M. JAUNDICE
Increase load of bilirubin to be
Jaundice and Hyperbilirubinemia in the Newborn
➔ Hyperbilirubinemia: common, benign problem
in neonates
➔ Jaundice: observed during 1st wk after birth in
60% of term infants & 80% of preterm infants
➔ Yellow color results from accumulation on
unconjugated, nonpolar, lipid-soluble bilirubin
pigment in the skin
➔ Unconjugated bilirubin:
◆ Indirect-acting by nature of van den
Bergh reaction
◆ End product of heme-protein
catabolism from enzymatic reactions by
heme-oxygenase & biliverdin reductase
& non enzymatic reducing agents in the
reticuloendothelial cells
➔ Jaundice may be partly caused by deposition of
pigment from conjugated bilirubin
◆ end product from indirect,
unconjugated bilirubin that has
undergone conjugation in the liver cell
microsome by the enzyme uridine
diphosphoglucuronic acid
(UDP)-glucuronyl transferase to form
polar, water-soluble glucuronide of
bilirubin (direct-reacting)
➔ Bilirubin: antioxidant
➔ Elevations of indirect, unconjugated bilirubin:
potentially neurotoxic
➔ Conjugated form: not neurotoxic
➔ Direct hyperbilirubinemia: indicates potentially
serious hepatic disorders or systemic illness
Etiology
➔ Neonatal period: metabolism of bilirubin is in
transition from fetal stage to adult stage
➔ Fetal stage: placenta is the principal route of
elimination of lipid-soluble, unconjugated
bilirubin
➔ Adult stage: water-soluble conjugated form is
excreted from hepatic cells into biliary system
& GI
➔ Unconjugated hyperbilirubinemia: caused or
increased by any factor that
A.
metabolized by the liver (hemolytic
anemias, polycythemia, bruising or
internal hemorrhage, shortened red
blood cell (RBC) life as a result of
immaturity or transfusion of cells,
increased enterohepatic circulation,
infection)
B. Damages or reduces activity of
transferase enzyme or other related
enzymes (genetic deficiency, hypoxia,
infection, thyroid deficiency)
C. Competes for or blocks the transferase
enzyme (drugs & other substances
requiring glucuronic acid conjugation)
D. Leads to an absence or decreased
amounts of enzyme or to reduction of
bilirubin uptake by liver cells (genetic
defect, prematurity)
➔ Gene polymorphisms in hepatic uridine
diphosphate glucuronyltransferase isoenzyme
1A1 (UGT1A1) & solute carrier organic anion
transporter 1B1 (SLCO1B1) (alone or in
combination): influence incidence of neonatal
hyperbilirubinemia
➔ Toxic effects of elevated serum concentrations
of unconjugated bilirubin: increased by factors
that reduce the retention of bilirubin in the
circulation (hypoproteinemia, displacement of
bilirubin from it's binding sites on albumin by
competitive binding of drugs such as
sulfisoxazole & moxalactam, acidosis, &
increased free fatty acid concentration
secondary to hypoglycemia, starvation, or
hypothermia)
➔ Neurotoxic effects: directly related to
permeability of blood-brain barrier & nerve
cell membranes and neuronal susceptibility to
injury
◆ Adversely influenced by asphyxia,
prematurity, hyperosmolality, infection
➔ Early & frequent feeding: decreases serum
levels of bilirubin
➔ Breastfeeding & dehydration: increase serum
levels of bilirubin
 ➔ Delay in passage of meconium, which contains 1
mg bilirubin/dL: contribute to jaundice by
enterohepatic recirculation after deconjugation
by intestinal glucuronidase
➔ Oxytocin (in the mother) & chemicals in the
nursery such as phenolic detergents: may
produce unconjugated hyperbilirubinemia
Metabolism of bilirubin in the neonatal period
➔ Neonatal production rate of bilirubin: 6-8
mg/kg/hr
➔ Adults: 3-4 mg/kg/hr
➔ Water-insoluble bilirubin is bound to albumin
➔ At plasma-hepatocyte interface, a liver
membrane carrier (bilitranslocase) transports
bilirubin to a cytosolic binding protein (ligandin
