Purpose and Goal: CEARP #1098

  • Describe the etiology of hemorrhagic disease of the newborn.
  • Describe the management of hemorrhagic disease of the newborn.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for Successful Completion

  • Successfully complete the post-test.
  • Complete the evaluation form.

Date

  • April 2014 - April 2016

Learning Objectives

  • Describe the etiology of hemorrhagic disease of the newborn.
  • Describe the indications for vitamin K administration during the newborn period.
  • Identify at least two controversies regarding vitamin K administration.

Introduction

  • Hemorrhagic disease of the newborn
    • First described in 1894
    • Linked to vitamin K in 1939
     
  • Also known as vitamin K deficiency bleeding
  • Newborn infants are at risk due to:
    • Inability to obtain vitamin K
    • Inability to synthesize vitamin K
     

Vitamin K

  • Vitamin K is a fat-soluble vitamin
    • Easily depleted
    • Not readily stored
    • Requires dietary intake
     
  • There are three forms of vitamin K.
    • Vitamin K1, present in green leafy vegetables
    • Vitamin K2, synthesized by GI bacterial flora
    • Vitamin K3, synthetic water-soluble form
     
  • Appropriate levels of Vitamin K are essential for:
    • Blood coagulation
    • Bone metabolism
    • Vascular stability
    • Cell growth
    • Apoptosis
     

Hemostasis

  • Vitamin K1 plays a major role in coagulation.
  • Necessary for synthesis of clotting factors
    • Activates factors II, VII, IX and X
    • Activates protein C and protein S
     

Vitamin K Deficiency

  • Deficiency is common in the newborn.
  • Increased with decreasing gestational age
  • Caused by:
    • Inadequate placental transfer
    • Deficient hepatic stores
    • Lack of intestinal flora
    • Limited dietary sources
     
  • Recommended daily intake is 1 mcg/kg/day.
  • Cow's milk formula contains 50-100 mcg/liter.
  • Colostrum contains 0.2-0.3 mcg/liter.
  • Human milk contains 1-5 mcg/liter.

Vitamin K Deficiency Bleeding

  • Deficiency may cause unexpected bleeding.
    • Skin
    • Umbilical cord
    • Gastrointestinal
    • Urinary tract
    • Intracranial
     
  • Incidence is 0.25%-1.7% during first week of life.
  • Onset may occur as late as 2-12 weeks of life.
  • Occurs primarily in infants who did not receive vitamin K
  • Presents with:
    • Tarry or bloody stools
    • Petechiae
    • Bloody urine
    • Umbilical cord oozing
    • Nose or mouth bleeding
    • Severe or prolonged jaundice
     
  • Classified as early, classic or late onset

Early Onset

  • First 24 hours of life
  • Incidence is 6%-12%
  • Severe hemorrhage may be refractory.
  • Caused by exposure to medications
  • Maternal medications interfere with metabolism.
    • Anticonvulsants
    • Anticoagulants
    • Antitubercular medications
     
  • May be prevented by giving mothers vitamin K injections.
  • Presents with:
    • Cephalohematoma
    • Intracranial hemorrhage
    • Intrathoracic bleeding
    • Intra-abdominal bleeding
     

Classic Onset

  • First week of life
  • Incidence is 0.5%-1.5%
  • Caused by illness or delayed feedings
  • Most common in exclusively breastfed infants
  • Presents with:
    • Umbilical cord bleeding
    • Skin bruising and bleeding
    • Nose and mouth bleeding
    • Gastrointestinal bleeding
    • Circumcision bleeding
     

Late Onset

  • First 2-3 months
    • May be seen from 8 days to 6 months
    • Peaks between 3 and 6 weeks
     
  • Incidence is 5-116 per 100,000 births.
  • Caused by lack of vitamin K prophylaxis
  • Most common in exclusively breastfed infants
  • Also common in infants:
    • With intestinal malabsorption
      • Biliary atresia
      • Cholestatic jaundice
      • Cystic fibrosis
      • Alpha-1 antitrypsin deficiency
       
