Are the Ingredients in the Newborn Vitamin K Shot Safe?
Today on the blog, I’m sharing an excerpt from my book. Chapter 3 of the book covers newborn medical procedures, including in-depth discussions of the history and science of the vitamin K shot and erythromycin eye ointment. Recognizing that some parents are concerned about the ingredients in the vitamin K shot, I really dug into the details on these, but then I ended up making this section an appendix so as not to bog down the chapter with too much chemistry. This is one of the those topics where a Google search turns up a lot of misinformation that can be very misleading to concerned parents, so I wanted this information to be accessible on the Internet as well as in the pages of my book.
In the U.S. and many other countries around the world, a single intramuscular injection of vitamin K is recommended for all newborns soon after birth. Vitamin K is necessary for normal blood clotting. Without it, any small internal injury – which might normally clot and heal quickly – could turn into a dangerous hemorrhage. During pregnancy, vitamin K transport across the placenta is very poor (1), so babies are effectively born deficient in vitamin K. Breast milk is also very low in vitamin K, further limiting the supply of this nutrient in exclusively breastfed babies until they start solid foods (2,3). The newborn vitamin K shot corrects this deficiency, preventing rare but potentially devastating vitamin K deficiency bleeding (VKDB). It has been routinely given in the U.S. since 1961, when it was officially recommended by the AAP (4). This is an evidence-based recommendation. The shot is safe and effective. Of all the many questions that I researched for my book, this one was one of the few that had a crystal clear answer. There’s just no good reason to decline the vitamin K shot and leave your newborn at risk for VKDB.
But over the last few years, we’ve seen some evidence that more parents have been declining the newborn vitamin K shot for their babies. In November 2013, the CDC reported an alarming cluster of 4 babies with late VKDB, all born in the Nashville, Tennessee area and treated at Vanderbilt University Medical Center. Doctors at Vanderbilt later published a case series of these babies, plus a fifth case (5). Four had bleeding in their brains, and two of them required emergency brain surgery. All had been healthy babies at birth and had been breastfed, and none had received the vitamin K shot. In a paper published in Pediatrics in 2014, researchers in Alberta, Canada, reported that the rate of refusal of the vitamin K shot had increased there between 2006 and 2012 and that parents who declined vitamin K were also more likely to choose not to vaccinate their kids (6).
When I started researching the vitamin K shot, I found lots of scary blog posts about ingredients in the shot. These invariably pulled information from the package insert for vitamin K but failed to put it in context or attempt to understand what it means.
It’s really important to know that the package insert of a pharmaceutical product is a legal document. It doesn’t represent the most relevant medical and safety information of the product in question. In fact, it contains a ton of information that is irrelevant to you and your baby, but it is there because it is required by FDA regulations. The package insert of the vitamin K shot includes warnings about all adverse reactions that have been documented with each ingredient, even when those incidents occurred in different drugs, different patient populations (for example, very sick premature babies), in much larger doses, or during long-term intravenous infusions (different from a one-time intramuscular shot). The same is true of vaccine package inserts. This wording can give drug companies some legal protection, which was described in this article in The New York Times: “Listing every inkling of an adverse reaction can help drug companies in lawsuits, Dr. Duke said. If someone sues about a side effect that is listed in the drug’s package insert, the company can say patients have been warned.”
But all of this means that package inserts can sound pretty scary, and it gives anti-vitamin K bloggers plenty of material for trying to frighten parents away from the shot. That’s why I wanted to look carefully at each ingredient, the dose included, and published information on safety.
The first step to understanding information like this is to not be afraid of unfamiliar chemical names. Everything in the world is made up of chemicals, including us. When scanning an ingredient list, whether or not you can pronounce the names or if they are natural or synthetic tells us nothing about their safety. Consider these examples: Dihydrogen monoxide is water. (I know that’s a tired example, but it’s such a good one.) Ascorbic acid, α-tocopherol, and pantothenic acid are all vitamins found in food and needed by our bodies (they’re commonly known as vitamin C, vitamin E, and vitamin B5). Lacto-N-tetraose and LS-tetrasaccharide are two types of human milk oligosaccharides, naturally-occurring sugars found in human milk that contribute to the development of a baby’s microbiome and immune system. If you really want to understand chemical safety, you have to get past those daunting names and look at data, which is what I did for my book.
With all of that said, here’s the excerpt:
Appendix A: Are the Ingredients in the Newborn Vitamin K Shot Safe?
From The Science of Mom: A Research-Based Guide to Your Baby’s First Year
In chapter 3, I discuss the evidence for giving the vitamin K shot at birth. Despite its proven benefits, some parents opt out of giving their newborns this shot. When asked why, one of the common concerns is that the shot contains “toxins” (5). I’ve carefully evaluated each ingredient and concluded that this fear is unfounded. The vitamin K shot is safe. All of the ingredients serve important roles in the efficacy and safety of the shot, and none pose toxicological concerns in the amounts used.
