Hemorrhagic disease in newborn

Hemorrhagic disease in newborn is now called vitamin K deficiency bleeding, is a bleeding problem that occurs in some newborns during the first few days of life. Hemorrhagic disease of the newborn can separate into three categories based on the timing of the presentation. Early hemorrhagic disease in newborn presents within 24 hours after birth, classic hemorrhagic disease in newborn presents within the first week, and late hemorrhagic disease in newborn presents between one to twelve weeks of life ¹⁾. Vitamin K deficiency bleeding can cause bruising or bleeding in nearly every organ of the body. Almost half of vitamin K deficiency bleeding cases involve bleeding in the brain and brain damage.

Vitamin K refers to a group of fat-soluble compounds. There are several vitamin K-dependent proteins involved in blood clotting, bone development, and cardiovascular health. Vitamin K deficiency can contribute to significant bleeding, poor bone development, osteoporosis, and increased cardiovascular disease ²⁾. According to the National Academy of Science Food and Nutrition Board, the dietary requirements are based on the intake of healthy adults, and the adequate intake is 120 and 90 ug/day for men and women, respectively ³⁾.

Babies are at risk for vitamin K deficiency bleeding for the first 6 months of life. That’s because most of the vitamin K the body makes comes from the foods you eat and the healthy bacteria in your intestines. Until they start eating solid food at about 6 months of age, babies don’t have enough naturally produced vitamin K. And nursing moms don’t pass enough vitamin K in their breast milk to protect their babies from vitamin K deficiency bleeding.

Who is affected by vitamin K deficiency bleeding?

Vitamin K deficiency may result in bleeding in a very small percentage of babies. Babies at risk for developing vitamin K deficiency bleeding include the following:

• Babies who do not receive preventive vitamin K in an injection at birth
• Exclusively breastfed babies (breast milk contains less vitamin K than cow’s milk formula)
• Babies whose mothers take anticonvulsants (for seizures) and anticoagulants (for clotting disorders).

How often are babies affected with vitamin K deficiency bleeding?

Since babies can be affected until they are 6 months old, healthcare providers divide vitamin K deficiency bleeding into three types; early, classical and late. The chart below helps explain these three different types.

• Early and classical vitamin K deficiency bleeding are more common, occurring in 1 in 60 to 1 in 250 newborns, although the risk is much higher for early vitamin K deficiency bleeding among those infants whose mothers used certain medications during the pregnancy.
• Late vitamin K deficiency bleeding is rarer, occurring in 1 in 14,000 to 1 in 25,000 infants ⁴⁾.
• Infants who do not receive a vitamin K shot at birth are 81 times more likely to develop late vitamin K deficiency bleeding than infants who do receive a vitamin K shot at birth ⁵⁾.

What can I do to prevent my baby from getting vitamin K deficiency bleeding?

The good news is that vitamin K deficiency bleeding is easily prevented by giving babies a vitamin K shot into a muscle in the thigh. One shot given just after birth will protect your baby from vitamin K deficiency bleeding. In order to provide for immediate bonding and contact between the newborn and mother, giving the vitamin K shot can be delayed up to 6 hours after birth.

Why do some parents delay or refuse their newborn’s vitamin K injection?

A study in the early 1990s suggested a link between the vitamin K shot and childhood cancer. Many studies since then have found no connection between vitamin K and cancer. But that misinformation is still readily available online. As a result, some families are delaying or skipping the vitamin K shot or looking for other ways for their infants to receive vitamin K.

Since 1961, the American Academy of Pediatrics has recommended supplementing low levels of vitamin K in newborns with a single shot of vitamin K given at birth ⁶⁾.

The American Academy of Pediatrics recommendations on Vitamin K ⁷⁾:

• Vitamin K should be given to all newborn infants as a single, intramuscular dose of 0.5 to 1 mg.
• Additional research should be conducted on the efficacy, safety, and bioavailability of oral vitamin K to prevent late vitamin K deficiency bleeding.
• Health care professionals should promote awareness among families of the risks of late vitamin K deficiency bleeding associated with inadequate vitamin K prophylaxis from current oral dosage regimens, particularly for newborns who are breastfed.

Some European countries let families choose an oral form of vitamin K. But this is far less effective than the shot at preventing bleeding, especially in the brain. Oral vitamin K is not available for newborns in the United States.

