NEONATAL JAUNDICE MEDICAL CARE

neonatal jaundice medical care:
Phototherapy and exchange transfusion are the therapeutic modalities used most widely in infants with neonatal jaundice.
Phototherapy :
Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia. This therapeutic principle was discovered rather serendipitously in England in the 1950s and now is arguably the most widespread therapy of any kind (excluding prophylactic treatments) used in newborns.

Phototherapy is effective because three reactions can occur when bilirubin is exposed to light, as follows:
• Initially, photooxidation was believed to be responsible for the beneficial effect of phototherapy. However, although bilirubin is bleached through the action of light, the process is slow and is now believed to contribute only minimally to the therapeutic effect of phototherapy.

• Configurational isomerization is a very rapid process that changes some of the predominant 4Z, 15Z bilirubin isomer to water-soluble isomers in which one or both of the intramolecular bonds are opened (E,Z; Z,E; or E,E). In human infants, the 4Z,15E isomer predominates, and at equilibrium conditions, the isomer constitutes 20% of circulating bilirubin after a few hours of phototherapy. This proportion is not influenced significantly by the intensity of light.

• Structural isomerization consists of intramolecular cyclization, resulting in the formation of lumirubin. This process is enhanced by increasing the intensity of light. During phototherapy, lumirubin may constitute 2-6% of the total serum bilirubin concentration.

The photoisomers of bilirubin are excreted in bile and, to some extent, in urine. The half-life of lumirubin in serum is much shorter than that in E isomers, and lumirubin is the primary pigment found in bile during phototherapy. Thus, although the E isomers predominate in serum, lumirubin is mostly responsible for the therapeutic effect of phototherapy of lowering the serum bilirubin level.

Bear in mind when initiating phototherapy that lowering of the total serum bilirubin concentration is only part of the therapeutic benefit. Since photo-isomers, by virtue of their water-soluble nature, should not be able to cross the blood-brain barrier, phototherapy reduces the risk of bilirubin-induced neurotoxicity as soon as the lights are turned on. At any given total serum bilirubin concentration, the presence of 20-25% of photo-isomers means that only 75-80% of the total bilirubin is present in a form that can enter the brain.

Phototherapy can be administered in a number of ways. To understand the benefits and limitations of the various approaches, some basic principles regarding wavelength and types of light are discussed below with comments and suggestions regarding each system.

First, wavelength must be considered. Bilirubin absorbs light primarily around 450 nm. However, the ability of light to penetrate skin is also important; longer wavelengths penetrate better. In practice, light is used in the white, blue, and green wavelengths.

Second, a dose-response relationship exists between the amount of irradiation and reduction in serum bilirubin up to an irradiation level of 30-40 μW/cm2/nm. Most phototherapy units deliver much less energy, some at or near the minimally effective level, which appears to be approximately 6 μW/cm2/nm.

Third, the energy delivered to the infant's skin decreases with increasing distance between the infant and the light source. This distance should not be greater than 50 cm (20 in) and can profitably be less provided the infant's temperature is monitored.

Fourth, the efficiency of phototherapy depends on the amount of bilirubin that is irradiated. Irradiating a large skin surface area is more efficient than irradiating a small area, and the efficiency of phototherapy increases with serum bilirubin concentration.

Fifth, the nature and character of the light source may affect energy delivery. Irradiation levels using quartz halide spotlights are maximal at the center of the circle of light and decrease sharply towards the perimeter of the circle. Large infants and infants who can move away from the circle's center may receive less efficient phototherapy.

Although green light theoretically penetrates the skin better, it has not been shown unequivocally to be more efficient in clinical use than blue or white light. Since green light makes babies look sick and is unpleasant to work in, green light has not gained widespread acceptance.

Blue fluorescent tubes are widely used for phototherapy. Narrow-spectrum blue lamps (special blue) appear to work best, while ordinary blue fluorescent lamps are probably equivalent to standard white daylight lamps. Blue lights may cause discomfort in hospital staff members, which can be ameliorated by mixing blue and white tubes in the phototherapy unit. In the regular neonatal nursery at the author's institution, one white fluorescent tube in each of the outermost positions of the phototherapy unit is used, with special blue tubes for the remaining positions.

White (daylight) fluorescent tubes are less efficient than special blue lamps; however, decreasing the distance between infants and lamps can compensate for the lower efficiency. Use of reflecting materials also helps. Thus, in developing countries where the cost of special blue lamps may be prohibitive, efficient phototherapy is accomplished with white lamps.

White quartz lamps are an integral part of some radiant warmers and incubators. They have a significant blue component in the light spectrum. When used as spotlights, the energy field is strongly focused towards the center, with significantly less energy delivered at the perimeter, as discussed above.

Quartz lamps also are used in single or double banks of 3-4 bulbs attached to the overhead heat source of some radiant warmers. The energy field delivered by these is much more homogeneous than that of spotlights, and the energy output is reasonably high. However, since the lamps are fixed to the overhead heater unit, the ability to increase energy delivery by moving lights closer to infants is limited.

