INTRODUCTION — Nearly all newborn infants develop elevated bilirubin levels (ie, total serum bilirubin [TSB] >1 mg/dL [17 micromol/L], which is the upper limit of normal for adults). As TSB levels increase, the newborn may develop visible jaundice. Neonates with severe hyperbilirubinemia (defined as TSB >25 mg/dL [428 micromol/L] in term and late preterm newborns [gestational age (GA) ≥35 weeks]) are at risk for developing bilirubin-induced neurotoxicity.
The initial management of unconjugated hyperbilirubinemia in term and late preterm newborn infants is reviewed here, including details regarding phototherapy. Management of newborns who require escalated care and/or exchange transfusion for unconjugated hyperbilirubinemia is discussed separately. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia".)
Other related issues are discussed separately:
●Pathogenesis and etiology of neonatal hyperbilirubinemia (see "Etiology and pathogenesis of neonatal unconjugated hyperbilirubinemia")
●Risk factors, clinical manifestations, and neurologic complications of neonatal hyperbilirubinemia (see "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia")
●Screening for hyperbilirubinemia in term and late preterm newborns (see "Screening for hyperbilirubinemia in term and late preterm newborn infants")
●Hyperbilirubinemia in preterm infants (GA <35 weeks) (see "Unconjugated hyperbilirubinemia in preterm infants <35 weeks gestation")
●Conjugated (direct) hyperbilirubinemia in newborns (see "Causes of cholestasis in neonates and young infants")
DEFINITIONS — The following terms are used throughout this topic:
●Benign neonatal hyperbilirubinemia is a transient and normal increase in bilirubin levels occurring in nearly all newborn infants. It was previously referred to as "physiologic jaundice."
●Severe neonatal hyperbilirubinemia is defined as a total serum or plasma bilirubin (TSB) >25 mg/dL (428 micromol/L). It is associated with an increased risk for developing bilirubin-induced neurotoxicity.
●Extreme neonatal hyperbilirubinemia is defined as a TSB >30 mg/dL (513 micromol/L). It is associated with a higher risk for developing bilirubin-induced neurotoxicity, including irreversible chronic encephalopathy.
●Bilirubin-induced neurology disorders (BIND) result from selective brain damage from free (unbound) bilirubin crossing the blood-brain barrier and binding to brain tissue. The spectrum of neurotoxic injury, including subtle dysfunction and acute and chronic bilirubin encephalopathy (ABE and CBE, respectively), is collectively referred to as BIND. The manifestations of BIND, ABE, and CBE are described separately. (See "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia", section on 'Consequences of severe hyperbilirubinemia'.)
Assessment of neonatal hyperbilirubinemia is based upon total bilirubin rather than unconjugated bilirubin levels alone because neonatal hyperbilirubinemia is mostly due to increased bilirubin production, resulting primarily in unconjugated bilirubin. Cholestasis, which presents with primarily elevated conjugated (direct) bilirubin, is a rare cause of neonatal hyperbilirubinemia. (See "Etiology and pathogenesis of neonatal unconjugated hyperbilirubinemia" and "Causes of cholestasis in neonates and young infants".)
GOALS — The goals of managing neonatal hyperbilirubinemia are to prevent severe hyperbilirubinemia and bilirubin-induced neurologic disorders (BIND) while avoiding unnecessary interventions which can interfere with successful initiation of breastfeeding and parent/caregiver bonding with the newborn. Thus, the treatment thresholds discussed below are meant to reflect the point at which the benefits of treatment likely exceed potential downsides [1]. (See 'Thresholds for treatment' below.)
The decision of when to initiate and escalate therapy are based upon the newborn's risk of developing severe hyperbilirubinemia and BIND. The most important risk factor for BIND is the severity and duration of bilirubin exposure. Additional risk factors are summarized in the tables (table 1 and table 2) and discussed separately. (See "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia", section on 'Risk factors for neurotoxicity'.)
Our approach is generally consistent with guidance from the American Academy of Pediatrics (AAP), the Canadian Paediatric Society (CPS), and the United Kingdom's National Institute of Health and Clinical Excellence (NICE) guidelines [1-3]. Links to these and other society guidelines are provided separately. (See 'Society guideline links' below.)
SUPPORTIVE CARE — Newborns with hyperbilirubinemia should receive adequate nutrition and hydration since this enhances bilirubin elimination. Maintaining adequate urine output is critical for newborns receiving phototherapy since its principal mechanism involves excreting lumirubin (the main photoproduct of bilirubin) in the urine. (See 'Initial intervention (phototherapy)' below.)
Feeding — Breastfeeding is encouraged for newborns with hyperbilirubinemia, as it is for all newborns. The benefits of breastfeeding are discussed separately. (See "Infant benefits of breastfeeding".)
Key aspects of optimizing feeding include promoting human milk feeding, enhancing maternal milk production, and avoiding excessive weight loss (defined as >10 percent of birth weight (BW) in the first few days after birth) [4]. These issues are discussed separately. (See "Initiation of breastfeeding".)
For breastfed infants with inadequate intake, excessive weight loss (>10 percent of BW), and/or who evidence of hypovolemia, supplemental feeds should be provided with human milk, either expressed maternal milk (preferred) or pasteurized donor milk [4,5]. Formula supplementation is discouraged but may be used if these preferred sources of human milk are not available or not chosen. Enteral feeding is preferred over intravenous (IV) hydration because it enhances excretion of bilirubin through enterohepatic circulation. (See "Initiation of breastfeeding", section on 'Assessment of intake'.)
During phototherapy, newborns should continue oral feedings by breast, bottle, or other methods (eg, cup). Breastfeeding may need to be temporarily halted if the newborn's total serum or plasma bilirubin (TSB) level is very elevated. If this occurs, bottle feedings should be provided and breastfeeding should be resumed as soon as possible once the TSB improves. (See 'Technique' below.)
Intravenous hydration — Most newborns with hyperbilirubinemia do not require IV hydration since oral feeding with or without supplementation generally provides adequate hydration. However, for newborns with dehydration, hypovolemia, and/or hypernatremia due to inadequate oral intake, IV hydration may be necessary [5]. In addition, we suggest IV hydration for newborns who require an escalated level of care (ie, those who have TSB levels at or approaching the threshold for exchange transfusion), as discussed separately. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia", section on 'IV hydration'.)
Initial treatment of hypovolemia consists of a 10 to 20 mL/kg bolus of isotonic fluids (eg, normal saline). If required, ongoing IV hydration consists of crystalloid fluid (typically 10 percent dextrose with one-quarter normal saline) at a maintenance rate (ie, 60 to 80 mL/kg per day for newborns <48 hours old; 80 to 100 mL/kg per day for those ≥48 hours old). Subsequent adjustments are based on measurement of serum electrolytes. (See "Fluid and electrolyte therapy in newborns".)
