Vitamin K and Hemorrhagic Disease of the Newborn

TH Tulchinsky MD MPH Braun School of Public Health, Hebrew University-Hadassah, UniversityJerusalem

Topics
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
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
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
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.