No parent enjoys the thought of their little one getting a shot. But a single injection of vitamin K can protect a baby from a serious, even deadly preventable bleeding disorder.

Why do ALL babies need a vitamin K shot, can’t I just wait to see if my baby needs it?

No, waiting to see if your baby needs a vitamin K shot may be too late. Babies can bleed into their intestines or brain where parents can’t see the bleeding to know that something is wrong. This can delay medical care and lead to serious and life-threatening consequences. All babies are born with very low levels of vitamin K because it doesn’t cross the placenta well. Breast milk contains only small amounts of vitamin K. That means that ALL newborns have low levels of vitamin K, so they need vitamin K from another source. A vitamin K shot is the best way to make sure all babies have enough vitamin K. Newborns who do not get a vitamin K shot are 81 times more likely to develop severe bleeding than those who get the shot.

Overall, what are the risks and benefits of the vitamin K shot?

The risks of the vitamin K shot are the same risks that are part of getting most any other shot. These include pain or even bruising or swelling at the place where the shot is given. A few cases of skin scarring at the site of injection have been reported. Only a single case of allergic reaction in an infant has been reported, so this is extremely rare. Reports of anaphylactoid reactions are rare but are an estimated incidence of 3/10,000 doses, and associations point to the intravenous route in more severe cases. The emulsifying agents, specifically polyoxyethylated castor oil, has been implicated as the cause of the anaphylactoid reaction in most cases ⁸⁾.

Although there have been concerns about some other risks, like a risk for childhood cancer or risks because of additional ingredients, none of these risks have been proven by scientific studies.

The main benefit of the vitamin K shot is that it can protect your baby from vitamin K deficiency bleeding, a dangerous condition that can cause long-term disability or death. In addition, the diagnosis and treatment of vitamin K deficiency bleeding often includes multiple and sometimes painful procedures, such as blood draws, CT scans, blood transfusions, or anesthesia and surgery.

The American Academy of Pediatrics has recommended the Vitamin K shot since 1961, and has repeatedly stood by that recommendation because the risks of the shot don’t outweigh the risks of vitamin K deficiency bleeding, which are based on decades of evidence and decades of experience with babies who were hospitalized or died from vitamin K deficiency bleeding.

Your child’s doctor is the best person to talk to about vitamin K. Like you, your child’s doctor wants to see your children grow up safe and healthy and wants to support your efforts to make the best decisions for their health. If you have concerns about vitamin K, talk to your child’s doctor.

Can the other ingredients in the shot cause problems for my baby? Do we really know that the vitamin K shot is safe?

Yes, the vitamin K shot is safe. Vitamin K is the main ingredient in the shot. The other ingredients make the vitamin K safe to give as a shot. One ingredient keeps the vitamin K mixed in the liquid; another keeps the liquid from being too acidic. One of the ingredients is benzyl alcohol, a preservative. Benzyl alcohol is a common ingredient in many medications.

In the 1980s, doctors recognized that very premature infants who were in neonatal intensive care units might become sick from benzyl alcohol toxicity because many of the medicines and fluids needed for their intensive care contained benzyl alcohol as a preservative. Although the toxicity was only reported for very premature infants, since then doctors have tried to minimize the amount of benzyl-alcohol-containing medications they give. Clearly, the small amount of benzyl alcohol in the vitamin K shot is not enough to be dangerous, even when given in combination with other medications that also contain small amounts of this preservative.

The dose of the shot seems high. Is that too much for my baby?

No, the dose in the vitamin K shot is not too much for babies. The dose of vitamin K in the shot is high compared to the daily requirement of vitamin K. But remember babies don’t have much vitamin K when they are born and won’t have a good supply of vitamin K until they are close to six months old. This is because vitamin K does not cross the placenta and breast milk has very low levels of vitamin K.

The vitamin K shot acts in two ways to increase the vitamin K levels. First, part of the vitamin K goes into the infant’s bloodstream immediately and increases the amount of vitamin K in the blood. This provides enough vitamin K so that the infant’s levels don’t drop dangerously low in the first few days of life. Much of this vitamin K gets stored in the liver and it is used by the clotting system. Second, the rest of the vitamin K is released slowly over the next 2-3 months, providing a steady source of vitamin K until an infant has another source from his or her diet.

