Vitamin K

August 28, 2005

This article came from Edda West's fine newsletter.

------------------

Vitamin K

By Karin Rothville DipCBEd.

For the last 40 or 50 years, it has become a generally accepted fact that

vitamin K prevents haemorrhagic disease of the newborn, and routine

administration of vitamin K to all newborns has been recommended.3, 6,

21, 34, 72 This recommendation has been questioned because results

released in 1990 from a study by Golding and colleagues26 in the UK

showed a two to three times increased risk of childhood cancers,

especially leukaemia, in children given prophylactic drugs (usually

intramuscular vitamin K) in their first week. A further study in 1992

seemed to confirm this risk.25

There was widespread anxiety among parents when these findings were

published. Parents were, understandably, reluctant to have their baby

receive a substance that could predispose it to cancer in childhood, and

many health workers were also reluctant to give, without prescription, a

possibly cancer-causing substance to prevent a disease that few, if any,

of them had ever seen. These concerns are not the first time that vitamin

K safety has been questioned. So, what is the controversy about vitamin

K? And does it predispose babies to childhood cancer?

WHAT IS VITAMIN K AND WHAT DOES IT DO?

Vitamin K is a fat-soluble substance which triggers off the

blood-clotting process. Blood clotting is a complex process and can be

described as a sequence of three stages, requiring up to 12 different

coagulation factors.72 The liver needs vitamin K to synthesise four of

these factors. Vitamin K is also needed for the formation of other

proteins found in plasma, bone and kidney.33, 58

As with other fat-soluble vitamins, a normal flow of bile and pancreatic

juice is necessary for digestion, and the presence of dietary fat,

especially short-chain fatty acids, enhances absorption. Absorbed vitamin

K is transported via the lymph into the systemic circulation.58

Normally, a significant portion (up to 55%) of absorbed vitamin K is

excreted so the amount in the body is small and its turnover is rapid

(about 30 hours).58 Vitamin K is stored and re-utilised in the body for

3-4 weeks.33

Vitamin K is found in many foods. Leafy, dark green and deep yellow

vegetables are the best sources.58 Alfalfa18 is a good source; and milk

and dairy products, eggs, cereals, fruits and other vegetables also

provide small but significant amounts. As the liver of adults contains

about equal amounts of plant and animal forms of Vitamin K, it is assumed

that vitamin K is produced in the intestinal tract by bacterial flora.

One of the reasons given for the low levels of vitamin K in newborn

babies is because their gut has not yet been colonised by the required

bacteria.

Recommended daily dietary intakes of vitamin K58CategoryAgeAmount

((g)Infants0 – 110Children1 – 3154 – 6207 – 1025Adolescents11 – 143015 –

1835Adult Male19 – 70+45Adult Female19 – 70+35Pregnancy+ 10Lactating+ 20

The dietary requirements for vitamin K in infants and children are

estimates and are based on weight and growth rates as compared to adults.

Many unsupplemented breasfed infants do not show clinical signs of

vitamin K deficiency on intakes of less than 3 (g daily and the mean

requirement for infants is estimated to be 5 (g daily based on weight.

The higher amount of 10(g is recommended for prevention of Haemorrhagic

Disease of the Newborn.58

WHAT IS HAEMORRHAGIC DISEASE OF THE NEWBORN?

Haemorrhagic Disease of the Newborn (HDN) is a bleeding disorder

associated with low levels of vitamin K in newborn babies. It was first

defined in 1894 by Townsend69 as spontaneous external or internal

bleeding occurring in newborn infants not due to trauma, accident or

inherited bleeding disorders such as haemophilia. Previously, there were

no generally agreed upon criteria to determine causes of haemorrhaging,

so any diagnosis was based solely on the opinion of the attendant medical

personnel.

Infants are born with low levels of vitamin K23 compared to adults and

this is termed ‘vitamin K deficiency’. Up to 50% of babies develop this

‘vitamin K deficiency’, but bleeding occurs in only a fraction of these

cases.37 In most it starts after birth, becomes

Page 2

progressively more severe over 48-60 hours, then spontaneously corrects

itself by 72-120 hours.9

HDN has always been rare – in Britain where maternity units practised a

selective policy of vitamin K administration, the incidence was no more

than 1 in 20,000 in the years 1972-80. Estimates for late onset HDN are

4-8 per 100,000.45 Incidence also seems to vary from country to country.

HDN is divided into three categories: Early onset HDN occurs in the first

24 hours. It is very rare and mainly associated with mothers who have

taken anticonvulsant, antibiotic, antituberculous or anticoagulant drugs

during pregnancy. Classic HDN occurs in the first week after birth. It is

manifested by the oozing of blood from the intestines, the nose, the cord

site and broken skin sites. Bruising at sites where there has been no

trauma can also appear. Late onset HDN occurs after the first week, with

a peak incidence between the second and sixth weeks, and about half the

cases present with intracranial bleeding (bleeding into the brain).

WHAT ARE THE RISK FACTORS FOR HDN?

There has been some debate over the years as to whether or not HDN is

actually caused by vitamin K deficiency. Certainly, giving vitamin K does

arrest bleeding in the majority of cases, but this does not mean that

vitamin K deficiency causes HDN. One may as well say that an antibiotic

deficiency causes bacterial infection. There is also no consensus as to

what level of vitamin K in plasma protects against HDN. Some researchers

have found no evidence of vitamin K deficiency in babies in their

studies43, 49 and other factors have also been suggested.52, 73, 74

Most, if no all, of the reported cases of late onset HDN have presented

with problems which affect the baby’s ability to absorb or utilise

vitamin K.45, 56 These include: hepatitis, cystic fibrosis, chronic

diarrhoea, bile duct atresia, alpha-1-antitrypsin deficiency, coeliac

disease of insufficient plasma transport capacity. Subclinical

cytomegalovirus has also been implicated. Vitamin K-responsive bleeding

syndrome has been well documented after antibiotic therapy, especially

with cyclosporins.33

There are other factors which place the newborn at higher risk. These

include pre-term birth (as the liver is very immature), low birth weight,

instrumental or traumatic delivery, bruised or bleeding in the first few

days after birth, requiring surgery or circumcision, taking inadequate

feeds and breastfeeding.33

BREASTFEEDING – WHY IS IT A RISK?