THRESHOLDS FOR TREATMENT
Symptomatic patients — Newborns with elevated total serum or plasma bilirubin (TSB) levels in association with signs of acute bilirubin encephalopathy (ABE) generally require escalation of care and exchange transfusion. Signs and symptoms of ABE include lethargy, hyper- or hypotonia, poor suck, high-pitched cry, recurrent apnea, opisthotonos, retrocollis, seizures (table 3). Symptomatic newborns require escalation of care even if the TSB level is not above the treatment threshold. Phototherapy should be provided while preparations are made to perform exchange transfusion. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia".)
However, newborns with signs of ABE in the setting of TSB levels that are below the treatment threshold should undergo evaluation for other etiologies since ABE is unusual at TSB levels <20 mg/dL (342 micromol/L); most reported cases of ABE have occurred at TSB levels ≥30 mg/dL (513 micromol/L). (See "Clinical features, diagnosis, and treatment of neonatal encephalopathy", section on 'Investigations' and "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia", section on 'Acute bilirubin encephalopathy (ABE)'.)
Asymptomatic patients — The American Academy of Pediatrics (AAP) has established hour-specific TSB thresholds for initiating treatment of neonatal hyperbilirubinemia [1]. Thresholds for initiating phototherapy vary depending upon the newborn's gestational age (GA) and other risk factors for neurotoxicity (table 2):
●Phototherapy thresholds for newborns without risk factors for neurotoxicity (other than GA) (figure 1A)
●Phototherapy thresholds for newborns with at least one risk factor for neurotoxicity (other than GA) (figure 1B)
Treatment decisions should be guided by TSB values not transcutaneous bilirubin (TcB) measurements. If initial screening was performed with a TcB device and the value is >15 mg/dL (257 micromol/L) or within 3 mg/dL (51 micromol/L) of the phototherapy TSB threshold, it should be confirmed with a TSB level. However, if the TcB level is above the treatment threshold, phototherapy should be initiated while awaiting confirmation. (See "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Bilirubin testing methods'.)
●TSB at or above the treatment threshold – For newborns with TSB at or above the threshold for treatment (figure 1A-B), treatment should be initiated promptly [1].
For most patients, the initial intervention consists of phototherapy. (See 'Initial intervention (phototherapy)' below.)
However, infants with TSB levels that are approaching or above the threshold for exchange transfusion (figure 2A-B) require escalation of care and possible exchange transfusion, as discussed separately. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia".)
●TSB near threshold – Newborns with TSB levels that are <2 mg/dL (34 micromol/L) below the phototherapy threshold (figure 1A-B) are at high risk of subsequently needing treatment [1,6].
We suggest initiating phototherapy early (ie, at near-threshold TSB values rather than waiting for TSB to cross the treatment threshold) if the newborn has any of the following clinical risk factors for progressive hyperbilirubinemia [7]:
•Early-onset jaundice (within first 24 hours after birth)
•ABO or Rhesus (Rh) incompatibility
•Rapidly rising bilirubin levels (ie, increasing by ≥0.3 mg/dL [5 micromol/L] per hour in the first 24 hours or ≥0.2 mg/dL [3 micromol/L] per hour thereafter)
•Significant bruising or cephalohematoma
For newborns with near-threshold TSB levels who lack clinical risk factors for progressive hyperbilirubinemia, treatment should be individualized depending on parent/caregiver preference. The use of subthreshold phototherapy in this setting may reduce the risk of readmission, but could also result in unnecessary exposure to phototherapy, impede newborn-parent/caregiver bonding, and prolong birth hospitalization [7]. Home phototherapy is an option for some newborns with near-threshold TSB levels if there are no clinical risk factors and additional criteria are met. This is discussed below. (See 'Home phototherapy' below.)
If treatment is not provided, close follow-up is warranted, as discussed separately. (See "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Approach based upon bilirubin level'.)
Newborns with near-threshold TSB values within the first 24 hours of birth should undergo evaluation for hemolytic conditions, if not already performed. This is discussed separately. (See "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Testing for hemolysis'.)
●TSB below threshold – Newborns with TSB levels that are >2 mg/dL (34 micromol/L) below the phototherapy threshold (figure 1A-B) generally do not require treatment. However, there is still a risk that the TSB level could subsequently rise, particularly during the first 72 to 96 hours after birth [1]. Thus, some newborns in this category will require repeat testing, depending on their age and the timing of discharge from the birth hospitalization. Details regarding the need for reassessment and follow-up after newborn bilirubin screening are summarized in the table (table 4) and discussed in greater detail separately. (See "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Approach based upon bilirubin level'.)
INITIAL INTERVENTION (PHOTOTHERAPY) — Phototherapy is the most commonly used intervention to treat and prevent severe hyperbilirubinemia. It is a safe and effective intervention to reduce total serum or plasma bilirubin (TSB) levels based upon its extensive use in millions of infants over six decades [5,8,9]. It decreases or blunts the trajectory of TSB levels regardless of the etiology of hyperbilirubinemia [10-12].
The introduction of phototherapy in the latter half of the twentieth century represented a pivotal shift in the management of neonatal hyperbilirubinemia and dramatically reduced rates of severe hyperbilirubinemia. (See "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia", section on 'Trends over time'.)
However, since the early 2000s, there have been growing concerns that phototherapy may be overprescribed and that its use may unnecessarily prolong birth hospitalization and impede maternal bonding and breastfeeding [13].
The following sections provide guidance on administering and monitoring phototherapy and discuss the efficacy and adverse effects of this intervention. Our suggested approach is generally consistent with the 2022 American Academy of Pediatrics (AAP) guidelines. The updated treatment thresholds established by the AAP panel aim to define the point at which the benefits of phototherapy likely outweigh the potential harms [1]. These thresholds are based largely upon expert opinion rather than definitive evidence.
It is important to recognize that the treatment thresholds in the 2022 AAP guidelines are higher than in previous guidelines. The updated guidelines assume that treatment will begin promptly. Delays in starting therapy are considerably more likely to result in dangerously high TSB levels compared with the earlier treatment approach.
Like any other therapeutic intervention, clinical judgment is required to ensure appropriate and correct dosing of phototherapy based on an individualized risk/benefit assessment for the newborn, thereby avoiding under- or overuse of phototherapy. Phototherapy should be prescribed only with appropriate approved light sources and only when threshold or near-threshold TSB levels are reached. (See 'Thresholds for treatment' above and 'Light sources and devices' below.)
Pretreatment laboratory evaluation — Pretreatment testing for newborns who require phototherapy includes the following:
●Confirmatory TSB level, if the newborn does not have a recent TSB level or if initial screening was performed with a transcutaneous bilirubin measurement
●Testing for hemolysis, if not already performed. This includes:
•Hemoglobin/hematocrit
•Reticulocyte count
•Peripheral blood smear examination
•Direct antiglobulin test (DAT) in newborns born to mothers with O or Rhesus (Rh) D negative blood types, or with positive maternal antibody screen (see "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Tests to perform')
•Glucose-6-phosphate dehydrogenase (G6PD) enzyme activity
•End-tidal carbon monoxide (ETCOc) testing, if available (see "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Testing for hemolysis')
Administration
Technique
●Positioning the newborn – When initiating phototherapy, the newborn should be placed supine, with body exposed and the area covered by the diaper minimized (for hygiene only), and eyes shielded with an opaque orbital shield (figure 3). Care should be taken to prevent the shield from covering the nose or sliding off the orbits.
