Neonatal jaundice

Last updated

Neonatal jaundice
Other namesNeonatal hyperbilirubinemia, neonatal icterus, jaundice in newborns
Jaundice in newborn.jpg
Jaundice in a newborn
Specialty Pediatrics
Symptoms Yellowish discoloration of the skin and white part of the eyes [1]
Complications Seizures, cerebral palsy, kernicterus [1]
Usual onsetNewborns [1]
TypesPhysiologic, pathologic [1]
Causes Red blood cell breakdown, liver disease, infection, hypothyroidism, metabolic disorders [2] [1]
Diagnostic method Based on symptoms, confirmed by bilirubin [1]
TreatmentMore frequent feeding, phototherapy, exchange transfusions [1]
Frequency>50% of babies [1]

Neonatal jaundice is a yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels. [1] Other symptoms may include excess sleepiness or poor feeding. [1] Complications may include seizures, cerebral palsy, or kernicterus. [1]

Contents

In most of cases there is no specific underlying physiologic disorder. [2] In other cases it results from red blood cell breakdown, liver disease, infection, hypothyroidism, or metabolic disorders (pathologic). [2] [1] A bilirubin level more than 34 μmol/L (2 mg/dL) may be visible. [1] Concerns, in otherwise healthy babies, occur when levels are greater than 308 μmol/L (18 mg/dL), jaundice is noticed in the first day of life, there is a rapid rise in levels, jaundice lasts more than two weeks, or the baby appears unwell. [1] In those with concerning findings further investigations to determine the underlying cause are recommended. [1]

The need for treatment depends on bilirubin levels, the age of the child, and the underlying cause. [1] [3] Treatments may include more frequent feeding, phototherapy, or exchange transfusions. [1] In those who are born early more aggressive treatment tends to be required. [1] Physiologic jaundice generally lasts less than seven days. [1] The condition affects over half of babies in the first week of life. [1] Of babies that are born early about 80% are affected. [2] Globally over 100,000 late-preterm and term babies die each year as a result of jaundice. [4]

Sign and symptoms

Bronze baby syndrome (dark pigmentation of skin).

The primary symptom is yellowish discoloration of the white part of the eyes and skin in a newborn baby. [1] Other symptoms may include excess sleepiness or poor feeding. [1]

A bilirubin level more than 34 μmol/L (2 mg/dL) may be visible. [1] For the feet to be affected level generally must be over 255 μmol/L (15 mg/dL). [1]

Complications

Prolonged hyperbilirubinemia (severe jaundice) can result in chronic bilirubin encephalopathy (kernicterus). [5] [6] Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus. [7]

Infants with kernicterus may have a fever [8] or seizures. [9] High pitched crying is an effect of kernicterus.[ citation needed ]

Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment. [10]

Causes

In newborns, jaundice tends to develop because of two factors—the breakdown of fetal hemoglobin as it is replaced with adult hemoglobin and the relatively immature metabolic pathways of the liver, which are unable to conjugate and so excrete bilirubin as quickly as an adult. This causes an accumulation of bilirubin in the blood (hyperbilirubinemia), leading to the symptoms of jaundice.[ citation needed ]

If the neonatal jaundice is not resolved with simple phototherapy, other causes such as biliary atresia, Progressive familial intrahepatic cholestasis, bile duct paucity, Alagille syndrome, alpha 1-antitrypsin deficiency, and other pediatric liver diseases should be considered. The evaluation for these will include blood work and a variety of diagnostic tests. Prolonged neonatal jaundice is serious and should be followed up promptly. [11]

Severe neonatal jaundice may indicate the presence of other conditions contributing to the elevated bilirubin levels, of which there are a large variety of possibilities (see below). These should be detected or excluded as part of the differential diagnosis to prevent the development of complications. They can be grouped into the following categories:

Neonatal jaundice
Unconjugated bilirubin Conjugated bilirubin
Pathologic Physiological jaundice of neonates Hepatic Post-hepatic
Hemolytic Non-hemolytic
Intrinsic causesExtrinsic causes

Unconjugated

Hemolytic

Intrinsic causes of hemolysis
Extrinsic causes of hemolysis

Non-hemolytic causes

Conjugated (Direct)

Liver causes

Post-liver

Non-organic causes

Breastfeeding jaundice

"Breastfeeding jaundice" (or "lack of breastfeeding jaundice") is caused by insufficient breast milk intake, [13] resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This leads to increased enterohepatic circulation, resulting in increased reabsorption of bilirubin from the intestines. [14] Usually occurring in the first week of life, most cases can be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production. [15]

