Phototherapy for Jaundice
Jaundice refers to the yellow appearance of the skin that occurs with the deposition of bilirubin in the dermal and subcutaneous tissue. Normally in the body, bilirubin is processed through the liver, where it is conjugated to glucuronic acid by the enzyme uridine diphosphate glucuronyl transferase (UGT) 1A1. This conjugated form of bilirubin is then excreted into the bile and removed from the body via the gut. When this excretion process is low following birth, does not work efficiently, or is overwhelmed by the amount of endogenously produced bilirubin, the amount of bilirubin in the body increases, resulting in hyperbilirubinemia and jaundice.
Jaundice occurs in as many as 60% of all normal newborns within the first week of life.  Jaundice in the newborn can occur from an underlying pathological condition, such as isoimmune hemolysis or an RBC enzyme deficiency. However, it is more commonly due to the normal physiological inability of the newborn infant to process bilirubin adequately due to the combined effects of increased RBC turnover and a transient deficit in bilirubin conjugation in the liver.  This type of nonpathologic jaundice is referred to as physiologic jaundice of the newborn. 
In most infants with physiologic jaundice, bilirubin concentrations do not rise to a point that requires treatment. However, in some infants with exaggerated physiologic jaundice, and in many infants with pathologic jaundice, bilirubin in the blood reaches very high concentrations that put the infant at risk for acute and chronic bilirubin encephalopathy (kernicterus). In these cases, treatment aimed at decreasing bilirubin concentration is required in order to avoid kernicterus. Etiologies of hyperbilirubinemia in newborns are provided in the image below.
Effective treatments to decrease bilirubin levels in infants with severe jaundice include phototherapy and exchange transfusion.
The effect of light on jaundice in neonates, and the ability of light to decrease serum bilirubin levels, was first described by Cremer et al in 1958.  This observation led to the development of light sources for use in the treatment of infants with hyperbilirubinemia, a treatment now referred to as phototherapy. Since its inception, phototherapy has been effectively used as a relatively inexpensive and noninvasive method of treating neonatal hyperbilirubinemia. [4, 5] The decline in the number or exchange transfusions in recent years is, at least in part, likely a direct reflection of the effectiveness of phototherapy at treating hyperbilirubinemia. In modern neonatal ICUs (NICUs) exchange transfusions are rare and are only used as a rescue therapy to avoid kernicterus in newborns with severe jaundice when phototherapy is inadequate.
At its most basic, phototherapy refers to the use of light to convert bilirubin molecules in the body into water soluble isomers that can be excreted by the body. The absorption of light by normal bilirubin (4Z,15Z-bilirubin) results in the creation of 2 isomeric forms of bilirubin: structural isomers and configurational isomers. The main structural isomer of bilirubin is Z-lumirubin. The main configurational isomer of bilirubin is 4Z,15 E -bilirubin. Configurational isomerization is reversible, and structural isomerization is irreversible. Both the configurational and structural isomers of bilirubin are less lipophilic than normal bilirubin and can be excreted into bile without undergoing glucuronidation in the liver. Some of the configurational isomers of bilirubin, however, revert back to the native form after excretion into bile and can be reabsorbed via enterohepatic circulation in the gut. Structural bilirubin isomers, like Z-lumirubin, can also be excreted in the urine.
The absorptions of light by bilirubin also results in the generation of excited-state bilirubin molecules that react with oxygen to produce colorless oxidation products, or photooxidation products. This process occurs more slowly than configurational or structural isomerization. Photooxidation products are primarily excreted in the urine. The image below provides a schematic of the conversion of normal bilirubin to configurational isomers, structural isomers, and photooxidation products and the respective routes of excretion from the body.
Prior studies have shown that approximately 5-40 infants per 1,000 in the United States require phototherapy in the newborn nursery, and an equal number require readmission to the hospital for phototherapy after discharge from the nursery.  The specific total serum bilirubin concentration at which phototherapy should be initiated varies and depends on several factors, including the total serum bilirubin level, the infants gestational age, age of the infant in hours at the time of testing, and any individual risk factors for hyperbilirubinemia.