●Deliver phototherapy from above and below – Light should be delivered to as much of an infant's skin as possible with a combination of light sources both above and below the newborn [14]. (See 'Light sources and devices' below.)
In a meta-analysis of three randomized trials (203 term newborns), double phototherapy was more effective than single phototherapy for reducing TSB levels (mean difference 3 mg/dL [52 micromol/L]; 95% CI 0.2-6.3 mg/dL [4-108 micromol/L]) [14].
●Minimize interruptions – Interruptions to phototherapy should be minimized.
•For newborns with TSB <20 mg/dL (342 micromol/L), phototherapy can be interrupted intermittently for feeding and/or parent/caregiver holding.
•For newborns with TSB ≥20 mg/dL (342 micromol/L), phototherapy should be administered continuously, without interruptions for parent/caregiver holding or during feeding (ie, newborns should be fed with a bottle while under phototherapy) until the TSB falls below this level.
Dosing — The effectiveness of phototherapy depends upon the dose given (irradiance), the amount of skin surface area exposed, and the amount of time phototherapy is given [1].
●Irradiance – Effective phototherapy requires an irradiance of at least 30 microW/cm2/nm with light at a blue to blue-green wavelength (460 to 490 nm; optimal at 478 nm) [1]. This is ideally provided with a narrow-spectrum blue light-emitting diode (LED) light, as discussed below. (See 'Light sources and devices' below.)
Factors that can affect irradiance include the light source used (wavelength, bandwidth, and intensity) and the distance between the light and infant. The product of the irradiance and body surface area (BSA) is known as the spectral power and provides an index of the total dose of phototherapy provided [9].
Historically, the term "intensive phototherapy" was used for phototherapy applied with an irradiance of at least 30 microW/cm2/nm, whereas the terms "standard" or "conventional" phototherapy were used for phototherapy applied at a lower irradiance. However, intensive phototherapy is now the standard of care and we no longer make a distinction between "intensive" versus "standard" phototherapy.
●Maximize skin exposure – Effective phototherapy requires that light is delivered to as much of a newborn's BSA as possible. Ideally, phototherapy is provided with devices placed above and below the infant. (See 'Technique' above and 'Light sources and devices' below.)
●Maximize time under phototherapy – Effective phototherapy requires that the newborn spend as much time under phototherapy as possible. Interruptions should be limited. For newborns with TSB ≥20 mg/dL (342 micromol/L), phototherapy should be administered continuously, with no interruptions for feeding or caregiver holding. (See 'Technique' above.)
Light sources and devices — Devices using blue LED lamps are the optimal light sources for phototherapy, as they deliver high intensity narrow-band light at the optimal wavelength without emitting ultraviolet (UV) light. Other light sources include fluorescent tubes or halogen bulbs [15].
●Preferred light source: Blue LED lights – Blue LED lights (eg, Bilisoft 2.0 [General Electric], BiliTouch [Motif], Blue Spot PT [General Electric], neoBLUE [Natus], Skylife [Neolight]) use high-intensity gallium nitride gas that emit light at a peak wavelength of 470±10 nm. They are commercially available as overhead lights, underneath pads/mattresses, and blankets [8,16,17]. We prefer these devices over non-LED devices because blue LEDs deliver high intensity narrow-band light in the absorption spectrum of bilirubin without generating heat or emitting UV light. LED-based mattresses are preferable to pads or blankets because they are large enough to cover most of the BSA of a term infant.
The available clinical trial evidence suggests that blue LED devices have comparable efficacy compared with non-LED devices [18,19]. In a meta-analysis of five trials involving 511 term and late preterm newborns with hyperbilirubinemia, rates of TSB decline were similar for newborns treated with LED phototherapy compared with non-LED phototherapy (0.2 mg/dL [3 micromol/L] per hour in both) [19]. In another meta-analysis that included the same five trials plus one additional trial (total 630 newborns), the duration of phototherapy was similar in both groups [18]. Adverse effects (skin rashes, hypothermia, and hyperthermia) were rare in both groups.
●Fluorescent and halogen lights – Devices using fluorescent lights (eg, BiliBed [Medela], BiliLite [Olympic]) or fiberoptic halogen lights (eg, BiliBlanket [General Electric], Wallaby 3 [Respironics]) were commonly used in the past and are still widely available. We generally prefer blue LED lights over these devices for the reasons outlined above. However, if a blue LED device is not available, fluorescent and halogen lights are acceptable alternatives. Fiberoptic blankets or pads generate little heat and can be placed close to the infant, providing higher irradiances than fluorescent lights [20]. However, blankets are typically small and rarely cover sufficient BSA to be effective when used alone in term infants. They can be used as an adjunct to overhead lights if an LED pad/mattress is not available. Fiberoptic blankets also can be used during feedings when overhead lighting is discontinued. This is particularly helpful for infants with severe hyperbilirubinemia.
●Alternative in resource-limited settings: Filtered sunlight – Phototherapy using indirect (filtered) sunlight appears to be a reasonable alternative for treating mild-to-moderate hyperbilirubinemia in resource-limited settings if phototherapy devices are not readily available. Commercially available window tinting films transmit blue light while filtering harmful UV and infrared light. This reduces the risk of sunburn and other harmful effects of UV radiation. Based upon clinical trials performed in resource-limited settings, filtered sunlight using window tinting films appears to have similar efficacy for reducing TSB levels compared with conventional phototherapy [21-23].
●Direct sunlight NOT recommended – Direct sunlight, which includes UV radiation, is not recommended as a therapeutic option to treat or prevent hyperbilirubinemia. Exposure to direct sunlight is associated considerable risks, including:
•Sunburn
•Hyperthermia
•Hypovolemia from heat and increased fluid losses
•Long-term risk of skin malignancies (see "Risk factors for the development of melanoma", section on 'Ultraviolet radiation' and "Cutaneous squamous cell carcinoma: Epidemiology and risk factors", section on 'Ultraviolet radiation')
Home phototherapy — Home phototherapy is less disruptive to the family and is an option for discharged newborns with TSB levels near the TSB threshold for phototherapy (ie, <2 mg/dL [34 micromol/L] below to ≤1 mg/dL [17 micromol/L] above the threshold) [24].
