Neonatal Jaundice (1 of 6)

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Neonatal Jaundice (1 of 6)

Yes

No

Yes

No

1Newborn infant presents w/ signs

suggestive of jaundice

2

ASSESSMENTIs the infant <24 hr old?

ALTERNATIVE DIAGNOSIS

• Assess need for measurements of bilirubin levels

3DIAGNOSIS

Does lab results support jaundice?

4EVALUATION

• Determine cause of jaundice• Assess severity of jaundice

A Non-pharmacologic therapy• Phototherapy• Exchange transfusion• Proper nutrition

B Pharmacologic therapy• IV immunoglobulin (IVIg)

Not all products are available or approved for above use in all countries.Specifi c prescribing information may be found in the latest MIMS.

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© MIMS Pediatrics 2019

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1 NEONATAL JAUNDICE

• Yellowish discoloration of the skin & sclera in infants <28 days old due to the accumulation of serum bilirubin levels of >85 µmol/L (>5 mg/dL)

• Jaundice typically presents on the 2nd-3rd day of lifePhysiologic Jaundice• More common in breastfed than in bottlefed neonates • Occurs in neonates <14 days old• Caused by an abrupt increase in bilirubin load of the liver after birth • May extend beyond 14 days in term infants & >21 days in preterm infants Pathologic Jaundice• Occurs in neonates >14 days old• Caused by underlying diseases such as ABO incompatibility, sepsis, liver disease, glucose-6-phosphate dehy-

drogenase (G6PD) defi ciency, metabolic disorders• May develop into kernicterus if the following are present:

- Signs of acute bilirubin encephalopathy - Increasing serum bilirubin of >8.5 µmol/L/hr - Gestational age >37 weeks w/ serum bilirubin of >340 µmol/L

2 ASSESSMENT

• Jaundice that appears in a newborn <24 hours old is most likely nonphysiologic & needs further evaluation - Visible jaundice in the feet may be an indication to check bilirubin level

• Visual estimation of bilirubin level is often inaccurate & unreliable• Danger signs in a newborn infant w/ jaundice:

- Changes in brainstem evoked auditory potentials (eg decreased amplitude, prolonged latencies) - Changes in muscle tone - Seizures - Altered cry characteristics

• � e above fi ndings require prompt attention to prevent kernicterus• All infants should be routinely monitored for jaundice by nursing staff & physicians

- Assessment for jaundice should be done every 8-12 hours in a well-lit room, preferably in daylight by a window - Detection of jaundice is aided by fi nger pressure on the skin which reveals the underlying color of the skin & subcutaneous tissue

- Jaundice is usually fi rst seen on the face & forehead then progresses caudally to the trunk & extremities - More intense jaundice may be associated w/ drowsiness - Stool color should be monitored for all patients w/ jaundice; clay-colored stools may indicate cholestasis

Risk Factors for Severe Hyperbilirubinemia in Infants >35 Weeks of Gestation• Jaundice observed in the fi rst 24 hours of life• Total serum bilirubin (TSB) & transcutaneous bilirubinometry (TcB) in high-risk zone• Blood group incompatibility• Cephalohematoma or signifi cant bruising• Sibling who received phototherapy• Exclusive breastfeeding• Gestational age 35-36 weeks• East Asian race as defi ned by mother’s description

3 DIAGNOSIS

Transcutaneous Bilirubinometry (TcB) • A noninvasive way to measure serum bilirubin using handheld devices• May be used as an initial screening test to detect possible development of hyperbilirubinemia • Said to be equivalent to total serum bilirubin & may decrease the need for more invasive TSB measurements;

however, more studies may be needed to validate tests that measure TcBTotal Serum Bilirubin (TSB) • Measured if jaundice appears excessive for an infant’s age, when TcB level is >200 µmol/L (12 mg/dL), or if

there is any doubt about the degree of jaundice• Often the only test needed for infants who present w/ moderate jaundice on the 2nd or 3rd day of life & who

do not have features suggesting pathologic jaundice

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4 EVALUATIONPossible Causes of JaundiceUnconjugated Hyperbilirubinemia• Hemolysis resulting from ABO blood group incompatibility, infection, red blood cell (RBC) membrane defects

