neonatal jaundice2

7/28/2019 Neonatal Jaundice2

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Neonatal Jaundice

Alan Gill MD

1/2/03


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Objectives

Understand etiology and pathophysiology

of neonatal jaundice and kernicterus

Identify high risk conditions

Understand limits of clinical exam

Describe appropriate evaluation

Apply appropriate treatment to term andnear term infants


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Epidemiology

Clinical Jaundice (> 5mg%)

65% full-term infants (> 37 weeks in AAP

guideline)

peak 3-5 days

80% preterm infants

peak 5-7 days

Exaggerated Hyperbilirubinemia

(>12.8mg%)

4% African-Americans

6-10% Caucasian

25%

Asian (>20mg% in 2%)


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Effect of Type of Feeding

2/3 of breastfeeding infants will have

chemical jaundice for 2-3 weeks

TSB > 12mg% in 12% BF vs. 4% FF

TSB > 15mg% in 2% BF vs. 0.3% FF


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The hyperbili pendulum swings

AAP currently revising its 1994 guideline

JACHO alert due to several case reports

of kernicterus in healthy newborns

Especially near term 35-38 weeks,

dehydrated breastfeeding, and with

extremely high bilirubin levels


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Incidence and Cause of Severe

Hyperbilirubinemia in term newborns

73/51,387 newborns > 2,000 grams birth weight

and >36 week gestation reached 25mg/dl total

bili = 1.4/1,000

306 readmitted for hyperbili, (ave 18.5, range12.5-29.1)

94.8 % of unknown cause or breast feeding

3.6% ABO hemolytic disease

1.0% cephalohematoma/birth trauma

0 cases of sepsis


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Kernicterus Registry for term

and near-term infants 90 total since 1992 61with full data and readmitted in one week

20/61 jaundice noted by parent and nurse but not measured

until readmitted Predischarge total bili measured in only 16/61

10/16 95%, 15/16 40%, 1/16 < 40% bili/age

Peak total bili values median 38, range 21.5-50 mg/dl

No early F/U appoint (within 48 hours) in 44/61,instead come

back in 1-2 weeks,

Early appointments, 14 appointments made and kept, 7 early

and measured, 7 early and not measured, 3 appointments

not kept


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Kernicterus

Acute

First 1-2 days, poor feeding, stupor, hypotonia, seizures

3-7 days irritability, hypertonia of extensor muscles,fever

> 1 week hypertonia (opisthotonus, retrocollis), stupor

or coma, shrill cry

Chronic 1st year limited upward gaze, movement disorders

(chorea, ballismus, tremor), hearing loss

> 1 year old CP, movement disorders, hearing loss,

MR, gaze paresis


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Kernicterus Risk Factors

TSB level > 25-30 mg/dl

Acidosis

Increased free bilirubin low albumin, drug displacement

Blood-brain barrier disruption

prematurity, sepsis, ischemia


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Kernicterus cases

potentially correctable causes Early discharge (


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Common Clinical Risk Factors

for Severe Hyper-bilirubinemia

Jaundice in the first 24 hours

Visible jaundice at discharge

Previous jaundiced sibling Near term gestation 35-38 weeks

Exclusive breastfeeding

East Asian (4), Mediterranean (1), African origin(12) (G6PD deficiency), 19/61 kernicterus cases= G6PD

Bruising, cephalohematoma, birth trauma

Hemolysis risk, O + maternal blood type, sepsis


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Overproduction

Infection

Viral hepatitis

TORCH

Sepsis DIC

Immune Hemolysis

Rh isoimmunization

Atypical Antibody

isoimmune Inherited RBC membrane

defects

Spherocytosis,Elliptocytosis

Stomatocytosis,pyknocytosi

s

Inherited RBC enzymes G6PD deficiency

Pyruvate kinase deficiency

Hemoglobinopathies Thallesemias, sickle cell

(rare due to fetal Hgbprotection)

Other Infant of diabetic mother

Polycythemia Birth trauma


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Glucose 6 Phosphate

Deficiency Most frequent inherited RBC disorder

X linked recessive, more likely in boys

Can be triggered by infection, medications

Class 1-5 depending on level of deficiency

Present in 10% of African American male newborns but notexpressed, needs another yet to be defined cofactor

