sTANDARD TREATMENT Guidelines

6
Detection, Management and Prevention
of Hyperbilirubinemia in Term and Late
Preterm Newborn Infants

august 2017
HEALTH M
AL
Ministry of Health & Family Welfare
NATION

ISSI N
O

Government of India
 HEALTH M
AL

NATION

ISSI N
O
sTANDARD TREATMENT Guidelines
Detection, Management and Prevention of
Hyperbilirubinemia in Term and Late Preterm
Newborn Infants

august 2017

Ministry of Health & Family Welfare

Government of India
©2017

Ministry of Health and Family Welfare

Government of India, Nirman Bhawan
New Delhi-110 011

Reproduction of any excerpts from this documents does not require permission from
the publisher so long it is verbatim, is meant for free distribution and the source is
acknowledged.

ISBN: 978-93-82655-21-3

Design by: Macro Graphics Pvt. Ltd. (www.macrographics.com)

 Table of Contents

Introduction 1

The purpose of the Guideline 2

Approach of the Guideline 3

Key Clinical Issues that will be Covered in this Guideline  4

Key Recommendations 7

1. Screening and Assessment 7

2. Management and Treatment 17

Methodology of Development of Guideline 25

Formation of the STG Group 25

References 29

Appendix - A  33

Table of Contents iii

 Introduction

J aundice refers to the yellow discoloration of the skin and the sclera caused by the
accumulation of a pigment (bilirubin) in the skin and mucous membranes. It is seen
in neonates when the serum bilirubin levels exceed 5-7 mg/dL. Approximately 60% of
term and 80% of preterm infants develop jaundice in the first week of life, and about
10% of breastfed infants are still jaundiced at 1 month.

Visible jaundice usually appears between 24 to 72 hours of age. The total serum bilirubin
(TSB) level usually rises in term infants by 3 days of age and then falls. In preterm infants,
the peak level occurs around 3 to 7 days after birth. It may take weeks before the TSB
levels falls under 2 mg/dL in both term and preterm infants. Jaundice is not an indication
of an underlying disease for most infants, and this early jaundice (termed ‘physiological
jaundice’) is generally harmless.

Hyperbilirubinemia typically refers to serum bilirubin levels beyond the normal range and
is a common problem in neonates. (1)A significant proportion of these neonates develop
pathological jaundice (jaundice requiring treatment) during the first week of life (2). It
is also one of the leading causes of hospitalization in the first week of life globally (3-5).
The overall incidence of hyperbilirubinemia (>15 mg/dL) has been reported as 3.3% in
intramural neonates and 22.1%in extramural neonates(2).

Timely and appropriate treatment with phototherapy and/or exchange transfusion

is effective in decreasing excessive bilirubin levels. However, failure of instituting
appropriate therapy results in acute bilirubin encephalopathy (ABE) which if
not treated immediately, might go on to develop kernicterus and other long term
neurological deficits including cerebral palsy, sensorineural hearing loss, intellectual
difficulties or gross developmental delays (6-10). It is estimated that nearly 5,00,000

Introduction 1
term and late preterm neonates globally are affected by severe hyperbilirubinemia
annually and around one-fourth of them die and 63,000 survive with neurological
disability (11). Three-fourth of these affected infants reside in sub-Saharan Africa and
South Asia (12).

The purpose of the guideline

There is a need for a standard guideline for the management of neonatal hyperbilirubinemia
in term and late preterm newborn infants in India. The context for the detection,
management and prevention of neonatal hyperbilirubinemia in India is different from
other countries.

The published evidence based guidelines on early detection, management and prevention of
neonatal hyperbilirubinemia by various bodies including American Academy of Pediatrics
(13) and National Institute for Health and Clinical Excellence (14)primarily takes care of
the need of high income countries. The low and middle-income countries including India
are following these guidelines due to dearth of literature and absence of such evidence
based guidelines from their own setting.

There is an increased incidence of significant hyperbilirubinemia in India due to

various risk factors including racial and genetic factors, widespread practice of
exclusive breastfeeding, higher prevalence of G6PD deficiency in some parts of the
country, more neonates with low albumin at birth, higher bilirubin levels in summer
season due to dehydration, blood group incompatibilities and infections(15, 16).
Lack of knowledge among mother and family members about jaundice (17) and
poor transport facilities especially in rural areas often results in delay in seeking
medical advice. The situation is further compounded by “why worry” attitude among
healthcare professionals especially in the dearth of substantial data documenting
bilirubin induced neurological dysfunction (BIND)on arrival to health facility(18).
Inadequate knowledge among healthcare professionals, limited facilities for clinical
investigations, lack of standardised protocol for management (including absence of
monitoring serum bilirubin while under phototherapy) and inconsistent functional
status of available phototherapy devices, often results in inappropriate treatment
thus resulting in BIND(19-22). Even the lack of exchange transfusion facilities at
majority of the healthcare setting due to non-availability of blood or expertise results
in permanent neurological dysfunction which could be easily avoided by doing early
exchange transfusion.

