Management

TREATMENT OF HYPERBILIRUBINEMIA

“Regardless of the cause, the goal of

therapy is to prevent neurotoxicity related to
indirect-reacting bilirubin while not causing
undue harm.”
Primary Treatment Modalities

Phototherapy Exchange Transfusion

PHOTOTHERAPY

 Clinical jaundice and indirect hyperbilirubinemia are reduced by exposure to high-intensity

light

 Bilirubin in the skin absorbs light energy

 photoisomerization :conversion of toxic unconjugated bilirubin into an unconjugated

configurational isomer, which can then be excreted in bile without conjugation.
Phototherapy

 Dark skin does not reduce the efficacy of phototherapy.

 Maximal intensive phototherapy:

using “special blue” fluorescent tubes, placing the lamps within 15-20 cm (6-8 inches) of the
infant, and putting a fiberoptic phototherapy blanket under the infant’s back to increase the
exposed surface area.

 decreased the need for exchange transfusion in term and preterm infants with hemolytic and
nonhemolytic jaundice.
 ● Risk Factors: isoimmune
hemolytic disease, G6PD
deficiency, asphyxia,
significant lethargy,
temperature instability,
sepsis, acidosis, or albumin
3.0 g/dL
● (if measured).

Bhutani Nomogram
Phototherapy

 Serum bilirubin levels and hematocrit should be monitored every 4-8 hr in infants with
hemolytic disease and those with bilirubin levels near toxic range for the individual infant.

 Skin color cannot be relied on for evaluating the effectiveness of phototherapy; the skin of
babies exposed to light may appear to be almost without jaundice in the presence of marked
hyperbilirubinemia.
Phototherapy

 Phototherapy should not be used as a substitute when indications for exchange transfusion are
present.

 phototherapy may reduce the need for repeated exchange transfusions in infants with
hemolysis.

 It should be discontinued as soon as the indirect bilirubin concentration has reduced to levels
considered safe with respect to the infant’s age and condition.
Complications of Phototherapy

A. Loose stools
B. Erythematous macular rash
C. Purpuric rash associated with transient porphyrinemia
D. Overheating
E. Dehydration (increased insensible water loss, diarrhea)
F. Hypothermia from exposure
G. A benign condition called “bronze baby syndrome,”
Bronze Baby Syndrome

● Refers to a dark, grayish brown skin discoloration sometimes noted in infants undergoing
phototherapy.

● The discoloration may result from photo-induced modification of porphyrins, which are often
present during cholestatic jaundice and may last for many months.

● Almost all infants observed with this syndrome have had significant elevation of direct-reacting
bilirubin and other evidence of obstructive liver disease

● Despite the bronze baby syndrome, phototherapy can continue if needed.

Exchange Transfusion

● Double-volume exchange transfusion is performed if intensive phototherapy has failed to

reduce bilirubin levels to a safe range and the risk of kernicterus exceeds the procedural risk.
● Risk factors :
● Isoimmune hemolytic
disease, G6PD
deficiency, asphyxia,
significant lethargy,
● temperature instability,
sepsis, acidosis.
Potential Risks
● metabolic acidosis,
● electrolyte abnormalities
● Hypoglycemia
● hypocalcemia
● Thrombocytopenia
● volume overload
● arrhythmias
● NEC
● Infection
● graft-versus-host disease
● death.
Exchange Transfusion

● This widely accepted treatment is repeated if necessary to keep indirect bilirubin levels in a
safe range

● The appearance of clinical signs suggesting kernicterus is an indication for exchange

transfusion at any level of serum bilirubin
Contraindication

● Phototherapy is contraindicated in the presence of porphyria.

 Before phototherapy is initiated, the infant’s eyes should be closed and adequately covered to
prevent light exposure and corneal damage.

