PHOTOTHERAPY FOR PHOTOTHERAPY FOR NEONATAL JAUNDICENEONATAL JAUNDICE

By: ChoirunnisaBy: Choirunnisa

030.05.057030.05.057

ABSTRACTABSTRACT Jaundice is the most common condition that requires Jaundice is the most common condition that requires

medical attention in newborns.medical attention in newborns. The yellow coloration of the skin and sclera in newborns The yellow coloration of the skin and sclera in newborns

with jaundice is the result of accumulation of with jaundice is the result of accumulation of unconjugated bilirubin. unconjugated bilirubin.

Reflects a normal transitional phenomenon. Reflects a normal transitional phenomenon. However, in some infants, serum bilirubin levels may However, in some infants, serum bilirubin levels may

excessively rise, unconjugated bilirubin is neurotoxic and excessively rise, unconjugated bilirubin is neurotoxic and can cause death in newborns and lifelong neurologic can cause death in newborns and lifelong neurologic sequelae in infants who survive (sequelae in infants who survive (kernicteruskernicterus).).

Jaundice is observed during the 1st week of life in Jaundice is observed during the 1st week of life in approximately 60 % term infants and 80 % of preterm approximately 60 % term infants and 80 % of preterm infant.infant.

ABSTRACTABSTRACT

Regardless of the cause, the goal of Regardless of the cause, the goal of theraphy is to prevent the concentration of theraphy is to prevent the concentration of indirect-reacting bilirubin in the blood from indirect-reacting bilirubin in the blood from reaching levels at which neurotoxicity may reaching levels at which neurotoxicity may occur.It is recommended that occur.It is recommended that phototherapy and, if unsucceful, exchange phototherapy and, if unsucceful, exchange transfusion be used to keep the maximal transfusion be used to keep the maximal total serum bilirubin bellow levels indicatedtotal serum bilirubin bellow levels indicated

Normal bilirubin metabolismNormal bilirubin metabolism In the first oxidation step, biliverdin is formed from heme through the action In the first oxidation step, biliverdin is formed from heme through the action

of heme oxygenase of heme oxygenase

water-soluble biliverdin is reduced to bilirubin water-soluble biliverdin is reduced to bilirubin

unconjugated bilirubin is transported in the plasma tightly bound to albumin. unconjugated bilirubin is transported in the plasma tightly bound to albumin.

Albumin is bound to a receptor on the cell surface when the bilirubin-Albumin is bound to a receptor on the cell surface when the bilirubin-albumin complex reaches the hepatocytealbumin complex reaches the hepatocyte

After uptake by the liver, it is converted into two isomeric monoglucuronides After uptake by the liver, it is converted into two isomeric monoglucuronides and a diglucuronide (direct bilirubin) by the enzyme and a diglucuronide (direct bilirubin) by the enzyme uridinediphosphoglucuronosyltransferase 1A1 (UGT1A1). The water-soluble uridinediphosphoglucuronosyltransferase 1A1 (UGT1A1). The water-soluble glucuronides are excreted in bileglucuronides are excreted in bile

Without glucuronidation, bilirubin cannot be excreted in bile or urine Without glucuronidation, bilirubin cannot be excreted in bile or urine

Phototherapy converts bilirubin to yellow photoisomers and colorless oxidation Phototherapy converts bilirubin to yellow photoisomers and colorless oxidation products that are less lipophilic than bilirubin and do not require hepatic products that are less lipophilic than bilirubin and do not require hepatic conjugation for excretion. Photoisomers are excreted mainly in bile, anconjugation for excretion. Photoisomers are excreted mainly in bile, an

oxidation products predominantly in urine.oxidation products predominantly in urine.

Physiologic JaundicePhysiologic Jaundice

The level of indirect bilirubin in umbilical cord serum is 1-The level of indirect bilirubin in umbilical cord serum is 1-3 mg/dl and rises at a rate of less than 5 mg/dl/24 hr, 3 mg/dl and rises at a rate of less than 5 mg/dl/24 hr, thus jaundice become visible on the 2nd-3rd day, usually thus jaundice become visible on the 2nd-3rd day, usually peaking between the 2nd and 4th days at 5-6 mg/dl and peaking between the 2nd and 4th days at 5-6 mg/dl and decreasing to below 2 mg/dl between the 5th and 7th decreasing to below 2 mg/dl between the 5th and 7th days of life. Indirect bilirubin levels in full term infants days of life. Indirect bilirubin levels in full term infants decline to adult level (1 mg/dl) by 10-14 days of life.decline to adult level (1 mg/dl) by 10-14 days of life.

