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Bilirubin
Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases. It is responsible for the yellow color of bruises, the yellow color of urine (via its reduced breakdown product, urobilin), the brown color of faeces (via its conversion to stercobilin), and the yellow discoloration in jaundice. It has also been found in plants.[1] [edit] Chemistry Bilirubin consists of an open chain of four pyrrole-like rings (tetrapyrrole). In heme, by contrast, these four rings are connected into a larger ring, called a porphyrin ring. Bilirubin is very similar to the pigment phycobilin used by certain algae to capture light energy, and to the pigment phytochrome used by plants to sense light. All of these contain an open chain of four pyrrolic rings. Like these other pigments, some of the double-bonds in bilirubin isomerize when exposed to light. This is used in the phototherapy of jaundiced newborns: the E,E-isomer of bilirubin formed upon light exposure is more soluble than the unilluminated Z,Z-isomer. Some textbooks and research articles show the incorrect geometric isomer of bilirubin. [2] The naturally occurring isomer is the Z,Zisomer. [edit] Function Bilirubin is created by the activity of biliverdin reductase on biliverdin, a green tetrapyrrolic bile pigment that is also a product of heme catabolism. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin, has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.[3][4] [edit] Metabolism [edit] Unconjugated (indirect) Erythrocytes (red blood cells) generated in the bone marrow are disposed of in the spleen when they get old or damaged. This releases hemoglobin, which is broken down to heme as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the reticuloendothelial cells of the spleen. This unconjugated bilirubin is not soluble in water. It is then bound to albumin and sent to the liver. [edit] Conjugated (direct) In the liver it is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated bilirubin remains in the large intestine and is metabolised by colonic bacteria to urobilinogen, which is further metabolized to stercobilinogen, and finally oxidised to stercobilin. This stercobilin gives feces its brown color. Some of the urobilinogen is reabsorbed and excreted in the urine along with an oxidized form, urobilin. [edit] In urine Under normal circumstances, a tiny amount of bilirubin is excreted in the urine if any. If the liver's function is impaired or when biliary drainage is blocked, some of the conjugated bilirubin leaks out of the hepatocytes and appears in the urine, turning it dark amber. However, in disorders involving hemolytic anemia, an increased number of red blood cells are broken down, causing an increase in the amount of unconjugated bilirubin in the blood. Because the unconjugated bilirubin is not water-soluble, one will not see an increase in bilirubin in the urine. Because there is no problem with the liver or bile systems, this excess unconjugated bilirubin will go through all of the normal processing mechanisms that occur (e.g., conjugation, excretion in bile, metabolism to urobilinogen, reabsorption) and will show up as an increase in urine urobilinogen. This difference between increased urine bilirubin and increased urine urobilinogen helps to distinguish between various disorders in those systems.

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[edit] Toxicity Unconjugated hyperbilirubinaemia in a neonate can lead to accumulation of bilirubin in certain brain regions with consequent irreversible damage to these areas manifesting as various neurological deficits, seizures, abnormal reflexes and eye movements. This type of neurological injury is known as kernicterus. The neurotoxicity of neonatal hyperbilirubinemia manifests because the bloodbrain barrier has yet to develop fully, and bilirubin can freely pass into the brain interstitium, whereas more developed individuals with increased bilirubin in the blood are protected. Aside from specific chronic medical conditions that may lead to hyperbilirubinaemia, neonates in general are at increased risk since they lack the intestinal bacteria that facilitate the breakdown and excretion of conjugated bilirubin in the feces (this is largely why the feces of a neonate are paler than those of an adult). Instead the conjugated bilirubin is converted back into the unconjugated form by the enzyme -glucuronidase and a large proportion is reabsorbed through the enterohepatic circulation.

Physiological jaundice
Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This common condition is called physiological jaundice. This pattern of hyperbilirubinemia has been classified into two functionally distinct periods. Phase one 1. 2. Term infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204 umol/l (12 mg/dL). Preterm infants - jaundice lasts for about 2 week, with a rapid rise of serum bilirubin up to 255 umol/l (15 mg/dL).

