Introduction
Jaundice in newborns is a yellowish discoloration of the skin and eyes due to the accumulation of bilirubin in these tissues. Almost all neonates (Approximately 60 % term and 80 % preterm infants) present with jaundice in the first week of life. If bilirubin levels remain high, infants are at risk of bilirubin-induced neurological dysfunction
Pathogenesis
Bilirubin is produced from the breakdown of heme proteins. Afterward, it is transported to the liver with the help of albumin. In the liver, it undergoes conjugation to form water-soluble forms that are excreted through urine and stools.
Physiological Jaundice appears from 24 to 72 hours of age and peaks by 4 to 5 days in term neonates and later in preterm neonates. It disappears by 10 – 14 days and attributed to physiological immaturity.
Pathological jaundice appears within 24 hours of birth and the rate of rising of bilirubin is more than 0.2 mg/dl/hr and exceeding 15 mg/dl.
Factors that are responsible for increases in neonatal jaundice are increase production of bilirubin, ineffective hepatic uptake, deficient conjugation of bilirubin, and increased enterohepatic conjugation.
The cause of the increase in the production of bilirubin could be hemolytic as well as non-hemolytic.
Table 1
Hemolytic Causes |
Other causes |
1. Immune Mediated hemolysis -
Rh, ABO and other minor blood
group incompatibilities
2. Red Cell membrane defects-
Hereditary Spherocytosis,
Elliptocytosis etc
3. Red cell enzyme deficiencies -
G6PD deficiency, Pyruvate
kinase deficiency etc
4. Hemoglobinopathies -
Alpha and Beta thalassemia
|
Sepsis, DIC, Extravascular blood
(hematomas like cephalohematoma),
polycythaemia, IDM babies
|
Increased enterohepatic circulation
in breast milk jaundice, pyloric stenosis and obstruction and ileus of intestine |
The common reason for decreased or impaired conjugation is seen in physiological hyperbilirubinemia, preterms, breastfeeding jaundice, and hypothyroidism. Rare syndromes like Criggler-Najjar type 1 and 2, Gilbert Syndrome also cause decreased clearance.
Clinical Features
The common reason for decreased or impaired conjugation is seen in physiological hyperbilirubinemia, preterms, breastfeeding jaundice, and hypothyroidism. Rare syndromes like Criggler-Najjar type 1 and 2, Gilbert Syndrome also cause decreased clearance.
Investigations
- Transcutaneous bilirubin measurement – It works on the principle of multi-wavelength spectral reflectance from yellow skin color.
- Point of care testing analyzers - POCT analyzers are now widely used in NICU for bilirubin measurements in addition to blood gas and electrolytes using spectrophotometry.
- Serum Bilirubin measurements – Mainly Diazo dye binding, spectrophotometry, or oxidation by bilirubin oxidase or by potassium ferricyanide methods are used for the bilirubin measurements.
- End Tidal Carbon monoxide estimation – Carbon monoxide is produced in equimolar concentration when hemoglobin is oxidized. Its measurement in-breath is an alternative means of detecting jaundice.
- Other tests – depending upon the etiology of the jaundice relevant tests can be done.
Treatment
- Phototherapy – Phototherapy has become a standard of care for unconjugated jaundice in infants. It acts by configurational isomerization, structural isomerization, and photooxidation. It involves exposing the naked infant to blue, cool white, or green light of wavelength 450 – 460 nm. The number of devices that can be used to give phototherapy are halogen spotlight, fluorescent tubes (Mainly CFL), fibreoptic blankets, and gallium light-emitting diodes (LED) phototherapy.
Several guidelines have been developed for initiating phototherapy like the AAP Subcommittee of hyperbilirubinemia management and NICE guidelines. People in remote areas can use various apps to decide whether phototherapy is required or not ex: Bili app. However there are no evidence-based guidelines for starting phototherapy in preterm infants, reference books provide tables depending upon expert opinion.
Phototherapy can be stopped when serum bilirubin levels fall below 2 mg/dl below the threshold level. Rebound level of bilirubin or early follow up is needed in case of prematurity, DCT positive cases, and treatment started within 72 hours.
An inability to see a decline in bilirubin of 1-2 mg/dl after 4 – 6 hours and/or keep bilirubin below the exchange transfusion level is the failure of phototherapy.
Universal screening before discharge either with TSB or TcB for prediction of severe bilirubinemia in infants is recommended by experts. Hour specific nomogram with clinical risk factors provides guidance for subsequent follow-ups.
- Exchange transfusion - Exchange transfusion is used for avoiding bilirubin toxicity when other therapeutic modalities have failed or not sufficient. In this procedure infants, blood is replaced by fresh whole blood in equal portions.
Complications
Bilirubin is a potential neurotoxin; free bilirubin can enter the brain and cause apoptosis and necrosis of cells. Bilirubin induced neurologic dysfunction is divided into acute and chronic forms (kernicterus). Acute BIND progresses through three stages early, intermediate, and advanced. Acute BIND can be reversible if treated promptly or it may lead to chronic permanent neurological dysfunction (kernicterus). Kernicterus is the yellowish staining of brain stem nuclei and cerebellum. It develops within the first year of age. It leads to choreoathetosis cerebral palsy, sensorineural hearing loss, upward gaze abnormalities, and dental enamel hypoplasia.
1. American Academy of pediatric subcommittee on hyperbilirubinemia. Management of hyperbilirubinemia in new-born infants 35 or more weeks of gestation. Pediatrics. 2004; 114-297.
2. Volpe JJ. Bilirubin and brain injury. In: Neurology of the newborn 4th ed. Philadelphia: W B Saunders; 2001.
3. Kirk JM. Neonatal jaundice – a critical review of role and practice of bilirubin analysis. Ann Clin Biochem. 2008; 45: 452-462.
4. Canadian Pediatric Society. Position Statement: FN (2007-02). Guidelines for detection, management, and prevention of hyperbilirubinemia in term and late preterm new-born infants. Pediatr Child Health. 2007; 12 Supplement B: 1B-12B.
5. Alastair J, Wood J. Neonatal Hyperbilirubinemia. N Engl J Med, Vol 344, No. 8: 581-590.
6. Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near term newborns. Pediatrics 1999; 103:6.