HIGH BILIRUBIN COUNT: APNEA AND OTHER SYMPTOMS, VIT K DANGERS

High Bilirubin Count: Apnea and Other Symptoms
Symptoms in a case misdiagnosed as SBS/NAI (Non-Accidental Trauma)

http://www.deep-picture.com/8BECC560-8E66-4250-A88B-
591C1ACB49EE.W5Doc?frames=no&
ctBilirubin
Bilirubin concentration
Definition
cBilirubin is the total concentration of bilirubin in plasma. The systematic
symbol for arterial blood is cBilirubin(aP). The analyzer symbol may be ctBil.

What does cBilirubin tell you
Bilirubin is formed as a result of the catabolism of hemoglobin. Typically, the major part of bilirubin in plasma comes from the breakdown of red cells. Most of the initially produced unconjugated bilirubin is in plasma reversibly bound to albumin, but the unbound part is toxic.

Clinical interpretation
Hyperbilirubinemia is due to increased production, decreased elimination, or a combination of both.

A. Increased production:
Hemolysis
Common causes:
* Infection
* Chemical-toxical reaction
* Immunization (auto-immune disease or iso-immunization)
* Hereditary disease

B. Decreased elimination:
Intrahepatic cholestasis
Common causes:
* Viral infection (hepatitis of any kind)
* Primary biliary cirrhosis
* Toxic reactions (medicaments)

Several diseases in the newborn, i.e., immunization, infection, hypothyroidism, biliary atresia, and galactosemia, may cause hyperbilirubinemia, and although in most cases this is simple hyperbilirubinemia, the clinician has to be aware of underlying disease. Signs of such are high cBilirubin in cord blood, early (< 24 hrs.) hyperbilirubinemia, steep increase in cBilirubin, and prolonged hyperbilirubinemia.

http://www.ingentaconnect.com/content/bsc/ejci/2003/00000033/00000009/art00012
Enterohepatic cycling of bilirubin as a cause of 'black' pigment gallstones in adult life - L Vitek, MC Carey - European Journal of Clinical Investigation, 2003 - ingentaconnect.com

... diets replete in refined sugars: high sucrose diets ... Gilbert’s syndrome, feeding refined carbohydrate diets results in elevated plasma bilirubin levels [79 ...

http://findarticles.com/p/articles/mi_g2601/is_0009/ai_2601000958
Neonatal jaundice :Description: Bilirubin, a by-product of the breakdown of hemoglobin (the oxygen-carrying substance in red blood cells), is produced when the body breaks down old red blood cells. Normally, the liver processes the bilirubin and excretes it in the stool. Hyperbilirubinemia means there is a high level of bilirubin in the blood. This condition is particularly common in newborn infants. Before birth, an infant gets rid of bilirubin through the mother's blood and liver systems. After birth, the baby's liver has to take over processing bilirubin on its own. Almost all newborns have higher than normal levels of bilirubin. In most cases, the baby's systems continue to develop and can soon process bilirubin. However, some infants may need medical treatment to prevent serious complications which can occur due to the accumulation of bilirubin.

Causes & symptoms
In newborn infants, the liver and intestinal systems are immature and cannot excrete bilirubin as fast as the body produces it. This type of hyperbilirubinemia can cause jaundice to develop within a few days after birth. About one-half of all newborns develop jaundice, while premature infants are much more likely to develop it. Hyperbilirubinemia is also more common in some populations, such as Native American and Asian*. All infants with jaundice should be evaluated by a health care provider to rule out more serious problems.

(* Baby Casey is part Korean)

Hyperbilirubinemia and jaundice can also be the result of other diseases or conditions. Hepatitis, cirrhosis of the liver, and mononucleosis are diseases that can affect the liver. Gallstones, a blocked bile duct, or the use of drugs or alcohol can also cause jaundice.

Extremely high levels of bilirubin in infants may cause kernicterus, a form of brain damage. Signs of severe hyperbilirubinemia include listlessness, high-pitched crying, apnea (periods of not breathing), arching of the back, and seizures. If severe hyperbilirubinemia is not treated, it can cause mental retardation, hearing loss, behavior disorders, cerebral palsy, or death.

http://www.cdc.gov/ncidod/dvbid/yellowfever/vaccine/qa.htm
(Further information can be found at MMWR 2001;50:343-5.)

Q. What were the clinical manifestations of the rare but severe illness recently reported in recipients of yellow fever vaccine?

A. The seven persons who were reported with severe multisystemic illness after yellow fever vaccination exhibited the following:

Onset: Within 5 days after yellow fever vaccination.

Symptoms, signs, laboratory findings: Fever, lymphocytopenia, thrombocytopenia, mild to moderate elevation of hepatocellular enzymes, hypotension, and respiratory failure occurred in all patients. Most of the patients also had headache, confusion, vomiting, myalgias, renal failure requiring hemodialysis, hyperbilirubinemia, and severe metabolic acidosis.

The potential association between yellow fever vaccine and subsequent severe multisystemic illness has initiated further investigation.

References
Chan RC, Penney DJ, Little D, et al. Hepatitis and death following vaccination with 17D-204 yellow fever vaccine. Lancet 2001;358:121-2.

Martin M, Tsai TF, Cropp B, Chang GJ, et al. Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases. Lancet 2001;358:98-104.
Vasconcelos PF, Luna EJ, Galler R, et al. Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. Lancet 2001;358:91-7.

Centers for Disease Control and Prevention. Notice to readers: Fever, jaundice, and multiple organ system failure associated with 17D-derived yellow fever vaccination, 1996–2001. MMWR 2001;50:343-5.

http://www.whale.to/vaccine/yurko.html

"The Issue of the Birth Weight: It is well known that newborn infants of diabetic mothers tend to be larger and plumper (macrosomia) than nondiabetic mothers, a response to increased nutrient supply and hypersecretion of insulin by the fetal pancreas. However, a large retrospective review by Dr. Evelyne Rey of Montreal has also found that infants born from mothers with gestional diabetes have higher rates of newborns who are large-for-gestional-age, in addition to having complications of hypoglycemia and hyperbilirubinemia;(11). For this reason, the recorded birth weight for Baby Alan of 5 pounds and 8 ounces may have been falsely elevated, with an increased proportion of adipose tissue in relation to other tissues and organs.

