Kernicterus: Difference between revisions
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{{SK}} [[Chronic]] [[bilirubin]] [[encephalopathy]] | {{SK}} [[Chronic]] [[bilirubin]] [[encephalopathy]] | ||
==Overview== | ==Overview== | ||
'''Kernicterus''' is [[irreversible]] [[brain]] [[damage]] due to [[chronic]] high levels of [[unconjugated]] [[bilirubin]] in the baby`s [[blood]] which is not treated early. [[Hyperbilirubinemia]] frequently occurs in [[majority]] of [[newborn]] [[infants]] but mostly it is [[benign]] and in [[severe]] [[cases]] can [[progress]] to kernicterus and [[developmental]] [[abnormalities]]. The [[risk]] of [[bilirubin]] [[induced]] [[neurologic]] [[damage]] and kernicterus are more in [[preterm]] than [[term]] [[neonates]] and the [[former]] [[suffer]] [[adverse]] [[effects]] at [[lower]] [[total]] [[bilirubin]] [[levels]] with [[worse]] [[long-term]] [[outcomes]]. [[Liver]] [[metabolizes]] and [[excretes]] [[bilirubin]]. [[During]] [[pregnancy]], the [[mother`s]] [[liver]] does it for the [[baby]]. After [[birth]], some of the [[baby`s]] [[liver]] [[enzyme]] not well [[developed]] [[specially]] in [[preterm]], [[bilirubin]] [[raises]] in the [[baby`s]] [[blood]] and [[accumulates]] in the [[skin]] and [[sclera]] of [[eyes]] and [[cause]] [[jaundice]]. When the [[jaundice]] gets [[severe]], The [[tissues]] [[protecting]] the [[brain]] (the [[blood-brain barrier]]) are [[immature]] in [[newborns]]. [[Bilirubin]] [[penetrates]] the [[brain]] and is [[deposited]] in the [[basal ganglia]],[[hippocampus]], [[geniculate bodies]] and [[cranial nerve nuclei]] causing [[irreversible]] [[damage]]. Depending on the [[level]] of [[exposure]], the [[effects]] [[range]] from [[unnoticeable]] to [[severe]] [[brain damage]]. When the [[jaundice]] occurs within ([[24 hours]]) of [[life]] is always [[pathological]], whereas it [[happens]] after 24 hours of [[life]], it can be [[physiological]]. [[Several]] [[underlying]] [[pathologic]] [[processes]] [[responsible]] for [[hyperbilirubinemia]] are [[G6PD]] [[deficiency]], [[Crigler-Najjar]] [[syndrome]], [[Gilbert]] [[syndrome]], [[hemolytic]] [[disorders]], and a [[decreased]] [[ability]] to [[conjugate]] [[bilirubin]] in [[neonates]] and [[infants]]. [[Newborn]] [[babies]] are often [[polycythemic]], meaning they have too many [[red blood cell]]s. When they [[break]] [[down]] the [[cells]], one of the [[byproducts]] is [[bilirubin]], which [[circulates]] in the [[blood]] and [[causes]] [[Neonatal_jaundice|jaundice]]. When [[hyperbilirubinemia]] occurs in [[adult]] and [[older]] [[children]], it is [[frequently]] due to [[liver]] [[abnormalities]]. | '''Kernicterus''' is [[irreversible]] [[brain]] [[damage]] due to [[chronic]] high levels of [[unconjugated]] [[bilirubin]] in the baby`s [[blood]] which is not treated early. [[Hyperbilirubinemia]] frequently occurs in [[majority]] of [[newborn]] [[infants]] but mostly it is [[benign]] and in [[severe]] [[cases]] can [[progress]] to kernicterus and [[developmental]] [[abnormalities]]. The [[risk]] of [[bilirubin]] [[induced]] [[neurologic]] [[damage]] and kernicterus are more in [[preterm]] than [[term]] [[neonates]] and the [[former]] [[suffer]] [[adverse]] [[effects]] at [[lower]] [[total]] [[bilirubin]] [[levels]] with [[worse]] [[long-term]] [[outcomes]]. [[Liver]] [[metabolizes]] and [[excretes]] [[bilirubin]]. [[During]] [[pregnancy]], the [[mother`s]] [[liver]] does it for the [[baby]]. After [[birth]], some of the [[baby`s]] [[liver]] [[enzyme]] not well [[developed]] [[specially]] in [[preterm]], [[bilirubin]] [[raises]] in the [[baby`s]] [[blood]] and [[accumulates]] in the [[skin]] and [[sclera]] of [[eyes]] and [[cause]] [[jaundice]]. When the [[jaundice]] gets [[severe]], The [[tissues]] [[protecting]] the [[brain]] (the [[blood-brain barrier]]) are [[immature]] in [[newborns]]. [[Bilirubin]] [[penetrates]] the [[brain]] and is [[deposited]] in the [[basal ganglia]],[[hippocampus]], [[geniculate bodies]] and [[cranial nerve nuclei]] causing [[irreversible]] [[damage]]. Depending on the [[level]] of [[exposure]], the [[effects]] [[range]] from [[unnoticeable]] to [[severe]] [[brain damage]]. When the [[jaundice]] occurs within ([[24 hours]]) of [[life]] is always [[pathological]], whereas it [[happens]] after 24 hours of [[life]], it can be [[physiological]]. [[Several]] [[underlying]] [[pathologic]] [[processes]] [[responsible]] for [[hyperbilirubinemia]] are [[G6PD]] [[deficiency]], [[Crigler-Najjar]] [[syndrome]], [[Gilbert]] [[syndrome]], [[hemolytic]] [[disorders]], and a [[decreased]] [[ability]] to [[conjugate]] [[bilirubin]] in [[neonates]] and [[infants]]. [[Newborn]] [[babies]] are often [[polycythemic]], meaning they have too many [[red blood cell]]s. When they [[break]] [[down]] the [[cells]], one of the [[byproducts]] is [[bilirubin]], which [[circulates]] in the [[blood]] and [[causes]] [[Neonatal_jaundice|jaundice]]. When [[hyperbilirubinemia]] occurs in [[adult]] and [[older]] [[children]], it is [[frequently]] due to [[liver]] [[abnormalities]]. | ||
Some [[medications]], such as the [[antibiotic]] [[co-trimoxazole]] (a combination of [[trimethoprim]]/[[sulfamethoxazole]]) may [[induce]] this [[disorder]] in the [[baby]], either when taken by the [[mother]] or given [[directly]] to the [[baby]], due to [[displacement]] of [[bilirubin]] from binding [[sites]] on [[serum albumin]]. The [[bilirubin]] is then [[free]] to [[pass]] into the [[Central Nervous System]], because the [[baby's]] [[blood-brain barrier]] is not fully [[developed]]. In the ([[first 48 hrs of life]]), A [[baby]] should be [[checked]] for [[jaundice]] and if it is [[discharged]] before 72 hrs, the [[baby]] should be seen after 2 days. The [[treatment]] is [[phototherapy]] and [[exchange]] [[transfusion]]. | Some [[medications]], such as the [[antibiotic]] [[co-trimoxazole]] (a combination of [[trimethoprim]]/[[sulfamethoxazole]]) may [[induce]] this [[disorder]] in the [[baby]], either when taken by the [[mother]] or given [[directly]] to the [[baby]], due to [[displacement]] of [[bilirubin]] from binding [[sites]] on [[serum albumin]]. The [[bilirubin]] is then [[free]] to [[pass]] into the [[Central Nervous System]], because the [[baby's]] [[blood-brain barrier]] is not fully [[developed]]. In the ([[first 48 hrs of life]]), A [[baby]] should be [[checked]] for [[jaundice]] and if it is [[discharged]] before 72 hrs, the [[baby]] should be seen after 2 days. The [[treatment]] is [[phototherapy]] and [[exchange]] [[transfusion]]. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdulkerim Yassin, M.B.B.S[2]
Synonyms and keywords: Chronic bilirubin encephalopathy
Overview
Kernicterus is irreversible brain damage due to chronic high levels of unconjugated bilirubin in the baby`s blood which is not treated early. Hyperbilirubinemia frequently occurs in majority of newborn infants but mostly it is benign and in severe cases can progress to kernicterus and developmental abnormalities. The risk of bilirubin induced neurologic damage and kernicterus are more in preterm than term neonates and the former suffer adverse effects at lower total bilirubin levels with worse long-term outcomes. Liver metabolizes and excretes bilirubin. During pregnancy, the mother`s liver does it for the baby. After birth, some of the baby`s liver enzyme not well developed specially in preterm, bilirubin raises in the baby`s blood and accumulates in the skin and sclera of eyes and cause jaundice. When the jaundice gets severe, The tissues protecting the brain (the blood-brain barrier) are immature in newborns. Bilirubin penetrates the brain and is deposited in the basal ganglia,hippocampus, geniculate bodies and cranial nerve nuclei causing