2 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
Though the guidelines published by National Neonatology Forum,India (NNF 2010) (22)
have tried to provide a practical framework for managing neonatal hyperbilirubinemia
in Indian setting, these guidelines are meant for only tertiary care health facilities. In
view of the above stated reasons and opening of Special Care Newborn Units (SCNUs)
and private health facilities delivering level II neonatal care in a big way; the current
guideline has been developed for the management of neonatal hyperbilirubinemia
in late preterm and term infants in the Indian context for health care facilities
at all levels.

Approach of the guideline

The guidelines have been commissioned to enable a systematic cost-effective approach
for the detection, management and evaluation of neonatal hyperbilirubinemia in late
preterm and term infants in India. This guideline and its accompanying implementation
tools in the form of a quick reference guide, flow charts, and quality standards will serve as
a valuable reference material for healthcare providers, patients and administrators. While
formulating these guidelines the main outcome measures taken into consideration have
been mortality, incidence of acute bilirubin encephalopathy, incidence of chronic bilirubin
encephalopathy, hearing Loss, incidence of exchange transfusion, incidence of severe
hyperbilirubinemia, duration of phototherapy and incidence of readmissions required for
hyperbilirubinemia
yy This guideline has a primary care focus and a public health approach. The focus of the
primary care is to improve the early detection and the timely treatment to prevent
long term neurological deficits. Increasing awareness among public especially
mother and family members at the time of discharge about the need for jaundice
evaluation in first week of life in face of early discharges from health facilities in India
will improve this dismal situation and result in improving intact survival.
yy These guidelines will also facilitate effective advocacy and mobilisation of requisite
resources for the optimal care of newborn infants with hyperbilirubinemia at all
levels.
yy The guideline presented covers detection, management and prevention of
hyperbilirubinemia in term and late preterm newborn infants in primary, secondary
and tertiary care setting and includes an algorithmic approach (figure 1) to a
newborn with or at risk of hyperbilirubinemia.

Introduction 3
Population
Groups that will be covered

a) Neonates ≥ 35 weeks

Groups that will not be covered

a) Preterm neonates < 35 weeks

b) Neonates with conjugated hyperbilirubinemia

Health Care Setting

a) Primary care

b) Secondary and tertiary care

Disease or risk condition

At risk or having jaundice

Key Clinical issues that will be covered in this

guideline
I. Screening and Diagnosis
1.1 What should be the screening protocol for detection of jaundice in neonates?

1.2 Which neonates are at a higher risk of hyperbilirubinaemia?

1.3 What is the accuracy of transcutaneous bilirubinometry in recognising neonatal

hyperbilirubinaemia and how should it be done?

1.4 How will you interpret serum bilirubin levels and manage hyperbilirubinaemia?

1.5 What should be optimum discharge and follow-up timing and the assessment
policy to minimize the subsequent risk of severe hyperbilirubinemia and acute
bilirubin encephalopathy?

4 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
 1.6 What should be included in the formal assessment of a neonate with neonatal
hyperbilirubinaemia?

1.7 How can we prevent severe hyperbilirubinemia?

II. Treatment of hyperbilirubinemia

2.1 Phototherapy

2.2 Exchange transfusion

2.3 Other modalities

2.4 What should be the frequency of long term follow up of neonates with
hyperbilirubinemia and what all should be evaluated at follow up?

2.5 Information and support which should be given to parents/caregivers of neonates

with neonatal hyperbilirubinaemia?

Introduction 5
 Key Recommendations

1. Screening and assessment

1.1 What should be the screening protocol for detection of
jaundice in neonates? (14,22)

Recommendation
1. Healthcare professionals should all look for jaundice (visual inspection) in
babies (Figure 1)

2. Assessment of all newborns for jaundice should be done every 12 hours

especially in the initial 3 to 5 days.

3. Monitoring for development of severe neonatal jaundice may be needed till

end of first week of postnatal life.

1.2 Which neonates are at a higher risk of hyperbilirubinaemia?

(13, 22)

Recommendation
Identify neonates as being more likely to develop significant hyperbilirubinaemia if they
have ANY of the following factors:
yy Gestational age under 38 weeks
yy A previous sibling with neonatal hyperbilirubinaemia requiring phototherapy

Key Recommendations 7
 yy Mother’s intention to breastfeed exclusively
yy Visible jaundice in the first 24 hours of life.
yy Visible jaundice at discharge
yy Setting of blood group incompatibility
yy High prevalence of G6PD deficiency, primipara mother
yy Weight loss at discharge >3% per 24 h of age or >7% cumulative weight loss

Figure 1: Approach to an infant with jaundice

Perform visual assessment (VA) of jaundice: every 12 h during initial 3 to 5 days of life.
VA can be supplemented with transcutaneous bilirubinometry (TcB), if available

Step 1: Does the baby have serious jaundice*?