Lab testing: Smear hemolysis, Coombs neg,RBC assay for G6PD

High levels = normal Normal levels = normal unless high retic count which may be

deficiency falsely covered by high retic count, normal is 10.8-16.2 u/g Hb

Low levels = low


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Decreased Clearance

Impaired excretion inthe enterohepaticcircuit Prematurity

Breast Milk Jaundice Late onset enzyme

competition

Structural

Bowel obstruction

Pyloric stenosis

Meconium ileus

Biliary atresia

Albumin Displacement Drug induced

Impaired metabolism Endocrine

Hypothyroid

Hypopituitary

Inherited Metabolic Inborn errors of metab

galactosemia

Tyrosinosis

Hypermethioninemia

Crigler-Nijjarsyndrome

Gilbert syndrome

Rotor syndrome

Cystic fibrosis

Alpha-1 antitrypsin


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Medications increasing bilirubin

Sulfisoxazole (displacement or G6PD

hemolysis)

Ceftriaxone (displacement from albumin) Nitrofurantoin (capable of inducing G6PD

hemolysis, manufacturer warns against use at

term, no reported case of hemolytic anemia in

an in-utero exposed newborn)

Streptomycin, Benzyl alcohol,

Chloramphenicol


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Breast feeding and Jaundice

Two peaks

Early days 2-5

Associated with inadequate volume and calories

Do not treat with dextrose water

Supplement with formula, cup or nipple attachedbutterfly tubing

Late, persisting for weeks, Mothers milk contains

5-pregnane-3, 20--diol, or nonesterified long

chain fatty acids that competitively inhibit glucuronyltransferase

Contains a glucuronidase

Will diagnostically decline rapidly if breast milk not

given for 12-24 hrs, bili declining by up to 2 mg/dl/12hr


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Breast feeding and Jaundice

Watch for weight loss and urine output dehydration in first 3-5 days of life,

10% weight loss, < 5 wet diapers per day by day 3 oflife

supplement if dehydration

Approximately one third of healthy breast fednewborns will have persistent jaundice after 2weeks

should not be direct bilirubin (dark urine orlight stools)

do not have to interrupt breast feeding

investigate those lasting beyond 3 weeks


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Questions for Jaundice

Term healthy physiologic vs. pathologic or

preterm or ill?

How high is the total serum bilirubin?

What treatment is indicated?

What follow-up is needed?


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Neonatal Jaundice

Physiologic or Pathologic? Physiologic

Term 37 weeks Healthy

Higher red cell turnover

Shorter red cell lifespan Decreased ability to excrete

Average full term newbornpeaks at 5-6 mg/dl total bili

Peak at 3-5th day of life,

onset after 24 hours Peaks 7 days in Asian and

preterm

Hematocrit drops in 1st month

Average term 51 to 44@1mo

2 SD term 42 to 33 @1mo

Pathologic

Onset in first 24 hours

direct bili >1.5 mg/dl

dark urine, pale stool

rate of rise > 0.5mg/dl/hour

ill neonate with sepsis or

asphyxia, or symptomatic

Prematurity

+ Family hx of G6PD,hemolysis

hemolytic disease such

as ABO incompatibility

poor response to rx

persistence > 3 weeks


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Direct hyperbilirubinemia:

PathologicDirect Bilirubin 1.5 mg/dl

hepatitis

biliary obstruction, atresia infection: viral (TORCH) or sepsis

inborn errors of metabolism, galactosemia,

tyrosinosis, cystic fibrosis, alpha 1

antitrypsin

hyperalimentation

hypothyroidism


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Clinical Signs of Neonatal Jaundice as

a Symptom of Other Disease

Vomiting

Lethargy

Poor feeding

Hepatosplenomegal

y

Excessive weight

loss Apnea

Tachypnea

Pallor

Rubor

Temperature

instability

Birth injury


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Clinical Factors Suggesting Hemolytic

Disease

Family history of significant hemolytic

disease

Sibling with severe neonatal jaundice

Ethnicity suggestive of inherited disease Asians

Greeks

Sardinians

Sephardic Jews

Black


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Zone 1 head - clavicle 5

Zone 2 clavicle-umbilicus 6-8

Zone 3 umbilicus-knees 9-12

Zone 4 knees-ankles 13-15

Zone 5 palms + soles 15

Clinical Exam:

Unreliable


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Clinical Exam: Unreliable


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Clinical Exam: Unreliable

Poor correlation inter-observer and with

serum bilirubin

Best cut appears to be jaundice to nipples

for bili > 12.0 mg/dl

97% sensitive

SnOut (negative high sensitivity test helps rule out

disease)

19% specific

Arch Pediatr Adolesc Med. 2000; 154:391-4


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Measurements

Estimates of serum bilirubin concentrations that are based

solely on clinical examination are not reliable

Serum bilirubin

Transcutaneous bilirubin Older devices affected by skin pigmentation

Newer multi-wavelength spectral reflectance

correlate 0.88 with the serum value,

example SpectRx, 3 mg/dl

? Confirm values > 40% per age

Carbon monoxide exhaled


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Transcutaneous Accuracy

Data of 99 measurements within 30 min of serum total bili


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AAP Provisional Committee for Quality Improvement

Subcommittee on Hyperbilirubinemia

Comprehensive literature review

Retrospective

Epidemiologic data

The recommendations that follow....are based on

evidence when appropriate data exist and derived from

consensus when data is lacking. In these guidelines, the AAP has attempted to describe a

range of acceptable practices, recognizing that adequate

data are not available from the scientific literature to

provide more precise recommendations.

