Jaundice in newborn babies under 28 days

This guideline covers diagnosing and treating jaundice, which is caused by increased levels of bilirubin in the blood, in newborn babies (neonates). It aims to help detect or prevent very high levels of bilirubin, which can be harmful if not treated.

# Context
Jaundice is one of the most common conditions needing medical attention in newborn babies. Jaundice refers to the yellow colouration of the skin and the sclerae (whites of the eyes) caused by the accumulation of bilirubin in the skin and mucous membranes. It is caused by a raised level of bilirubin in the body, a condition known as hyperbilirubinaemia.
Approximately 60% of term and 80% of preterm babies develop jaundice in the first week of life, and about 10% of breastfed babies are still jaundiced at 1 month. For most babies, jaundice is not an indication of an underlying disease, and this early jaundice (termed 'physiological jaundice') is usually harmless.
Breastfed babies are more likely than bottlefed babies to develop physiological jaundice within the first week of life. Prolonged jaundice  that is, jaundice persisting beyond the first 14 days  is also seen more commonly in breastfed babies. Prolonged jaundice is usually harmless, but can sometimes be an indication of serious liver disease.
Jaundice has many possible causes, including blood group incompatibility (most commonly rhesus or ABO incompatibility), other causes of haemolysis (breaking down of red blood cells), sepsis (infection), liver disease, bruising and metabolic disorders. Deficiency of a particular enzyme, glucose6phosphatedehydrogenase, can cause severe neonatal jaundice. Glucose6phosphatedehydrogenase deficiency is more common in certain ethnic groups and runs in families.
Bilirubin is mainly produced from the breakdown of red blood cells. Red cell breakdown produces unconjugated (or 'indirect') bilirubin, which circulates mostly bound to albumin although some is 'free' and hence able to enter the brain. Unconjugated bilirubin is metabolised in the liver to produce conjugated (or 'direct') bilirubin which then passes into the gut and is largely excreted in stool. The terms direct and indirect refer to the way the laboratory tests measure the different forms. Some tests measure total bilirubin and do not distinguish between the two forms.
In young babies, unconjugated bilirubin can penetrate the membrane that lies between the brain and the blood (the bloodbrain barrier). Unconjugated bilirubin is potentially toxic to neural tissue (brain and spinal cord). Entry of unconjugated bilirubin into the brain can cause both shortterm and longterm neurological dysfunction (bilirubin encephalopathy). The term kernicterus is used to denote the clinical features of acute or chronic bilirubin encephalopathy, as well as the yellow staining in the brain associated with the former. The risk of kernicterus is increased in babies with extremely high bilirubin levels. Kernicterus is also known to occur at lower levels of bilirubin in term babies who have risk factors, and in preterm babies.
Clinical recognition and assessment of jaundice can be difficult, particularly in babies with darker skin tones. Once jaundice is recognised, there is uncertainty about when to treat, and there is widespread variation in the use of phototherapy and exchange transfusion. There is a need for more uniform, evidencebased practice and for consensusbased practice where such evidence is lacking. This guideline provides guidance regarding the recognition, assessment and treatment of neonatal jaundice. The advice is based on evidence where this is available and on consensusbased practice where it is not.
In 2016, we reviewed the evidence on tests for recognising neonatal jaundice, bilirubin thresholds for retesting, and the type and procedure for phototherapy. New and updated recommendations have been added on bilirubin thresholds for retesting and the type of phototherapy to use.# Recommendations
People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.
Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.

# Threshold table
Note that there is variability between assays from different manufacturers in reported bilirubin measurement. Healthcare professionals should consult their local pathology laboratory when interpreting threshold tables.
Age (hours)
Bilirubin measurement (micromol/litre)
Action
Start phototherapy
Perform an exchange transfusion unless the bilirubin level falls below threshold while the treatment is being prepared

# Information for parents or carers
Offer parents or carers information about neonatal jaundice that is tailored to their needs and expressed concerns. This information should be provided through verbal discussion backed up by written information. Care should be taken to avoid causing unnecessary anxiety to parents or carers. Information should include:
factors that influence the development of significant hyperbilirubinaemia
how to check the baby for jaundice
what to do if they suspect jaundice
the importance of recognising jaundice in the first 24 hours and of seeking urgent medical advice
the importance of checking the baby's nappies for dark urine or pale chalky stools
the fact that neonatal jaundice is common, and reassurance that it is usually transient and harmless
reassurance that breastfeeding can usually continue. 