 Body temperature should be monitored

 infant should be shielded from bulb breakage

Neonatal Sepsis
• Infections in the newborn are often classified by their timing relative to
birth and include congenital, perinatal, early-onset, and late-onset
disease.
• Congenital infection:
denotes infection acquired in utero. Such infections are generally caused by viral or other
non-bacterial organisms and are often associated with injury to developing organs
• Perinatal infection:
indicates acquisition around the time of delivery.
• Early-onset infection:
occurs in the 1st wk of life and is generally the consequence of infection caused by
organisms acquired during the perinatal period.
• Late-onset infection:
occurs between 7 and 30 days of life and may include bacteria, viruses, or other
organisms that are typically acquired in the postnatal period.
• Neonates are uniquely prone to invasive disease because of their lack of fully responsive
innate immunity

• Compared to older infants, newborns are often treated empirically while awaiting results
of laboratory investigations.

• Preterm infants are particularly susceptible to infection because of their decreased innate
immune and barrier defenses and their prolonged stay in hospital settings.
• Up to 10% of infants have infections in the 1st month of life.

• Newborn infection is more common in areas with limited access to healthcare than in
areas with well-established healthcare infrastructure.

• The overall incidence of neonatal sepsis ranges from 1 to 5 cases per 1,000 live births.
Early-Onset Infections

• In most cases, the fetus or neonate is not exposed to potentially pathogenic bacteria until
the membranes rupture and the infant passes through the birth canal and/or enters the
extrauterine environment.

• The human birth canal is colonized with aerobic and anaerobic organisms that may
result in ascending amniotic infection and/or colonization of the neonate at birth.

• Vertical transmission of bacterial agents that infect the amniotic fluid and vaginal canal
may occur in utero or, more often, during labor and delivery
Chorioamnionitis

• to the clinical syndrome of intrauterine infection, which includes maternal fever, with or
without local or systemic signs of chorioamnionitis (uterine tenderness, foul-smelling
vaginal discharge/amniotic fluid, maternal leukocytosis, maternal and/or fetal
tachycardia).

• Chorioamnionitis may also be asymptomatic, diagnosed only by amniotic fluid analysis or

pathologic examination of the placenta.

• The rate of histologic chorioamnionitis is inversely related to gestational age at birth and
directly related to duration of membrane rupture.
• Chorioamnionitis was thought to result from infection of the amniotic fluid but is now
better defined by the term intrauterine inflammation or infection at birth.

• This is defined by fetal tachycardia, maternal leukocytosis (>15,000 cells in the absence
of corticosteroids), purulent fluid from the cervical os, biochemical or microbiologic
amniotic fluid changes consistent with infection, and fever (≥39.0°C/10.2°F)

• At 18 hr of membrane rupture, the incidence of early-onset disease with group B

streptococcus (GBS) increases significantly
• Bacterial colonization does not always result in disease.
• Factors influencing which colonized infant will experience disease:
• Prematurity
• Underlying illness
• Invasive procedures
• Inoculum size
• Virulence of the infecting organism
• Genetic predisposition
• The innate immune system
• Host response
• And transplacental maternal antibodies.
• Aspiration or ingestion of bacteria in amniotic fluid may lead to congenital pneumonia or
systemic infection, with manifestations becoming apparent before delivery (fetal distress,
tachycardia), at delivery (failure to breathe, respiratory distress, shock), or after a latent
period of a few hours (respiratory distress, shock).

• Aspiration or ingestion of bacteria during the birth process may lead to infection after an
interval of 1-2 days.

• Resuscitation at birth, particularly if it involves endotracheal intubation, insertion of an

umbilical vessel catheter, or both, is associated with an increased risk of bacterial
infection.
Late-Onset Infections

• After birth, neonates are exposed to infectious agents in the neonatal intensive care unit
(NICU), the nursery, or in the community.

• Postnatal infections may be transmitted by direct contact with hospital personnel, the
mother, or other family members; from breast milk (HIV, CMV); or from contaminated
equipment.

• The most common source of postnatal infections in hospitalized newborns is hand

contamination of healthcare personnel, underscoring the importance of handwashing.
Infection in Premature Infants

• The most important neonatal factor predisposing to infection is prematurity or LBW.

