Dietary Intake in Infants and Their Adequacy

The average intake of phylloquinone in infants fed human milk during the first 6 months of life has been reported to be less than 1 μg/day; this is approximately 100-fold lower than the intake in infants fed a typical supplemented formula. This big disparity between intakes is reflected in plasma levels.

Using the detection of PIVKA-II as a marker of sub-clinical deficiency, a study from Germany concluded that a minimum daily intake of about 100 ml of colostral milk (that supplies about 0.2-0.3 μg of phylloquinone) is sufficient for normal haemostasis in a baby of about 3 kg during the first week of life. Similar conclusions were reached in a Japanese study which showed a linear correlation between the prevalence of PIVKA-II and the volume of breast milk ingested over 3 days; 95 percent of infants with detectable PIVKA-II had average daily intakes of less than about 120 ml, but the marker was not detectable when intakes reached 170 ml/day.

Factors of relevance to classical vitamin K deficiency bleeding

The liver stores of vitamin K in the newborn infant differ both qualitatively and quantitatively from that in adults. First, phylloquinone levels at birth are about one-fifth those in adults and second, bacterial menaquinones are undetectable. The resistance to placental transport of vitamin K to the human foetus is well-established. Thereafter, the limited available data suggest that hepatic stores of menaquinones build up gradually, becoming detectable at around the second week of life but only reaching adult concentrations after 1 month of age. A gradual increase in liver stores of menaquinones may reflect the gradual colonisation of the gut by enteric microflora.

A practical problem in assessing the functional status of vitamin K in the neonatal period is that there are both gestational and postnatal increases in the four vitamin K-dependent procoagulant factors which are unrelated to vitamin K status. This means that unless the deficiency state is quite severe, it is very difficult to interpret clotting factor activities as a measure of vitamin K sufficiency. The best diagnostic tool of the adequacy of vitamin K stores for neonates is by the detection of PIVKA-II by immunoassays. The use of this marker has clearly shown that there is a temporary dip in the vitamin K status of infants exclusively fed human milk in the first few days after birth. The fact that the degree of this dip is associated with human-milk intakes and is less evident or abolished in infants given artificial feeds or prophylactic vitamin K at birth shows that the detection of PIVKA-II reflected a dietary lack of vitamin K.

Factors of relevance to late vitamin K deficiency bleeding

The natural tendency for human-milk-fed infants to develop a sub-clinical vitamin K deficiency in the first 2–3 days of life is self-limiting. Comparisons between untreated human-milk-fed infants with others who had received vitamin K or supplementary feeds clearly suggest that this improvement in vitamin K–dependent clotting activity is due to an improved vitamin K status. After the first week, vitamin K–dependent clotting factor increases are more gradual, and it is not possible from clotting factor assays to differentiate between the natural post-natal increase in the synthesis of the core proteins from an improved vitamin K status leading to greater functional activity.

Use of the most sensitive assays for PIVKA-II shows that there is still evidence of suboptimal vitamin K status in infants solely fed human milk between the ages of 1 and 2 months. Deficiency signs are less common in infants who have received adequate vitamin K supplementation or who have been formula fed.

References:

Greer, F.R. Marshall, S. Cherry, J. & Suttie, J.W. 1991. Vitamin K status of lactating

mothers, Human milk and breast-feeding infants. Pediatr., 88: 751-6.

von Kries, R., Becker, A. & Göbel, U. 1987. Vitamin K in the newborn: influence of nutritional factors on acarboxy-prothrombin detectability and factor II and VII clotting activity Eur J. Pediatr., 146: 123-7.

von Kries, R., Shearer, M.J., Haug, M., Harzer, G. & Göbel, U. 1988. Vitamin K deficiency and vitamin K intakes in infants. In: Current advances in vitamin K research. Suttie J.W., ed. p.515-23. New York: Elsevier.

Motohara, K., Matsukane, I., Endo, F., Kiyota, Y. & Matsuda, I. 1989. Relationship of milk intake and vitamin K supplementation to vitamin K status in newborns.

Pediatrics, 84: 90-3.

Shearer, M.J. 1988. The assessment of Human vitamin K status from tissue measurements. In: Current advances in vitamin K research. Suttie J.W., ed. p. 437-52. New York: Elsevier.

Shearer, M.J. 1992. Vitamin K metabolism and nutriture. Blood Revs., 6: 92-104.

Lane, P.A. & Hathaway, W.E. 1985. Vitamin K in infancy. J. Pediatr., 106: 351-9.

Kayata, S., Kinberg, C., Greer, F.R. & Suttie, J.W. 1989. Vitamin K1 and K2 in infant

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McDonald, M.M. & Hathaway, W.E. 1983. Neonatal hemorrhage and thrombosis. Semin. Perinatol., 7: 213-25.

Motohara, K., Endo, F. & Matsuda, I. 1985. Effect of vitamin K administration on

acarboxy prothrombin (PIVKA-II) levels in newborns. Lancet, ii: 242-4.

Widdershoven, J., Lambert, W., Motohara, K., Monnens, L., de LeenheeR, A., Matsuda, I. & Endo, F. 1988. Plasma concentrations of vitamin K1 and PIVKA-II in bottle-fed and breast-fed infants with and without vitamin K prophylaxis at birth. Eur. J. Pediatr., 148: 139-42.

Motohara, K., Endo, F. & Matsuda, I. 1986. Vitamin K deficiency in breast-fed infants

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