# Care for all babies
Identify babies as being more likely to develop significant hyperbilirubinaemia if they have any of the following factors:
gestational age under 38 weeks
a previous sibling with neonatal jaundice requiring phototherapy
mother's intention to breastfeed exclusively
visible jaundice in the first 24 hours of life. 
Ensure that adequate support is offered to all women who intend to breastfeed exclusively. For information on breastfeeding support, see NICE's guideline on postnatal care. 
In all babies:
check whether there are factors associated with an increased likelihood of developing significant hyperbilirubinaemia soon after birth
examine the baby for jaundice at every opportunity especially in the first 72 hours. 
Parents, carers and healthcare professionals should all look for jaundice (visual inspection) in babies. 
When looking for jaundice (visual inspection):
check the naked baby in bright and preferably natural light
examine the sclerae and gums, and press lightly on the skin to check for signs of jaundice in 'blanched' skin. 
Do not rely on visual inspection alone to estimate the bilirubin level in a baby with suspected jaundice. 
Do not measure bilirubin levels routinely in babies who are not visibly jaundiced. 
Do not use any of the following to predict significant hyperbilirubinaemia:
umbilical cord blood bilirubin level
endtidal carbon monoxide (ETCOc) measurement
umbilical cord blood direct antiglobulin test (DAT) (Coombs' test). 

## Additional care
Ensure babies with factors associated with an increased likelihood of developing significant hyperbilirubinaemia receive an additional visual inspection by a healthcare professional during the first 48 hours of life. 

## Urgent additional care for babies with visible jaundice in the first 24 hours
In all babies with suspected or obvious jaundice in the first 24 hours of life, measure and record the serum bilirubin level urgently (within 2 hours). 
In all babies with suspected or obvious jaundice in the first 24 hours of life, continue to measure the serum bilirubin level every 6 hours until the level is both:
below the treatment threshold
stable and/or falling. 
Arrange a referral to ensure that an urgent medical review is conducted (as soon as possible and within 6 hours) for babies with suspected or obvious jaundice in the first 24 hours of life to exclude pathological causes of jaundice. 
Interpret bilirubin levels according to the baby's postnatal age in hours and manage hyperbilirubinaemia according to the threshold table and the treatment threshold graphs. 

## Care for babies more than 24 hours old
Measure and record the bilirubin level urgently (within 6 hours) in all babies more than 24 hours old with suspected or obvious jaundice. 

## How to measure the bilirubin level
Use serum bilirubin measurement for babies:
in the first 24 hours of life or
who have a gestational age of less than 35 weeks. 
In babies who have a gestational age of 35 weeks or more and who are over 24 hours old:
use a transcutaneous bilirubinometer to measure the bilirubin level
if a transcutaneous bilirubinometer is not available, measure the serum bilirubin
if a transcutaneous bilirubinometer measurement indicates a bilirubin level greater than 250 micromol/litre, measure the serum bilirubin to check the result
use serum bilirubin measurement if bilirubin levels are at or above the relevant treatment thresholds for their age, and for all subsequent measurements. 
Do not use an icterometer to measure bilirubin levels in babies. 

# Management and treatment of hyperbilirubinaemia

## Information for parents or carers on treatment
Offer parents or carers information about treatment for hyperbilirubinaemia, including:
anticipated duration of treatment
reassurance that breastfeeding, nappychanging and cuddles can usually continue. 
Encourage mothers of breastfed babies with jaundice to breastfeed frequently, and to wake the baby for feeds if necessary. 
Provide lactation/feeding support to breastfeeding mothers whose baby is visibly jaundiced. 

