Controversies Concerning Vitamin K and the Newborn

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PEDIATRICS Vol. 112 No. 1 July 2003, pp. 191-192

http://pediatrics.aappublications.org/cgi/content/full/112/1/191

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POLICY STATEMENT

Controversies Concerning Vitamin K and the Newborn

Committee on Fetus and Newborn

ABSTRACT

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BACKGROUND

RECOMMENDATIONS

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Prevention of early vitamin K deficiency bleeding (VKDB) of the newborn, with

onset at birth to 2 weeks of age (formerly known as classic hemorrhagic disease

of the newborn), by oral or parenteral administration of vitamin K is accepted

practice. In contrast, late VKDB, with onset from 2 to 12 weeks of age, is most

effectively prevented by parenteral administration of vitamin K. Earlier concern

regarding a possible causal association between parenteral vitamin K and

childhood cancer has not been substantiated. This revised statement presents

updated recommendations for the use of vitamin K in the prevention of early and

late VKDB.

Abbreviations: VKDB, vitamin K deficiency bleeding

BACKGROUND

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BACKGROUND

RECOMMENDATIONS

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Vitamin K deficiency may cause unexpected bleeding (0.25%–1.7% incidence)

during the first week of life in previously healthy-appearing neonates (early

vitamin K deficiency bleeding [VKDB] of the newborn [formerly known as classic

hemorrhagic disease of the newborn]). The efficacy of neonatal vitamin K

prophylaxis (oral or parenteral) in the prevention of early VKDB is firmly

established. It has been the standard of care since the American Academy of

Pediatrics recommended it in 1961.1

Late VKDB, a syndrome defined as unexpected bleeding attributable to severe

vitamin K deficiency in infants 2 to 12 weeks of age, occurs primarily in

exclusively breastfed infants who have received no or inadequate neonatal

vitamin K prophylaxis. In addition, infants who have intestinal malabsorption

defects (cholestatic jaundice, cystic fibrosis, etc) may also have late VKDB.

The rate of late VKDB (often manifesting as sudden central nervous system

hemorrhage) ranges from 4.4 to 7.2 per 100 000 births, according to reports from

Europe and Asia.2,3 When a single dose of oral vitamin K has been used for

neonatal prophylaxis, the rate has decreased to 1.4 to 6.4 per 100 000 births.

Parenteral neonatal vitamin K prophylaxis prevents the development of late VKDB

in infants, with the rare exception of those with severe malabsorption

syndromes.2

Oral administration of vitamin K has been shown to have efficacy similar to that

of parenteral administration in the prevention of early VKDB.4–6 However,

several countries have reported a resurgence of late VKDB coincident with

policies promoting the use of orally administered prophylaxis, even with

multiple-dose regimens. In a 1997 review of these experiences by Cornelissen et

al,7 surveillance data from 4 countries revealed oral prophylaxis failures of

1.2 to 1.8 per 100 000 live births, compared with no reported cases after

intramuscular administration. Newborns receiving incomplete oral prophylaxis

tended to have a higher risk of developing VKDB, with rates of approximately 2

to 4 per 100 000. Small daily oral doses, as practiced in the Netherlands, may

decrease the risk of late VKDB8 and approach the efficacy of the parenteral

route; however, this needs to be better studied.

Draper and Stiller,9 using other data from Great Britain, have questioned the

results of earlier studies of Golding et al10,11 that attempted to show an

association between intramuscular vitamin K administration in newborns and an

increased incidence of childhood cancer. Using data from the National Registry

of Childhood Tumors, they estimated the cumulative incidence of childhood

leukemia. Three sources of data, including the estimates from Golding et al,

provided rates of intramuscular vitamin K use over the same time frame. Their

analyses failed to show a correlation between increased use of intramuscular

vitamin K and the incidence of childhood leukemia.

The Vitamin K Ad Hoc Task Force of the American Academy of Pediatrics12 reviewed

the reports of Golding et al and other information regarding the US experience13

and concluded that there was no association between the intramuscular

administration of vitamin K and childhood leukemia or other cancers.

Additional studies that have since been conducted by other investigators have

not supported a clinical relationship between newborn parenteral administration

of vitamin K and childhood cancer. Ross and Davies14 published a review of the

evidence in 2000. They found no randomized or quasi-randomized evidence of an

association between parenteral vitamin K prophylaxis and cancer in childhood.

Ten case-control studies were identified, of which 7 found no relationship and 3

found only a weak relationship of neonatal administration of intramuscular or

intravenous vitamin K with the risk of solid childhood tumors or leukemia.

Recent research on the pathogenesis of childhood leukemia additionally weakens

the plausibility of a causal relationship between parenteral administration of

vitamin K and cancer. Investigations by Wiemels et al15 suggest a prenatal

origin of childhood leukemia. They found an acute lymphocytic

leukemia-associated gene in 12 children with newly diagnosed acute lymphocytic

leukemia and postulated that an in utero chromosomal translocation event

combined with a postnatal promotional event results in clinical leukemia.

Although intramuscular administration of vitamin K could conceivably be a

postnatal promotional event, a genetic etiologic explanation further lessens the

likelihood of a clinically significant relationship between intramuscular

administration of vitamin K and leukemia.

