To summarize the principles and application of phototherapy consistent with the current 2022 American Academy of Pediatrics “Clinical Practice Guideline Revision for the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.”
Relevant literature was reviewed regarding phototherapy devices in the United States, specifically those that incorporate blue to blue-green light-emitting diode, fluorescent, halogen, or fiberoptic light sources, and their currently marketed indications.
The efficacy of phototherapy devices varies widely because of nonstandardized use of light sources and configurations and irradiance meters. In summary, the most effective and safest devices have the following characteristics: (1) incorporation of narrow band blue-to-green light-emitting diode lamps (∼460–490 nm wavelength range; 478 nm optimal) that would best overlap the bilirubin absorption spectrum; (2) emission of irradiance of at least 30 µW/cm2/nm (in term infants); and (3) illumination of the exposed maximal body surface area of an infant (35% to 80%). Furthermore, accurate irradiance measurements should be performed using the appropriate irradiance meter calibrated for the wavelength range delivered by the phototherapy device.
With proper administration of effective phototherapy to an infant without concurrent hemolysis, total serum or plasma bilirubin concentrations will decrease within the first 4 to 6 hours of initiation safely and effectively.
Translation to Clinical Practice (see Appendix I for grading definition):
The intensity and spectral output of phototherapy devices and its illuminated body surface area (BSA) or “light footprint” impact their potential effectiveness in treating hyperbilirubinemia (Aggregate Evidence Quality Grade A). Clinical effectiveness should be evaluated and monitored during use (Aggregate Evidence Quality Grade A). Blocking the light source or reducing exposed BSA should be avoided (Aggregate Evidence Quality Grade B). Further development of phototherapy devices should focus on the standardization of irradiance meters, improvements in design allowing for parent-infant bonding, and identification of safety limits (minimal and maximal) of light wavelengths and irradiances emitted. Along with the incorporation of new evidence provided in the current 2022 American Academy of Pediatrics “Clinical Practice Guideline Revision for the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation,”1 the Committee on the Fetus and Newborn offers this technical report to summarize the principles and application of phototherapy to facilitate safe and effective treatment of neonates with the goal of preventing hyperbilirubinemia and phototherapy-associated adverse effects.
Introduction
Phototherapy is prescribed for treating neonatal hyperbilirubinemia and is performed by exposing newborn infants to light in the blue-green wavelength range (460–490 nm), preferably at an optimal peak of 478 nm2,3 and at an irradiance of 25 to 35 µW/cm2/nm to at least 1 surface of the body (ventral or dorsal).4 The photoconversion of the unconjugated bilirubin molecule mostly occurs in the microcirculation of the skin with almost immediate photo-isomerization to the excretable water soluble 4E,15Z photoisomer, peaking within 120 minutes. About 20% of bilirubin is converted to the 4Z,15E photoisomer and 5% to lumirubin. This transformation results in a presumably rapid decrease of excessive unconjugated bilirubin concentrations and the subsequent reduction of potential exposure to neurotoxicity.5 Further decline in total serum/plasma bilirubin (TSB) concentrations are attributable to natural excretion in bile and stools. Phototherapy is an essential intervention for severe hyperbilirubinemia, especially in neonates at high risk. The timing of intervention is guided by performing serial measurements of TSB concentrations and screening for the presence of intrinsic risk factors for bilirubin neurotoxicity. Although clinical trial data that show that phototherapy directly prevents kernicterus are scant,6 there is sufficient evidence that its use reduces the risk of bilirubin neurotoxicity as well as the use of exchange transfusions (particularly in extremely preterm infants).6 Failure of response to phototherapy is unusual unless complicated by an increased rate of bilirubin production attributable to the presence of hemolysis or use of inappropriate (or ineffective) phototherapy devices. The available current evidence and consensus for the application of phototherapy can be translated to institutional policies for standardized implementation for its safety and effectiveness. This report outlines a standardized approach to the use of phototherapy consistent with the 2022 American Academy of Pediatrics (AAP) “Clinical Practice Guideline Revision for the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.”1
Clinical Impact
Clinical trials have validated the efficacy of phototherapy in reducing unconjugated hyperbilirubinemia (TSB >25 mg/dL [>428 µmol/L]). Initiation of phototherapy is clinically determined when a specific range of TSB threshold values based on a newborn infant’s gestational age (in weeks), postnatal age (in hours), and the presence or absence of risk factors associated with bilirubin neurotoxicity is reached.1,7
The TSB thresholds should provide a sufficient margin of safety and take into account interlaboratory variations in TSB measurements,8 the biologic vulnerability of an individual infant, the rapidity of an infant’s response to phototherapy, and the balance between risks of over- and undertreatment.9 The effectiveness of phototherapy depends on the efficacy of the device used and the net gradient between an infant’s rates of bilirubin production and elimination. Phototherapy needs to be delivered in measurable doses (irradiance), which makes it conceptually similar to pharmacotherapy.4
I. Commercial Light Sources
A wide selection of commercial phototherapy devices is available in the United States that comply with US Food and Drug Administration standards. A complete discussion of devices is beyond the scope of this review; some of the common types of devices are listed for comparison in Table 1. They are best categorized according to their light source: (1) fluorescent-tube devices that emit different colors (cool white daylight, blue, special blue, 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) high-intensity narrow band light-emitting diodes (LEDs) or metal halide bulbs, used with fiberoptic light in pads, blankets, or spotlights; and (4) LEDs incorporated into overhead, underneath, and circumferential (360°) illumination. LED light sources are preferred because they can deliver the recommended specific light wavelengths in narrow bandwidths with minimal heat generation.
Comparison of Commercial LED-based Phototherapy Devices
| Device (Manufacturer) . | Footprint . | Light Source . | Bandwidth . | Peak . | Footprint Irradiance . | Estimated Life, hours . |
|---|---|---|---|---|---|---|
| neoBLUE, (Natus Medical, Inc) | Overhead source; blanket: 1152 (48 × 24) | Blue LED | 450–475 | 458 | 15 μW/cm2/nm or intensive at 35 μW/cm2/nm; 30 μW/cm2/nm | >50 000 |
| GE. Bilisoft 2.0 (large pad) | 25 × 30 cm | Blue LED | 445–470 | — | 49 μW/cm2/nm; (±25%; at 9 points | >50 000 |
| neoLight (Skylife) | 767 cm2 | Blue LED | — | — | 38.9/56.3 μW/cm2/nm | 25 000 |
| Device (Manufacturer) . | Footprint . | Light Source . | Bandwidth . | Peak . | Footprint Irradiance . | Estimated Life, hours . |
|---|---|---|---|---|---|---|
| neoBLUE, (Natus Medical, Inc) | Overhead source; blanket: 1152 (48 × 24) | Blue LED | 450–475 | 458 | 15 μW/cm2/nm or intensive at 35 μW/cm2/nm; 30 μW/cm2/nm | >50 000 |
| GE. Bilisoft 2.0 (large pad) | 25 × 30 cm | Blue LED | 445–470 | — | 49 μW/cm2/nm; (±25%; at 9 points | >50 000 |
| neoLight (Skylife) | 767 cm2 | Blue LED | — | — | 38.9/56.3 μW/cm2/nm | 25 000 |
II. Standards for Phototherapy Devices
Comparisons of commercially available phototherapy devices using in vitro photodegradation methodologies may not accurately predict clinical efficacy because of variable rates of bilirubin production and elimination as well penetration of light through the skin.10 Factors to consider in prescribing and implementing phototherapy using a particular device include: (1) the emission wavelength range of the light source; (2) the light intensity (dose, irradiance) delivered; (3) the percent exposed BSA of the infant (ventral, dorsal, or both) that can be illuminated; and (4) commercially availability. Efficacy is measured by the rate of reduction in TSB concentrations but may be impacted by variations in infant skin thickness and maturation and hematocrit.11
A. Light Wavelength
The visible white light spectrum ranges from approximately 400 to 700 nm. The bilirubin molecule absorbs visible light most strongly in the blue region of the spectrum (range: 460–490 nm). Specific peak wavelength around 478 nm is the optimum wavelength for absorption by bilirubin in competition with hemoglobin, skin pigments, and light scattering in the dermis.4,6 Upon exposure to this blue light, unconjugated bilirubin bound to human serum albumin undergoes efficient, reversible configurational (Z → E) isomerization, and much less efficient structural isomerization to a ring closed product called lumirubin. Both products are found in infants undergoing phototherapy. Yet, there is evidence that the transformation to lumirubin is primarily responsible for the phototherapy effect4,12,13 (see Appendix II).