We use home phototherapy only if all of the following conditions are met [1]:
•Gestational age ≥38 weeks
•≥48 hours postnatal age
•Clinically well with adequate feeding
•No known hyperbilirubinemia neurotoxicity risk factors (table 2)
•No previous phototherapy
•TSB ≤1 mg/dL (17 micromol/L) above the phototherapy treatment threshold
•An LED-based phototherapy device can be available in the home immediately
•TSB can be measured daily
Home phototherapy should not be used in newborns with any clinical risk factors for severe or progressive hyperbilirubinemia (table 1), especially hemolytic disease. Its efficacy and safety in this setting remain unproven.
When appropriate selection criteria are used, home phototherapy is a convenient and valued option for some families. Home phototherapy was particularly useful during the height of the COVID-19 pandemic [25,26]. However, the cost-effectiveness of appropriately prescribed home phototherapy has not been established.
The efficacy and safety of home phototherapy were evaluated in a clinical trial involving 147 newborns >36 weeks gestation with treatment-level hyperbilirubinemia at >48 hours postnatal age and without other clinical risk factors (ie, no hemolytic disease, infection, or other illness) who randomized to home or in-hospital phototherapy [27]. TSB trajectories and duration of phototherapy were similar in both groups (median of 18 hours for both). Among patients randomized to home therapy, three patients (4 percent) required hospital admission for worsening hyperbilirubinemia; all instances were attributed to caregiver misunderstanding of the instructions for using the device. No infant in either group required exchange transfusion.
Similar findings have been noted in observational studies using similar criteria for selecting candidates for home phototherapy. In these studies, rehospitalization rates ranged from 0 to 6 percent and no newborns required exchange transfusion [24,28-31].
Mechanism — This principal mechanism by which phototherapy reduces bilirubin levels is by irreversibly converting bilirubin primarily into lumirubin, which is not neurotoxic and is more soluble than bilirubin [32]. Lumirubin is then excreted without conjugation into bile and urine. The conversion is caused by direct exposure to photons emitted by the light source as bilirubin passes through superficial capillaries in the skin. Photo-alteration of bilirubin occurs at specific wavelengths of blue-to-blue-green light (460 to 490 nm, optimal at 478 nm). Other mechanisms that may account for a small proportion of bilirubin elimination include photo-oxidation to polar molecules and photoisomerization to the less toxic 4Z,15Z bilirubin isomer.
General efficacy — The efficacy of phototherapy for treatment of neonatal hyperbilirubinemia is supported by landmark clinical trials performed in the 1970s to 1980s [10,11,33,34] and by decades of clinical experience since that time. In the available randomized and nonrandomized trials comparing phototherapy to supportive care alone, phototherapy lowered TSB levels and reduced the need for exchange transfusion by approximately 10 to 25 percent [10-12,35]. Phototherapy's impact on reducing exchange transfusion in the modern era may be even greater. This is because current thresholds for performing exchange transfusion are considerably higher than during the earlier era when these studies were carried out. Thus, many patients who "failed" phototherapy and went on to exchange transfusion in these early studies would not be treated with exchange transfusion in the modern era. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia", section on 'Criteria for exchange transfusion'.)
Limited data suggest that phototherapy may improve indirect measures of brain function in the short-term (eg, brainstem auditory evoked response [BAER]) [36,37]. Data regarding phototherapy’s impact on long-term neurologic outcomes (eg, neurodevelopmental disability, chronic bilirubin encephalopathy [CBE; previously referred to as kernicterus]), are limited and inconclusive [35,38,39].
Despite the lack of conclusive evidence directly linking phototherapy to a reduction in CBE, it is reasonable to surmise that phototherapy likely reduces risk of CBE since CBE occurs exclusively in neonates with extreme hyperbilirubinemia and phototherapy effectively prevents such high levels [40]. (See "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia", section on 'Chronic bilirubin encephalopathy (kernicterus)'.)
Studies comparing the efficacy of different types of phototherapy are discussed elsewhere:
●Blue LED versus non-LED phototherapy (see 'Light sources and devices' above)
●Double versus single phototherapy (see 'Technique' above)
●Home versus in-hospital phototherapy (see 'Home phototherapy' above)
Adverse effects
●Short-term effects – Modern-day phototherapy devices using blue LED lights generate minimal heat and do not emit UV light. They are generally safe and well tolerated. They are less likely to cause short-term adverse effects (eg, rashes, hyperthermia, fluid losses) compared with older phototherapy devices that used fluorescent or halogen lights [9].
Potential short-term adverse effects of phototherapy using blue LEDs include:
•Interruption of breastfeeding – Breastfeeding may be interrupted during phototherapy, since treatment ideally should be continuous. The use of fiberoptic blankets can minimize interruptions in breastfeeding during the birth hospitalization. In an observational study of 4441 infants from a national registry, phototherapy had minimal effects on future breastfeeding [41]. Although phototherapy was associated with a decrease in exclusive breastfeeding during the first four months of life, there were similar rates of any breastfeeding up to nine months of age for infants who received phototherapy versus those who did not.
•Bronze baby syndrome – Bronze baby syndrome is an uncommon reversible skin condition manifested by a transient dark, grayish-brown discoloration of the skin and urine [42]. It occurs in infants with cholestatic jaundice (conjugated bilirubin >2 mg/dL) treated with phototherapy and is caused by integumentary deposition of bronze-colored pigments, mainly due to photoisomers [42,43]. There is no known neurotoxicity associated with this syndrome; it usually resolves without sequelae within weeks after discontinuation of phototherapy as the pigments are slowly eliminated [44]. Thus, there is no contraindication to the use of phototherapy in infants with dual or mixed hyperbilirubinemia (ie, due to both unconjugated and conjugated bilirubin). However, experts in the field have cautioned against the use phototherapy for infants with predominantly conjugated bilirubin (>50 percent of the TSB level), as there is no observed benefit of phototherapy in infants with excessive cholestasis (high direct bilirubin). Bronze baby syndrome is not an indication for an exchange transfusion nor an indication to withhold phototherapy for those at imminent risk for developing ABE.
Other reported short-term adverse effects of phototherapy are due mostly to the effects of UV light and increased heat produced by older devices that used fluorescent or halogen lights [9]. Adverse effects associated with these light sources include:
•Transient, benign, erythematous rashes
•Hypovolemia caused by increased insensible water losses
•Hyperthermia
Studies involving extremely preterm (EPT) neonates suggest that exposure phototherapy (particularly using older devices) in that population may have adverse physiologic consequences, including oxidative stress, altered cytokine levels, and changes in cerebral and kidney blood flow. These effects have only been reported in EPT neonates, as discussed separately. (See "Unconjugated hyperbilirubinemia in preterm infants <35 weeks gestation", section on 'Benefit and risk'.)
●Potential long-term effects — It remains uncertain whether neonatal phototherapy is associated with any long-term sequelae when used appropriately.
