Neonatal Jaundice

Types Of Neonatal Jaundice

Jaundice can be classified into a few different types in newborns. They are as follows:

• Physiological jaundice: This is the most common type and is normal. Physiological jaundice develops in most newborns by the 2nd or 3rd day. It occurs after the development of the liver and it starts to get rid of excess bilirubin. Physiological jaundice usually isn’t serious and goes away on its own within two weeks. 

• Pathological jaundice: Jaundice is considered pathologic if it presents within the first 24 hours after birth, with a rise in the total serum bilirubin level more than 5 mg per dL per day or is higher than 17 mg per dL. It can present itself in infants who have signs and symptoms suggestive of serious illness.

• Breastfeeding jaundice: this type of jaundice is more common in babies that are breastfed and it is the baby’s first week of life. It happens due to a lack of breast milk due to nursing difficulties or because your milk hasn’t come in yet. Breastfeeding jaundice may take longer to go away.

• Breast milk jaundice: Substances in breast milk can affect how the baby’s liver breaks down bilirubin leading to bilirubin buildup. Breast milk jaundice may appear after your baby’s first week of life and may take a month or more to disappear.

Are you a new mom or mom to be? Then, you might have a lot of apprehensions about breastfeeding. Read about 7 things that you must be aware of breastfeeding.
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Symptoms Of Neonatal Jaundice

Babies who are born premature (too early) are more likely to develop jaundice than full-term babies. The main sign is yellowing of the skin and the whites of the eyes which usually appears between the second and fourth day after birth. Bilirubin levels typically peak between the third and seven days after birth.

To check for jaundice in the newborn, press gently on your baby's forehead or nose. The sign of jaundice is the skin looks yellow in the area that was pressed, in case of mild jaundice. If the baby doesn't have jaundice, the skin color should simply look slightly lighter than its normal color for a moment.

Along with the skin becoming yellow, other symptoms that are quite rare include:

• Very light yellow or very dark brown urine. 

• Yellow mustard color (normal) to light beige stool.

Always examine the baby in good lighting conditions, most preferably the natural daylight. Read more about 5 essential tips to keep your baby healthy.
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Causes Of Neonatal Jaundice

The causes of neonatal hyperbilirubinemia can be divided into two distinct categories namely:

• Unconjugated hyperbilirubinemia: Also called direct hyperbilirubinemia usually results from increased production, impaired uptake by the liver, and decreased conjugation of bilirubin.

• Conjugated hyperbilirubinemia: Pathologic elevation of conjugated or direct bilirubin concentration higher than 2 mg/dL or more than 20% of total bilirubin.

Unconjugated hyperbilirubinemia(UHB) or indirect hyperbilirubinemia

Based on the mechanism of bilirubin elevation, the etiology of unconjugated hyperbilirubinemia can be subdivided into the following three categories:

1. Increased bilirubin production: This is due to the following causes:

• Immune-mediated hemolysis - Which includes blood group incompatibilities such as ABO and Rhesus (RH) incompatibility. If the mother's blood has antibodies that do not work with the blood type of a baby, the newborn will experience blood incompatibility and ABO and RH are the two most common types of incompatibilities.

Blood group testing is done to determine a person's blood group (A, B, AB, or O) and Rh type. Understand better about blood grouping and how it is done.
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• Non-immune mediated hemolysis: That includes : 

  • RBC membrane defects like hereditary spherocytosis and elliptocytosis (changes in the shapes of RBCs) 

  • RBC enzyme defects like glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinases deficiency

  • Sequestration like a blood clot or bleeding between the skull and scalp, intracranial hemorrhage; polycythemia (type of blood cancer), and sepsis.

2. Decreased bilirubin clearance: It is due to the following syndromes:

• Crigler Najjar syndrome: Is a severe condition characterized by hyperbilirubinemia.

• Gilbert’s syndrome: A common, harmless liver condition in which the liver doesn't properly process bilirubin.

3. Miscellaneous causes: Other miscellaneous causes include: 

• Congenital hypothyroidism

• Drugs like sulfa drugs, ceftriaxone, and penicillins

• Intestinal obstruction

• Pyloric stenosis (blockage of food from entering the small intestine)

• Breast milk jaundice

• Breastfeeding jaundice

• Diabetes in the mother of the infant 

Gestational diabetes mellitus (GDM), defined as diabetes diagnosed during pregnancy, affects a significant proportion of women worldwide. Read more about gestational diabetes: causes, risk factors, and symptoms.
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Conjugated hyperbilirubinemia(CHB) or direct hyperbilirubinemia

The causes of neonatal CHB are extensive and can be classified into the following categories:

1. Obstruction of biliary flow

• Biliary atresia (blockage of the bile duct)

• Choledochal cysts (congenital bile duct anomaly)

• Neonatal sclerosing cholangitis (obstructive fibrosis of the bile ducts)

• Neonatal cholelithiasis (gallbladder stones in infants)

2. Infections

• Cytomegalovirus (CMV) 

• Human immunodeficiency virus (HIV)

• Rubella

• Herpes virus

• Syphilis, 

• Toxoplasmosis

• Urinary tract infection (UTI)

• Septicemia

3. Genetic causes

• Alagille syndrome: An inherited condition in which bile builds up in the liver because there are too few bile ducts to drain the bile.

