Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

physiologic hyperbilirubinemia

1st line – reassurance and observation

Back
ACUTE
|
physiologic hyperbilirubinemia
1st line – 

reassurance and observation

Jaundice is physiologic if it occurs in the second postpartum day and resolves in 7-10 days and transcutaneous measurement is normal.

No treatment is required for physiologic jaundice.

pathologic hyperbilirubinemia: unconjugated

1st line – immediate exchange transfusion

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
acute bilirubin encephalopathy
1st line – 

immediate exchange transfusion

Signs of acute bilirubin encephalopathy include hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry, or recurrent apnea, even if the total serum bilirubin is falling.[7]​​

This is a medical emergency.

Start as soon as blood can be arranged for the exchange transfusion. The rationale is to remove the unconjugated bilirubin by doing a double-volume exchange transfusion, which should allow the bilirubin to move out of the brain tissue and hence decrease the risk of neurologic toxicities. An exchange transfusion will also remove antibodies responsible for hemolytic anemia. In severe cases of erythroblastosis and/or hydrops, it will also correct anemia. Cross-matched washed packed red blood cells mixed with thawed adult fresh-frozen plasma is preferred for exchange transfusions.

There is insufficient evidence to support or refute the use of single-volume exchange transfusion as opposed to double-volume exchange transfusion in jaundiced newborns.[77]

The major potential complications of the procedure include electrolyte disturbances, bleeding, infection, cardiac arrhythmias, thrombosis with embolization, necrotizing enterocolitis, and graft-versus-host disease.

Plus – phototherapy

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
acute bilirubin encephalopathy
Plus – 

phototherapy

Treatment recommended for ALL patients in selected patient group

Start phototherapy while preparing for the exchange transfusion and continue phototherapy after the exchange transfusion. Continue to plot total serum bilirubin (TSB) levels for gestational age and hour after birth on nomograms to assess need for continued phototherapy or repeat exchange transfusions.[7]​​​

Risk factors for hyperbilirubinemia neurotoxicity include a gestational age <38 weeks, albumin <3.0 g/dL, serious illness in the newborn infant (e.g., sepsis or significant clinical instability in the previous 24 hours), or isoimmune hemolytic disease, glucose-6-phosphate deficiency, or other hemolytic conditions.[7]​​

Phototherapy uses light energy to cause photochemical reactions to transform bilirubin into isomers that are less lipophilic and more easily excretable, and make breakdown products that do not require conjugation in the liver. Bilirubin absorbs visible light most strongly in the blue region of the spectrum (around 460 nm) and the most effective phototherapy wavelengths are from 460-490 nm, optimally 478 nm.[48][49]​ Units use light-emitting diode (LED), halogen, fluorescent, or fiberoptic light sources to produce these wavelengths.[49]

LED phototherapy units are preferred due to their reduced heat production and subsequent reduction in insensible water loss.[49]​ LED phototherapy with overhead use (versus illumination from beneath the infant) shortened the mean duration of phototherapy and increased the rate of decrease in TSB compared to conventional phototherapy using compact fluorescent or halogen lamps.[50][51][52][53] [ Cochrane Clinical Answers logo ] ​

Maximal body surface area illumination (35% to 80%) is advised.[49]​ Double-light phototherapy is often considered to be more effective than single-light or fiberoptic phototherapy, with an irradiance of at least 30 microwatts/cm² at a wavelength of 478 nm.[7]​​[49][50]​​​

Fiberoptic phototherapy units are alternatives to conventional phototherapy in term neonates.​​[50][51][58][59]​​​ [ Cochrane Clinical Answers logo ] ​​ Special blue compact fluorescent lamp phototherapy had no superiority over special blue standard length tube light phototherapy in terms of efficacy and adverse effects on the neonate and effects on nursing staff.[60]

The risk/benefit profile is excellent, with immediate onset of action upon switching on the phototherapy lights. Adverse effects are generally mild and include insensible water loss, loose stools, skin rash, and potential retinal damage. These can be prevented by maintaining adequate hydration and ensuring the baby wears eye shields during phototherapy; however, there is no evidence to support this recommendation.[49] It is important that a clinician monitors and maintains adequate hydration, nutrition and temperature control during phototherapy.[49]

Breast-feeding/bottle-feeding can be continued in most circumstances while on phototherapy.