Several authors have noted the higher incidence of HDN in solely

breastfed babies.9, 30 The incidence has been quoted as 1 in 1200.30

Studies comparing breastmilk with formula and cow’s milk have shown that

breastmilk is lower in vitamin K.22, 28, 32 Breastmilk substitutes are

heavily supplemented with vitamin K, however, it is possible that, like

iron, vitamin K is biologically more available to the baby from

breastmilk, and so such high levels are not necessary.

Measured levels of vitamin K in breastmilk seemed to vary depending on

the type of measurement used; however, they all come out lower than cow’s

milk. Fournier22 and Greer28 found levels of around 8-9(g/l, which would

mean that if a baby was taking in about 500ml per day, it would be

getting the recommended 3-5(g daily.

Vitamin K content and availability are greater in the hind milk because

of its higher fat content and vitamin K levels are also higher in

colostrum.32 As an extra plus, breastmilk contains thromboplastin, one of

the factors in blood clotting.18

Vitamin K levels in the breastmilk rise markedly in response to the

mother eating vitamin K rich foods or taking vitamin K supplements.29, 54

Nishiguchi found no cases of low vitamin K levels in breastfed infants

whose mothers had been given supplements, as opposed to infants who had

only been given 1 or 2 doses of oral vitamin K.54

Unrestricted access to the breast in the early days after birth is

important, due to the higher levels of vitamin K in colostrum. The

importance of early feeding has been recognised since the 1940’s. Babies

who have been fed within their first 24 hours have significantly better

coagulation times than babies not fed until after 24 hours.24

It is essential that, to receive the full complement of vitamin K in

breastmilk, the baby completely finishes one breast before being offered

the other. Any practice that involves restricting either the baby’s time

at the breast or the number of feeds will not allow the baby to receive

optimum amounts of vitamin K and will also prolong the time it takes for

the baby’s intestine to be colonised by friendly, vitamin K manufacturing

bacteria.

THE HISTORY OF VITAMIN K USE TO PREVENT HDN.

The search for the cause of HDN began in 1913 when Whipple82 postulated

that a lack of prothrombin activity could be a cause of HDN. In 1929,

Henrik Dam14 noticed that chicks fed a fat-free diet suffered

subcutaneous and intramuscular haemorrhages, which could be prevented if

the chicks were fed seeds, cereals and green, leafy plants. Dam described

the condition as a vitamin deficiency and named the deficient vitamin

‘vitamin K’, from the Danish word ‘koagulation’.

Research in 19378 found that prothrombin times in normal neonates were

between 30-60% adult levels, falling to 15-30% on day two, and then

gradually rising again until about day 10. This research led to the

continuing belief that these low levels in the newborn are a deficiency

and need to be corrected.

In 1939, vitamin K1 was isolated from alfalfa by Dam, for which he later

received the Nobel Prize, along with Doisy, who isolated vitamin

K2.45 Further research in 1939 by Waddell and Guerry81 found that low

plasma prothrombin levels could be elevated by the administration of oral

vitamin K.

Armed with this ‘proof’ that vitamin K deficiency caused HDN, vitamin K

was synthesised and various trials were commenced

Page 3

to ascertain which was the most effective amount and route to use in

prophylaxis.

It is difficult for us to assess these trials nowadays as they were

mostly neither double blind nor well controlled. The dosage of vitamin K

given, the route of administration and the time of administration all

varied. In many cases, the conclusions did not seem to match the

results.72

Some of the studies assessed the effect on neonatal vitamin K levels if

the mother was given vitamin K during labour.72 Results varied, with the

effectiveness of the vitamin K given depending on how soon the woman gave

birth and the dosage given. More recent studies have shown increases in

cord blood levels where mothers were supplemented antenatally with

vitamin K.1, 66 Two showed a significant difference between the

supplemented and unsupplemented groups and found that the effect of

prenatal vitamin K persisted until the fifth day after birth.1

Because of the variations in results from these early studies, further

research focussed on treating the baby after birth. One particular study

done in 194231 was intended to determine the minimal effective oral dose

of Synkavite (K3), a water-soluble synthetic form of vitamin K. The

results showed that very small daily doses were effective and that a dose

of 5(g daily would probably prevent the development of HDN, except in

early onset cases. The study also found that 1.25mg was effective in

lowering an excessively high prothrombin time to normal. However, the

author admitted that several workers found prothrombin deficiencies in

babies with no abnormal bleeding.

By 1950, most maternity units had a policy of giving infants oral vitamin

K (usually Synkavite) immediately after birth.70 This prevented the fall

in prothrombin levels that occurred in the first few days and,

presumably, the risk of excessive bleeding. This risk was higher in male

babies because of routine circumcision, and, indeed, vitamin K proved to

be of great clinical value in preventing post-circumcision bleeding.75

Then, in the mid-1950’s, reports of increased jaundice and kernicterus

(brain damage caused by high bilirubin levels) associated with vitamin K

prophylaxis began circulating. Reviews of maternity units found that some

were giving Synkavite in doses exceeding 50mg.70 It was established that

high doses of Synkavite caused haemolysis (destruction of red blood

cells) and high serum bilirubin levels.48

Researchers and medical professionals queried the safety aspects of

vitamin K, and there were many conflicting reports on the appropriate

dosages. Some researchers queried the need for vitamin K at all, quoting

results from studies that showed no difference in prothrombin times or

vitamin K plasma levels between babies that bled and babies that

didn’t.72

Eventually, a newer preparation, intramuscular vitamin K1

(phytomenadione), was developed and approved for use, solely on the

grounds that it appeared to cause less haemolysis. Phytomenadione (trade

names Konakion (Roche) or Aquamephyton (Merck, Sharpe & Dohme)) is a

synthetic petrochemical derived from 2-methyl 1,4-naptha-quinone in a

polyethoxylated castor oil base.18 In the US, polysorbate-80 is used as a

base instead of polyethoxylated castor oil.15

In spite there being no long term trials of these preparations, the

American Academy of Pediatrics recommended that phytomenadione be

administered prophylactically to all newborn babies.72 The use of oral

vitamin K preparations fell out of favour in the USA and the ‘safer’

intramuscular route became the route of choice.