• Alpha-1 antitrypsin deficiency: An inherited condition that raises your risk for lung and liver disease. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs. 

• Galactosemia: A disorder that affects how the body processes a sugar called galactose.

• Fructosemia: Also called hereditary fructose intolerance is one of the more common errors in metabolism of the newborns.

• Tyrosinemia type 1: A genetic disorder characterized by elevated blood levels of the amino acid tyrosine.

• Cystic fibrosis: An inherited disorder that causes severe damage to the lungs, digestive system, and other organs in the body.

• Progressive familial intrahepatic cholestasis (PFIC): A disorder that causes progressive liver disease, which typically leads to liver failure. 

• Aagenaes syndrome: A form of idiopathic familial intrahepatic cholestasis associated with lymphedema of the lower extremities. 

• Dubin-Johnson syndrome: A condition characterized by jaundice, which is a yellowing of the skin and whites of the eyes.

• Bile acid synthesis disorders (BSAD): Are a group of rare metabolic disorders characterized by defects in the creation (synthesis) of bile acids.

4. Miscellaneous

• Idiopathic neonatal hepatitis: An uncommon syndrome of prolonged obstructive jaundice associated with giant cell transformation in the liver and patent bile ducts.

• Parenteral nutrition-induced cholestasis: is a progressive rise in alkaline phosphatase and/or conjugated bilirubin and is diagnosed in patients who receive nutrition through the veins (IV) to develop cholestasis (reduced flow of bile from the liver).

• Gestational alloimmune liver disease/neonatal hemochromatosis: Is a clinical condition in which severe liver disease in the newborn is accompanied by extrahepatic siderosis (deposition of excessive iron)

• Hypotension: Low blood pressure under 90/60 mm/Hg.

Risk Factors For Neonatal Jaundice

ABO incompatibility, Rh incompatibility, and G6PD deficiency are the most common risk factors for the development of neonatal jaundice. Other risk factors include:

• Maternal diabetes

• Race of the mother

• Premature birth

• Height of the mother

• Polycythemia ( a type of blood cancer)

• Male sex of the newborn

• Cephalohematoma (blood clot between the skull and the scalp)

• Medications like sulfa drugs, penicillin and ceftriaxone.

• Trisomy 21 ( also known as down’s syndrome)

• Weight loss during pregnancy

• Breastfeeding

Diagnosis Of Neonatal Jaundice

Jaundice is mainly diagnosed based on the baby's appearance. However, it's still necessary to measure the level of bilirubin to determine the severity of jaundice to decide the course of treatment. Tests to detect jaundice and measure bilirubin levels include:

Clinical physical examination 

Dermal staining of bilirubin may be used as a clinical guide to the level of jaundice. Dermal staining in newborns progresses in a cephalo-caudal (head to toe) direction. The doctor should follow these to do the physical examination of the newborn:

• The newborn should be examined in good daylight. 

• The doctor should apply pressure on the skin with the fingers to peel the skin and the underlying color of the skin and subcutaneous tissue should be noted. 

• Newborns who are detected with yellow skin beyond the thighs should have an urgent laboratory confirmation for bilirubin levels. 

Note: Clinical assessment is unreliable if a newborn has been receiving phototherapy and has dark skin.

Laboratory tests

Bilirubin levels can be checked through the following:

• Biochemical: The gold standard method for bilirubin estimation is the total and conjugated bilirubin assessment based on the van den Bergh reaction. It is a chemical used to measure the levels of bilirubin.

• Bilimeter: Spectrophotometry is the base of the bilimeter and it assesses total bilirubin in the serum. Spectrophotometry is a method to measure how much a chemical substance absorbs light by measuring the intensity of light as a beam of light passes through a sample solution. Because of the predominant unconjugated form of bilirubin, this method has been found to be a useful method in neonates.

• Transcutaneous bilirubinometer: This method is non-invasive and uses the bilirubin staining in the skin. The accuracy of the instrument depends on the variation of skin pigmentation and thickness.

Clinical approach

The first step in the evaluation of any newborn with jaundice is to differentiate between physiological and pathological jaundice. It consists of checking for the following: 

• Dependency on preterm: Babies who are born before their term needs to be evaluated in a different manner based on the degree of prematurity and birth weight.