Yes No

Step 2: Does the infant have significant

Start jaundice to require TSB measurement#?
phototherapy$
Yes No
Measure TSB level and determine if baby
requires phototherapy or exchange
transfusion (refer to Management) Continued observation every 12
to 24 hr for initial 3 to 5 days
Step 3: Determine the cause of
jaundice (Table 2)and provide
supportive and follow up care
*
Serious jaundice (Any one of following):
a. Presence of visible jaundice in first 24 h
b. Yellow palms and soles anytime
c. Signs of acute bilirubin encephalopathy or kernicterus: hypertonia, abnormal posturing such as arching, retrocollis,
opisthotonus or convulsion, fever, high pitched cry)
d. IF AVAILABLE: Serum bilirubin or TcB value more than 95th centile as per age specific nomogram( 23)
#
Measure serum bilirubin if:
a. Jaundice in first 24 hour
b. Beyond 24 hr: if on visual assessment or by transcutaneous bilirubinometry, TSB is likely to be more than 12 to 14
mg/dL or approaching phototherapy range or beyond.
c. If you are unsure about visual assessment
$
Though it is important to start immediate phototherapy, it is also important to document serum bilirubin simultaneously.

8 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
1.3 What is the accuracy of transcutaneous bilirubinometry in
recognising neonatal hyperbilirubinaemia and how should it
be done?

1.3.1 Clinical examination for jaundice

Essential steps for screening and assessment of jaundice*

1. Examine the baby in bright natural light. Alternatively, the baby can be
examined in white fluorescent light. Make sure there is no yellow/ off white
background.

2. Make sure the baby is naked.

3. Examine blanched skin and gums or sclerae

4. Depth of jaundice (degree of yellowness) should be carefully noted as it is

an important indicator of level of jaundice and it does not figure out in
Kramer’s rule ) (figure 2)

A deep yellow staining (even in absence of yellow soles or palms) is often associated with
sever jaundice and therefore TSB should be estimated in such circumstances.

*Important notes

1. Visual inspection of jaundice is believed to be unreliable, but if it is performed properly (i.e. examining
a naked baby in bright natural light and in absence of yellow background), it has reasonable accuracy
particularly when TSB is less than 12 to 14 mg/dL

2. Absence of jaundice on visual inspection reliably excludes the jaundice.

3. All newborns with visible jaundice should be evaluated with TcB or TSB

4. If transcutaneous bilirubinometer is available, use it in babies with a gestational age of 35 weeks or

more and postnatal age of more than 24 hours and if it indicates a bilirubin level greater 14 mg/dL,
check serum bilirubin.

Key Recommendations 9
 Figure 2: The extent of jaundice (Kramer’s rule)(24)

1. Face 5-7 mg/dL

2. Chest 8-10 mg/dL
3. Lower abdomen/thigh 12 to 15 mg/dL
4. Arms/ lower legs 15 to18 mg/dL
5. Soles/Palms >15 mg/dL

1.3.2 Transcutaneous and total serum bilirubin

Measurement of bilirubin
Transcutaneous bilirubinometry (TcB)

1. TcB is a useful adjunct to TSB measurement, and routine employment of TcB

can reduce need for blood sampling by nearly 30%.

2. Current devices are costly and have a significant recurring cost of

consumables such as disposable tips etc.

3. TcB can be used in infants of 35 weeks or more of gestation after 24 hr.

10 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
 4. TcB becomes unreliable once TSB level goes beyond 14 mg/dL.

5. Hour specific TcB can be used for prediction of subsequent hyperbilirubinemia.

TcB value below 50th centile for age would rule out the risk of subsequent
hyperbilirubinemia with high probability (high negative predictive value)(23)

6. Trends in TcB values by measuring 12 hr apart would have a better predictive

value than a single value.

Measurement of TSB

a. Indication of TSB measurement:

i. Jaundice in first 24 hour

ii. Beyond 24 hr: if visually assessed jaundice is likely to be more than 14 mg/
dL or approaching the phototherapy range or beyond.

iii. If you are unsure about visual assessment

iv. During phototherapy, for monitoring progress and after phototherapy to

check for rebound in select cases (such as those with hemolytic jaundice)

b. Frequency of TSB measurement depends upon the underlying cause

(hemolytic versus non-hemolytic) and severity of jaundice as well as host
factors such as age and gestation. In general, in non-hemolytic jaundice in
term babies, TSB can be performed every 12 hr depending upon age of the
baby. As opposed to this, a baby with Rh isoimmunisation would require TSB
measurement every 6 to 8 hours during initial 24 to 48 hours or so.

c. Methods of TSB measurements

i. Biochemical: High performance liquid chromatography (HPLC) remains

the gold standard for estimation of TSB. However, this test is not
universally available and laboratory estimation of TSB is usually performed
by Vanden Bergh reaction. It has marked inter laboratory variability with
coefficient of variation being up to 10 to 12 percent for TSB and over 20
percent for conjugated fraction. (25)

ii. Micro method for TSB estimation: It is based on spectrophotometry and

estimates TSB on a micro blood sample. It is useful in neonates, as bilirubin
is predominantly unconjugated and can be done bedside.

Key Recommendations 11
1.4 How will you interpret serum bilirubin levels and manage
hyperbilirubinaemia?

Recommendation
Interpret serum bilirubin levels according to the baby's postnatal age in hours and
manage hyperbilirubinaemia as per the guidelines.

1. American Academy of Paediatrics (AAP) criteria should be used for

making decision regarding phototherapy or exchange transfusion in
these infants. AAP provides two age-specific nomograms- one each for
phototherapy and exchange transfusion. The nomograms have lines
for three different risk categories of neonates (Figure 2 and 3). These
lines include one each for lower risk babies (38 wk or more and no risk
factors), medium risk babies (38 wk or more with risk factors, or 35 wk to
37 wk and without any risk factors) and higher risk (35 wk to 37 wk and
with risk factors).