irreversible damage. Depending on the level of exposure, the effects range from unnoticeable to severe brain damage. When the jaundice occurs within (24 hours) of life is always pathological, whereas it happens after 24 hours of life, it can be physiological. Several underlying pathologic processes responsible for hyperbilirubinemia are G6PD deficiency, Crigler-Najjar syndrome, Gilbert syndrome, hemolytic disorders, and a decreased ability to conjugate bilirubin in neonates and infants. Newborn babies are often polycythemic, meaning they have too many red blood cells. When they break down the cells, one of the byproducts is bilirubin, which circulates in the blood and causes jaundice. When hyperbilirubinemia occurs in adult and older children, it is frequently due to liver abnormalities. Some medications, such as the antibiotic co-trimoxazole (a combination of trimethoprim/sulfamethoxazole) may induce this disorder in the baby, either when taken by the mother or given directly to the baby, due to displacement of bilirubin from binding sites on serum albumin. The bilirubin is then free to pass into the Central Nervous System, because the baby's blood-brain barrier is not fully developed. In the (first 48 hrs of life), A baby should be checked for jaundice and if it is discharged before 72 hrs, the baby should be seen after 2 days. The treatment is phototherapy and exchange transfusion.
Historical Perspective
- Kernicterus was first discovered by Christrian Georg Schmorl, a German Pathologist, in 1904 [1].
- The association between hyperbilirubinemia and kernicterus was made in 1875[1].
Classification
- Based on the duration of symptoms, bilirubin encephalopathy may be classified as either acute, subtle or chronic.
- Acute bilirubin encephalopathy: comprises the cute illness caused by severe hyperbilirubinemia. The sign and symptom includes decreased feeding, lethargy, hypotonia and/or hypertonia, high-pitched cry, retrocollis and opisthotonus, setting-sun sign, fever, seizures, and may be death.
- Subtle bilirubin encephalopathy/Bilirubin induced neurologic dysfunction: defined by the presence of insidious developmental disorders without the classical findings of kernicterus. This may presents with neurodevelopmental disorders such as sensory and sensorimotor integration disorders, hypotonia, ataxia or clumsiness, aphasia, and auditory neuropathy which is impaired auditory brainstem reflexes with normal otoacoustic emissions or cochlear microphonic responses.
- Chronic bilirubin encephalopathy: the long-term outcome of acute bilirubin encephalopathy and composed of a tetrad of clinical characteristics that are typically appear after one year of age:
- Abnormal motor control, movements, and muscle tone;
- An auditory processing disturbance with or without hearing loss;
- Oculomotor impairments, especially impairment of the upward vertical gaze; and
- An auditory processing disturbance with or without hearing loss;
- Abnormal motor control, movements, and muscle tone;
Pathophysiology
The neonatal hyperbilirubinemia occurs due to increased production or limited excretion of indirect or unconjugated bilirubin. Newborns baby, especially preterm neonates, have higher rates of bilirubin production than adults, because an increased red cells turnover and a shorter life span. In newborn neonates, unconjugated bilirubin is not easily excreted, and there is limited bilirubin congugation which lead to physiologic jaundice. Excessive physiologic jaundice occurs at values above 7 to 17 mg/dl [104 to 291 μmol/l]). Serum bilirubin concentrations greater than 17 m/dl in full-term infants are no longer considered physiologic and pathologic causes should be identified, of which the most common are Crigler-Najjar syndrome, Gilbert syndrome, hemolytic disorders, and a reduced ability to conjugate bilirubin in newborn babies[3].
