Phototherapy to Prevent Severe Neonatal Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation
- Vinod K. Bhutani, MD,
- the Committee on Fetus and Newborn
OBJECTIVE: To standardize the use of phototherapy consistent with the American Academy of Pediatrics clinical practice guideline for the management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.
METHODS: Relevant literature was reviewed. Phototherapy devices currently marketed in the United States that incorporate fluorescent, halogen, fiber-optic, or blue light-emitting diode light sources were assessed in the laboratory.
RESULTS: The efficacy of phototherapy units varies widely because of differences in light source and configuration. The following characteristics of a device contribute to its effectiveness: (1) emission of light in the blue-to-green range that overlaps the in vivo plasma bilirubin absorption spectrum (∼460–490 nm); (2) irradiance of at least 30 μW·cm−2·nm−1 (confirmed with an appropriate irradiance meter calibrated over the appropriate wavelength range); (3) illumination of maximal body surface; and (4) demonstration of a decrease in total bilirubin concentrations during the first 4 to 6 hours of exposure.
RECOMMENDATIONS (SEE APPENDIX FOR GRADING DEFINITION): The intensity and spectral output of phototherapy devices is useful in predicting potential effectiveness in treating hyperbilirubinemia (group B recommendation). Clinical effectiveness should be evaluated before and monitored during use (group B recommendation). Blocking the light source or reducing exposed body surface should be avoided (group B recommendation). Standardization of irradiance meters, improvements in device design, and lower-upper limits of light intensity for phototherapy units merit further study. Comparing the in vivo performance of devices is not practical, in general, and alternative procedures need to be explored.
Clinical trials have validated the efficacy of phototherapy in reducing excessive unconjugated hyperbilirubinemia, and its implementation has drastically curtailed the use of exchange transfusions.1 The initiation and duration of phototherapy is defined by a specific range of total bilirubin values based on an infant's postnatal age and the potential risk for bilirubin neurotoxicity.1 Clinical response to phototherapy depends on the efficacy of the phototherapy device as well as the balance between an infant's rates of bilirubin production and elimination. The active agent in phototherapy is light delivered in measurable doses, which makes phototherapy conceptually similar to pharmacotherapy. This report standardizes the use of phototherapy consistent with the American Academy of Pediatrics clinical practice guideline for the management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.
I. COMMERCIAL LIGHT SOURCES
A wide selection of commercial phototherapy devices is available in the United States. A complete discussion of devices is beyond the scope of this review; some are described in Tables 1 and 2. Phototherapy devices can be categorized according to their light source as follows: (1) fluorescent-tube devices that emit different colors (cool white daylight, blue [B], special blue [BB], turquoise, and green) and are straight (F20 T12, 60 cm, 20 W), U-shaped, or spiral-shaped; (2) metal halide bulbs, used in spotlights and incubator lights; (3) light-emitting diodes (LEDs) or metal halide bulbs, used with fiber-optic light guides in pads, blankets, or spotlights; and (4) high-intensity LEDs, used as over- and under-the-body devices.
II. STANDARDS FOR PHOTOTHERAPY DEVICES
Methods for reporting and measuring phototherapy doses are not standardized. Comparisons of commercially available phototherapy devices that use in vitro photodegradation techniques may not accurately predict clinical efficacy.2 A recent report explored an approach to standardizing and quantifying the magnitude of phototherapy delivered by various devices.3Table 1 lists technical data for some of the devices marketed in the United States.3 Factors to consider in prescribing and implementing phototherapy are (1) emission range of the light source, (2) the light intensity (irradiance), (3) the exposed (“treatable”) body surface area illuminated, and (4) the decrease in total bilirubin concentration. A measure of the effectiveness of phototherapy to rapidly configure the bilirubin molecule to less toxic photoisomers (measured in seconds) is not yet clinically available.
A. Light Wavelength
The visible white light spectrum ranges from approximately 350 to 800 nm. Bilirubin absorbs visible light most strongly in the blue region of the spectrum (∼460 nm). Absorption of light transforms unconjugated bilirubin molecules bound to human serum albumin in solution into bilirubin photoproducts (predominantly isomers of bilirubin).2,4,5 Because of the photophysical properties of skin, the most effective light in vivo is probably in the blue-to-green region (∼460–490 nm).2 The first prototype phototherapy device to result in a clinically significant rate of bilirubin decrease used a blue (B) fluorescent-tube light source with 420- to 480-nm emission.6,7 More effective narrow-band special blue bulbs (F20T12/BB [General Electric, Westinghouse, Sylvania] or TL52/20W [Phillips]) were subsequently used.8,9 Most recently, commercial compact fluorescent-tube light sources and devices that use LEDs of narrow spectral bandwidth have been used.9,–,14 Unless specified otherwise, plastic covers or optical filters need to be used to remove potentially harmful ultraviolet light.
Devices with maximum emission within the 460- to 490-nm (blue-green) region of the visible spectrum are probably the most effective for treating hyperbilirubinemia.2,4 Lights with broader emission also will work, although not as effectively. Special blue (BB) fluorescent lights are effective but should not be confused with white lights painted blue or covered with blue plastic sheaths, which should not be used. Devices that contain high-intensity gallium nitride LEDs with emission within the 460- to 490-nm regions are also effective and have a longer lifetime (>20 000 hours), lower heat output, low infrared emission, and no ultraviolet emission.
