The reported link between intramuscular vitamin K, childhood malignancy, and leukemia has created difficulties about the appropriate prophylaxis of vitamin K-deficiency bleeding (VKPD) in neonates (1,2). Oral vitamin K1 administered at birth is effective in normal formula-fed infants but may not prevent late VKPD in breast-fed infants in whom the deficiency of vitamin K is exacerbated by the low vitamin K content of human breast milk.
A number of oral vitamin K prophylactic regimens have been evaluated, varying from a single dose of 1 mg vitamin K at birth (3) to three oral doses of 1 mg (4) or multiple oral doses (5), including oral administration of mixed micellar preparations of vitamin K (6).
Although prospective studies have demonstrated efficacy of these regimens in normal infants (5,6), it is clear that even the micellar preparation of vitamin K may not protect breast-fed infants with underlying liver disease from VKPD. This is particularly tragic, because the morbidity and mortality resulting from late VKPD are high and can be reversed (or prevented) by a single intramuscular injection of 1 mg vitamin K.
The problem is how best to prevent VKDP in high-risk infants, especially those with liver disease. Because the epidemiologic data have demonstrated a link between intramuscular vitamin K and childhood malignancy, it is unrealistic to attempt to reintroduce intramuscular injections at birth for all neonates. However, it may be possible to ensure that all breast-fed infants receive daily supplements of oral vitamin K1 (25 μg) in drop formulation, as is already marketed in The Netherlands (5). Furthermore, in addition to the recommendation of oral vitamin K prophylaxis for breast-fed infants, it should be reiterated that all breast-fed infants who have prolonged jaundice should not only have liver disease excluded (7) but should have urgent coagulation tests performed to exclude and prevent VKPD (8).
1. Golding J, Birmingham K, Greenwood R, Mott M. Intramuscular vitamin K and childhood cancer. BMJ
2. Passmore SJ, Draper G, Brownbill P, Kroll M. Case control studies if relation between childhood cancer and neonatal vitamin K administration: retrospective case-control study. BMJ
3. Von Kries R. Neonatal vitamin K prophylaxis for all. BMJ
4. Loughnan P, Chaot K, Elliott E, Henderson, McDougall P. Haemorrhagic disease in Australia 1994: Report from the Australian Paediatric Surveillance Unit (abstract). J Paediatr Child Health
5. Cornelissen M, von Kreis R, Loughnan P, Schubiger G. Prevention of vitamin K deficiency: Efficacy of different multiple oral doses schedules of vitamin K. Eur J Pediatr
6. Schubiger G, Tonz O, Gruter J, Shearer MJ. Vitamin K concentration in breastfed neonates after oral or intramuscular administration of a single dose of a new mixed micellar preparation of phylloquinone. J Pediatr Gastroenterol Nutr
7. Mackinley GA. Jaundice persisting beyond 14 days after birth. BMJ
8. Mahedevan S, Beath SV, McKiernan PJ, Kelly DA. The vitamin K debacle and infants with cholestatic liver disease. Arch Dis Child