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Jaundice, Neonatal: Treatment & Medication
Updated: May 4, 2009
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Treatment
Medical Care
Phototherapy, intravenous immune globulin, and exchange transfusion are the most widely used therapeutic modalities 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 is now arguably the most widespread therapy of any kind (excluding prophylactic treatments) used in newborns.
Phototherapy is effective because 3 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 isomers 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 about 20% of circulating bilirubin after a few hours of phototherapy. This proportion is not significantly influenced 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. Because photoisomers, by virtue of their water-soluble nature, should not be able to cross the blood-brain barrier, phototherapy may reduce 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 photoisomers means that only 75-80% of the total bilirubin may be 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 450-460 nm. However, the ability of light to penetrate skin is also important; longer wavelengths penetrate better. Thus, lamps with output predominantly in the blue region of the spectrum (460-490 nm) are probably most effective. In practice, light is used in the white, blue, and green wavelengths.
Second, a dose-response relationship may be observed between the amount of irradiation and reduction in serum bilirubin up to an irradiation level of 30-40 µW/cm2/nm. Many older phototherapy units deliver much less energy, some at or near the minimally effective level, which appears to be approximately 6 µW/cm2/nm. On the other hand, newer phototherapy units, when properly configured and with the use of reflecting blanket and curtains may deliver light energy above the 40 µW/cm2/nm suggested to be the saturation level.
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 probably be less (down to 10 cm) 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. Because 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.
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 are also 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, because 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 is also 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)
"Double" and "triple" phototherapy, which implies the concurrent use of 2 or 3 phototherapy units to treat the same patient, has often been used in the treatment of infants with very high levels of serum bilirubin. The studies that appeared to show a benefit with this approach were performed with old, relatively low-yield phototherapy units. Newer phototherapy units provide much higher levels of irradiance, which may in fact be close to the apparent saturation level of bilirubin photoisomerization. Whether double or triple phototherapy also confers a benefit with the newer units, has not been tested in systematic trials.
Indications for phototherapy are 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 was subsequently 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. However, recent data have shown that treatment with intravenous immune globulin (IVIG) in infants with Rh or ABO isoimmunization can significantly reduce the need for exchange transfusions. At the author's institution, a tertiary center where exchange transfusions used to be frequent, only 0-2 such procedures per year are performed, and IVIG has replaced exchange transfusion as the second-line treatment in infants with isoimmune jaundice.
- 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. Numerous people would prefer to add a test for serum albumin at higher bilirubin levels because 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. New analytical tools for measurement of unbound bilirubin have greatly simplified the process, but the effect on clinical practice remains to be seen.
- Numerous 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.7 The survey revealed a significant disparity in guidelines.
- Media file 1 shows a box-and-whisker plot of the range of serum bilirubin values that trigger phototherapy and exchange transfusion, respectively, in these NICUs. 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.
The graph represents indications for phototherapy and exchange transfusion in infants (with a birthweight of 3500 g) in 108 neonatal ICUs.
The left panel shows the range of indications for phototherapy, whereas the right panel shows the indications for exchange transfusion. Numbers on the vertical axes are serum bilirubin concentrations in mg/dL (lateral) and mmol/L (middle). In the left panel, the solid line refers to the current recommendation of the American Academy of Pediatrics (AAP) for low-risk infants, the line consisting of long dashes (- - - - -) represents the level at which the AAP recommends phototherapy for infants at intermediate risk, and the line with short dashes (-----) represents the suggested intervention level for infants at high risk.
In the right panel, the dotted line (......) represents the AAP suggested intervention level for exchange transfusion in infants considered at low risk, the line consisting of dash-dot-dash (-.-.-.-.) represents the suggested intervention level for exchange transfusion in infants at intermediate risk, and the line consisting of dash-dot-dot-dash (-..-..-..-) represents the suggested intervention level for infants at high risk.
Intensive phototherapy is always recommended while preparations for exchange transfusion are in progress. The box-and-whisker plots show the following values: lower error bar = 10th percentile; lower box margin = 25th percentile; line transecting box = median; upper box margin = 75th percentile; upper error bar = 90th percentile; and lower and upper diamonds = 5th and 95th percentiles, respectively. - In 2004, the AAP published new guidelines for the management of hyperbilirubinemia in healthy full-term newborns.8 These guidelines have been plotted on Media file 1.
- The 2004 AAP guidelines represent a significant change from the 1994 guidelines.8 Thus, the emphasis on preventive action and risk evaluation is much stronger. An algorithm aids in the assessment of risk and the decision about further management and follow-up (see Media file 2). The committee that wrote the guidelines has carefully assessed the strength of the scientific evidence on which the guidelines are based.