(eg G6PD defi ciency), RBC enzyme defects, hemoglobinopathies• Physiologic jaundice which results from increased bilirubin production brought about by accelerated destruction

of RBCs, decreased excretory capacity secondary to low levels of ligandin in hepatocytes, & low activity of the bilirubin-conjugating enzyme uridine diphosphate glucuronyltransferase (UDPGT)

• Breastfeeding which may give rise to decreased bilirubin clearance • Polycythemia, bruising, internal hemorrhage, mutations of glucuronyltransferase, infant of mother w/ diabetes Conjugated Hyperbilirubinemia• Neonatal hepatitis, sepsis, TORCH infection, urinary tract infection • Rare: Biliary atresia, inborn errors of metabolism Laboratory Tests for Determining Cause of Jaundice• Laboratory tests that will be requested will depend on the indications found in an infant• Hematology: Hemoglobin & hematocrit, direct Coomb’s test, peripheral blood fi lm, reticulocyte count, blood

type & Rh determination in infant & mother • Screening for G6PD defi ciency in infants from high-risk populations• Total & conjugated bilirubin to identify cholestasis• Liver function tests: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl

transferase (GGT), alkaline phosphatase - A GGT/ALT ratio >1 is highly suggestive of biliary obstruction

• Sepsis evaluation in infants who appear ill: Urinalysis, urine culture, tests for parasitic & viral infections • Measurement of end tidal carbon dioxide in breath as an index of bilirubin production• Serum albumin to help evaluate risk of bilirubin toxicity• � yroid function tests• Imaging of the liver & biliary tract including ultrasonography & radionuclide imagingClinical Assessment of Severity• Jaundice appears in a cephalo-caudal direction• For clinical assessment, the Kramer’s Rule may be used to estimate the range of indirect bilirubin levels

AREA LEVEL INDIRECT BILIRUBINmmol/L mg/dL

Head & neck 1 68-133 4-8Upper trunk 2 85-204 5-12Lower trunk & thighs 3 136-272 8-16Arms & lower legs 4 187-306 11-18Palms & soles 5 ≥306 ≥18

Source: Ministry of Health Malaysia. Clinical practice guidelines: management of neonatal jaundice (second edition). 2015.

PRINCIPLES OF THERAPY• Consider TSB levels, infant’s age in hours & presence of risk factors to determine need for therapyIndications for Treating Neonatal Jaundice• When TSB level exceeds the threshold in the nomogram• A TSB level >25 mg/dL (428 μmol/L) at any time is a medical emergency & indicates prompt hospital admission

& initiation of treatment• For preterm infants, initiation of phototherapy or exchange transfusion depends on the gestational age

Gestational Age(weeks)

Phototherapy Exchange TransfusionTSB (μmol/L) TSB (mg/dL) TSB (μmol/L) TSB (mg/dL)

<28 86 >5 188-239 11-1428-29 103-137 6-8 205-239 12-1430-31 137-171 8-10 222-274 13-1632-33 171-205 10-12 257-308 15-18>34 205-239 12-14 291-325 17-19

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A NON-PHARMACOLOGICAL THERAPYPhototherapy• Phototherapy creates water soluble bilirubin isomers which are excreted in the bile & urine, resulting in lower

serum bilirubin levels & decreased risk of bilirubin-induced neurotoxicity• Has been shown to be most eff ective in very small preterm infants & least eff ective in severely growth retarded

full-term infants• Conventional phototherapy in the hospital should consist of irradiance in the blue-green spectrum (400-500

nm) of at least 15 µW/cm2/nm that is delivered to as much of the infant’s surface as possible - � e wavelength at the blue-green spectrum lets light penetrate the skin well & be maximally absorbed by bilirubin

- � e most eff ective light sources for phototherapy are special blue fl uorescent tubes or specially designed light-emitting diode light

