Galloway K, Isaacson L, Keyte S

Bastyr MSN DPD

Micronutrients debate

Vitamin K Prophylaxis for Newborns: Oral Supplementation is

Sufficient to Prevent Vitamin K Deficiency Bleeding
Vitamin K: Pro of Con
Kelly Galloway
Vitamin K intramuscular (i.m.) prophylaxis has been continuously proven to be the most
effective way of preventing vitamin K deficiency bleeding (VKDB). The following five articles
will display the effectiveness of vitamin K intramuscular prophylaxis, as well as limitations with
oral vitamin K supplementation. A study by Cornelissan et al. showed that at 2 weeks, 1 month,
and 3 months of age, serum vitamin K levels were higher in the infants who received the i.m.
prophylaxis compared to infants who received the oral supplementation. A study by Wariyar et al
showed VKDB emergence in infants whose parents did not comply with the oral
supplementation, as well as VKDB emergence in infants with cholestasis. To expand on
cholestasis and VKDB, Pereira et al studied the intestinal absorption of oral vitamin K
supplementation in infants with cholestasis. These infants were unable to absorb the supplements
and therefore developed late VKDB. Croucher et al studied the compliance of mothers who had
been instructed to administer 2 oral doses to their infants after the initial dose at birth. Here, 10
percent did not receive the first dose, and approximately 60 percent did not receive the second
dose. Lastly, to reiterate, a study by Mcninch et al observed the plasma vitamin K concentrations
of two groups of infants, with the i.m. receiving group always having higher vitamin K levels. In
conclusion, these studies all show the effectiveness of vitamin k oral prophylaxis may be limited,
while i.m. prophylaxis is the most effective way to protect against VKDB.

References:
1.

Cornelissen EA, Kolle LA, De abreu RA, et al. Effects of oral and
intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting
factors in breast fed infants. Arch Dis Child. 1992; 67(10):1250-4

2.

Croucher C, Azzopardi D. Compliance with recommendations for giving

vitamin K to newborn infants. BMJ. 1994;308(6933):894-5.

3.

Mcninch, A W, Upton, C, Samuels, M, Plasma Concentrations after oral or

intramuscular vitamin K in neonates. Archives of Disease in Cildhood, 1985,
60, 814-818

4.

Wariyar U, Hilton S, Pagan J, Tin W, Hey E. Six years' experience of

prophylactic oral vitamin K. Arch Dis Child Fetal Neonatal Ed.
2000;82(1):F64-8.

5.

Pereira, S. P. Intestinal Absorption of Mixed Micellar Phylloquinone (vitamin

K1) Is Unreliable in Infants with Conjugated Hyperbilirubinaemia: Implications
for Oral Prophylaxis of Vitamin K Deficiency Bleeding. Archives of Disease in
Childhood - Fetal and Neonatal Edition 88.2 (2003): 113F-18. Web.

CornelissenEA,KolleLA,DeabreuRA,etal.Effectsoforalandintramuscular
vitaminKprophylaxisonvitaminK1,PIVKAII,andclottingfactorsinbreastfed
infants.ArchDisChild.1992;67(10):12504
Populationand/orproblem
This study was a randomized clinical trial aiming to establish the effects of oral and
intramuscular administration of vitamin K at birth on plasma vitamin K concentrations of
vitamin K, clotting factors, and proteins induced by vitamin K absence (PIVKA-II).
Enrolled were a total of 331 infants delivered in the University Hospital of Nijmegen or
at home in the presence of a midwife.
Intervention
The neonates received vitamin K prophylaxis on the first or second day of life. One group
consisting of 165 infants received 1 mg vitamin K orally. The second group of 166
infants received 1 mg vitamin K intramuscularly. Sample of 5 ml of blood were taken at 2
weeks, 1 and 3 months of age. Activities of clotting factors VII and X were measured by
chromogenic substrate assay. PIVKA-II was assayed by an enzyme linked
immunosorbent assay. Vitamin K was extracted from 1 ml serum samples.
ComparisonorcontrolNo control group was described for this study.
Outcomeresultsandconclusions
At the 3 month follow up, PIVKA-II levels were higher in the vitamin K intramuscular
group than the vitamin K oral group. Blood coagulability and factors VII and X were not
significantly different in the two infant groups at the 3 month follow-up. However,
vitamin K plasma concentrations were higher in the intramuscular group at 2 weeks, 1,
and 3 months following prophylaxis.
Figure2: Mean(SD)vitamin K, plasma concentrations in breastfed infants at 2 weeks, I
month, and 3 months of age after either oral or intramuscular vitamin K prophylaxis at
birth.To summarize, a single oral administration of 1 mg vitamin K may not offer
complete protection against late biochemical vitamin K deficiency.

WariyarU,HiltonS,PaganJ,TinW,HeyE.Sixyears'experienceofprophylactic
oralvitaminK.ArchDisChildFetalNeonatalEd.2000;82(1):F648.

