KERNICTERUS FOLLOW UP MEDICAL CARE

Further Outpatient Care:
• To help insure that infants may reach their maximum neurodevelopmental potential, referring babies with chronic bilirubin encephalopathy to a neurodevelopmental pediatrician skilled in caring for these patients is important. Early identification of and intervention for neurodevelopmental deficits has been shown to positively impact an infant's long-term neurodevelopmental prognosis.

• The numerous areas of uncertainty surrounding the diagnosis and treatment of hyperbilirubinemia in the infant, coupled with the infrequency of sequelae, make it easy to become cavalier about the evaluation of a jaundiced infant. However, remember that physiologic hyperbilirubinemia is a diagnosis of exclusion, and kernicterus, when it occurs, is a devastating and legally indefensible sequela.

• Sepsis must always be excluded in the jaundiced infant. Uncommon, but treatable, metabolic causes of jaundice include hypothyroidism and galactosemia. The first sign of occult immune or nonimmune hemolytic disease may be hyperbilirubinemia.

Transfer:
The recently reported cases of kernicterus have occurred in near-term or term infants who were discharged from the hospital fewer than 48 hours after birth. Most infants discharged at fewer than 72 hours after birth have clearly not reached their physiologic peak bilirubin level prior to discharge. Any infant at risk for significant hyperbilirubinemia and possible neurotoxicity should be cared for in a nursery capable of rendering appropriate care for the hyperbilirubinemia and any contributing diagnoses. A recently published nomogram predicts which babies may be at risk for significant disease, based on hour-of-life–specific bilirubin levels. Infants whose levels fall in the high-intermediate and high-risk zones should be closely monitored in a nursery capable of caring for sick newborns; they may require transfer from the birth hospital to a regional perinatal center.

Deterrence/Prevention:
• Prevention:
Prevention of hyperbilirubinemia is the best way to minimize the incidence of kernicterus. However, because some babies develop kernicterus with relatively modest bilirubin levels, no known absolute level of bilirubin exists below which the infant is completely safe. Additionally, because other factors contribute to the ability of bilirubin to cross the blood-brain barrier, management of these components must be appropriately attended to.

• Serum bilirubin:
Total serum bilirubin comprises a conjugated fraction (loosely called direct bilirubin) and an unconjugated fraction (indirect bilirubin). They are additive. However, the indirect fraction is composed of bound bilirubin (bound to albumin), lumirubin if the baby is under phototherapy (unbound but water-soluble and unlikely to cross the blood-brain barrier), and free bilirubin. The free component is potentially toxic, but its exact serum level cannot be readily measured.

o Risk of reduction of serum bilirubin
􀂃 The current level of knowledge does not recognize the physiologic benefits of bilirubin, despite the multiple mechanisms operant in the neonate to promote and preserve hyperbilirubinemia. In vitro experiments have demonstrated a potent antioxidant capability of bilirubin, more so than the currently identified mechanisms.
􀂃 An emerging field of research in human medicine is the role of oxidative injury in the development of various pathologic processes, which may be contributory to many neonatal diseases, such as retinopathy of prematurity, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis. Recent observational studies in the neonate have demonstrated an inverse correlation between peak serum bilirubin levels and the development of these various pathologies. Investigation into this line of research continues.

• Phototherapy
o Irradiance with light in the blue-green spectrum (440-480 nm) induces a photochemical reaction that changes the bilirubin molecule into other photoisomers that are water-soluble, readily excretable, and unlikely to cross the blood-brain barrier into the lipid-rich neuronal tissue. Such conversion begins immediately upon exposure of the skin surface to the light.
o The most important photoreaction is an irreversible structural isomerization of bilirubin into a water-soluble substance called lumirubin, which is then excreted in the bile. Reversible configurational isomerization and photo-oxidation also contribute somewhat to the effectiveness of phototherapy to reduce free bilirubin in the baby.
o To be effective, adequate skin surface must be exposed to the appropriate wavelength, with enough intensity (lux) to induce the desired reaction. Serum bilirubin levels should be closely monitored during phototherapy. A decrease of measured bilirubin by 1-2 mg/dL over a 4- to 6-hour period is an appropriate response to phototherapy.
o Various devices are commercially available to facilitate provision of phototherapy. Models include overhead lights, blankets, and swaddling devices; selection is based on abilities to cover a broad surface area, ease of administration, and personal preference.
o When to initiate phototherapy is a thorny clinical issue, compounded by the difficulties posed by early discharge in following these cases. In 1994, the AAP published a practice parameter for the management of hyperbilirubinemia in the healthy term and near-term infant. Some have criticized it for being overly aggressive, while others think it may be too lenient. A recently published nomogram correlated serum bilirubin levels in the first several hours of life with subsequent risk for significant disease. This reference can be helpful when deciding how closely to follow the cases of babies being discharged home before their bilirubin levels have peaked. Since its development, some experts have recommended universal bilirubin screening (performed with the state metabolic screen to minimize blood draws) before discharge.
o Current measurement of serum bilirubin has been limited to direct hematologic measurement. Transcutaneous measurement devices have recently become commercially available. The manufacturers claim excellent reliability and validity in babies of all skin types and colors. At present, this technology is not in widespread use.