A baby born before the 37th week of pregnancy is considered to be a preemie or premature baby. Here are a few tips to take care of a premature baby at home.
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• Evidence of hemolysis: Hemolytic jaundice should be considered if there is:

  • Onset of jaundice within 24 hrs

  • Presence of pallor( pale appearance) and hydrops (swelling)

  • Presence of hepatosplenomegaly (enlargement of spleen and liver)

  • Presence of hemolysis (destruction of RBCs) on the smear of peripheral blood

  • Increased count of reticulocyte (>8%)

  • Rapid rise of bilirubin (>5 mg/dl in 24 h or >0.5 mg/dl/hr) 

  • Family history.

Prevention Of Neonatal Jaundice

There’s no real way to prevent neonatal jaundice. But certain measures can be taken to create awareness like:

• Government and public health organizations should arrange seminars, workshops and train mothers regarding neonatal jaundice. 

• Medical scientists should develop new treatments and preventive measures having little or no side effects and capable of recovering babies more effectively. 

• Partners should screen their ABO blood groups as well as Rh factor before marriage. 

• Marriages between closely related individuals should be avoided.

After birth, the baby should be tested for blood incompatibilities.If the baby does have jaundice, there are ways to prevent it from becoming more severe. They are:

• Making sure the baby is getting enough nutrition through breast milk. 

• Feeding the baby 8 to 12 times a day for the first several days. This ensures bilirubin passes through their body more quickly.

• Giving 1 to 2 ounces of formula every 2 to 3 hours for the first week in case the baby is not on breast milk. 

• Monitoring the baby for the first five days of life for the symptoms of jaundice, such as yellowing of the skin and eyes.

Specialist To Visit

Most cases of neonatal jaundice are normal, but sometimes it can be an indicator of an underlying medical condition. The doctor to consult in this case is a pediatrician. Contact the doctor if:

• The spread of jaundice is more severe and rapid.

• The baby’s yellow coloring gets darker.

• The baby develops a fever over 38°C (100°F).

• The baby is not taking milk, appears restless or lethargic, and cries at a high pitch.

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Treatment Of Neonatal Jaundice

Treatment is usually only needed in babies with high levels of bilirubin in the blood. Usually, the condition gets better within 10 to 14 days and will not cause any harm to the baby. 

The treatments are recommended to reduce the risk of a rare but serious complication of newborn jaundice and kernicterus, which can cause brain damage. If the baby's jaundice does not improve over time, or tests show high levels of bilirubin in their blood, they may be treated with the following: 

Phototherapy

Phototherapy is treatment with a special type of light (not sunlight). It's sometimes used to treat newborn jaundice by making it easier for your baby's liver to break down and remove the bilirubin from your baby's blood.

Phototherapy aims to expose your baby's skin to as much light as possible. This procedure consists of:

• Placing the baby under a light either in a cot or incubator with their eyes covered.

• A break is given after 30 minutes to feed the baby, change their nappy and cuddle them.

• Intensified phototherapy may be offered if the baby's jaundice does not improve.

• This involves increasing the amount of light used or using another source of light, such as a light blanket, at the same time.

• Treatment cannot be stopped for breaks during intensified phototherapy.

During phototherapy, the baby's temperature is regularly monitored to make sure they're not getting too hot, and look for signs of dehydration. Intravenous fluids may be needed if the baby is becoming dehydrated and not able to drink enough.

The bilirubin levels will be tested every 4 to 6 hours, in the beginning, to check if the treatment is working and once the bilirubin levels stabilize or start to fall, they will be checked every 6 to 12 hours.

Phototherapy will be stopped once the bilirubin levels fall to a safe level, (which usually takes 2 days). It is generally very effective for neonatal jaundice and has few side effects.

Note: As long as the level of bilirubin is not very high, the phototherapy treatment can be done at home with a special blanket called a “bili” blanket.

Exchange transfusion

If the baby has a very high bilirubin level in their blood or phototherapy has not been effective, they may need a complete blood transfusion, known as an exchange transfusion.

During an exchange transfusion, a thin plastic tube will be placed in blood vessels in the umbilical cord, arms, or legs to remove the blood. The blood is replaced with blood from someone with the same blood group. As the new blood will not contain bilirubin, the overall level of bilirubin in the baby's blood will fall quickly.

The baby will be closely monitored throughout the transfusion process to treat any problems that may arise, such as bleeding. Post the transfusion the baby's blood will be tested within 2 hours of treatment to check if the process was successful.

The procedure may need to be repeated if the level of bilirubin in your baby's blood remains high.

Intravenous immunoglobulin (IVIG)

If the jaundice is caused by RH incompatibility intravenous immunoglobulin (IVIG) may be used. IVIG is usually only used if phototherapy alone has not worked and the level of bilirubin in the blood is continuing to rise.