The Issue of Hyperbilirubinemia: The term, hyperbilirubinemia, denotes an excess of bilirubin, a condition which is potentially neurotoxic. Kernicterus is a neurologic sysndrome resulting from deposition of unconjugated bilirubin in the brain. It can occur at much lower levels of serum bilirubin in sick or premature infants than in healthy, full-term babies. While toxic levels for healthy infants is listed at or above 25 mgs/dL in current pediatric texts, levels as low or lower than l0 mgs/dL can cause brain damage in a sick or premature infant.(12) Other predisposing factors to kernicterus include acidosis, hypoxia, administration of free fatty acids (administered by nasogastric tube in the newborn intensive care unit), salicylates (aspirin) and antibiotics (both administered during newborn hospitalization), and pitocin (the mother’s labor was induced with pitocin).

http://www.in.gov/isdh/programs/breastfeeding/handbook/common_questions.htm
Jaundice and Breastfeeding
“A review of available follow-up data for apparently healthy term infants whose serum bilirubin concentrations were as high as 25 mg/dl showed no apparent ill effects for these concentrations.”1

“Some evidence indicates that frequent breastfeeding (8-10 times per 24 hours) may reduce the incidence of hyperbilirubinemia.” 1

“Supplementing nursing with water or dextrose-water will not lower serum bilirubin levels in jaundiced, healthy, breastfeeding infants.”1

“When an indirect serum bilirubin concentration is elevated by some pathologic cause, there is no reason to discontinue breastfeeding.”1

“In the absence of dehydration, routine supplementation (with dextrose-water) of infants receiving phototherapy is not indicated.” 1

1 American Academy of Pediatrics and American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care (4th Edition). Elk Grove Village, IL: AAP, 151, 183-188, 1997. The Academy of Breastfeeding Medicine Protocols on Supplementary Feedings & Mastitis

The following article relates to "premies" but logically might also affect full term newborns. http://www.nature.com/jp/journal/v25/n6/full/7211295a.html

Original Article
Journal of Perinatology (2005) 25, 386–390. doi:10.1038/sj.jp.7211295
Published online 21 April 2005
Transient Bilirubin Encephalopathy and Apnea of Prematurity in 28 to 32 Weeks Gestational Age Infants

Sanjiv B Amin MD1, Lama Charafeddine MD2 and Ronnie Guillet MD, PhD2

1. 1Department of Pediatrics (S.B.A), Division of Neonatology, University of Maryland, Baltimore, MD, USA
2. 2Department of Pediatrics (L.C., R.G.), Division of Neonatology, Children's Hospital at Strong, Rochester, NY, USA

Correspondence: Sanjiv B. Amin, MD, University of Maryland School of Medicine, Division of Neonatology, 22, South Greene Street, N5W68, University Center, Baltimore, MD 21201, USA

OBJECTIVE:
Apnea of prematurity (AoP) is, in part, a reflection of brainstem-mediated respiratory control system maturation. We previously demonstrated changes in brainstem function in relation to hyperbilirubinemia (bilirubin encephalopathy, [BE]) as evaluated by auditory brainstem evoked responses (ABR) in infants 28 to 32 weeks gestational age (GA). We hypothesized that in this population, as bilirubin increases and causes auditory brainstem dysfunction, respiratory control system may also be adversely affected leading to increased frequency of AoP.

Transient Bilirubin Encephalopathy
The charts of 100, 28 to 32 weeks GA infants, admitted to the Neonatal Intensive Care Unit of Golisano Children's Hospital at Strong, Rochester, NY from July 1996 to July 1998 who participated in the transient BE study were examined retrospectively.

Other Articles:
http://pediatrics.aappublications.org/cgi/content/full/116/3/e343

http://www.draligus.com/3607h-neonatal-jaundice-follow-up.html

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5030a3.htm
August 03, 2001 / 50(30);643-5
Notice to Readers: Fever, Jaundice, and Multiple Organ System Failure Associated With 17D-Derived Yellow Fever Vaccination, 1996--2001

At the June 2001 meeting of the Advisory Committee for Immunization Practices (ACIP), seven cases of multiple organ system failure (MOSF) in recipients of 17D-derived yellow fever (YF) vaccine were presented (1--3). In response, an ACIP working group was formed to review the cases, assess the risk for serious adverse events following YF vaccination, and consider revision of the 1990 YF vaccination recommendations (4). This notice summarizes these cases and describes an enhanced surveillance program designed to refine risk estimates and improve histopathologic documentation of MOSF potentially associated with YF vaccination.

Derived from the original 17D YF vaccine strain, the live, attenuated 17D-204 and 17DD YF strains are the most commonly used YF vaccines (5). In 1999 and 2000, two Brazilian residents aged 5 and 22 years became ill after receiving 17DD YF vaccine administered during a campaign initiated in response to a local YF epidemic. During 1996--2001, five persons aged 56--79 years, including four U.S. residents and one Australian resident (two countries where YF is not endemic) became ill after receiving 17D-204 YF vaccine administered in anticipation of international travel. Two of the five persons were planning to travel to countries where local YF transmission had never been reported.

All seven persons became ill within 2--5 days of vaccination and required intensive care; six died. None had documented immunodeficiency, and all were in their usual state of health before vaccination. Illness was characterized by fever, lymphocytopenia, thrombocytopenia, mild-to-moderate elevation of hepatocellular enzymes, hypotension with poor tissue perfusion, and respiratory failure. Most patients also had headache, vomiting, myalgias, hyperbilirubinemia, and renal failure requiring hemodialysis.

http://content.nejm.org/this_week/344/8/index.shtml
Drug Therapy: Neonatal Hyperbilirubinemia
Newborn infants have high rates of bilirubin production and low rates of bilirubin metabolism and clearance, and transient hyperbilirubinemia is therefore very common. Pathologic hyperbilirubinemia occurs in newborn infants with hemolytic anemia and those with hepatic disorders characterized by impaired bilirubin metabolism. Bilirubin is toxic, especially to neurons, and can cause kernicterus, poor feeding, muscle hypotonia and hypertonia, seizures, and death. This article reviews the pathogenesis of and risk factors for pathologic hyperbilirubinemia in newborn infants, current methods of predicting severe hyperbilirubinemia, and its prevention and treatment.

Title: Vitamin E deficiency in the pathogenesis of haemolysis and hyperbilirubinaemia of neonatal jaundice.
Author: Ojo, C.O. : Dawodu, A.H. : Osifo, B.O.A.
Citation: J-Trop-Pediatr. Oxford : Oxford University Press. Oct 1986. v. 32 (5) p. 251-254. charts.

