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Vitamin K Abstracts

I have been doing a lit review on vitamin K but am just starting out so haven't looked over most of the abstracts let alone read the articles here are some. I also found but didn't include here an abstract from Budapest that said that the oral dose immediately after birth was not as effective as an oral dose given at the time of the first milk feed. now they might have a point here because colostrum is laxative in its effect.

J Pediatr 1995 Aug;127(2):301-304
Twenty-seven years of experience with oral vitamin K1 therapy in neonates.
Clark FI, James EJ
Department of Pediatrics, Children's Hospital, University of Missouri, Columbia, USA.

Healthy term infants born at the University of Missouri have received vitamin K prophylaxis as a single oral dose since 1967. A retrospective study was undertaken to determine whether either hemorrhagic disease of the newborn or any unexplained intracranial hemorrhage occurred in an infant who received orally administered vitamin K, but none could be found in three separate databases. We conclude that we have met our duty of providing appropriate care.

J Pediatr Gastroenterol Nutr 1993 May;16(4):435-439
Vitamin K1 concentration in breast-fed neonates after oral or intramuscular administration of a single dose of a new mixed-micellar preparation of phylloquinone.
Schubiger G, Tonz O, Gruter J, Shearer MJ
Children's Hospital, Lucerne, Switzerland.

The plasma disposition of a new mixed-micellar preparation (KONAKION MM, Roche) of phylloquinone (vitamin K1) has been studied in 25 healthy, fully breast-fed, newborn babies, randomized to receive a single dose of either 1.5 mg i.m. (11 babies) or 3 mg p.o. (14 babies). Venous blood samples were collected at 25 h, 4 days, and 24 days. After p.o. administration, the median plasma phylloquinone concentration increased to 89 ng/ml after 24 h, then decreased to 51 ng/ml after 4 days; the respective concentrations after i.m. injection were 146 ng/ml and 34 ng/ml. The higher plasma phylloquinone level in the i.m. group after 24 h was not statistically significant compared with that of the p.o. group, but the reversed higher concentration in the p.o. group after 4 days was significant (p < &0.01). After 24 days the median plasma phylloquinone had decreased to 0.44 ng/ml (range 0.19-1.44) and 1.05 ng/ml (range 0.37-1.87) in the p.o. and i.m. groups, respectively. There was a significant difference between these plasma concentrations (p < &0.01). They were within or above the reference adult fasting range (0.17-0.68 ng/ml). The narrow range of plasma concentrations at 24 h and 4 days suggests a greater consistency of absorption from this micellar preparation than from other emulsion-based preparations. Further studies are required to assess the long-term protection of a single oral dose against late hemorrhagic disease of the newborn. Until such time, breast-fed babies given this preparation orally should receive (an) additional dose(s). 

Arch Pediatr 1995 Apr;2(4):328-332
Efficacy of oral administration of a micellaar solution of vitamin K during the neonatal period.
[Article in French]
Maurage C, Dalloul C, Moussa F, Cara B, Dudragne D, Lion N, Amedee-Manesme O
Service de pediatrie R-gastroenterologie et nutrition, hopital Clocheville, CHU Tours, France.

BACKGROUND--Oral administration of vitamin K to neonates is quite satisfactory for preventing hemorrhagic disease of the newborn. The aim of this study is to test efficacy of a micellar solution of vitamin K at birth. POPULATION AND METHODS--Thirty full term infants, exclusively breast-fed during the first month of life, were included in this study. Seven of them (control group Cos) were given oral supplementation with 5 mg vitamin K1, cremophor; 15 other infants were given oral supplementation with 3 mg micellar solution of vitamin K1 (group MMos) and 7 were given an intramuscular injection of 1.5 mg micellar solution of vitamin K1 (group MMim). Prothrombin time activity and plasma vitamin K concentration were measured in the cord blood, 24 +/- 12 hours and 1 month after supplementation. RESULTS--No hemorrhage was seen and tolerance to vitamin K was good in the 3 groups. Mean prothrombin time activity was 54% in the cord blood, around 55% and 75%, 24 hrs and 1 month after supplementation, respectively; only one infant had low value (41%) by 1 month despite normal plasma vitamin K concentration. Two infants had low plasma vitamin K1 concentration by the second control despite normal prothrombin time activity; one belonged to the MMos group and the other to the Cos group. Mean values of plasma vitamin K1 concentration were higher by 1 month in the MMos group. CONCLUSION--A unique dose of micellar solution of vitamin K given orally at birth seems effective to prevent hemorrhagic disease.