## How to manage hyperbilirubinaemia
Note that there is variability between assays from different manufacturers in reported bilirubin measurement. Healthcare professionals should consult their local pathology laboratory when interpreting threshold tables.
Use the bilirubin level to determine the management of hyperbilirubinaemia in all babies (see the threshold table and the treatment threshold graphs). 
Do not use the albumin/bilirubin ratio when making decisions about the management of hyperbilirubinaemia. 
Do not subtract conjugated bilirubin from total serum bilirubin when making decisions about the management of hyperbilirubinaemia (see management thresholds in the threshold table and the treatment threshold graphs). 

# Measuring and monitoring bilirubin thresholds before and during phototherapy

## Before starting phototherapy
In babies who are clinically well, have a gestational age of 38 weeks or more and are more than 24 hours old, and who have a bilirubin level that is below the phototherapy threshold but within 50 micromol/litre of the threshold (see the threshold table and the treatment threshold graphs), repeat bilirubin measurement as follows:
within 18 hours for babies with risk factors for neonatal jaundice (those with a sibling who had neonatal jaundice that needed phototherapy or a mother who intends to exclusively breastfeed)
within 24 hours for babies without risk factors. 
In babies who are clinically well, have a gestational age of 38 weeks or more and are more than 24 hours old, and who have a bilirubin level that is below the phototherapy threshold by more than 50 micromol/litre (see the threshold table and the treatment threshold graphs), do not routinely repeat bilirubin measurement. 
Do not use phototherapy in babies whose bilirubin does not exceed the phototherapy threshold levels in the threshold table and the treatment threshold graphs. 

## During phototherapy
During phototherapy:
repeat serum bilirubin measurement 46 hours after initiating phototherapy
repeat serum bilirubin measurement every 612 hours when the serum bilirubin level is stable or falling. 

## Stopping phototherapy
Stop phototherapy once serum bilirubin has fallen to a level at least 50 micromol/litre below the phototherapy threshold (see threshold table and the treatment threshold graphs). 
Check for rebound of significant hyperbilirubinaemia with a repeat serum bilirubin measurement 1218 hours after stopping phototherapy. Babies do not necessarily have to remain in hospital for this to be done. 

## Type of phototherapy to use
Do not use sunlight as treatment for hyperbilirubinaemia. 
Use phototherapy (phototherapy given using an artificial light source with an appropriate spectrum and irradiance. This can be delivered using light-emitting diode , fibreoptic or fluorescent lamps, tubes or bulbs) to treat significant hyperbilirubinaemia (see the threshold table and the treatment threshold graphs) in babies. 
Consider intensified phototherapy (phototherapy that is given with an increased level of irradiance with an appropriate spectrum. Phototherapy can be intensified by adding another light source or increasing the irradiance of the initial light source used) to treat significant hyperbilirubinaemia in babies if any of the following apply :
the serum bilirubin level is rising rapidly (more than 8.5 micromol/litre per hour)
the serum bilirubin is at a level within 50 micromol/litre below the threshold for which exchange transfusion is indicated after 72 hours or more since birth (see threshold table and the treatment threshold graphs)
the bilirubin level fails to respond to initial phototherapy (that is, the level of serum bilirubin continues to rise, or does not fall, within 6 hours of starting phototherapy). 
If the serum bilirubin level falls during intensified phototherapy to a level 50 micromol/litre below the threshold for which exchange transfusion is indicated reduce the intensity of phototherapy. 

## Information for parents or carers on phototherapy
Offer parents or carers verbal and written information on phototherapy including all of the following:
why phototherapy is being considered
why phototherapy may be needed to treat significant hyperbilirubinaemia
the possible adverse effects of phototherapy
the need for eye protection and routine eye care
reassurance that short breaks for feeding, nappy changing and cuddles will be encouraged
what might happen if phototherapy fails
rebound jaundice
potential longterm adverse effects of phototherapy
potential impact on breastfeeding and how to minimise this. 