The diagnosis of physiologic jaundice in term or preterm The diagnosis of physiologic jaundice in term or preterm infant can be established only by precluding known infant can be established only by precluding known causes of jaundice on the basis of the history and clinical causes of jaundice on the basis of the history and clinical and laboratory findingand laboratory finding

Pathological JaundicePathological Jaundice

(1)It appears in the 1st 24-36 hr of life, (1)It appears in the 1st 24-36 hr of life, (2)Serum bilirubin is rising at a rate faster than 5 mg/dl/24hr (2)Serum bilirubin is rising at a rate faster than 5 mg/dl/24hr (3)Serum bilirubin is greater than 12 mg/dl in fullterm ( especially in the (3)Serum bilirubin is greater than 12 mg/dl in fullterm ( especially in the

absence of risk factor) or 10-14 mg/dl in preterm infants,absence of risk factor) or 10-14 mg/dl in preterm infants,(4)Jaundice persists after 10-14 days of life,(4)Jaundice persists after 10-14 days of life,(5)Direct-reacting bilirubin is greater than 2 mg/dl at any time. (5)Direct-reacting bilirubin is greater than 2 mg/dl at any time.

Among other factors suggesting a non physiologic cause of jaundiceAmong other factors suggesting a non physiologic cause of jaundiceare a family history of hemolytic disease, palor, hepatomegaly,are a family history of hemolytic disease, palor, hepatomegaly,splenomegaly, failure of phototherapy to lower bilirubin, vomiting,splenomegaly, failure of phototherapy to lower bilirubin, vomiting,lethargy, poor feeding, excessive weight loss, apnea, bradycardia,lethargy, poor feeding, excessive weight loss, apnea, bradycardia,abnormal vital signs ( including hypothermia), light colored stools, darkabnormal vital signs ( including hypothermia), light colored stools, darkurine positive for bilirubin, and signs of kernicterusurine positive for bilirubin, and signs of kernicterus

PhototherapyPhototherapy

Phototherapy is the primary treatment in Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia. neonates with unconjugated hyperbilirubinemia. This therapeutic principle was discovered rather This therapeutic principle was discovered rather serendipitously in England in the 1950s and now serendipitously in England in the 1950s and now is arguably the most widespread therapy of any is arguably the most widespread therapy of any kind (excluding prophylactic treatments) used in kind (excluding prophylactic treatments) used in newborns. newborns.

The goal of therapy is to lower the concentration The goal of therapy is to lower the concentration of circulating bilirubin or keep it from increasing. of circulating bilirubin or keep it from increasing.

Mechanisme of phototherapyMechanisme of phototherapy

Phototherapy achieves this by using light energy to Phototherapy achieves this by using light energy to change the shape and structure of bilirubin, converting it change the shape and structure of bilirubin, converting it to molecules that can be excreted even when normal to molecules that can be excreted even when normal conjugation is deficient Absorption of light by dermal and conjugation is deficient Absorption of light by dermal and subcutaneous bilirubin induces a fraction of the pigment subcutaneous bilirubin induces a fraction of the pigment to undergo several photochemical reactions that occur at to undergo several photochemical reactions that occur at very different rates. very different rates.

The products are less lipophilic than bilirubin, and unlike The products are less lipophilic than bilirubin, and unlike bilirubin, they can be excreted in bile or urine without the bilirubin, they can be excreted in bile or urine without the need for conjugation. The relative contributions of the need for conjugation. The relative contributions of the various reactions to the overall elimination of bilirubin are various reactions to the overall elimination of bilirubin are unknown. unknown.

Bilirubin absorbs light maximally in the blue Bilirubin absorbs light maximally in the blue range (420-470 nm) . Bilirubin in the skin range (420-470 nm) . Bilirubin in the skin absorbs light energy, which by absorbs light energy, which by photoisomerization converts the toxic native photoisomerization converts the toxic native unconjugated 4Z,15Z-bilirubin into the unconjugated 4Z,15Z-bilirubin into the unconjugated configurational isomer 4Z,15E-unconjugated configurational isomer 4Z,15E-bilirubin. The later is the product of a reversible bilirubin. The later is the product of a reversible reaction and is excreted in bile without any need reaction and is excreted in bile without any need for conjugation. Phototherapy also converts for conjugation. Phototherapy also converts native bilirubin, by an irreversible reaction, to the native bilirubin, by an irreversible reaction, to the structural isomer lumirubin, which is excreted by structural isomer lumirubin, which is excreted by the kidneys in the conjugated state.the kidneys in the conjugated state.