or Y protein, aka glutathione S-transferase),
which prevents back-absorption to plasma
➔ Bilirubin converted to → bilirubin
monoglucuronide (BMG)
➔ Neonates excrete more BMG than adults
➔ In fetus, conjugated lipid-insoluble BMG &
bilirubin diglucuronide (BDG): must be
deconjugated by tissue B-glucuronidases to
facilitate placental transfer of lipid-soluble
unconjugated bilirubin across placental
membranes
➔ After birth, intestinal or milk-containing
glucuronidases: contribute to enterohepatic
recirculation of bilirubin & development of
hyperbilirubinemia
Clinical Manifestations
➔ Jaundice: usually appears during early neonatal
period
➔ Jaundice from deposition of indirect bilirubin in
the skin: bright yellow or orange
➔ Jaundice of obstructive type (direct bilirubin):
greenish or muddy yellow cast
➔ Jaundice usually becomes apparent in
cephalocaudal progression (face → abdomen
→ feet) as serum levels increase
➔ Dermal pressure: reveal anatomic progression
of jaundice
◆ Face: 5 mg/dL
◆ Mid-abdomen: 15 mg/dL
◆ Soles: 20 mg/dL
➔ Clinical examination CANNOT reliably estimate
serum levels
➔ Noninvasive techniques for transcutaneous
measurement of bilirubin that correlate w/
serum levels: used to screen infants
➔ Determination of serum bilirubin level:
indicated in px w/ elevated age-specific
transcutaneous bilirubin measurement →
jaundice → risk for hemolysis or sepsis
➔ Infants w/ severe hyperbilirubinemia: lethargy &
poor feeding; without treatment, can progress
to acute bilirubin encephalopathy (kernicterus)
Differential Diagnosis
➔ Distinction between physiologic & pathologic
jaundice relates to:
◆ Timing
◆ Rate of rise
◆ Extent of hyperbilirubinemia
➔ Some of same causes of physiologic jaundice
can result in pathologic jaundice:
◆ Large RBC mass
◆ Decreased capacity for bilirubin
conjugation
◆ Increased enterohepatic circulation
➔ Evaluation should be determined on basis of:
◆ Risk factors
◆ Clinical appearance
◆ Severity of hyperbilirubinemia
Check Table 123.3 (Nelson’s, page 954)
➔ Jaundice present at birth or w/in 1st 24 hrs after
birth: pathologic; requires immediate attention
◆ Erythroblastosis fetalis
◆ Concealed hemorrhage sepsis
◆ Congenital infections
◆ Syphilis
◆ Cytomegalovirus
◆ Rubella
◆ Toxoplasmosis
➔ Hemolysis: rapid rise in serum bilirubin (>0.5
mg/dL/hr, anemia, pallor, reticulocytosis,
hepatosplenomegaly, positive family history
➔ Unusually high proportion of direct-reacting
bilirubin: jaundice in infants who received
 intrauterine transfusions for erythroblastosis
fetalis
➔ Jaundice that appears on 2nd or 3rd day:
physiologic; may represent more severe form
◆ Familial nonhemolytic icterus
(Crigler-Najjar Syndrome)
◆ Early-onset breastfeeding jaundice
➔ Jaundice appearing after 3rd day & w/in 1st
week: bacterial sepsis or urinary tract infection,
syphilis, toxoplasmosis, CMV, enterovirus
➔ Jaundice secondary to extensive ecchymosis or
blood extravasation: occur during 1st day or
later, premature infants
➔ Polycythemia: may lead to early jaundice
➔ Differential diagnosis for jaundice first
recognized after the 1st week of life:
◆ Breast milk jaundice
◆ Septicemia
◆ Congenital atresia or paucity of bile
ducts
◆ Hepatitis
◆ Galactosemia
◆ Hypothyroidism
◆ CF
◆ Congenital hemolytic anemia crisis
related to RBC morphology & enzyme
deficiencies
➔ Differential diagnosis for persistent jaundice
during the 1st month of life:
◆ Hyperalimentation-associated
cholestasis
◆ Hepatitis
◆ Cytomegalic inclusion disease
◆ Syphilis
◆ Toxoplasmosis
◆ Familial nonhemolytic icterus
◆ Congenital atresia of the bile ducts
◆ Galactosemia
◆ Inspissated bile syndrome following
HDN
➔ Physiologic jaundice may be prolonged for
several weeks: infants w/ hypothyroidism or
pyloric stenosis
