PEDIATRICS Vol. 121 No. 5 May 2008, pp. 1048-1049 (doi:10.1542/10.1542/peds.2008-0558)
COMMENTARY |
Making Life Safe for Canaries
Retired Pediatrician, Newcastle Upon Tyne, United Kingdom
Key Words: HDN, hemorrhagic disease of the newborn
I can still remember the words written in red ink at the bottom of my essay: "You had a promising idea, but its development was disappointing." Many think that we already know all we really need to know about the use of vitamin K, but I fear my old headmaster might have viewed things rather more critically.
The speed with which people realized how vitamin K could be used to almost eliminate the risk of hemorrhagic disease of the newborn (HDN) was impressive. Indeed, the first article to describe clinical use appeared only 4 years after Danish biochemist Henrik Dam1 described his discovery in Nature in 1935. Use spread rapidly in Europe and America once a commercial product became available in the late 1940s, and when a single dose did not suffice to stop not just classic HDN but also intraventricular hemorrhage in the preterm infant, people started administering bigger doses. It did not take long after that for reports to appear that linked the use of the water-soluble analog menadione (the only preparation then commercially available) with an epidemic of severe jaundice and kernicterus.
Panic subsided when a fat-soluble product, phylloquinone (vitamin K1), became available a few years later, because it did not present the same hazard. Indeed, this product has dominated the market in Europe and North America ever since, in much the same way as menaquinone, a member of the K2 series, has dominated the market in Japan and much of Asia. What most people do not remember is that no formal studies were ever performed to establish what dose might be appropriate to give before it became standard practice to give every infant a 1-mg dose irrespective of weight at birth (because that was the dose provided by the standard ampoule) and to give it intramuscularly, simply because that was the only product available. Commerce dictated to medicine rather than the other way round.
The fact that this dose was 10 times that used in the only controlled trial of efficacy ever undertaken2 and >100 times the amount that 1 early study suggested was needed on a daily basis3 went unheralded. So, too, did the finding that, although the prothrombin time of breastfed infants decreased more than that of bottle-fed infants in the first few days of life, much of that decrease could be curbed by simply allowing the infant rather more breast milk.4 Breast milk was known to contain less vitamin K than cow's milk (or the formula feeds then coming into vogue), but milk was not really the problem. Lack of milk was the main problem, especially because hospital-born infants were often only put to the breast for a very limited time once every 4 hours.
We now know that the 1-mg dose, when administered intramuscularly, provides protection from not only early vitamin K deficiency bleeding (as HDN is now known) but also the risk of vitamin-deficiency bleeding throughout the first 3 months of life. The true efficacy of this chance choice of dose, however, was only fully appreciated after the policy had been in place for 30 years. It took even longer for evidence to emerge that giving a 500-g infant the same dose as a 5000-g infant can cause liver overload (and K1 2,3-epoxide accumulation).5
Even less was known about the right dose to provide when oral prophylaxis first became a common strategy in Europe 15 years ago—an alternative that parents could choose in some countries6 and the standard approach in several others. It took time for clinicians to appreciate that, because body stores only have a short turnover time, sustained protection requires repeat dosing. It has taken even longer to establish what that dose should be, because late vitamin K deficiency bleeding (bleeding in an infant >1 week old) is really very rare, even in exclusively breastfed infants. Although this makes epidemiologic studies slow, costly, and labor intensive, it does not make the lack of any commercially sponsored postmarketing surveillance any more acceptable. It does, however, make the innovative approach described by van Hasselt et al7 all the more noteworthy.
Their approach was to use a canary. Miners once used canaries because, if the bird stopped singing, that was a sure sign that miner's damp (either carbon monoxide or methane) was starting to accumulate. van Hasselt et al used 2 national biliary atresia registers in much the same way to detect what the infants at greatest risk of late vitamin K deficiency bleeding need. If politicians had a clearer understanding of what such registers can achieve, they might support their role more robustly.
So finally, therefore, after 70 years, we are starting to get a clearer idea of what sort of oral supplement could protect even the most vulnerable, exclusively breastfed infant in the first few months of life. Once we have that answer, we need to address the real challenge: the fact that most of the world's infants are still not getting the K (for "koagulation") vitamin that Henrik Dam discovered. Many are still in need of vitamin D, too.8 Can someone come up with a single inexpensive product that answers both these needs? There will be no Nobel prize awarded, I think, for the speed with which these 2 "promising ideas" have been "developed."
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FOOTNOTES |
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Accepted Feb 29, 2008.
Address correspondence to Edmund Hey, DM E-mail: shey{at}easynet.co.uk
The author has indicated he has no financial relationships relevant to this article to disclose.
Opinions expressed in these commentaries are those of the author and not necessarily those of the American Academy of Pediatrics or its Committees.
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REFERENCES |
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 TOP REFERENCES |
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- Dam H. The anti-hemorrhagic vitamin of the chick: occurrence and chemical nature. Nature. 1935;135 (18):652 –653
- Sutherland JM, Glueck HI, Gleser G. Hemorrhagic disease of the newborn: breast feeding as a necessary factor in the pathogenesis.
Am J Dis Child. 1967;113
(5):524
–533
[Abstract/Free Full Text] - Sells RL, Walker SA, Owen CA. Vitamin K requirements of the newborn infant. Proc Soc Exp Biol Med. 1941;47 (2):441 –445[CrossRef]
- Gellis SS, Lyon RA. The influence of the diet of the newborn on the prothrombin index. J Pediatr. 1941(4);19 :495 –502[CrossRef][Web of Science]
- Clarke P, Mitchell SJ, Wynn R, et al. Vitamin K prophylaxis for preterm infants: a randomized, controlled trial of 3 regimens. Pediatrics. 2006;118 (6). Available at: www.pediatrics.org/cgi/content/full/118/6/e1657
- Clarke P, Shearer MJ. Vitamin K deficiency bleeding: the readiness is all.
Arch Dis Child. 2007;92
(9):741
–743
[Free Full Text] - van Hasselt PM, de Koning TJ, Kvist N, et al. Prevention of vitamin K deficiency bleeding in breastfed infants: lessons from the Dutch and Danish biliary atresia registries.
Pediatrics. 2008;121
(4):e857
–e863
[Abstract/Free Full Text] - Dawodu A, Wagner CL. Mother-child vitamin D deficiency: an international perspective.
Arch Dis Child. 2007;92
(9):737
–740
[Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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