Vitamin K and Hemorrhagic
Disease of the Newborn
TH Tulchinsky MD MPH
Braun School of Public Health,
Hebrew University-Hadassah,
Jerusalem
Topics
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1. Disease
2. Vitamin K
3. Experience of the USA
4. Experience of Israel
5. Other countries
6. Summary of PH importance
7. References
History
• Townsend in Boston (1864) described 50 cases of
“hemorrhagic disease of the newborn” during first 2
weeks of life
• In 1929, Vitamin K isolated from alfalfa by Dam and
Doisy (Nobel Prize, 1942), and conducted clinical trials
showing Vitamin K protects against HDN
• 1961, Am Acad Pediatrics and Am College Obstetrics
and Gynecology recommended routine prophylaxis with
Vit K for all newborns
• Controversy in Britain in 1990s resolved to satisfaction
of AAP, ACOG, Canada, Australia, New Zealand and
others
Primary HDN
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Often fatal condition
Diffuse hemorrhage in otherwise healthy infant
During the first week of life
Particularly in low birth weight babies
Results of low levels of prothrombin and other
vitamin K dependent clotting factors, (Factors II,
VII, IX and X) caused by vitamin K deficiency
• An exaggerated of physiologic deficiency of clotting
factors normal in the first few days of life
• Incidence between 2.5 to 17.0 per thousand
newborns not given vitamin K prophylactically
Late HDN
• Between 2-12 weeks of life,
• Especially in breast-fed babies.
• Immaturity of liver affects production of
clotting factors
• Late HDN primarily in breast fed infants
without or inadequate vitamin K rates of 4.47.2/100,000 live births
Common Clinical Manifestations
• Bleeding in the
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gastrointestinal tract
urinary tract
umbilical stump
nose
scalp
intracranial hemorrhage
Shock
death
American Academy of Pediatrics 1961
• Prophylactic use of Vit K recommended by the
American Academy of Pediatrics, and by the
American College of Obstetricians and Gynecologists
since 1961.
• Up until 1987, administration of vit K at birth was
mandatory in only five states in the US
• AAP recommendation renewed in 1993 and remains
current
New York State Review
• We reviewed vital statistics in New York State finding
infant deaths and hospitalizations attributed to neonatal
hemorrhagic conditions (HDN)
• Case record reviews showed absence of recorded giving of
vitamin K in 65% of HDN deaths
• Vit K was not included in standing orders in any of 22
NYS hospitals contacted
• This review led to vit K being made a mandatory newborn
care procedure in NY State Public Health Code in 1989
Israel Experience
• Vit K was widely used
• However far from universal practice in the 1970s
• In 1977, HDN deaths in Israel were 131/100,000 live
births, declining to 31/100,000 live births in 1984 and
3/100,000 in 1988
• In 1984, administration of vit K was made mandatory
for newborn care by the Ministry of Health
• A large decline in deaths from intracranial and
intraventricular hemorrhage, may be partly due to
routine use of vitamin K.
Renewed Interest in Vit K
• Since the 1980s attention – UK, Europe, Japan, Canada,
Australasia and Middle East
• HDN and vit K deficiency reported in both developed
and developing countries where it is not routinely used,
or where use may be waning
• Controversy re oral versus parenteral use of routine Vit
K largely resolved
• Intramuscular administration within the first 6 hours
after birth more effective in preventing both early and
late HDN
Other Countries
• Still not routine in Japan, Germany, UK
• Routine prophylactic Vitamin K for newborns
adopted in
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Canada
Australia
New Zealand
Croatia, 1988
Public Health Importance
• Japanese incidence of HDN reported as 1/1,700 in breast
fed babies and 1:4,500 in all infants
• Of these, 82% were reported to have intracranial
hemorrhage (ICH)
• NDN still significant; even more in developing countries
e.g. India, Thailand, Singapore and Taiwan
• Thailand reports incidence of 35-72/100,000 births
• ICH not always identified as HND related and may be
significant factor in birth-related cerebral palsies
Recommended Implementation
• Mandatory within 6 hours of birth
• Cost $1.00 including syringe per child
• “Moderately cost-effective” (between $250-999 per
DALY saved - estimates range from $52-533) –
World Bank
• Requires standing orders and Ministry of Health
regulation
• Professional initiative and support
Summary
• Deficiency of Vit K remains a significant worldwide
cause of neonatal morbidity and mortality
• Routine prophylactic use of vitamin K should always be
used to prevent HDN (“good public health practice”)
• Administration by intramuscular injection (0.5-1.0 mgm)
within 6 hours of birth is preferable
• May be given orally as 3 doses spread over the first 4
weeks of life
• Vit K showing up in literature on osetoporosis
• A safe, inexpensive preventive procedure that should be
mandatory component of newborn care.
Bibliography
• American Academy of Pediatrics, Committee of Nutrition. Vitamin
K compounds and the water-soluble analogues: use in therapy and
prophylaxis in pediatrics. Pediatrics. 1961;28:501-506.
• Motohara K et al. Severe vitamin K deficiency in breast-fed infants.
J Paediatrics, 1984;105:943-945.
• Lane PA, Hathaway WE. Vitamin K in infancy. J Pediatrics.
1985;106:351-359.
• Caravella SJ et al. Health codes for newborn care. Pediatrics.
1987;80:1-5.
• Shearer MJ. Vitamin K and vitamin K dependant proteins. Br J
Hematology. 1990;75:156-162.
• McNinch AW and Tripp JH. Haemorrhagic disease of the newborn in the British
Isles: two year prospective study. BMJ, 1991;303:1105-1109.
• American Academy of Pediatrics. Vitamin K Ad Hoc Task Force.
Controversies concerning vitamin K and the newborn. Pediatrics.
1993;91:1001-1002.
Bibliography, Continued
• Tulchinsky TH, et al. Mandating vitamin K prophylaxis for
newborns in New York State. Am J Public Health, 1993;83:11661168.
• Von Kries R. Neonatal vitamin K: prophylaxis for all. BMJ.
1991;303:1083-1084.
• Hanawa Y, Maki M, Murata B et al. The second nation-wide survey
in Japan of vitamin K deficiency in infancy. European J Pediatr.
1988;147:472-477.
• Visctora CG, Van Heake P. Vitamin K prophylaxis in less developed
countries: policy issues and relevance to breast-feeding promotion.
Am J Public Health, 1998;88:203-209.
• Zipursky A. Prevention of vitamin K deficiency in newborns. Br J
Haematology. 1999;104:430-437.