Breast milk jaundice

Whereas breastfeeding jaundice is a mechanical problem, breast milk jaundice is a biochemical occurrence and the higher bilirubin possibly acts as an antioxidant. Breast milk jaundice occurs later in the newborn period, with the bilirubin level usually peaking in the sixth to 14th days of life. This late-onset jaundice may develop in up to one third of healthy breastfed infants. [16]

  1. The gut is sterile at birth and normal gut flora takes time to establish. The bacteria in the adult gut convert conjugated bilirubin to stercobilinogen which is then oxidized to stercobilin and excreted in the stool. In the absence of sufficient bacteria, the bilirubin is de-conjugated by brush border β-glucuronidase and reabsorbed. This process of re-absorption is called enterohepatic circulation. It has been suggested that bilirubin uptake in the gut (enterohepatic circulation) is increased in breast fed babies, possibly as the result of increased levels of epidermal growth factor (EGF) in breast milk. [17] Breast milk also contains glucoronidase which will increase deconjugation and enterohepatic recirculation of bilirubin.
  2. The breast-milk of some women contains a metabolite of progesterone called 3-alpha-20-beta pregnanediol. This substance inhibits the action of the enzyme uridine diphosphoglucuronic acid (UDPGA) glucuronyl transferase responsible for conjugation and subsequent excretion of bilirubin. In the newborn liver, activity of glucuronyl transferase is only at 0.1-1% of adult levels, so conjugation of bilirubin is already reduced. Further inhibition of bilirubin conjugation leads to increased levels of bilirubin in the blood. [18] However, these results have not been supported by subsequent studies. [19]
  3. An enzyme in breast milk called lipoprotein lipase produces increased concentration of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase, which again leads to decreased conjugation and subsequent excretion of bilirubin. [20]

Physiological jaundice

Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This is called physiological jaundice. This pattern of hyperbilirubinemia has been classified into two functionally distinct periods. [21]

  1. Term infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204 μmol/L (12 mg/dL).
  2. Preterm infants - jaundice lasts for about two weeks, with a rapid rise of serum bilirubin up to 255 μmol/L (15 mg/dL).
  1. Preterm infants - phase two can last more than one month.
  2. Exclusively breastfed infants - phase two can last more than one month.

Mechanisms involved in physiological jaundice include:

Diagnosis

Diagnosis is often by measuring the serum bilirubin level in the blood. [3] In those who are born after 35 weeks and are more than a day old transcutaneous bilirubinometer may also be used. [3] The use of an icterometer, a piece of transparent plastic painted in five transverse strips of graded yellow lines, is not recommended. [3]

Transcutaneous bilirubinometer

This is hand held, portable and rechargeable but expensive. When pressure is applied to the photoprobe, a xenon tube generates a strobe light, and this light passes through the subcutaneous tissue. The reflected light returns through the second fiber optic bundle to the spectrophotometric module. The intensity of the yellow color in this light, after correcting for the hemoglobin, is measured and instantly displayed in arbitrary units.[ citation needed ]

Pathological jaundice

Any of the following features suggests pathological jaundice:[ citation needed ]

  1. Clinical jaundice appearing in the first 24 hours or greater than 14 days of life.
  2. Increases in the level of total bilirubin by more than 8.5 μmol/L (0.5 mg/dL) per hour or (85 μmol/L) 5 mg/dL per 24 hours.
  3. Total bilirubin more than 331.5 μmol/L (19.5 mg/dL) (hyperbilirubinemia).
  4. Direct bilirubin more than 34 μmol/L (2.0 mg/dL).

The signs which help detect pathological jaundice are the presence of intrauterine growth restriction, stigma of intrauterine infections (e.g. cataracts, small head, and enlargement of the liver and spleen), cephalohematoma, bruising, signs of bleeding in the brain's ventricles. History of illness is noteworthy. Family history of jaundice and anemia, family history of neonatal or early infant death due to liver disease, maternal illness suggestive of viral infection (fever, rash or lymphadenopathy), maternal drugs (e.g. sulphonamides, anti-malarials causing red blood cell destruction in G6PD deficiency) are suggestive of pathological jaundice in neonates.[ citation needed ]