Kasai operation (hepatic portoenterostomy)

Newborns diagnosed with biliary atresia or Type IVb choledochal cyst require a Kasai operation (hepatic portoenterostomy) to allow for bile drainage. This procedure should preferably be done within two months of life for the best outcomes. 

Other treatments

Treatment of conjugated hyperbilirubinemia depends on the cause such as:

• If jaundice is caused by an underlying health problem, such as an infection, this usually needs to be treated.

• Metabolic causes of cholestasis respond well when there is an improvement in the primary disorder and liver functions.

• Parenteral nutrition (PN)-induced cholestasis is managed with cyclic PN, reducing the duration of exposure and starting initial feeds as early as possible. Manganese and copper content of PN should be reduced to minimize liver injury.

Home-care For Neonatal Jaundice

Neonatal jaundice is quite common here are a few tips to take care of newborns at home:

• Keep the pediatrician updated about any changes in the baby’s condition and call immediately if the yellowing of the baby’s skin becomes darker than before.

• Make sure that the baby is well-fed.

• Even the cause of jaundice may be breastfeeding, continuing to feed the infant in accordance with the doctor’s guidelines.

• Breastfeeding should be done at least 8 to 12 times a day, whereas bottle-fed infants should be given at least 6 to 10 feedings in a day.

• Expose the newborn to direct sunlight for prolonged periods.

• Monitor the baby carefully to see if there is any rise in the temperature, loss of appetite, or restlessness. 

• Ensure that the baby is hydrated sufficiently.

• Feed the baby frequently with supplementation to prevent weight loss.

Complications Of Neonatal Jaundice

Newborns with severe hyperbilirubinemia are at a higher risk of developing the following complications:

1. Bilirubin-induced neurologic dysfunction (BIND)

It refers to the clinical signs associated with bilirubin toxicity such as hypotonia (decreased muscle tone) followed by hypertonia (increased muscle tone) and/or opisthotonus (muscle spasm) or retrocollis (repetitive muscle contraction in the neck) and is typically divided into acute and chronic phases. It occurs as bilirubin binds different parts of the brain causing neurotoxicity.

2. Acute bilirubin encephalopathy (ABE)

Potentially devastating conditions that can lead to death or life-long neurodevelopmental handicaps. It is characterized by lethargy, hypotonia, and decreased suck. At this stage, the disease is reversible.

3. Chronic bilirubin encephalopathy (kernicterus)

If ABE progresses, then the infants can develop kernicterus, which is then irreversible. It occurs due to brain damage as a result of high serum bilirubin levels. It manifests as involuntary twitching, cerebral paralysis, seizures, arching, posturing, gaze abnormality, and hearing loss.

4. Neonatal cholestasis

Patients with neonatal cholestasis are at risk of developing liver failure, cirrhosis, and even hepatocellular carcinoma (liver cancer) in a few cases. Long-standing cholestasis may also lead to failure in gaining weight and fat-soluble vitamin deficiencies.

Alternative Therapies For Neonatal Jaundice

The common option for treating neonatal hyperbilirubinemia and preventing any neurologic damage is the use of phototherapy and/or exchange transfusion. Some of the alternatives in the treatment of neonatal jaundice are:

Metalloporphyrins

Metalloporphyrins (synthetic heme analogs) are competitive inhibitors of heme oxygenase, the rate-limiting enzyme in bilirubin production. Their use has been proposed as an attractive alternative strategy for preventing or treating severe hyperbilirubinemia.

Specifically, tin-protoporphyrin (SnPP) and tin-mesoporphyrin (SnMP) are being used experimentally to prevent and treat neonatal hyperbilirubinemia.

Natural remedies

1. Magnesium: A study showed that pregnant women who took 250 mg of magnesium daily for 6 weeks can reduce the risk of excess bilirubin production. 

Try adding magnesium-rich foods to your diet if you’re pregnant or breastfeeding. Read more about tests to detect magnesium deficiency.
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2. Probiotics: Probiotic supplementation in newborns can help significantly improve jaundice symptoms by decreasing bilirubin levels that cause jaundice and helping the body clear out excess bilirubin.

3. Barely seed flour: Researchers have found that barley seed flour sifted over a baby’s skin along with light exposure improved jaundice in newborn babies. The barley flour acts as an antioxidant and helps decrease indirect bilirubin levels. This is a traditional Iranian remedy.

Living With Neonatal Jaundice

Though it may look scary, neonatal jaundice generally clears on its own and is very common in newborns. The way to manage it would be to be aware of it and follow simple steps like:

• Keep an eye on the newborn to look for yellowing of the skin

• Make sure that the baby is well-fed and has enough nutrition

• Expose the baby to direct sunlight (preferably between 7-9 am)

• Breastfeed the baby adequately

• Look out for sings like lethargy, restlessness or high pitched cries

• Keep the baby comfortable

• Be in constant touch with the pediatrician to monitor baby’s symptoms