Absorption of light transforms unconjugated bilirubin molecules bound to human serum albumin in solution into bilirubin photoproducts (predominantly isomers of bilirubin).10,13,14 The most effective light is in the blue-to-green (∼460 to 490 nm) region, in which bilirubin absorption is maximal and light penetration of the skin is good.10,15,16 The original prototype phototherapy device designed and used by Cremer et al17 resulted in a clinically significant rate of TSB decrease with a blue fluorescent-tube light source with 420- to 480-nm emission.12,17 More effective narrow-band special blue bulbs (F20T12/BB [General Electric, Westinghouse, Sylvania] or TL52/20W [Phillips]) were subsequently developed and used.18,19 Most recently, commercial compact fluorescent-tube light sources and devices use LEDs of narrow spectral bandwidths.19–24 Recent in vitro experiments and clinical studies have provided evidence that administration of light in the blue-green region (478 nm) is optimal, and it is anticipated that this light wavelength will be incorporated into future commercial devices.2,3,25,26
Key Safety Measures
Attention to the configuration of marketed devices, the nature of the light source, and overall ambient temperature conditions is required to minimize the risk of hypothermia or hyperthermia. Safety measures may include use of a warmer bed, incubator or kangaroo (skin-to-skin) care, provision of adequate nutrition, and adherence to safe sleep practices.
Applications in Practice
Devices emitting narrow wavelength light within the blue-green (460 to 490 nm, 478 nm optimal) region of the visible light spectrum are currently the most effective for treating neonatal hyperbilirubinemia.10,13,27 Lights with broader wavelengths or non-LED light sources may also work, although not as effectively, and may also be potentially harmful because of production of unnecessary heat and other adverse effects including increased evaporative losses, oxidative stress, and skin DNA damage.4,28,29 Because hemoglobin serves as a major competitor of bilirubin for light absorption, the efficacy of phototherapy is dependent on the hematocrit. For example, polycythemia could reduce therapeutic efficiency.11
Special blue fluorescent tube lights are also effective but do not deliver in a narrow band of light and may be associated with heat and evaporative water loss. Devices that incorporate blue or blue-green (460 to 490 nm) LEDs are the most effective, have a long lifetime (>20 000 hours), low heat output, low infrared (IR) emission, and no ultraviolet (UV) emission.
Location of Phototherapy Use
Commercial phototherapy devices can be configured for clinical use in multiple settings in the hospital. Earlier reports suggested the potential for home use as well,30 but there remains a paucity of evidence comparing the effectiveness of home versus hospital-based phototherapy. However, a recent report31 of carefully selected neonates demonstrated home phototherapy can be delivered safely with minimal need for subsequent hospitalization and presumed cost savings. Key factors for successful use of home phototherapy include: the selection of low-risk patients, availability of daily health-supervised visits for which health care providers receive payment to manage equipment and monitor the newborn infant’s well-being, and ability to track serial TSB measurements and provision of family support. Criteria for home phototherapy use are explicitly outlined in the 2022 AAP Clinical Practice Guideline Revision.1 Infants at any perceived risk for acute bilirubin encephalopathy are not candidates for home treatment and instead may require emergency phototherapy within an inpatient care facility. Other locations include those that provide the ability to initiate and maintain phototherapy during neonatal transport and in the emergency department while awaiting inpatient placement.
B. Irradiance
Light intensity or energy output of a device is defined as irradiance and refers to the number of photons (spectral energy) that are delivered per unit area (cm2) of exposed skin.7 The dose of phototherapy is a measure of the irradiance delivered for a specific duration and exposed BSA. Determination of an in vivo dose-response relationship may be confounded by the optical properties of an infant’s skin and rates of bilirubin production and elimination.7 Irradiance is measured with a radiometer (W/cm2) or spectroradiometer (µW/cm2/nm) over a given wavelength band. Table 1 compares the irradiance footprints of the most popular devices in the United States as measured with their specific irradiance meter. It is important to note that the use of radiometers not recommended by the manufacturer may measure wavelengths that do not penetrate skin well or are suboptimal or useless for phototherapy and, therefore, have little or no value.
A direct relationship between irradiance and the rate of in vivo TSB concentration decrease was only described in the report of a study of term “healthy” infants with nonhemolytic hyperbilirubinemia (peak values: 15 to 18 mg/dL [257 to 308 µmol/L]) using fluorescent Philips daylight (TL20W/54), white (TL20W/52), or special blue (TLAK 40W/03) lamps.32–34 The AAP has recommended that for intensive phototherapy, an irradiance of 30 µW/cm2/nm (range 25 to 35) of blue-green light at around 478 nm in the range 460 to 490 nm be applied.1,7 Decline in TSB concentrations may flatten as irradiance doses exceed >35 µW/cm2/nm.32,33 Safety and benefits of much higher doses have yet to be reported and could potentially have adverse effects on tissues and organs, as described in a recent review.35 Currently, no single method is in general use for measuring total phototherapy doses. In addition, the calibration methods, wavelength responses, and geometries when multiple devices are used have not been standardized. Consequently, different radiometers may show different values for the same light source, so, in general, radiometers recommended by the manufacturer of the specific device should be used.10 Visual estimations of brightness and use of ordinary photometric or colorimetric light meters are inappropriate.7,27
Applications in Practice
Maximal irradiance can be achieved by bringing a light source close to the infant7 ; however, halogen or tungsten lights should not be used because of the possibility for heat-generated burns. Furthermore, with some devices (especially spotlights), decreasing the distance to an infant may severely reduce the exposed BSA. Irradiance distribution in the illuminated area (or footprint) of a device is rarely uniform, and measurements taken at the center of the footprint can greatly exceed those at the periphery and are variable among phototherapy devices, especially for spotlights, but in contrast, not for LED devices.7 Ideal distance and orientation of the light source are maintained according to the specific manufacturer’s operational recommendations. The irradiance of all lamps decreases variably over time with use; manufacturers may provide useful lifetime estimates to estimate when irradiance may be expected to decrease. A record of therapy provided is best described by duration, number of devices, daily measure at skin level exposure, and percent of BSA exposed.