Abstract: A study involving 37 jaundiced neonates (ages 1-19 days) and 29 normal neonate controls assessed whether vitamin E deficiency plays a role in the onset of neonatal jaundice. Blood analyses revealed significantly low levels of vitamin E and glucose-6-phosphate dehydrogenase (G6PD) activity with concomitant elevations of unconjugated bilirubin and percent hemolysis. Negative correlations in jaundice were found between vitamin E and bilirubin and between vitamin E and percent hemolysis, and a positive relation was found between vitamin E and G6PD. The results indicate that the increase in hemolysis and bilirubin may be due to a vitamin E deficiency, particularly in G6PD-deficient erythrocytes.

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Newborns: Vitamin K Injection--Hyperbilirubinemia (and other dangers)

Vitamin K injections can cause symptoms misdiagnosed as SBS, or which can be misdiagnosed as additional signs of abuse

http://www.vaccination.inoz.com/VitaminK.html

Vitamin K --Is this really safe and necessary?
Bronwyn Hancock October 2003

The reason given for administration of Vitamin K is to prevent haemorrhagic disease
in newborns. However consider the following points:

The form of Vitamin K injected

· The body does not readily utilise synthetic vitamins and minerals. The vitamin K
administered by hospitals to newborns is the synthetic phytonadione. The natural forms of vitamin K that are found in many foods, particularly in vegetables such as collard greens, spinach, broccoli, asparagus, brussels sprouts and salad greens, are a different form – they are called phylloquinone or menaquinone. Certain bacteria in the intestinal tract also produce menaquinones.

· Apart from its synthetic nature, it is based on plant Vitamin K and injected. The body utilises vitamins and minerals that are found in plants and creates the human form it needs, but this is after they go through the digestion process, which obviously does not occur with injections.

· "Little is known about the metabolic fate of vitamin K. Almost no free unmetabolised vitamin K appears in bile or urine," states both the 1988 and 1998 Physician's Desk Reference (PDR). "This is especially important due to the fact that it is a fat-soluble vitamin and therefore can accumulate in the body," wrote Vitamin K Resources (VKR) in the extremely well-documented and footnoted 1999 article, Intramuscular Vitamin K Injection: Is K OK?he amount of Vitamin K administered

Toxic ingredients accompanying the Vitamin K

· The vitamin K injections administered by hospitals and manufactured by Merck and Roche and Abbott contain benzyl alcohol as a preservative. The 1989 PDR states that, "there is no evidence to suggest that the small amount of benzyl alcohol contained in AquaMEPHYTON (Merck's vitamin K injection product), when used as recommended, is associated with toxicity." Interestingly, in November 1988, the French medical journal, Dev Pharmacol Ther, published a paper regarding benzyl alcohol metabolism and elimination in babies. The report stated that "...we cannot directly answer the issue of safety of 'low doses' of benzyl alcohol as found in some medications administered to neonates. This study confirms the immaturity of the benzoic acid detoxification process in premature newborns."

· Roche's vitamin K product KONAKION contains ingredients such as phenol (carbolic acid-a poisonous substance distilled from coal tar), propylene glycol (derived from petroleum and used as an antifreeze and in hydraulic brake fluid) and acetic acid (an astringent antimicrobial agent that may drastically reduce the amount of natural vitamin K that would have otherwise been produced in the digestive tract). As reported in the PDR and as published in the IM vitamin K packet inserts for Merck, Roche and Abbott, "Studies of carcinogenicity, mutagenesis or impairment of fertility have not been conducted with Vitamin K1 Injection (Phytonadione Injection, USP)."

· The Vitamin K injection can be in a base of polyethoxylated castor oil.

· Vitamin K injections also contain hydrochloric acid and lecithin.

Effects of Vitamin K administration

· The manufacturers warn on the product insert: "Severe reactions, including fatalities, have occurred during and immediately after intravenous injection of phytonadione even when precautions have been taken to dilute the vitamin and avoid rapid infusion..."

· The Vitamin K shot has been linked to leukaemia, including acute lymphoblastic leukaemia, which is characterized by an increased number of white corpuscles in the blood, and accounts for about 85 percent of childhood leukaemia. Research carried out by Dr. Louise Parker, of the Sir James Spence Institute of Child Health in Newcastle upon Tyne, produced the most startling results. Dr. Louise Parker was quoted in the British Medical Journal in 1998 as stating, "It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal IM vitamin K administration increases the risk of early childhood leukemia.".

The British Journal of Cancer published "Factors associated with childhood cancer" by J. Golding, et al, in 1990. The report indicated that universally administered IM vitamin K injections significantly increase our children's chances of developing childhood cancer. A follow-up study published two years later in the British Medical Journal (Golding J, Paterson K, Greenwood R, Mott M. Intramuscular vitamin K and childhood cancer. BMJ 1992; 305:341-346.) reinforced the findings of the previous study. The authors' comments, in keeping with scientific style, are conservatively stated, but parents who are concerned about the health of their babies will read "danger" between the following lines: "The only two studies so far to have examined the relation between childhood cancer and intramuscular vitamin K have shown similar results and

the relation is biologically plausible. The prophylactic benefits against haemorrhagic disease are unlikely to exceed the potential adverse effects from intramuscular vitamin K..."

The chance of your child developing leukaemia from the Vitamin K shot is estimated to be about one in 500 (MIDIRS Midwifery Digest, Vol 2 #3, September 1992)

· Animal studies have linked large doses of vitamin K to a variety of conditions that include anaemia, liver damage, kidney damage and death.

· Interestingly the common problem that occurs these days of jaundice in newborns has only been reported since the introduction of Vitamin K administration.

· According to the product insert, adverse reactions include haemolysis (or hemolysis - American spelling) (meaning breakdown of red blood cells), haemolytic anaemia (a disorder characterised by chronic premature destruction of red blood cells), hyperbilirubinemia (too much bilirubin in blood) and jaundice (yellow skin and eyes resulting from hyperbilirubinemia), and allergic reactions include face flushing, gastrointestinal upset, rash, redness, pain or swelling at injection site and itching skin. It also warns that large enough doses can cause brain damage in infants and/or impairment to liver function. Hypoxia has also been published as having occurred in infants after Vitamin K administration.

The necessity (or lack of necessity) for administration of Vitamin K

· The bleeding condition the Vitamin K shot is supposed to prevent occurs at a rate that is far lower (in a non-Vitamin K injected child) than the rate of occurrence of leukaemia. The haemorrhaging condition may occur in approximately 1 in 10,000 live births.

· The condition also will not necessarily be prevented by Vitamin K because it can be caused by other factors than a lack of Vitamin K (e.g. See Arch Dis Child 1999; 81:278 (September)). In fact, vaccination is a major cause of haemorrhaging.