In Britain, after the jaundice scare of the1950’s, many maternity units

began to practice a selective policy, giving vitamin K only to babies at

risk of haemorrhaging. McNinch reported in 1980 that less than half the

maternity units in the UK gave vitamin K to all newborns.47 Some of these

babies were given oral prophylaxis and some were given intramuscular

prophylaxis.

In Germany, almost all newborn infants who required medical care and

instrumental deliveries were given intramuscular vitamin K, and some

healthy newborns also received it.76 Records have not always been kept in

New Zealand hospitals, so it is impossible to say whether or not vitamin

K was given routinely and by which route.17

Although vitamin K use seemed to prevent most cases of HDN, there was

still controversy. Not everyone believed vitamin K deficiency was the

cause of HDN. In 1977, van Doorm et al 52, 73, 74 suggested that HDN

could be caused by a heparin-like inhibitor in the newborn and he

concluded that babies given their first feed soon after birth do not have

a vitamin K deficiency. Other researchers agreed with van Doorn.49 In

1980, Malia et al43 could find no evidence of vitamin K deficiency in

babies in their study and concluded that low levels of vitamin K

dependent clotting factors were due to the immature liver. The authors of

these studies questioned whether vitamin K prophylaxis was really

necessary for healthy newborns.

Then, starting in November 1980, there was a cluster of six cases of HDN

in Britain, all within 17 months.46 Half of these cases were classic HDN,

the other half were a new manifestation of HDN – late onset.

LATE ONSET HDN

Late onset HDN was first reported in 1977.5 It mainly occurs in breastfed

infants and ( to ¾ of cases have an underlying liver disorder or

malabsorption syndrome,15 rather than insufficient dietary intake of

vitamin K. This means the liver cannot adequately synthesise blood

clotting factors or store adequate amounts of vitamin K. Liver function

cannot be easily diagnosed at birth without a range of invasive tests and

thus there exists an unknown risk of haemorrhaging.

Many factors contribute to poor liver function, including hepatitis,

cystic fibrosis, antibiotic therapy, biliary atresia, alpha-1-antitrypsin

deficiency, a-beta-lipoproteinaemia, coeliac disease, chronic diarrhoea

and exposure to pharmacologic agents such as anticonvulsants, rifampin,

isoniazid cephalosporins and coumarin compounds33 When tested, most of

the reported cases of late onset HDN had hepatitis, liver malfunction or

enzyme

Page 4

deficiencies.6, 35, 51, 80

Birkbeck6 believes there are two processes at work – low levels of

prothrombin and vitamin K-dependent clotting factors VII, IX and X at

birth, and a further fall in these in the neonatal period. In his view

the initial low levels are not due to vitamin K deficiency as levels of 2

other non-vitamin K-dependent factors, XI and XII are also often reduced.

Thus, the situation at birth may be simply due to hepatic immaturity.

Birkbeck6 also reports that HDN is almost unknown in central Africa and

he suggests an environmental mechanism as the cause. Associated with

this, a discussion paper from the University of Amsterdam42 raises the

idea that by-products of our industrial society such as PCBs, PCDDs and

PCDFs are the cause of late onset HDN. These chemicals can induce enzymes

in the liver which cause liver damage and prolong prothrombin time.

Although overseas studies have reported contamination of breastmilk by

these pollutants, a NZ Department of Health study on breastmilk reported

that levels of these contaminants were at the lower end of the scale.7

The Health Department is currently conducting another study to see if

levels have changed over the past few years.

There seems to be a seasonal variance, with most cases of late onset HDN

occurring in the warmer months.6 It has been suggested that the mother

could have contracted a viral infection during pregnancy in the colder

months and this has crossed the placenta. Since viruses have an affinity

for the liver and mucous membranes, they can affect intestinal absorption

and liver function.67

Another suggested cause of late onset HDN includes use of the food

antioxidant BHT (butylated hydroxytoluene), which has produced vitamin K

deficiency.68 BHT is present in many processed foods, including

margarine. Our Western diets consist of a lot of processed food, and to

reduce fat intakes, margarine is recommended rather than butter. The

polyunsaturated fat in margarine is an inhibitor of vitamin K

absorption.68 Both of these factors could have an effect on the amount of

vitamin K available to pass through to the baby. A high level of vitamin

K in the mother’s blood is necessary to ensure adequate transplacental

transfer of vitamin K.9, 33 It is important for the baby to have adequate

stores of vitamin K in its liver at birth to prevent bleeding until its

feeding and gut flora are established.

Of the six cases of HDN in Britain in 1980-1982, all were breastfed and

none had received vitamin K at birth.46 Two of the cases were in the

high-risk group – one was born by caesarean section and had an epileptic

mother treated with phenytoin, and the other had an alcoholic mother who

had taken anti-depressants – and obviously should have received vitamin K

at birth.

These cases prompted a call for the re-introduction of routine

prophylaxis. Many opposed the idea of unnecessarily injecting otherwise

healthy babies so studies40, 47, 55, 79 were therefore conducted to

determine whether oral vitamin K was as effective as intramuscular. It

was also proposed that oral vitamin K would be more cost-effective and

thus better suited for use in Third World countries.55 Results of these

studies varied. Some showed that oral vitamin K was effective in

preventing classic haemorrhagic disease but not as effective as

intramuscular vitamin K in preventing late onset HDN.47, 55, 78 Others

found oral as effective, especially a 10 year study conducted on 38,000

infants in Sweden where no cases of HDN were observed over that period.40

Tripp and McNinch reported no cases in 25,000 babies in their maternity

unit where only those at risk were given intramuscular prophylaxis and

the rest oral prophylaxis.70

In spite of these findings that oral vitamin K prophylaxis was not

effective in preventing late onset HDN, it continued to be used in

British maternity units, especially for low risk infants.

RISKS OF VITAMIN K PROPHYLAXIS

Konakion ampoules contain phenol, propylene glycol38 and polyethoxylated

castor oil as a non-ionic surfactant. Studies in animals given

polyethoxylated castor oil have shown a severe anaphylactic reaction

associated with histamine release. Strong circumstantial evidence

implicates polyethoxylated castor oil in similar reactions in humans.