Treatment

The bilirubin levels for initiative of phototherapy varies depends on the age and health status of the newborn. However, any newborn with a total serum bilirubin greater than 359 μmol/L ( 21 mg/dL) should receive phototherapy. [25]

Phototherapy

Phototherapy is the main treatment of neonatal jaundice Phototherapy1.jpg
Phototherapy is the main treatment of neonatal jaundice

Babies with neonatal jaundice may be treated with colored light called phototherapy, which works by changing trans-bilirubin into the water-soluble cis-bilirubin isomer. [26] [27] [28] : 2533 

The phototherapy involved is not ultraviolet light therapy but rather a specific frequency of blue light. The light can be applied with overhead lamps, which means that the baby's eyes need to be covered, or with a device called a biliblanket, which sits under the baby's clothing close to its skin. [27]

The use of phototherapy was first discovered, accidentally, at Rochford Hospital in Essex, England, when a nurse, Sister Jean Ward, noticed that babies exposed to sunlight had reduced jaundice, and a pathologist, Dr. Perryman, who noticed that a vial of blood left in the sun had turned green. Drs Cremer, Richards and Dobbs put together these observations, [29] leading to a landmark randomized clinical trial which was published in Pediatrics in 1968; it took another ten years for the practice to become established. [27] [30] Massage therapy could be useful in addition to phototherapy in order to reduce the phototherapy duration. However, it does not appear to reduce the requirement for phototherapy in the treatment of neonatal jaundice. [31]

Recent studies from several countries show that phototherapy can safely and effectively be performed in the family's home, and since 2022 home phototherapy is recommended as an alternative to readmission to hospital in the American national guidelines. [32] [33] [34] However, there have been several reports about the possible relationship between neonatal phototherapy and the increased risk of future cancer. A recent systematic review has found that there may be a statistically significant association between phototherapy and various hematopoietic cancers (especially myeloid leukemia). [35]

Exchange transfusions

Much like with phototherapy the level at which exchange transfusion should occur depends on the health status and age of the newborn. It should however be used for any newborn with a total serum bilirubin of greater than 428 μmol/L ( 25 mg/dL ). [25] [28] : 2533 

Research

Penicillamine was studied in the 1970s in hyperbilirubinemia due to ABO hemolytic disease. [36] While tin mesoporphyrin IX may decrease bilirubin such use is not recommended in babies. [36] Preclinical studies have looked at minocycline to help prevent neurotoxicity. [36] Clofibrate may decrease the duration of phototherapy. [36] Evidence as of 2012 however is insufficient to recommend its use. [37]

Related Research Articles

<span class="mw-page-title-main">Jaundice</span> Abnormal pigmentation symptom for disease of the liver

Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine.

<span class="mw-page-title-main">Bilirubin</span> Chemical compound

Bilirubin (BR) is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the destruction of aged or abnormal red blood cells. In the first step of bilirubin synthesis, the heme molecule is stripped from the hemoglobin molecule. Heme then passes through various processes of porphyrin catabolism, which varies according to the region of the body in which the breakdown occurs. For example, the molecules excreted in the urine differ from those in the feces. The production of biliverdin from heme is the first major step in the catabolic pathway, after which the enzyme biliverdin reductase performs the second step, producing bilirubin from biliverdin.

Liver function tests, also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), albumin, bilirubin, and others. The liver transaminases aspartate transaminase and alanine transaminase are useful biomarkers of liver injury in a patient with some degree of intact liver function.

<span class="mw-page-title-main">Kernicterus</span> Medical condition

Kernicterus is a bilirubin-induced brain dysfunction. The term was coined in 1904 by Christian Georg Schmorl. Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is neurotoxic when its concentration in the blood is too high, a condition known as hyperbilirubinemia. Hyperbilirubinemia may cause bilirubin to accumulate in the grey matter of the central nervous system, potentially causing irreversible neurological damage. Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage and even death.

<span class="mw-page-title-main">Gilbert's syndrome</span> Medical condition

Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority. Many people never have symptoms. Occasionally jaundice may occur.

<span class="mw-page-title-main">Hemolytic disease of the newborn</span> Fetal and neonatal alloimmune blood condition

Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells. The fetus can develop reticulocytosis and anemia. The intensity of this fetal disease ranges from mild to very severe, and fetal death from heart failure can occur. When the disease is moderate or severe, many erythroblasts are present in the fetal blood, earning these forms of the disease the name erythroblastosis fetalis.