· The bacteria that should quickly colonise the gut (in a baby who is breastfed and not given antibiotics directly or as one of the ingredients in vaccines, including most likely the Hepatitis B vaccine) produces Vitamin K anyway, as mentioned above.

· As early as April 17, 1977, an article in one of the world's most esteemed medical journals, the Lancet, discredited the policy of routine vitamin K injections. "We conclude that healthy babies, contrary to current beliefs, are not likely to have a vitamin K deficiency... the administration of vitamin K is not supported by our findings..." Van Doorm et al stated in the Lancet article. VKR cited 21 peer-reviewed reports that had been published in prominent medical journals. All of them concur that policies that mandate the universal injection of newborn babies are not based on sound science. There has been much peer-reviewed evidence generated which questions the efficacy of routine vitamin K injections as sound public health policy.

· Naturopathic physicians and others who successfully adhere to a more natural approach to healthcare advocate that high-risk mothers should increase the amount of vitamin K available to the foetus, and then the breastfeeding infant, by eating adequate amounts of green leafy vegetables and other foods high in Vitamin K, such as alfalfa, brussels sprouts, cabbage, cauliflower, spinach, turnip greens, asparagus, oats and green tea.

· Commonsensically, VKR poses the question, "...how could God (or nature) have erred so badly as to give all newborn babies only an infinitesimal fraction of their required vitamin K? Surely the human race could not have survived to this point if all newborns were born with this deficiency and none being administered at birth until very recently." So ironically, when a Vitamin K deficiency does occur the probable cause(s) would be some other artificial, unnecessary interference, which just so happens to be something that one might say is fairly characteristic of modern medical treatments.

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http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20V)/VITAMIN%20K.html The comprehensive resource for physicians, drug and illness information Illnesses information

VITAMIN K
General Monograph,
Phytonadione
Hypoprothrombinemia Therapy

"Action And Clinical Pharmacology: Vitamin K compounds are fat soluble naphthoquinones. Phytonadione (vitamin K1 ) and vitamin K2 occur in a variety of natural materials and are synthesized by certain bacteria in the gastrointestinal tract; however, commercially prepared phytonadione is synthetically produced..."

Manufacturers' Warnings In Clinical States: Severe reactions, including fatalities, have occurred during and immediately after i.v. phytonadione injection even when precautions have been taken to dilute the phytonadione solution and to avoid rapid infusion. These severe reactions, which may occur in patients receiving phytonadione for the first time, resemble hypersensitivity or anaphylaxis, including shock and cardiac or respiratory arrest. Therefore, use of the i.v. route should be restricted to those situations where other routes are not feasible and the serious risk involved is considered justified.

Benzyl alcohol contained in some products has been associated with toxicity in newborns. Toxicity appears to have resulted from administration of large amounts (100 to 400 mg/kg daily) of benzyl alcohol in these neonates. Products containing benzyl alcohol should be used cautiously in newborns who are also receiving other benzyl alcohol-containing medications. In each case, the attending physician must weigh the potential benefits against the possible risks.

Precautions: Because the liver is the site of prothrombin biosynthesis, hypoprothrombinemia resulting from hepatocellular damage is not corrected by administration of vitamin K. Repeated large doses of vitamin K are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. Failure to respond to vitamin K may indicate that a coagulation defect exists or that the condition is unresponsive to vitamin K.

Vitamin K does not counteract the anticoagulant effect of heparin. Dietary supplements high in vitamin K (³0.7 mg/day) can block the effect of oral anticoagulants.

Vitamin K1 promotes the synthesis of prothrombin by the liver but does not directly reverse the effects of oral anticoagulants. Immediate coagulant effect should not be expected. It takes up to 2 hours for a measurable improvement in the prothrombin time. Whole blood or component therapy may also be necessary if bleeding is severe or if there is no response to phytonadione. Vitamin K1 is not a clotting agent, but overzealous therapy with phytonadione may restore conditions which originally permitted thromboembolic phenomena. Keep dosage as low as possible, and check prothrombin time regularly as clinical conditions indicate.

Newborns should be observed for vitamin K deficiency. The incidence of vitamin K deficiency is higher in breast-fed infants. This increase may be partly due to lower concentrations of vitamin K in human milk than in cow's milk formula or it may be due to the smaller volume of milk infants may receive in their first few days of life, especially those exclusively breast-fed. Therefore, because an infant's milk intake cannot be predicted at birth, it is recommended that vitamin K prophylaxis be given to all newborns. (Infants have been breastfed since the beginning of time.)

Drug Interactions: Anticoagulants (coumarin): Anticoagulant effects are antagonized by vitamin K. Temporary resistance to prothrombin depressing anticoagulants may result from vitamin K administration, especially when relatively large doses have been given. Therefore, when reinstituting anticoagulant therapy, it may be necessary to use larger doses of the prothrombin depressing anticoagulant or to use one that acts on a different principle, such as heparin.

Broad Spectrum Antibiotics, Quinidine, Quinine and High Dose Salicylates: Requirements for vitamin K may be increased. (see Indications).

Children: In newborns, particularly premature infants, hyperbilirubinemia and hemolytic anemia have been reported. The risk is much less with phytonadione than other vitamin K preparations unless high doses (10 to 20 mg) are given.

Pregnancy: Inadequate information exists as to whether vitamin K may affect fertility in human males or females or have a teratogenic potential or other adverse effect on the fetus. Large amounts of vitamin K in pregnancy, however, can cause jaundice in the newborn.

Lactation: Vitamin K may appear in human breast milk. Problems in humans have not been reported with the intake of normal daily requirements.

Adverse Reactions: Deaths have occurred following i.v. administration of phytonadione (see Warnings).

Transient flushing sensations and peculiar sensations of taste have been observed following phytonadione injection as well as rare instances of dizziness, rapid and weak pulse, profuse sweating, brief hypotension, dyspnea, and cyanosis. Bronchospasm, shock, cardiac and/or respiratory arrest may also occur.

Pain, swelling, and tenderness at the injection site may occur. The possibility of allergic sensitivity (i.e., rash, urticaria), including an anaphylactoid reaction, should be kept in mind.

Large doses of vitamin K or its analogues may further depress liver function in patients with severe hepatic disease and thereby further decrease the concentration of prothrombin.

Neonates: In infants (particularly premature babies), excessive doses of vitamin K analogs during the first few days of life may cause hyperbilirubinemia; this in turn may result in severe hemolytic anemia, hemoglobinuria, kernicterus, leading to brain damage or even death. Immaturity is apparently an important factor in toxic reactions to vitamin K analogs, as full term and larger premature infants show greater tolerance than smaller premature infants.