Practice Parameter: Management of

Hyperbilirubinemia in the Healthy Term Newborn

Pediatr ics 1994;94:558-565 & 1995;95:458-461


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Guideline Recommendations:

Evaluation

Maternal prenatal testing

ABO & Rh(D) typing

Antibody screen for isoimmune antibodies

Save cord blood for direct Coombs, blood

type, and Rh whenever:

mother has not had any prenatal care

mother is Rh negative

mothers blood type is Group O


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Laboratory Testing

Bilirubin, total and direct

clinical suspicion

Type, Rh, direct coombs, CBC, retic,

smear O positive mother, (1 in 5 coombs + with significant hyperbili)

Onset jaundice in < 24 hours,

Total bili 95% for age

Hct < 40, or suspicion of hemolysis

Family history hemolytic anemia, severe neonatal jaundice,

Ethnic origin for G6PD

G6PD for bili > 15 + appropriate ethnic group


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IncreasedIndirectBilirubin

Positive Coombs

IsoimmunizationRh

ABO

Other

Negative Coombs


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Direct Coombs Testing

Strongly positive:

Rh

Kell

Kidd Duffy

Negative or weakly

positive:

Anti-A


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Set-up

Mothers blood type = O

Infants blood type = A or B

15% of all pregnancies in the U.S.

3% develop clinically significant jaundice

50% occur in the first born


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Hemolysis consider present if

Hct < 45%

Abnormal blood smear with 3-4+

spherocytes

Reticulocyte count is 4.5% in the first 72

hrs, or

Reticulocyte count is >1-2% in the first 1-2wks.

ABO Incompatibility


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Positive Coombs

IsoimmunizationRh

ABO

Other

Negative Coombs

Hematocrit

High

Twin transfusion

Maternal fetal transfusionDelayed cord clamping

SGA infant

Normal or Low


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Positive Coombs

IsoimmunizationRh

ABO

Other

Negative Coombs

Hematocrit

High

Twin transfusion

Maternal fetal transfusionDelayed cord clamping

SGA infant

Normal or Low


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Normal or Low Hematocrit

Reticulocyte CountD1=7

D3=3

D7=1


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D3=3

D7=1Increased

RBC Morphology

Normal


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D3=3

D7=1Increased

RBC Morphology

Characteristic Non-specific

Spherocytosis G6PD deficiency

Eliptocytosis Pyruvate kinase deficiency

Stomatocytosis Other hereditary enzyme deficiencyDIC

Normal


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D3=3

D7=1Increased

RBC Morphology


Spherocytosis G6PD def.

Eliptocytosis PK def.

Stomatocytosis Other hered.enzyme def.

DIC

Normal

Extravascular Blood

Cephalohematoma

Other hemorrhage


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D3=3

D7=1Increased

RBC Morphology





DIC

Normal

Extravascular Blood

Cephalohematoma

Other hemorrhage

Increased EHCBreastfeeding

Pyloric stenosis

SBO or LBO

Swallowed blood


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D3=3

D7=1Increased

RBC Morphology





DIC

Normal

Extravascular Blood

Cephalohematoma

Other hemorrhage

Increased EHCBreastfeeding

Pyloric stenosis

SBO or LBO

Swallowed blood

Metabolic-Endocrine

Cong. glucuronyl trans.deficiency

Galactosemia

Hypothyroidism

Infants of DM mothers


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Pre-discharge bilirubin

% pre-discharge

bilirubin

Probability of

subsequent high bili

>95% 2/5

76-95% 1/8

40-75% 1/46


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Pre-discharge bilirubin

Hours of life 40% 75% 95%

24 hours 5 mg/dl 6.5 mg/dl 8 mg/dl

48 hours 7.5 mg/dl 11 mg/dl 13 mg/dl

72 hours 11 mg/dl 13.5 mg/dl 16 mg/dl

96 hours 12 mg/dl 15 mg/dl 17 mg/dl


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Follow-up

Farnoff has shown that babies discharged

at 48-72 hours have same risk of severe

hyperbili as those discharged


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The Rate of Rise

Newborns are not once a day modules, bilirubinis rising until peak at day 3-5

In first 24 hours if jaundiced recheck in 4 hoursand calculate rate of rise

24-48 hours consider calculate rate of rise in 8-12 hours with second total bilirubin