•Seizures ‒ Phototherapy in newborns appears to be associated with a small increased risk of neonatal and childhood seizures, particularly in boys [45,46]. This was illustrated by a large cohort study which found a weak association between phototherapy and risk of childhood seizures after adjusting for confounding factors (hazard ratio [HR] 1.22, 95% CI 1.05-1.42) [46]. The overall adjusted risk of experiencing seizures by age 10 years was 2.4 per 1000 children for children who received neonatal phototherapy; the risk was higher for boys compared with girls (3.7 per 1000 boys versus 0.8 per 1000 girls). There was no apparent association between phototherapy and febrile seizures. The study did not provide any data on neonatal seizures associated with ABE, nor did it provide details on the types of phototherapy devices used, or duration and irradiance of phototherapy exposure.
It is unclear whether the modest increased risk of seizures in this population is due to exposure to phototherapy or exposure to elevated bilirubin levels. Exposure to elevated TSB levels in the newborn period can cause bilirubin neurotoxicity which may be evidenced by changes in electroencephalography amplitudes and overt clinical seizures. (See "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia", section on 'Consequences of severe hyperbilirubinemia'.)
Further research is needed to better understand the causal mechanism of seizures associated with exposure to neonatal phototherapy. Nevertheless, these results highlight the concerns of overtreatment causing unnecessary exposure with potential adverse effects.
•Childhood cancer ‒ Concerns have been raised that exposure to neonatal phototherapy may be associated with increased risk of childhood cancer. However, there is considerable uncertainty regarding this association since it is challenging to adequately control for confounding factors (eg, severity of hyperbilirubinemia, exposure to direct sunlight). In addition, many studies did not differentiate between different types of light source, some of which do not filter out UV radiation. As described above, modern day phototherapy devices using blue LEDs do not emit UV light and should theoretically carry minimal risk of DNA damage. (See 'Light sources and devices' above.)
If phototherapy is an independent risk factor for childhood cancer, the effect is modest at most. Nevertheless, the concern of potential long-term risk of cancer serves as another reminder that phototherapy should be prescribed judiciously.
In a retrospective cohort study of 499,621 infants born at ≥35 weeks gestational age (GA) between 1995 and 2011 at a single healthcare network, there was a higher incidence of childhood cancer among children exposed to phototherapy compared with unexposed controls; however, after controlling for confounding variables with multivariate regression analysis, the association was no longer statistically significant (adjusted HR 1.28, 95% CI 0.92-1.77) [47]. A subsequent study from the same healthcare network included 139,000 children (GA ≥35 weeks) born between 1995 to 2017 and used propensity score analysis in attempt to better adjust for confounding variables. In this study, phototherapy did not appear to be independently associated with increased risk of cancer over a mean follow-up of eight years (HR 1.13, 95% CI 0.83-1.15) [48].
A study that used linked state-wide data from California with follow-up to one year of age from 1998 to 2007 demonstrated that cancer was diagnosed more frequently for infants with diagnostic codes for phototherapy compared with those without such codes (33 versus 21 per 100,000 patients, relative risk [RR] 1.6, 95% CI 1.2-2.0) [49]. In a propensity-score adjusted analysis, a small increased risk still remained for any cancer (adjusted odds ratio [aOR] 1.4, 95% CI 1.1-1.9), myeloid leukemia (aOR 2.6, 95% CI 1.3-5.0) and kidney cancer (aOR 2.5, 95% CI 1.2-5.1). Because of the higher baseline risk of cancer, the risk of cancer was higher in patients with Down syndrome.
•Skin manifestations ‒ Data are conflicting regarding the association between phototherapy and pigmented skin lesions. Although a review of studies that used blue light phototherapy (using broadband blue fluorescent tubes, which also emit wavelengths in the UV region) reported an increased risk of melanocytic nevi in children and adolescents [50], other reports did not find an association between phototherapy and melanocytic nevi [51,52]. One of the studies reported there was an increased risk of café-au-lait macules but not melanocytic nevi [52].
•Unproven retinal effects ‒ The effect of phototherapy on the retina of treated infants is not known; however, animal studies suggest that retinal degeneration may occur after 24 hours of continuous exposure [53]. As a result, the retina and lens of all neonates treated with phototherapy are covered to eliminate any potential exposure to light, including the risk of "glare." Spontaneous closure of eyelids serves as a primary infantile response and eye shades serve as additional aides for comfort and protection.
•No effect on childhood asthma and allergic diseases ‒ There is limited evidence that moderate levels of hyperbilirubinemia are associated with increased risk childhood asthma or other allergic diseases (ie, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria), but phototherapy does not appear to alter this risk [54,55].
•No effect on food allergies – Neither neonatal hyperbilirubinemia nor phototherapy appear to be associated with food allergies [55].
MONITORING DURING PHOTOTHERAPY — Appropriate monitoring during phototherapy includes all of the following:
●The dose of phototherapy applied to the newborn should be recorded, including irradiance and time exposed.
●Newborn's vital signs, including temperature (monitored every eight hours).
●Hydration status (intake and output) – Maintaining adequate hydration enhances bilirubin elimination, as discussed above (see 'Supportive care' above). Modern-day light-emitting diode (LED) phototherapy is generally not associated with increased fluid loss because they generate little heat. Excessive fluid loss is a concern if older non-LED phototherapy devices are used.
●Follow-up total serum or plasma bilirubin (TSB) levels, as discussed below. (See 'Response to treatment' below.)
RESPONSE TO TREATMENT
Repeat TSB measurements — For most newborns receiving phototherapy, a follow-up total serum or plasma bilirubin (TSB) level should be checked within 6 to 12 hours after starting treatment [1]. However, earlier follow-up TSB (ie, in two hours) is warranted for newborns requiring escalation of care, as discussed separately. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia", section on 'Monitoring'.)
Of note, measurements using transcutaneous bilirubin (TcB) devices are not reliable in patients undergoing phototherapy and should not be used in this setting [1,56,57]. Management decisions regarding phototherapy should be guided by TSB values. (See "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Bilirubin testing methods'.)
Expected response — Effective phototherapy results in a decline of TSB of at least 2 to 3 mg/dL (34 to 51 micromol/L) within four to six hours. A decrease in TSB can be detected as early as two hours after initiating treatment. Twenty-four hours of phototherapy can effectively reduce TSB levels by 25 to 40 percent [20,58,59].
Subsequent management — Subsequent laboratory monitoring and phototherapy changes are made based on the response:
●If TSB levels have effectively declined, subsequent TSB measurements can be obtained every 8 to 12 hours. Feeding and holding by the parents/caregivers can be reinstated if they had been stopped. (See 'De-escalating therapy' below.)
●If TSB levels have declined less than expected, phototherapy administration should be verified and adjusted accordingly (see 'Technique' above). Interruptions in phototherapy (eg, for feeding or parent/caregiver holding) should be minimized or prohibited. TSB should be rechecked within four to six hours.
●If TSB levels are close to (ie, <2 mg/dL [34 micromol/L] below) or at the exchange transfusion threshold, care should be escalated. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia".)
