(BQ) Part 2 book “Key topics in neonatology” has contents: Maternal drug abuse, mechanical ventilation, metabolic acidosis, multiple pregnancy, necrotising enterocolitis, neonatal surgery, n eural tube defects, n eurological evaluation, patent ductus arteriosus,… and other contents.
Jaundice All neonates have a transient rise in bilirubin, and some 30–50% become visibly jaundiced Preterm and term infants become jaundiced for similar reasons as follows: • increased bilirubin load on the liver due to a high red cell mass, the shorter survival of the neonatal erythrocyte, and the increased intestinal reabsorption of bilirubin (the enterohepatic circulation) • decreased hepatic uptake of bilirubin from the circulation • impaired bilirubin conjugation The bilirubin excretory pathway is therefore both overloaded and operationally inefficient, leading to a transient unconjugated hyperbilirubinaemia that peaks around day three, fades rapidly over the next three days, and clears by days 10–14 Hyperbilirubinaemia is more pronounced and almost universal in preterm infants, as a result of hepatic and gastrointestinal immaturity The delayed initiation of enteral feeds in sick preterm infants (which further enhances the enterohepatic circulation) and the slower maturation of hepatic bilirubin uptake and conjugation contribute to the greater magnitude and duration of jaundice in these infants Jaundice in neonates is considered as either physiological or pathological Physiological jaundice is the consequence of transient immaturity and the inefficiency of the bilirubin conjugation and excretory pathways Prematurity, bruising, polycythaemia, breast-feeding, and other factors can increase physiological jaundice (sometimes to the point of needing treatment) Jaundice is pathological and important if: • It is in the first 24 h of life—haemolysis until proven otherwise • It is associated with another illness • The bilirubin concentration is above the normal range • It has become prolonged (>10 days at term; >14 days in preterm infants) Term infants The 97th percentile for bilirubin concentration in the first few days of life in the well, breast-fed term baby is approximately 250 µmol/l, and it is 210 µmol/l in the formulafed baby These thresholds of concentration and time may therefore be taken as levels above which jaundice should be investigated for potentially pathological causes They are not thresholds for initiating treatment, nor are they thresholds below which pathological causes for jaundice are absent Vigilance is always needed Key topics in neonatology 252 Investigations In the well term infant who clinically looks jaundiced enough to need treatment, the following are required: • serum bilirubin concentration • blood group and Coombs’ test Further tests are not indicated unless the need for treatment is confirmed by a high bilirubin concentration without evidence of haemolytic disease Tests on treated infants should include: • urine culture • urine reducing sugars (to exclude galactosuria, which tests positive on Clinitest, but negative on Clinistix) • further estimates of total bilirubin concentration • liver-function tests and conjugated/unconjugated bilirubin assays that may be needed to exclude cholestasis, especially if the jaundice is prolonged Some specific hepatic causes of jaundice are discussed under ‘Liver disorders’ Worldwide, glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most important cause of jaundice, especially in Southeast Asian and African countries In the UK, it is justifiable to screen jaundiced male infants who are of an ethnic origin that has a high prevalence of G6PD deficiency Management The literature on bilirubin-induced brain injury in both term and preterm infants is both complex and voluminous, suggesting that no simple relationship exists between peak serum bilirubin levels and later adverse neurodevelopmental outcome However, there is unequivocal evidence of the neuropathological damage (kernicterus) that severe hyperbilirubinaemia can cause Kernicterus is a pathological diagnosis characterised by macroscopic yellow staining of specific subcortical nuclei and brainstem cranial nuclei, with microscopic evidence of neuronal damage in those nuclei The long-term neurological sequelae of this include deafness and choreoathetoid CP The aim of treating hyperbilirubinaemia is therefore to prevent bilirubin-related neurodevelopmental handicap while avoiding harm The cornerstones of hyperbilirubinaemia management are phototherapy and exchange transfusion Experts differ on what constitutes ‘appropriate guidelines’ for these two interventions, and no ‘evidence-based guidelines’ exist Generally, if the baby is well and is feeding well, and the concentration of bilirubin is below the treatment level, no further action should be taken unless the jaundice deepens or becomes prolonged If the bilirubin concentration is above the treatment threshold and likely to rise to a point where kernicterus is a risk, phototherapy is needed (see Table 1) Untreated severe hyperbilirubinaemia can cause fits, opisthotonos, and, indeed, death in Jaundice 253 the neonate There is continuing debate about the threshold above which kernicterus is likely to occur Recent work suggests that in well term infants without haemolytic disease (including G6PD deficiency) it is higher than originally thought The term ‘vigintiphobia’ (fear of the figure 20) was coined to reflect paediatricians’ fear of the total bilirubin concentration rising above 20 mg/dl (340 µmol/l) lest kernicterus should ensue Now, a gentler approach to jaundice is used, and