Causes
Bilirubin is a yellow pigment produced by the breakdown of hemoglobin in old or hemolyzed red blood cells. High levels of bilirubin is due to either increased production, decreased hepatic uptake, impaired conjugation, or increased enterohepatic circulation. Kernicterus is caused by very high levels of indirect or unconjugated bilirubin in the blood which crosses blood brain barrier and yellow staining of brain tissues that leads to brain damage and hearing loss[3].
Differentiating Kernicterus from other Diseases
Kernicterus must be differentiated from other diseases that cause movement disorder, visual or auditory impairment such as Cerebral palsy, Head trauma, Neonatal sepsis, Congenital TORCH infections, Hypoxic-ischemic brain injury in the newborn, Fetal alcohol syndrome and Cretinism/pediatric hypothyroidism[4].
Epidemiology and Demographics
Kernicterus happens in all parts of the world. Geographic areas where glucose-6-phosphate dehydrogenase-deficiency is common, the risk of kernicterus is higher. The incidence rate of kernicterus in Sweden is 1.3 per 100 000 births which is slightly higher than that in other population-based studies in high-resource settings. The incidence rate of kernicterus in Canada, California, and Denmark, has been reported to be 0.5 to 1 per 100 000 births, whereas in Norway, the incidence rate has been estimated to be less than 0.5 per 100 000 births[5]. The risk of kernicterus is higher in male newborns than female. However, the mechanism is unknown[6].
Risk Factors
Screening
There is insufficient evidence to recommend routine screening for kernicterus[8].
Natural History, Complications, Prognosis
Kernicterus is a very rare type of brain damage that occurs in a newborn with severe jaundice.The term kernicterus, which refers to yellow staining of the brainstem nuclei (Greek for ‘jaundice of the nuclei’). The prognosis of kernicterus depends on the severity and time to intervention. With early intervention, there may be full recovery. However, a late diagnosis can cause Permanent brain damage, enamel dysplasia, paralysis of upward gaze and, intellectual deficits, Hearing loss and Death..[9]
Diagnosis
History and Symptoms
- Acute bilirubin encephalopathy presents with;
Weakness lethargy poor feeding Extensor hypertonia retrocollis opisthotonus and hypotonia are generally seen in this phase.
Hypotonia Hyperreflexia Delayed achievement of milestones Visual and auditory defects Choreathetoid cerebral palsy Hepatomegaly or splenomegaly on phyical examination are indicative of a hemolytic cause.[4]
physical Examination
- vital signs: Afebrile, tachycardia, dyspnea, and impaired oxygen saturation.
Laboratory Findings
Total and direct bilirubin, Blood type mother and infant, Coomb test, Reticulocyte count and transcutaneous bilirubin measurement is helpful in a few cases[4].
ECG
There are no ECG findings associated with Kernicterus.
x-ray
There are no x-ray findings associated with Kernicterus.
Echocardiography or Ultrasound
There are no Echocardiography findings associated with Kernicterus.
CT Scan
CT Scan is not routinely indicated to diagnose kernicterus. It may help in ruling out other causes of encephalopathy[4].
MRI
MRI is not routinely indicated to diagnose kernicterus. It may help in ruling out other causes of encephalopathy[4].
Other Imaging Findings
Advanced MRI including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may give good understanding of the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy[10]..
Other Diagnostic Studies
Brainstem evoked auditory response (BEAR) aid to diagnose the most common complication of bilirubin toxicity i.e., hearing impairmen. Complete blood count, Serum electrolytes and lumbar puncture to rule out sepsis[4]..