2. TSB value is taken for decision making and direct fraction should NOT be
reduced from it. The babies at lower and higher risk have their cut-offs at
approximately 2 mg/dL higher or 2 mg/dL lower than that for medium risk
babies, respectively.

3. Risk factors include presence of isoimmune hemolytic anemia, G6PD

deficiency, asphyxia, temperature instability, hypothermia, sepsis, significant
lethargy, acidosis and hypoalbuminemia.*

*Routine estimation of serum albumin is not recommended

12 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
 Figure 3: Guidelines for phototherapy in hospitalized infants
of 35 or more weeks gestation.

Key Recommendations
13
Figure 4 : Guidelines for exchange transfusion in hospitalized
infants of 35 or more week’s gestation.

14 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
1.5 What should be optimum discharge and follow-up timing and
the assessment policy to minimize the subsequent risk of severe
hyperbilirubinemia and acute bilirubin encephalopathy? (22)
In India, healthy neonates are usually discharged after 24-48 h of normal delivery.
In some facilities with high obstetric case load or absence of adequate manpower
neonates are discharged even before completing first 24 h of age. Discharge after
delivery by cesarean section is more variable with length of stay varying from 3 to 7
days. Due to continuing rise of bilirubin and absence of supervision for ensuring optimal
feeding, neonates discharged home before completing 48-72 h of age are at high risk
of developing undetected pathological hyperbilirubinemia. In India, this risk may be
further aggravated due to absence of any formal system of follow-up home-visits
by health care personnel (e.g. public health nurse) and due to traditional practice of
confinement of mother-baby dyad at home for first few weeks after delivery. Neonates
delivered at home are also at high risk of undetected pathological hyperbilirubinemia
due to same reasons.

The strategy of follow up of all neonates although desirable, is not feasible due to
relative shortage of health care personnel and inability of some families to return
for follow-up. Therefore follow-up plan may be devised based on pre-discharge risk
assessment (Table 1).

Table 1: Suggested follow-up policy (13)

Scenario Age at discharge Follow-up

24-72 h 48 h after discharge

None of risk factors* present
>72 h Follow-up optional

24-48 h 24 h after discharge

Any risk factor* present
After 48 hours 48 h after discharge

*History of jaundice needing treatment in previous sibling, setting of blood group incompatibility, visible
jaundice at discharge, gestation <38 completed weeks, high prevalence of G6PD deficiency, primipara
mother, weight loss at discharge >3% per 24 h of age or >7% cumulative weight loss,
**may need a repeat visit depending on physician’s assessment

Key Recommendations 15
1.6 What should be included in the formal assessment of a neonate
with neonatal hyperbilirubinaemia? (14)

Recommendation
All neonates should undergo a complete clinical examination including evaluation
of intensity of jaundice (24), breast feeding adequacy#, pallor, splenomegaly,
cephalhematoma or other signs of birth trauma, and evaluation for lethargy, poor
feeding, general activity and tone.

1. All pregnant women should be tested for ABO and Rh (D) blood types. (14)
2. If a mother has not had prenatal blood grouping or is Rh-negative, a direct
anti-body test (or Coombs’ test), blood type, and an Rh (D) type on the infant’s
(cord) blood are strongly recommended. (14)
3. DO NOT use the albumin/bilirubin ratio when making decisions about the
management of hyperbilirubinaemia (14)
4. Do not subtract conjugated bilirubin from total serum bilirubin when making
decisions about the management of hyperbilirubinaemia. (14)
5. In addition to a full clinical examination by a suitably trained healthcare
professional, carry out the following tests in babies with hyperbilirubinaemia
(Table 2) as part of an assessment for underlying disease and treatment
threshold graphs.
Table 2: Tests to be done in babies with hyperbilirubinaemia
Indications Assessments
Infant receiving Measure TSB; blood type and DCT (if mother is ‘O’ or Rh negative);
phototherapy G6PD status; peripheral smear and reticulocyte count
Jaundice present Total and direct (or conjugated) bilirubin level, thyroid profile (T3, T4,
beyond 3 weeks of age* TSH), urine for reducing substances (galactosemia), urine r/m, urine c/s
Important Note*
 Exclude cephalohematoma on examination
 Exclude Rh isoimmunisation
 Excessive weight loss (more than 10%)
 Breast feeding jaundice due to inadequate breast feeding is common
 Presence of direct hyperbilirubinemia (direct bilirubin more than 2 mg/dL at any age) requires specific
investigations and care which is beyond the scope of this guideline

# Breast feeding is considered adequate if infant passes urine 6 to 8 times in 24 hours, sleeps for 2 to 3 hours
after feeds and gains weight adequately after initial 7 to 10 days.

16 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
1.7 How can we prevent severe hyperbilirubinemia?(13, 14)

Recommendation
1. All women should be encouraged to breastfeed 8 to 12 times a day

2. Supplementation is recommended only for dehydrated newborns and

where weight loss from birth is >10%. Expressed breastmilk is the preferred
supplementation.