Indication Indication

After the presence of pathologic After the presence of pathologic hyperbilirubinemia has been esthabilish. hyperbilirubinemia has been esthabilish.

Guidelines published by the American Guidelines published by the American Academy of Pediatrics in 2004 (Table Academy of Pediatrics in 2004 (Table 1&2)1&2)

TABLE 1 : Suggested maximal indirect serum bilirubin concentration (mg/dl)TABLE 1 : Suggested maximal indirect serum bilirubin concentration (mg/dl) in preterm infants in preterm infants

BirthweightBirthweight uncomplicateduncomplicated complicatedcomplicated

<1000 <1000 12-13 12-13 10-12 10-12

1000-1250 1000-1250 12-14 12-14 10-12 10-12

1251-1499 1251-1499 14-16 14-16 12-14 12-14

1500-1999 1500-1999 16-20 16-20 15-17 15-17

2000-2500 2000-2500 20-22 20-22 18-20 18-20

Approach to indirect hyperbilirubinemia in healthy term infants without Approach to indirect hyperbilirubinemia in healthy term infants without hemolisishemolisis

Age (hr) Age (hr) Phototherapy Phototherapy Intensive Intensive phototherapy and phototherapy and preparation for preparation for excahange excahange tranfusion tranfusion

Exchange Exchange transfusion if transfusion if phototherapy fail phototherapy fail

<24 <24 Not seen in Not seen in “healthy” infants “healthy” infants

Not seen in Not seen in “healthy” infants “healthy” infants

Not seen in Not seen in “healthy” infants “healthy” infants

24-4824-48 >15-18 >15-18 ≥ ≥ 2525 ≥≥20 20

49-7249-72 ≥≥18-20 18-20 ≥≥3030 ≥≥25 25

>72 >72 ≥≥2020 ≥≥30 30 ≥≥25 25

>2wk >2wk Probably is due to Probably is due to a serious a serious underlying causes underlying causes

Probably is due to Probably is due to a serious a serious underlying causes underlying causes

Probably is due to Probably is due to a serious a serious underlying causes underlying causes

Indication (cont.)Indication (cont.)

Prophylactic phototherapy in VLBW infants Prophylactic phototherapy in VLBW infants Any infant who returns to the hospital with Any infant who returns to the hospital with

significant jaundice within the first 1-2 weeks of significant jaundice within the first 1-2 weeks of birth should be immediately triaged with birth should be immediately triaged with measurement of transcutaneous bilirubin. High measurement of transcutaneous bilirubin. High values should result in immediate initiation of values should result in immediate initiation of treatment .If such a measuring device is not treatment .If such a measuring device is not available, or if the infant presents with any kind available, or if the infant presents with any kind of neurological symptoms, the infant should be of neurological symptoms, the infant should be put in maximally efficient phototherapy as an put in maximally efficient phototherapy as an emergency procedure emergency procedure

Contraindication Contraindication

Congenital porphyria, a family history of Congenital porphyria, a family history of porphyria ; severe blistering and agitation porphyria ; severe blistering and agitation during phototherapy could be a sign of during phototherapy could be a sign of congenital porphyria.congenital porphyria.

Complicaton Complicaton

Loose stools, erythematous, macular rash, rare Loose stools, erythematous, macular rash, rare purpuric and bullous eruptions have also been purpuric and bullous eruptions have also been reported in infants with severe cholestatic reported in infants with severe cholestatic jaundice who are receiving phototherapy jaundice who are receiving phototherapy

Overheating and dehydration(increase Overheating and dehydration(increase insensible water loss, diarrhea) insensible water loss, diarrhea)

A recent study suggested that intensive A recent study suggested that intensive phototherapy might increase the number of phototherapy might increase the number of atypical melanocytic nevi identified at school atypical melanocytic nevi identified at school age, although other research has not shown this age, although other research has not shown this association. association.

Bronze baby syndrome, in which the skin, Bronze baby syndrome, in which the skin, serum, and urine develop a dark, grayish-brown serum, and urine develop a dark, grayish-brown discoloration. discoloration.