- Light tubes should be placed as close to the infant as possible (30-50 cm from the infant) - � e infant should be placed in the supine position, naked except for diapers to expose maximum body surface area, & eyes should be covered

• Intensive phototherapy, which consists of at least 30 µW/cm2/nm, should be started when TSB levels reach 3 mg/dL (51 µmol/L) above the level of conventional phototherapy or when TSB levels continuously increase by >0.5 mg/dL/hr (8.5 µmol/L/hr)

• Additional body surface area exposure may be achieved by lining the bassinet w/ aluminum foil or a white cloth• Infant’s eyes should be properly protected during phototherapy to prevent retinal damage• Fluid supplementation is not given routinely but is based on infant’s weight loss, urine output & urine specifi c gravity• Complications from phototherapy are rare

- Grayish-brown discoloration of the urine, serum & skin may develop in infants w/ cholestatic jaundice (bronze baby syndrome)

- Severe blistering & photosensitivity in infants may occur in infants w/ congenital erythropoietic porphyria• Sunlight exposure as a substitute for phototherapy is not recommended because sunburn is a serious danger

given that exposure of a large body surface area is required• A decrease of 30-40% in the initial bilirubin level may be expected 24 hours after start of phototherapy in

infants >35 weeks age of gestation• In infants w/ extremely high bilirubin levels, a decline of at least 0.5-1 mg/dL may be expected in the fi rst

4-8 hours of phototherapy• A continuing rise in bilirubin levels despite phototherapy usually means that hemolysis is present• Frequency of TSB monitoring depends on previous measurements

TSB level in mg/dL Repeat TSB≥25 2-3 hours

20 to 25 3-4 hours14 to <20 4-5 hours

Continues to decrease 8-12 hours<14 Discontinue phototherapy &

consider repeat TSB after 24 hoursAdapted from: Moerschel SK, Cianciaruso LB, Tracy LR. A practical approach to neonatal jaundice. Am Fam Physician. 2008;

77:1255-1262.• � e TSB level for discontinuing phototherapy depends on the age at which phototherapy was started & the

cause of the hyperbilirubinemia Exchange Transfusion• Exchange transfusion is recommended when an infant’s TSB level exceeds the threshold set in the nomogram

(>5 mg/dL [85 µmol/L] above exchange transfusion level) or when TSB >25 mg/dL (428 µmol/L) • Exchange transfusion should be done immediately in any infant w/ jaundice & signs of acute bilirubin

encephalopathy which include hypotonia or hypertonia, opistothonus, fever, poor feeding & lethargy, even if the TSB level is falling

• In almost all cases, exchange transfusion is performed only when phototherapy fails to keep the bilirubin level below the exchange transfusion level

• Trained staff should perform the procedure in a neonatal intensive care unit• Intensive phototherapy is recommended in preparation for an exchange transfusion• Complications of exchange transfusion include infection, thromboembolization, hemolysis of transfused

blood, acidosis, serum electrolyte abnormalities, bradycardia & vasospasm

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A NON-PHARMACOLOGICAL THERAPY (CONT’D)Nutrition• If possible, breastfeeding should be continued

- Optimal breastfeeding 8-12 x/day increases removal of bilirubin through the gastrointestinal tract - Supplemental breast milk or formula may be given to infants w/ insuffi cient oral intake, dehydration or excessive weight loss

• Hydration - Adequacy of oral intake should be evaluated in an infant who lost >10% of birth weight - Infant should be referred to a specialist if w/ weight loss of >7% of birth weight & for close monitoring for severe hyperbilirubinemia

- If infant’s oral intake is unreliable, give IV fl uids

B PHARMACOLOGIC TREATMENTIV Immunoglobulin (IVIg)• In an infant w/ isoimmune hemolytic disease, administration of IVIg is recommended if the TSB is rising in

spite of intensive phototherapy or the TSB level is within 2-3 mg/dL of the exchange transfusion level• May reduce the need for exchange transfusions in Rh & ABO hemolytic disease• Has been shown to decrease RBC destruction & limit the rate of increase in bilirubin levels in infants w/ Rh