Risk factors for the development of severe hyperbilirubinemia and kernicterus include isoimmune hemolytic disease, glucose-6-phosphate deficiency, asphyxia, significant lethargy, temperature instability, sepsis, acidosis, and hypoalbuminemia (< 3g/dL).  To aid physicians in the decision on when to initiate phototherapy, the American Academy of Pediatrics Subcommittee on Hyperbilirubinemia developed guidelines on the management of hyperbilirubinemia in newborns 35 or more weeks’ gestation.  This guideline includes an algorithm for the management of jaundice in the newborn nursery as well as guidelines for the initiation of phototherapy based on total serum bilirubin levels, gestational age, age of the infant in hours, and individual risk factors.
No evidence-based guidelines are available on the indication for phototherapy in premature infants less than 35 weeks’ gestation. However, several commonly used reference texts provide tables. [7, 8] A commonly used rule of thumb in the NICU is to start phototherapy when the total serum bilirubin level is greater than 5 times the birth weight. Thus, in a 1-kg infant, phototherapy is started at a bilirubin level of 5 mg/dL; in a 2-kg infant, phototherapy is started at a bilirubin level of 10mg/dL and so on. 
This article discusses the clinical procedure for providing phototherapy for neonatal jaundice.
Few contraindications to phototherapy are recognized. These include the concomitant use of photosensitizing medications, a diagnosis of congenital erythropoietic porphyria, or a family history of porphyria.  Infants with cholestatic jaundice and direct hyperbilirubinemia who are exposed to phototherapy may experience a dark, gray-brown discoloration of the skin, commonly known as ”bronze-baby syndrome.” The etiology of this discoloration is unknown but is possibly due to porphyrin accumulation. The skin discoloration that occurs with bronze-baby syndrome is transient and disappears with the discontinuation of phototherapy.  The presence of direct hyperbilirubinemia is not a contraindication to phototherapy. 
The effectiveness of phototherapy at converting bilirubin into configurational isomers, structural isomers, and photooxidation products is determined by the dose of phototherapy provided to the infant. The dose of phototherapy depends on several factors, including the spectral wave length of light, the spectral irradiance delivered to the infant’s skin, and the total spectral power (average spectral irradiance delivered across the surface area of the infant). Factors that affect phototherapy are described in the image below.
Light in the blue region of the spectrum, near 460 nm, is most strongly absorbed by bilirubin. However, only light that penetrates the skin and is absorbed by bilirubin provides the needed photochemical effect. Tissue penetration increases as the wavelength of the light increases. Thus, one must balance the use of a higher wavelength of light, which more readily penetrates tissue, with the use of a wavelength that is more readily absorbed by bilirubin, which may penetrate less deeply. With this in mind, light in the 460-490 nm wavelength is probably the most effective for use during phototherapy. 
Spectral irradiance is measured in watts per centimeter, or microwatts per square centimeter per nanometer (mW/cm2 per nm) over a wavelength band. Higher spectral irradiance results in a more rapid decline in the bilirubin levels.  Spectral irradiance increases as the distance from the light source to the infant’s skin deceases.  Different phototherapy devices deliver significantly different levels of irradiance. The American Academy of Pediatrics defines standard phototherapy as 8-10 mW/cm2 per nm and intensive phototherapy as more than 30 mW/cm2 per nm in the 430-490 nm band. 
Spectral power increases as the amount of skin exposed to phototherapy increases. Ways to increase surface area exposure include removal of clothing and increasing the number of lights/lighting devices used to deliver phototherapy. Infants receiving phototherapy should be left only in their diaper, allowing adequate surface area exposure for phototherapy. The use of lights both above and below an infant effectively doubles the area of exposure. Several manufacturers produce fiberoptic pads that can be placed under the infant. The Bili Bassinet (Olympic Medical; Seattle, WA) is one commercial device that provides special blue fluorescent tubes that emit light in the 460-490 nm wavelength, both above and below the infant.
The dose of phototherapy, in mW/cm2 per nm, should be measured during phototherapy using a commercially available radiometer. These devices typically measure the spectral irradiance of phototherapy in the 425-475 or 400-480nm band wavelength. The radiometer used to measure irradiance should be the one recommended by manufacturer of the light source. Due to variance in the strength of phototherapy over the surface of the infant, and because measurements of spectral irradiance can differ greatly depending on where on the infant the measurement is made, taking several measures in different locations on the infant and averaging the values is important. 