C. Optimal BSA
An infant’s total BSA36 is influenced by their disproportionate head size, especially in the preterm infant. Complete (100%) exposure of the total BSA to light is impractical and limited by use of eye masks and diapers. Circumferential illumination (total BSA exposure of >80%) from devices placed at multiple directions to yield 360° exposure have been achieved. In clinical practice, exposure is usually planar: ventral with overhead light sources or dorsal with phototherapy mattresses or blankets. Approximately 35% of the total BSA (ventral or dorsal) is exposed with either method. Changing the infant’s position while receiving phototherapy may place the infant at risk for unsafe nonsupine sleep positions.37 Several well-designed studies have demonstrated the lack of any beneficial effect of changing infant position under phototherapy.37–39 Percent of exposed BSA using the most appropriate light source rather than the number of devices (double, triple, etc) is clinically more relevant.27,28 Use of more than 1 phototherapy device can improve effectiveness by increasing a greater available skin surface illumination, but care must be taken to avoid interference and presence of shadows and, thereby, ensure a uniformly irradiated light footprint.7
Applications in Practice
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 BSA. Circumferential phototherapy maximizes the exposed area and is especially effective in infants with extreme hyperbilirubinemia. Combining several types of devices, such as those placed overhead with those placed below the infant or bassinet, such as pads or mattresses, could increase the BSA exposed. For an infant in an incubator, the light emission is best delivered perpendicular to the surface of the incubator to minimize reflectance, shadows, and loss of efficacy.7,27 The delineation of effectiveness by using single, double, or triple phototherapy fails to account for the specific extent BSA exposed, the specific wavelength of light sources used, and the measured uniformity of irradiance delivered at the skin surface level.
D. Rate of Response: Decrease in TSB Concentration
The clinical impact of phototherapy should normally become evident within 4 hours of initiation with an anticipated decrease in TSB concentrations of >2 mg/dL (34 µmol/L). A minimal reduction in the TSB concentration rise may suggest a “plateau effect” and may be considered a partial response.7 The rate of clinical response depends on an infant’s rate of bilirubin production (even more so during ongoing hemolysis), enterohepatic circulation, and bilirubin elimination; the degree of tissue bilirubin deposition32,33,40 ; and the rates of the photochemical reactions of bilirubin. Conversion of bilirubin molecules to nontoxic photoisomers occurs within seconds of light exposure and reaches a plateau by 2 hours.10,14,41 Timely implementation of phototherapy for excessive hyperbilirubinemia (TSB >25 mg/dL [>428 µmol/L]), even while medical procedures are being conducted, is sometimes referred to as the “crash-cart” approach.42,43 This rapid implementation practice has been reported to reduce the need for exchange transfusion and possibly minimize the severity of bilirubin neurotoxicity.
Applications in Practice
Serial measurements of TSB concentrations used to monitor the effectiveness of phototherapy by the timed rate of TSB decline (mg/dL per hour) should be based on the current 2022 AAP Clinical Practice Guideline Revision.1
E. Duration of Light Exposure
Phototherapy can be administered continuously or intermittently (ie, cycled). The benefits of either strategy have not been demonstrated consistently in the literature nor opined by clinical case reports and practice options. In view of potential adverse effects of excessive photon exposure, it is prudent to limit the total duration of light exposure or “irradiance dose.” Since the advent of phototherapy, small trials in term or near-term infants have reported that brief light exposure to 15 minutes per hour resulted in equivalent reduction of TSB concentrations as compared with continuous phototherapy17,44–47 ; this clinical practice for extremely low birth weight infants is currently under investigation. In current practice, total duration of phototherapy is determined by serial monitoring of TSB concentration (dependent of frequency of testing) and its discontinuation once a target TSB concentration is reached.
Exposure Strategies:
Continuous: uninterrupted exposure (as with “escalation of care”).
Continual: brief interruptions for infant handling, parental bonding, and breastfeeding.
Intermittent (cycled): timed intervals (in minutes or hours) of nonexposure. Cycled phototherapy in extremely low birth weight infants has been proposed as light exposure is cycled usually at 15 minutes on and 45 minutes off per hour48 and is currently under clinical investigation.
III. Evidence for Effective Phototherapy
Light-emission characteristics of phototherapy devices help in predicting their effectiveness (Aggregate Evidence Quality Grade B, Appendix I). Clinical effectiveness of a specific device, known before use, allows for individualized monitoring during its application (Aggregate Evidence Quality, Grade A) for a safer implementation strategy. Local guidelines (instructions) for routine clinical use should be made available to clinical staff. Obstructing the light source and reducing the exposed BSA must be avoided (Aggregate Evidence Quality, Grade B). Important action items for phototherapy based on contemporary recommendations1 are summarized in Table 2. These considerations have been incorporated into policies and procedures at several diverse high-resource settings. In low-resource locations, the most relevant evidence-based practice should be sought. The Food and Drug Administration has not approved use of any improvised technologies that have been modified and adapted for cost-savings. Although such improvised devices may be innovative, they still must meet minimum efficacy and safety standards and approval by local institutional regulatory agencies.
