1. VITAMIN K DEFICIENCY BLEEDING
Lydia Snyder
PGY 1
February 19, 2010

2. What year did the AAP recommend IM Vitamin K for all newborns?
1961

3. Baby H Term male repeat C- section Apgars 9, 9 B.W. 4075 grams LGA
Accuchecks WNL
Breast feeding
22 yo G2P2 mom, married
ROM 6 hours
Maternal labs: Rubella Immune, RPR NR, Hep B neg, GC,Chlamydia unknown, HIV neg, GBS neg
Maternal blood type: A+

4. Parents decline Hepatitis B, erythromycin ointment, and Vitamin K shot
No, Thanks
Parents decline Hepatitis B, erythromycin ointment, and Vitamin K shot
What prompted parents to make this decision.? Stated they had done research on the topic. What is out in the media?
Newborn routine. Think about….Why do we give Vitamin K? How big of a deal is it if they don’t get vitamin K?

5. Objectives 1. Role of Vitamin K
2. Neonatal predisposition to Vitamin K Deficiency bleeding
3. Types of Vitamin K Deficiency bleeding
4. Efficacy of Oral versus IM Vitamin K
5. Controversy/fears regarding Vitamin K
6. AAP recommendations

6. Role of Vitamin K Anti-hemorrhagic factor
Essential cofactor needed to synthesize functional clotting factor II, VII, IX, X
Phylloquinone (K1) : Plants
Menaquinone (K2): Intestinal bacteria
Fat soluble: Requires bile salts for absorption
Vit k is cofactor for gamma-glutamyl carboxylase enzyme that converts glutamate residues in protein to gamma carboyxglutamate necessary for protein function.

7. Why are neonates vitamin K deficient?
All newborns have low concentration of Vitamin K
1. Poor placental transfer
2. Sterile newborn gut
3. Low amount in breast milk
4. Immature liver
Phylloquinone Amount in colostrum : 2microgram/L Amount in mature human milk, 1 microgram/L
Amount in formula ~60 microgram/L
Per day average infant gets 1 microgram breast feeding vs. 50 microgram formula feeding

8. Vitamin K deficiency bleeding
Hemorrhagic Disease of the Newborn
Low level of Vitamin K dependent clotting factors: % of plasma concentration of adults
Incidence Classical type: %
Incidence Late type: Europe 5-7 per 100,000 live births
Diagnosis: Bleeding +
Prolonged PT
Normal fibrinogen and platelet count
Rapid correction of PT/bleeding cessation after vitamin K
Vit k dependent clotting factors have short half life, Body has low capacity for storing vit k
Clotting factors reach adult values by 6 weeks of age.
Giving vit K after birth prevents further drop in factors.
Vit K to mother prenatally does not prevent infant deficiency
DX: prolonged PT, normal fibrinogen and platelet count, rapid correction of PT after vitamin K

9. 3 types: Vitamin K deficiency Bleeding
Early
1st 24 hours
Maternal drug use: Warfarin, Phenytoin, Rifampin, INH
Bleeding: Scalp, umbilical, GI, intracranial
Classical
DOL1-7
Idiopathic, Poor breast feeding
Bleeding: Umbilical, circmumcision, Mucosal(ENT), GI, intracranial
Late
Week 2- 6 months. Usually 2-12 weeks
Idiopathic, Hepatobiliary dysfunction, Malabsorption disease
Bleeding: Intracranial(30-60%), skin, GI
Although incidence is low, mortality/morbidity are high if no vitamin k is given to newborns.
Especially if they have Intracranial hemorrhage! Mortality of %. High morbidity with neurological complications.
Cephalohematoma, subgaleal. Drugs that interfere with vitamin k
Late: biliary atresia, alpha 1 antirypsin deficiency, cystic fibrosis, abx therapy sometimes

10. Oral versus IM Vitamin K
Pros:
Noninvasive
Not painful
Cheaper
Cons:
Compliance
Multiple doses
Unpredictable absorption
Less effective in preventing late VKDB
Pros:
1 time dose
Effective prevention of classical and late VKDB
Cons:
Invasive
Painful
Hematoma at site
Worldwide practice varies from one country to another.
IM: preventative except for rare cases of malabsorption syndrome
IM higher peak, sustained longer
IM reduces VKDB classical and late to <0.2 per 100,000