Eye protection should be placed on all infants receiving phototherapy. The need for eye protection is based on animal data that phototherapy may be damaging to the retina.  Various commercially available infant eye shields are available for use. In addition to eye shields, many centers also prescribe lubricating eye drops (carboxymethylcellulose sodium) for infant receiving phototherapy. The infant’s temperature should be closely monitored while receiving phototherapy. This is especially important in infant under halogen lights because these emit significant amounts of heat and can cause hyperthermia. Unclothed infants in basinets under fluorescent or light-emitting diode (LED) devices are at risk for hypothermia, especially if they are in an area with a low ambient temperature. Premature infants and infants unable to maintain body temperature in a basinet should be placed on a radiant warmer or in an isolette while receiving phototherapy in order to maintain normothermia.
The use of photosensitizing medications should be avoided while infants are receiving phototherapy. Medications used in the newborn period that have been linked to phototoxic reactions include nonsteroidal anti-inflammatory drugs (ibuprofen), diuretics (furosemide, hydrochlorothiazide), and certain antibiotics (doxycycline, tetracycline, ciprofloxacin, ofloxacin, levofloxacin, and sulfonamides). In general, however, photosensitivity from medications are most likely to occur after exposure to light in the UV-A (320- 400 nm) and UV-B (290-302 nm) ranges.  Because phototherapy does not produce significant UV-A or UV-B light, phototoxic reactions in infants receiving these medications are rare. 
Phototherapy has been safely used for the treatment of neonatal jaundice for over 40 years. Complications from phototherapy are rare and generally mild. The two most notable complications include increased insensible water loss and cutaneous reactions in infants with cholestatic jaundice receiving phototherapy.
Phototherapy with halogen spot lights can increase cutaneous blood flow and increase insensible water loss through the skin. This is especially important in premature infants whose skin barrier function is compromised due to immaturity and is more permeable to water. Contemporary studies in premature infants undergoing phototherapy with halogen spot lights have shown transepidermal water loss increases of 20-26%, despite constant temperature and relative humidity. [11, 13] Phototherapy is thought to increases skin blood flow by a mechanism known as photorelaxation.  The pathway of this mechanism is not completely understood but is believed to be caused by S-nitrosothiols mediated nitric oxide release. 
Due to this increase in insensible water loss, recommendations have been made to increase maintenance fluid by 10 mL/kg/d in premature infants exposed to conventional phototherapy.  Additional intravenous fluids are not required in term infants who are maintaining adequate oral intake.  Increases in transepidermal water loss in premature infants have not been documented with LED-based phototherapy. 
A dark, greyish-brown discoloration of the skin may develop in infants with cholestatic jaundice and direct hyperbilirubinemia exposed to phototherapy. This reaction is commonly referred to as bronzed-baby syndrome. This discoloration of the skin is transient and resolves with cessation of phototherapy.  Bolus and purpuric reactions of the skin have also been reported in infants with severe cholestatic jaundice receiving phototherapy. This is thought to be due to sensitization by accumulation of porphyrins. 
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Taylor L Sawyer, DO, MEd, FAAP, FACOP Associate Professor of Pediatrics, University of Washington School of Medicine; Director, Neonatal-Perinatal Fellowship, Seattle Children’s Hospital
Taylor L Sawyer, DO, MEd, FAAP, FACOP is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics, American College of Osteopathic Pediatricians, American Medical Association, American Osteopathic Association, Association of American Medical Colleges, International Pediatric Simulation Society, Society for Simulation in Healthcare
Disclosure: Nothing to disclose.
Daniel P Chiles, DO Chief Resident, Department of Pediatrics, Tripler Army Medical Center
Disclosure: Nothing to disclose.
Luke J Lindley, MD Resident Physician, Department of Pediatrics, Tripler Army Medical Center
Disclosure: Nothing to disclose.
Dharmendra J Nimavat, MD, FAAP Associate Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine; Staff Neonatologist, Clinical Director, NICU Regional Perinatal Center, HSHS St John’s Children’s Hospital
Dharmendra J Nimavat, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association of Physicians of Indian Origin
Disclosure: Nothing to disclose.
Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research
Disclosure: Nothing to disclose.
The views expressed in this manuscript are those of the author(s) and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.
Phototherapy for Jaundice
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