There is concern that adequate vitamin K prophylaxis be provided to the

increasing numbers of newborns who are breastfed exclusively to avoid an

increased risk of late VKDB with its associated intracranial hemorrhage.7

RECOMMENDATIONS

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Because parenteral vitamin K has been shown to prevent VKDB of the newborn and

young infant and the risks of cancer have been unproven, the American Academy of

Pediatrics recommends the following:

Vitamin K1 should be given to all newborns as a single, intramuscular dose of

0.5 to 1 mg.16

Additional research should be conducted on the efficacy, safety, and

bioavailability of oral formulations and optimal dosing regimens of vitamin K to

prevent late VKDB.

Health care professionals should promote awareness among families of the risks

of late VKDB associated with inadequate vitamin K prophylaxis from current oral

dosage regimens, particularly for newborns who are breastfed exclusively.

Committee on Fetus and Newborn, 2002–2003

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Lillian Blackmon, MD, Chairperson

G. Batton, MD

F. Bell, MD

A. Engle, MD

P. Kanto, Jr, MD

Gilbert I. , MD

Warren Rosenfeld, MD

Ann R. Stark, MD

*Carol A. , MD

Past Committee Member

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J. Barrington, MD

Canadian Paediatric Society

Tonse Raju, MD, DCH

National Institutes of Health

E. Riley, MD

American College of Obstetricians and Gynecologists

Kay M. Tomashek, MD

Centers for Disease Control and Prevention

Carol Wallman, MSN, RNC, NNP

National Association of Neonatal Nurses

Staff

Jim Couto, MA

*Lead author

REFERENCES

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REFERENCES

American Academy of Pediatrics, Committee on Nutrition. Vitamin K compounds and

the water-soluble analogues: use in therapy and prophylaxis in pediatrics.

Pediatrics.1961; 28 :501 –507[Abstract]

von Kreis R, Hanawa Y. Neonatal vitamin K prophylaxis. Report of Scientific and

Standardization Subcommittee on Perinatal Haemostasis. Thromb Haemost.1993; 69

:293 –295[iSI][Medline]

Motohara K, Endo F, Matsuda I. Screening for late neonatal vitamin K deficiency

by acarboxyprothrombin in dried blood spots. Arch Dis Child.1987; 62 :370

–375[Abstract]

O’Connor ME, Addiego JE Jr. Use of oral vitamin K1 to prevent hemorrhagic

disease of the newborn infant. J Pediatr.1986; 108 :616 –619[iSI][Medline]

McNinch AW, Upton C, s M, et al. Plasma concentrations after oral or

intramuscular vitamin K1 in neonates. Arch Dis Child.1985; 60 :814

–818[Abstract]

Schubiger G, Gruter J, Shearer MJ. Plasma vitamin K1 and PIVKA-II after oral

administration of mixed-micellar or cremophor EL-solubilized preparations of

vitamin K1 to normal breast-fed newborns. J Pediatr Gastroenterol Nutr.1997; 24

:280 –284[iSI][Medline]

Cornelissen M, Von Kries R, Loughnan P, Schubiger G. Prevention of vitamin K

deficiency bleeding: efficacy of different multiple oral dose schedules of

vitamin K. Eur J Pediatr.1997; 156 :126 –130[iSI][Medline]

von Kries R, Hachmeister A, Gobel U. Can 3 oral 2 mg doses of vitamin K

effectively prevent late vitamin K deficiency bleeding? Eur J Pediatr.1999;

158(suppl 3) :S183 –S186[iSI][Medline]

Draper GJ, Stiller CA. Intramuscular vitamin K and childhood cancer. BMJ.1992;

305 :709

Golding J, Paterson M, Kinlen LJ. Factors associated with childhood cancer in a

national cohort study. Br J Cancer.1990; 62 :304 –308[iSI][Medline]

Golding J, Greenwood R, Birmingham K, Mott M. Childhood cancer, intramuscular

vitamin K, and pethidine given during labour. BMJ.1992; 305 :341

–346[iSI][Medline]

American Academy of Pediatrics, Vitamin K Ad Hoc Task Force. Controversies

concerning vitamin K and the newborn. Pediatrics.1993; 91 :1001

–1003[iSI][Medline]

Devesa SS, Silverman DT, Young JL Jr, et al. Cancer incidence and mortality

trends among whites in the United States, 1947–84. J Natl Cancer Inst.1987; 79

:701 –770[iSI][Medline]

Ross JA, Davies SM. Vitamin K prophylaxis and childhood cancer. Med Pediatr

Oncol.2000; 34 :434 –437[iSI][Medline]

Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute

lymphoblastic leukaemia in children. Lancet.1999; 354 :1499

–1503[iSI][Medline]

American Academy of Pediatrics, American College of Obstetricians and

Gynecologists. Guidelines for Perinatal Care. 3rd ed. Washington, DC: American

College of Obstetricians and Gynecologists; 1992

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PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics

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Nothing surprising here. It never stops does it? They know the majority of the

populace is totally asleep and blind to what they are trully doing. It makes me

sick.