Neonatal Jaundice

Babies who are born prematurely 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 seventh days after birth.

To check for jaundice in the newborn, press gently on your baby's forehead or nose. If the skin appears yellow in the area that was pressed, this may indicate mild jaundice. If the baby does not have jaundice, the skin color should appear 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, preferably in natural daylight. Read more about 5 essential tips to keep your baby healthy.

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

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

Conjugated hyperbilirubinemia: This refers to a pathologic elevation of conjugated or direct bilirubin concentration higher than 2 mg/dL or more than 20% of total bilirubin.

Unconjugated hyperbilirubinemia (UHB): 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: This includes blood group incompatibilities such as ABO and Rhesus (RH) incompatibility. If the mother's blood contains antibodies that do not match the baby's blood type, the newborn will experience blood incompatibility. ABO and RH are the two most common types of incompatibilities.
   • Non-immune mediated hemolysis: This includes:
     • RBC membrane defects like hereditary spherocytosis and elliptocytosis (changes in the shapes of RBCs)
     • RBC enzyme defects like glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency
     • Sequestration due to conditions like blood clots or bleeding between the skull and scalp, intracranial hemorrhage, polycythemia, and sepsis.
2. Decreased bilirubin clearance: This is due to the following syndromes:
   • Crigler Najjar syndrome: A severe condition characterized by hyperbilirubinemia.
   • Gilbert’s syndrome: A common, harmless liver condition in which the liver does not properly process bilirubin.
3. Miscellaneous causes: Other 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, it affects a significant proportion of women worldwide.

Conjugated hyperbilirubinemia (CHB): The causes of neonatal CHB 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 due to a deficiency of bile ducts.
   • Alpha-1 antitrypsin deficiency: An inherited condition that raises the risk for lung and liver disease.
   • Galactosemia: A disorder affecting how the body processes a sugar called galactose.
   • Fructosemia: Also known as hereditary fructose intolerance, it is one of the more common errors in metabolism in newborns.
   • Tyrosinemia type 1: A genetic disorder characterized by elevated blood levels of the amino acid tyrosine.
   • Cystic fibrosis: An inherited disorder causing severe damage to the lungs, digestive system, and other organs.
   • Progressive familial intrahepatic cholestasis (PFIC): A disorder leading to progressive liver disease and potential 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): A group of rare metabolic disorders characterized by defects in the 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: A progressive rise in alkaline phosphatase and/or conjugated bilirubin in patients receiving nutrition through intravenous means.
   • Gestational alloimmune liver disease/neonatal hemochromatosis: A clinical condition with severe liver disease in the newborn accompanied by extrahepatic siderosis.
   • Hypotension: Low blood pressure under 90/60 mm/Hg.

• ABO incompatibility
• Rh incompatibility
• G6PD deficiency
• 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 such as sulfa drugs, penicillin, and ceftriaxone
• Trisomy 21 (also known as Down syndrome)
• Weight loss during pregnancy
• Breastfeeding

Jaundice is mainly diagnosed based on the baby's appearance. However, it is still necessary to measure the level of bilirubin to determine the severity of jaundice and 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 steps during 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 observe the underlying color of the skin and subcutaneous tissue.
• Newborns with yellow skin beyond the thighs should have 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 methods:
• Biochemical: The gold standard method for bilirubin estimation is the total and conjugated bilirubin assessment based on the van den Bergh reaction, a chemical used to measure bilirubin levels.
• Bilimeter: Spectrophotometry is the basis of the bilimeter, which assesses total bilirubin in the serum. This method measures how much a chemical substance absorbs light by evaluating the intensity of light as it passes through a sample solution. Due to the predominant unconjugated form of bilirubin, this method has proven useful in neonates.
• Transcutaneous bilirubinometer: This non-invasive method uses bilirubin staining in the skin. The accuracy of the instrument depends on variations in skin pigmentation and thickness.

