Vitamin K and Hemorrhagic Disease of the Newborn

							Vitamin K and Hemorrhagic
  Disease of the Newborn

    TH Tulchinsky MD MPH
  Braun School of Public Health,
   Hebrew University-Hadassah,
           Jerusalem
                 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 4.4-
  7.2/100,000 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;83:1166-
  1168.
• 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.