Key Action Statements Related to Phototherapy Prescription as Recommended and Quoted1
| . | Key Actions for Implementation . | Clinical Considerations . |
|---|---|---|
| 1 | TSB should be used as the definitive diagnostic test used to guide all interventions. | Virtually all treatment studies are based on TSB levels. |
| 2 | TSB should be measured if the transcutaneous bilirubin (TcB) reading is within 3.0 mg/dL of the phototherapy treatment threshold, if the TcB exceeds the phototherapy treatment threshold, or if the TcB is ≥15 mg/dL. | Both TSB and TcB are good screening tests. But TcB measurements are not accurate enough to determine treatment decisions. |
| 3 | If more than one TcB or TSB measurement is available, the rate of rise may be used to identify possible hemolysis. A rapid rate of rise (≥0.3 mg/dL per hour in the first 24 hours or ≥0.2 mg/dL per hour thereafter) is exceptional and is suggestive of ongoing hemolysis. | Home phototherapy for infants already discharged can help avoid readmission. |
| 4 | Intensive phototherapy is recommended at the thresholds based on gestational age, neurotoxicity risk factors, and age of the infant in hours. | Intensive phototherapy can reduce TSB levels and decrease the need for escalation of care, including the need for exchange transfusion, to prevent kernicterus. |
| 5 | For newborns who have already been discharged and then develop a TSB above the phototherapy threshold, treatment with a home LED-based phototherapy device rather than readmission to the hospital is an option for infants who meet specific listed criteria. | Home phototherapy for infants already discharged can help avoid readmission. |
| 6 | For hospitalized infants, TSB should be measured to verify efficacy after starting phototherapy. Timing of TSB testing should be guided by the TSB trajectory (ie, rate of rise, mg per hour) and infant age. | Early identification of infants without adequate response to phototherapy can lead to earlier escalation of care, potentially averting the need for an exchange transfusion and possibly preventing kernicterus. |
| 8 | Clinicians should evaluate the underlying cause or causes of hyperbilirubinemia in infants who require phototherapy. Glucose-6-phosphate dehydrogenase enzyme activity should be measured in any infant with jaundice of unknown cause whose TSB rises despite intensive phototherapy, whose TSB rises suddenly or rises after an initial decline, or who requires escalation of care. | Identifying the cause of hyperbilirubinemia might identify a previously unrecognized diagnosis that leads to the need for additional care. |
| 9 | It is an option to discontinue phototherapy when the TSB has declined by 2 to 4 mg/dL below the hour-specific threshold at the initiation of phototherapy. The decision to discontinue phototherapy should be individualized to consider the TSB level at which phototherapy was initiated, the cause of the hyperbilirubinemia, the difference between the TSB level and the phototherapy threshold, and the risk of rebound hyperbilirubinemia. | Discontinuing phototherapy as soon as it is safe reduces unnecessary exposure to phototherapy while minimizing the risk of rebound hyperbilirubinemia. |
| 10 | Infants who received phototherapy <48 hours of age, with a gestational age <38 weeks, with a positive direct antiglobulin test (DAT), or suspected of having hemolytic disease should have a follow-up TSB measure 8 to 12 hours after phototherapy discontinuation and on the following day. All other infants who received phototherapy should have a follow-up TSB within 1 to 2 days after phototherapy discontinuation. The need for additional TSB testing will depend on the post-phototherapy TSB level and trajectory. TSB should be measured unless it has been ≥24 hours since phototherapy was stopped, in which case it is an option to use TcB. | Following up closely with infants discharged early or with hyperbilirubinemia risk factors can lead to more timely identification of those who need treatment. Infants who required phototherapy should be followed closely because of the risk of rebound hyperbilirubinemia. TcB is reliable after 24 hours of phototherapy and can therefore be used instead of TSB. |
| 11 | Care should be escalated when an infant’s TSB level is at or above the exchange transfusion threshold or within 0 to 2 mg/dL below the exchange transfusion threshold (referred to as the “escalation of care” level). | “Escalation of care” below the exchange transfusion threshold may prevent the need for an exchange transfusion or allow for a timelier exchange transfusion if it is necessary, which could help prevent kernicterus. |
| 12 | Infants requiring “escalation of care” should receive intravenous hydration and emergent intensive phototherapy as soon as possible. If the TSB level continues to rise despite this intervention, a neonatologist should be consulted about transfer to a NICU. | Emergent intensive phototherapy and correction of hydration deficit can increase the rate of decline in TSB levels and prevent the need for an exchange transfusion. |
| 13 | A TSB should be measured at least every 2 hours from the start of the escalation of care period until the escalation of care period ends. | Frequent measurement of TSB provides timely guidance regarding the efficacy of phototherapy and the possible need for an exchange transfusion. |
| . | Key Actions for Implementation . | Clinical Considerations . |
|---|---|---|
| 1 | TSB should be used as the definitive diagnostic test used to guide all interventions. | Virtually all treatment studies are based on TSB levels. |
| 2 | TSB should be measured if the transcutaneous bilirubin (TcB) reading is within 3.0 mg/dL of the phototherapy treatment threshold, if the TcB exceeds the phototherapy treatment threshold, or if the TcB is ≥15 mg/dL. | Both TSB and TcB are good screening tests. But TcB measurements are not accurate enough to determine treatment decisions. |
| 3 | If more than one TcB or TSB measurement is available, the rate of rise may be used to identify possible hemolysis. A rapid rate of rise (≥0.3 mg/dL per hour in the first 24 hours or ≥0.2 mg/dL per hour thereafter) is exceptional and is suggestive of ongoing hemolysis. | Home phototherapy for infants already discharged can help avoid readmission. |
| 4 | Intensive phototherapy is recommended at the thresholds based on gestational age, neurotoxicity risk factors, and age of the infant in hours. | Intensive phototherapy can reduce TSB levels and decrease the need for escalation of care, including the need for exchange transfusion, to prevent kernicterus. |
| 5 | For newborns who have already been discharged and then develop a TSB above the phototherapy threshold, treatment with a home LED-based phototherapy device rather than readmission to the hospital is an option for infants who meet specific listed criteria. | Home phototherapy for infants already discharged can help avoid readmission. |
| 6 | For hospitalized infants, TSB should be measured to verify efficacy after starting phototherapy. Timing of TSB testing should be guided by the TSB trajectory (ie, rate of rise, mg per hour) and infant age. | Early identification of infants without adequate response to phototherapy can lead to earlier escalation of care, potentially averting the need for an exchange transfusion and possibly preventing kernicterus. |
| 8 | Clinicians should evaluate the underlying cause or causes of hyperbilirubinemia in infants who require phototherapy. Glucose-6-phosphate dehydrogenase enzyme activity should be measured in any infant with jaundice of unknown cause whose TSB rises despite intensive phototherapy, whose TSB rises suddenly or rises after an initial decline, or who requires escalation of care. | Identifying the cause of hyperbilirubinemia might identify a previously unrecognized diagnosis that leads to the need for additional care. |
| 9 | It is an option to discontinue phototherapy when the TSB has declined by 2 to 4 mg/dL below the hour-specific threshold at the initiation of phototherapy. The decision to discontinue phototherapy should be individualized to consider the TSB level at which phototherapy was initiated, the cause of the hyperbilirubinemia, the difference between the TSB level and the phototherapy threshold, and the risk of rebound hyperbilirubinemia. | Discontinuing phototherapy as soon as it is safe reduces unnecessary exposure to phototherapy while minimizing the risk of rebound hyperbilirubinemia. |
| 10 | Infants who received phototherapy <48 hours of age, with a gestational age <38 weeks, with a positive direct antiglobulin test (DAT), or suspected of having hemolytic disease should have a follow-up TSB measure 8 to 12 hours after phototherapy discontinuation and on the following day. All other infants who received phototherapy should have a follow-up TSB within 1 to 2 days after phototherapy discontinuation. The need for additional TSB testing will depend on the post-phototherapy TSB level and trajectory. TSB should be measured unless it has been ≥24 hours since phototherapy was stopped, in which case it is an option to use TcB. | Following up closely with infants discharged early or with hyperbilirubinemia risk factors can lead to more timely identification of those who need treatment. Infants who required phototherapy should be followed closely because of the risk of rebound hyperbilirubinemia. TcB is reliable after 24 hours of phototherapy and can therefore be used instead of TSB. |
| 11 | Care should be escalated when an infant’s TSB level is at or above the exchange transfusion threshold or within 0 to 2 mg/dL below the exchange transfusion threshold (referred to as the “escalation of care” level). | “Escalation of care” below the exchange transfusion threshold may prevent the need for an exchange transfusion or allow for a timelier exchange transfusion if it is necessary, which could help prevent kernicterus. |
| 12 | Infants requiring “escalation of care” should receive intravenous hydration and emergent intensive phototherapy as soon as possible. If the TSB level continues to rise despite this intervention, a neonatologist should be consulted about transfer to a NICU. | Emergent intensive phototherapy and correction of hydration deficit can increase the rate of decline in TSB levels and prevent the need for an exchange transfusion. |
| 13 | A TSB should be measured at least every 2 hours from the start of the escalation of care period until the escalation of care period ends. | Frequent measurement of TSB provides timely guidance regarding the efficacy of phototherapy and the possible need for an exchange transfusion. |
IV. Safety and Protective Measures
A clinician skilled in newborn care should assesses a neonate’s clinical status during phototherapy to ensure adequate hydration and temperature control (especially when heat-generating phototherapy devices are used) as well as providing nutrition by promoting breastfeeding. TSB levels are serially assessed by clinicians who concurrently monitor for onset of progressive signs of acute bilirubin encephalopathy associated with unexpected or sudden onset of extreme hyperbilirubinemia for the infant’s age. These signs include deteriorating or altered feeding patterns, lethargy, inconsolability, high pitched crying, hypotonia or hypertonia, opisthotonus, retrocollis, or fever.1 As discussed in the 2022 AAP clinical practice guideline revision,1 although questions have been raised about safety of phototherapy, 6 decades of phototherapy use in newborn infants 35 or more weeks of gestation has not resulted in any clinical evidence of irreversible or serious side effects (discussed below).