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http://proliberty.com/observer//19990710.htm
From the July 1999 Idaho Observer:

National standard mandates newborn vitamin K injection
Ignorance becomes tacit consent for the questionable neonatal procedure

by Don Harkins

In cooperation with a “national standard,” most, if not all states have mandated that U.S. hospitals routinely administer to all newborns a synthetic, fat-soluble vitamin K injection (generic name phytonadione) that exceeds an infant's recommended daily dietary intake of the vitamin by 100 times.

Peer reviewed journals have linked large doses of vitamin K to childhood cancers and leukemia. Animal studies have linked large doses of vitamin K to a variety of conditions that include anemia, liver damage, kidney damage and death.

“Little is known about the metabolic fate of vitamin K. Almost no unmetabolized vitamin K appears in bile or urine,” states both the 1988 and 1998 Physician's Desk Reference (PDR).

“This is especially important due to the fact that it is a fat-soluble vitamin and therefore can accumulate in the body,” wrote Vitamin K Resources (VKR) in the extremely well-documented and footnoted 1999 article, Intramuscular Vitamin K Injection: Is K OK?

In the 1988 PDR, Merck's literature states that “A single intramuscular dose of AquaMEPHYTON (Merck brand vitamin K injection) 0.5 to 1 mg within one hour of birth is recommended.”

Merck's 1998 PDR entry for AquaMEPHYTON has removed adverse reaction liability from the pharmaceutical giant by stating, “The American Academy of Pediatrics (AAP) recommends that Vitamin K1 be given to the newborn.”

Vitamin K injections are ostensibly administered to newborns to prevent vitamin K deficiency bleeding (such as hemophilia) that may occur in approximately 1 in 10,000 live births. “This figure would probably be much lower if high risk newborns were excluded [from this figure],” wrote VKR.

Parents who wish to refuse the shot must do so in writing prior to the birth of their baby. Parental ignorance of the state-mandated injection is considered by hospitals as tacit consent authorizing them to administer the potentially damaging synthetic vitamin dose to newborns.

Five post partem nurses from hospitals in Idaho, Washington and Oregon stated that they “routinely administer vitamin K injections to newborns,” as if all of them were reading from the same script. According to a seasoned Sacred Heart Medical Center (Spokane, WA) Birthplace nurse named Terri, “Routine vitamin K injections are in cooperation with the federal standard.”

She also said that Washington hospitals are mandated by state code to provide the injections to all newborns. Terri acknowledged that parents who wish to refuse the shot must present the refusal to the hospital in writing before the baby is born.

Scientists question intelligence of universal IM vitamin K injections

Dr. Louise Parker was quoted in the British Medical Journal in 1998 as stating, “It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal IM vitamin K administration increases the risk of early childhood leukemia.”

The British Journal of Cancer published “Factors associated with childhood cancer” by J. Golding, et al, in 1990. The report indicated that universally administered IM vitamin K injections significantly increase our children's chances of developing childhood cancer.

A follow-up study published two years later in the British Medical Journal reinforced the findings of the previous study. The authors' comments, in keeping with scientific style, are conservatively stated, but parents who are concerned about the health of their babies will read “danger” between the following lines: “The only two studies so far to have examined the relation between childhood cancer and intramuscular vitamin K have shown similar results and the relation is biologically plausible. The prophylactic benefits against haemorrhagic disease are unlikely to exceed the potential adverse effects from intramuscular vitamin K...”

Both studies recommend that policies should be adopted to administer IM vitamin K injections only to high risk babies. Babies who have been identified as being at risk for vitamin K deficiency include those born to mothers who took drugs or antibiotics during pregnancy, premature babies and babies who are born cesarean. Mothers who had maternity diets low in high vitamin K foods or had diets that were low in fat have also been identified as being more likely to bear vitamin K deficient babies.

Naturopathic physicians and others who successfully adhere to a more natural approach to healthcare advocate that high-risk mothers should increase the amount of vitamin K available to the fetus during pregnancy by eating adequate amounts of green leafy vegetables. It is also recommended that mothers continue to eat vitamin K rich foods after giving birth so that their infants will receive the natural form of the vital vitamin through their breast milk.

As early as April 17, 1977, an article in one of the world's most esteemed medical journals, the Lancet, discredited the policy of routine vitamin K injections. “We conclude that healthy babies, contrary to current beliefs, are not likely to have a vitamin K deficiency....the administration of vitamin K is not supported by our findings...” Van Doorm, et al stated in the Lancet article.

VKR cited 21 peer-reviewed reports that had been published in prominent medical journals. All of them concur that policies which mandate the universal injection of newborn babies are not based in sound science.

There has been much peer-reviewed evidence generated which questions the efficacy of routine vitamin K injections as sound public health policy. Why, then, since publication of the July, 1987 article in Pediatrics “Health codes for newborns” when it was stated that only five states required hospitals to administer neonatal vitamin K injections, are they now mandated by most, if not all states?

Commonsensically, VKR poses the question, “...how could God (or nature) have erred so badly as to give all newborn babies only an infinitesimal fraction of their required vitamin K? Surely the human race could not have survived to this point if all newborns were born with this deficiency and none being administered at birth until very recently.”

Although there seems to be no evidence to support universal IM vitamin K injections among the newborn from a public health standpoint, the medical establishment, as informed by the Food and Drug Administration, the AAP and as supplied by the pharmaceutical companies such as Merck, Roche Laboratories and Abbott Laboratories, continues to endorse state mandated, routine IM vitamin K injections.

Eye of newt, spleen of bat?

The body most readily utilizes vitamins and minerals that are found in plants. The body less readily utilizes synthetic vitamins and minerals. The vitamin K administered by hospitals to newborns is the synthetic phytonadione. The natural forms of vitamin K that are found in many foods, particularly in vegetables such as collard greens, spinach, broccoli, asparagus, brussels sprouts and salad greens, are called phylloquinone or menaquinone. Certain bacteria in the intestinal tract also produce menaquinones.

The vitamin K injections administered by hospitals and manufactured by Merck and Roche and Abbott are not only synthetic but, according to the packet inserts and the PDR, contain benzyl alcohol as a preservative.

The 1989 PDR states that, “there is no evidence to suggest that the small amount of benzyl alcohol contained in AquaMEPHYTON (Merck's vitamin K injection product), when used as recommended, is associated with toxicity.”

