Jaundice in children

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Anaya, M.D.[2]

Synonyms and keywords: Jaundice in kids; hyperbilirubinemia

Overview

Historical Perspective

  • The word 'Jaundice' was derived from the french word for yellow which is jaune.[1]
  • Earliest known texts of Icterus neonatorum dates back to the medical records of the Providence Lying-in Hospital in the late 19th century. A phenomenon observed amongst several neonates in their first week of stay and attributed to breastfeeding which was the predominant way neonates were fed.
  • A severe form termed Icterus gravis was better understood in the 1940s when advances in immunology and genetics led to the discovery of the Rh group of red cell antigens explaining its frequent recurrences in families after a first child becomes affected. These advances in hemolytic diseases birthed effective treatment modalities and screening methods that included maternal serology and amniocentesis in the perinatal period.
  • The Baby Boom Years of the 1960s which was flanked by an increase in birth rates led to the development of the Rh-immune antiglobulin. This was as a result of a corresponding rise in the rate of neonatal jaundice. Thus, Rh erythroblastosis became very rare with screening and immunoglobulin prophylaxis during the antenatal period. [2]
  • The principles behind Phototherapy were first discovered at Rochford General Hospital, Essex in the 1950s. Babies taken outside to the warm sunshine with the aim of taking a break from the confines of an incubator literarily became less yellow than before. Subsequently, lab results further confirmed this discovery. [3]

Classification

  • Jaundice may be classified into two broad categories based on time of onset and cause of jaundice.
    • Physiologic jaundice:
      • Seen after the first 24 hours of life.
      • Serum bilirubin levels never rise >5mg/dl daily and maximum concentration is about 12mg/dl and 14mg/dl in full terms and preterms respectively.
      • Reaches the highest levels in the 4th-5th days and resolves within 2 weeks in both full-term and preterm infants.
      • Infants usually appears well.
    • Pathological jaundice:
      • Appears anytime from the first few hours of life.
      • Serum bilirubin levels rise at a rate of >5mg/dl per day or 0.5mg/dl per hour and maximum concentration is usually >12mg/dl and >14mg/dl in full terms and preterms respectively.
      • Infants appear ill and pale with abnormal discoloration of urine and stool.[1]

Pathophysiology

  • Jaundice is caused by hyperbilirubinemia which is high concentrations of bilirubin in the bloodstream.
  • Hyperbilirubinemia can result from abnormalities in the metabolism of bilirubin which could occur at any stage from its production, hepatic metabolism, and its post hepatic transport.
  • Hemoglobin released from the breakdown of old or defective red blood cells is composed of heme and globin. Globin is broken down into its component amino acids and recycled while heme is split into iron and biliverdin by the enzyme, heme oxygenase in the reticuloendothelial system. Iron is transferred to ferritin and used again to make hemoglobin while biliverdin is converted to bilirubin by biliverdin reductase. [1]
  • Bilirubin, which is water-insoluble becomes coupled to albumin and transported into hepatic cells for conjugation.
  • This albumin-bilirubin compound is broken down and the unconjugated bilirubin enters the cytosol of hepatocytes to be conjugated to glucuronic acid in the endoplasmic reticulum by the enzyme, Uridine diphosphate glucuronosyltransferase (UDPGT). [4]
  • Conjugated bilirubin is secreted into bile and then into the small intestine after being stored in the gall bladder. It eventually gets to the colon where it is acted upon by bacterial flora and deconjugated to urobilinogen. Most of these are excreted into feces as the brown pigment, stercobilin, and the rest is reabsorbed into the blood, converted to yellow urobilin which is eventually excreted into the urine. [5]
  • Conjugated or unconjugated hyperbilirubinemia gives a clue as to the defective mechanism/point in the system responsible for the metabolism of bilirubin.

Causes

Disease name] may be caused by [cause1], [cause2], or [cause3].

OR

Common causes of [disease] include [cause1], [cause2], and [cause3].

OR

The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

OR

The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.

