Vitamin K deficiency bleeding in infants
In infants up to around age 6 months, vitamin K deficiency, although rare, represents a significant public health problem throughout the world. The deficiency syndrome is traditionally known as haemorrhagic disease of the newborn or more recently, to give a better definition of the cause, vitamin K deficiency bleeding (VKDB).
The time of onset of VKDB is more unpredictable than previously supposed and it is now useful to recognise three syndromes: early, classic, and late. Until the 1960s, VKDB was considered to be solely a problem of the first week of life. Then, in 1966, came the first reports from Thailand of a new vitamin K deficiency syndrome that typically presented between 1 and 2 months of life and is now termed late VKDB. In 1977 Bhanchet and colleagues, who had first described this syndrome, summarised their studies of 93 affected Thai infants, establishing the idiopathic history, preponderance of breast-fed infants (98 percent), and high incidence of intracranial bleeding (63 percent).
More reports from South East Asia and Australia followed, and in 1983 McNinch et al. reported the return of VKDB in the United Kingdom. This increased incidence was ascribed to a decrease in the practice of vitamin K prophylaxis and to an increased trend towards exclusive human milk feeding. Human milk has lower concentrations of vitamin K than do infant milk formulas.
Without vitamin K prophylaxis, the incidence of late VKDB (per 100,000 births), based on acceptable surveillance data, has been estimated to be 4.4 in the United Kingdom, 7.2 in Germany, and as high as 72 in Thailand. Of real concern is that late VKDB, unlike the classic form, has a high incidence of death or severe and permanent brain damage resulting from intracranial haemorrhage.
Epidemiologic studies worldwide have identified two major risk factors for both classic and late VKDB: exclusive human milk feeding and the failure to give any vitamin K prophylaxis. The increased risk for infants fed human milk compared with formula milk is probably related to the relatively low concentrations of vitamin K (phylloquinone) in breast milk compared with formula milks. For classic VKDB, studies using the detection of under-carboxylated prothrombin or proteins induced by vitamin K absence (PIVKA)-II as a marker of sub-clinical vitamin K deficiency have suggested that it is the low cumulative intake of human milk in the first week of life rather than an abnormally low milk concentration per se that seems to be of greater relevance. Thus, classic VKDB may be related, at least in part, to a failure to establish early breast-feeding.
For late VKDB other factors seem to be important because the deficiency syndrome occurs when breast-feeding is well established and mothers of affected infants seem to have normal concentrations of vitamin K in their milk. Instead some (although not all) infants who develop late haemorrhagic disease of the newborn are later found to have abnormalities of liver function that may affect their bile acid production and result in a degree of malabsorption of vitamin K. The degree of cholestasis may be mild and its course may be transient and self-correcting, but affected infants will have increased dietary requirements for vitamin K because of a reduced absorption efficiency.
Vitamin K prophylaxis in infants
Because bleeding can occur spontaneously and because no screening test is available, it is now common paediatric practice to protect all infants by giving vitamin K supplements in the immediate perinatal period. Vitamin K prophylaxis has had a chequered history but in recent years has become a high-profile issue of public health in many countries throughout the world. The reasons for this are twofold. First there is now a convincing body of evidence showing that without vitamin K prophylaxis, infants have a small but real risk of dying from or being permanently brain damaged by vitamin K deficiency in the first 6 months of life.
The other, much less certain evidence stems from a reported epidemiologic association between vitamin K given intramuscularly (but not orally) and the later development of childhood cancer. The debate, both scientific and public, which followed this and other publications has led to an increase in the use of multiple oral supplements instead of the traditional single intramuscular injection (usually of 1 mg of phylloquinone) given at birth. Although most of the subsequent epidemiologic studies have not confirmed any cancer link with vitamin K, the issue is still not resolved.
Vitamin K in adults
In adults, primary vitamin K–deficient states that manifest as bleeding are almost unknown except when the absorption of the vitamin is impaired as a result of an underlying pathology.
References:
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