Treatment
Medical Therapy
Fluid supplementation in term infants presenting with severe hyperbilirubinemia decreases the rate of exchange transfusion and duration of phototherapy. The management of kernicterus is to prevent neurotoxicity by reducing bilirubin levels. The mainstays of therapy to prevent and treat hyperbilirubinemia are:
- Exchange Transfusion Therapy.
- Phototherapy - uses light to convert insoluble bilirubin into water-soluble forms that can be excreted by the body.
- Intravenous Immunoglobulins (IVIG) - Administration of IVIG to newborns with hyperbilirubinemia due to ABO hemolytic disease with positive direct Coomb test decreases the need for exchange transfusion without causing immediate adverse effects[4].
Surgery
The mainstay of treatment for kernicterus is medical therapy. Surgery is may be needed to treat the causes of hyperbilirubinemia such as in biliary atresia[11].
Primary Prevention
Preventing jaundice by advising the mother to breasting feed her baby every 2-3 hrs a day. Giving water or dextrose water for breast feeding infants is not recommeded because it will not prevent hyperbilirubinemia[12].
Secondary Prevention
Identify and evaluat jaundice.
Post delivery, check serum bilirubin levels in all newborns with jaundice in the first 24 hours.
Know that visual estimation of bilirubin levels is inaccurate.
Monitor preterm( i.e less than 37 weeks) newborns closely.
Do a thorough risk assessment for all newborns.
Educate the parents about jaundice and alarm them.
Treat jaundiced neonates based on the bilirubin leves with phototherapy or exchange transfusion[12].
References
- ↑ 1.0 1.1 [+https://doi.org/10.1542/neo.4-2-e33 "Kernicterus: Past, Present, and Future | American Academy of Pediatrics"] Check
|url=value (help). - ↑ Das S, van Landeghem FKH (2019). "Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus". Diagnostics (Basel). 9 (1). doi:10.3390/diagnostics9010024. PMC 6468386. PMID 30823396.
- ↑ 3.0 3.1 Dennery PA, Seidman DS, Stevenson DK (2001). "Neonatal hyperbilirubinemia". N Engl J Med. 344 (8): 581–90. doi:10.1056/NEJM200102223440807. PMID 11207355.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 "Kernicterus - StatPearls - NCBI Bookshelf".
- ↑ Alkén J, Håkansson S, Ekéus C, Gustafson P, Norman M (2019). "Rates of Extreme Neonatal Hyperbilirubinemia and Kernicterus in Children and Adherence to National Guidelines for Screening, Diagnosis, and Treatment in Sweden". JAMA Netw Open. 2 (3): e190858. doi:10.1001/jamanetworkopen.2019.0858. PMC 6583272 Check
|pmc=value (help). PMID 30901042. - ↑ Freudenberger DC, Shah RD (2021). "A narrative review of the health disparities associated with malignant pleural mesothelioma". J Thorac Dis. 13 (6): 3809–3815. doi:10.21037/jtd-20-3516. PMC 8264689 Check
|pmc=value (help). PMID 34277071 Check|pmid=value (help). - ↑ "What are Jaundice and Kernicterus? | CDC".
- ↑ Trikalinos TA, Chung M, Lau J, Ip S (2009). "Systematic review of screening for bilirubin encephalopathy in neonates". Pediatrics. 124 (4): 1162–71. doi:10.1542/peds.2008-3545. PMID 19786450.
- ↑ "Kernicterus Article".
- ↑ Wisnowski JL, Panigrahy A, Painter MJ, Watchko JF (2014). "Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise". Semin Perinatol. 38 (7): 422–8. doi:10.1053/j.semperi.2014.08.005. PMC 4250342. PMID 25267277.
- ↑ Sumida W, Uchida H, Tanaka Y, Tainaka T, Shirota C, Murase N; et al. (2017). "Review of redo-Kasai portoenterostomy for biliary atresia in the transition to the liver transplantation era". Nagoya J Med Sci. 79 (3): 415–420. doi:10.18999/nagjms.79.3.415. PMC 5577027. PMID 28878446.
- ↑ 12.0 12.1 "A Practical Approach to Neonatal Jaundice - American Family Physician".