3. Routine supplementation with intravenous fluids, honey or dextrose water for

newborns with jaundice is not recommended

4. No interruption of breastfeeding should be done for any jaundice.

2. Management and treatment

Therapeutic options in management of hyperbilirubinemia

2.1 Phototherapyfor the management of hyperbilirubinemia (14)*

yy Phototherapy can be delivered by light - emitting diode (LED) or fibreoptic or

fluorescent lamps or tubes or bulbs.#
yy Do not use sunlight as treatment for hyperbilirubinaemia. Exposing the baby
to sunlight does not help in treatment of jaundice and is associated with risk of
sunburn and therefore should be avoided.

* Rash, overheating, dehydration and diarrhoea are the most common side effects of phototherapy. It has
photo oxidative effects and hence the parenteral nutrition fluid and some drugs need to be adequately
covered during phototherapy

# See Appendix A for different phototherapy equipment available in Indian Market

Key Recommendations 17
 Starting phototherapy
yy Use serum bilirubin levels ONLY for decision making for starting phototherapy
yy Intensive phototherapy must be ensured for neonates nearing exchange
transfusion threshold. Phototherapy can be intensified by adding another light
source or increasing the irradiance of the initial light source used.
yy Increase the area of exposure to light by using double surface phototherapy for
severe jaundice.*
yy It is not necessary to measure spectral irradiance before each use of phototherapy;
however it is important to perform periodic checks of phototherapy units to
make sure that an adequate irradiance is being delivered.
yy Phototherapy thresholds presented on seventh day may be used for rest of the
neonatal period.

* Severe jaundice defined earlier

Stopping phototherapy
yy There is no standard for discontinuing phototherapy. For infants who are
readmitted after their birth hospitalization (usually for TSB levels of 18 mg/dL
or higher), phototherapy may be discontinued when the serum bilirubin level
falls below 13 to 14 mg/dL.

Discharge and follow up after phototherapy

yy If phototherapy is used for infants with hemolytic diseases or is initiated early
and discontinued before the infant is 3 to 4 days old, a follow-up bilirubin
measurement within 24 hours after discharge is recommended.
yy For infants who are readmitted with hyperbilirubinemia and then discharged,
significant rebound is rare, but a repeat TSB measurement or clinical follow-up
24 hours after discharge is a clinical option.
yy Checking serum bilirubin 24 h after discharge to check for rebound is
optional

18 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
 Tips for delivering safe and effective phototherapy
yy Protect the eyes with eye patches/covers

yy Keep the baby naked with a small nappy to cover the genitalia

yy Place the baby as close to the lights as the manufacturers’ instructions allow.

yy Routine position change while the baby is under phototherapy is not

recommended.

yy Phototherapy does not have to be continuous and can be interrupted for

feeding, clinical procedures, and to allow maternal bonding.#

yy Using white cloth or aluminum foil around the light source to reflect light back
onto the baby, making sure not to impede the airflow that cools the bulbs is
optional

yy Do not place anything over the top of the phototherapy unit. This may block air
vents or light and items may fall on the baby

yy Encourage frequent breastfeeding. Unless there is evidence of dehydration,

supplementing breastfeeding or providing IV fluids is unnecessary

yy Giving frequent feeding will prevent excessive weight loss and temperature
from rising

yy Visual assessment of jaundice during phototherapy is unreliable

yy Ensure all phototherapy equipment is maintained and used according to the

manufacturers’ guidelines.

# Important note

 The guideline notes that there is no evidence to support the safe use of intermittent phototherapy at
moderate or high levels of serum bilirubin (mild hyperbilirubinemia defined as a total bilirubin level of up
to 12 mg/dL and high defined as levels above 20 mg/dL in full-term infants. Bilirubin levels between these
values indicated moderate hyperbilirubinemia)

 Change tube lights every 6 months (or usage time >1200 hrs) whichever is earlier; or if tube ends blacken
or if tubes flicker. Life of Compact Fluorescent lamps is 3000 hours while that of LED bulbs is 30,000 to
50,000 hours.

Key Recommendations 19
 Failure of phototherapy (22)
yy For those infants in the exchange or pre-exchange bilirubin zone, failure of
phototherapy has been defined as an inability to observe a decline in bilirubin
of 1-2 mg/dL after 4-6 hours and/or to keep the bilirubin below the exchange
transfusion level.
yy Exchange transfusion is recommended if the TSB rises to these levels despite
intensive phototherapy.
yy For readmitted infants, if the TSB level is above the exchange level,
repeat TSB measurement every 2 to 3 hours and consider exchange if
the TSB remains above the levels indicated after intensive phototherapy
for 6 hours. However, an exchange transfusion (ET) should be performed
at the slightest suspicion of bilirubin encephalopathy irrespective of the
bilirubin value.