Polyethoxylated castor oil, when given to patients over a period of

several days, can also produce abnormal lipoprotein electrophoretic

patterns, alterations in blood viscosity and erythrocyte aggregation (red

blood cell clumping). Individuals sensitive to this base are

contraindicated from using Konakion. New Ethicals Compendium also warns

that the use of Konakion can cause jaundice and kernicterus in infants.53

Other listed side effects include flushing, sweating, cyanosis, a sense

of chest constriction, and peripheral vascular collapse. Local cutaneous

and subcutaneous changes may occur in areas of repeated intramuscular

injections.

This synthetic, injectable vitamin K formulation was never subjected to a

randomised, controlled trial. In new drugs that are to be used for

prophylaxis, the usual risk/benefit analysis does not apply, since the

individual is not ill. The ethical principle of non-maleficence (primum

non nocere – first do no harm) applies and the trials must thus be larger

in order to identify any previously unrecognised side effects.65 Since

this did not happen, nor was there any long term follow up, we actually

have little idea of the effects of this drug on newborn babies.

The risks of injecting vitamin K into a newborn baby are nerve or muscle

damage as the preparation must be injected deeply into the muscle, not

subcutaneously under the skin. There is also the documented risk of

injecting the baby with the syntocinon intended for the mother.30, 70 As

stated in the product information,53 infants can suffer from jaundice or

kernicterus (brain damage from a build-up of bile pigments in the brain)

from Konakion. Infants who have the enzyme deficiency G6PD (glucose 6

phosphate dehydrogenase) are at particular risk from vitamin K.30 The

other risk factor is the possible increased chance of childhood cancer.

THE LINK BETWEEN CHILDHOOD CANCER AND INTRAMUSCULAR VITAMIN K

In 1970, a national cohort study of 16,193 infants born in one week in

April was begun in Britain.26 This study was to test

Page 5

hypotheses about childhood cancers and their associated factors.

Thirty-three of the children had developed cancer by age 10 and were

compared with 99 control children, matched on maternal age, parity and

social class. One of the unlooked-for risk factors was the administration

of prophylactic drugssuch as vitamin K in the first week after birth – a

nearly three-fold risk. This association fitted no prior hypothesis and

the authors recommended that their finding be tested in another series of

cases.

The authors of the study approached Roche, the manufacturers of Konakion,

for funding for a further trial to examine the findings more closely.

Roche was not interested until, a few months later, the media reported

the results of the study and that vitamin K given to babies might cause

childhood cancer. Roche then decided to fund a new study.27

The new study25 was a case-control study of 195 children with cancer born

at either of two hospitals in Bristol, England, compared with 588 healthy

children also born at these hospitals. One hospital predominantly gave

vitamin K orally and the other intramuscularly. The authors found a

nearly two-fold risk of leukaemia in children who had received

intramuscular vitamin K.

These findings were extremely worrying. Golding calculated that the extra

cases of leukaemia caused by vitamin K injection could be as many as 980

in the UK alone.25 These results were supported by reports of the

potential carcinogenicity of vitamin K from Israels et al, who suggested

that low vitamin K levels in the newborn protect against the risk of

mutations during a period of rapid cell growth and division.39 Pizer et

al did not find any association between the route of vitamin K

administration and mutations in cells but concluded that his study was

too small to show any real effect.62 Another study reported no increase

in abnormalities in newborn infants, but, with only 12 infants, the study

was too small to show any real effect.10 It is worth noting that after an

intramuscular dose of vitamin K, the baby’s plasma levels are almost 9000

times the normal adult levels.47 It has also been suggested that the

cancer-causing agent could be a metabolite, N-epoxide, or some other

component of the solution other than vitamin K itself.15

Golding’s study was criticised by many. One of the reasons was that the

authors had to make assumptions for some cases, as the information on

vitamin K administration was not clearly recorded. In spite of this,

expert epidemiologists considered that the results were plausible and so

could not be lightly dismissed.15 Further studies were proposed to answer

the question of cancer and vitamin K.

In 1993, results from three retrospective studies on vitamin K and

childhood cancer were published. The studies were done in the USA,

Denmark and Sweden.41, 57, 19 These studies, although large, did not

confirm the association between intramuscular vitamin K and childhood

cancer. One of the studies not only showed no association between IM

vitamin K and childhood cancer, it also showed no association between

maternal smoking and childhood cancer, a finding totally at odds with the

results from many other studies.19 The other two studies were also not

comparable to the British study. One because of differences in type of

vitamin K given41 and the other because of the use of birth cohorts with

differing regimens of vitamin K usage.57

Because of the design flaws in these studies, there was still a need for

further case-control studies. Results from two were published in 1996.2,

77 They had carefully matched controls and more accurate information on

whether vitamin K had been given or not, and by which route. One of the

studies2 reported no association between intramuscular vitamin K and

childhood cancer and the other77 found a risk of leukaemia, but only when

cases were compared with local controls (i.e. from the same hospital) and

not with controls randomly selected from the whole area under study.

This, although suggestive, was not followed up but dismissed as a chance

finding related to multiple testing.

The suggestion was then put forward that, as these studies had failed to

show a definite association between intramuscular vitamin K and childhood

cancers, worries about any potential cancer risk should be abandoned.83

At that time, four more studies on vitamin K and cancer were in

progress.44, 59, 60, 61 The results from these four studies were

published in 1998. Two of them failed to confirm any increased risk of

childhood cancers.44 61 One of the other studies showed a twofold risk of

acute lymphoblastic leukaemia among 1-6 year olds,59 the other showed a

significant risk for all cancers.60

So, the jury is still out on whether there is an increased risk of

childhood leukaemia with the intramuscular form of vitamin K. Some

recommend that intramuscular vitamin K should still be used, as the risk

of leukaemia “seems more hypothetical than real”.76 Others believe that

public confidence in IM vitamin K has been severely shaken and will be

difficult to restore fully. They recommend an oral regimen similar to

that used in the Netherlands of 25(g daily, given by the mother. This

would avoid the grossly unphysiological peaks of vitamin K from both the

IM route and the present oral route.71

ORAL VITAMIN K VS INTRAMUSCULAR

The two main problems with giving vitamin K orally are that there is no

licensed oral formulation, meaning that babies receive the intramuscular

form orally, and that compliance with three oral doses is poor as many

doctors and midwives are reluctant to give an unlicensed formula.13 The

use of unlicensed preparations may theoretically expose professionals to

litigation in the event of prophylactic failure or unforeseen adverse

events.2

Roche, the manufacturers of Konakion, state that they do not recommend

the administration of Konakion solution orally.63 Their reasons are: that

they have no clinical studies to support oral use, phenol, which has been

reported to be an irritant to newborns mouths, is used as a preservative,

the variability in the production of bile salts in newborns may affect

absorption, that Konakion given orally has a small association with

anaphylactic reactions.