Phase two - bilirubin levels decline to about 34 umol/l (2 mg/dL) for 2 weeks, eventually mimicking adult values. 1. 2. Preterm infants - phase two can last more than 1 month. Exclusively breastfed infants - phase two can last more than 1 month.

[edit] Causes Possible mechanisms involved in physiological jaundice 1. Increase bilirubin load on liver cells: Increased red blood cell (RBC) volume Increased labeled bilirubin Increased circulation of bilirubin in the liver Decreased RBC survival

2. Defective hepatic uptake of bilirubin from blood plasma: Decreased ligadin (Y protein) Increased binding of Y proteins by other anions Decreased liver uptake especially in phase two

3. Defective billirubin conjugation: Decreased UDPG activity

4. Defective bilirubin excretion [edit] Pathological Jaundice of Neonates (Unconjugated Pathological Hyperbilirubinemia)

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Any of the following features characterizes pathological jaundice: 1. 2. 3. 4. Clinical jaundice appearing in the first 24 hours. Increases in the level of total bilirubin by more than 8.5 umol/l (0.5 mg/dL) per hour or (85 umol/l) 5 mg/dL per 24 hours. Total bilirubin more than 331.5 umol/l (19.5 mg/dL) (hyperbilirubinemia). Direct bilirubin more than 34 umol/l (2.0 mg/dL).

[edit] Differentiating Physiological and Pathological Jaundice The aim of clinical assessment is to distinguish physiological from pathological jaundice. The sign which helps to differentiate pathological jaundice of neonates from physiological jaundice of neonates are presence of intrauterine retardation, stigma of intrauterine infections (e.g. cataracts, microcephaly, hepatosplenomegaly etc.), cephalhematoma, bruising, signs of intra ventricular hemorrhage etc. History of illness is noteworthy. Family history of jaundice and anemia, family history of neonatal or early infant death due to liver disease, maternal illness suggestive of viral infection (fever, rash or lymphadenopathy), Maternal drugs (e.g. Sulphonamides, anti-malarials causing hemolysis in G-6-PD deficiency) are suggestive of pathological jaundice in neonates. [edit] Causes of jaundice In neonates, jaundice tends to develop because of two factors - the breakdown of fetal hemoglobin as it is replaced with adult hemoglobin and the relatively immature hepatic metabolic pathways which are unable to conjugate and so excrete bilirubin as quickly as an adult. This causes an accumulation of bilirubin in the blood (hyperbilirubinemia), leading to the symptoms of jaundice. If the neonatal jaundice does not clear up with simple phototherapy, other causes such as biliary atresia, PFIC, bile duct paucity, Alagille's syndrome, alpha 1 and other pediatric liver diseases should be considered. The evaluation for these will include blood work and a variety of diagnostic tests. Prolonged neonatal jaundice is serious and should be followed up promptly. Severe neonatal jaundice may indicate the presence of other conditions contributing to the elevated bilirubin levels, of which there are a large variety of possibilities (see below). These should be detected or excluded as part of the differential diagnosis to prevent the development of complications. They can be grouped into the following categories: Neonatal jaundice

Unconjugated bilirubin

Conjugated bilirubin

Pathologic

Physiological jaundice of Neonates

Hepatic

Posthepatic

Hemolytic

Non-hemolytic

Intrinsic causes [edit] Non Conjugated [edit] Hemolytic

Extrinsic causes

[edit] Intrinsic causes of hemolysis Membrane conditions

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o Spherocytosis o Hereditary ellipsoidosis Systemic conditions o Sepsis o Arteriovenous malformation Enzyme conditions o Glucose-6-phosphate dehydrogenase deficiency (also called G6PD deficiency) o Pyruvate kinase deficiency Globin synthesis defect o sickle cell disease o Alpha-thalassemia

[edit] Extrinsic causes of hemolysis Alloimmunity (The neonatal or cord blood gives a positive direct Coombs test and the maternal blood gives a positive indirect Coombs test) o Hemolytic disease of the newborn (ABO)[3] o o o o o

Rh disease Hemolytic disease of the newborn (anti-Kell) Hemolytic disease of the newborn (anti-Rhc) Other blood type mismatches causing hemolytic disease of the newborn Breast milk feeding.