One randomized controlled trial reported that aggressive phototherapy did not impact the outcome of neurodevelopmental impairment or death in extremely low birth weight (ELBW) infants (birth weight <1000 g) compared with conservative phototherapy.[64] However, a systematic review of 9 studies showed that prophylactic phototherapy may reduce long-term neurodevelopmental impairment.[65] [ Cochrane Clinical Answers logo ]  While aggressive phototherapy did reduce the rate of neurodevelopmental impairment alone, there was an increase in mortality among infants with birth weights 500-750 g.[64] Hence, an aggressive phototherapy approach is not recommended for ELBW infants.

It may be prudent to initiate phototherapy strictly at threshold values (i.e., avoiding prophylactic treatment) and to terminate it once serum bilirubin falls below these levels because of an association between neonatal phototherapy and an increased risk of childhood epilepsy (not febrile seizures), particularly in boys.[62][63] 

A decision to discontinue phototherapy can be considered when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy.[7]​ If there are risk factors for rebound hyperbilirubinemia (gestational age <38 weeks, age <48 hours at the start of phototherapy, hemolytic disease), then a longer period of treatment is an option.[7]​ A follow-up bilirubin test is required after discontinuing phototherapy after at least 12 hours, and preferably 24 hours to allow time to demonstrate any rebound hyperbilirubinemia.[7]​​

Plus – hydration

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
acute bilirubin encephalopathy
Plus – 

hydration

Treatment recommended for ALL patients in selected patient group

Intravenous fluid supplementation may result in a faster decline of bilirubin levels.[67][68]

Otherwise, maintain hydration with enteral breast milk or formula.

Consider – intravenous immune globulin (IVIG)

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
acute bilirubin encephalopathy
Consider – 

intravenous immune globulin (IVIG)

Treatment recommended for SOME patients in selected patient group

In infants with isoimmune hemolytic disease, IVIG treatment may be commenced if the total serum bilirubin is rising despite intensive phototherapy or the total serum bilirubin (TSB) level is within 2-3 mg/dL of the exchange level, although the quality of evidence supporting this therapy is low.[74]​ Based on current evidence, it is recommended that IVIG treatment in infants ≥35 weeks of gestational age with a positive direct antiglobulin test be limited to those in whom the TSB is rising despite intensive phototherapy or is near the exchange level (within 2-3 mg/dL) and there is concern that an exchange transfusion may not occur in a timely manner.[7]​​[61]

Primary options

immune globulin (human): 0.5 to 1 g/kg intravenously over 2 hours; repeat in 12 hours if necessary

1st line – phototherapy

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
total serum bilirubin above the phototherapy threshold
1st line – 

phototherapy

Phototherapy is recommended based on the total serum bilirubin (TSB) thresholds in correlation with gestational age, hyperbilirubinemia neurotoxicity risk factors, and age of the infant in hours.[7]​​ Thresholds are provided in the American Academy of Pediatrics guidelines.[7] Clinicians should consult local guidelines for treatment thresholds.​​

While there is limited information, it has been suggested that phototherapy may limit familial bonding. Hence, it would be advisable to balance the benefit versus adverse effects of treatment threshold of phototherapy treatment in the management of hyperbilirubinemia in infants ≥35 weeks of gestational age.[7]​​[61]

Risk factors for hyperbilirubinemia neurotoxicity include a gestational age <38 weeks, albumin <3.0 g/dL, serious illness in the newborn infant (e.g., sepsis or significant clinical instability in the previous 24 hours), or isoimmune hemolytic disease, glucose-6-phosphate deficiency, or other hemolytic conditions.[7]​​

Escalation of care should be initiated when an infant’s TSB reaches or exceeds 2 mg/dL below the exchange transfusion threshold, to prevent the need for an exchange transfusion and possibly to prevent kernicterus.[7]​ This includes optimal management in a neonatal intensive care unit, intravenous hydration and intensive phototherapy.[7]​​[67][68]​​​ TSB should be measured at least every 2 hours from the start of the escalation-of-care period.[7]​ Blood should be sent for total and direct-reacting serum bilirubin, CBC, serum albumin, serum chemistries, and type and crossmatch.