## General care of the baby during phototherapy
During phototherapy:
place the baby in a supine position unless other clinical conditions prevent this
ensure treatment is applied to the maximum area of skin
monitor the baby's temperature and ensure the baby is kept in an environment that will minimise energy expenditure (thermoneutral environment)
monitor hydration by daily weighing of the baby and assessing wet nappies
support parents and carers and encourage them to interact with the baby. 
Give the baby eye protection and routine eye care during phototherapy. 
Use tinted headboxes as an alternative to eye protection in babies with a gestational age of 37 weeks or more undergoing phototherapy. 

## Monitoring the baby during phototherapy
During phototherapy:
using clinical judgement, encourage short breaks (of up to 30 minutes) for breastfeeding, nappy changing and cuddles
continue lactation/feeding support
do not give additional fluids to babies who are breastfed. Maternal expressed milk is the additional feed of choice if available, and when additional feeds are indicated. 
During intensified phototherapy:
do not interrupt phototherapy for feeding but continue administering intravenous/enteral feeds
continue lactation/feeding support so that breastfeeding can start again when treatment stops.Maternal expressed milk is the additional feed of choice if available, and when additional feeds are indicated. 

## Phototherapy equipment
Ensure all phototherapy equipment is maintained and used according to the manufacturers' guidelines. 
Use incubators or bassinets according to clinical need and availability. 
Do not use white curtains routinely with phototherapy as they may impair observation of the baby. 

# Factors that influence the risk of kernicterus
Identify babies with hyperbilirubinaemia as being at increased risk of developing kernicterus if they have any of the following:
a serum bilirubin level greater than 340 micromol/litre in babies with a gestational age of 37 weeks or more
a rapidly rising bilirubin level of greater than 8.5 micromol/litre per hour
clinical features of acute bilirubin encephalopathy. 

# Formal assessment for underlying disease
In addition to a full clinical examination by a suitably trained healthcare professional, carry out all of the following tests in babies with significant hyperbilirubinaemia as part of an assessment for underlying disease (see threshold table and the treatment threshold graphs):
serum bilirubin (for baseline level to assess response to treatment)
blood packed cell volume
blood group (mother and baby)
DAT (Coombs' test). Interpret the result taking account of the strength of reaction, and whether mother received prophylactic antiD immunoglobulin during pregnancy. 
When assessing the baby for underlying disease, consider whether the following tests are clinically indicated:
full blood count and examination of blood film
blood glucose6phosphate dehydrogenase levels, taking account of ethnic origin
microbiological cultures of blood, urine and/or cerebrospinal fluid (if infection is suspected). 

# Care of babies with prolonged jaundice
In babies with a gestational age of 37 weeks or more with jaundice lasting more than 14 days, and in babies with a gestational age of less than 37 weeks and jaundice lasting more than 21 days:
look for pale chalky stools and/or dark urine that stains the nappy
measure the conjugated bilirubin
carry out a full blood count
carry out a blood group determination (mother and baby) and DAT (Coombs' test). Interpret the result taking account of the strength of reaction, and whether mother received prophylactic antiD immunoglobulin during pregnancy
carry out a urine culture
ensure that routine metabolic screening (including screening for congenital hypothyroidism) has been performed. 
Follow expert advice about care for babies with a conjugated bilirubin level greater than 25 micromol/litre because this may indicate serious liver disease. 

# Intravenous immunoglobulin
Use intravenous immunoglobulin (IVIG) (500 mg/kg over 4 hours) as an adjunct to continuous intensified phototherapy in cases of rhesus haemolytic disease or ABO haemolytic disease when the serum bilirubin continues to rise by more than 8.5 micromol/litre per hour. 
Offer parents or carers information on IVIG including:
why IVIG is being considered
why IVIG may be needed to treat significant hyperbilirubinaemia
the possible adverse effects of IVIG
when it will be possible for parents or carers to see and hold the baby. 