[edit] Non-hemolytic causes Cephalohematoma Polycythemia Sepsis Hypothyroidism Gilbert's syndrome Crigler-Najjar syndrome

[edit] Conjugated [edit] Hepatic causes Infections o Sepsis o Hepatitis B o TORCH infections Metabolic o Galactosemia o Alpha-1-antitrypsin deficiency o Cystic fibrosis Drugs Total parenteral nutrition Idiopathic

[edit] Post-hepatic Biliary atresia Bile duct obstruction

[edit] Non-organic causes

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[edit] Breast feeding jaundice "Breastfeeding jaundice" or "lack of breastfeeding jaundice," is caused by insufficient breast milk intake, [4] resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This can usually be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production. Passage of the baby through the vagina during birth helps stimulate milk production in the mother's body, so infants born by cesarean section are at higher risk for this condition. [edit] Breast milk jaundice Whereas breast feeding jaundice is a mechanical problem, breast milk jaundice is more of a biochemical problem. The term applies to jaundice in a newborn baby on. First, at birth, the gut is sterile, and normal gut flora takes time to establish. The bacteria in the adult gut convert conjugated bilirubin to stercobilinogen which is then oxidized to stercobilin and excreted in the stool. In the absence of sufficient bacteria, the bilirubin is de-conjugated by brush border -glucuronidase and reabsorbed. This process of re-absorption is called enterohepatic circulation. Second, the breast-milk of some women contains a metabolite of progesterone called 3-alpha-20-beta pregnanediol. This substance inhibits the action of the enzyme uridine diphosphoglucuronic acid (UDPGA) glucuronyl transferase responsible for conjugation and subsequent excretion of bilirubin. In the newborn liver, activity of glucuronyl transferase is only at 0.11% of adult levels, so conjugation of bilirubin is already reduced. Further inhibition of bilirubin conjugation leads to increased levels of bilirubin in the blood[citation needed]. Third, an enzyme in breast milk called lipoprotein lipase produces increased concentration of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase, which again leads to decreased conjugation and subsequent excretion of bilirubin[citation needed].

Despite the advantages of breast feeding, there is a strong association of breast feeding with neonatal hyperbilirubinemia and thus risk of kernicterus, though this is uncommon. Serum bilirubin levels may reach as high as 30 mg/dL. Jaundice should be managed either with phototherapy or with exchange blood transfusion as is needed. Breast feeds however need not be discontinued. The child should be kept well hydrated and extra feeds given.

Neonatal respiratory distress syndrome

Hyaline membrane disease; Infant respiratory distress syndrome (IRDS); Respiratory distress syndrome in infants; RDS - infants Last reviewed: May 9, 2011. Neonatal respiratory distress syndrome (RDS) is most commonly seen in premature infants. The condition makes it difficult to breathe. Causes, incidence, and risk factors Neonatal RDS occurs in infants whose lungs have not yet fully developed. The disease is mainly caused by a lack of a slippery, protective substance called surfactant, which helps the lungs inflate with air and keeps the air sacs from collapsing. This substance normally appears in fully developed lungs. Neonatal RDS can also be the result of genetic problems with lung development. The earlier a baby is born, the less developed the lungs are and the higher the chance of neonatal RDS. Most cases are seen in babies born before 28 weeks. It is very uncommon in infants born full-term (at 40 weeks).