Phototherapy uses light energy to cause photochemical reactions to transform bilirubin into isomers that are less lipophilic and more easily excretable, and make breakdown products that do not require conjugation in the liver. Bilirubin absorbs visible light most strongly in the blue region of the spectrum (around 460 nm) and the most effective wavelengths are from 460-490 nm, optimally 478 nm.[7]​​[48][49]​​​​​​​​

As first-line therapy, double-light phototherapy is often considered to be more effective than single-light or fiberoptic phototherapy, with an irradiance of at least 30 microwatts/cm² at a wavelength of 478 nm.[49][50][51]​ Units use light-emitting diode (LED), halogen, fluorescent, or fiberoptic light sources to produce these wavelengths.[49]

LED phototherapy units are preferred due to their reduced heat production and subsequent reduction in insensible water loss.[49]​ LED phototherapy with overhead use (versus illumination from beneath the infant) shortened the mean duration of phototherapy and increased the rate of decrease in TSB compared to conventional phototherapy using compact fluorescent or halogen lamps.[50][51][52][53]​​​​ [ Cochrane Clinical Answers logo ] ​​​​​

Maximal body surface area illumination (35% to 80%) is advised.[49]​ Double-light phototherapy is often considered to be more effective than single-light or fiberoptic phototherapy, with an irradiance of at least 30 microwatts/cm² at a wavelength of 478 nm.[7][49][50]​​

Fiberoptic phototherapy units are alternatives to conventional phototherapy in term neonates.​​[50][51][58][59] [ Cochrane Clinical Answers logo ] ​ Special blue compact fluorescent lamp phototherapy had no superiority over special blue standard length tube light phototherapy in terms of efficacy and adverse effects on the neonate and effects on nursing staff.[60]

The risk/benefit profile is excellent, with immediate onset of action upon switching on the phototherapy lights. Adverse effects are generally mild and include insensible water loss, loose stools, skin rash, and potential retinal damage. These can be prevented by maintaining adequate hydration and ensuring the baby wears eye shields during phototherapy; however, there is no evidence to support this recommendation.[49] It is important that a clinician monitors and maintains adequate hydration, nutrition and temperature control during phototherapy.[49]

One randomized controlled trial reported that aggressive phototherapy did not impact the outcome of neurodevelopmental impairment or death in extremely low birth weight (ELBW) infants (birth weight <1000 g) compared with conservative phototherapy.[64] However, a systematic review of 9 studies showed that prophylactic phototherapy may reduce long-term neurodevelopmental impairment.[65] [ Cochrane Clinical Answers logo ] ​​ While aggressive phototherapy did reduce the rate of neurodevelopmental impairment alone, there was an increase in mortality among infants with birth weights 500-750 g.[64] Hence, an aggressive phototherapy approach is not recommended for ELBW infants.

It may be prudent to initiate phototherapy strictly at threshold values (i.e., avoiding prophylactic treatment) and to terminate it once serum bilirubin falls below these levels because of an association between neonatal phototherapy and an increased risk of childhood epilepsy (not febrile seizures), particularly in boys.[62][63]

TSB should be measured within 12 hours after starting phototherapy - the timing of this measurement and frequency of TSB monitoring is based on the age of the child, presence of hyperbilirubinemia neurotoxicity risk factors, and the level and rate of rise of the TSB.[7]​ A decision to discontinue phototherapy can be considered when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy.[7]​ If there are risk factors for rebound hyperbilirubinemia (gestational age <38 weeks, age <48 hours at the start of phototherapy, hemolytic disease) then a longer period of treatment is an option.​[7]

A follow-up bilirubin test is required after discontinuing phototherapy after at least 12 hours, and preferably 24 hours to allow time to demonstrate any rebound hyperbilirubinemia.[7]​​

Plus – hydration

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
total serum bilirubin above the phototherapy threshold
Plus – 

hydration

Treatment recommended for ALL patients in selected patient group

Treat any dehydration and maintain hydration with enteral breast milk or formula.

