Haemorrhagic Disease of Newborn

Synonym: Vitamin K deficient bleeding in the newborn.

Haemorrhagic disease of the newborn is due to deficiency of clotting factors as a result of vitamin K deficiency. Haemorrhagic disease of the newborn was first described over a hundred years ago¹ but its relationship to vitamin K was not realised until 40 years later. Vitamin K is required for the production of clotting factors II, VII, IX and X. It is involved in the normal clotting of blood, it is present in some plants and is also synthesized 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 (HDN). The body has very limited ability to store the vitamin.

• If HDN occurs within 24 hours of birth, it is called early HDN
• If it happens between day 1 and day 7 of life, it is called classic HDN
• Between weeks 2 and 12 of life, it is called late HDN.

Late HDN 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 new born babies.

The incidence of late HDN 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 HDN and 56% late HDN.² This survey sought all cases of HDN 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.

• Children who are entirely breastfed have a 20 times greater risk of developing HDN 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 breastfed 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 HDN.
• Warm environmental temperatures also predispose babies to developing late HDN.
• Unsuspected liver disease, especially alpha-one-antitrypsin deficiency increases the risk.
• Malabsorption of fat soluble vitamins due to diarrhoea, coeliac disease or cystic fibrosis.

Early Haemorrhagic Disease of the Newborn

Early HDN, is limited to babies whose mothers received various drugs during pregnancy. Early HDN 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 Haemorrhagic Disease of the Newborn

Classic HDN occurs both in babies whose mothers were receiving various forms of medication during pregnancy, and also babies who are exclusively breast fed. The bleeding in classic HDN 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 Haemorrhagic Disease of the Newborn

Late HDN occurs predominantly in exclusively breastfed 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 HDN produces the greatest morbidity and mortality amongst the infants due to sudden bleeding into the CNS. The results may include³:-

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

If HDN 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 or bottle fed

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

• 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, to ascertain the extent of the bleed.

Immediate Management

• When HDN 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 injection can produce a haematoma in a coagulation disorder and the intravenous route can produce an anaphylactoid reaction.
• 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

Babies with late HDN 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, they may require surgery or intracranial shunts to reduce intracranial pressure.

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

• In a review of all reported cases of HDN up to 1993, 14% of all cases died and 40% had long term neurological deficit.⁴
• Most severe cases are late HDN. Mortality in this type can be 25 to 50%.

All forms of HDN 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 HDN, and where possible therapeutic regimes are altered.

The greatest reduction has resulted from the routine administration of vitamin K in all new born babies, usually at birth. This is given either in the form of an intramuscular injection or a series of oral supplements and, as a consequence, HDN is now rarely seen in the UK and other countries where this policy has been adopted. The intramuscular route is preferred⁵ 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.⁶

A Cochrane review⁷ concluded that a single dose (1.0 mg) of intramuscular vitamin K after birth is effective in the prevention of classic HDN. Either intramuscular or oral (1.0 mg) vitamin K prophylaxis improves biochemical indices of coagulation status at 1-7 days. Neither intramuscular nor oral vitamin K has been tested in randomized trials with respect to effect on late HDN. Oral vitamin K, either single or multiple dose, has not been tested in randomized trials for its effect on either classic or late HDN. In babies before 32 weeks gestation 0.5mg would appear to suffice.⁸