Synonym: haemorrhagic disease of the newborn (HDN), vitamin K deficient bleeding in the newborn

Vitamin K deficiency bleeding (VKDB) is now the preferred term for haemorrhagic disease of the newborn (HDN). This is due to deficiency of clotting factors as a result of vitamin K deficiency. VKDB was first described over a hundred years ago but its relationship to vitamin K was not realised until 40 years later.¹ Vitamin K is required for the production of clotting factors II, VII, IX and X. It is involved in the normal clotting of blood, is present in some plants and is also synthesised by some E. coli in the gut. All newborn infants have low levels of vitamin K and are at risk of developing haemorrhagic disease of the newborn. The body has very limited ability to store the vitamin.

• Early VKDB occurs within 24 hours of birth.
• Classic VKDB happens between day 1 and day 7 of life.
• Late VKDB occurs between week 2 and week 12 of life.

Late VKDB can result in significant morbidity and mortality due to intracranial haemorrhage and has resulted in most developed countries having in place a protocol for giving supplemental vitamin K to all newborn babies.

Epidemiology

The incidence of late VKDB in the developed world is about 4-25 per 100,000 births. In the UK the incidence is reported as 8.6 per 100,000 of which 44% were classic VKDB and 56% late VKDB.² This survey sought all cases of VKDB in the British Isles, including the Republic of Ireland, from December 1987 to March 1990. Only 27 cases were found, of which 25 were confirmed and 2 probable.

Sex incidence is equal.

Prophylaxis has reduced the incidence considerably.

Risk factors

• Children who are entirely breast-fed have a 20 times greater risk of developing VKDB than those who receive formula milk, due to the low level of vitamin K in breast milk and also the low levels of bacteria which help to synthesize vitamin K in the guts of breast-fed babies.
• Several drugs such as isoniazid, rifampicin, anticoagulants and anticonvulsant agents, which have been taken by the mother, make the infant at risk of developing early VKDB.
• Warm environmental temperatures also predispose babies to developing late VKDB.
• Unsuspected liver disease, especially alpha-one-antitrypsin deficiency increases the risk.
• Malabsorption of fat-soluble vitamins due to diarrhoea, coeliac disease or cystic fibrosis.

Presentation

Early vitamin K deficiency bleeding

Early VKDB is limited to babies whose mothers received various drugs during pregnancy (see Risk factors above). It presents with bleeding at sites related to the trauma of birth, such as:

• Bleeding from scalp monitor site
• Cephalhaematoma, especially after ventouse delivery
• Intracranial bleeding after a traumatic delivery may cause irritability and convulsions
• Intrathoracic bleeding can produce blood-stained sputum, with or without respiratory distress
• Intra-abdominal bleeding may present as melaena
• Tachycardia due to exsanguination

Classic vitamin K deficiency bleeding

Classic VKDB occurs both in babies whose mothers were receiving various forms of medication during pregnancy and also in babies who are exclusively breast-fed. The bleeding in classic VKDB most often affects non-vital organs such as:

• Gastrointestinal bleeding
• Bleeding from the skin and mucous membranes, e.g. nose and gums
• Prolonged bleeding following circumcision
• Bleeding from the umbilical stump

Late vitamin K deficiency bleeding

Late VKDB occurs predominantly in exclusively breast-fed infants, but may also occur in babies with malabsorption syndromes who are unable to absorb the fat-soluble vitamin K. Children on long-term antibiotics may also develop altered gut flora with decreased synthesis of vitamin K by E. coli. Late VKDB produces the greatest morbidity and mortality amongst the infants due to sudden bleeding into the central nervous system. The results may include:³

• Subarachnoid haemorrhage (90%)
• Subdural haemorrhage
• Parenchymal haemorrhage
• Intraventricular haemorrhage
• Irritability
• Convulsions
• Weakness of arms and/or legs
• Blindness
• Coma

History

If VKDB is suspected, it is important to go over certain aspects of history:

• Drugs taken in pregnancy
• Gestation at delivery
• Type and length of delivery
• Feeding history, especially if breast-fed or bottle-fed

Differential diagnosis

• Haemophilia (boys)
• Trauma
• Accidental or non-accidental injury
• Disseminated intravascular coagulopathy
• Thrombocytopenia including maternal isoimmune thrombocytopenia
• Necrotising enterocolitis
• Intussusception

Investigations

• FBC
• Clotting screen, including prothrombin time, coagulation time and partial thromboplastin time.
• CXR or ultrasound scan may confirm intrathoracic bleed.
• CT or MRI scan if intracranial haemorrhage or other major haemorrhage suspected.