Breast-feeding/bottle-feeding can be continued in most circumstances while on phototherapy. Oral supplementation with water or glucose is not recommended.[7]​ Temporary interruption of breast-feeding is very rarely needed, but it may be considered for specific clinical scenarios in which rapid reduction in TSB is urgently needed or if phototherapy is unavailable.[7]​​

Intravenous hydration is usually reserved for neonates receiving phototherapy with bilirubin levels close to the exchange value. Such intravenous fluid supplementation may result in a faster decline of bilirubin levels.[67][68]

1st line – exchange transfusion

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
total serum bilirubin levels at or above the exchange transfusion threshold
1st line – 

exchange transfusion

An urgent exchange transfusion should be performed for infants if the total serum bilirubin (TSB) is at or above the exchange transfusion threshold.[7]​​

Risk factors for hyperbilirubinemia neurotoxicity include a gestational age <38 weeks, albumin <3.0 g/dL, serious illness in the newborn infant (e.g., sepsis or significant clinical instability in the previous 24 hours), or isoimmune hemolytic disease, glucose-6-phosphate deficiency, or other hemolytic conditions.[7]​​

Start as soon as the blood can be arranged for the exchange transfusion. Continue phototherapy while waiting to start the procedure, stop while doing the transfusion, and restart phototherapy as soon as the exchange transfusion is completed.

The rationale is to remove the unconjugated bilirubin by doing a double-volume exchange transfusion, which should allow the bilirubin to move out of the brain tissue and hence decrease the risk of neurologic toxicities. An exchange transfusion will also remove antibodies responsible for hemolytic anemia. In severe cases of erythroblastosis and/or hydrops, it will correct anemia. Cross-matched washed packed red blood cells mixed with thawed adult fresh-frozen plasma is preferred for exchange transfusions.

There is insufficient evidence to support or refute the use of single-volume exchange transfusion as opposed to double-volume exchange transfusion in jaundiced newborns.[77]

The major potential complications of the procedure include electrolyte disturbances, bleeding, infection, cardiac arrhythmias, thrombosis with embolization, necrotizing enterocolitis, and graft-versus-host disease.

Plus – phototherapy

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
total serum bilirubin levels at or above the exchange transfusion threshold
Plus – 

phototherapy

Treatment recommended for ALL patients in selected patient group

Provide intensive phototherapy for babies while awaiting exchange transfusion and continue phototherapy after exchange transfusion. Continue to use nomograms to plot total serum bilirubin (TSB) levels for gestational age and hour after birth, and assess requirement for further phototherapy or repeat exchange transfusions.[7]​​ 

Risk factors for hyperbilirubinemia neurotoxicity include a gestational age <38 weeks, albumin <3.0 g/dL, serious illness in the newborn infant (e.g., sepsis or significant clinical instability in the previous 24 hours), or isoimmune hemolytic disease, glucose-6-phosphate deficiency, or other hemolytic conditions.[7]​​

Phototherapy uses light energy to cause photochemical reactions to transform bilirubin into isomers that are less lipophilic and more easily excretable, and make breakdown products that do not require conjugation in the liver. Bilirubin absorbs visible light most strongly in the blue region of the spectrum (around 460 nm) and the most effective phototherapy wavelengths are from 460-490 nm, optimally 478 nm.[7][48][49]

Units use light-emitting diode (LED), halogen, fluorescent, or fiberoptic light sources to produce these wavelengths.[49]

LED phototherapy units are preferred due to their reduced heat production and subsequent reduction in insensible water loss.[49]​ LED phototherapy with overhead use (versus illumination from beneath the infant) shortened the mean duration of phototherapy and increased the rate of decrease in TSB compared to conventional phototherapy using compact fluorescent or halogen lamps.​​[50][51][52][53] [ Cochrane Clinical Answers logo ] ​​​ 

Maximal body surface area illumination (35% to 80%) is advised.[49]​ Double-light phototherapy is often considered to be more effective than single-light or fiberoptic phototherapy, with an irradiance of at least 30 microwatts/cm² at a wavelength of 478 nm.[7][49][50]

Fiberoptic phototherapy units are alternatives to conventional phototherapy in term neonates.​​[50][51][58][59]​​ [ Cochrane Clinical Answers logo ] ​ Special blue compact fluorescent lamp phototherapy had no superiority over special blue standard length tube light phototherapy in terms of efficacy and adverse effects on the neonate and effects on nursing staff.[60]