kernicterus is considered to be a significant risk only above a bilirubin concentration of 450 µmol/l in this group of infants The setting of this value also sets the level (450 µmol/l) at which exchange transfusion to prevent kernicterus is mandatory In turn, phototherapy is started when the bilirubin concentration is 100 µmol/l below this exchange line In well term infants, therefore, phototherapy is started at bilirubin concentrations as low as 80 µmol/l on day one, rising to 350 µmol/l on day three and later Neither phototherapy nor exchange transfusion is harmless, and they should be initiated only if necessary There is, however, a greater risk of kernicterus at lower concentrations of bilirubin if the baby is preterm, has haemolytic disease, G6PD deficiency, hypoalbuminaemia, or acidosis, or is receiving any drugs that may displace bilirubin from the albumin-binding sites The thresholds for action have therefore to be reduced accordingly Preterm infants There are insufficient coherent data on jaundice in preterm infants below 35 weeks’ gestation to develop scientific evidence-based guidelines about phototherapy Table contains some published recommendations and some extrapolations from them A few observations should be noted Despite the near universal finding of clinical jaundice in VLBW infants, kernicterus has virtually disappeared in this group of infants It has been suggested that this might be as a consequence of the general improvements in neonatal intensive care or the increased readiness to use phototherapy However, a report (published in 2001) of kernicterus in two infants at 31 weeks’ (serum bilirubin 224 µmol/l) and 34 weeks’ gestation (serum bilirubin 251 µmol/l), neither of whom was ill, have once more raised concerns about what levels of bilirubin are safe in preterm infants Phototherapy From its introduction by Cremer and colleagues (Rochford General Hospital in Essex, UK, 1958), phototherapy has evolved into a widely accepted and highly effective medical therapy for jaundice to such a degree that even senior trainees in neonatology are now increasingly unsure as to how to perform an exchange transfusion safely The greatest impact of phototherapy has been in VLBW infants, where it has made exchange transfusions virtually obsolete There have been several recent developments in phototherapy technology Some fibre-optic phototherapy systems (‘biliblankets’) are now as effective as conventional phototherapy, and infants need not have their eyes covered Key topics in neonatology 254 (when the bili-blanket is wrapped around the baby) The efficacy of phototherapy is related to the surface area of the infant exposed to the phototherapy lights This may readily be increased by placing an infant on a fibre-optic pad with a bank of conventional free-standing phototherapy units above and around the infant The spectral radiance may be greatly increased by reducing the distance Table Guidelines for initiating phototherapy for jaundice Postnatal age and bilirubin level (µmol/l) for phototherapy Gestation ≤27 weeks or 350 between the light source and the infant (but not too close to cause burns!) Lining the sides of the incubator with reflecting aluminium foil may further enhance the efficacy of phototherapy and avoid the need for an exchange transfusion The most effective light source currently available is provided by special blue fluorescent tubes, which provide light mainly in the blue-green spectrum (which best penetrates the skin and is maximally absorbed by bilirubin) These should be used when bilirubin levels are approaching exchange levels However, provided the bilirubin level is controlled by phototherapy, it is reasonable for phototherapy to be interrupted for feeds and parental visits Finally, the bilirubin isomer, lumirubin, is excreted in bile and urine, so adequate hydration is important It is not essential, however, to provide additional ‘phototherapy fluids’ as long as the infant is not subjected to heat stress and the skin temperature is kept constant (by servo-control) Complications of phototherapy • purpuric bullous eruptions (rare) • diarrhoea from a decreased gut transit time • hypothermia (naked infant in a cool environment) • heat stress (increased fluid loss) and skin burns • bronze baby syndrome (with conjugated hyperbilirubinaemia) Exchange transfusion When hyperbilirubinaemia cannot be controlled by phototherapy alone, an exchange transfusion is required in order to protect the infant from the permanent neurodevelopmental sequelae which characterise kernicterus This is the only option Jaundice 255 available for an infant requiring an urgent reduction in serum bilirubin that is at toxic levels It is the preferred therapy in severe haemolytic anaemia, as it corrects the anaemia and removes the excess bilirubin Commonly, a double volume exchange is undertaken; that is, a calculated blood volume equal to twice the infant’s blood volume is exchanged This volume is calculated quite simply as: volume=infant’s weight (kg)×85 ml×2 (or 170 ml/kg) When performing an exchange transfusion in sick (especially preterm) infants, fresh CMV-negative blood (350 between the light source and the infant (but not too close to cause burns!) Lining.. .Key topics in neonatology 25 2 Investigations In the well term infant who clinically looks jaundiced enough to need treatment, the following are required: • serum bilirubin concentration... improvements in neonatal intensive care or the increased readiness to use phototherapy However, a report (published in 20 01) of kernicterus in two infants at 31 weeks’ (serum bilirubin 22 4 µmol/l)