Fiberoptic light also is used in phototherapy units. These units deliver high energy levels, but to a limited surface area. Efficiency may be comparable to that of conventional low-output overhead phototherapy units but not to that of overhead units used with maximal output. Drawbacks of fiberoptic phototherapy units include noise from the fan in the light source and decrease of delivered energy with aging and/or breakage of the optic fibers.
Advantages include the following:
• Low risk of overheating the infant
• No need for eye shields
• Ability to deliver phototherapy with the infant in a bassinet next to the mother's bed
• Simple deployment for home phototherapy
• The possibility of irradiating a large surface area when combined with conventional overhead phototherapy units (double/triple phototherapy)

Indications for phototherapy are discussed as follows:
• The purpose of treating neonatal jaundice is to avoid neurotoxicity. Thus, indications for treatment have been based on clinical studies of infants who developed kernicterus. Historical data, much of which was derived from infants with hemolytic jaundice, appeared to suggest that total serum bilirubin levels greater than 350 μmol/L (20 mg/dL) were associated with increased risk of neurotoxicity, at least in full-term infants.

• As treatment of premature infants became more widespread and increasingly successful during the last half of the 20th century, autopsy findings and follow-up data suggested that immature infants were at risk of bilirubin encephalopathy at lower total serum bilirubin levels than mature infants. Treatment was initiated at lower levels for these infants.

• Until the 1940s, a truly effective treatment was not available. At that time, exchange transfusion was shown to be feasible and subsequently was used in the treatment of Rh-immunized infants with severe anemia, hyperbilirubinemia, or hydrops. However, exchange transfusion is not without risk for the infant, and only with the discovery of phototherapy did neonatal jaundice start to become an indication for treatment on a wider scale. Once phototherapy was shown to be a rather innocuous treatment, lights were turned on at lower serum bilirubin values than those that had triggered exchange transfusion. Exchange transfusion became the second-line treatment when phototherapy failed to control serum bilirubin levels.

• Clearly, the scientific data on which current therapeutic guidelines are based have very significant shortcomings. Unfortunately, because the endpoint of bilirubin neurotoxicity is permanent brain damage, a randomized study to reassess the guidelines is ethically unthinkable.

• In most neonatal wards, total serum bilirubin levels are used as the primary measure of risk for bilirubin encephalopathy. Quite a number of people would prefer to add a test for serum albumin at higher bilirubin levels, since bilirubin entry into the brain, a sine qua non for bilirubin encephalopathy, increases when the bilirubin-albumin ratio exceeds unity. Tests for bilirubin-albumin binding or unbound bilirubin levels are used by some but have failed to gain widespread acceptance.

• A number of guidelines for the management of neonatal jaundice have been published, and even more appear to be in local use without submission for critical review. In a survey published in 1996, the author analyzed clinical practices in this field based on responses from 108 neonatal intensive care units (NICUs) worldwide. The survey revealed a significant disparity in guidelines.

o Evidently, an infant might receive an exchange transfusion in one NICU for a serum bilirubin level that would not trigger phototherapy in many other NICUs. This disparity illustrates how difficult it has been to translate clinical data into sensible treatment guidelines.

o In 1994, the American Academy of Pediatrics (AAP) published guidelines for the management of hyperbilirubinemia in healthy full-term newborns.

o The AAP guidelines were controversial at the time of publication and continue to be a topic of discussion and disagreement among bilirubin experts. Briefly, the objections raised focused mainly on the fact that the AAP guidelines were untested and unproven. In addition, it has been noted that the AAP standard refers to "healthy term newborns," a designation that may be difficult to apply without testing every newborn for congenital hemolytic disease.

o The above discussion clarifies the finding that therapeutic guidelines for neonatal jaundice are difficult to substantiate with solid scientific facts. At present, the wisest choice may be to apply guidelines that have been in local use for a period sufficient to prove that no cases of kernicterus occurred while the guidelines were followed.

o These guidelines have been in use for a quarter of a century in most of Norway, and no known cases of kernicterus have occurred in infants in whom serum bilirubin levels were kept below the stated limits.

o Readers who are working in different ethnic or geographic situations should not apply these guidelines uncritically to their own populations but must consider factors unique to their settings. Such factors may include racial characteristics, prevalence of congenital hemolytic disease, and environmental concerns.

Key points in the practical execution of phototherapy are maximizing energy delivery and the available surface area.

• The infant should be naked except for diapers (use these only if deemed absolutely necessary and cut them to minimum workable size), and the eyes should be covered to reduce risk of retinal damage.

• Check the distance between the infant's skin and the light source. With fluorescent lamps, the distance should be no greater than 50 cm (20 in). This distance may be reduced if temperature homeostasis is monitored to reduce the risk of overheating.