Eye injury and nasal occlution from the Eye injury and nasal occlution from the bandages are uncommon bandages are uncommon

The combination of hyperbilirubinemia and The combination of hyperbilirubinemia and phototherapy can produce DNA-strand breakage phototherapy can produce DNA-strand breakage and other effects on cellular genetic material and other effects on cellular genetic material

Hypocalcemia Hypocalcemia

Important Factors in the Efficacy of Important Factors in the Efficacy of Phototherapy Phototherapy

Irradiance (energy output) of the light sourceIrradiance (energy output) of the light source The dose of phototherapy should be checked The dose of phototherapy should be checked

with the use of a commercially available with the use of a commercially available radiometer designed for that purpose radiometer designed for that purpose

The type of light source The type of light source The infant's distance from the light (the nearer The infant's distance from the light (the nearer

the light source, the greater the irradiance) and the light source, the greater the irradiance) and the area of skin exposed the area of skin exposed

TechniqueTechnique

Special blue fluorescent tubes, placing the lamp Special blue fluorescent tubes, placing the lamp within 15-20 cm of the infant within 15-20 cm of the infant

Placing fiberopticphototherapy blanket under the Placing fiberopticphototherapy blanket under the infant’s back to increase the exposed surface infant’s back to increase the exposed surface area area

The infant should be naked except for diapers The infant should be naked except for diapers The infant’s eyes should be closed and The infant’s eyes should be closed and

adequately covered to prevent exposure to light adequately covered to prevent exposure to light Body temperature should be monitored Body temperature should be monitored

TechniqueTechnique

Follow UpFollow Up

Timing of follow-up serum bilirubin testing must Timing of follow-up serum bilirubin testing must be individualized. In infants admitted with be individualized. In infants admitted with extreme serum bilirubin values (>500 µmol/L or extreme serum bilirubin values (>500 µmol/L or 30 mg/dL), monitoring should occur every hour 30 mg/dL), monitoring should occur every hour or every other hour or every other hour

Reductions in serum bilirubin values of 85 Reductions in serum bilirubin values of 85 µmol/L/h (5 mg/dL/h) have been documented µmol/L/h (5 mg/dL/h) have been documented under such circumstances. In infants with more under such circumstances. In infants with more moderate elevations of serum bilirubin, moderate elevations of serum bilirubin, monitoring every 6-12 hours is probably monitoring every 6-12 hours is probably adequate. adequate.

Follow up (Follow up (cont.)cont.)

Serum bilirubin level and hematocrit should be monitored Serum bilirubin level and hematocrit should be monitored every 4-8 hr in infant with hemolytic disease or those every 4-8 hr in infant with hemolytic disease or those with bilirubin levels near the range considered toxic for with bilirubin levels near the range considered toxic for the individual infant.others, particularly older infants, may the individual infant.others, particularly older infants, may be monitored at 12-24 hr intervals. Monitoring should be monitored at 12-24 hr intervals. Monitoring should continue for at least 24 hr after cessation of continue for at least 24 hr after cessation of phototherapy in patients with hemolytic disease because phototherapy in patients with hemolytic disease because unexpected rises in serum bilirubin sometimes occur and unexpected rises in serum bilirubin sometimes occur and require further treatment. Skin color cannot be relied on require further treatment. Skin color cannot be relied on for evaluating the effectiveness of phototherapy,the skin for evaluating the effectiveness of phototherapy,the skin of babies exposed to light may appear to be almost of babies exposed to light may appear to be almost without jaundice in the presence of marked without jaundice in the presence of marked hyperbilirubinemia.hyperbilirubinemia.

Follow up (cont)Follow up (cont) VLBW infants receiving phototherapy for 1-3 VLBW infants receiving phototherapy for 1-3

days have peak serum bilirubin concentration days have peak serum bilirubin concentration about half those of untreated infants. In about half those of untreated infants. In premature infants without significant hemolysis, premature infants without significant hemolysis, serum bilirubin usually decline 1-3 mg/dl after serum bilirubin usually decline 1-3 mg/dl after 12-24 hr of conventional phototherapy and peak 12-24 hr of conventional phototherapy and peak levels may be decreased by 3-6 mg/dl. In some levels may be decreased by 3-6 mg/dl. In some infants with a total serum bilirubin level greater infants with a total serum bilirubin level greater than 30 mg per deciliter (513 µmol per liter), than 30 mg per deciliter (513 µmol per liter), intensive phototherapy can result in a decline of intensive phototherapy can result in a decline of as much as 10 mg per deciliter (171 µmol per as much as 10 mg per deciliter (171 µmol per liter) within a few hours.liter) within a few hours.

Discontinuation of phototherapyDiscontinuation of phototherapy

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

It should be discontinued as soon as the It should be discontinued as soon as the indirect bilirubin concentration has been reduced indirect bilirubin concentration has been reduced to levels considered safe in view of the infant’s to levels considered safe in view of the infant’s age and condition.age and condition.

Discontinuation of phototherapyDiscontinuation of phototherapy(cont(cont))

Although there are no firm standards for discontinuing treatment, Although there are no firm standards for discontinuing treatment, phototherapy can be safely stopped in infants treated during the phototherapy can be safely stopped in infants treated during the birth hospitalization when the total serum bilirubin falls below the birth hospitalization when the total serum bilirubin falls below the level at which phototherapy was initiated.level at which phototherapy was initiated.