# Exchange transfusion
Offer parents or carers information on exchange transfusion including:
the fact that exchange transfusion requires that the baby be admitted to an intensive care bed
why an exchange transfusion is being considered
why an exchange transfusion may be needed to treat significant hyperbilirubinaemia
the possible adverse effects of exchange transfusions
when it will be possible for parents or carers to see and hold the baby after the exchange transfusion. 
Use a doublevolume exchange transfusion to treat babies:
whose serum bilirubin level indicates its necessity (see threshold table and the treatment threshold graphs) and/or
with clinical features and signs of acute bilirubin encephalopathy. 
During exchange transfusion do not:
stop continuous intensified phototherapy
perform a singlevolume exchange
use albumin priming
routinely administer intravenous calcium. 
Following exchange transfusion:
maintain continuous intensified phototherapy
measure serum bilirubin level within 2 hours and manage according to the threshold table and the treatment threshold graphs. 

# Other therapies
Do not use any of the following to treat hyperbilirubinaemia:
agar
albumin
barbiturates
charcoal
cholestyramine
clofibrate
Dpenicillamine
glycerin
manna
metalloporphyrins
riboflavin
traditional Chinese medicine
acupuncture
homeopathy. # Putting this guideline into practice
NICE has produced tools and resources to help you put this guideline into practice.
Putting recommendations into practice can take time. How long may vary from guideline to guideline, and depends on how much change in practice or services is needed. Implementing change is most effective when aligned with local priorities.
Changes recommended for clinical practice that can be done quickly  like changes in prescribing practice  should be shared quickly. This is because healthcare professionals should use guidelines to guide their work  as is required by professional regulating bodies such as the General Medical and Nursing and Midwifery Councils.
Changes should be implemented as soon as possible, unless there is a good reason for not doing so (for example, if it would be better value for money if a package of recommendations were all implemented at once).
Different organisations may need different approaches to implementation, depending on their size and function. Sometimes individual practitioners may be able to respond to recommendations to improve their practice more quickly than large organisations.
Here are some pointers to help organisations put NICE guidelines into practice:
. Raise awareness through routine communication channels, such as email or newsletters, regular meetings, internal staff briefings and other communications with all relevant partner organisations. Identify things staff can include in their own practice straight away.
. Identify a lead with an interest in the topic to champion the guideline and motivate others to support its use and make service changes, and to find out any significant issues locally.
. Carry out a baseline assessment against the recommendations to find out whether there are gaps in current service provision.
. Think about what data you need to measure improvement and plan how you will collect it. You may want to work with other health and social care organisations and specialist groups to compare current practice with the recommendations. This may also help identify local issues that will slow or prevent implementation.
. Develop an action plan, with the steps needed to put the guideline into practice, and make sure it is ready as soon as possible. Big, complex changes may take longer to implement, but some may be quick and easy to do. An action plan will help in both cases.
. For very big changes include milestones and a business case, which will set out additional costs, savings and possible areas for disinvestment. A small project group could develop the action plan. The group might include the guideline champion, a senior organisational sponsor, staff involved in the associated services, finance and information professionals.
. Implement the action plan with oversight from the lead and the project group. Big projects may also need project management support.
. Review and monitor how well the guideline is being implemented through the project group. Share progress with those involved in making improvements, as well as relevant boards and local partners.
NICE provides a comprehensive programme of support and resources to maximise uptake and use of evidence and guidance. See our into practice pages for more information.
Also see Leng G, Moore V, Abraham S, editors (2014) Achieving high quality care  practical experience from NICE. Chichester: Wiley.# Recommendations for research
In 2010, the guideline committee made the 5 recommendations for research. As part of the 2016 update, the standing committee made an additional recommendation for research on parent and healthcare professional experience of phototherapy.

# Breastfeeding and hyperbilirubinaemia
What are the factors that underlie the association between breastfeeding and jaundice?

## Why this is important
Breastfeeding has been shown to be a factor in significant hyperbilirubinaemia. The reasons for this association have not yet been fully elucidated.
This question should be answered by studying infants in the first 28 days of life receiving different feeding types (breast milk, formula feeds or mixed feeds). Infants who do not develop significant hyperbilirubinaemia should be compared with infants with significant hyperbilirubinaemia. The outcomes chosen should include maternal factors, neonatal factors and blood analyses.