11. Efficacy of various form/doses
Cornelissen et al. surveillance study in Netherlands, Germany, Australia, Switzerland incidence of late VKDB
Australia: 325,000 newborns (1 mg IM Vitamin K)  0 cases
Australia: 325,000 newborns (1mg birth, DOL 3-5, DOL )  8 cases, 1.5 per
Germany:1,200,000 newborns (1 mg birth, DOL 4-10, DOL ) 32 cases, 1.8 per
Switzerland: 83,000 newborns ( 2mg oral mixed micellar preparation DOL 1 &4)  4 cases, 1.2 per
Netherlands: 439,000 newborns (1mg birth + 25µg daily week 1-13): 5 cases, 0 per
On prevention of late VKDB mid 1990’s. population healthy well appearing newborns.
Incidence without any prophylaxis is 5-7 per 100,000
Incomplete prophylaxis, lack compliance increased incidence risk
Netherlands: does not provide prevention in those with biliary atresia. Poor absorption

12. UVA Newborn Nursery Routine: Single 1 mg IM Vitamin K
If parents decline: Oral Vitamin K 2 birth, Day 7, Day 30
What about Baby H?

13. Vitamin K Controversy: Link to Cancer ?
1990- Golding et al. prospective cohort study: factors associated with childhood cancer
33 children with cancer out of 16, 193 births in Great Britain in 1970
Logistic regression analysis: Independent significant factors were maternal smoking and IM vitamin K
Outcome: Potential increased risk of childhood cancer with intramuscular vitamin K use in newborns
Golding also did case control study in 1992 concluding an associated risk of cancer with IM vit K, not oral. 2x risk of leukemia.
Other cancers included: Wilms, lymphoma, brain tumor, retinoblastoma, sarcoma of humerus
Logistic regression predict discrete outcome from set of variables
A prospective study watches for outcomes, such as the development of a disease, during the study period and relates this to other factors such as suspected risk or protection factor(s). The study usually involves taking a cohort of subjects and watching them over a long period

14. Vitamin K Controversy: Link to Cancer ?
Draper and Stiller: Data from National Registry of childhood tumors in Great Britain failed to show association between increase in IM vitamin K use and occurrence of childhood leukemia
> 10 studies (ecologic, case control, and cohort) concluded there is no association between Vitamin K and increased risk of childhood cancer
Vitamin K Ad Hoc Task Force of AAP 2003: no association
4 Ecologic studies- no evidence that intro of IM vit K resulted in increase in childhood leukemia incidence
4/5 Case control – only 1 of 5 showed increased risk of ALL only in age 1-5
2 Cohort studies- no association
1 pooled analysis of 6 case control studies- no association
1 UK national population based case control study- most comprehensive- no association
AAP reviewed Golding et al reports and US incidence of leukemia- concluded no association b/w vit k and cancer

15. AAP Policy Statement on Vitamin K
Vitamin K proven to decrease VKDB
Vitamin K1 should be given to all newborns as a single intramuscular dose of 0.5 to 1 mg
Promote awareness of risks of late VKDB with inadequate vitamin K prophylaxis with oral form
No proven risk of childhood cancer with IM Vitamin K

16. Resources
Golding J, Paterson M, Kinlen U. Factors associated with childhood cancer in a national cohort study. Br I Cancer. 1990;62:
Golding J, Greenwood R, Birminham K, Mott M. Childhood cancer, intramuscular vitamin K, and pethidine given during labour. Br Med J.1992;305:
Draper GJ, Stiller CA. Intramuscular vitamin K and childhood cancer. Br Med J. 1992;305:709
American Academy of Pediatrics, Vitamin K Ad Hoc Task Force. Controversies concerning vitamin K and the newborn. Pediatrics. 1993;91: 1001–1003
Ross JA, Davies SM. Vitamin K prophylaxis and childhood cancer. Med Pediatr Oncol. 2000;34:434–437
Cornelissen M, Von Kries R, Loughnan P, Schubiger G. Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K. Eur J Pediatr. 1997;156:126–130
American Academy of Pediatrics, Controversies Concerning Vitamin K and the Newborn Pediatrics 2003;112;
von Kries R, Hachmeister A, Göbel U. Can 3 oral 2 mg doses of vitamin K effectively prevent late vitamin K deficiency bleeding? Eur J Pediatr 1999;158:S183–6.
Shearer, Martin, Vitamin K deficiency bleeding (VKDB) in early infancy, Blood Reviews 23 (2009) 49–59
Fear NT, Roman E, Ansell E, Simpson J, Day N, Eden OB. United Kingdom Childhood Cancer Study Investigators. Vitamin K and childhood cancer: a report from the United Kingdom childhood cancer study. Br J Cancer 2003;89:1228–31.
Klebanoff MA, Read JS, Mills JL, Shiono PH. The risk of childhood cancer after neonatal exposure to vitamin K. N Engl J Med1993;329:905–908.
Passmore SJ, Draper G, Brownbill P, Kroll M. Case-control studies of relation between childhood cancer and neonatal vitamin K administration. Br Med J 1998;316:178–184.