Page 6

The preparation was also unpleasant to taste and babies were inclined to

spit it out82 or to vomit it back up. Only about half of an orally

administered dose is absorbed.47 Even so, the plasma concentrations in

babies who were given oral vitamin K reached 300 times the adult levels,

before dropping off slightly after about 24 hours.47

After the publication of Golding’s studies, further trials were done on

oral vitamin K prophylaxis and whether it gave longer term protection. In

1992, Cornelissen11 found plasma vitamin K concentrations were higher in

the group given IM vitamin K than the oral group, but blood

coagulability, activities of factors VII, X and PIVKA-II concentrations

showed no differences. By 3 months follow-up, vitamin K levels had

dropped in both groups but more in the oral group. He suggests that

neither give long term protection. One would assume that babies should be

producing their own vitamin K by 3 months and, if not, what other

mechanism could be hindering this process.

Von Kries et al78 studied repeated oral vitamin K prophylaxis in Germany,

with 3x 1 mg doses and found that it was not as effective as a 1mg

intramuscular dose at birth. Another study by Cornelissen et al12

reported on the effectiveness of differing regimens of oral vitamin K in

four different countries – the Netherlands, Germany, Switzerland and

Australia (two differing regimes). In the Netherlands, babies are given

25 (g daily oral vitamin K for 3 months with I mg given at birth either

orally for healthy newborns or intramuscularly for unwell babies. In

Germany, the regime is 3 x 1 mg oral doses as was also the case in

Australia from 1993 to 1994. In Switzerland 2 oral doses of a new

‘mixed-micellar’ oral vitamin K is given. The Netherlands had the lowest

failure rate – 0 per 100,000. In Australia, where the regime was changed

in 1994 from oral to IM, the failure rate was 1.5 per 100,000 for oral

and 0.9 per 100,000 for IM, showing that 3 oral doses are less effective

at preventing late onset HDN than one IM dose of vitamin K. Even if Roche

are persuaded to bring the mixed-micellar preparation into New Zealand,

results from Switzerland (failure rate of 1.2 per 100,000)12 show that

further study needs to be done on the most effective timing of the doses.

If New Zealand parents wish their baby to receive oral vitamin K, the

recommended regimen is for 3 x 1mg doses, 1 at birth, 1 at 5 days and 1

at 6 weeks.6, 20 It is up to parents to ensure that their baby receives

all 3 doses if they choose this form of prophylaxis.

CONCLUSION

It would seem an anachronism that babies are born with a deficiency of

such an essential vitamin and require supplementation. In fact, although

there have been many studies on differing aspects of vitamin K

prophylaxis, there has only been one39 on the possible reasons for and

the advantages (if any) of the physiological levels of vitamin K in

newborns.

The risks of prophylaxis for the majority of babies who are at low risk

of HDN are also not understood. As plasma vitamin K levels in newborns

reach 300 times normal adult levels for oral and almost 9000 times for IM

vitamin K47, some research needs to be done on the effects this may have.

Studies have shown that physiological levels of vitamin K maintain a

careful balance between coagulation and anti-coagulation and we have no

idea what the effects of upsetting that delicate balance would be.

The number of children currently developing cancer during childhood is

much higher than the number developing a life threatening or permanently

disabling problem as a result of late onset HDN. The risk of childhood

cancer is estimated to be 1.4 per 1000, from the 1970 British cohort. If

IM vitamin K caused cancer, there would be 100 extra cases of cancer per

case of HDN prevented.16 This could mean that giving IM vitamin K to

every baby would be doing more harm than good.36

The decision rests on parents’ shoulders – the link between intramuscular

vitamin K and childhood cancer has not been definitively proved, nor has

it been completely disproved. It may be that an oral regimen as suggested

by Tripp and McNinch71 could be the answer to the dilemma. If this is the

case, then Roche needs to be lobbied to make the European preparations

available in New Zealand. In the meantime, the choice is between no

vitamin K, with the mother being aware of her dietary intake of vitamin

K, an oral regimen or the intramuscular formulation.

BIBLIOGRAPHY

Anai T, Hirota Y, Yoshimatsu J et al. Can prenatal vitamin K1

supplementation replace prophylaxis at birth? Obst Gynec 1993;81:251-4.

Ansell P, Bull D and Roman E. Childhood leukaemia and intramuscular

vitamin K: findings from a case-control study. BMJ 1996;313(7051):204-5.

Barton J, McNinch A. and Tripp J. Oral vitamin K prophylaxis and

frequency of late vitamin K deficiency bleeding (letter). Lancet 1994

343(8906):1168. Barton J, Tripp J. and McNinch A. Neonatal vitamin K

prophylaxis in the British Isles: current practice and trends. BMJ 1995;

310(6980):632-3. Bhanchet P, Tuchinda S, Hathirat P et al. A bleeding

syndrome in infants due to acquired prothrombin complex deficiency. Clin

Pediatr 1977;16:992 in, Hathaway W. New insights on vitamin K. Hematol

Oncol Clin North Am 1987;1(3):367-379. Birkbeck J. Vitamin K prophylaxis

in the newborn: a position statement of the Nutrition Committee of the

Paediatric Society of New Zealand. NZMJ 1988;101:421-2. Birkbeck J.

Despite the contamination breastmilk remains the best. NZ Doctor July

1990. Brinkhous K, H and Warner D. Plasma prothrombin level in

normal infancy and in hemorrhagic disease of the newborn. Am J Med. Sci

1937;193:475-479 in, Ruby C. Vitamin K prophylaxis: a historical

perspective. MIDIRS;7:3. son P and A. Parenteral vitamin K1:

the effective prophylaxis against haemorrhagic disease for all newborn

infants. NZMJ 14 March 1990. Cornelissen M, Smeets D, Merkx G et al.