Algorithm for the management of jaundice in the newborn nursery.
- Practitioners in North America are advised to follow the 2004 AAP guidelines. However, clinicians in different ethnic or geographic regions should tailor these guidelines as pertinent to their own populations and must consider factors that are unique to their medical practice settings. Such factors may include racial characteristics, prevalence of congenital hemolytic disorders, and environmental concerns. At present, the wisest course of action may be to apply local guidelines that have been successful in the prevention of kernicterus.
- With this background and the clear understanding that this is meant only as an example, Media file 3 shows the chart currently in use in most pediatric departments in Norway. These guidelines are the result of a 2006 consensus in the Neonatal Subgroup of the Norwegian Pediatric Society. The similarity between the Norwegian chart and the 2004 AAP guidelines are apparent.
Guidelines for management of neonatal jaundice currently in use in most pediatric departments in Norway. The guidelines were based on previously used charts and were created through a consensus process in the Neonatal Subgroup of the Norwegian Pediatric Society. These guidelines were adopted as national at the fall meeting of the Norwegian Pediatric Society. The reverse side of the chart contains explanatory notes to help the user implement the guidelines. A separate information leaflet for parents was also created.
- Media file 1 shows a box-and-whisker plot of the range of serum bilirubin values that trigger phototherapy and exchange transfusion, respectively, in these NICUs. 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.
Key points in the practical execution of phototherapy include maximizing energy delivery and the available surface area. Also consider the following:
- 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 down to 10-20 cm if temperature homeostasis is monitored to reduce the risk of overheating. Note that this does not apply to quartz lamps.
- 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.
- 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 significantly increased 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 orally fed, the preferred fluid is milk because it 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. 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 may 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.
- Wherever phototherapy is offered as a therapeutic modality, a device for measuring the irradiance delivered by the equipment used should be readily at hand. This assists in configuring the phototherapy set-up to deliver optimal efficiency.
Management of infants with extreme jaundice includes the following:
- Numerous cases have been reported in which infants have been readmitted to hospitals with extreme jaundice. In some cases, significant delays have occurred between the time the infant was first seen by medical personnel and the actual commencement of effective therapy.
- Any infant who returns to the hospital with significant jaundice within the first 1-2 weeks of birth should be immediately triaged with measurement of transcutaneous bilirubin. High values should result in immediate initiation of treatment. If such a measuring device is not available, or if the infant presents with any kind of neurological symptoms, the infant should be put in maximally efficient phototherapy as an emergency procedure, preferably by fast-tracking the infant to a NICU. Waiting for laboratory results is not necessary before instituting such therapy because no valid contraindications to phototherapy are possible in this scenario. Plans for an exchange transfusion do not constitute an argument for delaying or not performing phototherapy. Immediate benefit is obtained within minutes, as soon as conversion of bilirubin into water-soluble photoisomers is measurable.
- The need for intravenous hydration in such infants has been discussed. In the absence of clinical signs of dehydration there is no evidence that overhydration is helpful. If the infant is dehydrated, hydration should be given as clinically indicated. However, if the infant is able to tolerate oral feeding, oral hydration with a breast milk substitute is likely to be superior to intravenous hydration because it reduces enterohepatic circulation of bilirubin and helps "wash" bilirubin out of the bowel.
- Every hospital in which babies are delivered, or which has an emergency department in which infants may be seen, should consider developing a protocol and triage algorithm for rapid evaluation and management of jaundiced infants. The objective of such a protocol should be rapid recognition of risk severity and reduction in the time to initiate appropriate treatment.
Generally, phototherapy is very safe and 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 data suggest that this issue is not as important as previously believed. Rather than instituting blanket increases of fluid supplements to all infants receiving 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. In vitro and animal data have not demonstrated any implication for treatment of human neonates. However, because most hospitals use (cut-down) diapers during phototherapy, 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. The appropriate treatment of PDA has been reviewed.9
- Hypocalcemia appears to be more common in premature infants under phototherapy lights. This has been suggested to be mediated by altered melatonin metabolism. Concentrations of certain amino acids in total parenteral nutrition solutions subjected to phototherapy may deteriorate. Shield total parenteral nutrition solutions from light as much as possible.
- Regular maintenance of the equipment is required because accidents have been reported, including burns resulting from a failure to replace UV filters.
Intravenous immune globulin
In recent years, IVIG has been used for numerous immunologically mediated conditions. In the presence of Rh, ABO, or other blood group incompatibilities that cause significant neonatal jaundice, IVIG has been shown to significantly reduce the need for exchange transfusions.