Populationand/orproblem
A group of 182,000 infants in the north of England were studied between 1993 and 1998
and administered oral vitamin K to attempt to eliminate the risk of vitamin K deficiency
bleeding (VKDB) during the first three months of life.
Intervention
A 1 mg dose of vitamin K suspended in a medium chain triglyceride oil was delivered by
mouth to 182,000 infants within 12 hours of birth. The parents of the children were given
an additional three doses to give the baby once every two weeks after discharge. All
pediatricians in the Northern region were contacted at specific intervals and asked if they
encountered late vitamin K deficiency bleeding
Comparisonand/orcontrol
No control group was described for this study.
Outcomeresultsandconclusions
Four infants developed late vitamin K deficiency bleeding. Two bled despite receiving
the oral prophylaxis, due to an undiagnosed cholestasis. Two others developed late
vitamin K deficiency bleeding due to the parents lack of continuing oral supplementation
after discharge.
Giving oral dosages at regular intervals appear to be more effective than just giving one
or two oral doses before discharge. The likelihood of the infants receiving the appropriate
amount at the appropriate times, lies in the hands of the parents administering the oral
prophylaxis.
Infants receiving oral supplementation who have impaired liver function or cholestasis

will not be protected against late vitamin K deficiency bleeding.

Pereira,S.P.IntestinalAbsorptionofMixedMicellarPhylloquinone(vitaminK1)Is
UnreliableinInfantswithConjugatedHyperbilirubinaemia:ImplicationsforOral
ProphylaxisofVitaminKDeficiencyBleeding.ArchivesofDiseaseinChildhood
FetalandNeonatalEdition88.2(2003):113F18.Web.

Populationand/orproblem
The objective of this study was to compare the effectiveness of oral versus intramuscular
mixed micellar vitamin K prophylaxis in infants with cholestatic liver disease.
Cholestatic liver disease is a risk factor for, and could lead to vitamin K deficiency
bleeding (VKDB). Forty-four infants less than 6 months old with conjugated
hyperbilirubinaemia were used for this study.
Intervention
This was a randomized controlled study over an 18 month period. Forty-four infants,
aged 1-26 weeks with conjugated hyperbilirubinaemia were enrolled in this study after
being referred to the Pediatric Liver Service of Kings College Hospital.
Infants were randomly either given (a)1 mg mixed micellar K injection, or (b)2 mg
orally on the back of the tongue. Each prophylaxis was given to the infants as a single
dose in the morning. Blood samples were taken just before, as well as six hours after
administration of the medication, for 5 days. The blood samples were refrigerated
immediately and protected from light.
Comparisonand/orcontrol
Intestinal absorption of mixed micellar K in cholestatic infants was compared to that of
healthy infants from a previous study. Previously studied were 14 healthy newborns were
given the same oral dose within one hour of birth and serum K was measured 24 hours
later via drawing blood.
Outcomeresultsandconclusion

In the group of infants receiving intramuscular vitamin K, 90% had a high serum K levels
(median 139 ng/ml) at six hours. Additionally, the medium serum K levels remained
higher than that of oral administration at each serum measure point.
Due to the intestinal absorption of oral vitamin K being unreliable in
infants with hyperbilirubinaemia, there is an association between
cholestasis and late vitamin K deficiency bleeding in infants receiving
oral supplementation.

CroucherC,AzzopardiD.CompliancewithrecommendationsforgivingvitaminKto
newborninfants.BMJ.1994;308(6933):8945.
Populationand/orproblem
In 1993, 348 babies were born and the hospital in which they were birthed underwent a
change to follow the British Paediatric Associationss recommendations. This
recommended that oral vitamin K supplements should be given to newborn infants, and
repeated twice after discharge from the hospital.
Intervention
Mothers of the infants were contacted by telephone, and asked about the information they
had received about vitamin K, as well as their administration of vitamin K to their infant.
Mothers were instructed to administer the oral vitamin K supplement at day 7 and week 6
after discharge from the hospital.
Comparisonand/orcontrol
No comparison group was described for this study.
Outcomeresultsandconclusion
Within this study, 15 mothers did not have a telephone and 99 were unable to be
contacted. A total of 207 mothers answered the telephone questionnaire, and 2 of the 207
refused to allow their infant to receive any vitamin K.
The second dose of oral vitamin K should have been given at 7 days after discharge. The
community midwife administered it in 132 out of 143 cases. Only 57 children received
the oral supplementation at 6 weeks.
Compliance with the follow up doses of vitamin K was extremely poor. Greater than 10%
of the infants did not receive a second dose and approximately 60% did not receive a

third dose.

Mcninch,AW,Upton,C,Samuels,M,PlasmaConcentrationsafteroralor
intramuscularvitaminKinneonates.ArchivesofDiseaseinCildhood,1985,60,814
818
Populationand/orProblem
One hundred and seven healthy, breast-fed infants were studied. All infants received 1 mg
of vitamin K, orally or intramuscularly, at birth. A comparison was to be made between
the two methods of prophylaxis, by comparing plasma concentrations of vitamin K in the
first 24 hours after 1 mg supplementation.
Intervention
Stage 1: Three groups, each of 15 infants, received either intramuscular, oral vitamin K
supplementation at birth, or orally with the first feed. At 24 hours after the dose, each
infant had a blood sample taken.
Stage 2: Two groups of 20 infants received vitamin K prophylaxis at birth either
intramuscularly or orally. Most infants had only one blood sample taken at either 2, 4, 8,
12, or 24 hours after the dose.
Comparisonand/orcontrol
There was no control group described for this study.
OutcomeResultsandconclusion
The median plasma concentrations of vitamin K intramuscular injection was 10-20 times
higher than either of the groups given vitamin K orally.

Plasma concentrations after intramuscular prophylaxis exceeded those

in the oral groups at each comparable time. Peak median
concentrations of 1781 ng/ml at 12 hours, falling to 444 ng/ml at 24
hours.