Prolonged phototherapy has been associated with increased oxidant stress and lipid peroxidation49 and riboflavin deficiency.50 Thus, intravenous tubing and infusions that deliver multivitamins and intralipids may require protection from light exposure. Recent clinical reports of speculated adverse outcomes (eg, malignant melanoma, DNA damage, and skin changes), especially when using LED-based devices,29 have yet to be validated.1,7,27,51,52 Phototherapy does not exacerbate hemolysis.53 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.54 Key clinical considerations (Table 3) include:
Positioning: Ideally, newborn infants undergoing phototherapy should adhere to safe, supine sleep positions. Alternating between supine and prone positions does not reduce the duration of phototherapy compared with continuous supine positioning alone.37 Additionally, prone positioning has been associated with an increased risk of sudden infant death38 and is contrary to the established safe sleep practices for infants recommended to parents or caregivers when discharged from the hospital.39
Interruption of phototherapy: Continuous exposure to the light source may be reasonably briefly interrupted and the eye mask removed to allow for feeding and parent-infant bonding.1
Use of eye masks: Eye masks are used to shield an infant from the glare of the overhead lights. Preventing a theoretical risk of retinal damage has not been proven and may be similar to protection by closed eyelids. Retinal damage has been documented in the unpatched eyes of newborn monkeys exposed to phototherapy, but there are no similar data available from human newborn infants because eye patches have always been used.55–57 Retinal injury has not been reported after inadvertent displacement of eye masks, but efforts should be made to maintain the eye mask in place.
Use of diapers: Concerns for the long-term effects of continuous phototherapy exposure of the reproductive system have been raised but not substantiated.58–60 Diapers are used for hygienic purposes, and not for gonadal protection.
Other protective considerations: Devices used in environments with high humidity and oxygen must meet electrical and fire hazard safety standards.54
Concurrent clinical disorders: Phototherapy is contraindicated in infants with congenital porphyria or those treated with photosensitizing drugs.7
Key Clinical Considerations
| Considerations . |
|---|
| • Positioning, sleep posture, and medically-safe locations and environment |
| • Adjustments for infant’s gestational age |
| • Assessment for hemolysis and ensuing unpredictable response |
| • Availability of daily monitoring of patient and bilirubin level (either TcB or able to obtain TSB results in a timely manner) |
| • Appropriate supervision and a secure process for escalation of care if necessary |
| • Payer acceptance and appropriate payment to providers |
| Considerations . |
|---|
| • Positioning, sleep posture, and medically-safe locations and environment |
| • Adjustments for infant’s gestational age |
| • Assessment for hemolysis and ensuing unpredictable response |
| • Availability of daily monitoring of patient and bilirubin level (either TcB or able to obtain TSB results in a timely manner) |
| • Appropriate supervision and a secure process for escalation of care if necessary |
| • Payer acceptance and appropriate payment to providers |
V. Alternative Therapies
Natural Sunlight (Heliotherapy)
Sister Jean Ward’s initial observation and practice that sunlight had an ameliorative effect on hyperbilirubinemia led to the development of phototherapy devices. The sun emits blue-green light in the spectrum needed to most effectively convert bilirubin to its water‐soluble isomers for excretion. However, a significant fraction of sunlight is in the UV region (<400 nm), and this potentially damaging radiation can be effectively absorbed by various organic and biologic substances. Recently, the use of window-tinting films, which have the ability to block UVA (315–400 nm) and IR (>700 nm) radiation from the sun and to selectively transmit visible light including therapeutic blue light, was evaluated.61 Transmission of therapeutic blue-green light (400–520 nm) through films ranged from 24% to 83% compared with unfiltered solar radiation. Studies from countries with limited phototherapy resources have provided evidence in support of filtered sunlight coupled with close monitoring of temperature and overall clinical status. Efficacy of filtered-sunlight phototherapy has been shown in clinical studies in Nigeria,62–65 and the sun emits blue-green light in the spectrum needed to most effectively convert bilirubin to its water‐soluble isomers for excretion. Home exposure to natural sunlight exposes the infant to unwanted UV and IR radiation. Natural unfiltered sunlight cannot be applied at prescribed dosages. Undressing newborn infants and exposing them to natural sunlight in the home setting cannot be recommended given the concerns for hypothermia, hyperthermia, sunburn, and long‐term risk of various skin malignancies.
VI. Adjuvant Therapies
Adjuvant therapies for the prevention and treatment of hyperbilirubinemia either lack strong supportive evidence of efficacy and safety or theoretical considerations suggest more likely harm than benefit and are reviewed extensively in the 2022 AAP Clinical Practice Guideline Revision.1
VII. Risk of Phototherapy
Phototherapy use over the past 6 decades in newborn infants 35 or more weeks of gestation has been safe, effective, and beneficial to neonatal public health. When performed under medical supervision, no known significant or worrisome risks have been reported. However, concerns about photo-oxidative injury or superficial skin DNA damage have been raised in multiple studies that applied inconsistent light dosing. It has been suggested that phototherapy is associated with a small, statistical risk of subsequent cancer66 and epilepsy.67 Most of these epidemiologic reports are confounded by inconsistent use of devices and clinical practices, such as use of white light, inadvertent exposure to UV lights, or exposure to unfiltered direct sunlight. UV irradiation may occur with the use of fluorescent light sources for phototherapy, which could have some mutagenic risk, although likely very small and probably inconsequential in most cases. Our knowledge of potential risk of phototherapy comes from its use in extremely preterm neonates and observations from bench studies. The use of blue-green LED devices do not pose this risk but has been associated with some photo-oxidation in exposed tissues.29,68,69 The exact mechanism(s) by which LED light interacts with tissues to cause any injury is unknown but may be related to the degree of translucency in the skin of extremely preterm infants.70,71
Contraindications to the use of phototherapy are rare but include infants with known congenital porphyria or albinism. It may be used with caution among infants who have concurrent cholestasis and exfoliative dermatologic disorders. Phototherapy has no effect in reducing conjugated hyperbilirubinemia, and, if used, may lead to a slow reversible nontoxic bronzing of the skin. This report does not address the use of phototherapy in preterm infants (<32 weeks of gestation). A prudent clinician closely assesses for over-treatment and over prescription. Indeed, the Eunice Kennedy Schriver National Institute of Child Health and Development trial reporting on the use of phototherapy in the most vulnerable preterm infants (birth weight <750 g) suggests a Bayesian increase in mortality.71 At the time of this writing, another National Institutes of Health-sponsored trial is underway, comparing the use of continuous versus cycled phototherapy to assess the relative safety and efficacy of reducing phototherapy exposure. Although animal model studies are hypothesis-generating, their relevance to humans must be established in rigorous clinical studies that could include population surveillance studies. However, any recently reported associations between phototherapy, cancer risks, and epilepsy need further validation in prospective studies before any changes in current guidelines for clinical practice are warranted.