Analysis of chromosome aberrations and sister chromatid exchanges in

peripheral blood lymphocytes of newborns after vitamin K prophylaxis at

birth. Pediatr Res 1991;30:550-3. Cornelissen EAM, Kollée LAA, DeAbreu RA

et al. Effects of oral and intramuscular vitamin K prophylaxis on vitamin

K, PIVKA-II, and clotting factors in breastfed infants. Arch Dis Child

1992;67:1250-54. Cornelissen M, von Kries R, Loughnan P et al. Prevention

of vitamin K deficiency bleeding: efficacy of different multiple oral

dose schedules of vitamin K. Eur J Ped 1997;156(1):126-30. Croucher C.

and Azzopandi D. Compliance with recommendations for giving vitamin K to

newborn infants. BMJ 1994;308(6933):894-895. Dam H, Dyggve H, Larsen H

and Plum P. The relationship of vitamin K deficiency to hemorrhagic

disease of the newborn. Adv Pediatr 1952;5:129-153 (abstract). Darlow B.

Vitamin K deficiency haemorrhage: dilemmas over prophylaxis continue. NZ

Practice Nurse February 1995:35-37. Darlow B. and Nobbs P. The neonatal

vitamin K debate: IM vs. oral: two views. New Ethicals May 1993:11-18.

Dockerty J, Broadbent R and McNoe B. New Zealand hospital records

insufficient for vitamin K study. NZMJ 10 May 1995. Donley J. Vitamin K

in relation to haemorrhagic disease of the newborn. NZCOM Journal

December 1992.

Ekelund H, Finnstrom O, Gunnarskog I. et al. Administration of vitamin K

to newborn infants and childhood cancer. BMJ 1993;307(6896):89-91. Fetus

and Newborn Committee of the Paediatric Society of New Zealand. 1992.

Vitamin K administration in the newborn. Foetus and Newborn Society,

Canadian Pediatric Society. The use of vitamin K in the perinatal period.

Canad MAJ 1988;139:127-130. Fournier B, Sann L, Guillaumont M and Leclerq

M. Variations of phylloquinone concentrations in human milk at various

stages of lactation and in cow’s milk at various seasons. Am J Clin Nutr

187;45:551-8. Garrow D, Chisholm M. and Radford M. Vitamin K and

thrombotest values in full term infants. Arch Dis Child 1986;61:349-51.

Göbel U, Sonnenschein-Kosenow S, Petrich C and von Voss H. (Letter).

Lancet 1977;i:187-8. Golding J, Greenwood R, Birmingham K. et al.

Childhood cancer, intramuscular vitamin K and pethidine given during

labour. BMJ 1992;305 (6849):341-6. Golding J, Paterson M and Kinlen L.

Factors associated with childhood cancer in a national cohort study.

Brit. J Cancer 1990;62:304-8. Greenwood R. Vitamin K and childhood

cancer. MIDIRS 1994;4(3):258-9. Greer F, Marshall S, Cherry J and Suttie

J. Vitamin K status of lactating mothers, human milk, and breast-feeding

infants. Pediatrics 1991;88(4);751-6. Greer F, Marshall S, Foley A et al.

Improving the vitamin K status of breastfeeding infants with maternal

vitamin K supplements. Pediatrics 1997;99(1);88-92. Hall M. and

Pairaudeau P. The routine use of vitamin K in the newborn. Midwifery

1987;3(4):170-7. Hardwicke S. et al. Studies on the minimal effective

dose of a water-soluble vitamin K substitute in the prevention of

hypoprothrombinemia in the newborn infant. J Pediatr 1944;24:259-269

(abstract). Haroon Y, Shearer M, Rahim S et al. The content of

phylloquinone (vitamin k1) in human milk, cow’s milk and infant formula

foods determined by high performance liquid chromatography. J Nutr

1982;112:1105-17. Hathaway W. New insights on Vitamin K. Hematol Oncol

Clin North Am 1987;1(3):367-379. -Smart, D. Giving vitamin K to

newborn infants: a therapeutic dilemma. MJA 1996;165:414-5. Heron P, Cull

A., Bourchier D and Lees H. Avoidable hazard to New Zealand children:

case reports of haemorrhagic disease of the newborn. NZMJ 1988;101:507-8.

Hey, Edmund. Vitamin K – the debate continues. MIDIRS 1998;8(2):234-6.

Hilgartner, M. Vitamin K and the newborn. New Eng J Med

1993;329(13):957-8. Hull D. Vitamin K and childhood cancer. BMJ

1992;305:326-7. Israels l, Friesen E., Jansen A. and Israels E. Vitamin

K1 increases sister chromatid exchange in vitro in human leukocytes and

in vivo in fetal sheep cells: a possible role for ‘vitamin K deficiency’

in the fetus. Pediatr Res 1991;30:550-3. nsen F, Fielding P, Vinther

S et al. Vitamin K to neonates. Peroral versus intramuscular

administration. Acta Pediatr Scand 1991;80(3):304-7. Klebanoff M, Read J,

Mills J. et al. The risk of childhood cancer after neonatal exposure to

vitamin K. New Eng J Med. 1993;329(13):905-8. Koppe J, Pluim E and Olie

K. Breastmilk, PCBs, dioxins and vitamin K deficiency: discussion paper.

J Royal Soc. Medicine 1989;82:416-419 in, Donley, Joan. Vitamin K in

relation to haemorrhagic disease of the newborn. NZCOM Journal Dec 1992.

Malia R, Preston F and V. Evidence against vitamin K deficiency

in normal neonates. Thromb Haemost 1980;44:159. McKinney P, Juszczak E,

Findlay E, K. Case-control study of childhood leukaemia and cancer

in Scotland: findings for neonatal intramuscular vitamin K. BMJ

1998;316:173-7. McNinch A and Tripp J. Haemorrhagic disease of the

newborn in the British Isles: a two year prospective study. BMJ

1991;303(6810):1105-1109. McNinch A, Orme R and Tripp J. Haemorrhagic

disease of the newborn returns. Lancet 1983;i:1089-90 (abstract). McNinch

A, Upton C, s M et al. Plasma concentrations after oral or

intramuscular vitamin K1 in neonates. Arch Dis Child 1985;60:814-818.