Interestingly, in November, 1988, the French medical journal Dev Pharmacol Ther published a paper regarding benzyl alcohol metabolism and elimination in babies. The report stated that “...we cannot directly answer the issue of safety of 'low doses' of benzyl alcohol as found in some medications administered to neonates. This study confirms the immaturity of the benzoic acid detoxification process in premature newborns.”

The 1998 PDR still states, contrary to the published findings of French scientists in 1988, “there is no evidence to suggest that...”

There has been little reason to study the toxicological effects of benzyl alcohol over the last decade since state legislators have provided synthetic vitamin K manufacturers with the guaranteed marketplace of nearly every child born in a U.S. hospital.

Vitamin K injections manufactured as recently as 1995 contain hydrochloric acid “for pH adjustment.”

Roche's vitamin K product KONAKION contains ingredients such as phenol (carbolic acid -- a poisonous substance distilled from coal tar), propylene glycol (derived from petroleum and used as an antifreeze and in hydraulic brake fluid) and acetic acid (an astringent antimicrobial agent that may drastically reduce the amount of natural vitamin K that would have otherwise been produced in the digestive tract).

As reported in the PDR and as published in the IM vitamin K packet inserts for Merck, Roche and Abbott, “Studies of carcinogenicity, mutagenesis or impairment of fertility have not been conducted with Vitamin K1 Injection (Phytonadione Injection, USP).”

The purpose of this article is to alert expectant parents that their ignorance of federally-suggested, state mandated hospital policy is enough assent to authorize health care professionals to administer what may be a lethal or damaging overdose of a synthetic substance that comes with the following warning from the manufacturers: “Severe reactions, including fatalities, have occurred during and immediately after INTRAVENOUS injection of phytonadione even when precautions have been taken to dilute the vitamin and avoid rapid infusion...”

Please pass the preceeding information onto anybody you know who is expecting a baby. Afterall, we have the right to know what substances are being injected into our babies within the first hour of their lives. If we feel that a substance may be injurious to our baby, we have the right to refuse it.

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http://www.medscape.com/viewarticle/409632_7

Phytonadione Therapy in a Multiple-Drug Overdose: Adverse Effects of Vitamin K

Severe adverse effects are associated with intravenous phytonadione, such as cardiac irregularities, chest pain, cyanosis, decreased level of consciousness, circulatory collapse, rapid weak pulse, hypotension, and cardiac or respiratory arrest.[13] It is not known if these reactions are due to the drug or the injection vehicle.[13] Earlier reactions to vitamin K were thought to be due to polyoxyethylated castor oil (cremophor).[29-32]

The literature contains numerous cases of anaphylactic reactions[29, 30, 32-38] as well as fatalities[34, 35] with parenteral phytonadione. The recommended infusion rate of vitamin K is no faster than 1 mg/minute[13]; however, anaphylactic reactions have occurred with slower infusion rates[33, 37] as well as with repeated exposure to intravenous vitamin K.[30, 33, 34, 37]

Dermatologic reactions were reported after intravenous, subcutaneous, and intramuscular administration of vitamin K.[39] Two distinct types of local cutaneous reactions have been described. The more common one is a pruritic, erythematous, eczematoid, indurated plaque measuring 6-20 cm around the site of injection.[39-52] The acute reaction may resolve in 2-4 weeks with treatment with high-potency corticosteroids (e.g., fluocinonide, betamethasone dipropionate). The second type appears as a scleroderma or morphea-like reaction.[53-56] The onset can be weeks to months, and the skin change may last for years.[39] Dose does not appear to bear a relationship to the onset of these reactions. Liver disease was associated with most reports of vitamin K cutaneous hypersensitivity,[39, 41] but the pathophysiology is unclear.

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http://www.springerlink.com/content/v16l551682716431/

Anaphylactoid Reactions to Vitamin K

Louis D. Fiore1, Michael A. Scola1, Colleen E. Cantillon1 and Mary T. Brophy1
(1) Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, 150 South Huntington Avenue, Boston, MA, 02130

Abstract Anaphylactoid reactions in patients receiving intravenously administered vitamin K have been reported in the literature. To summarize the known data on anaphylactoid reactions from administration of vitamin K, we reviewed all published and unpublished reports of this adverse reaction. Published reports were obtained through medline (1966–1999) and EMBASE (1971–1999) searches of the English language literature and review of references from identified case reports. Unpublished reports were obtained using the Spontaneous Reporting System Adverse Reaction database of the United States Food and Drug Administration (FDA) between August 1968 and September 1997. All adverse drug reactions to vitamin K were categorized by route of drug administration, dose and standard adverse reaction code. In the FDA reports, we defined anaphylactoid reactions as any adverse drug reaction coded as either anaphylaxis, allergic reaction, apnea, dyspnea, death, heart arrest, hypotension, shock or vasodilatation. Additionally, all fatal and life-threatening FDA reported reactions were reviewed to determine if they could represent an anaphylactoid reaction missed by the above definition.
The literature review uncovered a total of 23 cases (3 fatal) of anaphylactoid reactions from intravenous vitamin K. The FDA database contained a total of 2236 adverse drug reactions reported in 1019 patients receiving vitamin K by all routes of administration. Of the 192 patients with reactions reported for intravenous vitamin K, 132 patients (69%%) had a reaction defined as anaphylactoid, with 24 fatalities (18%%) attributed to the vitamin K reaction. There were 21 patients with anaphylactoid reactions and 4 fatalities reported with doses of intravenous vitamin K of less than 5[emsp4 ]mgs. For the 217 patients with reactions reported due to vitamin K via a non-intravenous route of administration, 38 patients had reactions meeting the definition of anaphylactoid (18%%), with 1 fatality (3%%) attributed to the drug.
The absolute risk of an anaphylactoid reaction to intravenous vitamin K cannot be determined by this study, but the relatively small number of documented cases despite widespread use of this drug suggest that the reaction is rare. Anaphylactic reactions and case fatality reports were found even when intravenous vitamin K was given at low doses by slow dilute infusion. The pathogenesis of this reaction is unknown and may be multifactorial with etiologies including vasodilation induced by the solubilizing vehicle or immune-mediated processes. We conclude that use of intravenous vitamin K should be limited to patients with serious hemorrhage due to a coagulopathy that is secondary to a relative or absolute deficiency of vitamin K.

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http://poisonevercure.150m.com/vaccines7.htm
Neurosurgeon, Dr. Russell Blaylock, shares the science on how particular vaccine ingredients lead to convulsions, seizures, ADD, ADHD, autism...etc.