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In addition to prematurity, the following increase the risk of neonatal RDS: A brother or sister who had RDS Diabetes in the mother Cesarean delivery Delivery complications that reduce blood flow to the baby Multiple pregnancy (twins or more) Rapid labor

The risk of neonatal RDS may be decreased if the pregnant mother has chronic, pregnancy-related high blood pressure or prolonged rupture of membranes, because the stress of these situations can cause the infant's lungs to mature sooner. Symptoms The symptoms usually appear within minutes of birth, although they may not be seen for several hours. Symptoms may include: Bluish color of the skin and mucus membranes (cyanosis) Brief stop in breathing (apnea) Decreased urine output Grunting Nasal flaring Rapid breathing Shallow breathing Shortness of breath and grunting sounds while breathing Unusual breathing movement -- drawing back of the chest muscles with breathing

Signs and tests A blood gas analysis shows low oxygen and excess acid in the body fluids. A chest x-ray shows the lungs have a characteristic "ground glass" appearance, which often develops 6 to 12 hours after birth. Lab tests are done to rule out infection and sepsis as a cause of the respiratory distress. Treatment High-risk and premature infants require prompt attention by a neonatal resuscitation team. Despite greatly improved RDS treatment in recent years, many controversies still exist. Delivering artificial surfactant directly to the infant's lungs can be enormously important, but how much should be given and who should receive it and when is still under investigation. Infants will be given warm, moist oxygen. This is critically important, but needs to be given carefully to reduce the side effects associated with too much oxygen. A breathing machine can be lifesaving, especially for babies with the following: High levels of carbon dioxide in the arteries Low blood oxygen in the arteries Low blood pH (acidity)

It can also be lifesaving for infants with repeated breathing pauses. There are a number of different types of breathing machines available. However, the devices can damage fragile lung tissues, and breathing machines should be avoided or limited when possible.

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A treatment called continuous positive airway pressure (CPAP) that delivers slightly pressurized air through the nose can help keep the airways open and may prevent the need for a breathing machine for many babies. Even with CPAP, oxygen and pressure will be reduced as soon as possible to prevent side effects associated with excessive oxygen or pressure. A variety of other treatments may be used, including: Extracorporeal membrane oxygenation (ECMO) to directly put oxygen in the blood if a breathing machine can't be used Inhaled nitric oxide to improve oxygen levels

It is important that all babies with RDS receive excellent supportive care, including the following, which help reduce the infant's oxygen needs: Few disturbances Gentle handling Maintaining ideal body temperature

Infants with RDS also need careful fluid management and close attention to other situations, such as infections, if they develop. Expectations (prognosis) The condition often worsens for 2 to 4 days after birth with slow improvement thereafter. Some infants with severe respiratory distress syndrome will die, although this is rare on the first day of life. If it occurs, it usually happens between days 2 and 7. Long-term complications may develop as a result of too much oxygen, high pressures delivered to the lungs, the severity of the condition itself, or periods when the brain or other organs did not receive enough oxygen. Complications Air or gas may build up in: The space surrounding the lungs (pneumothorax) The space in the chest between two lungs (pneumomediastinum) The area between the heart and the thin sac that surrounds the heart (pneumopericardium)

Other complications may include: Bleeding into the brain (intraventricular hemorrhage of the newborn) Bleeding into the lung (sometimes associated with surfactant use) Blood clots due to an umbilical arterial catheter Bronchopulmonary dysplasia Delayed mental development and mental retardation associated with brain damage or bleeding Retinopathy of prematurity and blindness

Sepsis Neonatorum
Definition Symptoms Diagnosis Prognosis and Treatment

Sepsis in a newborn (sepsis neonatorum) is an infection that spreads throughout the babys body. Sepsis occurs in less than 1 percent of newborns (1 out of every 100), but accounts for up to 30 percent of deaths in the first few weeks of life. Infection is 5-10 times more common in premature newborns and in babies weighing less than 5 pounds than in normal-weight, full-term newborns.