ESCALATING THERAPY — Newborns with any of the following require escalation of care (algorithm 1):
●Signs of acute bilirubin encephalopathy (ie, lethargy, hyper- or hypotonia, poor suck, high-pitched cry, recurrent apnea, opisthotonos, retrocollis, seizures (table 3)).
●Rapidly rising total serum or plasma bilirubin (TSB) levels (ie, increasing by ≥0.3 mg/dL [5 micromol/L] per hour in the first 24 hours or ≥0.2 mg/dL [3 micromol/L] per hour thereafter) despite intensive phototherapy.
●TSB levels that are within 2 mg/dL (34 micromol/L) of the exchange transfusion threshold (figure 2A-B).
These patients are at risk of developing bilirubin-induced neurologic disorders (BIND) and may require exchange transfusion. Details regarding escalation of care and exchange transfusion are provided separately. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia".)
DE-ESCALATING THERAPY
Risk factors for rebound — Rebound hyperbilirubinemia is defined as a total serum or plasma bilirubin (TSB) level that reaches the phototherapy threshold within 72 to 96 hours of stopping phototherapy. Risk factors for rebound hyperbilirubinemia include (table 5) [60,61]:
●Gestational age (GA) <38 weeks.
●Early need for phototherapy (within 48 hours after birth).
●Hemolytic diseases (eg, alloimmune hemolytic disease, glucose-6-phosphate dehydrogenase [G6PD] deficiency). Infants with alloimmune hemolytic disease may have prolonged hemolysis. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Late anemia'.)
●TSB level close to the phototherapy threshold at the time of discontinuation.
In the available studies, rates of rebound hyperbilirubinemia in term and late preterm infants ranged from 5 to 24 percent [61-63]. In one large study, the risk of rebound was 2.5 percent among newborns ≥38 weeks gestation versus 10.2 percent among newborns 35 to <38 weeks gestation [62].
When rebound occurs, the rebound level is typically lower than the pretreatment TSB value [64].
Discontinuing phototherapy — The timing of phototherapy discontinuation depends on the newborn's TSB level and risk of developing rebound hyperbilirubinemia (see 'Risk factors for rebound' above):
●For newborns without rebound risk factors (table 5), we generally discontinue phototherapy when the TSB is ≥2 mg/dL (34 micromol/L) below the phototherapy threshold at the time of phototherapy initiation.
●For newborns with risk factors for rebound (table 5), a longer period of phototherapy may be warranted. In these newborns, we typically discontinue phototherapy when TSB is <12 mg/dL (205 micromol/L).
In our experience, the average duration of phototherapy is 24 to 48 hours unless the infant has ongoing excessive hemolysis (such in Rhesus [Rh] disease).
Follow-up testing — A follow-up TSB level should be measured 12 to 24 hours after discontinuing phototherapy to assess for rebound hyperbilirubinemia.
Measurements performed within 24 hours of stopping phototherapy should be performed with TSB and not transcutaneous bilirubin (TcB) since TcB is not reliable in newborns recently exposed to phototherapy. After 24 hours, either method is acceptable [1]. (See "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Bilirubin testing methods'.)
The timing of follow-up testing depends upon the newborn's risk of rebound (see 'Risk factors for rebound' above):
●For newborns with risk factors for rebound (table 5), TSB should be checked within 6 to 12 hours of discontinuing phototherapy. Discharge should not occur until the TSB result is obtained. A subsequent bilirubin level (either measured by TSB or TcB) should be obtained one day after stopping phototherapy; this can be performed in the hospital or outpatient setting.
●For all other newborns, a follow-up bilirubin level should be obtained the day after stopping phototherapy. Repeat testing can be performed in the outpatient setting with TSB or TcB device (the latter should be used only if testing is performed ≥24 after stopping phototherapy).
Retreatment — Criteria for retreating newborns who have previously received phototherapy are the same as criteria for treating newborns who never received phototherapy (figure 1A-B). (See 'Thresholds for treatment' above.)
SPECIAL CIRCUMSTANCES
Alloimmune hemolytic disease — Management of hyperbilirubinemia in newborns with alloimmune hemolytic disease of the newborn (HDN) is generally the same as for neonatal unconjugated hyperbilirubinemia more broadly. The mainstays of management include serial monitoring of total serum or plasma bilirubin (TSB) levels, oral hydration, and phototherapy. However, there are three key distinctions between managing hyperbilirubinemia in newborns with HDN compared with those without HDN:
●Consideration of the degree of anemia – In HDN, treatment is based not only on the TSB level, but also on the degree of anemia. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Management approach'.)
●Lower threshold for treatment – Because HDN is an important risk factor for neurotoxicity, a lower TSB threshold is used for starting phototherapy in these newborns compared with those without neurotoxicity risk factors (figure 1B). (See 'Thresholds for treatment' above.)
●Role of intravenous immune globulin (IVIG) – IVIG is suggested for newborns with HDN who have rising TSB levels despite phototherapy or if TSB is within 2 mg/dL (34 micromol/L) of the threshold for exchange transfusion [1]. This is discussed separately. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Immune globulin therapy'.)
Prolonged/delayed hyperbilirubinemia — For newborns with hyperbilirubinemia that persists or recurs beyond seven days after birth, additional evaluation should be performed to identify the underlying etiology.
●Causes – Causes of persistent hyperbilirubinemia include (see "Etiology and pathogenesis of neonatal unconjugated hyperbilirubinemia" and "Causes of cholestasis in neonates and young infants"):
•Breastmilk jaundice – In exclusively breastfed neonates, breastmilk jaundice is a common cause of persistent unconjugated hyperbilirubinemia lasting beyond one to two weeks. Hyperbilirubinemia in this setting is typically mild. Breastmilk jaundice is discussed in detail separately. (See "Etiology and pathogenesis of neonatal unconjugated hyperbilirubinemia", section on 'Breast milk jaundice'.)
•Inherited hemolytic anemia – Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common disorder in this category. Other inherited hemolytic anemias include other enzymopathies (eg, pyruvate kinase deficiency), hemoglobinopathies (eg, sickle cell disease, thalassemia), and membranopathies (eg, hereditary spherocytosis). (See "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency" and "Overview of hemolytic anemias in children", section on 'Intrinsic hemolytic anemias'.)
•Extravascular blood (eg, extensive bruising or cephalohematoma). (See "Neonatal birth injuries", section on 'Cephalohematoma' and "Neonatal birth injuries", section on 'Bruising and petechiae'.)
•Inherited disorders of bilirubin metabolism – These include Gilbert and Crigler-Najjar syndromes. Gilbert syndrome is a benign condition that causes mild unconjugated hyperbilirubinemia. It is unlikely to cause clinically significant hyperbilirubinemia unless there are other contributing factors (eg, breastmilk jaundice, hemolysis). By contrast, Crigler-Najjar syndrome is a rare disorder characterized by marked and persistent unconjugated hyperbilirubinemia. (See "Gilbert syndrome and unconjugated hyperbilirubinemia due to bilirubin overproduction" and "Crigler-Najjar syndrome".)