Vitamin K and Hepatitis B are mandated in most states to be given to newborns before they go home with mom. This has been proven to be a dangerous procedure at best. Potentially lethal.

Vitamin K

The marketed purpose of the Vitamin K injection is that newborns have very little to begin with. Vitamin K is essential for the ability of blood clotting should any injury occur. Another marketed purpose is the prevention of hemorrhagic diseases of the newborn (HDN). HDN is a bleeding disorder associated with low levels of vitamin K in newborn babies. It was first defined in 1894 by Townsend as spontaneous external or internal bleeding occurring in newborn infants. Diagnosis was based solely on the opinion of the attendant medical personnel because there was no criteria in determining the cause of hemorrhaging. Townsend did not label hemophilia as a cause of HDN. The vaccine is also marketed to be essential prior to surgery. Thus, supposedly prevents excessive bleeding.

Vitamin K is naturally stored and metabolized by the liver. The cell division that rapidly continues after birth depends on precise amounts of vitamin K to proceed at the proper rate. Introduction of levels that are 20,000 times the newborn level, the amount usually injected, can have devastating consequences.

Nursing naturally raises the infant's vitamin K levels very gradually after birth so that no disregulation occurs that would encourage leukemia development. This is the way the Creator designed it to be. The clotting system of the healthy newborn is well planned, and healthy breastfed infants do not suffer bleeding complications, even without any supplementation. While nursing infants demonstrate lower blood levels of vitamin K than the "recommended" amount, they show no signs of vitamin K deficiency. This can only lead to the question of how and where the “recommended” amount was brought about.

Vitamin K vaccinations are also marketed for newborns to prevent vitamin K deficiency bleeding (such as hemophilia) that may occur in approximately 1 in 10,000 live births. Hemophilia is the oldest known hereditary bleeding disorder of which there are two types: A and B (Christmas Disease). Low levels or the absence of a blood protein, essential for clotting, causes both. Patients with hemophilia A lack the blood clotting protein, factor VIII, and those with hemophilia B lack factor IX. There are about 20,000 hemophilia patients in the United States. Each year, about 400 babies are born with this disorder. Approximately 85% have hemophilia A and the remainder has hemophilia B.

The severity of hemophilia is related to the amount of the clotting factor in the blood. About 70% of hemophilia patients have less than one percent of the normal amount which leads to severe hemophilia. A small increase in the blood level of the clotting factor, up to five percent of normal, results in mild hemophilia with rare bleeding except after injuries or surgery. The most important challenges facing the hemophilia patient, health care provider, and research community today are safety of products used for treatment, management of the disease including inhibitor formation, irreversible joint damage, and life-threatening hemorrhage. Bleeding into the brain occurs mainly from three to seven weeks after birth in just over five out of 100,000 births. Forty percent of these infants suffer permanent brain damage or death.

The vitamin K inoculations administered by hospitals and manufactured by Merck and Roche and Abbott are synthetic. According to the packet inserts and the PDR, it contains benzyl alcohol as a preservative. In November, 1988, the French medical journal, Dev Pharmacol Ther, published a paper on benzyl alcohol metabolism and elimination in infants. The report stated, "...we cannot directly answer the issue of safety of ‘low doses’ of benzyl alcohol as found in some medications administered to neonates. This study confirms the immaturity of the benzoic acid detoxification process in premature newborns."

Vitamin K vacciness also contain hydrochloric acid "for pH adjustment." Roche’s vitamin K product KONAKION contains ingredients such as phenol, propylene glycol (derived from petroleum and used as an antifreeze and in hydraulic brake fluid) and acetic acid (an astringent antimicrobial agent that may drastically reduce the amount of natural vitamin K that would have otherwise been produced in the digestive tract). Phenol is a carbolic acid and is a poisonous substance which is distilled from coal tar. It has the ability to inhibit phagocyte activity, meaning it is toxic to all cells. Phenol is capable of disabling the immune system's primary response mechanism. It can also cause systemic poisoning, headache, shock, weakness, convulsions, kidney damage, cardiac failure, kidney failure, or death. Propylene glycol can cause serious damage to liver, heart and central nervous system.

The inoculations exceed an infants recommended daily dietary intake by over 100 percent. Peer reviewed journals have linked large doses of vitamin K to childhood cancers and leukemia. Animal studies have linked large doses of vitamin K to a variety of conditions that include anemia, liver damage, kidney damage and death.

There is possibly an 80 percent increased risk of developing childhood leukemia. Several controlled studies have shown this correlation to be most likely the case while many others suggest that it is unlikely. Six different studies suggest it is a 10 percent or 20 percent increased risk.

Cancer researchers say that the synthetic vitamin K vaccine may significantly increase the risk of childhood cancer. Researchers in 1990 noted an increased incidence of childhood cancer in children given vitamin K inoculations at birth. They also found that the vitamin K injection doubled the incidence of leukemia in children less than ten years of age. A study in 1992 revealed the same association between injected vitamin K and cancer. Literature reveals that there are 1.5 extra cases of leukemia per 100,000 children due to vitamin K injections.

Recent studies in England have pointed out an increased risk of childhood leukemia with Vitamin K inoculations. Numerous studies have failed to dispute the statistical link.

Britain started a national cohort study of 16,193 infants born in one week in April in 1970. Thirty-three of the children had developed cancer by age 10 and were compared with 99 control children. The authors of the study approached Roche, the manufacturers of Konakion, for funding for a further trial to examine the findings more closely. Naturally 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. The new study 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 administered vitamin K orally and the other intramuscularly. A nearly two-fold risk of leukaemia was found in children who had received intramuscular vitamin K.

Golding calculated that the extra cases of leukaemia caused by vitamin K injection could be as many as 980 in the UK alone. These results were supported by reports of the potential carcinogenicity of vitamin K from Israels et al. Pizer et al concluded that his study was too small to show any real effect. After an intramuscular dose of vitamin K, the baby’s plasma levels are almost 9000 times the normal adult levels. Many criticized Golding’s study. Despite the fact that assumptions were made for some cases because administration of vitamin K was not accurately recorded, expert epidemiologists considered that the results were plausible and so they could not be dismissed even in the slightest.

Two studies had carefully matched controls and more accurate information on whether vitamin K had been given or not, and by which route. One of the studies reported no association between intramuscular vitamin K and childhood cancer and the other 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 was dismissed. It was then assumed and decided that worries about any potential cancer risk should be abandoned.

