NEONATAL HYPERBILIRUBINEMIA


Pathophysiology

Causes of Neonatal Hyperpbilirubinemia

Evaluation of Neonatal Jaundice

When to Treat

How to Treat

 

PATHOPHYSIOLOGY

 

CAUSES OF NEONATAL HYPERBILIRUBINEMIA

I. Physiologic jaundice

  1. A normal process occurring in all newborns, caused by loss of placental excretory route at birth & other factors
  2. Bili usually <12.9mg/dl for f/t, <15 for preemies
  3. Bili should be <10 at 24h, tho? one source says should be <5
  4. Peaks by 2-4d; resolves by 1wk in f/t, 2wk in preemie

II. Breast milk jaundice

  1. Usual onset after day 5 of life; peak 10-15do
  2. Goes away if breastfeeding interrupted briefly, even if it?s restarted

III. Hematologic factors

  1. Hemolytic disease: ABO & Rh incompatibility, hereditary hemolytic syndromes e.g. hereditary spherocytosis. Onset & peak occur anytime
  2. RBC defects (sphero-, elliptocytosis; G6PD def., pyruvate kinase def.)
  3. Clotting disorders, inc. DIC
  4. Polycythemia and consequent hemolysis
  5. Extravasated blood, inc. cephalhematoma & swallowed blood; peaks 3-7d

IV. Metabolic factors, i.e. decreased hepatic clearance

  1. Congenital hypothyroidism
  2. Crigler-Najjar sd., awa Gilbert?s, Dubin-Johnson, Rotor, galactosemia, tyrosinosis
  3. Hypopituitarism

V. Increased enterohepatic circulation

  1. UGI obstruction, e.g. pyloric stenosis
  2. Gut surgery
  3. Hypomotility
  4. Volume depletion

VI. Sepsis

VII. Other factors which tend to increase bilirubin:

  1. East Asian ancestry
  2. Poor placental function in utero
  3. Maternal diabetes and fetal macrosomia
  4. Oxytocin in labor
  5. Male infant
  6. Prematurity
  7. No stool in 1st 24h of life
  8. Poor caloric intake

 

EVALUATION OF NEONATAL JAUNDICE (largely per AAP 2004 guidelines--see reference below)

I. Measure total bilirubin for:

  1. Any visible jaundice at < 24h old
  2. Jaundice "excessive for age" (though British "NICE" guidelines recommend measuring for all newborns with visible jaundice; BMJ 340:c2409, 2010-JW)
  3. Before discharge (alternatively, can just assess risk factors before discharge e.g. birth at < 35 weeks' gestation)
  4. Repeat Q4-24h depending on level, trend, and overall condition of infant
  5. Transcutaneous measurement of bilirubin
    1.  

II. Do workup for underlying cause if receiving phototherapy, appears ill, or bili rising rapidly (i.e. crossing percentiles), and no obvious explanation on Hx/Px:

  1. Total and (with the first measurement) direct bilirubin--If the latter is elevated, check u/a and culture as well as w/u for cholestasis and consider sepsis w/u
  2. CBC, reticulocyte count, and peripheral smear
  3. Direct antibody (Coombs' test) and blood type (ABO/Rh)
  4. G6PD screen if receiving phototherpay and (Asian or Mediterranean ancestry or poor response to phototherapy)
  5. TSH and galactosemia screening if sick of bili elevated at > 3wks of age
  6. End-tidal carbon monoxide may help identify cases of hemolysis

 

WHEN TO TREAT

I. General principles

  1. Thresholds for treatment less at earlier ages
  2. Healthy f/t's without hemolysis can probably tolerate any level of bili; kernicterus unknown in these kids with bili <20
  3. In preemies, kernicterus can occur with bili as low as 10, esp. with other illness

II. The following conditions predispose to kernicterus at lower bili levels, so consider them indications to lower bili thresholds for various treatments:

  1. Acidosis
  2. CNS dysfunction
  3. Tx with sulfa drugs
  4. Hypotension
  5. Hypothermia
  6. Hypoglycemia
  7. TPN with lipids
  8. Hypoalbuminemia
  9. Hypoxia (past or ongoing)
  10. Birthwt < 1.5kg

III. Treating prophylactically with phototherapy

  1. In a study in 242 neonates with ABO incompatibility and a positive Coombs test, born at 37wks' or longer gestation with birth weight > 2000g randomized to prophylactic phototherapy within first 24h of life vs. phototherapy only if total serum bilirubin rose to > 95%ile for age. The prophylactic phototherapy group had sig. lower total serum bilirubin levels at 24, and 48h old but not at 72h or 96h old; also had sig. less likelihood of requiring hospitalization > 48h (9% vs. 26%); no sig. diff. in readmission rates. (J. Perinatol. 25:590, 2005--JW)

IV. AAP 2004 guidelines re: phototherapy:

V. AAP 2004 guidelines re: Exchange Transfusion:

 

HOW TO TREAT

I. Adequate hydration--Supplementing nursing with water or dextrose-water doesn't lower bili per 2004 AAP guidelines

II. Breastfeeding issues

  1. Cessation of breastfeeding is traditionally advised
  2. AAP in their 2004 guidelines recommends continuing breastfeeding (as do British "NICE" guidelines; BMJ 340:c2409, 2010-JW)and/or supplementing with expressed-breast-milk or formula in a bottle, though AAP acknowledges that cessation of breastfeeding and substitution of formula is ass'd with more rapid fall in bilirubin

III. Treat secondary factors (see above) including volume depletion

IV. Phototherapy

  1. Creates H20-soluble photoisomers of bilirubin
  2. Suggested criteria for home phototherapy: >48h old, bili <18, negative w/u
  3. Speed of reduction of bili in 163 hyperbilirubinemic f/t neonates on phototherapy was less in exclusively breast-fed infants than in infants that were formula-fed (or both breast- and formula-fed) (Arch. Pediat. Adol. Med. 152:1187, 1998--AFP)
  4. If responds poorly to phototherapy, consider possibility of hemolysis or G6PD deficiency
  5. Risk factors for "rebound" hyperbilirubinemia after cessation of phototherapy include positive Coombs' test (OR 2.4), EGA < 37wks at birth (OR 3.2), and institution of phototherapy before 72h or life (OR 3.6) in one one prospective study (Arch. Dis. Child. 91:31, 2006--JW)
  6. British "NICE" guidelines (BMJ 340:c2409, 2010-JW) recommend stopping phototherapy once serum bilirubin is 2.9 mg/dL below the phototherapy threshold and repeating 12-18h after phototherapy is stopped

V. Exchange transfusion

VI. IV gamma-globulin can be effective adjunct to phototherapy in immune hemolytic disease

VII. Phenobarbital 5-8mg/kg/d (takes days to work)

VIII. Metalloporphyrins (experimental)

IX. Sn-Mesoporphyrin (6umol/kg IM x 1), an inhibitor of bilirubin production, was effective at reducing need for photoptherapy, compared with "usual care" (Peds. 103:1, 1999--JW)

(Sources include American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the Newborn Infant 35 or more Weeks of Gestation. Pediatrics 114:297, 2004).