J Pediatr Gastroenterol Nutr 1997 Mar;24(3):280-284
Plasma vitamin K1 and PIVKA-II after oral administration of mixed-micellar or cremophor EL-solubilized preparations of vitamin K1 to normal breast-fed newborns.
Schubiger G, Gruter J, Shearer MJ
Children's Hospital, Lucerne, Switzerland.

BACKGROUND: Vitamin K1 prophylaxis in neonates is required for prevention of vitamin K1 deficiency bleeding. Although intramuscular administration of vitamin K1 is safe, this invasive method is not generally accepted. We therefore examined the pharmacokinetics of two orally administered vitamin K1 preparations in normal, fully breast-fed newborns. METHODS: Within 1 hour of birth, each baby was randomized to a 2 mg dose of either a conventional Cremophor EL-solubilized preparation of vitamin K1 (Konakion drops, F. Hoffmann-La Roche, n = 16), or a new mixed-micellar preparation of vitamin K1 (Konakion MM, F. Hoffmann-La Roche, n = 14). The concentrations of vitamin K1-des-gamma-carboxyprothrombin (PIVKA-II), and total bound bilirubin were measured in plasma samples taken at 24 hours, 4 days, and 24 days after birth. RESULTS: The median concentration of plasma vitamin K1 was higher at all three time points in the group that received the mixed-micellar preparation, but the difference was only significant (p < &0.05) at 4 days. At 24 hours and 4 days, PIVKA-II was detectable in a significantly lower proportions of infants receiving the new mixed-micellar preparation than those receiving the Cremophor EL preparation (21% vs. 75% at 24 hours, p < &0.05 and 14% vs. 50% at 4 days, p < &0.05). None of the infants in the study had detectable PIVKA-II levels 24 days after birth. CONCLUSIONS: Our results suggest that when given orally, the mixed-micellar preparation is superior to the conventional formulation because it increases plasma vitamin K1 concentrations to higher levels, suggesting superior bioavailability, and decreases PIVKA-II concentrations more efficiently, suggesting a faster pharmacodynamic response.

Indian Pediatr 1992 Jul;29(7):857-859
Comparative study of oral versus injectable vitamin K in neonates.
Malik S, Udani RH, Bichile SK, Agrawal RM, Bahrainwala AT, Tilaye S
Department of Pediatrics and Hematology, T.N.M. College, Bombay.

One hundred term exclusively breast fed babies weighing more than 2.5 kg were evaluated to determine the efficacy of various modes and doses of Vitamin K to prevent hemorrhagic disease of newborn (HDN). The babies were grouped into four categories of 25 each: Group A--1 mg Vitamin K intramuscular (Menadione sodium disulphite) at birth; Group B--0.5 mg Vitamin K intramuscular; Group C--1 mg Vitamin K orally, and group D--no Vitamin K. The prothrombin index was estimated in all babies between 36-72 hours of age. The results revealed a prothrombin index in Groups A, B, C and D as 94.98 +/- 7.64%, 95.08 +/- 9.91%, 92.51 +/- 10.10% and 80.39 +/- 15.90%, respectively. The differences between Groups A, B and C were insignificant. However, Group D, prothrombin index was significantly reduced as compared with the other three groups. It is, therefore, concluded that oral Vitamin K is as effective as injectable Vitamin K and its usage is recommended in our country to reduce complications and costs of parenteral therapy.

Acta Paediatr Scand 1991 Mar;80(3):304-307
Vitamin K to neonates. Peroral versus intramuscular administration.
Jorgensen FS, Felding P, Vinther S, Andersen GE
Department of Gynecology and Obstetrics, Rigshospitalet, University of Copenhagen, Denmark.

In a randomized study of 300 infants, the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection. The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint. Prothrombin (antigen) and PIVKA II (acarboxyprothrombin) were also measured. All infants were observed for events of bleeding until discharge from the hospital, normally on the fifth day. No significant differences between the groups in any of the biochemical markers were observed. The 95% confidence limits of the differences were very narrow for all factors. No cases of bleeding were observed. We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn.