The AAP Evidence-Based Clinical Practice Guidelines Development and Implementation Manual notes that new data have emerged regarding potential phototherapy-related harms (Table 4), an emerging subject that was not previously covered. The committee has reviewed all relevant literature without a date restriction. Two systematic reviews (initial and expanded) were found to be conducted in accordance with the cited “Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guideline” to ascertain “What are the adverse clinically detectable effects of phototherapy in newborns?” with a comparator of nontreatment for increased risk of any adverse clinical outcome that is important to neonatal patients, their families, and/or the clinicians treating them. In addition, a review search of 45 manuscripts showed that phototherapy is associated with a statistically significant yet low overall risk of causing potential harm. Childhood seizures are one of the most serious, but infrequent, illnesses (adjusted 10-year excess risk of 2.4; 95% confidence interval: 0.6–4.1 per 1000 phototherapy-treated infants) associated with phototherapy used for hyperbilirubinemia. Regardless of this association, the rationale for such concurrence remains unclear thus far. However, this epidemiologic review reported an association but did not offer rationale for cause and effect. The current 2022 AAP Clinical Practice Guideline Revision1 notes that although the topic is understudied, there is some evidence that phototherapy may limit familial bonding with the newborn infant. In a single observational study, 70% mothers of infants born from 1987 to 1988 who had a diagnosis of jaundice and in whom breastfeeding was terminated were concerned that their infants’ care implied that their infant (<2500 g birth weight) had been moderately to severely ill and their concern remained at 1-month postnatal age after having received phototherapy in the NICU.72 It should be noted that clinical practice (including increased phototherapy utilization) and parental counseling (on phototherapy and breastfeeding) have been individualized and changed over the past 30 years.
Adverse Effects of Phototherapy in Newborn Infants
| Condition . | Net Findings and Conclusions . |
|---|---|
| Epilepsy or seizures | Phototherapy to treat hyperbilirubinemia in newborn infants is associated with an increased risk of developing epilepsy for males in early childhood. No excess risk for febrile seizures is seen. A slight risk in childhood seizures diagnosed at ≥60 days postnatal age after adjustment for bilirubin measurements is observed. Boys are more likely than girls to receive phototherapy treatment of hyperbilirubinemia and to be diagnosed with a childhood seizure. A valid, bias-independent causal relationship of this association needs to be demonstrated. Though phototherapy rather than TSB levels appears to be an independent predictor; use unadjusted hazard ratio of >2 or even 3 to avoid risk of biased over-interpretation. Here, the calculated value of 1.2 is modest.74 The potential concern requires further inquiry. |
| Childhood asthma | Hyperbilirubinemia and phototherapy are both associated with an increased odds of being hospitalized for childhood asthma after 2 years of age. However, it is impossible to distinguish any phototherapy-associated effects on asthma from those because of hyperbilirubinemia. On the other hand, hyperbilirubinemia, but not phototherapy, is associated with an increased odds of a childhood asthma diagnosis after 1 year of age. Modest hyperbilirubinemia is associated with an increased risk of asthma, but this association is not observed at higher bilirubin levels. Phototherapy is unlikely to increase or decrease asthma risk. |
| Childhood allergic rhinitis | There is no association between phototherapy and childhood allergic rhinitis. Neonatal jaundice is associated with a childhood allergic rhinitis diagnosis before 10 years of age. |
| Allergic conjunctivitis | Hyperbilirubinemia and phototherapy are both associated with an increased odds of developing asthma and allergic rhinitis; but it is impossible to attribute adverse allergic outcomes to either hyperbilirubinemia or phototherapy. |
| Atopic dermatitis | Although neonatal jaundice is linked to an increased rate of childhood atopic dermatitis, phototherapy is not associated with an atopic dermatitis diagnosis. |
| Eczema | Phototherapy is not linked to an increased rate of childhood eczema. |
| Urticaria | Phototherapy is not linked to an increased rate of childhood urticaria. |
| Wheezing or nebulizer or inhaler use | No association is found between phototherapy or bilirubin levels and allergic sensitization, wheezing, or nebulizer or inhaler use. |
| Food allergies | No studies to date have quantitatively assessed the association between jaundice or phototherapy and food allergies. It is impossible to separate jaundice-associated effects from those because of phototherapy. |
| Maternal concerns about overall health | Mothers of infants who had a jaundice diagnosis are more concerned about their infants’ overall health at 1-month postnatal age. Maternal concerns are increased if their infant received in-hospital phototherapy. It should be noted that clinical practice (including increased phototherapy utilization) and parental counseling (on phototherapy and breastfeeding) may have changed over the last 28 y since these data were published. |
| Neurodevelopment (Denver Developmental Screening Test at 1 y of age) | Treatment with phototherapy as a newborn does not appear to affect neurodevelopment as measured at 1 year of age or by maternal-infant attachment at 1 year of age. |
| Outpatient visits | Small increases in outpatient visits before 1 year of age are seen with neonatal jaundice (36%) and phototherapy (73%), most often occurring in the first 2 postnatal months. Phototherapy and jaundice diagnoses are associated with only small increases in first-year outpatient visit rates, consistent with mild contributions to the vulnerable child syndrome. |
| Exclusive breastfeeding | Phototherapy may be associated with a decreased odds of exclusive breastfeeding during postnatal months 1 to 4. However, phototherapy is not associated with a change in the odds of any breastfeeding. Although there is a decrease in the odds of any breastfeeding at 12 months postnatally, it seems unlikely that phototherapy is the cause. It is unclear whether phototherapy has a more adverse effect on breastfeeding than other interventions. |
| Breastmilk feeding | Phototherapy during birth hospitalization is not associated with reduced breastmilk feeding at the 2-month well-child visit. This observation may not be applicable to hospital systems that do not actively support maternal lactation during phototherapy. Therefore, lactation support should be encouraged. |
| Visual orientation | Infants that receive phototherapy may have short-term changes in visual orientation. Results may not apply to infants whose eyes are not covered during phototherapy or who are not separated from their parents. Infants that received phototherapy may have had short-term changes in visual orientation. Results may not apply to infants whose eyes are not covered during phototherapy or who are not separated from their parents. Currently, the data to suggest that hyperbilirubinemia impacts visual outcomes need further validation.75 |
| Childhood cancers | Hyperbilirubinemia is not associated with childhood cancers, but the data do not directly estimate the effect of phototherapy on cancer. |
| Childhood malignant melanoma | No association is found between phototherapy and the development of childhood malignant melanoma. |
| Non-Hodgkins lymphoma | Phototherapy and jaundice are not associated with leukemia or non-Hodgkin’s lymphoma in young adults. |