# Transcutaneous bilirubin screening and risk factors
What is the comparative effectiveness and costeffectiveness of universal predischarge transcutaneous bilirubin screening alone or combined with a risk assessment in reducing jaundicerelated neonatal morbidity and hospital readmission?

## Why this is important
There is good evidence that a risk assessment that combines the result of a timed transcutaneous bilirubin level with risk factors for significant hyperbilirubinaemia is effective at preventing later significant hyperbilirubinaemia.
This question should be answered by studying the effects of timed predischarge transcutaneous bilirubin levels and timed predischarge transcutaneous bilirubin levels combined with risk assessment. The study population should consist of babies in the first 28 days of life, with subgroups including nearterm babies and babies with dark skin tones. The interventions should be compared with standard care (discharge without timed transcutaneous bilirubin level), and the outcomes chosen should include significant hyperbilirubinaemia, costeffectiveness and parental anxiety.

# Transcutaneous bilirubinometers
What is the comparative accuracy of the Minolta JM103 and the BiliChek when compared to serum bilirubin levels in all babies?

## Why this is important
The accuracy of transcutaneous bilirubinometers (Minolta JM103 and BiliChek) has been adequately demonstrated in term babies below treatment levels (bilirubin less than 250 micromol/litre). New research is needed to evaluate the accuracy of different transcutaneous bilirubinometers in comparison to serum bilirubin levels in all babies.
This question should be answered by comparing bilirubin levels taken using different transcutaneous bilirubinometers with bilirubin levels assessed using serum (blood) tests. The study population should comprise babies in the first 28 days of life, with subgroups including preterm babies, babies with dark skin tones, babies with high levels of bilirubin and babies after phototherapy. The outcomes chosen should include diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value), parental anxiety, staff and parental satisfaction with test and cost effectiveness.

# Interruptions during phototherapy
How frequently and for how long can phototherapy be interrupted without adversely effecting clinical outcomes?

## Why this is important
The effectiveness and tolerability of intermittent phototherapy has been adequately demonstrated in term babies at low treatment levels (bilirubin less than 250 micromol/litre). New research is needed to evaluate the effectiveness and tolerability of different frequencies of interruptions of different durations.
The study population should comprise babies in the first 28 days of life in phototherapy. Interruptions of 45 or 60 minutes would be made either on demand, every hour or every 2 hours, and compared with interruptions of up to 30 minutes every 3 hours. The outcomes chosen should include effectiveness in terms of the mean decrease in bilirubin levels and the mean duration of phototherapy. Extra outcomes could include adverse effects, parental bonding and parental anxiety, staff and parental satisfaction with treatment and cost effectiveness.

# National registries
National registries are needed of cases of significant hyperbilirubinaemia, kernicterus and exchange transfusions.

## Why this is important
There is good evidence that prospective surveys in the UK and data from a national kernicterus register in the US can help to identify root causes of kernicterus and acute bilirubin encephalopathy.
The study population should comprise all children with a peak bilirubin level greater than 450 micromol/litre, which is the threshold for an exchange transfusion recommended by NICE. The intervention would be maternal, prenatal, perinatal and neonatal factors. The outcomes chosen should be shortcomings in clinical and service provision to prevent recurring themes in kernicterus cases.

# Parent and healthcare professional experience of phototherapy
What is the experience and acceptability of phototherapy from the perspective of parents and healthcare professionals?

## Why this is important
There is a gap in the evidence about parental and healthcare professional experience and acceptability of phototherapy. The committee agreed that the need for this research should be supported, especially given the greater awareness of the crucial importance of close and early skin contact between babies and their carers. The study should be a qualitative study of newborn babies (term and preterm) with a diagnosis of jaundice but who are otherwise well. Outcomes should include both parental and staff experience, including access for bonding and breastfeeding.