➔ Regardless of gestation or time of appearance of
jaundice, px w/ significant hyperbilirubinemia &
w/ sx or signs require complete diagnostic
evaluation
◆ Determination of direct & indirect
bilirubin fractions
◆ Hemoglobin
◆ Reticulocyte count
◆ Blood type
◆ Coombs test
◆ Examination of peripheral blood smear
➔ Indirect hyperbilirubinemia, reticulocytosis, &
smear w/ evidence of RBC destruction:
hemolysis
➔ In the absence of blood group incompatibility:
non-immunologically induced hemolysis
➔ Reticulocyte count, coombs test result, & direct
bilirubin are normal: physiologic or pathologic
indirect hyperbilirubinemia may be present
➔ If indirect hyperbilirubinemia is present,
diagnostic possibilities:
◆ Hepatitis
◆ Congenital bile duct disorders (biliary
atresia, paucity of bile ducts, Byler
disease)
◆ Cholestasis
◆ Inborn errors of metabolism
◆ CF
◆ Congenital hemosiderosis
◆ Sepsis
Check Table 123.3 (Nelson’s page 954)
Check Table 123.4 (Nelson’s page 955)
Physiologic Jaundice (Icterus Neonatorum)
➔ Normal indirect bilirubin in umbilical cord
serum: 1-3 mg/dL; rises at rate of <5 mg/dL/24
hrs
➔ Jaundice becomes visible on 2nd or 3rd day
➔ Peak between 2nd-4th day at 5-6 mg/dL
➔ Decreasing to <2 mg/dL between 5th-7th days
after birth
➔ Physiologic; increased bilirubin production due
to breakdown of fetal RBCs combined w/
transient limitation in conjugation of bilirubin by
immature neonatal liver
➔ 6-7% full-term infants : indirect bilirubin levels
>13 mg/dL
➔ <3% full-term infants: >15 mg/dL ◆ Intestinal obstruction
➔ Risk factors: ➔ Jaundice w/ pyloric stenosis: result of caloric
◆ Maternal age deprivation, deficiency of hepatic
◆ Race (chinese, japanese, korean, native UDP-glucuronyl transferase, increase in
american) enterohepatic circulation of bilirubin from ileus
◆ Maternal diabetes ➔ Premature infants: rise in serum bilirubin same
◆ Prematurity or slower but of longer duration than in term
◆ Drugs (vitamin K, novobiocin) infants
◆ Altitude ➔ Peak levels of 8-12 mg/dL: not reached until
◆ Polycythemia 4th-7th day
◆ Male sex ➔ Jaundice infrequently observed after 10th day,
◆ Trisomy 21 maturation of mechanisms for bilirubin &
◆ Cutaneous bruising excretion
◆ Blood extravasation ➔ Diagnosis of physiologic jaundice in term or
(cephalohematoma) preterm infants: excluding known causes of
◆ Oxytocin induction jaundice on basis of history, clinical findings, &
◆ Breastfeeding lab data
◆ Weight loss (dehydration or caloric ➔ A search to determine cause of jaundice:
deprivation) ◆ Appears in 1st 24 -36 hrs after birth
◆ Delayed bowel movement ◆ Serum bilirubin is rising at a rate faster
◆ Family history or sibling who had than 5 mg/dL/24hr
jaundice ◆ Serum bilirubin >12 mg/dL in full-term
➔ Infants w/o risk factors: indirect bilirubin levels infant (absence of risk factors) or 10-14
rarely rise >23 mg/dL; infants w/ several risk mg/dL in preterm
factors are more likely to have higher bilirubin ◆ Jaundice persists after 10-14 days after
levels birth
➔ Breastfeeding, variant-glucuronosyltransferase ◆ Direct bilirubin fraction is >2 mg/dL at
(1A1), & alterations of organic anionic any time
transporter-2 gene: increase risk of ➔ Factors suggesting pathologic cause of jaundice:
hyperbilirubinemia ◆ Family hemolytic disease
➔ Predicting w/c neonates are at risk for ◆ Pallor
exaggerated physiologic jaundice: hour-specific ◆ Hepatosplenomegaly
bilirubin levels in the 1st 24-72 hrs of life ◆ Splenomegaly
➔ Transcutaneous measurements of bilirubin: ◆ Failure of phototherapy to lower
linearly correlated w/ serum levels; can be used bilirubin level
for screening ◆ Vomiting
➔ Indirect bilirubin levels in full-term infants: ◆ Lethargy
decline to adult levels (1 mg/dL) by 10-14 days ◆ Poor feeding
of life ◆ Excessive weight loss