Differentiating Jaundice in children from other Diseases

  • Differentials for jaundice are very limited however some skin discolorations in healthy individuals can look like jaundice in certain circumstances.
  • Use of the antimalarial and antihelminthic drug, Quinacrine can cause yellowish discoloration of the skin of individuals who take it.
  • Excessive consumption of fruits and vegetables high in carotenes such as carrots and sweet potatoes can cause a skin discoloration termed as Carotenoderma.
  • The above differentials spares the mucus membranes and sclera. [1][4]

Epidemiology and Demographics

  • The prevalence of jaundice varies among patient populations.
  • In infants born at term, 60% will develop jaundice in their first-week life. This rises to 80% in preterms. [1]
  • 5-10% of neonates will require being admitted for the treatment of pathological jaundice. [6]
  • Causes of jaundice also vary with age groups. In newborns, immature hepatic conjugation, hemolysis, and certain congenital disorders are top causes while Hepatitis A infection is a cause seen more in older children.
  • Death rate is 0.28 per 1 million live births. [4]

Age

  • Patients of all age groups may develop Jaundice.
  • It is more commonly observed in newborns and the elderly populations. [4]

Gender

  • Gender predilection can be observed in the etiology of jaundice.
  • An example is the documented male preponderance of Glucose-6-Phosphate dehydrogenase (G6PD) deficiency with an incidence of 4.5% males to 0.5% in females. [7]

Race

  • Racial predilection for Jaundice is observed in a cause of unconjugated hyperbilirubinemia, Gilbert syndrome.
  • This is caused by a genetic mutation in the gene responsible for the production of the enzyme, UDPGT. It is a diagnosis of exclusion and symptoms are triggered by stressful situations like dehydration, illness.
  • It has a prevalence of 5-10% in Caucasian and Asian populations. [7]

Risk Factors

  • Common risk factors in the development of Jaundice in children are:
    • Family history of jaundice
    • Family history of a child born with jaundice
    • Hyperthyroidism in mother
    • Medication use by mother
    • Gestational Diabetes Mellitus (GDM)
    • Race (Asian)
    • Age >25 years
    • ABO incompatibility
    • Rh incompatibility
    • Exclusive breastfeeding
    • Inability to breastfeed adequately
    • Primiparity
    • Oxytocin use during labor
    • Prematurity
    • Weight loss(child)
    • Male gender
    • Polycythemia
    • Cephalhematoma, hematoma in spleen or liver, resulting in excessive hemolysis with red blood cell breakdown
    • Trisomy 21
    • G6PD deficiency
    • Congenital infection (TORCHES) [8] [1]

Natural History, Complications and Prognosis

  • It is essential for every clinician to note that jaundice is not always a benign condition therefore, extensive investigation of a child with jaundice is necessary to prevent severe complications.
  • Bilirubin-induced neurological dysfunction (BIND) seen in the setting of extremely high unconjugated bilirubin levels is a rare complication.
  • It is a condition in which high levels of unconjugated bilirubin crosses the immature blood-brain-barrier of neonates and binds to glial tissue and brainstem nuclei.
  • Lack of colonic bacteria in neonates also predisposes them to this outcome due to increased enterohepatic reabsorption of deconjugated bilirubin.
  • Bilirubin encephalopathy, a catastrophic neurologic outcome known as Kernicterus or death are likely complications if treatment is either delayed or not promptly instituted.
  • Early symptoms of kernicterus are:
    • Poor feeding
    • Irritability
    • High-pitched cry
    • Apnea
    • Floppy muscles
  • As the illness progresses, more severe symptoms are:
    • Seizures
    • Muscular spasms
    • Cerebral palsy
    • Learning problems
    • Loss of hearing [9]
  • Prognosis of jaundice in children especially is very good with prompt diagnosis and treatment. However, conjugated hyperbilirubinemia from obstructions of the hepatic and biliary tree have poorer outcomes. [4]

Diagnosis

Symptoms

  • Symptoms of Jaundice in children may include the following:
    • Yellowish discoloration of the skin, sclera, and mucous membrane
    • Time of onset and duration
    • Progression. Involvement up to what body part?
    • Poor feeding
    • Irritability
    • Fever
    • Pruritus
    • Rash
    • Pains in the joints
    • Recent travel history
    • Diarrhea
    • Urine and stool color change
    • Anorexia
    • Weight loss
    • Body pains like abdominal discomfort/pains?