| Leukemias | Phototherapy and neonatal jaundice are associated with childhood leukemias. Data are not adjusted for the degree of hyperbilirubinemia nor for intensity or duration of phototherapy. Lymphocytic leukemia: Neither phototherapy or neonatal jaundice is found to increase the odds of developing childhood lymphatic leukemia, data are not adjusted for the degree of hyperbilirubinemia or phototherapy intensity or duration. Childhood myeloid leukemia: phototherapy and neonatal jaundice are associated with an increased odds of developing childhood myeloid leukemia. However, this association is no longer statistically significant after excluding children with a Trisomy 21 diagnosis. Data are not adjusted for the degree of hyperbilirubinemia nor for phototherapy intensity or duration. |
| Skin cancer | No difference in skin cancer risk is detected in infants exposed to phototherapy. In adjusted analyses, no statistically significant elevation in the risk for cancer is found. Unadjusted analyses do show an elevated risk. Given their elevated baseline risk for leukemia, children with Trisomy 21 may be at an even higher risk for leukemias after phototherapy. Adjusted analyses indicated that phototherapy may slightly increase the risk of cancer in the first postnatal year. |
| Solid tumors | Phototherapy may be associated with a slightly increased risk of solid tumors in childhood; however, it is not possible to rule out increasing bilirubin concentration as a potential confounder, since a jaundice diagnosis is also associated with cancer, bilirubin concentrations are not available, and phototherapy would likely be initiated at higher bilirubin levels compared with untreated jaundice. Adjusted hazard ratios for any cancer and for solid tumor cancers, but not for hematopoietic cancers, significantly increase with age for infants exposed to phototherapy. An adjusted analysis has shown that phototherapy may slightly increase the risks of childhood malignancies and benign tumors cancer in the first postnatal year. However, it is not possible to rule out increasing bilirubin concentration as a potential confounder or to evaluate the impact of phototherapy intensity or duration on outcomes. |
| Childhood melanocytic nevi | No association is found between phototherapy as reported via parent survey and childhood melanocytic nevus count at ages 2–7 years. An association at ages 8–9 between neonatal phototherapy exposure and an increased 2- to 5-mm nevus count has been reported. There is no association found between phototherapy and total nevus count at age 9 years. A twin comparison study has demonstrated an association between blue light phototherapy exposure and increased numbers of both melanocytic skin and uveal lesions. A meta-analysis of published studies did not demonstrate a significantly higher mean number of melanocytic nevi after exposure to phototherapy. |
| Condition . | Net Findings and Conclusions . |
|---|---|
| Epilepsy or seizures | Phototherapy to treat hyperbilirubinemia in newborn infants is associated with an increased risk of developing epilepsy for males in early childhood. No excess risk for febrile seizures is seen. A slight risk in childhood seizures diagnosed at ≥60 days postnatal age after adjustment for bilirubin measurements is observed. Boys are more likely than girls to receive phototherapy treatment of hyperbilirubinemia and to be diagnosed with a childhood seizure. A valid, bias-independent causal relationship of this association needs to be demonstrated. Though phototherapy rather than TSB levels appears to be an independent predictor; use unadjusted hazard ratio of >2 or even 3 to avoid risk of biased over-interpretation. Here, the calculated value of 1.2 is modest.74 The potential concern requires further inquiry. |
| Childhood asthma | Hyperbilirubinemia and phototherapy are both associated with an increased odds of being hospitalized for childhood asthma after 2 years of age. However, it is impossible to distinguish any phototherapy-associated effects on asthma from those because of hyperbilirubinemia. On the other hand, hyperbilirubinemia, but not phototherapy, is associated with an increased odds of a childhood asthma diagnosis after 1 year of age. Modest hyperbilirubinemia is associated with an increased risk of asthma, but this association is not observed at higher bilirubin levels. Phototherapy is unlikely to increase or decrease asthma risk. |
| Childhood allergic rhinitis | There is no association between phototherapy and childhood allergic rhinitis. Neonatal jaundice is associated with a childhood allergic rhinitis diagnosis before 10 years of age. |
| Allergic conjunctivitis | Hyperbilirubinemia and phototherapy are both associated with an increased odds of developing asthma and allergic rhinitis; but it is impossible to attribute adverse allergic outcomes to either hyperbilirubinemia or phototherapy. |
| Atopic dermatitis | Although neonatal jaundice is linked to an increased rate of childhood atopic dermatitis, phototherapy is not associated with an atopic dermatitis diagnosis. |
| Eczema | Phototherapy is not linked to an increased rate of childhood eczema. |
| Urticaria | Phototherapy is not linked to an increased rate of childhood urticaria. |
| Wheezing or nebulizer or inhaler use | No association is found between phototherapy or bilirubin levels and allergic sensitization, wheezing, or nebulizer or inhaler use. |
| Food allergies | No studies to date have quantitatively assessed the association between jaundice or phototherapy and food allergies. It is impossible to separate jaundice-associated effects from those because of phototherapy. |
| Maternal concerns about overall health | Mothers of infants who had a jaundice diagnosis are more concerned about their infants’ overall health at 1-month postnatal age. Maternal concerns are increased if their infant received in-hospital phototherapy. It should be noted that clinical practice (including increased phototherapy utilization) and parental counseling (on phototherapy and breastfeeding) may have changed over the last 28 y since these data were published. |
| Neurodevelopment (Denver Developmental Screening Test at 1 y of age) | Treatment with phototherapy as a newborn does not appear to affect neurodevelopment as measured at 1 year of age or by maternal-infant attachment at 1 year of age. |
| Outpatient visits | Small increases in outpatient visits before 1 year of age are seen with neonatal jaundice (36%) and phototherapy (73%), most often occurring in the first 2 postnatal months. Phototherapy and jaundice diagnoses are associated with only small increases in first-year outpatient visit rates, consistent with mild contributions to the vulnerable child syndrome. |
| Exclusive breastfeeding | Phototherapy may be associated with a decreased odds of exclusive breastfeeding during postnatal months 1 to 4. However, phototherapy is not associated with a change in the odds of any breastfeeding. Although there is a decrease in the odds of any breastfeeding at 12 months postnatally, it seems unlikely that phototherapy is the cause. It is unclear whether phototherapy has a more adverse effect on breastfeeding than other interventions. |
| Breastmilk feeding | Phototherapy during birth hospitalization is not associated with reduced breastmilk feeding at the 2-month well-child visit. This observation may not be applicable to hospital systems that do not actively support maternal lactation during phototherapy. Therefore, lactation support should be encouraged. |
| Visual orientation | Infants that receive phototherapy may have short-term changes in visual orientation. Results may not apply to infants whose eyes are not covered during phototherapy or who are not separated from their parents. Infants that received phototherapy may have had short-term changes in visual orientation. Results may not apply to infants whose eyes are not covered during phototherapy or who are not separated from their parents. Currently, the data to suggest that hyperbilirubinemia impacts visual outcomes need further validation.75 |
| Childhood cancers | Hyperbilirubinemia is not associated with childhood cancers, but the data do not directly estimate the effect of phototherapy on cancer. |