Meyer T and Angus J. The effect of large doses of Synkavit in the

newborn. Arch Dis Child 1956;31: 212-5 in, Ruby, C. Vitamin K: a

historical perspective. MIDIRS 1997;7(3):362-4. Mori P, Bisogni C, Odino

S et al. (letter). Lancet 1977;ii:188. Motohara K, Endo F and Matsuda I.

Screening for late neonatal vitamin K deficiency by acarboxyprothrombin

in dried blood spots. Arch Dis Child 1987;62:370-375. Motz R. Late

haemothorax after oral vitamin K. NZMJ 11 November 1992:459. Muller A.,

van Doorm J and Hemker H. Heparin-like inhibitor of blood coagulation in

normal newborn. Nature 1977;267:616-7. New Ethicals Compendium; 3c:

303-304. Nishiguchi T, Saga K, Sumimoto K. et al. Vitamin K prophylaxis

to prevent neonatal vitamin K deficient intracranial haemorrhage in

Shizuoka prefecture. Brit J Obstet Gynec 1996;103 (11):1078-84. O’Connor

M. and Addiego J. Use of oral vitamin K1 to prevent hemorrhagic disease

of the newborn infant. J Pediatr 1986;108:616-9. O’Connor M, Livingstone

D, Hannah J. and Wilkins D. Vitamin K deficiency and breastfeeding. Am J

Dis Child 1983;137:601-2 Olsen J, Hertz H, Blinkenberg K. et al. Vitamin

K regimens and incidence of childhood cancer in Denmark. BMJ

1994;308(6933):895-6 in, Greenwood, R. Vitamin K and childhood cancer.

MIDIRS 1994;4(3):258-260 Olson J. Recommended dietary intakes (RDI) of

vitamin K in humans. Am J Clin Nutr 1987;45:687-92. L, Cole M,

Craft A, Hey E. Neonatal vitamin K administration and childhood cancer in

the north of England: retrospective case-control study. BMJ

1998;316:189-93. Passmore S, Draper G, Brownbill P, Kroll M. Case-control

studies of relation between childhood cancer and neonatal vitamin K

administration: retrospective case-control study. BMJ 1998;316:178-84.

Passmore S, Draper G, Brownbill P, Kroll M. Ecological studies of

relation between hospital policies on neonatal vitamin K administration

and subsequent occurrence of childhood cancer. BMJ 1998;316:184-9 Pizer

B, Boyse J, Hunt L. and Mott M. Neonatal vitamin K administration and in

vivo somatic mutation. Mutat Res 1995;347:135-9. Roche Products Ltd.

Position statement re: Konakion injection given orally. Roche Products

Ltd. New oral vitamin K formulation for newborns (press release). Welwyn

Garden City, 30 Aug 1996. Ruby . Vitamin K prophylaxis: a

historical perspective. MIDIRS 1997;7(3):362-4. Shearer M. et al. Plasma

vitamin K1 in mothers and their newborn babies. Lancet 1982:460-3 in,

Hathaway, W. New insights on vitamin K. Hematol Oncol Clin North Am

1987;1(3):367-379. son, J. The vitamin K conundrum. Maternity

Alliance Action Newsletter July/August 1992. Suzuki H, Nakao T and Hiraga

K. Vitamin K deficiency in male rats fed diets containing butylated

hydroxytoluene (BHT). Toxicol Appl Pharmacol 1979;50:261-6 in, Birkbeck

J. Vitamin K prophylaxis in the newborn: a position statement of the

Nutrition Committee of the Paediatric Society of New Zealand. NZMJ

1988;101:421-2. Townsend C. The hemorrhagic disease of the newborn. Arch

Pediatr 1894;11:559-562 in, Birkbeck J. Vitamin K prophylaxis in the

newborn: a position statement of the Nutrition Committee of the

Paediatric Society of New Zealand. NZMJ 1988;101:421-2. Tripp J. and

McNinch A. Haemorrhagic disease and vitamin K. Arch Dis Child

1987;62:436-7. Tripp J and McNinch A. The vitamin K debacle: cut the

Gordian knot but first do no harm. Arch Dis Child 1998;79:295-299. Vail,

B. Vitamin K prophylaxis and hemorrhagic disease of the newborn. ICEA

Review 1985;9(3). Van Doorm J and Hemker H. Vitamin K deficiency in the

newborn (letter). Lancet 1977;ii:708-9. Van Doorm J, Muller A. and

Hemker, H. Heparin-like inhibitor, not vitamin-K deficiency, in the

newborn (letter). Lancet 1977;i:852-3. Vietti T, T, J and

Pritchard J. Observations on the prophylactic use of vitamin K in the

newborn. J Pediatr 1960;56(3);343-6 (abstract). Von Kries R. Neonatal

vitamin K prophylaxis: the Gordian knot still awaits untying. BMJ

1998;316 (7126):161. Von Kries R, Göbel U, Hachmeister A. et al. Vitamin

K and childhood cancer: a population based case-control study in Lower

Saxony, Germany. BMJ 1996;313(7051):199-203. Von Kries R, Hachmeister A

and Göbel U. Repeated oral vitamin K prophylaxis in West Germany:

acceptance and efficacy. BMJ 1995;310 (6987):1097-8. Von Kries R, Kreppel

S, Becker A, Tangermann R and Göbel U. Acarboxyprothrombin activity after

oral prophylactic vitamin K. Arch Dis Child 1987;62: 938-40. Von Kries R,

Shearer M and Göbel U. Vitamin K in infancy. Eur J Pediatr

1988;147:106-12. Waddell W. and Guerry D. The role of vitamin K in the

etiology, prevention and treatment of hemorrhage in the newborn infant. J

Ped 1939;15:802 in, Ruby, C. Vitamin K prophylaxis: a historical

perspective. MIDIRS 1997;7(3):362-4. Whipple G. Hemorrhagic disease;

antithrombin and prothrombin factors. Arch Intern Med. 1913;12:637-641

in, Birkbeck, J. Vitamin K prophylaxis in the newborn: a position

statement of the Nutrition Committee of the Paediatric Society of New

Zealand. NZMJ 1988;101:421-2. Zipursky A. Vitamin K at birth. BMJ

1994;313(1051):179-180.