<span class="mw-page-title-main">Bili light</span> Medical therapeutic tool to treat newborn jaundice

A bili light is a light therapy tool to treat newborn jaundice (hyperbilirubinemia). High levels of bilirubin can cause brain damage (kernicterus), leading to cerebral palsy, auditory neuropathy, gaze abnormalities and dental enamel hypoplasia. The therapy uses a blue light (420–470 nm) that converts bilirubin into an (E,Z)-isomer that can be excreted in the urine and feces. Soft goggles are put on the child to reduce eye damage from the high intensity light. The baby is kept naked or only wearing a diaper, and is turned over frequently to expose more of the skin.

<span class="mw-page-title-main">Crigler–Najjar syndrome</span> Rare inherited disorder affecting the metabolism of bilirubin

Crigler–Najjar syndrome is a rare inherited disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red blood cells. The disorder results in a form of nonhemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants. The disorder is inherited in an autosomal recessive manner. The annual incidence is estimated at 1 in 1,000,000.

In ABO hemolytic disease of the newborn maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

Hemolytic disease of the newborn (anti-Kell1) is the second most common cause of severe hemolytic disease of the newborn (HDN) after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective.

Hemolytic disease of the newborn (anti-Rhc) can range from a mild to a severe disease. It is the third most common cause of severe HDN. Rh disease is the most common and hemolytic disease of the newborn (anti-Kell) is the second most common cause of severe HDN. It occurs more commonly in women who are Rh D negative.

<span class="mw-page-title-main">Lucey–Driscoll syndrome</span> Medical condition

Lucey–Driscoll syndrome is an autosomal recessive metabolic disorder affecting enzymes involved in bilirubin metabolism. It is one of several disorders classified as a transient familial neonatal unconjugated hyperbilirubinemia.

Neonatal cholestasis refers to elevated levels of conjugated bilirubin identified in newborn infants within the first few months of life. Conjugated hyperbilirubinemia is clinically defined as >20% of total serum bilirubin or conjugated bilirubin concentration greater than 1.0 mg/dL regardless of total serum bilirubin concentration. The differential diagnosis for neonatal cholestasis can vary extensively. However, the underlying disease pathology is caused by improper transport and/or defects in excretion of bile from hepatocytes leading to an accumulation of conjugated bilirubin in the body. Generally, symptoms associated with neonatal cholestasis can vary based on the underlying cause of the disease. However, most infants affected will present with jaundice, scleral icterus, failure to thrive, acholic or pale stools, and dark urine.

Hemolytic disease of the newborn (anti-RhE) is caused by the anti-RhE antibody of the Rh blood group system. The anti-RhE antibody can be naturally occurring, or arise following immune sensitization after a blood transfusion or pregnancy.

<span class="mw-page-title-main">Breastfeeding</span> Feeding of babies or young children with milk from a womans breast

Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be pumped and fed to the infant. The World Health Organization (WHO) recommends that breastfeeding begin within the first hour of a baby's life and continue as often and as much as the baby wants. Health organizations, including the WHO, recommend breastfeeding exclusively for six months. This means that no other foods or drinks, other than vitamin D, are typically given. The WHO recommends exclusive breastfeeding for the first 6 months of life, followed by continued breastfeeding with appropriate complementary foods for up to 2 years and beyond. Of the 135 million babies born every year, only 42% are breastfed within the first hour of life, only 38% of mothers practice exclusive breastfeeding during the first six months, and 58% of mothers continue breastfeeding up to the age of two years and beyond.

Neonatal hypoglycemia occurs when the neonate's blood glucose level is less than the newborn's body requirements for factors such as cellular energy and metabolism. There is inconsistency internationally for diagnostic thresholds. In the US, hypoglycemia is when the blood glucose level is below 30 mg/dL within the first 24 hours of life and below 45 mg/dL thereafter. In the UK, however, lower and more variable thresholds are used. The neonate's gestational age, birth weight, metabolic needs, and wellness state of the newborn has a substantial impact on the neonates blood glucose level. There are known risk factors that can be both maternal and neonatal. This is a treatable condition. Its treatment depends on the cause of the hypoglycemia. Though it is treatable, it can be fatal if gone undetected. Hypoglycemia is the most common metabolic problem in newborns.