Management

Immediate management

• When VKDB is suspected, vitamin K should be given as a supplement as soon as possible. This will result in a reduction in the bleeding time within a few hours. The injection should be subcutaneous. An intramuscular (IM) injection can produce a haematoma in a coagulation disorder and the intravenous route can produce an anaphylactoid reaction.
• Infants of mothers taking drugs that inhibit vitamin K are at risk of early VKDB and should receive 1 mg IM as soon as possible after birth.⁴ Classic VKDB is prevented by IM as well as by oral administration of 1 mg vitamin K.⁵ In babies before 32 weeks' gestation, 0.5 mg would appear to suffice.⁶
• Babies with severe bleeding or intracranial haemorrhage may require fresh frozen plasma to be given in addition to vitamin K in order to arrest the bleeding as soon as possible.
• Babies who have lost a large amount of their circulating volume may require transfusions with whole blood.

Long-term management

In exclusively breast-fed infants, single IM administration at birth is also effective in preventing (rare) late VKDB, but single oral administration is not. If given orally, prophylaxis should be continued by either weekly administration of 1 mg till 12 weeks or repeating 2 mg at weeks 1 and 4.⁴

Babies with late VKDB who have suffered intracranial bleeds will require assessment from a specialist team to help minimise the long-term sequelae of the bleed. They will require early and continuing physiotherapy to minimise spasticity and retain function; they may require nutritional assistance if unable to swallow or suck, and they may require surgery or intracranial shunts to reduce intracranial pressure.

Complications

The complications of VKDB mainly relate to bleeds involving the central nervous system, and 40% of children who survive will have some form of long-term neurological handicap

Prognosis

• In a review of all reported cases of VKDB up to 1993, 14% of all cases died and 40% had long-term neurological deficit.⁷
• Most severe cases are late VKDB. Mortality in this type can be 25 to 50%.

Prevention

All forms of VKDB are now far less common due to understanding of the aetiology. Routine antenatal screening of all mothers has allowed for the early identification of babies who may be at risk of early VKDB, and where possible therapeutic regimes are altered.

The greatest reduction has resulted from the routine administration of vitamin K in all newborn babies, usually at birth. This is given either in the form of an IM injection or a series of oral supplements and, as a consequence, VKDB is now rarely seen in the UK and other countries where this policy has been adopted. The IM route is preferred⁸ and seems to be more effective.² In the early 1990s there was a suggestion that administration of vitamin K was associated with an increased risk of childhood cancers but larger studies have failed to substantiate this. Expert opinion is very much that benefit outweighs any adverse effects.⁹

Document references

1. Townsend C, The Haemorrhagic Disease of the Newborn. Arch Pediatr 1894, 11:559
2. McNinch AW, Tripp JH; Haemorrhagic disease of the newborn in the British Isles: two year prospective study. BMJ. 1991 Nov 2;303(6810):1105-9. [abstract]
3. Chaou WT, Chou ML, Eitzman DV; Intracranial hemorrhage and vitamin K deficiency in early infancy. J Pediatr. 1984 Dec;105(6):880-4. [abstract]
4. Van Winckel M, De Bruyne R, Van De Velde S, et al; Vitamin K, an update for the paediatrician. Eur J Pediatr. 2009 Feb;168(2):127-34. Epub 2008 Nov 4. [abstract]
5. Puckett RM, Offringa M; Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev. 2000;(4):CD002776. [abstract]
6. Costakos DT, Greer FR, Love LA, et al; Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg. Am J Perinatol. 2003 Nov;20(8):485-90. [abstract]
7. Loughnan PM, McDougall PN; Epidemiology of late onset haemorrhagic disease: a pooled data analysis. J Paediatr Child Health. 1993 Jun;29(3):177-81.
8. No authors listed; Controversies concerning vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics. 2003 Jul;112(1 Pt 1):191-2. [abstract]
9. Zipursky A; Prevention of vitamin K deficiency bleeding in newborns. Br J Haematol. 1999 Mar;104(3):430-7. [abstract]

Internet and further reading

• Neonatal Bleeding Disorders (pdf) - US Site
• Nimavat DJ; Sherman MP; Hemorrhagic Disease of Newborn. eMedicine. September 2009.
• Vitamin K deficiency and haemorrhagic disease of the newborn, UNICEF. (1997)

Acknowledgements