Excerpt from Hemorrhagic Disease of Newborn

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Background

The more appropriate term for hemorrhagic disease of newborn is vitamin K deficiency bleeding (VKDB). Historically, all bleeding disorders in the newborn were grouped together under the diagnosis of hemorrhagic disease of the newborn (HDN). With methods available today for the accurate diagnosis of other factor deficiency states and immune thrombocytopenias, VKDB can be distinguished from other disorders by exclusion and appropriate analysis of these other factors involved in coagulation.

Vitamin K is a fat-soluble vitamin that can be absorbed from the GI tract in the presence of bile salts. Vitamin K is required for the production of coagulation factors II, VII, IX, and X in the liver. Because of the short half-life of these factors, and the small amounts of vitamin K that can be stored in the body, inadequate intake of vitamin K can result in deficiency in a short period of time. PIVKA, inactive precursor proteins induced in vitamin K's absence, are measurable and can be used as an indicator of vitamin K deficiency.

The 3 forms of vitamin K are as follows:

• K1: Phylloquinone, found in dairy products, green vegetables, and vegetable oils, is an aqueous, colloidal solution of vitamin K1.
• K2: Menaquinone, which is synthesized by gut flora.
• K3: Menadione is a synthetic, water soluble form that is no longer used medically because of its ability to produce hemolytic anemia.

Pathophysiology

Newborns are relatively vitamin K deficient for a variety of reasons. Factors that can contribute to this deficiency include low vitamin K stores at birth, poor placental transfer of vitamin K, low levels of vitamin K in breast milk, and sterility of the gut. Because standard commercial infant formulas contain supplemental vitamin K, VKDB is almost exclusively a problem of breastfed infants. Infants with inadequate intake are at higher risk.

The most common sites of bleeding are the umbilicus, mucous membranes, GI tract, circumcision, and venipunctures. Hematomas at sites of trauma, such as large cephalohematomas and bruising, are also common findings. Intracranial bleeding can occur and is the main cause of mortality and long-term morbidity.

Frequency

United States

In the United States, routine intramuscular administration of vitamin K immediately after birth has made VKDB an uncommon occurrence. The frequency of VKDB is variably reported, from 0.25-1.7% in the first week of life. The frequency in a given US population depends upon the frequency of breastfeeding. Late VKDB (2-12 wk) appears to be prevented with parenteral administration of vitamin K, as well.

International

The frequency of VKDB in countries outside the United States varies with the use of vitamin K prophylaxis, the efficacy of prophylaxis programs, frequency of breastfeeding, and the vitamin K content of locally available formulas.

Late VKDB has fallen from 4.4-7.2/100,000 births to 1.4-6.4/100,000 births in reports from Asia and Europe after regimens for prophylaxis were instituted.

Mortality/Morbidity

Intracranial hemorrhage (ICH) is uncommon in classic VKDB but can be observed in more than 50% of infants with late-onset VKDB. ICH is responsible for nearly all mortality and all long-term sequelae resulting from VKDB.

Race

No racial predilection exists, but breastfeeding practices can result in apparent racial disparities.

Sex

No apparent sex predilection exists.

Age

VKDB can occur in 3 general time frames.

• Early onset, at less than 24 hours after birth, rarely occurs and is almost always associated with maternal medications that interfere with vitamin K, such as anticonvulsants, anticoagulants, and antibiotics. Postnatal administration of vitamin K has no effect in preventing early-onset disease. Maternal vitamin K supplementation that is administered prenatally may prevent this form of VKDB.
• The classic onset of VKDB is 2-7 days after birth in breastfed infants.
• Late-onset VKDB occurs after 2 weeks of life. In addition to breastfeeding, risk factors include diarrhea, hepatitis, cystic fibrosis (CF), celiac disease, and alpha1-antitrypin deficiency or absence of prophylaxis in otherwise healthy infants. Late-onset VKDB tends to be more severe than early-onset or classic disease and has a high frequency of ICH.

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