We deal with vaccinations. Part 25. Vitamin K

2024 Author: Seth Attwood | [email protected]. Last modified: 2023-12-16 15:55

1. One of the procedures that almost every baby undergoes immediately after birth in most developed countries is the injection of vitamin K. Vitamin K plays an important role in the blood clotting process, and a lack of it is believed to lead to hemorrhagic neonatal disease (VKDB).

2. Vitamin K in neonates: facts and myths. (Lippi, 2011, Blood Transfus)

Vitamin K was discovered in the early 1930s when a Danish biochemist discovered that chickens fed a low-fat, cholesterol-free diet developed subcutaneous and intramuscular bleeding. The vitamin was named with the letter K for coagulation.

Vitamin K1 is found in leafy green vegetables such as spinach, Swiss chard, turnips, cabbage (also cauliflower, Brussels sprouts, kale), some fruits (avocado, banana, kiwi), and some vegetable oils. Vitamin K2 is synthesized by many types of gut bacteria, but this is probably not a particularly significant source.

The IOM recommended daily intake of the vitamin is 120 mcg for men and 90 mcg for women. In Europe, the recommended dose is much lower.

The recommended dose for infants is 2 mcg / day. Breast milk contains 1-4 mcg / liter.

There are 3 types of hemorrhagic disease of newborns (which since 1999 has been called VKDB - Vitamin K deficiency bleeding).

1) Early (in the first 24 hours after birth). It is observed almost exclusively in infants whose mothers took drugs inhibiting vitamin K (anticonvulsants and anti-tuberculosis drugs, some antibiotics, coumarin, etc.). It is observed in 6-12% (among those taking medications) and usually passes hard.

2) Classic (24 hours - 7 days after birth). Associated with inadequate nutrition. It is observed in 0.25-1.5% (according to old data) and 0-0.44% (according to new data), and usually passes easily. Includes bleeding from the umbilical cord as well as bleeding after circumcision or injection.

3) Late (2-12 weeks after birth). Associated with exclusive breastfeeding (HS) (as vitamin K is added to infant formula) and is associated with vitamin K malabsorption due to liver disease and insufficient vitamin intake. The morbidity in children who did not receive vitamin K on exclusive hepatitis B is 1 in 15-20,000. It is difficult (mortality 20% and frequent neurological consequences).

An obvious paradox in neonatal homeostasis is that coagulation tests are not indicative of bleeding. Today it is clear to us that the physiology of hemostasis in childhood differs significantly from the physiology in adults. Human and animal studies indicate that neonatal clotting rates differ from adults quantitatively but not qualitatively. [12]

The hemostatic system is fully formed at the age of 3-6 months. Therefore, it is important to recognize that differences between adults and infants are likely physiological and are not always indicative of pathology.

Both oral and intramuscular vitamin K supplementation protects against the classic form of VKDB. However, a single oral dose does not protect all infants from late VKDB.

3. Vitamin K deficiency bleeding (VKDB) in early infancy. (Shearer, 2009, Blood Rev)

Even in developed countries, there is little accurate data on the prevalence of classic VKDB. In a British study in 1988-90, the incidence was ~ 1: 20,000, that is, it did not differ from the incidence of late VKDB. In the 1930s, the incidence in Oslo was 0.8%. In studies in Cincinnati in the 1960s, the incidence was 1.7% among infants on HB. But these data cannot be representative, since the hospital served primarily the poor blacks.

Poverty predisposes to classic VKDB, and in poor countries the incidence is significantly higher than in developed countries.

Late VKDB is often preceded by warning bleeding that should be investigated.

4. Vitamin K prophylaxis for prevention of vitamin K deficiency bleeding: a systematic review.(Sankar, 2016, J Perinatol)

Systematic review of the effectiveness of the injection.

Among those who did not receive vitamin K, the incidence of late VKDB in poor countries is 80 per 100,000, and in rich countries 8.8 per 100,000.