J Med Assoc Thai 1989 Jan;72 Suppl 1:125-129
Vitamin K prophylaxis in the neonates by oral route with different dosages.
Pintadit P, Isarangkura PB, Chalermchandra K, Pongcharoen S, Sasanakul W, Chulajata R, Green GM

This paper evaluated the effect of VKP in the neonates by oral route with different dosages compared to the standard parenteral route giving a single dose at birth. Two hundred and thirty-six healthy, breast-fed infants were divided into 4 groups receiving vitamin K1 1 mg intramuscularly and 2, 3, 5 mg orally during 2-4 hours after birth. The vitamin K dependent clotting factors were measured by the thrombotest at the age of 2 weeks and 4-6 weeks. The result showed no statistical differences among these 4 groups regarding the mean prothrombin complex level and the number of PC deficient subjects. Vitamin K prophylaxis in the newborn babies by 2 mg oral route would be benefit and can be applied routinely as well as 1 mg parenteral route to prevent both HDN and APCD syndrome particularly in breast fed infants. The routine practice of giving vitamin K1 prophylaxis 2 mg orally or 0.5-1 mg intramuscularly should be recommended to all newborn infants. Giving VKP by oral route is practical for developing countries because of simple way of administration, low cost, low toxicity, as well as high efficacy.

Acta Paediatr 1996 Oct;85(10):1137-1139
Neonatal vitamin K prophylaxis in Denmark: three years' experience with oral administration during the first three months of life compared with one oral administration at birth.
Hansen KN, Ebbesen F
Department of Neonatology, County Hospital of Aalborg, Denmark.

A Danish surveillance group established after the introduction of oral vitamin K prophylaxis monitored Danish cases with late onset vitamin K deficiency bleeding by regular questionnaires to all paediatric departments. Six cases were reported, one of whom died and three are severely handicapped. All cases occurred among an estimated 134,500 infants given a single oral 1 mg vitamin K dose at birth. No cases have been reported so far during the existent regimen: 2 mg at birth and 1 mg weekly orally administered vitamin K during the first 3 months of life, given to at least 163,000 infants. The present study is concordant with the only other study on weekly peroral prophylaxis published. We consider the mentioned weekly regimen safe and appropriate.

nvest Clin 1995 Jun;36(2):83-93
Effects of the administration of vitamin K on the activity of Factor II, VII and X in healthy newborns.
[Article in Spanish]
Arteaga-Vizcaino M, Torres-Espina M, Redondo L, Soto-Torres L, Diez-Ewald M, Vizcaino-Salazar G, Torres-Guerra E, Fernandez N
Instituto de Investigaciones Clinicas, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.

The study was designed to know the effect of oral vitamin K (VK) treatment, on clotting factors II-VII-IX-X and the protein induced by VK absence from factor II (PIVCA II) on full term infants. Seventy healthy newborns were studied and each was randomly placed in one of two groups: Group A, newborns that received human milk and milk formula (mixed feeding)and group B, newborns that were exclusively breast fed. These groups were also divided in two subgroups: I received 2mg of VK1 orally and II (control) did not receive VK. Clotting activity of the coagulation factors and PIVCA II was determined from blood plasma obtained immediately after birth and 48 hours after VK administration. Basal activity of the factors analyzed was similar in all groups with values ranging from 25% to 40%. After 48 hours a significant increase in all factors studied and a decrease of PIVKA II was observed in those children who received oral VK. The results suggest that oral VK effectively increases VK dependent factors and prevents the risk of hemorrhagic disease in the newborn, with the advantage of being less traumatic and less risky to the infant than intramuscular VK.

Well you might want to look at this one, it says that you can use injectable orally!

Indian Pediatr 1995 Aug;32(8):863-867
Effect of oral water soluble vitamin K on PIVKA-II levels in newborns.
Sharma RK, Marwaha N, Kumar P, Narang A
Division of Neonatology, Postgraduate Institute of Medical Education and Research, Chandigarh.

Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost, pain, anxiety to parents and risk of transmission of infection. Oral route is a better alternative. Oral absorption of vitamin K has been shown to be equally good using special oral preparations. However, this preparation is not available in India. A prospective study was carried out on 51 full term, healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K (menadione sodium bisulphite) could be as effective. Fourteen babies received 1 mg vitamin K intramuscularly, 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth. PIVKA-II levels were measured in cord blood and at 72-78 hours of age in all babies as a marker of vitamin K deficiency. The overall PIVKA-II prevalence in cord blood was 64.7%. At 72-78 hours, PIVKA-II was present in 50% of babies in IM group, 58.3% of babies in oral group and in 76.9% of babies in 'no vitamin K' group (p > 0.05). The PIVKA-II levels decreased or did not change at 72-78 hours in 91.6% of babies in oral group versus 92.8% of babies in IM group (p > 0.05). On the other hand, PIVKA-II levels increased in 30.7% of babies who did not receive vitamin K as against in 7.8% of babies receiving vitamin K in either form (p < &0.05). Hence, vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K (menadione sodium bisulphite) given orally to term healthy babies is effective in preventing vitamin K deficiency state.