Anemia of Prematurity - Portal Neonatal

Pathophysiology: Bilirubin staining can be noted on autopsy of fresh specimens in the regions of
the basal ganglia, hippocampus, substantia nigra, and brainstem nuclei. Such staining can occur in
the absence of severe hyperbilirubinemia; in this situation, factors influencing permeability of the
blood-brain barrier (eg, acidosis, infection) and the amount of unbound (versus albumin-bound)
bilirubin may play a role.
Characteristic patterns of neuronal necrosis leading to the clinical findings consistent with chronic
bilirubin encephalopathy are also essential in the pathophysiology of this entity. Bilirubin staining of
the brain without accompanying neuronal necrosis can be observed in babies who did not
demonstrate clinical signs of bilirubin encephalopathy but who succumbed from other causes. This
staining is thought to be a secondary phenomenon, dissimilar from the staining associated with
kernicterus.
Frequency:
• In the US: The exact incidence of kernicterus is unknown. A pilot kernicterus registry
following the cases of babies with kernicterus in the United States reports 80 babies with
chronic kernicterus enrolled in the registry from 1984-1998. All babies reported in the
registry had been discharged from the hospital fewer than 72 hours after birth. Most of
these babies (60%) were term infants. Total serum bilirubin levels at the time of
presentation with the classic physical signs of kernicterus ranged from 26-50 mg/dL. Sixtyseven
percent of the patients were male, 54% were white, and 95% were breastfed. Severe
hemolytic processes were identified in 19 out of 80 babies; glucose-6-phosphate
dehydrogenase (G6PD) deficiency was diagnosed in 18 out of 80, galactosemia occurred
in 2 out of 80, and Crigler-Najjar syndrome type I occurred in 1. Nine babies were
diagnosed with sepsis. In 21 out of 74 infants, no etiology for the severe hyperbilirubinemia
was discovered. Three out of 80 infants died.
Mortality/Morbidity: Classic kernicterus has been defined in the term infant. Increasing experience
with premature babies indicates that the clinical presentation in premature infants may be
somewhat different. Especially in the premature infant with significant hyperbilirubinemia,
concomitant ongoing pathologies may make identifying the cause of death specifically as
kernicterus difficult. Neurologic sequelae of bilirubin encephalopathy are variable, and correctly
attributing some long-term neurologic deficits to kernicterus as opposed to other neonatal
conditions may be difficult.
• In the kernicterus registry mentioned previously, 3 out of 80 patients died (3.75%). How
many other patients died without being reported to the registry is unknown, as is the
experience in countries other than the United States, especially countries with a high
prevalence of hereditary hemolytic disorders.
• Of those patients reported to the kernicterus registry, 66 out of 77 (86%) had chronic
kernicterus, 61 of which had severe disease. Ten out of 77 (13%) had no discernible
sequelae when older than 1 year.
Race: Asian and Hispanic babies born either in their native countries or in the United States and
Native American and Eskimo infants have higher production levels of bilirubin than white infants.
African American infants have lower production levels (see Image 1). The reasons for these racial
differences have not been fully elucidated.
Sex: Male infants have consistently higher levels of serum bilirubin than do female infants.
Age: Acute bilirubin toxicity appears to occur in the first few days of life of the term infant. Preterm
infants may be at risk of toxicity for slightly longer than a few days. If injury has occurred, the first
phase of acute bilirubin encephalopathy appears within the first week of life.