Routine prevention strategies are not without pitfalls. The usual prophylactic dose (1 mg) is 1000 times the recommended daily requirement. Studies have shown an increased frequency of sister chromatid metabolism in lymphocytes and mutagenic activity at such high concentrations. In addition, intramuscular administration can cause local trauma, vascular and nerve damage, abscesses, and muscle hematoma. Unsurprisingly, some countries resist universal prophylaxis and instead use selective prophylaxis only for newborns at increased risk of bleeding.

Classic VKDB: One study showed a 27% reduction in the risk of bleeding due to injection and 81% for serious bleeding. Another study showed an 82% reduction in bleeding after circumcision.

There are no randomized trials of the effect of prophylaxis on late VKDB. In observational studies, the risk of late VKDB is reduced by 98% in injected patients.

A systematic review by Cochrane found no difference in blood clotting after intramuscular versus oral administration.

Oral vitamin supplementation is cheaper and has no theoretical risk of mutagenicity.

Previously, synthetic vitamin K3 (menadione) was used, which has been associated with an increased risk of hemolysis and kernicterus.

Vitamin K3 (Vikasol) is still used to prevent VKDB in Russia and Ukraine.

5. Vitamin K1 (phytomenadione / phylloquinone) has been used in developed countries since the early 1960s. (Hereinafter, vitamin K means K1).

Injections from the following manufacturers are currently available:

AquaMEPHYTON (Merck)

6. A new mixed micellar preparation for oral vitamin K prophylaxis: randomized controlled comparison with an intramuscular formulation in peast fed infants. (Greer, 1998, Arch Dis Child)

Those who received 3 oral doses (Konakion MM) had higher vitamin K levels for 8 weeks compared to those who received intramuscular injection.

7. There have been many more studies comparing the effectiveness of intramuscular and oral vitamin K.

Most concluded that oral administration was no less effective than intramuscular administration: [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15].

But there have also been studies showing that oral administration is less effective than intramuscular administration in preventing late VKDB: [1]

8. Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K. (Cornelissen, 1997, Eur J Pediatr)

This study compares different prevention regimens in 4 countries. The authors conclude that 3 oral doses are less effective than injection. But it used the previous version of Konakion (which also contained phenol and propylene glycol). In the Netherlands, a daily dose of 25 mcg was used, which was as effective as the injection.

In subsequent studies, however, it turned out that several cases of VKDB were still reported in the Netherlands among infants with predisposing liver disease who received oral vitamin K.

Denmark started giving 1 mg per week by mouth for 3 months, and this reduced the incidence of late VKDB to zero.

29% of the oral vitamin is absorbed in the intestines.

Those born in the summer had a significantly higher blood clotting status than those born in the spring.

9. Vitamin K prophylaxis to prevent neonatal vitamin K deficient intracranial haemorrhage in Shizuoka prefecture. (Nishiguchi, 1996, p J Obstet Gynaecol)

In Japan, the likelihood of intracranial hemorrhage was 1 in 4,000 newborns before vitamin K use. In Germany and the United Kingdom, where vitamin K is used, the likelihood of hemorrhage was 1 in 30,000.

Infants' blood clotting status was significantly higher when breastfeeding mothers were given vitamin K2 (15 mg / day from day 14 postpartum for two weeks).

10. Are peast-fed infants vitamin K deficient? (Greer, 2001, Adv Exp Med Biol)

Breast milk contains very little vitamin K (~ 1 μg / L). But if the mother consumes more than 1 μg / kg / day during pregnancy and lactation, this significantly increases the level of vitamin K in milk (up to 80 μg / L) and in the infant's blood plasma. 1 more]

11. Vitamin K in preterm peastmilk with maternal supplementation. (Bolisetty, 1998, Acta Paediatr)

Six nursing mothers received 2.5 mg / day of vitamin K1 orally for 2 weeks. After the first dose, the amount of vitamin K in milk increased from an average of 3 μg / L to 23 μg / ml, and after 6 days it stabilized at 64 μg / L.