The risk/benefit profile is excellent, with immediate onset of action upon switching on the phototherapy light. Adverse effects are generally mild and include insensible water loss, loose stools, skin rash, and potential retinal damage. These can be prevented by maintaining adequate hydration and ensuring the baby wears eye shields during phototherapy; however, there is no evidence to support this recommendation.[49] It is important that a clinician monitors and maintains adequate hydration, nutrition and temperature control during phototherapy.[49]

One randomized controlled trial reported that aggressive phototherapy did not impact the outcome of neurodevelopmental impairment or death in extremely low birth weight (ELBW) infants (birth weight <1000 g) compared with conservative phototherapy.[64] However, a systematic review of 9 studies showed that prophylactic phototherapy may reduce long-term neurodevelopmental impairment.[65] [ Cochrane Clinical Answers logo ] ​ While aggressive phototherapy did reduce the rate of neurodevelopmental impairment alone, there was an increase in mortality among infants with birth weights 500-750 g.[64] Hence, an aggressive phototherapy approach is not recommended for ELBW infants.

It may be prudent to initiate phototherapy strictly at threshold values (i.e., avoiding prophylactic treatment) and to terminate it once serum bilirubin falls below these levels because of an association between neonatal phototherapy and an increased risk of childhood epilepsy (not febrile seizures), particularly in boys.[62][63]

TSB should be measured within 12 hours after starting phototherapy - the timing of this measurement and frequency of TSB monitoring is based on the age of the child, presence of hyperbilirubinemia neurotoxicity risk factors, and the level and rate of rise of the TSB.[7]​ A decision to discontinue phototherapy can be considered when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy.[7]​ If there are risk factors for rebound hyperbilirubinemia (gestational age <38 weeks, age <48 hours at the start of phototherapy, hemolytic disease), then a longer period of treatment is an option.[7]​​

 A follow-up bilirubin test is required after discontinuing phototherapy after at least 12 hours, and preferably 24 hours to allow time to demonstrate any rebound hyperbilirubinemia.[7]​ 

Plus – hydration

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
total serum bilirubin levels at or above the exchange transfusion threshold
Plus – 

hydration

Treatment recommended for ALL patients in selected patient group

Intravenous fluid supplementation may result in a faster decline of bilirubin levels.[67][68]

Otherwise maintain hydration with enteral breast milk or formula.

Breast-feeding/bottle-feeding can be continued in most circumstances while on phototherapy. Oral supplementation with water or glucose is not recommended.[7]​ Temporary interruption of breast-feeding is very rarely needed, but it may be considered for specific clinical scenarios in which rapid reduction in total serum bilirubin is urgently needed or if phototherapy is unavailable.[7]​​

Consider – intravenous immune globulin (IVIG)

Back
ACUTE
|
pathologic hyperbilirubinemia: unconjugated
|
total serum bilirubin levels at or above the exchange transfusion threshold
Consider – 

intravenous immune globulin (IVIG)

Treatment recommended for SOME patients in selected patient group

In infants with isoimmune hemolytic disease, IVIG treatment may be commenced if the total serum bilirubin (TSB) level is rising despite intensive phototherapy or is within 2-3 mg/dL of an exchange transfusion level, although the quality of evidence supporting this therapy is low.[74]

Based on current evidence, it is recommended that IVIG treatment in infants ≥35 weeks of gestational age infants with a positive direct antiglobulin test be limited to those in whom the TSB is rising despite intensive phototherapy or is near the exchange level (within 2-3 mg/dL) and there is concern that an exchange transfusion may not occur in a timely manner.​[7][61]

Primary options

immune globulin (human): 0.5 to 1 g/kg intravenously over 2 hours; repeat in 12 hours if necessary

pathologic hyperbilirubinemia: conjugated

1st line – treatment of the underlying cause

Back
ACUTE
|
pathologic hyperbilirubinemia: conjugated
1st line – 

treatment of the underlying cause

Conjugated bilirubin measured within the first 24-48 hours of life and even after, should be normal (i.e., <95%). Neonates being investigated for conjugated hyperbilirubinemia should have prompt follow-up to rule out cholestasis and biliary atresia in a timely fashion.[75]​ The management of conjugated hyperbilirubinemia is dependent on its etiology. Consultation with an appropriate specialist may be required for further management, depending on the etiology found.

