Guidelines for Vitamin K Prophylaxis

The success of vitamin K prophylaxis has been so dramatic that many practitioners have never seen an infant afflicted with "Hemorrhagic Disease of the Newborn," now known as "Vitamin K Deficient Bleeding." It is a popular trend in some areas to refuse prophylaxis in an effort to keep things "natural" for the infant, however, it is important to keep in mind that the infants most at risk for the classic form of the disease are healthy babies who are exclusively breastfed.

Background

• Vitamin K is necessary for synthesis of factors II (prothrombin), VII, IX, and X
• Vitamin K is undetectable in cord blood
• Lactobacillus (primary gut flora in breastfed babies) does not synthesize vitamin K
• Breastmilk contains only small amounts of vitamin K (1 – 9 mcg/L); formula (53-66 mcg/L)

Problem

• Vitamin K Deficiency Bleeding (aka “Hemorrhagic Disease of the Newborn”) can result
• Incidence of VKDB reported varies from 1.5% to 0.001% , depending on population studied and feeding patterns (formula is protective since it’s supplemented with vit K)

Definitions / Presentation / Diagnosis / Treatment

Definitions

• Early onset disease – onset within first 24 hours
• Classic disease – onset between day 2 – 7
• Late onset disease – onset between 2 weeks and 6 months

Presentation

Items in italics are most common form of initial presentation.

• Clinical bleeding manifest in one or multiple areas:
  • oozing from umbilicus
  • cephalohematoma (early dz)
  • bleeding circumcision site
  • GI bleed (classic dz)
  • ENT mucosal bleeding
  • skin bruising
  • bleeding from injection sites
  • intraabdominal bleed
  • intrathoracic bleed
  • GU bleeding
  • intracranial bleed (late dz)

  Diagnosis

  • based on clinical bleeding with abnormal PT/INR
  • plts NL, fibrinogen NL, +/- anemia, +/- abnormal PTT, +/- decreased factor II,VII, IX,X levels

  Treatment

  • 1 mg vitamin K SQ (preferred) or IV (risk of anaphylaxis)
  • biochemical response (normalized PT) is rapid, 4 – 6 hours

  Risk Factors

  Early Disease

  • Maternal anti-sz meds that interfere with vitamin K metabolism (phenytoin, phenobarbital, carbamezepine, or primidone)
  • Maternal anti-coagulants (coumadin, aspirin)
  • Maternal antibiotics, especially cephalosporins

  Classic Disease

  • Breastfeeding exclusively

  Late Disease

  • Marginal levels of vitamin K in breast milk
  • Cystic fibrosis
  • Celiac disease
  • Chronic diarrhea
  • A1-antitrypsin deficiency
  • Hepatitis

  Prophylaxis

  In the United States:

  • 0.5mg – 1mg vitamin K IM at birth

  In some parts of Europe:

  • 2 – 4mg PO vitamin K after first feeding then 2mg at 2 – 4 weeks and again at 6 – 8 weeks
    OR
  • 2 – 4mg PO vitamin K after first feeding then 2mg within first week and weekly while breastfeeding
    OR
  • 2mg PO vitamin K after first feeding then 2mg within first week followed by 25mcg daily for 13 weeks

  Notes about Oral Regimens

  • there is no licensed PO form in the US. Some have given infants the injectible liquid by mouth, but this is an unstudied intervention -- there is no safety or effectiveness data available.
    
  • in countries that have gone to PO prophylaxis, failures (even with good compliance) have been reported . Failures have not been reported with IM prophylaxis.
  • since multiple doses are required, compliance is an issue with all oral regimens
    
  • maternal dietary changes have little effect on overall vitamin K status of newborn
  • maternal vitamin K supplements of 5mg/day (800% RDA) has been shown in one study to raise infant serum levels to near formula-fed levels, but there is no FDA approved multi-vitamin that contains this amount of vitamin K

  Addressing Parental Concerns

  Does vitamin K cause cancer?

  • One study published in the British Medical Journal in 1990 raised this concern, suggesting that the risk of cancer was doubled in babies who received vitamin K at birth.
  • Many studies since then in Europe and in US have refuted this claim and found no association between the two. Only one other study (aside from 1992 paper from the same author) suggested a possible association between vitamin K and the risk of ALL.
  • There is good consensus among experts that IM vitamin K prophylaxis is safe and is not associated with childhood cancer.

  Does vitamin K cause jaundice?

  • There were reports of hemolytic anemia and hyperbilirubinemia severe enough to cause kernicterus in the mid 1950s with high doses (50mg) of vitamin K2 (menadione). As a result, use of this form of vitamin K was abandoned. We now give infants vitamin K1 (phytonadione). Vitamin K1 has been associated with hyperbilirubinemia only in extremely high doses (25 – 30mg). The effect was particularly seen in premies, though it was also present - albeit to a lesser degree - in term infants. This has not been a problem when vitamin K1 is given in normal therapeutic doses (0.5 - 1mg).

  What other side effects have been reported?

  • Anaphylaxis, though most common after IV infusion, has rarely been reported with IM injection.
  • Scleroderma-like patch at the site of injection has been reported primarily in adults after repeated injections, though there are reports of 7 infants with similar dermatologic reactions (again, millions of doses are given without problems).

  JAbyMD, reviewed 5/06

  References

  • American Academy of Pediatrics, Committee on Fetus and Newborn. Controversies Concerning Vitamin K and the Newborn. Pediatrics 2003 July; 112(1):191-2.
  • Ross, JA, Davies SM. Vitamin K prophylaxis and childhood cancer. Med Pediatr Oncol. 2000 Jun;34(6):434-7.
  • Cornelissen, M., et al. Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K. Eur J Pediatr. 1997 Feb; 156(2):126-30.
  • Greer, FR, et al. Improving the vitamin K status of breastfeeding infants with maternal vitamin K supplements. Pediatr. 1997 Jan;99(1).