12. Vitamin K1 content of maternal milk: influence of the stage of lactation, lipid composition, and vitamin K1 supplements given to the mother. (von Kries, 1987, Pediatr Res)

The concentration of vitamin K in hind milk is higher than in foremilk, which is not surprising as hindmilk is known to be more fatty. The concentration of vitamin K in colostrum is higher than in mature milk and correlates with cholesterol levels.

The addition of vitamin K to the mothers' diet (0.5-3 mg) significantly increased the vitamin K concentration in milk.

13. Effect of Vitamin-K Dosage on Plasma-Bilirubin Levels in Premature Infants. (Bound, 1956, Lancet)

In the 1950s, newborns were given large doses of vitamin K2 (up to 90 mg). This study found that among premature infants who received 30 mg of vitamin K for three days, 38% had high bilirubin levels (over 18 mg / 100 ml) on day five, and among those who received 1 mg, only 4% had high bilirubin levels. (High bilirubin levels are neonatal jaundice.) More: [1] [2] [3] [4]

14. Overnutrition in Prenatal and Neonatal Life: A Problem? (Cochrane, 1965, Can Med Assoc J)

Recent studies have confirmed the toxic effects of excessive amounts of synthetic vitamin K given to newborns and premature infants. It was also found that the introduction of large amounts of vitamin K to the mother shortly before delivery leads to an increase in the level of bilirubin in the newborn. This substance, which was previously considered harmless, is dangerous if given in large quantities to mothers before childbirth, so much smaller doses are given today. Naturally occurring vitamin K does not have this effect.

15. Merck and other manufacturers report that neonatal jaundice may be dose related. [1] [2] [3]

16. Vitamin K status of premature infants: implications for current recommendations. (Kumar, 2001, Pediatrics)

Premature babies have very high vitamin K levels 2 weeks after injection. The authors suggest lowering the dose for premature babies.

17. Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg. (Costakos, 2003, Am J Perinatol)

In premature infants, the level of vitamin K on the second day after the injection (0.5-1 mg) was 1900-2600 times higher than the usual level in adults, and on the tenth day - 550-600 times higher. The vitamin level in the 0.5 mg group did not differ from the 1 mg group.

18. Plasma concentrations after oral or intramuscular vitamin K1 in neonates. (McNinch, 1985, Arch Dis Child)

The concentration of vitamin K in newborns 12 hours after injection was 9000 times higher and after 24 hours 2200 times higher than the usual concentration in an adult.

The concentration of vitamin K 4 hours after the oral dose is 300 times higher and after 24 hours 100 times higher than the usual concentration in an adult.

Cow's milk contains significantly more vitamin K. When babies were given 90 ml of cow's milk for the first 48 hours 40 years ago, this reduced the incidence rate from 0.8% to almost zero.

It reports that the blood clotting status in infants was dependent on the dose of breast milk in the first days of life. Those who received more than 100 ml of milk per day on days 3 and 4 had significantly higher levels than those who received less than 100 ml / day in the first 4 days. More: [1] Here it is reported that babies who were fed immediately after birth had significantly higher blood clotting status than babies who were fed 24 hours after birth.

19. Childhood cancer, intramuscular vitamin K, and pethidine given during labor. (Golding, 1992, BMJ)

Among those who received an intramuscular injection of vitamin K, the risk of cancer was 2 times higher. A similar result was obtained in another study by the same authors.

That is, preventing 30-60 cases of hemorrhagic disease will result in 980 additional cases of cancer.

It has always seemed physiologically flawed that evolution has allowed vitamin K deficiency to develop in normal breastfed infants, resulting in a low risk of hemorrhagic disease. The most likely explanation for this phenomenon is that there is some evolutionary advantage that outweighs this risk.

It is possible that a relative deficiency of vitamin K in the critical phase of rapid growth may protect vulnerable tissues from mutagenesis.