breast-feeding/breast milk jaundice

1st line – Optimization of breast-feeding + supplemental feeding

Back
ACUTE
|
breast-feeding/breast milk jaundice
1st line – 

Optimization of breast-feeding + supplemental feeding

“Suboptimal intake hyperbilirubinemia” associated with inadequate breast milk intake typically peaks on days 3-5 after birth and is frequently associated with excess weight loss. Early optimizing of breast-feeding and consideration of additional enteral intake if there is clinical or laboratory evidence that breast-feeding is compromised may help to mitigate the risk of subsequent hyperbilirubinemia.[7]​​[76]

“Breast milk jaundice” or the “breast milk jaundice syndrome,” in contrast, persists up to 3 months despite adequate human milk intake and optimal weight gain, and is almost always nonpathologic.[7]​​[76] Breastfed infants who are adequately hydrated should not routinely receive supplementation. Temporary supplementation with infant formula and temporary interruption of breast-feeding is very rarely indicated, and should be made jointly with the infant’s parents, when possible, after discussion of risks and benefits.[7]​​

2nd line – phototherapy

Back
ACUTE
|
breast-feeding/breast milk jaundice
2nd line – 

phototherapy

Phototherapy is recommended based on the total serum bilirubin (TSB) thresholds in correlation with gestational age, hyperbilirubinemia neurotoxicity risk factors, and age of the infant in hours.[7] Thresholds are provided in the American Academy of Pediatrics guidelines. Phototherapy should be initiated if the TSB level is above or at the threshold.[7]​ Clinicians should consult local guidelines for treatment thresholds.​​

While there is limited information, it has been suggested that phototherapy may limit familial bonding. Hence, it would be advisable to balance the benefit versus adverse effects of treatment threshold of phototherapy treatment in the management of hyperbilirubinemia in infants ≥35 weeks of gestational age.[7]​​[61]

Risk factors for hyperbilirubinemia neurotoxicity include a gestational age <38 weeks, albumin <3.0 g/dL, serious illness in the newborn infant (e.g., sepsis or significant clinical instability in the previous 24 hours), or isoimmune hemolytic disease, glucose-6-phosphate deficiency, or other hemolytic conditions.[7]​​

Escalation of care should be initiated when an infant’s TSB reaches or exceeds 2 mg/dL below the exchange transfusion threshold to prevent the need for an exchange transfusion and possibly to prevent kernicterus.[7]​ This includes optimal management in a neonatal intensive care unit, intravenous hydration and intensive phototherapy.[7]​​[67][68]​​ TSB should be measured at least every 2 hours from the start of the escalation-of-care period.[7]​ Blood should be sent for total and direct-reacting serum bilirubin, CBC, serum albumin, serum chemistries, and type and crossmatch.

Phototherapy uses light energy to cause photochemical reactions to transform bilirubin into isomers that are less lipophilic and more easily excretable, and make breakdown products that do not require conjugation in the liver. Bilirubin absorbs visible light most strongly in the blue region of the spectrum (around 460 nm) and the most effective phototherapy wavelengths are from 460-490 nm, optimally 478 nm.[7][48][49] Units use light-emitting diode (LED), halogen, fluorescent, or fiberoptic light sources to produce these wavelengths.[49]

LED phototherapy units are preferred due to their reduced heat production and subsequent reduction in insensible water loss.[49]​ LED phototherapy with overhead use (versus illumination from beneath the infant) shortened the mean duration of phototherapy and increased the rate of decrease in TSB compared to conventional phototherapy using compact fluorescent or halogen lamps.​​[50][51][52][53] [ Cochrane Clinical Answers logo ] ​​​ 

Maximal body surface area illumination (35% to 80%) is advised.[49]​ Double-light phototherapy is often considered to be more effective than single-light or fiberoptic phototherapy, with an irradiance of at least 30 microwatts/cm² at a wavelength of 478 nm.[7][49][50]​

Fiberoptic phototherapy units are alternatives to conventional phototherapy in term neonates.​​[50][51][58]​​[59] [ Cochrane Clinical Answers logo ] ​ Special blue compact fluorescent lamp phototherapy had no superiority over special blue standard length tube light phototherapy in terms of efficacy and adverse effects on the neonate and effects on nursing staff.[60]