Clinical approach: The first step in evaluating any newborn with jaundice is to differentiate between physiological and pathological jaundice. This involves checking for the following:

• Dependency on preterm: Babies born before their term need to be evaluated differently based on the degree of prematurity and birth weight. A baby born before the 37th week of pregnancy is considered a preemie or premature baby.
• Evidence of hemolysis: Hemolytic jaundice should be considered if there is:
• Onset of jaundice within 24 hours.
• 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 reticulocyte count (>8%).
• Rapid rise of bilirubin (>5 mg/dl in 24 hours or >0.5 mg/dl/hr).
• Family history.

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

• Government and public health organizations should arrange seminars and workshops to train mothers regarding neonatal jaundice.
• Medical scientists should develop new treatments and preventive measures with minimal side effects that can effectively help recover babies.
• Partners should screen their ABO blood groups and 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:

• Ensure the baby is receiving adequate nutrition through breast milk.
• Feed the baby 8 to 12 times a day for the first several days to help bilirubin pass through their body more quickly.
• Provide 1 to 2 ounces of formula every 2 to 3 hours for the first week if the baby is not breastfeeding.
• Monitor the baby for the first five days of life for symptoms of jaundice, such as yellowing of the skin and eyes.

Treatment is usually only needed in babies with high levels of bilirubin in the blood. Typically, the condition improves within 10 to 14 days and will not cause any harm to the baby. Treatments are recommended to reduce the risk of a rare but serious complication of newborn jaundice and kernicterus, which can lead to 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 is sometimes used to treat newborn jaundice by making it easier for the baby's liver to break down and remove bilirubin from the blood. Phototherapy aims to expose the 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 ensure they are not getting too hot, and to check for signs of dehydration. Intravenous fluids may be needed if the baby is becoming dehydrated and unable to drink enough.
  • The bilirubin levels will be tested every 4 to 6 hours initially to check if the treatment is effective. 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, phototherapy 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 if 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 address any problems that may arise, such as bleeding. After the transfusion, the baby's blood will be tested within 2 hours to check if the process was successful. The procedure may need to be repeated if the bilirubin level 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 bilirubin level in the blood continues 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 performed 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.

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 if the cause of jaundice may be breastfeeding, continue 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 short periods.
• Monitor the baby carefully for any rise in temperature, loss of appetite, or restlessness.
• Ensure that the baby is sufficiently hydrated.
• Feed the baby frequently with supplementation to prevent weight loss.

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

• Bilirubin-induced neurologic dysfunction (BIND): This condition refers to 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). BIND is typically divided into acute and chronic phases and occurs as bilirubin binds to different parts of the brain, causing neurotoxicity.
• Acute bilirubin encephalopathy (ABE): ABE is a potentially devastating condition that can lead to death or lifelong neurodevelopmental disabilities. It is characterized by lethargy, hypotonia, and decreased suck reflex. At this stage, the disease is reversible.
• Chronic bilirubin encephalopathy (kernicterus): If ABE progresses, infants may develop kernicterus, which is irreversible. This condition results from brain damage due to high serum bilirubin levels and manifests as involuntary twitching, cerebral paralysis, seizures, arching, posturing, gaze abnormalities, and hearing loss.
• Neonatal cholestasis: Infants with neonatal cholestasis are at risk of developing liver failure, cirrhosis, and, in some cases, hepatocellular carcinoma (liver cancer). Long-standing cholestasis may also lead to difficulties in weight gain and deficiencies in fat-soluble vitamins.

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

• 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.
• 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.
• Barley 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.

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

• Keep an eye on the newborn for yellowing of the skin.
• Ensure that the baby is well-fed and receives adequate nutrition.
• Expose the baby to direct sunlight (preferably between 7-9 am).
• Breastfeed the baby adequately.
• Look out for signs such as lethargy, restlessness, or high-pitched cries.
• Keep the baby comfortable.
• Maintain constant communication with the pediatrician to monitor the baby's symptoms.