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Mayo Medical School
To the Editor.—
We are concerned about the July 2003 American Academy of Pediatrics policy statement about vitamin K, "Controversies Concerning Vitamin K and the Newborn," which recommends a 0.5- to 1-mg dose for vitamin K in the newborn.1 We have reason to believe this dose is too high for some infants. The 4th and 5th editions of Pediatric Nutrition Handbook,2,3 by the American Academy of Pediatrics, recommends 0.3 mg/kg vitamin K for infants with birth weights <1000 g.2,3 Kumar et al4 documented that premature infants (28 weeks’ gestation, 90% formula fed) had excessively high plasma vitamin K levels of 130.7 ± 125.6 ng/mL on day 14 of life after receiving 1 mg of vitamin K intramuscularly shortly after birth and 71.2 ± 39.6 µg/kg per day from total parenteral nutrition (TPN).
In our study, "Vitamin K Prophylaxis for Preterm Infants: 1 mg versus 0.5 mg,"5 we reported extremely high plasma vitamin K levels in preterm infants who received their care at one neonatal intensive care unit in the Mayo Health System. Infants (22–32 weeks’ gestational age) were studied: group 1 received 1 mg of vitamin K, and group 2 received 0.5 mg of vitamin K. The day-2 plasma levels of vitamin K were 1900 to 2600 times higher on average (group 1 day-2 level: 1307.47 ± 552.39 ng/mL; group 2 day-2 level: 975.89 ± 820.86 ng/mL), and the day-10 vitamin K group 1 levels were 550 to 600 times higher on average (274.90 ± 255.32 ng/mL; group 2 day-10 level: 297.88 ± 213.70 ng/mL), relative to normal adult plasma values, whether an initial prophylaxis dose of 0.5 or 1 mg is used. Fasting adult plasma vitamin K is 0.5 ng/mL, and in infants unsupplemented with vitamin K plasma, vitamin K values are even lower than adults. The infants in our study received a lower amount of vitamin K via TPN vitamins and intralipid (fat) and enteral routes, compared with the patients in the Kumar et al study. In our study, the 1-mg vitamin K group received 53 ± 1.2 µg/kg per day and the 0.5-mg initial vitamin K group received 69.6 ± 18.48 µg/kg per day of vitamin K in TPN. Physicians cannot give less vitamin K in our TPN without giving less of other beneficial additives, including vitamins A and E. The more appropriate TPN multivitamin would provide 10 µg/kg per day of vitamin K.
The excessively high serum levels of vitamin K in our preterm infants are iatrogenic. Although there are no toxic effects of vitamin K reported in these infants, the functions of vitamin K at the cellular and molecular level are not fully understood.6,7 For example, new research demonstrates that vitamin K is present in the brain and has a role in the brain growth receptor system. Nature may be keeping tight control for a reason. Alternatively, new research demonstrates that vitamin K (nanomolar amounts) may prevent oxidative stress in developing oligodendrocytes and neurons.8 Certainly new revisions and/or updates of the vitamin K policy statement should specifically address the preterm infant and the controversies relevant to the preterm infant.
REFERENCES
Lillian R. Blackmon, MD, FAAP
Department of Pediatrics
Division of Neonatology
University of Maryland
Baltimore, MD 21201
On behalf of the Committee on Fetus and Newborn
We appreciate the opportunity to respond to the thoughtful letter from Drs Costakos and Porte. Regarding the title of the statement, they are quite correct that the content did not address the specific issue of the most appropriate dose for the very low birth weight newborn.1 With a single publication reporting markedly elevated serum concentrations at 2 weeks of age after an initial 1-mg dose of vitamin K and subsequent daily parenteral vitamin K in 10 infants of 
28 weeks’ gestation,2 the evidence for a controversy regarding the most appropriate prophylaxis dose was not convincing at the time the revision of the then-existing statement was in progress. The subsequent study conducted by Costakos et al3 and published after the statement was in press does add to our understanding of the needs of the extremely low birth weight infant. We note that although the recommended prophylaxis dosage for the <1000-g neonate of 0.3 mg is given in both the 4th and 5th editions of Pediatric Nutrition Handbook, in the discussion of the nutritional management of the preterm infant (chapters 5 and 2, respectively4,5) in both editions, a range of doses from 0.5 to 1 mg is stated in later chapters.6,7 It was this latter dose that was used in reaffirming the efficacy of intramuscular administration over the oral route for initial prophylaxis in recommendation 1 of the statement. The matter of the most appropriate dose relative to birth weight and gestational age will be revisited with the next revision to Guidelines for Perinatal Care.
REFERENCES
This article has been cited by other articles:
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  P. Clarke, S. J. Mitchell, R. Wynn, S. Sundaram, V. Speed, E. Gardener, D. Roeves, and M. J. Shearer Vitamin K Prophylaxis for Preterm Infants: A Randomized, Controlled Trial of Three Regimens Pediatrics, November 13, 2006; (2006) peds.2005-2742v1. [Abstract] [Full Text] [PDF]
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 H. Ashton, P. Gallagher, and B. Moore The adult psychiatrist's dilemma: psychostimulant use in attention deficit/hyperactivity disorder J Psychopharmacol, September 1, 2006; 20(5): 602 - 610. [Abstract] [PDF]
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 R. G. Ross Psychotic and Manic-like Symptoms During Stimulant Treatment of Attention Deficit Hyperactivity Disorder Am J Psychiatry, July 1, 2006; 163(7): 1149 - 1152. [Full Text] [PDF]
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D. T. Costakos Of Lobsters, Electronic Medical Records, and Neonatal Total Parenteral Nutrition Pediatrics, February 1, 2006; 117(2): e328 - e332. [Abstract] [Full Text] [PDF]
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