B. Measuring Light Irradiance
Light intensity or energy output is defined by irradiance and refers to the number of photons (spectral energy) that are delivered per unit area (cm2) of exposed skin.1 The dose of phototherapy is a measure of the irradiance delivered for a specific duration and adjusted to the exposed body surface area. Determination of an in vivo dose-response relationship is confounded by the optical properties of skin and the rates of bilirubin production and elimination.1 Irradiance is measured with a radiometer (W·cm−2) or spectroradiometer (μW·cm−2·nm−1) over a given wavelength band. Table 2 compares the spectral irradiance of some of the devices in the US market, as measured with different brands of meters. Often, radiometers measure wavelengths that do not penetrate skin well or that are far from optimal for phototherapy and, therefore, may be of little value for predicting the clinical efficacy of phototherapy units. A direct relationship between irradiance and the rate of in vivo total bilirubin concentration decrease was described in the report of a study of term “healthy” infants with nonhemolytic hyperbilirubinemia (peak values: 15–18 mg/dL) using fluorescent Philips daylight (TL20W/54, TL20W/52) and special blue (TLAK 40W/03) lamps.15,16 The American Academy of Pediatrics has recommended that the irradiance for intensive phototherapy be at least 30 μW·cm−2·nm−1 over the waveband interval 460 to 490 nm.1 Devices that emit lower irradiance may be supplemented with auxiliary devices. Much higher doses (>65 μW·cm−2·nm−1) might have (as-yet-unidentified) adverse effects. Currently, no single method is in general use for measuring phototherapy dosages. In addition, the calibration methods, wavelength responses, and geometries of instruments are not standardized. Consequently, different radiometers may show different values for the same light source.2
For routine measurements, clinicians are limited by reliance on irradiance meters supplied or recommended by the manufacturer. Visual estimations of brightness and use of ordinary photometric or colorimetric light meters are inappropriate.1,2 Maximal irradiance can be achieved by bringing the light source close to the infant1; however, this should not be done with halogen or tungsten lights, because the heat generated can cause a burn. Furthermore, with some fixtures, increasing the proximity may reduce the exposed body surface area. Irradiance distribution in the illuminated area (footprint) is rarely uniform; measurements at the center of the footprint may greatly exceed those at the periphery and are variable among phototherapy devices.1 Thus, irradiance should be measured at several sites on the infant's body surface. The ideal distance and orientation of the light source should be maintained according to the manufacturer's recommendations. The irradiance of all lamps decreases with use; manufacturers may provide useful-lifetime estimates, which should not be exceeded.
C. Optimal Body Surface Area
An infant's total body surface area17 can be influenced by the disproportionate head size, especially in the more preterm infant. Complete (100%) exposure of the total body surface to light is impractical and limited by use of eye masks and diapers. Circumferential illumination (total body surface exposure from multiple directions) achieves exposure of approximately 80% of the total body surface. In clinical practice, exposure is usually planar: ventral with overhead light sources and dorsal with lighted mattresses. Approximately 35% of the total body surface (ventral or dorsal) is exposed with either method. Changing the infant's posture every 2 to 3 hours may maximize the area exposed to light. Exposed body surface area treated rather than the number of devices (double, triple, etc) used is clinically more important. Maximal skin surface illumination allows for a more intensive exposure and may require combined use of more than 1 phototherapy device.1
Physical obstruction of light by equipment, such as radiant warmers, head covers, large diapers, eye masks that enclose large areas of the scalp, tape, electrode patches, and insulating plastic covers, decrease the exposed skin surface area. Circumferential phototherapy maximizes the exposed area. Combining several devices, such as fluorescent tubes with fiber-optic pads or LED mattresses placed below the infant or bassinet, will increase the surface area exposed. If the infant is in an incubator, the light rays should be perpendicular to the surface of the incubator to minimize reflectance and loss of efficacy.1,2
D. Rate of Response Measured by Decrease in Serum Bilirubin Concentration
The clinical impact of phototherapy should be evident within 4 to 6 hours of initiation with an anticipated decrease of more than 2 mg/dL (34 μmol/L) in serum bilirubin concentration.1 The clinical response depends on the rates of bilirubin production, enterohepatic circulation, and bilirubin elimination; the degree of tissue bilirubin deposition15,16,18; and the rates of the photochemical reactions of bilirubin. Aggressive implementation of phototherapy for excessive hyperbilirubinemia, sometimes referred to as the “crash-cart” approach,19,20 has been reported to reduce the need for exchange transfusion and possibly reduce the severity of bilirubin neurotoxicity.
Serial measurements of bilirubin concentration are used to monitor the effectiveness of phototherapy, but the value of these measurements can be confounded by changes in bilirubin production or elimination and by a sudden increase in bilirubin concentration (rebound) if phototherapy is stopped. Periodicity of serial measurements is based on clinical judgment.