    • Of Asian descent
     
  • Presents with:
    • Skin bruising and bleeding
    • Gastrointestinal bleeding
    • Intracranial bleeding
      • 40% risk of long-term morbidity
      • 10%-50% risk of mortality
       
     

Management and Treatment

  • Assessment of coagulation factors
    • Prolonged PT (prothrombin time)
    • Prolonged PTT (partial thromboplastin time)
    • Normal platelet count
    • Normal fibrinogen level
     
  • Diagnosis confirmed with administration of vitamin K
    • Vitamin K 1 mg IV should be given
    • IM dosing can cause bleeding.
    • Correction of PT should be seen.
    • Bleeding should be resolved.
     
  • May require transfusions if bleeding severe.
    • Fresh frozen plasma
    • Cryoprecipitate
    • Platelets
    • Packed red blood cells
     
  • CT scan to evaluate intracranial bleeding

Vitamin K Prophylaxis

  • Routine vitamin K injections for all newborns
    • 0.5-1.0 mg given intramuscularly
      • 0.5 mg for infants <1500 grams
      • 1.0 mg for infants >1500 grams
       
    • Generally given within one hour of birth
    • Provides protection for three months.
     
  • Recommended by the American Academy of Pediatrics
  • First recommended in the 1950s
  • Standard of care since 1961
  • Supportive breastfeeding practices
    • Start early and feed frequently
    • Hindmilk is higher in fat
      • Increased vitamin K in hindmilk
      • Breast should be regularly emptied
      • Time limits should be avoided
       
    • Breastfeeding mothers should increase vitamin K intake
     

Oral Vitamin K Prophylaxis

  • Variable rate of absorption
  • Does not provide consistent availability.
  • No FDA-approved form
    • Approved for use in Europe
    • Not approved for use in the USA
    • Injection form can be given orally.
     
  • Single dose at birth is not preventative.
  • Requires multiple doses:
    • 2 mg at birth
    • 2 mg at 1-2 weeks
    • 2 mg at 4-6 weeks
     
  • Can also be given as 1 mg weekly for three months.
  • Less effective prevention
    • Effective against early and classic 
    • Not effective against late-onset bleeding
     

Current Controversies

  • Exposure to preservatives
    • Benyzl alcohol
    • Associated with toxicity in the 1980s
    • Toxicity due to exposure to large doses
    • Reported cases associated with IV flush
    • Injection form contains 0.9%.
     
  • Childhood leukemia
    • One study reported IM injection-associated illness.
    •  Soft tissue cancers and leukemia
    • Several studies have disproved any association.
    • Studies verified by Canadian Pediatric Society
     
  • Hemolytic anemia
    • Seen with high doses of Vitamin K
    • Commonly seen in the 1950s
    • Caused by doses as high as 50 mg
    • Resolved with current dosing of 1 mg
     
  • Pain
    • Parent education is important.
    • Oral administration can avoid pain.
    • Use of 25% sucrose can alleviate pain.
    • Use of colostrum can alleviate pain.
    • Administration while breastfeeding can alleviate pain.
     

References

  1. Dunlap, M.M. Vitamin K Deficiency Bleeding of the Newborn. 2012. Growing Families, 16(8), p. 1-4.
  2. Woods, C.W. and Cederholm, C.K. 2013. Vitamin K Deficiency Bleeding. Advances in Neonatal Care, 13 (6), p. 402-407.
  3. Johnson, P.J. 2013. Vitamin K Prophylaxis in the Newborn: Indications and Controversies. Neonatal Network, 32(3), p. 193-199.
  4. Committee on Fetus and Newborn. 2003. Controversies Concerning Vitamin K and the Newborn. Pediatrics, 112, p.191-194.
  5. Pazirandeh, S. and Burns, D.L. 2014. UpToDate: Overview of Vitamin K  

Test and Evaluation

* Required fields