Preterm LBW infants have a 3- to 10-fold higher incidence of infection than full-term
normal-birthweight infants.
• Possible explanations include :
1. Maternal genital tract infection is considered to be an important cause of preterm
labor, with an increased risk of vertical transmission to the newborn
2. The frequency of intraamniotic infection is inversely related to gestational age (see
3. Premature infants have documented immune dysfunction;
4. Premature infants often require prolonged intravenous access, endotracheal
intubation, or other invasive procedures that provide a portal of entry or impair
barrier and clearance mechanisms, putting them at continued risk for hospital-
acquired infections.
CLINICAL MANIFESTATIONS

• The maternal history provides important information about maternal exposures to

infectious diseases, bacterial colonization, immunity (natural and acquired), and obstetric
risk factors (prematurity, prolonged ruptured membranes, maternal chorioamnionitis).

• Signs and symptoms in the neonate are often subtle and nonspecific.
 Temperature instability
 Tachypnea
 Lethargy
 Poor feeding
Diagnostics

• Cultures and cell counts are obtained from blood and urine.
• CSF should be sent for Gram stain, routine culture, cell count with differential, and
protein/glucose concentrations.
• Surface swabs, blood, and CSF are often obtained for HSV testing. Except for culture and
directed pathogen testing, no single laboratory test is completely reliable for diagnosis of
invasive infection in the newborn.
• Complete blood count may demonstrate elevated or decreased WBC count, often with a
shift toward more immature forms. Thrombocytopenia can be seen in systemic bacterial
or viral infection.
• Hyponatremia, acidosis, and other electrolyte abnormalities can be seen.
• Hyperbilirubinemia is nonspecific but may be an indication of systemic infection.
• Elevated serum transaminases may be a clue to systemic HSV or enterovirus infection.
• Various serum biomarkers have been investigated for their ability to identify infants with
serious bacterial infection (SBI).
• An immatureto-total phagocyte count (I/T ratio) (≥0.2) has the best sensitivity of the
neutrophil indices for predicting neonatal sepsis.
• After the newborn period, serum C-reactive protein (CRP) and procalcitonin have
demonstrated reasonable sensitivity and specificity for SBI.
• CRP may be monitored in newborn infants to assess response to therapy.
GENERAL APPROACH TO MANAGEMENT

• In the absence of specific signs of focal infection, therapy for presumed infection in the
neonate is often empirical and initiated on the basis of :
Fever or hypothermia
Listlessness
Irritability
Apneic episodes
• Antibiotics are chosen to cover the organisms typically causing neonatal sepsis, including
GBS, gram-negative organisms, Listeria, and Enterococcus.
• Since the latter 2 organisms are intrinsically resistant to cephalosporins, ampicillin is
generally included in the empirical treatment of infants with presumed neonatal infection
• An empirical regimen for suspected early-onset sepsis in a term or late preterm infant is:

Ampicillin 150 mg/kg/dose intravenously (IV) every 12 hr

Gentamicin 4 mg/kg/dose IV every 24 hr.

• This has long been a standard regimen for early-onset sepsis and provides coverage for the
most prevalent organisms, predominantly GBS and gram-negative ones.
• Ampicillin plus cefotaxime (if available) or cefepime may be substituted if the patient
presents with infection after discharge from the nursery, or when infection with ampicillin-
resistant E. coli is suspected.
• Ceftriaxone may be substituted if premature infants are ≥41 wk postconception age; it may
be used in term infants if they are not receiving ntravenous calcium or do not have
hyperbilirubinemia.
• Definitive therapy is based on identification and susceptibility of the offending organism.
In almost all circumstances, the least broad antibiotic with activity against the organism is
chosen.

• Duration of therapy depends on the organism and the site of infection. In neonates with
culture proven sepsis, the usual course of therapy is 10 days. Longer treatment courses
may be warranted if a specific focus of infection is identified (e.g., meningitis,
osteomyelitis, septic arthritis).

• Antimicrobial therapy should be altered based on the susceptibility profile of the pathogen
isolated.
• In infants with a negative blood culture but a clinical status that remains concerning for a
systemic infection, antibiotic therapy can be extended for as long as a total of 5 to 10
days.

• Sepsis is unlikely in these infants if they remain well and the blood culture is sterile at 48
hr.

• Empirical antibiotic therapy should be discontinued after 48 hr in these neonates.

Thank you