III. EVIDENCE FOR EFFECTIVE PHOTOTHERAPY
Light-emission characteristics of phototherapy devices help in predicting their effectiveness (group B recommendation) (see Appendix). The clinical effectiveness of the device should be known before and monitored during clinical application (group B recommendation). Local guidelines (instructions) for routine clinical use should be available. Important factors that need to be considered are listed in Table 3. Obstructing the light source and reducing the exposed body surface area must be avoided (group B recommendation).
These recommendations are appropriate for clinical care in high-resource settings. In low-resource settings the use of improvised technologies and affordable phototherapy device choices need to meet minimum efficacy and safety standards.
IV. SAFETY AND PROTECTIVE MEASURES
A clinician skilled in newborn care should assess the neonate's clinical status during phototherapy to ensure adequate hydration, nutrition, and temperature control. Clinical improvement or progression of jaundice should also be assessed, including signs suggestive of early bilirubin encephalopathy such as changes in sleeping pattern, deteriorating feeding pattern, or inability to be consoled while crying.1 Staff should be educated regarding the importance of safely minimizing the distance of the phototherapy device from the infant. They should be aware that the intensity of light decreases at the outer perimeter of the light footprint and recognize the effects of physical factors that could impede or obstruct light exposure. Staff should be aware that phototherapy does not use ultraviolet light and that exposure to the lights is mostly harmless. Four decades of neonatal phototherapy use has revealed no serious adverse clinical effects in newborn infants 35 or more weeks of gestation. For more preterm infants, who are usually treated with prophylactic rather than therapeutic phototherapy, this may not be true. Informed staff should educate parents regarding the care of their newborn infant undergoing phototherapy. Devices must comply with general safety standards listed by the International Electrotechnical Commission.21 Other clinical considerations include:
Interruption of phototherapy: After a documented decrease in bilirubin concentration, continuous exposure to the light source may be interrupted and the eye mask removed to allow for feeding and maternal-infant bonding.1
Use of eye masks: Eye masks to prevent retinal damage are used routinely, although there is no evidence to support this recommendation. Retinal damage has been documented in the unpatched eyes of newborn monkeys exposed to phototherapy, but there are no similar data available from human newborns, because eye patches have always been used.22,–,24 Purulent eye discharge and conjunctivitis in term infants have been reported with prolonged use of eye patches.25,26
Use of diapers: Concerns for the long-term effects of continuous phototherapy exposure of the reproductive system have been raised but not substantiated.27,–,29 Diapers may be used for hygiene but are not essential.
Other protective considerations: Devices used in environments with high humidity and oxygen must meet electrical and fire hazard safety standards.21 Phototherapy is contraindicated in infants with congenital porphyria or those treated with photosensitizing drugs.1 Prolonged phototherapy has been associated with increased oxidant stress and lipid peroxidation30 and riboflavin deficiency.31 Recent clinical reports of other adverse outcomes (eg, malignant melanoma, DNA damage, and skin changes) have yet to be validated.1,2,32,33 Phototherapy does not exacerbate hemolysis.34
V. RESEARCH NEEDS
Among the gaps in knowledge that remain regarding the use of phototherapy to prevent severe neonatal hyperbilirubinemia, the following are among the most important:
The ability to measure the actual wavelength and irradiance delivered by a phototherapy device is urgently needed to assess the efficiency of phototherapy in reducing total serum bilirubin concentrations.
The safety and efficacy of home phototherapy remains a research priority.
Further delineation of the short- and long-term consequences of exposing infants with conjugated and unconjugated hyperbilirubinemia to phototherapy is needed.
Whether use of phototherapy reduces the risk of bilirubin neurotoxicity in a timely and effective manner needs further exploration.
Clinicians and hospitals should ensure that the phototherapy devices they use fully illuminate the patient's body surface area, have an irradiance level of ≥30 μW·cm−2·nm−1 (confirmed with accuracy with an appropriate spectral radiometer) over the waveband of approximately 460 to 490 nm, and are implemented in a timely manner. Standard procedures should be documented for their safe deployment.
Committee on Fetus and Newborn, 2010–2011
Lu-Ann Papile, MD, Chairperson
Jill E. Baley, MD
Vinod K. Bhutani, MD
Waldemar A. Carlo, MD
James J. Cummings, MD
Praveen Kumar, MD
Richard A. Polin, MD
Rosemarie C. Tan, MD, PhD
Kristi L. Watterberg, MD
CAPT Wanda Denise Barfield, MD, MPH
Centers for Disease Control and Prevention
William H. Barth Jr, MD
American College of Obstetricians and Gynecologists
Ann L. Jefferies, MD
Canadian Paediatric Society
Rosalie O. Mainous, PhD, RNC, NNP
National Association of Neonatal Nurses
Tonse N. K. Raju, MD, DCH
National Institutes of Health
Kasper S. Wang
AAP Section on Surgery
M. Jeffrey Maisels, MBBCh, DSc
Antony F. McDonagh, PhD
David K. Stevenson, MD
Hendrik J. Vreman, PhD
This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication.
The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.
All technical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.
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- Copyright © 2011 by the American Academy of Pediatrics