| Childhood malignant melanoma | No association is found between phototherapy and the development of childhood malignant melanoma. |
| Non-Hodgkins lymphoma | Phototherapy and jaundice are not associated with leukemia or non-Hodgkin’s lymphoma in young adults. |
| Leukemias | Phototherapy and neonatal jaundice are associated with childhood leukemias. Data are not adjusted for the degree of hyperbilirubinemia nor for intensity or duration of phototherapy. Lymphocytic leukemia: Neither phototherapy or neonatal jaundice is found to increase the odds of developing childhood lymphatic leukemia, data are not adjusted for the degree of hyperbilirubinemia or phototherapy intensity or duration. Childhood myeloid leukemia: phototherapy and neonatal jaundice are associated with an increased odds of developing childhood myeloid leukemia. However, this association is no longer statistically significant after excluding children with a Trisomy 21 diagnosis. Data are not adjusted for the degree of hyperbilirubinemia nor for phototherapy intensity or duration. |
| Skin cancer | No difference in skin cancer risk is detected in infants exposed to phototherapy. In adjusted analyses, no statistically significant elevation in the risk for cancer is found. Unadjusted analyses do show an elevated risk. Given their elevated baseline risk for leukemia, children with Trisomy 21 may be at an even higher risk for leukemias after phototherapy. Adjusted analyses indicated that phototherapy may slightly increase the risk of cancer in the first postnatal year. |
| Solid tumors | Phototherapy may be associated with a slightly increased risk of solid tumors in childhood; however, it is not possible to rule out increasing bilirubin concentration as a potential confounder, since a jaundice diagnosis is also associated with cancer, bilirubin concentrations are not available, and phototherapy would likely be initiated at higher bilirubin levels compared with untreated jaundice. Adjusted hazard ratios for any cancer and for solid tumor cancers, but not for hematopoietic cancers, significantly increase with age for infants exposed to phototherapy. An adjusted analysis has shown that phototherapy may slightly increase the risks of childhood malignancies and benign tumors cancer in the first postnatal year. However, it is not possible to rule out increasing bilirubin concentration as a potential confounder or to evaluate the impact of phototherapy intensity or duration on outcomes. |
| Childhood melanocytic nevi | No association is found between phototherapy as reported via parent survey and childhood melanocytic nevus count at ages 2–7 years. An association at ages 8–9 between neonatal phototherapy exposure and an increased 2- to 5-mm nevus count has been reported. There is no association found between phototherapy and total nevus count at age 9 years. A twin comparison study has demonstrated an association between blue light phototherapy exposure and increased numbers of both melanocytic skin and uveal lesions. A meta-analysis of published studies did not demonstrate a significantly higher mean number of melanocytic nevi after exposure to phototherapy. |
Phototherapy is only initiated when there is concern of developing severe hyperbilirubinemia; however, discrimination of the association of adverse outcomes to either the degree of hyperbilirubinemia or of exposure to phototherapy or both has not been consistent. In addition, none of the reviewed studies addressed whether UV radiation had been filtered out from the light sources used for phototherapy.
Studies were unable to categorically differentiate or distinguish adverse outcomes that could be independently attributed to either the magnitude of hyperbilirubinemia or exposure to phototherapy. Therefore, treatment thresholds should be established that can balance the risk of adverse effects of phototherapy and its possible benefit at reducing TSB concentrations before reaching potential neurotoxic levels. These retrospective studies should also be interpreted by the ongoing evolution, over the past 30 years, of phototherapy devices that no longer incorporate heat-generating lamps and filter UV irradiation to avoid unnecessarily high irradiances.
VII. Research Needs
Many gaps in knowledge remain regarding the use of phototherapy. The following are among the most important:
A validated cost-effective device that can measure real-time wavelength and irradiance delivered by a phototherapy device is urgently needed to be able to assess the true efficiency of phototherapy in reducing TSB concentrations.
The safety and efficacy of home phototherapy for specific types of newborn infants at specific TSB thresholds remains a research priority.
Rigorously designed and appropriately powered studies (such as those evaluating the use of cycled [intermittent] phototherapy) are needed to definitively determine the potential long-term sequelae of phototherapy and of specific durations and magnitudes of both conjugated and unconjugated hyperbilirubinemia and concurrent glucose-6-phosphate dehydrogenase deficiency.
Design technologies that can continuously measure total photon dose (irradiance delivered to BSA in real time) to identify potential adverse outcomes.73
Summary
When implemented in a timely manner and performed with standardized procedures, phototherapy is a predominantly safe and noninvasive modality that will minimize risk of neonatal brain injury. Experts consider that the current prescribed thresholds1 can provide sufficient margin of safety to prevent bilirubin neurotoxicity in newborn infants ≥35 weeks of gestation.
Lead Authors
Vinod K. Bhutani, MD, FAAP
Ronald J. Wong, PhD
David Turkewitz, MD, FAAP
Daniel A. Rauch, MD, FAAP
Meredith E. Mowitz, MD, MS, FAAP
Wanda D. Barfield, MD, MPH, FAAP
Committee on Fetus and Newborn, 2022–2023
Eric Eichenwald, MD, FAAP, Chairperson
Namasivayam Ambalavanan, MD, FAAP
Charleta Guillory, MD, FAAP
Mark Hudak, MD, FAAP
David Kaufman, MD, FAAP
Camilia Martin, MD, FAAP
Ashley Lucke, MD, FAAP
Margaret Parker, MD, FAAP
Arun Pramanik, MD, FAAP
Kelly Wade, MD, FAAP
Liaisons
Timothy Jancelewicz, MD, FAAP – AAP Section on Surgery
Michael Narvey, MD – Canadian Pediatric Society
Russell Miller, MD – American College of Obstetricians and Gynecologists
RADM Wanda Barfield, MD, MPH, FAAP – Centers for Disease Control and Prevention
Lisa Grisham, APRN, NNP-BC – National Association of Neonatal Nurses
Consultants
David K. Stevenson, MD, FAAP
M. Jeffrey Maisels, MD, FAAP
Hendrik J. Vreman
Richard A. Polin, MD, FAAP
Angelo A. Lamola
Cody C. Arnold, MD, FAAP
Finn Ebbesen
Staff
Jim Couto, MA
Acknowledgments
The authors recognize the collective pioneering contributions of scholars, practitioners, scientists, photobiologists, and bilirubin researchers as well as a plethora of clinicians and bioengineers who have contributed to extensive body of literature and evidence for this breakthrough technology that has helped save lives and prevent neonatal brain injury. Thus, it is not a matter of “just turn the lights on” but that of trusting your own knowledge and judgment to assess benefits over risk of any human therapy.
Drs Bhutani, Wong, Turkewitz, Rauch, Morowizs, and Barfield conceptualized, collated data, and drafted the initial technical report; and all authors critically reviewed and revised the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.
Technical reports from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and external reviewers. However, technical reports from the American Academy of Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent.
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.
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.
FUNDING: No external funding.
FINANCIAL/CONFLICT OF INTEREST DISCLOSURE: The authors have indicated they have no potential conflicts of interest to disclose. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
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