& ABO isoimmunizationHuman Albumin• Reduces levels of unbound bilirubin by providing more binding sites thus preventing bilirubin toxicity • Further studies are needed to further prove the effi cacy of human albumin in neonatal jaundice Tin-mesoporphyrin (Stannsoporfi n) • � is drug may help prevent or treat hyperbilirubinemia by inhibiting production of heme oxygenase• Investigations are being conducted to prove the effi cacy & safety of this drug for the prevention of hyperbil-

irubinemia in infants at risk of developing jaundiceClofi brate• May help lower bilirubin levels in term infants w/ hyperbilirubinemia by increasing bilirubin elimination,

when used in combination w/ phototherapy• Further studies are needed to further prove the effi cacy of Clofi brate in neonatal jaundicePhenobarbitone (Phenobarbital)• Has shown potential for reducing bilirubin levels by stimulation of hepatic enzymes• � ere are limited studies proving Phenobarbitone’s safety & effi cacy for the management of neonatal jaundice

Not all products are available or approved for above use in all countries.Specifi c prescribing information may be found in the latest MIMS.

© MIM

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All dosage recommendations are for children w/ normal renal & hepatic function unless otherwise stated.Not all products are available or approved for above use in all countries.

Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information.

Specifi c prescribing information may be found in the latest MIMS.Please see the end of this section for the reference list.

Dosage Guidelines

IMMUNOGLOBULIN

Drug Dosage Remarks

IV Immunoglobulin (gamma-globulin, IVIg)

0.5-1 g/kg IV infusion over 2 hrMay repeat after 12 hr if necessary

Adverse Reactions• Renal eff ects (increased BUN or creatinine levels, acute renal

failure or tubular necrosis, oliguria); GI eff ects (N/V, abdominal cramps); Musculoskeletal eff ects (myalgia, arthralgia, chest, back or hip pain); Allergic reactions; Other eff ects (headache, chills, fever, chest tightness, dyspnea)

• Rarely: Rash• Local inj site reactionsSpecial Instructions• Assess volume status prior to initiation of therapy

INTRAVENOUS & OTHER STERILE SOLUTION

Drug Dosage Remarks

Human albumin Neonatal hyperbiliru-binemia associated w/ hemolytic disease of the newborn: 1 g/kg body wt via IV infusion before or during binding the exchange bilirubin or 5-15 mL/kg IV 30 min before the exchange infusion

Adverse Reactions• CV eff ects (tachycardia, hypotension); Dermatologic

eff ects (urticaria, rash); Other eff ects (N/V, chills, fever)Special Instructions• Use w/ caution in low cardiac reserve, marked

dehydration• Monitor for signs of increased venous pressure• Avoid rapid infusion; discontinue immediately if w/ signs

of circulatory overloading

ANTICONVULSANT

Drug Dosage Remarks

Phenobarbital (Phenobarbitone)

Usual dose: 30-125 mg PO 8 hrly up to 350 mg/day PO in divided doses orNewborn: 5-10 mg/kg/day PO<12 yr: 1-4 mg/kg PO 8 hrly

Adverse Reactions• Sedation (which usually decreases after repeated administration),

subtle mood changes, impairment of cognition & memory, depression. Prolonged administration may result in folate defi ciency, rarely megaloblastic anemia

• At high doses, nystagmus, resp depression or ataxia may occur. Overdose may result in severe resp depression, coma, CV depression, hypotension, shock & renal failure

• Rarely hypersensitivity, rashes, Stevens-Johnson syndrome or erythema multiforme. Hepatitis & hepatic failure have occurred

Special Instructions• Use w/ caution in patients w/ mild to moderate liver or renal dysfunction,

history of sedative/hypnotic addiction, resp disease, hypoadrenalism• Contraindicated in patients w/ severe renal/hepatic impairment, severe

resp depression, acute intermittent porphyria• Monitor CBC, liver function & mental status regularly

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Neonatal Jaundice (1 of 6)