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Complications experienced during birth, such as premature or prolonged rupture of the membranes or infection in the mother, put the newborn at increased risk of infection. Symptoms The onset of what is called early-onset neonatal sepsis is within six hours of birth in over half the cases and within 72 hours in the great majority of cases. Sepsis that begins four or more days after birth is called late-onest sepsis, and is probably an infection acquired in the hospital nursery (a nosocomial infection). In both types of neonatal sepsis, the infection may be only in the bloodstream, or may spread to the lungs (pneumonia), brain (meningitis), bone (osteomyelitis), joints, or other organs in the body. Typical symptoms of a newborn with sepsis include: listlessness (a very sleepy baby) feeding problems a high OR low temperature

Other symptoms include: difficulty breathing, rapid breathing, or apnea (when the baby stops breathing) seizures excessive jitteriness repeated vomiting or diarrhea a swollen abdomen

Diagnosis The organism that is causing the infection may be identified by taking cultures of the blood as well as from other sites of the body. Urine samples are often cultured for bacteria to look for an infection in the urinary tract. Because only small samples of blood and other body fluids are taken, sometimes no organism is found. However, the infant may still be treated if other laboratory studies or the infants clinical appearance strongly suggest an infection. Other laboratory studies that doctors use to detect an infection include the following: White Blood Cell Count and Differential: When an infant is fighting an infection, their white blood cell count may either go up, as the infants body produces more infection-fighting cells, or it might also go down if the infant has used up all of their white blood cells fighting the infection and can no longer keep up with their production of white cells. Another change that is seen when an infant is fighting an infection is an increase in the percentage of immature white cells. This is due to the increased production rate of white blood cells, such that more immature white blood cells are being released into the blood stream. This higher percentage of immature white cells is sometimes referred to as a left-shift, and is one of the things that can tell the doctors that the infant has an infection. C-Reactive Protein (CRP): This is a laboratory test that measures a protein that is a non-specific marker for inflammation and therefore infection. If the infant has two normal CRP levels measured 24 hours apart, then there is a 99% chance that the infant does not have an infection. Therefore, this test is most useful in ruling out an infection. Lumbar Puncture: If the doctor suspects meningitis, which is more common if something has grown in the babys blood culture, a spinal tap, or lumbar puncture will be performed. Lumbar punctures allow the doctor to obtain a small amount of cerebrospinal fluid (CSF), which is the protective fluid that surrounds the brain and the spinal cord. The CSF can then be cultured to determine if the bacteria has spread to the nervous system. The doctor, nurse practitioner, or physicians assistant will very carefully insert a special spinal needle between two vertebrae, or backbones, in the babys back at a level below where the actual spinal cord ends, so there is no danger that the needle will come into contact with the babys spinal cord. After a very small amount of fluid is removed, the needle is taken out, and a band-aid placed on the babys back.

Hemolytic disease of the newborn (ABO)

In ABO hemolytic disease of the newborn (also known as ABO HDN) maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies. The ABO blood group system is the best known surface antigen system, expressed on a wide variety of human cells. For Caucasian populations about one fifth of all pregnancies have ABO incompatibility between the fetus and the mother, but only a tiny minority develop symptomatic ABO HDN[1]. The latter only occurs in mothers of blood group O because they can produce enough IgG antibodies to cause hemolysis. Although very uncommon, cases of ABO HDN have been reported in infants born to mothers with blood groups A[2][3] and B[4].

ABO incompatibility
Last reviewed: May 13, 2008. ABO incompatibility is a reaction of the immune system that occurs if two different and not compatible blood types are mixed together. Causes, incidence, and risk factors A, B, and O are the three major blood types. The types are based on small substances (molecules) on the surface of the blood cells. In people who have different blood types, these molecules act as immune system triggers (antigens). Each person has a combination of two of these surface molecules. Type O lacks any molecule. The different blood types are: Type A (AA or AO molecules) Type B (BB or BO molecules) Type AB Type O

People who have one blood type form proteins (antibodies) that cause their immune system to react against other blood types. Being exposed to another type of blood can cause a reaction. This is important when a patient needs to receive blood (transfusion) or have an organ transplant. The blood types must be matched to avoid an ABO incompatibility reaction. For example: A patient with type A blood will react against type B or type AB blood A patient with type B blood will react against type A or type AB blood A patient with type O blood will react against type A, type B, or type AB blood

