By Dr. Namrata Todurkar
Neonatal jaundice is a very common condition in all newborn infants. It is usually self-limiting and not harmful in most term born neonates. However, in infants born preterm, it can last longer and can cause harm earlier than in term infants. Physicians assess the severity of jaundice by measurement of a component in blood called ‘bilirubin’. Timed serum bilirubin measurement analyzed in the context of both the infant’s gestational age and chronological age is the best available method for predicting the severity of jaundice.
What is the cause for jaundice?
Adult hemoglobin is designed to deliver optimum oxygen to tissues. However, fetal hemoglobin is designed to extract as much oxygen as possible from maternal blood, which makes it less efficient in delivering oxygen to tissues readily, as it tends to tightly attach to oxygen molecule. Therefore, all fetuses produce a large quantity of hemoglobin to compensate for this issue. After birth, oxygen is much more readily available in air and the special function of fetal hemoglobin is no longer required. Therefore, the newborn tries to get rid of the excess hemoglobin by destroying it in the liver and spleen. This is main cause of physiological jaundice (jaundice occurring due to normal metabolic processes) in neonates. The by-products of hemoglobin (bilirubin) should be excreted by the liver. Inability to do so, will result in accumulation of excess bilirubin resulting in jaundice.
Two types of bilirubin:
Bilirubin is said to be conjugated when an enzyme in the liver binds it to another substance in order to excrete it through the feces. However, the majority of bilirubin in an infant is the unconjugated variety and this form is amenable to treatment by phototherapy. A total conjugated bilirubin concentration greater than 20% of the total bilirubin concentration warrants further investigation. In this blog we will only be speaking about unconjugated bilirubin as it is the most common type.
Both physiological and non-physiological jaundice present in the same way. Common causes of non-physiological jaundice include:
1. Hemolysis (excessive destruction of red blood cells): blood group incompatibility such as those of ABO incompatibility (mother with O positive blood group and baby having either A positive or B positive blood group), Rh incompatibility (mother with a Rh negative blood group and baby having Rh positive blood group), minor groups incompatibility, and enzyme deficiencies such as G6PD deficiency, autoimmune hemolytic anemia, etc.
2. Decreased conjugation (normal process of combining bilirubin with an easily excretable substance in liver) such as in prematurity.
3. Increased ‘enterohepatic circulation’ such as lack of adequate oral feeding that includes insufficient breastfeeding or the infant not being fed because of illness, intestinal obstruction etc.
4. Extravasated blood: cephalhematoma (collection of blood underneath the scalp), extensive bruising etc.
The preterm perspective: Physiological jaundice can last longer than 2 weeks in preterm infants. Whereas, in a term neonate, the condition usually gets better within 10-14 days without causing any harm to the baby. The severe variety of jaundice can cross the blood brain barrier to affect the brain and result in bilirubin-induced neurological dysfunction (BIND) and lead to a condition called kernicterus. The sequelae include disordered visual gaze (ie. limitations of upward gaze), sensorineural hearing impairment, gait abnormalities (choreoathetoid cerebral palsy), and speech and language disorders.
Preterm infants, compared with term infants, are more vulnerable to the syndrome of BIND and kernicterus at lower bilirubin levels, because they are more likely to be sicker and have lower serum albumin level than their term newborn counterparts. Albumin is the predominant variety of protein in the body and bilirubin usually binds to albumin and this form is generally non-toxic in nature. When albumin stores in the body are low, most of the bilirubin is free and can easily cross the blood brain barrier. Since there has been no definitive evidence-based recommendation as to what level of bilirubin necessitates treatment in premature infants, it is a common practice to use a lower bilirubin level to initiate phototherapy and not uncommon to use of prophylactic phototherapy in extremely low birthweight (ELBW) infants.
Treatment:
Therapeutic options
1. Phototherapy:
Phototherapy remains the mainstay of treating hyperbilirubinemia in neonates. It is highly effective and carries an excellent safety track record of over 50 years. It acts by converting insoluble bilirubin (unconjugated) into soluble isomers that can be excreted in urine and feces. The bilirubin molecule isomerizes to harmless forms under blue-green light; and the light sources having high irradiance in this particular wavelength range are more effective than the others.
2. Exchange transfusion:
Double volume exchange transfusion (DVET) should be performed if the bilirubin levels reach the age specific cut-off for exchange transfusion or the infant shows signs of bilirubin encephalopathy irrespective of bilirubin levels.
3. Intravenous immunoglobulins (IVIG):
IVIG reduces hemolysis and production of jaundice in isoimmune hemolytic anemia (Rh isoimmunisation and ABO incompatibility) and thereby reduces the need for phototherapy and exchange transfusion. IVIG administration can cause intestinal injury and necrotizing enterocolitis.
4. IV hydration
Infants with severe jaundice and evidence of dehydration (ie. excessive weight loss) should be given IV hydration. An extra fluid intake decreases the need for exchange transfusion.
5. Other agents
There is no proven evidence of benefit of drugs like phenobarbitone, clofibrate, or steroids to prevent or treat jaundice in neonates and therefore these agents should not be employed in treatment of jaundiced infants.
Follow up: All jaundiced infants, especially high-risk infants, should continue to be closely monitored until feeding and weight gain are established, and the jaundice concentration starts to fall. Community services should include breastfeeding support and access to bilirubin testing. Infants requiring exchange transfusion or those who exhibit neurological abnormalities should be referred to regional multidisciplinary follow-up programs. Neurosensory hearing loss is of particular importance in infants with severe hyperbilirubinemia, and their hearing screen should include brainstem auditory evoked potentials.
Although neonatal jaundice may sound subtle and easy to treat, the sequelae of undetected or under-treated jaundice are mostly irreversible. This is one of the many reasons for frequent blood sampling in NICU and the reason behind those bright blue lights which everyone dislikes.
Dr. Namrata Todurkar, MBBS, MD (Pediatrics), DNB (Pediatrics). Fellowship in Neonatology from National Neonatology Forum India. Fellow in Neonatal-Perinatal Medicine at the University of British Columbia. Areas of interest: Neonatal nutrition, Fluid and Electrolyte Management, Inborn Errors, Neurodevelopmental follow-up of preterm infants. Dr. Todurkar is a volunteer blogger at CPBF.
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