The risk/benefit profile is excellent, with immediate onset of action upon switching on the phototherapy lights. Adverse effects are generally mild and include insensible water loss, loose stools, skin rash, and potential retinal damage. These can be prevented by maintaining adequate hydration and ensuring the baby wears eye shields during phototherapy; however, there is no evidence to support this recommendation.[49] It is important that a clinician monitors and maintains adequate hydration, nutrition and temperature control during phototherapy.[49]

One randomized controlled trial reported that aggressive phototherapy did not impact on the outcome of neurodevelopmental impairment or death in extremely low birth weight (ELBW) infants (birth weight <1000 g), compared with conservative phototherapy.[64] However, a systematic review of 9 studies showed that prophylactic phototherapy may reduce long-term neurodevelopmental impairment.[65] [ Cochrane Clinical Answers logo ] ​​ While aggressive phototherapy did reduce the rate of neurodevelopmental impairment alone, there was an increase in mortality among infants with birth weights 500-750 g.[64] Hence, an aggressive phototherapy approach is not recommended for ELBW infants.

It may be prudent to initiate phototherapy strictly at threshold values (i.e., avoiding prophylactic treatment) and to terminate it once serum bilirubin falls below these levels because of an association between neonatal phototherapy and an increased risk of childhood epilepsy (not febrile seizures), particularly in boys.[62][63]

TSB should be measured within 12 hours after starting phototherapy - the timing of this measurement and frequency of TSB monitoring is based on the age of the child, presence of hyperbilirubinemia neurotoxicity risk factors, and the level and rate of rise of the TSB.[7]​ A decision to discontinue phototherapy can be considered when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy.[7]​ If there are risk factors for rebound hyperbilirubinemia (gestational age <38 weeks, age <48 hours at the start of phototherapy, hemolytic disease), then a longer period of treatment is an option.​[7]

A follow-up bilirubin test is required after discontinuing phototherapy after at least 12 hours, and preferably 24 hours to allow time to demonstrate any rebound hyperbilirubinemia.[7]​ ​ 

Plus – hydration

Back
ACUTE
|
breast-feeding/breast milk jaundice
Plus – 

hydration

Treatment recommended for ALL patients in selected patient group

Breast-feeding/bottle-feeding can be continued in most circumstances while on phototherapy. Oral supplementation with water or glucose is not recommended.[7] Temporary interruption of breast-feeding is very rarely needed, but it maybe considered for specific clinical scenarios in which rapid reduction in total serum bilirubin is urgently needed or if phototherapy is unavailable.[7]​​

Intravenous hydration is usually reserved for neonates receiving phototherapy with bilirubin levels close to the exchange value. Such intravenous fluid supplementation may result in a faster decline of bilirubin levels.[67][68]

3rd line – exchange transfusion

Back
ACUTE
|
breast-feeding/breast milk jaundice
3rd line – 

exchange transfusion

An urgent exchange transfusion should be performed for infants if the total serum bilirubin is at or above the exchange transfusion threshold.​[7]

Risk factors for hyperbilirubinemia neurotoxicity include a gestational age <38 weeks, albumin <3.0 g/dL, serious illness in the newborn infant (e.g., sepsis or significant clinical instability in the previous 24 hours), or isoimmune hemolytic disease, glucose-6-phosphate deficiency, or other hemolytic conditions.[7]​​

Start as soon as the blood can be arranged for the exchange transfusion. Continue phototherapy while waiting to start the procedure, stop while doing the transfusion, and restart phototherapy as soon as the exchange transfusion is completed.

The rationale is to remove the unconjugated bilirubin by doing a double-volume exchange transfusion, which should allow the bilirubin to move out of the brain tissue and hence, decrease the risk of neurologic toxicities. An exchange transfusion will also remove antibodies responsible for hemolytic anemia. In severe cases of erythroblastosis and/or hydrops, it will correct anemia. Cross-matched washed packed red blood cells mixed with thawed adult fresh-frozen plasma is preferred for exchange transfusions.

There is insufficient evidence to support or refute the use of single-volume exchange transfusion as opposed to double-volume exchange transfusion in jaundiced newborns.[77]

The major potential complications of the procedure include electrolyte disturbances, bleeding, infection, cardiac arrhythmias, thrombosis with embolization, necrotizing enterocolitis, and graft-versus-host disease.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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