>48 hours if is < 75% for age can check in 24

hours Rate of rise of 0.5mg/dl/hour is too fast and

should be investigated


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Treatments

Food and stooling Removes via enterohepatic elimination

Phototherapy

forms lumirubin a water soluble compound effectiveness depends on spectrum and dose

Blue light 450nm most effective, green penetrates deepest

Standard 8 tubes of florescent white bulbs = 6-12microwatts/cm2

Fiber-optic blankets = up to 50 microwatts/cm2 Distance 15-20 cm

Exchange transfusion 2% mortality, 12% severe complications


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Effective Phototherapy

Infant in bassinette not incubator

needs to be within 15-20cm distance for blue or whiteflorescent bulbs

Halogen bulbs can burn, use manufacturers recs

Fiberoptic pads to give double phototherapy

Twice as effective as single in low birth weight

50% better than single in term newborns

Naked

Eye covers

Hydration

Breast milk or formula if not dehydrated

Milk plus IV hydration if dehydrated

G id li R d ti


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Guideline Recommendations:

Treatment

No evidence to support excess IV fluids

Phototherapy may be discontinued:

Term infant TSB < 14mg/dL Preterm infant (34-37weeks)

> 5-6 days old TSB @ 12

< 5 days old TSB @ 10

Ave. TSB rebound after PT stopped = 1mg/dL

1994 AAP G idelines


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1994 AAP Guidelines

For Healthy Term Physiologic

Age in hours ConsiderPhototherap

PhotoTherapy

Exchange ifPhoto fails

Exchangeand photo

25-48 12 15 20 25

49-72 15 18 25 30

>72 17 20 25 30

Intensive phototherapy should yield 1-2 mg/dl drop in 4-6 hr


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ABO incompatibility hemolysis

Generally phototherapy interventions are instituted

3mg/dl lower than those for non-hemolytic healthyterm in the 1994 guidelines

87.7% (202/230) did not require phototherapy

never were greater than total bili of 12 mg/dl Phototherapy for term healthy ABO coombs+

5mg/dl

24-48 hours = >10mg/dl

Exchange transfuse for >20mg/dl F/u Hct

All at 6 week

Earlier, one week if t bili > 15 mg/dl


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Management of Hyperbilirubinemia in the

Term Newborn: TSB levels mg/dLSick

2012-15> 72

2012-1549-72

2010-1225-48

187-10Up to 24

Exchange

Transfusion

PhototherapyAge

(hrs)

Harriet Lane Preterm Photo


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Harriet Lane Preterm Photo-

therapy Guidelines < 1 week old

>20>15>2500 gms

18-2010-151500-2500

gms

15-187-101000-1500

gms

12-15 mg/dl5-7 mg/dl500-1,000 gms

Consider

Exchange

Transfusion

PhototherapyWeight (kg)

2000 edition

weeks)37Preterm Newborn (


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)(:

TSB levels mg/dL

1710> 2000

158-101501-2000

10-126-81001-1500

8-104-6Up to 1000

Exchange

Transfusion

PhototherapyWeight (gm)


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Conclusions

Neonatal Jaundice is common (> 50% of

newborns)

Family history, maternal blood type andnewborn clinical setting help to define higher

risk groups

Unreliable clinical exam requires low threshold

for serum bilirubin

Nomograms of pre-discharge total bili per age

help prognostication/follow up testing plan

Early followup of all newborns discharged with


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References

Johnson, L et al, System-based approach to management ofneonatal jaundice and prevention of kernicterus, J Pediatr 2002,140:396-403

Subcommittee on Neonatal Hyperbili, Neonatal Jaundice andKernicterus, Pediatrics, 2001, p 763

AAP Practice Parameter: Management of Hyperbilirubinemia inthe Healthy Term Newborn, Pediatrics 1994, 94:588-565

Bhutani, V et al, Predictive Ability of a Predischarge hourspecific Serum Bilirubin for Subsequent SignificantHyperbilirubinemia in Healthy Term and Near-term Newborns,Pediatrics, Vol 103, #1, January 99, p 6-14

Moyer VA et al, Accuracy of Clinical Judgement in NeonatalJaundice, Arch Pediatr Adolesc Med, 2000; 154:391-394

www.cdc.gov/ncbddd/dd/kernicterus2.htm

neonatal jaundice2

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