Doesn’t the risk of bleeding from low levels of vitamin K only last a few weeks?

No, vitamin K deficiency bleeding can happen to otherwise healthy babies up to 6 months of age. The risk isn’t limited to just the first 7 or 8 days of life and vitamin K deficiency bleeding doesn’t just happen to babies who have difficult births. In 2013, the Centers for Disease Control and Prevention (CDC) investigated 4 cases of infants with bleeding from low levels of vitamin K. All four were over 6 weeks old when the bleeding started and they had been healthy and developing normally. None of them had received a vitamin K shot at birth.

Isn’t vitamin K deficiency bleeding really rare?

Vitamin K deficiency bleeding is rare in the United States, but only because most newborns get the vitamin K shot. Over the past two decades, many countries in Europe have started programs to provide vitamin K at birth – afterward, they all saw declines in the number of cases of vitamin K deficiency bleeding to very low levels. However, in areas of the world where the vitamin K shot isn’t available, vitamin K deficiency bleeding is more common, and many cases of vitamin K deficiency bleeding have been reported from these countries

In the early 1980s in England, some hospitals started giving vitamin K only to newborns that were thought to be at higher risk for bleeding. They then noticed an increase in cases of vitamin K deficiency bleeding. This tells us that giving vitamin K to prevent bleeding is what keeps vitamin K deficiency bleeding a rare condition – when vitamin K is not given to newborns, cases of bleeding occur and vitamin K deficiency bleeding stops being rare.

What happens when babies have low levels of vitamin K and get vitamin K deficiency bleeding?

Babies without enough vitamin K cannot form clots to stop bleeding and they can bleed anywhere in their bodies. The bleeding can happen in their brains or other important organs and can happen quickly. Even though bleeding from low levels of vitamin K or vitamin K deficiency bleeding does not occur often in the United States, it is devastating when it does occur. One out of every five babies with vitamin K deficiency bleeding dies. Of the infants who have late vitamin K deficiency bleeding, about half of them have bleeding into their brains, which can lead to permanent brain damage. Others bleed in their stomach or intestines, or in other parts of the body. Many of the infants need blood transfusions, and some need surgeries.

Can I increase vitamin K in my breast milk by eating different foods or taking multivitamins or vitamin K supplements?

Doctors encourage moms to eat healthy and take multivitamins as needed. Although eating foods high in vitamin K or taking vitamin K supplements can slightly increase the levels of vitamin K in your breast milk, neither can increase levels in breast milk enough to provide all of the vitamin K an infant needs.

When infants are born, their already low levels of vitamin K fall even lower. Infants need enough vitamin K to (a) make up for their extra-low levels, (b) start storing it in the liver for future use, and (c) ensure good bone and blood health. Breast milk – even from mothers supplementing with vitamin K sources – can’t provide enough to do all of these things.

My baby is so little. What can I do to make the vitamin K shot less painful and traumatic?

Babies, just like adults, feel pain, and it is important to reduce even small amounts of discomfort. Babies feel less pain from shots if they are held and allowed to suck.You can ask to hold your baby while the vitamin K shot is given so that your baby can be comforted by you. Breastfeeding while the shot is given and immediately after can be comforting too. All of these are things parents can do to ease pain and soothe their baby.

Remember that if your baby does not get the vitamin K shot, his or her risk of developing severe bleeding is 81 times higher than if he or she got the shot. Diagnosis and treatment of vitamin K deficiency bleeding often involves many painful procedures, including repeated blood draws.

Vitamin K deficiency bleeding causes

Vitamin K is a substance that your body needs to form blood clots and to stop bleeding. You get vitamin K from the food you eat. Some vitamin K is also made by the good bacteria that live in your intestines. Babies are born with very small amounts of vitamin K stored in their bodies, which can lead to serious bleeding problems if not supplemented. A deficiency in vitamin K is the main cause of vitamin K deficiency bleeding.