•Inborn errors of metabolism (IEM) and hypothyroidism – IEM (eg, galactosemia, tyrosinemia) and congenital hypothyroidism can cause prolonged or delayed neonatal hyperbilirubinemia. Newborns are routinely screened for these disorders. (See "Newborn screening".)
•Cholestasis – Cholestasis is characterized by elevated direct (or conjugated) bilirubin. Biliary atresia is an important cause of neonatal cholestasis. (See "Causes of cholestasis in neonates and young infants" and "Approach to evaluation of cholestasis in neonates and young infants".)
Sepsis (particularly urosepsis) is another important consideration in a newborn with elevated direct bilirubin, particularly if there are other concerning signs and symptoms. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates".)
●Evaluation – For newborns with hyperbilirubinemia lasting beyond the age of seven days, the evaluation includes the following:
•Physical examination to assess physical well-being and identify any concerning findings (eg, hepatomegaly).
•Direct bilirubin level to assess for cholestasis – The level used to define an abnormal direct bilirubin level in the neonate depends on the TSB. If the TSB is <5.0 mg/dL (85.5 micromol/L), a direct bilirubin >1.0 mg/dL (17.1 micromol/L) is abnormal; if the TSB is ≥5.0 mg/dL (85.5 micromol/L), a direct bilirubin >20 percent of the TSB is a worrisome finding. Higher levels are often associated with hepatomegaly, splenomegaly, pale acholic stools, and darkly pigmented urine. (See "Approach to evaluation of cholestasis in neonates and young infants", section on 'Total and conjugated bilirubin'.)
•G6PD activity (if not already performed). (See "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency", section on 'Confirmatory tests'.)
•Review the results of the newborn screen. (See "Newborn screening", section on 'Follow-up'.)
•Additional testing as warranted based upon clinical concern for any of the conditions listed above (eg, sepsis evaluation if the neonate has other concerning findings). (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Late-onset sepsis'.)
Clinically significant hyperbilirubinemia (ie, approaching or above the treatment threshold) at age >14 days and/or direct hyperbilirubinemia at any time during the neonatal period is concerning. Infants with either of these findings should undergo additional evaluation directed by expert consultation with pediatric gastroenterology, hematology, and metabolic specialists.
●Treatment – The threshold for treatment in these cases is based upon the hour-specific TSB thresholds summarized in the figures (figure 1A-B and figure 2A-B), which provide guidance up to age 14 days. Neonates with persistent hyperbilirubinemia at >14 days often have a mixed picture (ie, both elevated direct and unconjugated bilirubin). There are few data to guide treatment in these cases. Phototherapy can be used to reduce the unconjugated fraction (using the 14-day TSB threshold as the trigger for intervention). However, phototherapy is generally not useful if the direct bilirubin level is >50 percent of TSB. Neonates with mixed hyperbilirubinemia who are exposed to phototherapy may develop transient bronzing of the skin known as bronze baby syndrome. This condition is not harmful and usually resolves without sequelae after several weeks or months. (See 'Adverse effects' above.)
Newborns exposed to persistently high TSB levels for a prolonged time may be at increased risk for bilirubin-induced neurologic disorders (BIND). Such newborns are best managed in a care setting where they can receive prompt supportive care and close monitoring of neurologic signs (eg, using BIND scores (table 3)). In addition, these newborns' care should be directed in consultation with experts in pediatric gastroenterology, hematology, and metabolism. (See 'Supportive care' above and 'Thresholds for treatment' above.)
Preterm infants — Treatment of unconjugated hyperbilirubinemia in preterm infants <35 weeks GA is discussed separately. (See "Unconjugated hyperbilirubinemia in preterm infants <35 weeks gestation", section on 'Management approach'.)
UNPROVEN THERAPIES — The following agents have been investigated as potential treatments for neonatal unconjugated hyperbilirubinemia, but they do not play a role in routine management:
●Ursodeoxycholic acid (UCDA) – UCDA promotes emulsification of bile in the biliary ducts, increases bile flow, and enhances bile elimination into the gut [65]. Its use in neonates is limited to those who have predominantly conjugated (direct) hyperbilirubinemia or combined unconjugated and conjugated hyperbilirubinemia. Conjugated (direct) hyperbilirubinemia occurs in cholestatic conditions such as biliary atresia. Use of UCDA in this setting is discussed separately. (See "Biliary atresia", section on 'Choleretics'.)
●Phenobarbital – Phenobarbital increases the conjugation and excretion of bilirubin and has been shown to lower TSB levels in preterm newborns [66]. However, phenobarbital carries risks of potential adverse effects (eg, sedation, cardiopulmonary effects). Since there are safer alternatives, we recommend against using phenobarbital to treat neonatal hyperbilirubinemia.
●Metalloporphyrins – Synthetic metalloporphyrins (SnMP), such as tin mesoporphyrin, have been shown to reduce bilirubin production by competitive inhibition of heme oxygenase [67-75]. However, SnMP (or other metalloporphyrins) are not approved in the United States to treat neonatal hyperbilirubinemia and are not available for general use.
●Fibrates – Fibrates (eg, clofibrate and fenofibrate) have been studied as a potential treatment for neonatal hyperbilirubinemia predominantly in the setting of ABO incompatibility. Though some clinical trial evidence suggests that fibrates may reduce TSB levels, many of the trials had serious methodologic limitations [76,77]. In addition, the agent studied in most of these trials, clofibrate, has been taken off the market due to safety concerns. Thus, fibrates do not play a role in the management of neonatal hyperbilirubinemia.
OUTCOME
●Outcomes in newborns who receive timely treatment – For newborns with hyperbilirubinemia who are identified and treated appropriately, outcomes are excellent with minimal or no additional risk for adverse neurodevelopmental sequelae [40,78-80].
This was illustrated in a prospective cohort of >100,000 term or late preterm newborns, of whom 140 had total serum or plasma bilirubin (TSB) levels ≥25 mg/dL (428 micromol/L), including 10 newborns with TSB ≥30 mg/dL (513 micromol/L) [40]. Treatment included phototherapy in 136 newborns and exchange transfusions in five patients. At two-year follow-up, there were no reports of kernicterus in either the severely hyperbilirubinemic or control group. Scores on cognitive tests at two and six years of age were similar in both groups. Rates of reported behavioral problems and other parental/caregiver concerns were also similar in both groups. Children with severe neonatal hyperbilirubinemia were more likely to have subtle abnormalities on neurologic examination; however, the findings did not correlate with the degree and duration of hyperbilirubinemia.
In a study from the Collaborative Perinatal Project, which included >45,000 children who were born at ≥36 weeks gestation between 1959 and 1966 and who underwent cognitive evaluation at age seven and eight years, children who had severe neonatal hyperbilirubinemia in the context of alloimmune hemolytic diseases of the newborn (ie, positive direct antiglobulin test [DAT]) scored lower on cognitive testing compared with the control group [78]. Cognitive test scores among children with severe neonatal hyperbilirubinemia without a positive DAT were similar to the control group.