Physical Examination

  • Patients with jaundice usually appear yellow on the skin, mucous membranes, and/or sclera. A useful technique in assessing the severity of jaundice is by using the principle of skin discoloration progressing in a cephalo-caudal direction in newborns.
  • If discoloration has progresseed to the thigh level, samples for urgent serum bilirubin should be taken.
  • A limitation to this method is in infants who are already receiving phototherapy and those with darker colored skin.
  • Examination may be remarkable for other findings such as:
    • Irritable infant
    • Fever
    • Rash
    • Small or large for age
    • Lymph node enlargement
    • Muscle spasms
    • Unconsolable cry
    • Hepatomegaly
    • Splenomegaly

Laboratory Findings

  • Measuring the level of bilirubin.
    • Serum bilirubin from a blood sample. The total and conjugated portions are measured and the unconjugated fraction is measured by subtracting the conjugated fraction from the total.
    • Knowing the type of hyperbilirubinemia will guide further workup in identifying the cause of jaundice. Predominantly conjugated or mixed hyperbilirubinemia gives a clue of hepatic or post-hepatic etiology.
    • Transcutaneous bilirubinometer. The accuracy of this can be altered by skin thickness and color.
    • Bilimeter
  • Complete blood count with differentials and smear
  • Prothrombin time (PT)
  • Blood and Rh group
  • G6PD levels
  • Serum albumin
  • Liver function tests
    • AST
    • ALT
    • ALP
    • GGT
  • Viral serologies
    • Hepatitis A Virus (HAV)
    • HBV
    • HCV
    • HDV
    • HEV
  • Serology
  • Blood cultures
  • Urine microscopy, culture, and sensitivity
  • Stool microscopy, culture, and sensitivity
  • TORCH screening
  • Serum ferritin
  • Serum ceruloplasmin
  • Autoimmune antibodies

Electrocardiogram

  • There are no ECG findings associated with Jaundice in children.
  • It may be used to monitor cardiac rhythms during treatment.

X-ray

  • There are no x-ray findings associated with Jaundice in children.

Echocardiography/Ultrasound

  • There are no echocardiography findings associated with Jaundice in children.
  • Ultrasonography of the abdomen is used to screen for biliary atresia, choledochal cysts or cholestatic workup in the setting of conjugated hyperbilirubinemia.[7]

CT scan

  • CT scan of the abdomen is used to screen for biliary atresia, choledochal cysts, or cholestatic workup in the setting of conjugated hyperbilirubinemia.

MRI

  • MRI is used to screen for biliary atresia, choledochal cysts, or cholestatic workup in the setting of conjugated hyperbilirubinemia.

Other Imaging Findings

There are no other imaging findings associated with [disease name].

OR

[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

  • [Disease name] may also be diagnosed using [diagnostic study name].
  • Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

  • There is no treatment for [disease name]; the mainstay of therapy is supportive care.
  • The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
  • [Medical therapy 1] acts by [mechanism of action 1].
  • Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

  • Surgery is the mainstay of therapy for [disease name].
  • [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
  • [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

  • There are no primary preventive measures available for [disease name].
  • Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
  • Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 "StatPearls". 2020. PMID 30422525.
  2. https://www.rimed.org/medhealthri/2010-05/2010-05-154.pdf
  3. https://www.viapath.co.uk/news-and-press/the-birth-of-phototherapy
  4. 4.0 4.1 4.2 4.3 4.4 "StatPearls". 2020. PMID 31334972.
  5. https://www.rahulgladwin.com/noteblog/gastroenterology/jaundice.php
  6. Mishra S, Agarwal R, Deorari AK, Paul VK (2008). "Jaundice in the newborns". Indian J Pediatr. 75 (2): 157–63. doi:10.1007/s12098-008-0024-7. PMID 18334797.
  7. 7.0 7.1 7.2 Chee YY, Chung PH, Wong RM, Wong KK (2018). "Jaundice in infants and children: causes, diagnosis, and management". Hong Kong Med J. 24 (3): 285–292. doi:10.12809/hkmj187245. PMID 29807950.
  8. Mojtahedi SY, Izadi A, Seirafi G, Khedmat L, Tavakolizadeh R (2018). "Risk Factors Associated with Neonatal Jaundice: A Cross-Sectional Study from Iran". Open Access Maced J Med Sci. 6 (8): 1387–1393. doi:10.3889/oamjms.2018.319. PMC 6108787. PMID 30159062.
  9. https://www.nhs.uk/conditions/jaundice-newborn/complications/