• Cover the inside of the bassinet with reflecting material; white linen works well. Hang a white curtain around the phototherapy unit and bassinet. These simple expedients can multiply energy delivery by several fold.

• In the well baby unit at the author's institution, energy delivery was measured in the phototherapy bassinets in the horizontal and vertical planes corresponding to the level of the infant's back (when prone) and sides, respectively. Then, new fluorescent tubes were exchanged for the previously used lights and white linen was added as reflecting material in the bed and as curtains. These changes increased the energy delivered from 7-8 to 17-18 μW/cm2/nm in the horizontal plane and from 1 to 10-12 μW/cm2/nm in the vertical plane. The average time infants spent in phototherapy subsequently fell by 5 hours.

• When using spotlights, ensure that the infant is placed at the center of the circle of light, since photoenergy drops off towards the circle's perimeter. Observe the infant closely to ensure that the infant doesn't move away from the high-energy area. Spotlights are probably more appropriate for small premature infants than for larger near-term infants.

• Older data suggested that phototherapy was associated with increased insensible water loss; therefore, many clinicians have routinely added a certain percentage to the infant's estimated basic fluid requirements. Newer data suggest that if temperature homeostasis is maintained, fluid loss is not increased significantly by phototherapy. At the author's institution, routine fluid supplementation for infants under phototherapy is no longer recommended. Rather, the infant is monitored for weight loss, urine output, and urine specific gravity. Fluid intake is adjusted accordingly. In infants who are fed orally, the preferred fluid is milk, since milk serves as a vehicle to transport bilirubin out of the gut.

• Timing of follow-up serum bilirubin testing must be individualized. In infants admitted with extreme serum bilirubin values (>500 μmol/L or 30 mg/dL), monitoring should occur every hour or every other hour. At the author's institution, reductions in serum bilirubin values of 85 μmol/L/h (5 mg/dL/h) have been documented under such circumstances. In infants with more moderate elevations of serum bilirubin, monitoring every 6-12 hours is probably adequate.

• Expectations regarding efficacy of phototherapy must be tailored to the circumstances. In infants in whom serum bilirubin concentrations are still rising, a significant reduction of the rate of increase may be satisfactory. In infants in whom serum bilirubin concentrations are close to their peak, phototherapy should result in measurable reductions in serum bilirubin levels within a few hours. In general, the higher the starting serum bilirubin concentration, the more dramatic the initial rate of decline.

• Discontinuation of phototherapy is a matter of judgment, and individual circumstances must be taken into consideration. In practice, phototherapy is discontinued when serum bilirubin levels fall 25-50 μmol/L (1.5-3 mg/dL) below the level that triggered the initiation of phototherapy. Serum bilirubin levels often rebound after treatment has been discontinued, and follow-up tests should be obtained within 6-12 hours after discontinuation.

• Indications for prophylactic phototherapy are debatable. Phototherapy serves no purpose in an infant who is not clinically jaundiced. In general, the lower the serum bilirubin level, the less efficient the phototherapy. It seems more rational to apply truly effective phototherapy once serum (and skin) bilirubin has reached levels at which photons may do some good.

Generally, phototherapy is very safe, and it may have no serious long-term effects in neonates; however, the following adverse effects and complications have been noted:
• Insensible water loss may occur, but newer data suggest that this issue is not as important as previously believed. Rather than instituting blanket increases of fluid supplements to all infants under phototherapy, the author recommends fluid supplementation tailored to the infant's individual needs as measured through evaluation of weight curves, urine output, urine specific gravity, and fecal water loss.

• Phototherapy may be associated with loose stools. Increased fecal water loss may create a need for fluid supplementation.

• Retinal damage has been observed in some animal models during intense phototherapy. In an NICU environment, infants exposed to higher levels of ambient light were found to have an increased risk of retinopathy. Therefore, covering the eyes of infants undergoing phototherapy with eye patches is routine. Care must be taken lest the patches slip and leave the eyes uncovered or occlude one or both nares.

• The combination of hyperbilirubinemia and phototherapy can produce DNA-strand breakage and other effects on cellular genetic material. It has not been shown that these in vitro and animal data have any implication for treatment of human neonates. However, since most hospitals use cut-down diapers during PThpie, the issue of gonad shielding may be moot.

• Skin blood flow is increased during phototherapy, but this effect is less pronounced in modern servocontrolled incubators. However, redistribution of blood flow may occur in small premature infants. An increased incidence of patent ductus arteriosus (PDA) has been reported in these circumstances.

• Hypocalcemia appears to be more common in premature infants under phototherapy lights. It has been suggested that this is mediated by altered melatonin metabolism. Concentrations of certain amino acids in total parenteral nutrition (TPN) solutions subjected to phototherapy may deteriorate. Shield TPN solutions from light as much as possible.

• Regular maintenance of the equipment is required because accidents have been reported, including burns resulting from failure to replace UV filters.