2.2 Exchange transfusion for management of hyperbilirubinemia (14)

yy Exchange transfusion should be done by central or peripheral route aiming

replacement of double the baby’s blood volume and by skilled personnel in a
well-equipped centre.
yy Immediate EBT is recommended if infant shows signs of ABE or if TSB is ≥25
mg/dL above the recommended age and risk specific cut off TSB
yy For Rhesus isoimmunization, the best choice would be O (Rh) negative packed
cells suspended in AB plasma. O (Rh) negative whole blood or cross-matched
baby’s blood group (Rh negative) may also be used.
yy For ABO isoimmunization, O group (Rh compatible) packed cells suspended
in AB plasma or O group whole blood (Rh compatible with baby) should
be used.
yy In other situations baby’s blood group should be used. All blood must be cross
matched against maternal plasma.
yy Blood volume used: 2 x (80-100 ml/kg) x birth weight in kg.

20 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
2.3 Other modalities for management of hyperbilirubinemia (14)

yy No role of phenobarbitone, tin mesoporphyrin, Agar, Albumin, charcoal,

cholestyramine, clofibrate, glycerine, chinese herbs, homeopathy, acupuncture,
riboflavin or manna in management of hyperbilirubinemia
yy Routine use of Intravenous immunoglobulin (IVIg) for Rhhaemolytic
disease of newborn and ABOdisease is not recommended as evidence from
studies with lowrisk of bias indicates no benefit in Rhhaemolytic disease of
newborn and studies suggesting benefit in ABO incompatibility had a high
risk of bias. (26)

2.4 What should be the frequency of long term follow up of

neonates with hyperbilirubinemia and what all should be
evaluated at follow up?

yy When infants with hyperbilirubinemia are identified and treated appropriately,

the outcome is excellent with minimal or no additional risk for adverse
neurodevelopmental sequelae.

yy Neonates with hyperbilirubinemia requiring exchange transfusion require:

ŒŒ Follow up (at 3 months and 18 months postnatal age) for formal development
assessment

ŒŒ Hearing evaluation of these neonates by brain stem evoked response

audiometry (prior to 3 months)

yy Subsequent follow up of these neonates is 6 monthly (or more frequently (if the
developmental assessment mandates the same

yy Other follow up (for vaccination, growth and feeding can continue as for a
normal neonate)

Key Recommendations 21
2.4 What information and support should be given to parents/care
givers of babies with neonatal hyperbilirubinaemia?

Offer parents or care givers information about neonatal jaundice but should be
tailored to their needs and expressed concerns. This information should be provided
through verbal discussion backed up by written information whenever possible. (14)

Care should be taken to avoid causing unnecessary anxiety to parents or care-

givers.

Information should include:

yy Factors that influence the development of significant hyperbilirubinaemia
yy How to check the baby for jaundice
yy What to do if they suspect jaundice
yy The importance of recognising jaundice in the first 24 hours and of seeking
urgent medical advice
yy The importance of checking the baby’s nappies for dark urine or pale chalky
stools
yy The fact that neonatal jaundice is common, and reassurance that it is usually
transient and harmless when treated appropriately
yy Reassurance that breastfeeding should continue

Information about treatment including phototherapy

yy Anticipated duration of treatment
yy Reassurance that breastfeeding, nappy-changing and cuddles can usually
continue.
yy Encourage mothers of with jaundice to breastfeed frequently, and to wake the
baby for feeds if necessary.
yy Provide lactation/feeding support to mothers whose baby is visibly jaundiced.
yy Why phototherapy is being considered

22 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
 yy Why phototherapy may be needed to treat significant hyperbilirubinaemia

yy The possible adverse effects of phototherapy

yy The need for eye protection and routine eye care

yy Reassurance that short breaks for feeding, nappy changing and cuddles will not
alter course of jaundice and efficacy of phototherapy

yy What might happen if phototherapy fails

yy Rebound jaundice

yy Potential long-term adverse effects of phototherapy

Information on exchange transfusion

yy Offer parents or care givers information on exchange transfusion including:

yy The baby be admitted to an intensive care bed

yy Why an exchange transfusion is being considered

yy The possible adverse effects of exchange transfusions

yy When it will be possible for parents or care givers to see and hold the baby after
the exchange transfusion.

yy When it will be possible for parents or carers to see and hold the baby after the
exchange transfusion.

Key Recommendations 23
 Methodology of
Development of Guideline

A Task Force was constituted in December 2014 to guide the development of Standard
Treatment Guidelines (STG) in India for application in the National Health Mission. The
Task Force subsequently approved the draft STG development manual of India (Part 1) for
development of adapted guidelines. In addition, it approved a list of 14 topics recommended
by a subgroup of the task force appointed to select prioritized topics for STG development.
These 14 topics are from 10 clinical specialties for which the first set of STGs will be
developed. The topic of detection, management and prevention of hyperbilirubinemia in
term and late preterm newborn infants was dealt by the neonatology sub-group.

Formation of the STG group

A multidisciplinary group composed of a mix of primary care practitioners, family
medicine practitioners, teaching faculty, practicing and academic neonatologists, nurse
practitioners, voluntary sector representatives, and a patient representative was formed
by September 2015. The composition of the subgroup is mentioned in the table below.

Facilitator: Prof Praveen Kumar

Writing Team: Dr Anu Sachdeva, Dr Neeraj Arora, Dr Srinivas Murki, Dr Aparna

Chandrasekaran, Dr Shridhar Gopalakrishnan, Dr Deepak Chawla, Dr Mangla Bharti

Experts: Prof Vinod K Paul, Prof Ashok K Deorari

Primary care Practioner:

Nursing Practioner: Ms Meena Joshi

Patient participant

Methodology of Development of Guideline 25

Scoping the STG
The scope of the STG was discussed at the first clinical subgroup meeting in Delhi in
September 2015

Declaration of interests
All the members of the GDG declare no conflict of interest.