Because type O lacks any surface molecules, type O blood does not cause an immune response. This is why type O blood cells can be given to patients of any blood type. People with type O blood are called "universal donors." However, people with type O can only receive type O blood. Since antibodies are in the liquid part of blood (plasma), both blood and plasma transfusions must be matched to avoid an immune reaction. Symptoms The following are symptoms of transfusion reactions:

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Back pain Blood in urine Feeling of "impending doom" Fever Yellow skin (jaundice)

Signs and tests Bilirubin level is high Complete blood count (CBC) shows damaged red blood cells, may also show mild anemia Lab testing of patient's and donor's blood shows that they are not compatible

Treatment Treatment may include: Drugs used to treat allergic reactions (antihistamines) Drugs used to treat swelling and allergies (steroids) Fluids given through a vein (intravenous) Medicines to raise blood pressure if it drops too low

Expectations (prognosis) This can be a very serious problem which can even result in death. With the right treatment, a full recovery is likely. Complications Kidney failure Low blood pressure needing intensive care Death

Calling your health care provider Call your health care provider if you have recently had a blood transfusion or transplant and you have the symptoms listed above. Prevention Careful testing of donor and patient blood types before transfusion or transplant can prevent this problem. References 1. 2. McPherson RA, Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa: Saunders; 2006. Hoffman R, Benz E, Shattil S, Furie B, Cohen H. Hematology: Basic Principles and Practice. 4th ed. Philadelphia, Pa: Churchill Livingstone; 2004.

Rh incompatibility
Rh-induced hemolytic disease of the newborn Last reviewed: February 10, 2011.

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Rh incompatibility is a condition that develops when a pregnant woman has Rh-negative blood and the baby in her womb has Rhpositive blood. Causes, incidence, and risk factors During pregnancy, red blood cells from the unborn baby can cross into the mother's bloodstream through the placenta. If the mother is Rh-negative, her immune system treats Rh-positive fetal cells as if they were a foreign substance and makes antibodies against the fetal blood cells. These anti-Rh antibodies may cross back through the placenta into the developing baby and destroy the baby's circulating red blood cells. When red blood cells are broken down, they make bilirubin. This causes an infant to become yellow (jaundiced). The level of bilirubin in the infant's bloodstream may range from mild to dangerously high. Because it takes time for the mother to develop antibodies, firstborn infants are often not affected unless the mother had past miscarriages or abortions that sensitized her immune system. However, all children she has afterwards who are also Rh-positive may be affected. Rh incompatibility develops only when the mother is Rh-negative and the infant is Rh-positive. Thanks to the use of special immune globulins called RhoGHAM, this problem has become uncommon in the United States and other places that provide access to good prenatal care. Symptoms Rh incompatibility can cause symptoms ranging from very mild to deadly. In its mildest form, Rh incompatibility causes the destruction of red blood cells. After birth, the infant may have: Yellowing of the skin and whites of the eyes (jaundice) Low muscle tone (hypotonia) and lethargy

Signs and tests Before delivery, the mother may have an increased amount of amniotic fluid around her unborn baby (polyhydramnios). There may be: A positive direct Coombs test result Higher-than-normal levels of bilirubin in the baby's umbilical cord blood Signs of red blood cell destruction in the infant's blood

Treatment Because Rh incompatibility is preventable with the use of RhoGAM, prevention remains the best treatment. Treatment of an infant who is already affected depends on the severity of the condition. Infants with mild Rh incompatibility may be treated with: Feeding and fluids (hydration) Phototherapy using bilirubin lights

Expectations (prognosis) Full recovery is expected for mild Rh incompatibility.