All infants, regardless of sex, race, or ethnic background, are at higher risk for vitamin K deficiency bleeding until they start eating regular foods, usually at age 4-6 months, and until the normal intestinal bacteria start making vitamin K. This is because:

• At birth, babies have very little vitamin K stored in their bodies because only small amounts pass to them through the placenta from their mothers.
• The good bacteria that produce vitamin K are not yet present in the newborn’s intestines.
• Breast milk contains low amounts of vitamin K, so exclusively breastfed babies don’t get enough vitamin K from the breast milk, alone ⁹⁾.

Clinically significant vitamin K deficiency in adults is very rare and is usually limited to people with malabsorption disorders or those taking drugs that interfere with vitamin K metabolism ¹⁰⁾. In healthy people consuming a varied diet, achieving a vitamin K intake low enough to alter standard clinical measures of blood coagulation is almost impossible ¹¹⁾.

Vitamin K deficiency in the neonatal period is also seen in Hereditary Combined Vitamin K-dependent Clotting Factors Deficiency (VKCFD). Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X as well as natural anticoagulants protein C, protein S and protein Z.  Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is extremely rare with less than 30 cases worldwide and affects males and females equally ¹²⁾.

Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) presents in the newborn period in severe cases similar to vitamin K deficiency bleeding but can present later in life in milder cases. Common presentation occurs with severe spontaneous or surgical bleeding events. History of easy bruising and mucosal bleeding is frequent, and there can be developmental and skeletal abnormalities ¹³⁾.

Risk factors for vitamin K deficiency bleeding

Some things can put infants at a higher risk for developing vitamin K deficiency bleeding. Babies at greater risk include:

• Babies who do not receive a vitamin K shot at birth. The risk is even higher if they are exclusively breastfed.
• Babies whose mothers used certain medications, like isoniazid or medicines to treat seizures. These drugs interfere with how the body uses vitamin K.
• Babies who have liver disease; often they cannot use the vitamin K their body stores.
• Babies who have diarrhea, celiac disease, or cystic fibrosis often have trouble absorbing vitamins, including vitamin K, from the foods they eat.

Vitamin K deficiency bleeding prevention

Prophylaxis in newborns: 1 mg of vitamin K1 by intramuscular injection within 1 hour of birth. Alternatively, 2 mg of vitamin K1 orally at birth, at 4-6 days and at 4-6 weeks. Another alternative oral administration is 2 mg Vitamin K1 at birth and a subsequent weekly dose of 1 mg for three months. Intramuscular injection is preferable for efficacy ¹⁴⁾.

Intramuscular injection of vitamin K is preferable in all infants due to increased efficacy over oral administration. If orally administered and the newborn vomits or regurgitates within 1 hour of dose, repeating oral dose is appropriate. Oral administration should be avoided in preterm infants, infants with cholestasis, or in infants with other intestinal maladies that may interfere with absorption. Additionally, oral administration should be avoided in infants whose mother was taking Vitamin K interfering medications such as anticonvulsants.

The American Academy of Pediatrics recommends giving every newborn baby an injection of vitamin K after delivery (a single, intramuscular dose of 0.5 to 1 milligram (mg) vitamin K1 at birth), as well as supplementing feedings with infant formulas that contain vitamin K, to prevent this potentially life-threatening disease ¹⁵⁾.

Vitamin K deficiency bleeding signs and symptoms

Unfortunately, in the majority of cases of vitamin K deficiency bleeding, there are NO WARNING SIGNS before a life-threatening event starts. The bleeding can occur anywhere on the inside or outside of the body. When the bleeding occurs inside the body, it can be difficult to notice. Commonly, a baby with vitamin K deficiency bleeding will bleed into his or her intestines, or into the brain, which can lead to brain damage and even death. Infants who do not receive the vitamin K shot at birth can develop vitamin K deficiency bleeding at any time up to 6 months of age.

There are three types of vitamin K deficiency bleeding, based on the age of the baby when the bleeding problems start: early, classical and late (see Table 1 below).

The following are the most common signs and symptoms of vitamin K deficiency bleeding in babies. However, each baby may experience symptoms differently. Babies with vitamin K deficiency bleeding might develop any of the following signs and symptoms:

• Blood in the baby’s bowel movements
• Blood in the baby’s urine
• Bleeding around the umbilical cord
• Bruises, especially around the baby’s head and face
• Bleeding from the nose
• Skin color that is paler than before. For darker skinned babies, the gums may appear pale
• After the first 3 weeks of life, the white parts of your baby’s eyes may turn yellow.
• Stool that has blood in it, is black or dark and sticky (also called ‘tarry’), or vomiting blood
• Irritability, seizures, excessive sleepiness, or a lot of vomiting may all be signs of bleeding in the brain.