Funding source
NHSRC

Scheduled review
We plan to update the STG every 3 years.

Search and selection of evidence based guidelines

In view of the paucity of time available to develop this guideline, a decision was taken by
the Task Force for the Development of STGs for the National Health Mission that these
STGs would be adopted and/or adapted from existing evidence based guidelines to make
them relevant to our context, resource settings and priorities.

Search and select guidelines

We searched the electronic database MEDLINE via PubMed and the websites www.who.
int (World Health Organization), http://www.guideline.gov (National Guideline Clearing
House of US), http://www.nice.org.uk (National Institute for Clinical & Care Excellence,
UK), www.aap.org (American Academy of Pediatrics), http://www.cps.ca/(Canadian
Pediatric Society), and www.nnfi.org (National Neonatology Forum, India) to search for
existing guidelines on detection, management and prevention of hyperbilirubinemia of
term and late preterm infants.

Step 1
We used the following search strategy: (“jaundice, neonatal”[MeSH Terms] OR
(“jaundice”[All Fields] AND “neonatal”[All Fields]) OR “neonatal jaundice”[All Fields] OR
(“neonatal”[All Fields] AND “jaundice”[All Fields])) AND guideline [ptyp]which revealed 16

26 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
citations of which six were relevant citations. Additional search revealed two additional
guidelines. In addition, we identified another guideline – by National Neonatology Forum,
India – by hand searching.

Step 2
We evaluated the technical quality and the process of development of these guidelines by
the AGREE-GRS instrument (http:// www.agreetrust.org)

Step 3 Adaptation and adoption of recommendations

The Clinical practice guideline ‘Subcommittee on Hyperbilirubinemia’ for Management of
Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was published
by American Academy of Pediatrics in 2004. Thereafter the National Neonatology Forum,
India published the guidelines in 2010 which were adapted from American Academy of
Pediatrics guidelines. The National Collaborating Centre for Women’s and Children’s
Health commissioned by the National Institute for Health and Clinical Excellence published
the NICE guidelines for Neonatal jaundice in May 2010.

We have adopted and/or adapted from existing evidence based guidelines (Neonatal
Jaundice, NICE 2010; updated May 2016, Clinical practice guideline ‘Subcommittee on
Hyperbilirubinemia for Management of Hyperbilirubinemia in the Newborn Infant 35 or
More Weeks of Gestation’, American Academy of Pediatrics, 2004, National Neonatology
Forum, India guidelines, 2010) and tried to make them relevant to our context, resource
settings and priorities

Methodology of Development of Guideline 27

 References

1. Ip S, Chung M, Kulig J, et al. An evidence-based review of important issues

concerning neonatal hyperbilirubinemia. Pediatrics 2004;114:e130-53

2. Report 2002-2003: National Neonatal Perinatal Database Network. New Delhi:

National Neonatology Forum of India; 2004.

3. The Young Infants Clinical Signs Study Group. Clinical signs that predict
severe illness in children under age 2 months: a multicentre study. Lancet.
2008;371:135–42.

4. Burke BL, Robbins JM, Bird TM, Hobbs CA, Nesmith C, Tilford JM. Trends in
hospitalizations for neonatal jaundice and kernicterus in the United States,
1988–2005. Pediatrics. 2009;123:524–32.

5. Tomashek KM, Crouse CJ, Iyasu S, Johnson CH, Flowers LM. A comparison of
morbidity rates attributable to conditions originating in the perinatal period
among newborns discharged from United States hospitals, 1989–90 and 1999–
2000. Paediatr Perinat Epidemiol. 2006;20:24–34.

6. Mwaniki MK, Atieno M, Lawn JE, Newton CR. Long-term neurodevelopmental

outcomes after intrauterine and neonatal insults: a systematic review. Lancet.
2012;379:445–52.

7. Gladstone M. A review of the incidence and prevalence, types and aetiology

of childhood cerebral palsy in resource-poor settings. Ann Trop Paediatr.
2010;30:181–96.

8. Amin SB, Smith T, Wang H. Is neonatal jaundice associated with autism spectrum
disorders: a systematic review. J Autism Dev Disord. 2011;41:1455–63.

References 29
 9. Olusanya BO, Somefun AO. Sensorineural hearing loss in infants with
neonatal jaundice in Lagos: a community-based study. Ann Trop Paediatr.
2009;29:119–28.

10. Maulik PK, Darmstadt GL. Childhood disability in low- and middle-income
countries: overview of screening, prevention, services, legislation, and
epidemiology. Pediatrics. 2007;120Suppl 1:S1–55.

11. Olusanya BO, Ogunlesi TA, Kumar P, Boo NY, Iskander IF, Almeida DF,
Vaucher YE, and Slusher TM. Management of late-preterm and term infants
with hyperbilirubinaemia in resource-constrained settings. BMC Pediatr.
2015; 15: 39.

12. Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M, Ebbesen F, et al.

Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence
and impairment estimates for 2010 at regional and global levels. Pediatr Res.
2013;74Suppl 1:86–100.

13. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia.

Management of hyperbilirubinemia in the newborn infant 35 or more weeks of
gestation. Pediatrics. 2004 Jul;114(1):297-316.

14. Neonatal Jaundice 2010 Available at https://www.nice.org.uk/guidance/cg98/

evidence/full-guideline-245411821. Accessed on 18 May, 2016

15. Narang A, Gathwala G, Kumar P. Neonatal jaundice: an analysis of 551 cases.

Indian Pediatr 1997;34:429-32.

16. Olusanya BO, Ogunlesi TA, Slusher TM. Why is kernicterus still a major cause
of death and disability in low and middle-income countries? Arch Dis Child.
2014;99:1117–21.

17. Bhutani VK, Johnson LH. Managing the assessment of neonatal jaundice:
importance of timing. Indian J Pediatr. 2000 Oct;67(10):733-7.

18. Bhutani VK, Cline BK, Donaldson KM, Vreman HJ. The need to implement
effective phototherapy in resource-constrained settings. Semin Perinatol.
2011;35:192–7.

19. Cline BK, Vreman HJ, Faber K, Lou H, Donaldson KM, Amuabunosi E, et al.
Phototherapy device effectiveness in Nigeria: irradiance assessment and
potential for improvement. J Trop Pediatr. 2013;59:321–5.

30 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
20. Pejaver RK, Vishwanath J. An audit of phototherapy units. Indian J Pediatr.
2000;67:883–4.

21. Owa JA, Ogunlesi TA. Why we are still doing so many exchange blood transfusion
for neonatal jaundice in Nigeria. World J Pediatr. 2009;5:51–5.

22. NNF 2010. Available at http://aimaonline.org/iap-neochap-2013/uploads/

acd-corner/nnf_guidelines-2011.pdf. Accessed on 18th May, 2016
23. Bhutani VK, Stark AR, Lazzeroni LC, Poland R, Gourley GR, Kazmierczak
S, Meloy L, Burgos AE, Hall JY, Stevenson DK; Initial Clinical Testing
Evaluation and Risk Assessment for Universal Screening for
Hyperbilirubinemia Study Group. Predischarge screening for severe
neonatal hyperbilirubinemia identifies infants who need phototherapy. J
Pediatr. 2013 Mar;162 (3):477-482
24. Kramer LI.Advancement of dermal icterus in jaundiced newborn.Am J Dis
Child 1969;118:454-8.
25. van Imhoff DE, Dijk PH, Weykamp CW, Cobbaert CM, Hulzebos CV;
BARTrial Study Group. Measurements of neonatal bilirubin and albumin
concentrations: a need for improvement and quality control. Eur J Pediatr
2011;170:977-82.
26. Louis D, More K, Oberoi S, Shah PS. Intravenous immunoglobulin in
isoimmune haemolytic disease of newborn: an updated systematic review
and meta-analysis.
27. Arch Dis Child Fetal Neonatal Ed. 2014 Jul;99(4):F325-31. Epub 2014
Feb 10.

References 31
 Appendix - A

Phototherapy units available in the market

S.No. Type of unit Principals Dealer Unit cost (Rs.)
A. White fluorescent tube * * 20,000
(6 to 8; 20w)

Double surface 35,000

Fluorescent
B. Compact fluorescent Medela Rohit Surgials 60.000
lights (6 to 8; 21w) Phoenix Phoenix 25,000
Nice Neotech SBP Mediare 20,000
SS Technomed Global Medical Sys 20,000
Meditrin Meditrin 25,000
C.* Blue light (2 to 4; 20w) Atom Vishal Surgical 40,000-2,00,000
and white (2 to 4; 20w) Medela Rohit Surgical
Drager Drager
Wyer Rustagi Surgical
Ameda Medisphere
Heraeus Medex
Choongwae Global Medical
Phoenix Phoenix

Appendix - A 33
 S.No. Type of unit Principals Dealer Unit cost (Rs.)
D. Halogen bulb Datex-Ohmeda Phoenix 60,000-90,000
(Single; 150w; 21v) Olympic Rustagi Surgical
Hillrom Phoenix
E. Bili-Blanket Fibreoptic Ginevri Global Med 1,00,000-2,50,000
Bili BedTM Wallaby System
Medela Global Med.
Olympic System
Datex- Rohit Surgical
Ohmeda Rohit Surgical
Ibis medical Ibis medical

Principals Dealer
LED Shrichitra Shrichitra 40,000
Lullaby LED GE GE 60,000
LED high intensity spot Fanem Fanem 80,000
(Bilitron 3006/ Bilitron bed 5006/
Bilitron sky 5006)
LED high intensity spot Phoenix Phoenix 40,000
Sunshine LED SS technomed 40,000
Ibis medical Ibis Medical 50,000

34 Detection, Management and Prevention of Hyperbilirubinemia in Term and Late Preterm Newborn Infants
Note
Note
 HEALTH M
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NATION

ISSI N
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MINISTRY OF HEALTH AND FAMILY WELFARE

Government of India
Nirman Bhawan, New Delhi