At that time, four more studies on vitamin K and cancer were in progress. The results were published in 1998. One of the studies showed a twofold risk of acute lymphoblastic leukaemia among 1-6 year olds, another showed a significant risk for all cancers.

There are two problems in giving vitamin K orally. It is not a licensed oral formulation for one. Compliance with three oral doses is low since many physicians are reluctant to give an unlicensed formula. The use of unlicensed preparations could lead to litigation in the event of prophylactic failure or adverse events.

Roche, the manufacturers of Konakion, state that they do not recommend the administration of Konakion solution orally. 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.

The oral formula is distasteful and infants would instinctively spit it out or regurgitate it resulting in only half of an orally administered dose being absorbed. Still, 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.

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. (Yet, it is difficult to determine amongst all pediatric cancer patients if they developed their life threatening condition from vitamin K injection, the polio or other by other vaccines containing foreign RNA and DNA).

The only known reported cases of vitamin K toxicity result from having used the synthetic inoculated form. Vitam K inoculations can cause possibly fatal allergic reactions even during injection. The risks of injecting vitamin K into a newborn baby are nerve or muscle damage because it is injected deeply into the muscle, not subcutaneously under the skin.

wpe49F.jpg (16360 bytes)On the product insert, some reactions are listed: You may notice pain, swelling and tenderness at the injection site for a few days. Notify your doctor if you experience any of the following while taking this drug: chest pain, flushing, strange movements, rapid pulse, tightness of the chest, cramps. In the unlikely event you have an allergic reaction to this drug, seek medical attention immediately. nerve and muscle damage as the Vitamin K injection must be given deeply into the muscle. However, should a newborn experience any of these, it is incredibly difficult for them to “notify” anyone, difficult for the parents to see or understand the reason behind a newborns cries, and difficult for physicians to see these signs in infants. Majority of physicians are not educated or trained to fully examin an infant in discomfort for vaccine related symptoms. Instead, they are most likely to dismiss any vaccination link.

The following are from the vaccine product insert:

* Clinical Pharmacology: "little is known about the metabolic fate of Vitamin K".
* Contraindication: "Hypersensitivity to any component of this medication".
* Precautions: "Studies of carcinogenicity, mutagenesis, or impairment of fertility have not been conducted with phytonadione."
* Pediatric Use: "Hemolysis, jaundice, and hyperbiliruminemia in newborns, particularly in premature infants, may be related to the dose of phytonadione."
* Adverse reactions: "Deaths have occurred after intravenous administration…The possibility of allergic sensitivity should be kept in mind…Hyperbilirubinemia has been observed in the newborn following administration of phytonadione…"

Newborns are not pre-screened for allergic hypersensitivity.

Vitamin K1 in the form of Phytonadione, is a popular medication used to promote blood clotting. Preparations of Phytonadione are sold under trade names Mephyton, AquaMephyton, and Konakion.

Vitamin K is not a clotting agent in itself, and Vitamin K levels are not measured directly; only levels of other blood proteins with known dependence on Vitamin K

Jaundice is a common symptom of Vitamin K overdose. A recent pediatric statistic indicated the presence of clinical jaundice in more than half of all infants. Vitamin K shots are administered within an hour or so after birth. Clinical jaundice presents itself in the first few days after birth.

Tulchinsky paper: It was found that 12 of the 34 newborns (35%) whose medical records were reviewed already received a Vitamin K injection before presentation of any hemorrhaging symptoms. 16 of the newborns (47%) received Vitamin K after the onset of hemorrhagic symptoms. 6 newborns (18%) had no mention of Vitamin K in their medical records.

It was assumed that injection of Vitamin K had not been given if medical records contained no mention of it, even though the practice was popular at the time. There is no mandate to maintain accurate medical records of Vitamin K injection making the assumption worthy of great concern.

Then, in the mid-1950’s, circulating reports of increased jaundice and kernicterus (brain damage caused by high bilirubin levels) in infants given vitamin K prophylaxis began resulting in wide spread concern and lack of confidence in the procedure. Reviews of maternity units found that some were giving Synkavite in doses exceeding 50mg. It was established that high doses of Synkavite caused haemolysis (destruction of red blood cells) and high serum bilirubin levels.

Researchers and medical professionals questioned the safety aspects of vitamin K, and there were many conflicting reports on the appropriate dosages. Some researchers questioned the need for vitamin K at all.

Eventually, a newer preparation, intramuscular vitamin K1 (phytomenadione), was developed and approved with the presumption 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. In the US, polysorbate-80 is used as a base instead of polyethoxylated castor oil.

Despite the lack of long term trials of these formulations, the American Academy of Pediatrics recommended that phytomenadione be administered prophylactically to all newborn babies. The intramuscular route was deemed safer.

Merck’s 1998 PDR entry for AquaMEPHYTON has removed adverse reaction liability by stating, "The American Academy of Pediatrics (AAP) recommends that Vitamin K1 be given to the newborn."

Infant Formulas are supplemented with unnaturally high levels of vitamin K. The breastfed infant can be supplemented with several low oral doses of liquid vitamin K1 (possibly 200 micrograms per week for five weeks, totaling 1 milligram, even more gradual introduction may be better). Alternatively, the nursing mother can take vitamin K supplements daily or twice weekly for 10 weeks. (This does not alter fetal levels but supplementation of the nursing mother does increase breast milk and infant levels.)

Either of these provides a much safer rate of vitamin K supplementation. Maternal supplementation of 2.5 mg per day, recommended by one author, provides a higher level of vitamin K through breast milk than does formula. Formula provides 10 times the U.S. recommended daily allowance.

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Vitamin K:
controversy? what controversy?
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 K58
Category	Age	Amount (mg)
Infants	0 - 1	10
Children	1 - 3	15
	4 - 6	20
	7 - 10	25
Adolescents	11 - 14	30
	15 - 18	35
Adult Male	19 - 70+	45
Adult Female	19 - 70+	35
Pregnancy		+ 10
Lactating		+ 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 mg daily and the mean requirement for infants is estimated to be 5 mg daily based on weight. The higher amount of 10mg is recommended for prevention of Haemorrhagic Disease of the Newborn.58

WHAT IS HEMORRHAGIC 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 K 23 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 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:

1. 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.
2. 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.
3. 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 studies 43, 49 and other factors have also been suggested.52, 73, 74

Most, if not 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 8-9mg/l, which would mean that if a baby was taking in about 500ml per day, it would be getting the recommended 3-5mg 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 Edward 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 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 5mg 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 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 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 25mg 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:

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 mg 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.

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Dianne Jacobs Thompson Est. 2007
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