<span class="mw-page-title-main">Bilirubin glucuronide</span> Chemical compound

Bilirubin glucuronide is a water-soluble reaction intermediate over the process of conjugation of indirect bilirubin. Bilirubin glucuronide itself belongs to the category of conjugated bilirubin along with bilirubin di-glucuronide. However, only the latter one is primarily excreted into the bile in the normal setting.

Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.

Hyperbilirubinemia is a clinical condition describing an elevation of blood bilirubin level due to the inability to properly metabolise or excrete bilirubin, a product of erythrocytes breakdown. In severe cases, it is manifested as jaundice, the yellowing of tissues like skin and the sclera when excess bilirubin deposits in them. The US records 52,500 jaundice patients annually. By definition, bilirubin concentration of greater than 3 mg/ml is considered hyperbilirubinemia, following which jaundice progressively develops and becomes apparent when plasma levels reach 20 mg/ml. Rather than a disease itself, hyperbilirubinemia is indicative of multifactorial underlying disorders that trace back to deviations from regular bilirubin metabolism. Diagnosis of hyperbilirubinemia depends on physical examination, urinalysis, serum tests, medical history and imaging to identify the cause. Genetic diseases, alcohol, pregnancy and hepatitis viruses affect the likelihood of hyperbilirubinemia. Causes of hyperbilirubinemia mainly arise from the liver. These include haemolytic anaemias, enzymatic disorders, liver damage and gallstones. Hyperbilirubinemia itself is often benign. Only in extreme cases does kernicterus, a type of brain injury, occur. Therapy for adult hyperbilirubinemia targets the underlying diseases but patients with jaundice often have poor outcomes.

<span class="mw-page-title-main">Tin mesoporphyrin</span> Compound in biochemistry

