayama K (1982) Etiology of vitamin K deficiency in infants. Perinat Med 12:1029–1034 (in Japanese)
Nammacher MA, Willemin M, Hartmann JH, Guston LW (1970) Vitamin K deficiency infants beyond the neonatal period. J Pediatr 76:549–554
Payne DR, Hasegawa DK (1984) Vitamin K deficiency in newborns: a case report in alpha 1 antitrypsin deficiency and a review of factors predisposing to hemorrhage. Pediatrics 73:712–716
Poley JR, Humphrey GB (1974) Bleeding disorder in an infant associated with anicteric hepatitis. Clin Pediatr 13:1045–48
Rapaport S, Dodd K (1946) Hypoprothrombinemia in infants with diarrhea. Am J Dis Child 71:611–618
Roberts IF, McHugh PJ (1979) Late onset vitamin K deficiency (letter). Br Med J 278:749–750
Rodesch P, Caranel S, Winckler M (1976) Hypovitaminosis K in coeliac disease. Acta Paediatr Belg 29:123–125
Sann L, Leclercq M, Guillaumant M, Touyez R, Bethenod M, Bourgeay-Causse M (1985) Serum vitamin K 1 concentrations after oral administration of vitamin K 1 in low birth weight infants. J Pediatr 107:608–610
Seip M (1973) Effect of antiepileptic drugs in pregnancy on the fetus and newborn infant. Ann Clin Res 5:205–214
Shapiro AD, Jacobson LJ, Armon ME, Manco-Johnson MJ, Hulac P, Lane PA, Hathaway WME (1986) Vitamin K deficiency in the newborn infant: prevalence and perinatal risk factors. J Pediatr 109:675–680
Shearer MJ (1986) Assay of K vitamins in tissues by high performance liquid chromatography with special reference to ultraviolet detection. In: Chytil F, McCormick DM (eds) Methods in enzymology. Academic Press, Orlando, pp 235–251
Shearer MJ, Barkhan P, Webster GR (1970) Absorption and excretion of an oral dose of tritiated vitamin K 1 in man. Br J Haematol 18:297–308
Shearer MJ, McBurney A, Barkhan P (1974) Studies on the absorption and metabolism of phylloquinone (vitamin K 1). Vitam Horm 32:523–533
Shearer MJ, Rahim S, Barkhan P, Stimmler L (1982) Plasma vitamin K 1 in mothers and their newborn babies. Lancet II:460–463
Shearer MJ, Crampton OE, McCarthy PT, Mattock MB (1986) Vitamin K 1 in plasma: relationship to vitamin K status, age, pregnancy, diet and disease. Haemostasis 16 [Suppl 5]:83 (abstr)
Sutherland JM, Glueck HI, Gleser G (1967) Hemorrhagic disease of the newborn: breastfeeding as a necessary factor in the pathogenesis. AM J Dis Child 113:524–533
Sutor AH, Pancochar H, Niederhoff H, Pollmann H, Hilgenberg F, Palm D, Künzer W (1983) Vitamin K Mangelblutungen bei vier voll gestillten Säuglingen im Alter von 4–6 Wochen. DMW 108:1635–1639
Sutor AH, Pollmann H, v. Kries R, Thais H, Schindera F, Göbel U, Künzer W (1985) Vitamin K Mangelblutungen jenseits der Perinatalperiode. Weitere Beobachtungen. Monatsschr Kinderheilkd 132:608 (abstr)
Torstensen OL, Humphrey GB, Edson JR (1970) Cystic fibrosis presenting with severe hemorrhage due to vitamin K malabsorption: a report of 3 cases. Pediatrics 45:857–859
Verity CM, Carswell F, Scott GL (1983) Vitamin K deficiency causing infantile intracranial haemorrhage after the neonatal period (letter). Lancet I:1439
Visudhiphan P, Bhanchet P, Lakanapichanchat C, Chiemchanya S (1974) Intracranial haemorrhage in infants due to acquired prothrombin complex deficiency. J Neurosurg 41:14–18
Wefring KW (1962) Hemorrhage in the newborn and vitamin K prophylaxis. J Pediatr 61:686–691
Widdershoven J, Motohara K, Endo F, Matsuda I, Monnens L (1986) Influence of the type of feeding on the presence of PIVKA II in infants. Helv Paediatr Acta 41:25–28
Widdershoven J, Kollee L, van Munster P, Bosman AM, Monnens L (1986) Biochemical vitamin K deficiency in early infancy: diagnostic limitation of conventional coagulation tests. Helv Paediatr Acta 41:195–201
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kries, R.v., Shearer, M.J. & Göbel, U. Vitamin K in infancy. Eur J Pediatr 147, 106–112 (1988). https://doi.org/10.1007/BF00442204
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00442204
Key words
- Vitamin K deficiency
- Acarboxy-prothrombin
- Prophylaxis of vitamin K deficiency
- Newborns
- Infants