Jaundice is common in the neonatal period. If jaundice is severe it may lead to bilirubin encephalopathy (kernicterus). Mainly basal ganglia and auditory nucleus are affected, but any part of the brain is at risk. If unrecognised and untreated, it may result in death or severe neurodisability (choreoathetoid cerebral palsy and deafness). Therefore, it is important to identify jaundice, assess the severity with serum bilirubin, measurement identify the cause and treat.
Nearly 7 out of 10 normal neonates are jaundiced in first few days of life. There are several physiological reasons why they are jaundiced. They have high red cell mass at birth (due to the relatively hypoxic environment) short red blood cell life span of approximately 80 days and immature liver conjugation system, and the increased enterohepatic circulation due to sterile gut. The jaundice generally appears on second day of life. It is clinically visible when serum bilirubin reaches 85 micromoles per decilitre (5 mg/dl). It increases in severity until day 4–5 and gradually falls and disappears by day 10. This is known as physiological jaundice and does not usually require any treatment. It is important to remember that the physiological jaundice is Fig. 3.1: Schematic representation of the foetal circulation
diagnosis by exclusion. Therefore, every jaundiced baby should be carefully evaluated to rule out pathological causes.
If the jaundice appears on the first day of life even in preterm babies, it is deemed pathological and severe enough to require intervention. The same applies if it persists beyond the usual period; it needs investigation and treatment.
Early jaundice is generally secondary to haemolysis although it may be secondary to infection, extensive bruising and concealed haemorrhage. Haemolysis may be secondary to antibodies, or defects in the red cells structure or enzymes. Early jaundice, secondary to haemolysis from incompatible blood group like Rh isoimmunisation is a major cause of haemolytic jaundice although the incidence is declining with anti-D prophylaxis in Rh negative mothers. On the other hand, ABO isoimmunisation is increasing in importance. The jaundice secondary to ABO isoimmunisation is not severe enough to require exchange blood transfusion. Other minor blood group isoimmunisation can also produce neonatal jaundice. The red cell defects such as hereditary spherocytosis and glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency are not common, but important particularly when there is no obvious cause to explain the presence of jaundice or haemolysis.
The decision to treat jaundice is based on the gestational age of the baby and the postnatal age. Babies who are preterm should be treated at a lower serum bilirubin level than a baby born at term. The level of bilirubin needs treatment. Several factors like general well-being of the baby, severity of haemolysis, and presence of sepsis should be taken into consideration in determining the threshold for treatment.
Adequate hydration is important, as dehydration will increase the serum bilirubin level. Phototherapy and exchange transfusion are the mainstay of treatment. Phototherapy is very effective and acts by photoisomerisation and photo- oxidation of the bilirubin into water excretable forms. The light with wavelength of 450–500 nanometre (blue light) is very effective. Effectiveness of phototherapy can be maximised by increasing the intensity of light (double, triple or quadruple phototherapy) or maximum exposure of the body surface. Standard phototherapy units or bilibed or biliblanket administer phototherapy. The eyes are covered to protect them from exposure to light. Side effects include photodermatitis, temperature instability, loose stools and dehydration.
The effectiveness, availability and the ease of administration of phototherapy has reduced the need for exchange transfusion dramatically. In many places, phototherapy is administered at home with appropriate support and supervision.
Intravenous immunoglobulins is also effective in reducing the severity of haemolytic jaundice. It, together with phototherapy, is very effective and has reduced the need for exchange transfusion.
Exchange transfusion is becoming a rare procedure in developed countries as Rh isoimmunisation is on the decline and phototherapy is effective. The aim of exchange transfusions is to remove antibody coated red cells, antibodies in serum, reduce and correct anaemia. Double volume whole blood (or reconstituted red blood cells) is used for exchange transfusion through umbilical blood vessels. It is an invasive procedure and needs careful preparation, and monitoring. A person experienced in this procedure should do it.
The estimated blood volume of a term neonate is 85 ml/kg while that of a preterm neonate is about 100 ml/kg. Aliquots of 10 ml/kg are used per cycle, with the whole procedure lasting between 45 minutes and 90 minutes. Monitoring of vital signs with intermittent assessment of blood glucose, calcium and haemoglobin is recommended.
In order to ensure no loss of circulating volume, the pre- and post-procedure central venous pressure should be taken.
Rh isoimmunisation is generally recognised early in pregnancy and is monitored by ultrasound scans, cerebral arterial blood flow velocity and sometimes cordocentesis. If the haemolysis is significant, intrauterine transfusion through the umbilical cord is advocated. This procedure is usually carried out in a highly specialised centre. Rh negative blood is used for this procedure. Most babies may require phototherapy at birth and sometimes immunoglobulins but rarely exchange transfusion. They may continue to have on going haemolysis and may need red blood cell transfusion for several months. Blood for these transfusions must be CMV negative and be irradiated to prevent graft versus host reaction.
Case Study
A baby girl (twin1) was born at 28 weeks of gestation by emergency caesarean section for poor biophysical profile. She, the recipient of twin-to-twin transfusion, had in utero exchange transfusion and amnioreduction for ascites. Post-delivery, she had respiratory distress syndrome (RDS), anaemia, jaundice and Grade II intraventricular haemorrhage (IVH) bilaterally. She developed Staphylococcus aureus septicaemia (vancomycin sensitive) at 2 weeks of age and was treated with a 14-day course of intravenous antibiotics (vancomycin and cefotaxime); cerebrospinal fluid (CSF) examination was normal. She developed S. aureus thrombophlebitis with abscess formation in the right upper limb during the course of her septicaemia and this was drained. By day 14 blood cultures were negative, the abscess had healed and baby was clinically well. She was discharged home at the corrected gestational age of 33 weeks with an outpatient follow-up appointment.
Two weeks after discharge she was readmitted with episodes of vomiting and apnoea. Cranial ultrasound scan was normal; sepsis was excluded and a presumptive diagnosis of gastro- oesophageal reflux was considered although oesophageal pH study was normal. The vomiting gradually settled over next 3 weeks without any anti-reflux medications and she was discharged home.
In the neonatal follow-up clinic at 41 weeks of corrected gestational age, her head circumference was noted to be above the 50th centile (previously it was growing between 10th and 50th centile). Clinically the baby was well and the cranial ultrasound scan appeared normal. Subsequent review after 2 weeks showed a rapid increase in the head circumference (on 90th centile) with sutural separation and a few dilated scalp veins. The cranial ultrasound scan at this time showed multiple low echogenic areas and cranial CT scan established the diagnosis of multiple brain abscesses with surrounding oedema and a dilated left lateral ventricle.
Aspirate from the frontal lobe abscess grew S. aureus on culture. Echocardiogram, abdominal ultrasound, neutrophil functions and immunoglobulins (including IgG subclasses) were normal. The brain CT scan prior to discharge still showed fluid filled areas but a subsequent cranial brain CT scan was reported to be normal with complete resolution of the abscesses.
This case illustrates how the complications of neonatal sepsis can develop insidiously and present in unusual way and also, the importance of growth monitoring.
INTRAUTERINE GROWTH RESTRICTION