20. Case-control studies of relation between childhood cancer and neonatal vitamin K administration. (Passmore, 1998, BMJ)

Infants who are not at risk of bleeding have a 1 in 10,000 chance of bleeding. Among those who receive an injection, the chance of bleeding is 1 in a million.

In this study, cancer (mainly leukemia) was associated with intramuscular injection of vitamin K (OR = 1.44, CI: 1.00-2.08). Children who were diagnosed before 12 months of age were excluded from the study.

There have been several other studies that have not found a correlation between injection and an increased risk of cancer. This study did not find a correlation between injection and cancer in general, but did find a correlation with acute lymphoblastic leukemia up to 6 years of age (OR = 1.79).

At the moment, it is believed that there is no link between vitamin K injection and cancer. However, no randomized trials have been performed, and a small increase in risk cannot be ruled out.

The authors believe that injections should only be used for infants at risk.

21. Vitamin K and childhood cancer: analysis of individual patient data from six case-control studies. (Roman, 2002, p J Cancer)

The authors analyzed 6 studies on the relationship between vitamin K injection and cancer, and concluded that if you analyze the data in one way, then there is no association between the risk of leukemia and injection, and if the other, then there is a small association (OR = 1.21, CI: 1.02-1.44) … When one study was excluded from the analysis, the statistical significance disappeared (OR = 1.16, CI: 0.97-1.39)).

The authors conclude that although small effects cannot be ruled out, there is no conclusive evidence that vitamin K injection is associated with leukemia.

22. Experimental vitamin K deficiency and spontaneous metastases. (Hilgard, 1977, p J Cancer)

Cancer mice who had lowered dietary vitamin K levels had significantly fewer metastases than control mice. It was the level of vitamin K that influenced metastases, and not blood coagulation, because anticoagulants did not affect the number of metastases.

23. Observations on vitamin K deficiency in the fetus and newborn: has nature made a mistake? (Israels, 1995, Semin Thromb Hemost)

In fetuses of mammals and in avian embryos, vitamin K levels are significantly lower than in adults. It is not clear why a normal newborn enters the outside world in a state that requires immediate intervention. The question of why even adults do not have excess vitamin K stores also remains unanswered.

Benzapirene is a mouse carcinogen. In mice on a diet low in vitamin K, tumors after administration of this drug developed much more slowly than in mice on a normal diet.

In mice that were injected with vitamin K in addition to benzopyrene, tumors developed faster.

When mice were injected with vitamin K alone, without benzopyrene, tumors did not develop.

The authors suggest that low levels of vitamin K in the fetus are a secondary defense mechanism against xenobiotics that cross the placenta.

24. Why we need a clinical trial for vitamin K. (Slattery, 1994, BMJ)

The risk of hemorrhagic disease is increased by surgical procedures, asphyxia during labor, prolonged labor, high levels of protein in the urine of the mother and hepatitis B.

Vitamin K is given to babies at birth, but we still don't know if it poses a significant risk. Although vitamin K has been used for 30 years, the first study of its long-term effects was not published until 1992. Since the drug is given to so many people, even a small risk can lead to a large number of side effects. Therefore, it is important to establish the potential harm of prevention. Only a large randomized study of children at low risk of hemorrhagic disease, of whom one group will receive vitamin K and the other will not, can answer this question.

25. The CDC reports that all newborns are vitamin K deficient and that the injection is completely safe. Benzyl alcohol is used as a preservative, which is also completely safe and is used in many medicines. True, they write, in the 80s they discovered that premature babies can get sick from the toxicity of benzyl alcohol, since many drugs contain it as a preservative. But despite the fact that toxicity was found only in premature babies, doctors have since tried to minimize the amount of benzyl alcohol in the medicines they give babies. And it is understandable, they write (although they do not say where from), that the amount of benzyl alcohol in the injection is so low that it is safe.