The 2004 AAP guidelines suggest a dose range for IVIG of 500-1000 mg/kg.8
The authors routinely use 500 mg/kg infused intravenously over a period of 2 hours for Rh or ABO incompatibility when the total serum bilirubin levels approach or surpass the exchange transfusions limits. The authors have, on occasion, repeated the dose 2-3 times. In most cases, when this is combined with intensive phototherapy, avoiding exchange transfusion is possible. In the authors' institution, with about 750 NICU admissions per year, the use of exchange transfusions has decreased to 0-2 per year following the implementation of IVIG therapy for Rh and ABO isoimmunization.10 The authors do not use IVIG in the presence of hydrops. Anecdotally, IVIG appears less likely to be successful when the infant is anemic (Hb <10 g/dL).
Exchange transfusion
Exchange transfusion is indicated for avoiding bilirubin neurotoxicity when other therapeutic modalities have failed or are not sufficient. In addition, the procedure may be indicated in infants with erythroblastosis who present with severe anemia, hydrops, or both, even in the absence of high serum bilirubin levels.
Exchange transfusion was once a common procedure. A significant proportion was performed in infants with Rh isoimmunization. Immunotherapy in Rh-negative women at risk for sensitization has significantly reduced the incidence of severe Rh erythroblastosis. Therefore, the number of infants requiring exchange transfusion is now much smaller, and even large NICUs may perform only a few procedures per year. ABO incompatibility has become the most frequent cause of hemolytic disease in industrialized countries.
Early exchange transfusion has usually been performed because of anemia (cord hemoglobin <11 g/dL), elevated cord bilirubin level (>70 µmol/L or 4.5 mg/dL), or both. A rapid rate of increase in the serum bilirubin level (>15-20 µmol/L /h or 1 mg/dL/h) was an indication for exchange transfusion, as was a more moderate rate of increase (>8-10 µmol/L/h or 0.5 mg/dL/h) in the presence of moderate anemia (11-13 g/dL).
The serum bilirubin level that triggered an exchange transfusion in infants with hemolytic jaundice was 350 µmol/L (20 mg/dL) or a rate of increase that predicted this level or higher. Strict adherence to the level of 20 mg/dL has been jocularly referred to as vigintiphobia (fear of 20).
Currently, most experts encourage an individualized approach, recognizing that exchange transfusion is not a risk-free procedure, that effective phototherapy converts 15-25% of bilirubin to nontoxic isomers, and that transfusion of a small volume of packed red cells may correct anemia. Administration of IVIG (500 mg/kg) has been shown to reduce red cell destruction and to limit the rate of increase of serum bilirubin levels in infants with Rh and ABO isoimmunization (see above).
Current AAP guidelines distinguish between 3 risk categories: low, intermediate, and high.8 These correspond to 3 levels of suggested intervention, which increase from birth and plateau at age 4 days. Naturally, intervention levels associated with exchange transfusion are higher than those of phototherapy. Intensive phototherapy is strongly recommended in preparation for an exchange transfusion. In fact, intensive phototherapy should be performed on an emergency basis in any infant admitted for pronounced jaundice; do not await laboratory test results in these cases. Phototherapy has minimal side effects, whereas the waiting period for laboratory test results and blood for exchange can take hours and could constitute the difference between intact survival and survival with kernicterus. If phototherapy does not significantly lower serum bilirubin levels, exchange transfusion should be performed.
Many believe that hemolytic jaundice represents a greater risk for neurotoxicity than nonhemolytic jaundice, although the reasons for this belief are not intuitively obvious, assuming that total serum bilirubin levels are equal. In animal studies, bilirubin entry into or clearance from the brain was not affected by the presence of hemolytic anemia.
The technique of exchange transfusion, including adverse effects and complications, is discussed extensively elsewhere. For more information, please consult Hemolytic Disease of Newborn.
Other therapiesIn infants with breast milk jaundice, interruption of breastfeeding for 24-48 hours and feeding with breast milk substitutes often helps to reduce the bilirubin level. Evidence suggests that the simple expedient of supplementing feeds of breast milk with 5 mL of a breast milk substitute reduces the level and duration of jaundice in breast milk–fed infants. Because this latter intervention causes less interference with the establishment of the breastfeeding dyad, the authors prefer to use this approach rather than complete interruption of breast feeding in most cases.