Population-based studies from countries that have implemented national or regional guidelines for management of neonatal hyperbilirubinemia have also reported that adverse neurologic outcomes from neonatal hyperbilirubinemia are exceedingly rare when affected newborns are identified and treated promptly [79,80].
●Newborns with persistent or prolonged severe hyperbilirubinemia – If severe hyperbilirubinemia is not identified and treated promptly, there is a risk for substantial long-term neurologic impairment, as discussed separately. (See "Risk factors, clinical manifestations, and neurologic complications of neonatal unconjugated hyperbilirubinemia", section on 'Consequences of severe hyperbilirubinemia'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neonatal jaundice".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Jaundice in babies (The Basics)")
●Beyond the Basics topics (see "Patient education: Jaundice in newborn infants (Beyond the Basics)")
A list of frequently asked questions and answers for parents/caregivers is available through the American Academy of Pediatrics (AAP): www.healthychildren.org/English/ages-stages/baby/Pages/Jaundice.aspx
SUMMARY AND RECOMMENDATIONS
●Management goals – The goals of managing neonatal hyperbilirubinemia are to prevent severe hyperbilirubinemia and bilirubin-induced neurologic disorders (BIND) while avoiding unnecessary intervention which can interfere with successful initiation of breastfeeding and parent/caregiver bonding with the newborn. (See 'Goals' above.)
●Supportive care – Newborns with hyperbilirubinemia should receive adequate nutrition and oral hydration since this enhances bilirubin elimination. (See 'Supportive care' above.)
●Thresholds for treatment
•Symptomatic newborns – Newborns with elevated total serum or plasma (TSB) levels in association with signs of acute bilirubin encephalopathy (table 3) require escalation of care and possibly exchange transfusion (algorithm 1), as discussed separately. (See 'Symptomatic patients' above and "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia", section on 'Exchange transfusion'.)
•Asymptomatic newborns – TSB thresholds for treatment depend upon the newborn's gestational age (GA) and other risk factors for neurotoxicity (table 2). (See 'Asymptomatic patients' above.)
-Bilirubin at or above treatment threshold – For newborns with TSB at or above the threshold for phototherapy (figure 1A-B), we recommend phototherapy (Grade 1B). (See 'Initial intervention (phototherapy)' above.)
Newborns with TSB levels that are approaching or above the threshold for exchange transfusion (figure 2A-B) require escalation of care and possible exchange transfusion, as summarized in the figure (algorithm 1) and discussed separately. (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia", section on 'Criteria for escalating care'.)
-TSB near threshold – For newborns with TSB levels that are <2 mg/dL (34 micromol/L) below the phototherapy threshold (figure 1A-B) and with clinical risk factors for progressive hyperbilirubinemia (eg, onset of jaundice within first 24 hours after birth, ABO or Rhesus (Rh) incompatibility, rapidly rising TSB, significant bruising/cephalohematoma), we suggest starting phototherapy (Grade 2C). For newborns with near-threshold TSB levels in the absence of clinical risk factors, the decision to provide subthreshold phototherapy is individualized, depending on parent/caregiver preference. Home phototherapy may be an option if there are no clinical risk factors and additional criteria are met. (See 'Asymptomatic patients' above and 'Home phototherapy' above.)
-TSB below threshold – Newborns with TSB levels that are >2 mg/dL (34 micromol/L) below the phototherapy threshold (figure 1A-B)) generally do not require treatment. Details regarding the need for reassessment and follow-up after newborn TSB screening are summarized in the table (table 4) and discussed in greater detail separately. (See "Screening for hyperbilirubinemia in term and late preterm newborn infants", section on 'Approach based upon bilirubin level'.)
●Pretreatment laboratory testing – Laboratory testing prior to starting phototherapy includes (see 'Pretreatment laboratory evaluation' above):
•Confirmatory TSB level, if the newborn does not have a recent TSB level or if initial testing was performed with a transcutaneous bilirubin (TcB) measurement
•Hemoglobin/hematocrit
•Reticulocyte count
•Direct antiglobulin test (DAT) in newborns born to mothers with O or Rh D negative blood types
●Administering phototherapy – Effective phototherapy requires an irradiance of at least 30 microW/cm2/nm with light in the blue to blue-green wavelength (460 to 490 nm; optimal at 478 nm) applied continuously to as much of the skin surface as possible. (See 'Administration' above.)
•Technique – When initiating phototherapy, the newborn should be placed supine, with body exposed and the area covered by the diaper minimized, and eyes shielded with an opaque orbital shield (figure 3). Light should be delivered to as much of an infant's skin as possible with a combination of light sources both above and below the newborn. Interruptions to phototherapy should be minimized. (See 'Technique' above.)
•Devices – For all newborns receiving phototherapy, we suggest devices that use blue light-emitting diode (LED) lamps as the light source rather than non-LED light sources (Grade 2C). Blue LED devices appear to be equally effective in lowering TSB compared with older non-LED devices and they have the advantage of not emitting UV light or generating heat. (See 'Light sources and devices' above.)
●Response to treatment – A follow-up TSB level should be checked within 6 to 12 hours after starting phototherapy. (See 'Response to treatment' above.)
•If TSB levels have effectively declined, subsequent measurements can be obtained every 8 to 12 hours. Feeding and holding by the parents/caregivers can be reinstated if they had been stopped. (See 'De-escalating therapy' above.)
•If TSB levels have declined less than expected, phototherapy administration should be verified and adjusted accordingly (see 'Technique' above). Interruptions in phototherapy (eg, for feeding or parent/caregiver holding) should be minimized or prohibited. TSB should be rechecked within four to six hours.
•If TSB levels are close to (ie, <2 mg/dL [34 micromol/L] below) or at the exchange transfusion threshold, care should be escalated (algorithm 1). (See "Escalation of care for term and late preterm newborns with unconjugated hyperbilirubinemia".)
●Discontinuing phototherapy
•For newborns without risk factors for rebound (table 5), we generally discontinue phototherapy when the TSB is ≥2 mg/dL (34 micromol/L) below the phototherapy threshold. A follow-up bilirubin level should be obtained in the outpatient setting the day after stopping phototherapy. (See 'Discontinuing phototherapy' above.)
•For newborns with one or more risk factor for rebound (table 5), we typically discontinue phototherapy when TSB is <12 mg/dL (205 micromol/L). TSB should be checked within 6 to 12 hours of discontinuing phototherapy. Discharge should not occur until the TSB result is obtained. A subsequent bilirubin level should be obtained one day after stopping phototherapy (in the hospital or outpatient setting). (See 'Discontinuing phototherapy' above.)
●Outcome – For newborns with hyperbilirubinemia who are identified and treated appropriately, the outcome is excellent with minimal or no additional risk for adverse neurodevelopmental sequelae. (See 'Outcome' above.)