➔ Persistent indirect hyperbilirubinemia beyond 2 ◆ Apnea
weeks: ◆ Bradycardia
◆ Hemolysis ◆ Abnormal vital signs (hypothermia)
◆ Hereditary glucuronyl transferase ◆ Light-colored stools
deficiency ◆ Dark urine positive for bilirubin
◆ Breast milk jaundice ◆ Bleeding disorder
◆ Hypothyroidism ◆ Signs of kernicterus
 Jaundice associated with Breastfeeding
Pathologic Hyperbilirubinemia
➔ Jaundice & its underlying hyperbilirubinemia:
pathologic if the time of appearance, duration,
or pattern varies significantly from that of
physiologic jaundice, or if the course is
compatible w/ physiologic jaundice but other
reasons exist to suspect that the infant is at
special risk for neurotoxicity
➔ Risk factors for abnormal elevation of
unconjugated bilirubin:
◆ Asian race
◆ Prematurity
◆ Breastfeeding
◆ Weight loss
➔ Exaggerated physiologic jaundice &
hyperbilirubinemia of the newborn: primary
problem is deficiency or inactivity of bilirubin
glucuronyl transferase (Gilbert syndrome)
rather than excessive load of bilirubin for
excretion
➔ Combination of glucose-6-phosphate
dehydrogenase (G6PD) deficiency & mutation of
the promoter region of UDP-glucuronyl
transferase-1: indirect hyperbilirubinemia in the
absence of signs of hemolysis
➔ Nonphysiologic hyperbilirubinemia: mutations
in the gene for bilirubin UDP-glucuronyl
transferase
➔ Greatest risk associated w/ indirect
hyperbilirubinemia: development of
bilirubin-induced neurologic dysfunction; occurs
w/ high indirect bilirubin levels
➔ Kernicterus (bilirubin encephalopathy): depends
on the level of indirect bilirubin, duration of
exposure to bilirubin elevation, cause of
jaundice, infant’s well-being
➔ Neurologic injury including kernicterus: may
occur at lower bilirubin levels in preterm infants
& presence of asphyxia, intraventricular
hemorrhage, hemolysis, drugs that displace
bilirubin from albumin
➔ Exact serum indirect bilirubin level that is
harmful for VLBW infants is unclear
➔ Significant elevation in unconjugated bilirubin
(breast milk jaundice):
◆ Develops in 2% breastfed term infants
after the 7th day
◆ Maximal concentrations 10-30 mg/dL
during the 2nd-3rd wk
➔ Breastfeeding continued → bilirubin gradually
decreases but may persist for 3-10 weeks at
lower levels
➔ Nursing discontinued → serum bilirubin falls
rapidly; reaching normal range w/in a few days
➔ Resumption of breastfeeding → bilirubin
seldom returns to previously high levels
➔ Phototherapy: may be of benefit
➔ Kernicterus: can occur in px w/ breast milk
jaundice
➔ B-glucuronidase resulting in deconjugation of
bilirubin & increased enterohepatic circulation
& other factors in breast milk that might
interfere w/ bilirubin conjugation (pregnanediol,
free fatty acids)
➔ Late jaundice associated w/ breast milk
distinguished from early onset, accentuated
unconjugated hyperbilirubinemia
(breastfeeding jaundice): occurs in 1st week
after birth in breastfed infants, who normally
have higher bilirubin levels than formula-fed
infants
➔ Lower milk intake before breast milk production
→ dehydration → hemoconcentration of
bilirubin → fewer bowel movements →
increased enterohepatic circulation of bilirubin
➔ Prophylactic supplements of glucose water to
breastfed infants: higher bilirubin levels due to
reduced intake of higher-caloric density breast
milk; NOT indicated
➔ May reduce incidence of early breastfeeding
jaundice:
◆ Frequent breastfeeding (>10 in 24 hr)
◆ Rooming-in w/ night feeding
◆ Ongoing lactation support
➔ Supplementation w/ formula or expressed
breast milk: appropriate if intake seems
inadequate, weight loss is excessive, or infants
appear dehydrated
 ➔ Bilateral choreoathetosis w/ involuntary muscle
Kernicterus spasms, extrapyramidal signs, seizures, mental