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Complications Possible complications include: Brain damage due to high levels of bilirubin (kernicterus) Fluid buildup and swelling in the baby (hydrops fetalis) Problems with mental function, movement, hearing, speech, and seizures

Calling your health care provider Call your health care provider if you think or know you are pregnant and have not yet seen a doctor. Prevention Rh incompatibility is almost completely preventable. Rh-negative mothers should be followed closely by their obstetricians during pregnancy. Special immune globulins, called RhoGAM, are now used to prevent RH incompatibility in mothers who are Rh-negative. If the father of the infant is Rh-positive or if his blood type cannot be confirmed, the mother is given an injection of RhoGAM during the second trimester. If the baby is Rh-negative, the mother will get a second injection within a few days after delivery. These injections prevent the development of antibodies against Rh-positive blood. However, women with Rh-negative blood type must receive injections: During every pregnancy If they have a miscarriage or abortion After prenatal tests such as amniocentesis and chorionic villus biopsy After injury to the abdomen during pregnancy

References 1. Stoll BJ. Blood disorders. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 103. Review Date: 2/10/2011. Reviewed by: Kimberly G Lee, MD, MSc, IBCLC, Associate Professor of Pediatrics, Division of Neonatology, Medical University of South Carolina, Charleston, SC. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

Hemorrhagic disease of the newborn

Hemorrhagic disease of the newborn is a bleeding disorder that usually develops shortly after a baby is born.

Causes
A lack of vitamin K causes hemorrhagic disease of the newborn. Vitamin K plays an important role in blood clotting.

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Babies usually have low levels of vitamin K for a variety of reasons. Vitamin K doesn't move easily across the placenta from the mother to the baby. As a result, a newborn doesn't have much vitamin K stored up at birth. Also, there isn't much vitamin K in breast milk. Your baby may develop this condition if:

A preventive vitamin K shot is not given at birth (if vitamin K is given by mouth instead of as a shot, it must be given more than once and it may not be as effective) You take certain anti-seizure drugs

The condition is grouped into three categories:

Early onset hemorrhagic disease of the newborn is very rare. It occurs during the first hours of birth and certainly within 24 hours. Use of anti-seizure drugs or a blood thinner called coumadin during pregnancy is a common cause. Classic onset disease develops in breastfed infants who did not receive a vitamin K shot within the first week after birth. It is also rare. The late onset form is seen in infants older than 2 weeks up to 2 months old. It is more common in children who did not receive a vitamin K shot, and in those of Asian descent.

Newborns and infants with the following problems are more likely to develop this disorder:

Alpha1-antitrypsin deficiency Biliary atresia Celiac disease Cystic fibrosis Diarrhea Hepatitis

Symptoms
The condition causes bleeding. The most common areas of bleeding include:

A boy's penis if he has been circumcised Belly button area Gastrointestinal tract (may result in blood in the baby's bowel movements) Mucus membranes (such as the lining of the nose and mouth) Places where there has been a needle stick

There may also be:

Blood in the urine Bruising Raised lump on the baby's head (suggesting bleeding underneath one of the skull bones)

Exams and Tests

Blood clotting tests will be done.

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The diagnosis is confirmed if a vitamin K shot stops the bleeding and blood clotting time (prothrombin time) is within normal limits.

Treatment
Vitamin K is given if bleeding occurs. Patients with severe bleeding may need blood transfusions.

Outlook (Prognosis)
The outlook tends to be worse for babies with late onset hemorrhagic disease than other forms. There is a higher rate of bleeding inside the skull (intracranial hemorrhage) associated with the late onset condition.

Possible Complications

Bleeding inside the skull (intracranial hemorrhage), with possible brain damage Death Severe bleeding

When to Contact a Medical Professional

Call your doctor if your baby has any unexplained bleeding.

Prevention
The American Academy of Pediatrics recommends giving every baby a shot of vitamin K immediately after birth. This practice has helped prevent the condition, which is now rare in the U.S. The early onset form of the disease may be prevented by giving vitamin K shots to pregnant women who take anti-seizure medications.

Alternative Names
Vitamin K deficiency bleeding; VKDB