--------------------------------------------------------

Sheri Nakken, R.N., MA, Classical Homeopath

Vaccination Information & Choice Network, Nevada City CA & Wales UK

$$ Donations to help in the work - accepted by Paypal account

vaccineinfo@... voicemail US 530-740-0561

(go to http://www.paypal.com) or by mail

Vaccines - http://www.nccn.net/~wwithin/vaccine.htm

Vaccine Dangers On-Line course - http://www.nccn.net/~wwithin/vaccineclass.htm

Homeopathy On-Line course - http://www.nccn.net/~wwithin/homeo.htm

ANY INFO OBTAINED HERE NOT TO BE CONSTRUED AS MEDICAL

OR LEGAL ADVICE. THE DECISION TO VACCINATE IS YOURS AND YOURS ALONE.

******

" Just look at us. Everything is backwards; everything is upside down.

Doctors destroy health, lawyers destroy justice, universities destroy

knowledge, governments destroy freedom, the major media destroy information

and religions destroy spirituality " .... Ellner

September 14, 2005

Hi i,

It's not a vaccine, it's a shot they give to newborns in the hospital

to prevent a rare disorder that causes some babies to bleed into their

brain in the first three months after birth (hemorrhagic disease of

the newborn). Vitamin K is involved in blood clotting, and the theory

is that since newborns don't have the same levels of vit K in their

blood as adults, they are deficient in it, so they need this shot to

prevent this bleeding disorder. Breastfed babies who get no formula

are considered to be especially at high risk because breastmilk

doesn't contain much vit K and formula is loaded with artificially

high amounts of it.

But several studies have shown the vitamin K shot increases the risk

of early childhood leukemia and other childhood cancers, so many new

parents are questioning whether they want their newborns to get this

shot or not. Alternatives to having the shot are doing nothing about

vitamin K, increasing vit K in the breastfeeding mother's diet, having

the breastfeeding mother take a vitamin K supplement, and giving the

baby a vitamin K dose orally instead of injecting it. None of these

are accepted by our medical community, and parents have to sign a

waiver to refuse the vit K shot in the hospital.

Here is an article about it:

http://www.babyreference.com/VitaminKinjectORnot.htm

B

> HI everyone, I just joined last week but haven't had much time to get

> on. I was just reading up on the posts and am curious what this

> Vitamin K Vacc is all about? I have never heard of this one.

December 2, 2005

hey Amber,

If you feel that the benefits of the oral Vit outweigh the risks, and it

gives you peace of mind, then by all means why not use it? What are the

effects of the oral K? How soon can it be administered and still be

effective? And be certain to let placenta come on it's own and let cord

stop pulsing before clamping. At least have it accesible and make sure it's

a good source. At least, that's what I would do. You have to decide what

you're comfortable with without harming your baby. What does your midwife

say? I haven't researched this but sounds as if you need to do some more?

Follow your instinct.

LAurie>Oh

-- Vitamin K

Ivitamin K but I do have oral on hand in case I decide to go that route. My

only concern is this, my husbands sister has a severe clotting disorder. So

I am concerned that I should give the oral vitamin K profolacitly incase the

baby inheireted the disorder. If his sister didn't have this I wouldn't give

the vitamin K period but am on the fence since there is a possibility of the

baby having problems with clotting after the birth. Any input would be

really appreciated! Thanks Amber

December 2, 2005

Hi

We had an issue with this with our third child. Vit K is fat saluble,

which means that it is processed by the liver. The dose given in

hospitals is 300 times the RDA. Yes, that is not a typo- the dose

given in hospitals to infants is THREE HUNDRED TIMES the recommended

daily allowance. It is per weight, and for an average baby weight,

they are given what is equvilant to 300 times what would be considered

safe.

This taxes a brand new liver in a body that is less than one hour

outside of it's mothers womb (which is when the shot is given).

Putting this unecessary strain on the tiny liver causes a build up of

biliruben in the blood which causes - in many cases- jaundice.

Statistically, 50% of babies born in hosptials get jaundice. Go figure.

In more severe cases, studies have shown that the adverse affects can

lead to more serious illness including later development of lukemia.

(you can easily look this up if you google " compulsory vitamin K and

lukemia " .)

If you have had a drug problem during your pregnancy, if you abuse

alchohol during your pregnancy or if you take psycotropic (sp?) drugs,

or if you are severely mal-nourished, then your baby may be at some

risk for the rare blood condition. If none of these conditions exist

then your baby is NOT at risk.

I won't post any links to any statistical data because I feel that

when making these kinds of decisions one must do their own homework in

order to be confidant in their decision. These are the facts, you can

verify all of them easily.

It is a personal decision that should be left to the parent. My

" opinion " is that you should not. Again though, it is your choice NOT

THEIRS so in either case do not let them pressure you!

Best wishes to you!

Love

Laurette

December 2, 2005

Amber,

I'm sorry, I didn't read this post when I answered your first one. I

do not know the stats for the oral version, however, are you certain

that your sister in law having a clotting problem is a risk factor? I

would look up the risk factors for the disease and find out what the

exact dosage is.

Again, best wishes to you! I give you huge kudos for homebirth.

If I could go back and do it again, I would DEFINITLY do a homebirth!

I don't know if I'll have anymore or not, but if I do, I'm for sure

going for an HBA3C or at the very least VBA3C

Love

Laurette

>

> I know this was brought up a few weeks ago, but I am still uncertain

about

> the issue. Our baby is due in about 3 weeks and I am still going

back and

> forth on our decision about Vitamin K. I know that we do not want

the IM

> vitamin K but I am going back and forth about the oral version. I am

having

> a home birth so there is no pressure to do either and I wouldn't do

either

> except for my husband's sister has a severe clotting disorder that

could be

> passed on to the baby. So I don't know if the benefits to giving it

> profolacticly outweigh the risks if I don't give it and she by some

chance

> has the disorder as well. Any input would be great! Thanks Amber

>

> _________________________________________________________________

> FREE pop-up blocking with the new MSN Toolbar – get it now!

> http://toolbar.msn.click-url.com/go/onm00200415ave/direct/01/

>

January 20, 2006