Anytime you want to know whether a chemical is safe or effective, it is critical to look at the amount used, or the dose. A life-saving drug, for example, could be worthless if you didn’t take enough of it. It could also be toxic if you took too much. For the vitamin K shot, there are toxicological concerns with several of the ingredients, and these concerns are listed on the package insert for the vitamin K shot. However, in all cases, these were based on incidents using large, often continuous, intravenous doses of these ingredients, quite different from the one-time intramuscular dose of the vitamin K shot.
Two types of vitamin K shots are used in the United States. Both contain phytonadione, another name for vitamin K1, but they contain different “inactive” ingredients. Most hospitals use the preservative-free version for newborns, so let’s start with the ingredients in this one.
Ingredients in the Preservative-Free Vitamin K Shot:
- Propylene glycol acts as a solvent to keep the vitamin K in solution. (Vitamin K is fat-soluble, so just as oil and water don’t mix, it can’t simply be dissolved in water or saline for the injection.) Propylene glycol is commonly used in foods, supplements, and other medications, and in the amounts used, it is safe. Don’t confuse propylene glycol with ethylene glycol, a much more toxic chemical used in antifreeze. (If antifreeze is labeled “nontoxic antifreeze,” it’s probably made with propylene glycol.) According to the World Health Organization, propylene glycol is safe to consume in amounts up to 25 mg/kg of body weight per day. The vitamin K shot includes 10.4 mg of propylene glycol, or about 3.3 mg/kg for a 7-pound newborn (7,8). [This 2009 study estimated the amount of propylene glycol given to critically ill newborns in the NICU and found a median of 205 mg/kg/day of propylene glycol, much of it included in continuous IV infusions of medications over many days. The authors of the paper argue that these doses may be concerning. The tiny amount in the one-time vitamin K shot is not.]
- Polysorbate 80 is made from a plant-based sugar alcohol (sorbitol) and a fatty acid (oleic acid). It’s often used in ice cream to make it smoother (9), and it serves a similar purpose in the vitamin K shot. It is an emulsifier, helping fat-soluble vitamin K stay in solution. Polysorbate 80 was probably the culprit when an intravenous vitamin E product proved to be toxic in premature babies (an incident included on the package insert for the vitamin K shot), but these babies received more than 70 mg/kg daily for weeks and even months (10,11). The one-time vitamin K shot contains 10 mg of polysorbate 80 (about 3 mg/kg for a 7-pound baby), and there is no reason to believe that this amount is harmful to newborns (11).
- Sodium acetate anhydrous (0.17 mg) helps to maintain a neutral pH in the vitamin K shot. There are no toxicity concerns with this small amount. This ingredient does contain a small amount of aluminum, which is noted on some package inserts, but the amount is no more than 0.05 μg (a μg is 1/1000th of a milligram). At birth, a newborn’s body already contains 8,000 times this amount of aluminum (12).
- Glacial acetic acid (0.002 ml) is a weak acid and the main component of vinegar. It is used to adjust the pH and has no safety concerns as used in the vitamin K shot.
The second type of vitamin K shot used in the United States is less commonly used in newborns, but it is also safe. It contains the following ingredients:
- Benzyl alcohol prevents bacterial growth in the vitamin K shot. The WHO sets the safe daily intake of benzyl alcohol at no more than 5 mg/kg. The vitamin K shot is well below this level; it contains 4.5 mg, or about 1.4 mg/kg for a 7-pound newborn. The vitamin K package insert warns that benzyl alcohol can cause toxicity in newborns, but this requires much larger, daily, intravenous amounts (more than 99 mg/kg/day) (7,8,13). [Edited to add: Incidents of benzyl alcohol toxicity in premature infants occurred when water or saline preserved with benzyl alcohol – again, to prevent bacterial growth – was used to flush IV lines. Because of this, benzyl alcohol is no longer used for this purpose. An AAP review of inactive ingredients in pharmaceutical products states, “The toxic effects in newborns relate primarily to the use of preservative-containing flush solutions, which clearly are to be avoided in newborns. At low doses, such as those present when medications preserved with benzyl alcohol are administered, benzyl alcohol is safe for newborns.” (13)]
- Polyethoxylated castor oil acts as an emulsifier and solvent to keep vitamin K in solution and is used in many other drugs for this purpose. Very rarely, this ingredient has caused an anaphylactic reaction in patients receiving large doses by intravenous infusion, but there are no reported cases of this effect in newborns receiving the intramuscular vitamin K shot with this ingredient (14).
- Dextrose monohydrate is a fancy name for glucose, the simple sugar that circulates in our blood and fuels our cells. Much larger doses are routinely given to newborns that have low blood sugar. There are no safety concerns with this ingredient.
A third product, called Konakion MM, made by Roche Pharmaceuticals, is licensed for both oral and injectable use in Europe. First introduced in 1994 in Switzerland, this product contains glycocholic acid (a bile salt) and lecithin (a phospholipid) to disperse the fat-soluble vitamin K into small droplets, similar to the mixed micelles (hence the MM in the name) that are part of the normal digestion of fats and fat-soluble vitamins. The idea behind this preparation was that it would be more absorbable via the oral route, even for babies with liver disease and limited bile salts, but it hasn’t turned out to be much more effective than the other preparations at preventing late vitamin K deficiency bleeding (VKDB) in these babies (15,16).