Table 1. Three types of vitamin K deficiency bleeding

Vitamin K deficiency bleeding complications

Bleeding is the most significant complication because of vitamin K deficiency and is often fatal in infants. Increased fracture rates and cardiac disease may also be a complication. However, more research is required.

Vitamin K deficiency bleeding diagnosis

In addition to a complete medical history and physical examination, a diagnosis is based on signs of bleeding and laboratory tests for blood clotting times. The only clinically significant indicator of vitamin K status is prothrombin time (the time it takes for blood to clot).

Diagnostic criteria for vitamin K deficiency bleeding includes a prothrombin time (PT) greater than or equal to 4 times the normal value and one of the following:

1. Normal or increased platelet count with normal fibrinogen and absent degradation products
2. Prothrombin time normalization within 30 minutes after IV vitamin K administration
3. Increased levels of PIVKA-II ¹⁶⁾.

Prothrombin time has served as an indicator of vitamin K status because of the effect on plasma prothrombin; however, there must be approximately a 50% decrease in prothrombin before the prothrombin time becomes abnormal and is nonspecific ¹⁷⁾. In the absence of vitamin K, there is a production of PIVKA-II and is a sensitive marker for vitamin K deficiency status. PIVKA-II has minimal variability based on other factors such as age that influence vitamin K plasma and serum concentration ¹⁸⁾. Increased PIVKA-II levels start to become apparent in individuals consuming less than 60 mcg of vitamin K per day ¹⁹⁾. At birth, elevated PIVKA-II levels exist in 10-50% of newborns and 70% of non-supplemented healthy infants on day of life 4 or 5 ²⁰⁾. Direct measurement of vitamin K plasma levels show highly variable data influenced by the analytical method, nutritional and metabolic factors, and interference of lipid content. Liquid chromatography-tandem mass spectrometry is useful for determining vitamin K subtypes and concentration levels but is not readily available ²¹⁾.

When hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is suspected as the cause, a research laboratory can be employed to perform genotyping of gamma-glutamyl carboxylase and vitamin K2,3-epoxide reductase complex for confirmation ²²⁾.

Vitamin K deficiency bleeding treatment

Specific treatment for vitamin K deficiency bleeding will be determined by your baby’s doctor.

• Vitamin K deficiency bleeding: 1 to 2 mg vitamin K1 by slow intravenous or subcutaneous infusion. Severe bleeding may require fresh frozen plasma at a dose of 10-15 mL/kg ²³⁾
• Vitamin K deficiency due to malabsorption: Dependent on the disease. Malabsorption requires daily administration of high doses of oral vitamin K1 0.3 to 15 mg/day. If oral dosing is ineffective, consideration should be for parenteral vitamin K1 ²⁴⁾
• Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD): 10 mg vitamin K1 2-3 times per week by an oral dose by intravenous infusion. Fresh frozen plasma may be required during surgery or in cases of severe bleeding at a dose of 15-20 mL/kg. Prothrombin Complex Concentrates and recombinant Factor VII may also have utility during surgery or severe bleeding ²⁵⁾
• Vitamin K nutritional deficiency in adults: At least 120 and 90 ug/day for men and women respectively, by diet or oral supplementation to meet the National Academy of Science Food and Nutrition Board recommended intake.
• Chronic conditions: As more research becomes available, a larger dosage of oral vitamin K1 and K2 may be beneficial. No present guidelines are available.

Blood transfusions may also be needed if bleeding is severe.

Vitamin K deficiency bleeding prognosis

Prevention in neonates reduces the incidence of vitamin K deficiency bleeding significantly. Late vitamin K deficiency bleeding has the worse prognosis, with 50% of cases presenting with intracranial hemorrhage ²⁶⁾. Nutritional deficiencies in adults are difficult to evaluate given confounding factors such as overall quality of diet and differences in metabolism due to comorbid conditions or genetics but are considered to have an excellent prognosis. In hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD), with Vitamin K supplementation, there is a good prognosis with low impact on quality of life ²⁷⁾.