In contrast, in infants readmitted for phototherapy, hemolysis is less In contrast, in infants readmitted for phototherapy, hemolysis is less often the cause of their hyperbilirubinemia and treatment is begun at often the cause of their hyperbilirubinemia and treatment is begun at a higher initial level of total serum bilirubin . In these patients, a higher initial level of total serum bilirubin . In these patients, intensive phototherapy can result in a decrement of 30 to 40% in the intensive phototherapy can result in a decrement of 30 to 40% in the first 24 hours, with the most pronounced decline occurring in the first first 24 hours, with the most pronounced decline occurring in the first 4 to 6 hours; phototherapy can be discontinued when the total 4 to 6 hours; phototherapy can be discontinued when the total serum bilirubin level has fallen below 13 to 14 mg per deciliter .serum bilirubin level has fallen below 13 to 14 mg per deciliter .

ReboundRebound

A rebound in the total serum bilirubin level of 1 to 2 mg A rebound in the total serum bilirubin level of 1 to 2 mg per deciliter (17 to 34 µmol per liter) and occasionally per deciliter (17 to 34 µmol per liter) and occasionally more can occur after phototherapy is discontinued. more can occur after phototherapy is discontinued. Infants at increased risk of a clinically significant rebound Infants at increased risk of a clinically significant rebound are those born at less than 37 weeks' gestation, those are those born at less than 37 weeks' gestation, those with hemolytic disease, and those treated with with hemolytic disease, and those treated with phototherapy during the birth hospitalization.It is usually phototherapy during the birth hospitalization.It is usually unnecessary to keep an infant in the hospital to check for unnecessary to keep an infant in the hospital to check for rebound,but for infants who require phototherapy during rebound,but for infants who require phototherapy during their birth hospitalization and for those with well-defined their birth hospitalization and for those with well-defined hemolytic disease, a follow-up bilirubin level should be hemolytic disease, a follow-up bilirubin level should be obtained 24 hours after discharge.obtained 24 hours after discharge.

CONCLUSIONCONCLUSION

Neonatal jaundice is a yellowing of the skin and other tissues of a Neonatal jaundice is a yellowing of the skin and other tissues of a newborn infant caused by the accumulation of indirect unconjugated newborn infant caused by the accumulation of indirect unconjugated bilirubin in the skin due to an overall increase in the total bilirubin in bilirubin in the skin due to an overall increase in the total bilirubin in the blood.(5) Sufficiently elevated levels of Unconjugated bilirubin the blood.(5) Sufficiently elevated levels of Unconjugated bilirubin can lead to bilirubin encephalopathy and subsequently kernicterus, can lead to bilirubin encephalopathy and subsequently kernicterus, with devastating, permanent neurodevelopmental handicapswith devastating, permanent neurodevelopmental handicaps

Phototherapy is the primary treatment in neonates with Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia. Phototherapy converts bilirubin to unconjugated hyperbilirubinemia. Phototherapy converts bilirubin to yellow photoisomers and colorless oxidation products that are less yellow photoisomers and colorless oxidation products that are less lipophilic than bilirubin and do not require hepatic conjugation for lipophilic than bilirubin and do not require hepatic conjugation for excretion. Photoisomers are excreted mainly in bile, and oxidation excretion. Photoisomers are excreted mainly in bile, and oxidation products predominantly in urine. The fact that exchange products predominantly in urine. The fact that exchange transfusions are now so rare confirms the efficacy of phototherapy transfusions are now so rare confirms the efficacy of phototherapy for regulating plasma bilirubin concentrationsfor regulating plasma bilirubin concentrations

References References

Thor WR Hansen. Jaundice, Neonatal . Thor WR Hansen. Jaundice, Neonatal . Available at Available at http://http://www.eMedicine.comwww.eMedicine.com. . Accesed on November 28, 2008.Accesed on November 28, 2008.

Richard E, Robert,etc.Nelson textbook of Richard E, Robert,etc.Nelson textbook of pediatrics.7th ed.USA :Saunders ; 2004pediatrics.7th ed.USA :Saunders ; 2004

The New England Journal of Medicine.The New England Journal of Medicine. Phototherapy for Neonatal Jaundice. Available Phototherapy for Neonatal Jaundice. Available at : at : http://http://www.nejm.comwww.nejm.com/journal/pediatric/journal/pediatric. . Accessed on: November 11, 2008 .Accessed on: November 11, 2008 .