➔ Kernicterus (Bilirubin encephalopathy): deficiency, dysarthric speech, high-frequency
neurologic syndrome resulting from deposition hearing loss, squinting, defective upward eye
of unconjugated (indirect) bilirubin in basal movements
ganglia & brainstem nuclei ➔ Pyramidal signs, hypotonia, & ataxia
➔ Pathophysiology is multifactorial: ➔ Mildly affected infants: mild to moderate
◆ interaction between unconjugated neuromuscular incoordination, partial deafness,
bilirubin levels or “minimal brain dysfunction”; unapparent
◆ albumin binding & unbound bilirubin until child enters school
levels
◆ passage across BBB
◆ neuronal susceptibility to injury
➔ Bilirubin >20 mg/dL; 90% previously healthy,
predominantly breastfed, term & near-term
infants
➔ The more immature the infant, the greater the
susceptibility to kernicterus

Clinical Manifestations
➔ S & sx appear 2-5 days after birth in term
Incidence and Prognosis
infants; 7th day in preterm infants
➔ 30% infants w/ untreated hemolytic disease &
➔ Hyperbilirubinemia: may lead to
bilirubin levels >25-30 mg/dL
encephalopathy any time during neonatal
➔ Incidence at autopsy in hyperbilirubinemic
period
preterm infant: 2-16%
➔ Lethargy, poor feeding, loss of Moro reflex:
➔ Overt neurologic signs carry grave prognosis;
common initial signs
>75% die, 80% survivors have bilateral
➔ Infant may appear gravely ill & prostate, w/
choreoathetosis w/ involuntary muscle spasms
diminished tendon reflexes & respiratory
➔ Developmental delay, deafness, spastic
distress
quadriplegia
➔ Opisthotonos w/ bulging fontanel, twitching of
face or limbs, & a shrill, high-pitched cry may
Prevention
follow
➔ Predischarge universal screening for
➔ Advanced cases: convulsions & spasm; infants
hyperbilirubinemia & assessment of clinical risk
stiffly extending their arms in an inward rotation
factors for severe jaundice & bilirubin-induced
w/ fists clenched; rigidity is rare
neurologic dysfunction
➔ Severe neurologic signs → die
➔ Total serum bilirubin or transcutaneous bilirubin
➔ Survivors: seriously damaged but may appear to
management (interchangeably): recommended
recover & for 2-3 months show few
for initial screening
abnormalities
➔ Transcutaneous instruments: less accurate at
➔ Later in 1st yr: opisthotonos, muscle rigidity,
higher bilirubin levels (>15 mg/dL) or infants w/
irregular movements, convulsions recur
darker skin
➔ 2nd yr: opisthotonos & seizures abate but
➔ Transcutaneous levels >15 mg/dL or rising
irregular involuntary movements, muscle
rapidly: confirm w/ total serum bilirubin
rigidity or hypotonia increase steadily
➔ Serum values: measured once infant begins
➔ 3 yr: complete neurologic syndrome is apparent
phototherapy
 ➔ Transcutaneous measurement: may falsely
underestimate total bilirubin during
phototherapy
➔ Identify px at risk for hyperbilirubinemia &
candidates for targeted management:
◆ Hour-specific bilirubin nomogram
◆ Physical examination
◆ Clinical risk factors
➔ Potentially preventable causes of kernicterus:
1. Early discharge (<48 hrs) w/ no early
follow-up (w/in 48 hrs of discharge);
important in near term infants (35-37
week)
2. Failure to check bilirubin level in infant
noted to be jaundiced in the 1st 24 hrs
3. Failure to recognize presence of risk
factors for hyperbilirubinemia
4. Underestimation of severity of jaundice
by clinical(visual) assessment
5. Lack of concern regarding presence of
jaundice
6. Delay in measuring serum bilirubin level
despite marked jaundice or delay in
initiating phototherapy in elevated
bilirubin levels
7. Failure to respond to parental concern
regarding jaundice, poor feeding,
lethargy
➔ Determine before discharge each infant’s risk
factors
Check Fig. 123.12 Treatment of hyperbilirubinemia
(Nelson’s page 958)
➔ Recommended approach:
1. Any infant who is jaundiced before 24
hr requires measurement of total &
direct serum bilirubin levels; if
elevated, evaluate for hemolytic disease
2. Follow-up w/in 2-3 days of discharge to
all neonates discharged earlier than 48
hr after birth
➔ Early follow-up: for <38 weeks gestation
➔ Timing of follow-up: depends on age at
discharge & presence of risk factors
➔ Some cases, follow-up w/in 24 hrs is necessary
➔ Postdischarge follow-up: early recognition of
hyperbilirubinemia & disease progression
➔ Parental communication about infant’s skin
color & behavioral activities: addressed early &
frequently, including education about risks &
neurotoxicity
➔ Ongoing lactation promotion, education,
support, follow-up services: essential
throughout neonatal period
➔ Mothers advised to nurse infants every 2-3 hr &
AVOID routine supplementation w/ water or
glucose water to ensure adequate hydration &
caloric intake
Treatment of Hyperbilirubinemia
➔ Goal of therapy: prevent neurotoxicity related
to indirect-reacting bilirubin while not causing
undue harm
➔ Phototherapy & exchange transfusion: primary
treatment modalities to keep maximal total
serum bilirubin below pathologic levels
➔ Risk of injury to CNS from bilirubin must be
balanced against potential risk of treatment
➔ Phototherapy may require 6-12 hr to have
measurable effect; started at bilirubin levels
below those indicated for exchange transfusion
➔ Underlying medical causes of elevated bilirubin
& physiological factors that contribute to
neuronal susceptibility should be treated
◆ antibiotics for septicemia
◆ correction of acidosis
Phototherapy
➔ Clinical jaundice & indirect hyperbilirubinemia:
reduced by exposure to high-intensity light in
visible spectrum
➔ Bilirubin: absorbs light maximally in blue range
(420-470 nm)
➔ Broad-spectrum white, blue, & special
narrow-spectrum (super) blue lights: effective in
reducing bilirubin levels
➔ Bilirubin in skin absorbs light energy →
photochemical reactions
➔ Major products from phototherapy:
◆ Reversible photoisomerization reaction:
convert toxic native unconjugated
4Z,15Z-bilirubin to unconjugated
 configurational isomer, 4Z,15E-bilirubin
(can be excreted in bile w/o
conjugation)
◆ Lumirubin:
● Irreversible structural isomer
● Converted from native bilirubin
● Can be excreted by kidneys in
unconjugated state
➔ Therapeutic effect of phototherapy depends on:
◆ Light energy emitted in effective range
of wavelengths
◆ Distance between lights & infant
◆ Surface area of exposed skin
◆ Rate of hemolysis
◆ In vivo metabolism & excretion of
bilirubin
➔ Available commercial phototherapy units: vary
in spectral output & intensity of radiance
emitted; wattage can be accurately measured
only at the patient’s skin surface
➔ Dark skin: does not reduce efficacy of
phototherapy
➔ Maximal intensive phototherapy:
Check Fig. 123.13 (Nelson’s page 959)
➔ “Special blue” fluorescent tubes, placing lamps
w/in 15-20 cm (6-8 inches) of the infant, putting
fiberoptic phototherapy blanket under infant’s
back to increase exposed surface area
➔ When indications for exchange transfusion are
present, phototherapy should NOT be used as
substitute
➔ Phototherapy may reduce need for repeated
exchange transfusions in infants w/ hemolysis
➔ Conventional phototherapy is applied
continuously
◆ Infant is turned frequently for maximal
skin surface area exposure
◆ Discontinued as soon as indirect
bilirubin reduced to safe levels
➔ Serum bilirubin & hematocrit levels: monitored
every 4-8 hrs in infants w/ hemolytic disease &
those w/ bilirubin levels near toxic range
➔ Older neonates: monitored less frequently
➔ Serum bilirubin monitoring: continue for at least
24 hrs after cessation of phototherapy in px w/