26. The half-lethal dose of benzyl alcohol for mice is 0.48 g / kg. (Regular ethyl alcohol is 4 times less toxic than benzyl alcohol).

In total, the injection ampoule (from Hospira) contains 9 mg of benzyl alcohol per 2 mg of vitamin K. That is, approximately 0.7% of the half-lethal dose for a newborn (3 mg / kg).

Wikipedia reports that:

1) benzyl alcohol is very toxic to the eyes. Pure benzyl alcohol leads to corneal necrosis.

2) benzyl alcohol is toxic to newborns, it causes gasping syndrome.

Gasping syndrome is a disease that no longer exists. It was caused by the fact that the skin of newborns until the 1980s was rubbed with benzyl alcohol, from which some began to choke and die. The dose of benzyl alcohol for the development of this disease is 99 mg / kg.

Benzyl alcohol was known to be toxic at least in the early 1970s. This did not prevent it from being used without restriction on premature newborns until the early 80s, when it was proven to be toxic not only to dogs, but also to babies. But even this did not stop its use in injections, which are given on the first day after birth.

27. Amphastar releases vitamin K without benzyl alcohol. There, propylene glycol is used as a preservative. Propylene glycol is also used as an antifreeze and brake fluid, can cause kidney failure, and is a neurotoxin.

28. Amphastar also adds polysorbate 80 to vitamin K. Moreover, it contains 10 mg of polysorbate 80, which is 200 times more than in Gardasil. (Kanavit also contains polysorbate 80.)

Konakion MM does not contain benzyl alcohol, propylene glycol or polysorbate 80.

29. Hospira advises that intravenous administration of the vitamin can be fatal. Serious consequences and deaths were observed as a result of intramuscular injection. It is also reported that the drug contains aluminum, which can be toxic.

30. Anaphylactic shock due to vitamin K in a newborn and review of literature. (Koklu, 2014, J Matern Fetal Neonatal Med)

Babies are born with an immature innate immune system. Because their immune systems are weaker than in adults, they are less likely to develop an anaphylactic reaction. The possible mechanism of the formation of anaphylaxis in newborns has not yet been clarified.

Here is the first case of anaphylactic shock due to vitamin K injection. More: [1]

31. Nicolau syndrome is a gangrenous dermatitis caused by various medications. Vitamin K injection can also occasionally cause it.

Texier disease is a pseudo-sclerodermal reaction that occurs rarely after vitamin K injection and lasts for several years.

32. Sometimes it happens that instead of vitamin K, the infant is injected with methylergometrine. It is a psychedelic alkaloid that is used to prevent bleeding after childbirth. It is confused with vitamin K because they have similar ampoules. Among the babies who received it by mouth, all survived. And among those who received it with an injection, the mortality rate was 7.5%. [1] [2] [3] [4] [5] [6] [7]

33. Until 1999, it was believed that children begin to experience pain at 12 months of age.

34. Are There Long-Term Consequences of Pain in Newborn or Very Young Infants? (Page, 2004, J Perinat Educ)

For many years, doctors in the United States did not view pain in infants as a risk or a flaw in treatment decisions. Superficial observations have shown that pain relievers have some risks, and babies seem to have forgotten about pain anyway. After all, if the patient does not come back with complaints of pain, what can be especially important in it?

However, studies in the 1990s found that pain experienced in infancy has long-term consequences. For example, babies who were circumcised without lidocaine ointment suffered more pain during vaccination than those circumcised with lidocaine, who in turn suffered more than uncircumcised babies.

Newborn rat pups, which were separated from their mother for some time, showed suppression of the immune system and were more susceptible to metastases.

In rat pups that were injected with endotoxin in infancy, in adulthood, there was an exacerbated response to stress, increased susceptibility to metastases, and delayed wound healing, which indicates an inability to form an inflammatory response.

Pups that were exposed to pain through puncture in the paw showed increased pain sensitivity during adolescence. In adulthood, they showed great anxiety, social hypervigilance, and they were observed to have a craving for alcohol.