Oral bilirubin oxidase can reduce serum bilirubin levels, presumably by reducing enterohepatic circulation; however, its use has not gained wide popularity. The same may be said for agar or charcoal feeds, which act by binding bilirubin in the gut. Bilirubin oxidase is not available as a drug, and for this reason, its use outside an approved research protocol probably is proscribed in many countries.
Prophylactic treatment of Rh-negative women with Rh immunoglobulin has significantly decreased the incidence and severity of Rh-hemolytic disease.
Surgical Care
Surgical care is not indicated in infants with physiologic neonatal jaundice. Surgical therapy is indicated in infants in whom jaundice is caused by bowel or external bile duct atresia.
Consultations
For infants with physiologic neonatal jaundice, no consultation is required. Gastroenterologists and surgeons may be consulted regarding infants with jaundice resulting from hepatobiliary or bowel disease.
Diet
Breastfeeding concerns associated with neonatal jaundice are as follows:
- Incidence and duration of jaundice have increased as breastfeeding has become more popular. The factors in breast milk that contribute to this phenomenon are unclear. In selected infants, interruption of breastfeeding and its replacement for 24-48 hours by a breast milk substitute may be indicated. This decision should always be discussed in person with the mother before implementation. The authors' practice is now to first perform a trial of 5 mL of a hydrolyzed formula given after each breast meal. The authors typically try this for at least 1-2 days, with follow-up of bilirubin values. Only if this is unsuccessful do the authors occasionally attempt interruption of breast feeding.
- With increasing emphasis on breastfeeding, some new mothers may have difficulty admitting (even to themselves) to a lack of success in establishing lactation. Occasionally, infants of breastfeeding mothers are admitted to hospitals with severe jaundice. They typically weigh significantly less than their birthweight at a time when they should have regained and surpassed that weight. Presumably, the process is one of increased enterohepatic circulation, as bilirubin is left longer in the proximal gut for lack of milk to bind it and carry it onward and out. The author refers to this condition as lack-of-breast-milk jaundice. These infants may respond dramatically to phototherapy plus oral feedings of milk ad libitum.
Medication
Medications are not usually administered in infants with physiologic neonatal jaundice. However, in certain instances, phenobarbital, an inducer of hepatic bilirubin metabolism, has been used to enhance bilirubin metabolism. Several studies have shown that phenobarbital is effective in reducing mean serum bilirubin values during the first week of life. Phenobarbital may be administered prenatally in the mother or postnatally in the infant.
In populations in which the incidence of neonatal jaundice or kernicterus is high, this type of pharmacologic treatment may warrant consideration. However, concerns surround the long-term effects of phenobarbital on these children. Therefore, this treatment is probably not justified in populations with a low incidence of neonatal jaundice. Other drugs can induce bilirubin metabolism, but lack of adequate safety data prevents their use outside research protocols.
Intravenous immunoglobulin (IVIG) at 500 mg/kg has been shown to significantly reduce the need for exchange transfusions in infants with isoimmune hemolytic disease.10 The mechanism is unknown but may be related to the way the immune system handles red cells that have been coated by antibodies. Published experience is still somewhat limited, but administration of immunoglobulin does not appear to be likely associated with greater risks for the infant than an exchange transfusion.
A new therapy currently under development consists of inhibition of bilirubin production through blockage of heme oxygenase. This can be achieved through the use of metal mesoporphyrins and protoporphyrins. Apparently, heme can be directly excreted through the bile; thus, inhibition of heme oxygenase does not result in accumulation of unprocessed heme. This approach may virtually eliminate neonatal jaundice as a clinical problem. However, before the treatment can be applied on a wide scale, important questions regarding the long-term safety of the drugs must be answered. Also, in light of data suggesting that bilirubin may play an important role as a free radical quencher, a more complete understanding of this putative role for bilirubin is required before wholesale inhibition of its production is contemplated.
More on Jaundice, Neonatal |
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| Differential Diagnoses & Workup: Jaundice, Neonatal |
 Treatment & Medication: Jaundice, Neonatal |
| Follow-up: Jaundice, Neonatal |
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References
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Further Reading
Keywords
neonatal jaundice, icterus neonatorum, neonatal hyperbilirubinemia, physiologic jaundice, nonphysiologic jaundice, neonatal jaundice, unconjugated bilirubin, unconjugated hyperbilirubinemia, kernicterus, physiologic hyperbilirubinemia, Gilbert syndrome, hypertrophic pyloric stenosis, yellow skin, breastfeeding jaundice, breast milk jaundice, G-6-PD deficiency, galactosemia, hypothyroidism, birth trauma, hepatosplenomegaly, petechiae, microcephaly, polycythemia, diagnosis, treatment, yellow-colored baby, yellowed skin