hemolytic disease; unexpected rises in bilirubin
may occur, requiring further treatment
➔ Skin color: cannot be relied for evaluating
effectiveness of phototherapy
➔ Skin of babies exposed to light may appear w/o
jaundice in the presence of marked
hyperbilirubinemia
➔ IV fluid supplementation added to oral feedings:
beneficial for dehydrated px pr infants w/
bilirubin levels nearing those required for
exchange transfusion
➔ Complications associated with phototherapy:
◆ Loose stools
◆ Erythematous macular rash
◆ Purpuric rash associated w/ transient
porphyrinuria
◆ Overheating
◆ Dehydration (increased insensible water
loss, diarrhea)
◆ Hypothermia from exposure
◆ “Bronze baby syndrome”: benign; direct
hyperbilirubinemia
➔ Porphyria: phototherapy contraindicated
➔ Before phototherapy is initiated, infant’s eyes
should be closed & adequately covered to
prevent light exposure & corneal damage
➔ Body temp monitored
➔ Infant shielded from bulb breakage
➔ Irradiance: measured directly
➔ Infants w/ hemolytic disease: monitor
development of anemia; may require
transfusion
➔ Anemia may develop despite lowering of
bilirubin levels
➔ Long-term adverse biologic effects of
phototherapy are absent, minimal, or
unrecognized

Check Table 123.7 (Nelson’s page 960)
➔ Bronze baby syndrome
◆ Dark, grayish brown skin discoloration
sometimes noted in infants undergoing
phototherapy
◆ Significant elevation of direct-reacting
bilirubin & other evidence of
obstructive liver disease
◆ Discoloration due to photo-induced
modification of porphyrins, which are
often present in cholestatic jaundice
◆ May last for many months
◆ Phototherapy can continue if needed
Intravenous Immune Globulin
➔ IVIG: adjunctive treatment for
hyperbilirubinemia caused by isoimmune
hemolytic disease
➔ Recommended when serum bilirubin is
approaching exchange levels despite maximal
interventions including phototherapy
➔ IVIG (0.5-1.0 g/kg/dose; repeat in 12 hrs):
reduces need for exchange transfusion in ABO &
Rh hemolytic disease by reducing hemolysis
Metalloporphyrins
➔ Adjunct therapy for hyperbilirubinemia
➔ Sn-mesoporphyrin (snMP): drug candidate
◆ MOA: competitive enzyme inhibition of
rate-limiting conversion of
heme-protein to biliverdin
(intermediate metabolite in production
of unconjugated bilirubin) by
heme-oxygenase
➔ Single intramuscular dose on 1st day of life:
reduce need for phototherapy
➔ Beneficial when jaundice is anticipated, in px w/
ABO incompatibility or G6PD deficiency, when
blood products are objected to (Jehovah’s
witness)
➔ Complication: transient erythema in infant is
receiving phototherapy
➔ Reduce bilirubin levels & decrease need for
phototherapy & duration of hospital stay
Exchange Transfusion
➔ Double-volume exchange transfusion:
performed if intensive phototherapy has failed
to reduce bilirubin levels to a safe range & risk
of kernicterus exceeds procedural risk
➔ Complications:
◆ Metabolic acidosis
◆ Electrolyte abnormalities
◆ Hypoglycemia
◆ Hypocalcemia
◆ Thrombocytopenia
◆ Volume overload
◆ Arrhythmias
◆ NEC
◆ Infection
◆ Graft-versus-host disease
◆ Death
➔ Repeated if necessary to keep indirect bilirubin
levels in a safe range
➔ Appearance of clinical signs suggesting
kernicterus: indication for exchange transfusion
➔ Healthy full-term infant w/ physiologic breast
milk jaundice: tolerate concentration slightly
higher than 25 mg/dL w/ no apparent ill effect
➔ Kernicterus may develop in sick premature
infant at a significantly lower level
➔ Level approaching critical for infant: indication
for exchange transfusion during 1st or 2nd day
after birth, further rise is anticipated, but NOT
after 4th day in a term infant or after 7th day in
preterm infant
➔ Imminent fall may be anticipated as hepatic
conjugating mechanisms become more effective