o Risks of phototherapy
􀂃 Phototherapy by itself is generally considered safe in babies, except in some rare genetic skin disorders and congenital porphyria. However, some risks are associated with its use.
􀂃 Exposure to phototherapy causes photorelaxation of the peripheral vasculature, which can increase insensible fluid loss and lead to dehydration, especially in babies in open warmers. This, in turn, potentiates hyperbilirubinemia.
􀂃 Some extremely premature infants have reportedly experienced skin burns from fiberoptic blankets on which they were lying. Such devices should be used cautiously in infants with vulnerable skin.
􀂃 Concern exists about the risk of retinal damage in infants exposed to the extremely bright light of phototherapy. Accordingly, all infants should wear protective eye coverings while being treated.
􀂃 An observed increase in the prevalence of patent ductus arteriosis (PDA) has been shown to occur in premature infants receiving phototherapy, and foil shields to the chest have been shown to ameliorate this increase. The operant mechanism has not been elucidated fully but is thought to be related to the photorelaxation response observed in these babies' peripheral vascular beds.
􀂃 Bilirubin photosensitizes the skin, and skin damage is a theoretical risk. Bullous eruptions have been described in several infants with porphyrin abnormalities; congenital porphyria is a contraindication to the use of phototherapy.
􀂃 Bronze baby syndrome occurs in infants with direct hyperbilirubinemia who are exposed to phototherapy. This seems likely to be the result of dermal accumulation of coproporphyrins. Measurement of the direct fraction of total bilirubin should be performed in every baby before starting phototherapy.
􀂃 Phototherapy can interfere with maternal-child bonding at a critical time in the dyad's development. If a mother is breastfeeding, initiation of phototherapy introduces mechanical barriers to the breastfeeding process, which can be overwhelming at this critical time. Any comments about the role of breast milk in the development of hyperbilirubinemia may further sabotage this process. Altered parental perceptions of their infant from healthy to ill may further influence their short- and long-term interactions with their infant.

• Breastfeeding: The link between hyperbilirubinemia and breastfeeding has long been recognized, and, until recently, breastfeeding was typically interrupted in the jaundiced infant. Randomized controlled trials have shown that offering formula or dextrose water to the jaundiced breastfed infant actually increases total serum bilirubin levels and, thus, should not be advocated. Furthermore, this practice has also been shown to result in a decrease in breast milk intake after breastfeeding is reestablished. Study of the effect of continuing breastfeeding versus its interruption has not shown any untoward effect of continued breastfeeding. Because of the clear short- and long-term advantages to the infant of breast milk feeds, the evidence would indicate that breastfeeding should be continued in the infant who is well enough to have enteral feedings.

Complications:
The complications of acute bilirubin encephalopathy encompass the classic scope of chronic bilirubin encephalopathy described above. Abnormalities can be expected in the extrapyramidal system and in auditory and gaze function; dental dysplasia can be expected.

Prognosis:
The spectrum of neurologic disability from kernicterus can range from mild to severe. Attempts to correlate features of hyperbilirubinemia with prognosis for disability have failed. Despite multiple attempts, no definitive association has been identified between the degree of deficit and parameters such as total serum bilirubin level, duration of hyperbilirubinemia, presence of hemolytic disease, gestational age, birthweight, or concomitant systemic illness.

Patient Education:
• To facilitate the provision of appropriate evaluation and follow-up for babies without recognized risk factors, the AAP has published an hour-of-age-specific guideline that correlates total serum bilirubin levels with degree of risk and recommendations for follow-up.

The AAP recommends professional medical evaluation in 2-3 days for babies who are discharged from the hospital fewer than 48 hours after birth. Babies discharged fewer than 72 hours after birth may also be at risk, and they should be closely monitored as well. Other risk factors warranting additional vigilance may include unexplained family history of neonatal hyperbilirubinemia, near-term gestation, low birth weight, excessive bruising or hematomata, and ethnicity at risk for exaggerated hyperbilirubinemia. Parents should be informed of the importance of keeping these appointments, as well as be familiarized with the symptoms of poor feeding in breastfed babies and how to seek help.