A single case report of a baby having an anaphylactic reaction to an intramuscular injection of Konakion MM in Turkey was published in 2014 (17). The baby was treated and fully recovered, and the authors were not able to identify the cause of anaphylaxis, noting that anaphylaxis to lecithin or bile acids have never been reported. The authors also noted that theirs was the only report of this ever occurring, despite millions of doses of several different vitamin K preparations over more than half a century. Any time a baby is given a new medication or food, there is always a chance of an allergic reaction, so this is really an impressive safety record.
The package inserts for all vitamin K preparations note that it can cause jaundice (hyperbilirubinemia), and this is often mentioned in anti-vitamin K articles. However, these cases occurred in babies receiving 10 to 20 mg doses of a synthetic, water-soluble form of vitamin K, menadione, which is no longer used. A 1956 paper (18) reporting this problem concluded, “There is still a place for vitamin K in the prophylaxis and treatment of haemorrhagic disease but a dose of 1 to 2 mg is sufficient.” Because of this, the recommended dose (and preparation) was changed, and increased risk of jaundice has not been observed in babies who received the recommended dose.
Adapted from The Science of Mom: A Research-Based Guide to Your Baby’s First Year with permission from Johns Hopkins University Press.
If the ingredient list on the vitamin K shot seems a little overwhelming, I can understand how you might be tempted to opt out of the shot for your newborn. However, with all the digging I did for each of these ingredients, I see no reason to fear them. On the other hand, there is a very real and well-documented risk of skipping the newborn vitamin K shot – the risk that your baby could develop a life-threatening hemorrhage, most dangerously in the brain or gastrointestinal tract. If you’re considering declining the vitamin K shot, I urge you to first read Olive’s story, which is also included in my book with permission from her mother, who hopes she can prevent other babies from suffering as Olive did. Ensuring that your baby receives the vitamin K shot soon after birth is the most certain way to prevent the potentially devastating outcome of vitamin K deficiency bleeding.
- Mandelbrot, L. et al. Placental transfer of vitamin K1 and its implications in fetal hemostasis. Thromb. Haemost. 60, 39–43 (1988).
- Greer, F. Vitamin K status of lactating mothers and their infants. Acta Pædiatrica 88, 95–103 (1999).
- Greer, F. Vitamin K in human milk—still not enough. Acta Pædiatrica 93, 449–450 (2004).
- American Academy of Pediatrics (AAP). Policy Statement: Controversies concerning vitamin K and the newborn. Pediatrics 112, 191–192 (2003).
- Schulte, R. et al. Rise in Late Onset Vitamin K Deficiency Bleeding in Young Infants Due to Omission or Refusal of Prophylaxis at Birth. Pediatr. Neurol. (2014). doi:10.1016/j.pediatrneurol.2014.02.013
- Sahni, V., Lai, F. Y. & MacDonald, S. E. Neonatal vitamin K refusal and nonimmunization. Pediatrics 134, 497–503 (2014).
- Shehab, N., Lewis, C. L., Streetman, D. D. & Donn, S. M. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr. Crit. Care Med. 10, 256–259 (2009).
- Nordt, S. P. & Vivero, L. E. in Goldfrank’s Toxicologic Emergencies (eds. Nelson, L. S. et al.) (McGraw-Hill, 2011).
- Goff, H. D. Colloidal aspects of ice cream—A review. Int. Dairy J. 7, 363–373 (1997).
- Lorch, V. et al. Unusual Syndrome Among Premature Infants: Association With a New Intravenous Vitamin E Product. Pediatrics 75, 598 (1985).
- Smolinske, S. C. CRC Handbook of Food, Drug, and Cosmetic Excipients. (CRC Press, 1992).
- Mitkus, R. J., King, D. B., Hess, M. A., Forshee, R. A. & Walderhaug, M. O. Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. Vaccine 29, 9538–9543 (2011).
- American Academy of Pediatrics (AAP). ‘Inactive’ Ingredients in Pharmaceutical Products: Update (Subject Review). Pediatrics 99, 268–278 (1997).
- Riegert-Johnson, D. L. & Volcheck, G. W. The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review. Ann. Allergy. Asthma. Immunol. 89, 400–406 (2002).
- Greer, F. R. et al. A new mixed micellar preparation for oral vitamin K prophylaxis: randomised controlled comparison with an intramuscular formulation in breast fed infants. Arch. Dis. Child. 79, 300–305 (1998).
- Schubiger, G. et al. Prevention of vitamin K deficiency bleeding with oral mixed micellar phylloquinone: results of a 6-year surveillance in Switzerland. Eur. J. Pediatr. 162, 885–888 (2003).
- Koklu, E., Taskale, T., Koklu, S. & Ariguloglu, E. A. Anaphylactic shock due to vitamin K in a newborn and review of literature. J. Matern. Fetal Neonatal Med. 27, 1180–1 (2014).
- Meyer, T. C. & Angus, J. The Effect of Large Doses of Synkavit in the Newborn. Arch. Dis. Child. 31, 212–215 (1956).