Babies born prematurely (who have undergone much more painful medical procedures than those born at term) have decreased pain sensitivity.

In infants with multiple birth trauma, the risk of violent suicide was 4.9 times higher in men and 4% higher in women. But if the mother received opioids during childbirth, the risk of suicide was 31% lower for both sexes, compared to those born without an injury.

The authors conclude that although people do not remember early painful events, they are recorded somewhere in the body. The many medical procedures infants undergo, from heel shots to circumcisions, can change a child's development. Childhood pain should be avoided whenever possible and, if necessary, treated as carefully as for adult pain. Doctors and parents need to be aware that pain must be added to the risk list in order to make treatment decisions and to agree to the procedures the infant is subjected to. This consideration was not part of the traditional decision-making model for most doctors.

35. Iatrogenic pain in newborns as a risk factor for chronic pain syndromes. (Reshetnyak, 2017, Russian Journal of Pain)

Frequent painful irritations in newborns, especially premature babies, lead to central sensitization of those areas of the cerebral cortex that make up the leading part of the neuromatrix of pain and are responsible for the sensory, affective and cognitive components of pain perception. Central sensitization and dysfunction of the systems that regulate pain sensitivity are known to lead to the formation of chronic pain syndromes.

36. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. (Mercer, 2006, Pediatrics)

If you do not cut the umbilical cord immediately after birth, but wait at least 30-40 seconds, then the risk of intraventricular hemorrhage and sepsis is significantly reduced.

37.peastmilk, PCBs, dioxins and vitamin K deficiency: discussion paper. (Koppe, 1989, J R Soc Med)

The late form of hemorrhagic neonatal disease is a new disease that was described in 1985 and is observed only in children with exceptional hepatitis B. Breast milk in industrialized countries is contaminated with polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs).

Xenobiotics have been found in the milk of Dutch mothers, but they were not in the milk of a woman who recently immigrated from Suriname. In a woman who immigrated from Suriname 15 years ago, xenobiotics were also found.

PCBs, PCDDs and PCDFs are known to cause liver enlargement, increased blood clotting time, liver cirrhosis, etc. Clinical symptoms in infants whose mothers were poisoned with these substances included stunted growth, smaller head circumference, hirsutism, etc. Those who were fed breast milk containing PCBs experienced, among others, fatigue, anorekia, abdominal pain, vomiting and eczema. Fatty livers, pancreatic atrophy, and gastrointestinal hemorrhage were found in monkeys after a high dose. Millions of chicks that die from contaminated food experience subepicardial bleeding. Mice exhibit cleft palate, bleeding, and subcutaneous edema.

The authors tested the level of dioxins in the milk of 14 mothers. Mothers of 4 infants who had bleeding had significantly higher dioxin levels than ten other mothers. The authors believe that there is probably a causal relationship between PCBs, dioxins and furans in breast milk and late hemorrhagic disease. These xenobiotics are also possibly associated with prolonged neonatal jaundice. More: [1] [2]

38. Reasons for refusal of newborn vitamin K prophylaxis: implications for management and education.(Hamrick, 2016, Hosp Pediatr)

Among the parents who refused to receive vitamin K injections, the majority were white (78%), over 30 (57%), and with an academic background (65%). Most of them also refused the hepatitis B vaccine and erythromycin ointment for the eyes. They were mostly getting their information from the internet and were worried about synthetic and toxic ingredients, overdose, and side effects.

67% of them were aware of the risks of rejection, but most did not understand the potential danger of bleeding, especially the likelihood of intracranial hemorrhage and death.

In the hospital, where oral vitamin K was available, the injection refusal rate was significantly higher.

The authors conclude that the online information parents rely on is often unsupported by peer-reviewed scientific sources and encourages natural childbirth without medical intervention. The most important thing, the authors write, is that the specific problems that are covered on the sites on the Internet are not touched upon by doctors in their conversations with mothers.