Tin mesoporphyrin (SnMP), also known as stannsoporfin, is a synthetic metalloporphyrin, which consists of a group of competitive inhibitors of heme oxygenase, a rate-limiting enzyme in the heme catabolic pathway. Tin mesoporphyrin is one of the more potent metalloporphyrin compound out of all the others.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 "Neonatal Hyperbilirubinemia". Merck Manuals Professional Edition. August 2015. Retrieved 11 December 2017.
  2. 1 2 3 4 "Jaundice in newborn babies under 28 days | Guidance and guidelines". NICE. October 2016. Retrieved 11 December 2017.
  3. 1 2 3 4 "Jaundice in newborn babies under 28 days". NICE. October 2016. Retrieved 11 December 2017.
  4. ↑ Olusanya, BO; Teeple, S; Kassebaum, NJ (February 2018). "The Contribution of Neonatal Jaundice to Global Child Mortality: Findings From the GBD 2016 Study". Pediatrics. 141 (2): e20171471. doi: 10.1542/peds.2017-1471 . PMID   29305393.
  5. ↑ Juetschke, L.J. (2005, Mar/Apr). Kernicterus: still a concern. Neonatal Network, 24(2), 7-19, 59-62
  6. ↑ Colletti, JE; Kothari, S; Kothori, S; Jackson, DM; Kilgore, KP; Barringer, K (November 2007). "An emergency medicine approach to neonatal hyperbilirubinemia". Emerg. Med. Clin. North Am. 25 (4): 1117–35, vii. doi:10.1016/j.emc.2007.07.007. PMID   17950138.
  7. ↑ Watchko, JF (December 2006). "Hyperbilirubinemia and bilirubin toxicity in the late preterm infant" (PDF). Clin Perinatol. 33 (4): 839–52, abstract ix. doi:10.1016/j.clp.2006.09.002. PMID   17148008. Archived from the original (PDF) on 8 August 2017. Retrieved 26 September 2019.
  8. ↑ Shah, Z; Chawla, A; Patkar, D; Pungaonkar, S (March 2003). "MRI in kernicterus". Australas Radiol. 47 (1): 55–7. doi:10.1046/j.1440-1673.2003.00973.x. PMID   12581055.
  9. ↑ Malik, BA; Butt, MA; Shamoon, M; Tehseen, Z; Fatima, A; Hashmat, N (December 2005). "Seizures etiology in the newborn period". Journal of the College of Physicians and Surgeons--Pakistan. 15 (12): 786–90. PMID   16398972.
  10. ↑ Gómez, M; Bielza, C; Fernández del Pozo, JA; Ríos-Insua, S (2007). "A graphical decision-theoretic model for neonatal jaundice". Med Decis Making. 27 (3): 250–65. doi:10.1177/0272989X07300605. PMID   17545496. S2CID   14514900.
  11. ↑ Gilmour, Susan M (December 2004). "Prolonged neonatal jaundice: When to worry and what to do". Paediatrics & Child Health. 9 (10): 700–704. doi:10.1093/pch/9.10.700. ISSN   1205-7088. PMC   2724143 . PMID   19688078.
  12. 1 2 Click, R; Dahl-Smith, J; Fowler, L; DuBose, J; Deneau-Saxton, M; Herbert, J (January 2013). "An osteopathic approach to reduction of readmissions for neonatal jaundice". Osteopathic Family Physician. 5 (1): 17–23. doi:10.1016/j.osfp.2012.09.005. Archived from the original on 15 April 2013.
  13. ↑ Lynn C. Garfunkel; Jeffrey; Cynthia Christy (2002). Mosby's pediatric clinical advisor: instant diagnosis and treatment. Elsevier Health Sciences. pp. 200–. ISBN   978-0-323-01049-8 . Retrieved 14 June 2010.
  14. ↑ Leung, A. K.; Sauve, R. S. (1 December 1989). "Breastfeeding and breast milk jaundice". Journal of the Royal Society of Health. 109 (6): 213–217. doi:10.1177/146642408910900615. ISSN   0264-0325. PMID   2513410. S2CID   38974909.
  15. ↑ CDC (13 November 2020). "Jaundice". Centers for Disease Control and Prevention. Retrieved 12 July 2021.
  16. ↑ Dennis, Maj Beth L.; Porter, Meredith L. (15 February 2002). "Hyperbilirubinemia in the Term Newborn". American Family Physician. 65 (4): 599–606. PMID   11871676.
  17. ↑ Kumral, A; Ozkan H; Duman N; et al. (2009). "Breast milk jaundice correlates with high levels of epidermal growth factor". Pediatr Res. 66 (2): 218–21. doi: 10.1203/pdr.0b013e3181ac4a30 . PMID   19617811.
  18. ↑ Arias, IM; Gartner LM; Seifter S; Furman M (1964). "Prolonged neonatal unconjugated hyperbilirubinemia associated with breast feeding and a steroid, pregnane-3(alpha), 20(beta)-diol in maternal milk that inhibits glucuronide formation in vitro". J Clin Invest. 43 (11): 2037–47. doi:10.1172/jci105078. PMC   441992 . PMID   14228539.
  19. ↑ Murphy, J F; Hughes I; Verrier Jones ER; Gaskell S; Pike AW (1981). "Pregnanediols and breast-milk jaundice". Arch Dis Child. 56 (6): 474–76. doi:10.1136/adc.56.6.474. PMC   1627473 . PMID   7259280.
  20. ↑ Poland, R L; Schultz GE; Gayatri G (1980). "High milk lipase activity associated with breastmilk jaundice". Pediatr Res. 14 (12): 1328–31. doi: 10.1203/00006450-198012000-00011 . PMID   6782543.
  21. ↑ Porter, Meredith L.; Dennis, Maj Beth L. (15 February 2002). "Hyperbilirubinemia in the Term Newborn". American Family Physician. 65 (4): 599–606. ISSN   0002-838X. PMID   11871676.
  22. 1 2 3 Page 45 in: Obstetrics & Gynaecology, by B. Jain, 2002. ISBN   8180562107, 9788180562105
  23. ↑ McDonagh, A. F. (2007). "Movement of Bilirubin and Bilirubin Conjugates Across the Placenta". Pediatrics. 119 (5): 1032–1033, author 1033 1033. doi:10.1542/peds.2006-3669. PMID   17473108. S2CID   21269991.
  24. ↑ Harrison, K. L. (1979). "Fetal Erythrocyte Lifespan". Journal of Paediatrics and Child Health. 15 (2): 96–97. doi:10.1111/j.1440-1754.1979.tb01197.x. PMID   485998. S2CID   5370064.
  25. 1 2 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia (July 2004). "Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation". Pediatrics. 114 (1): 297–316. doi: 10.1542/peds.114.1.297 . PMID   15231951.
  26. ↑ Stokowski LA (December 2006). "Fundamentals of phototherapy for neonatal jaundice". Adv Neonatal Care. 6 (6): 303–12. doi:10.1016/j.adnc.2006.08.004. PMID   17208161. S2CID   31233601.
  27. 1 2 3 Jones, Clay (9 May 2014). "Separating Fact from Fiction in the Not-So-Normal Newborn Nursery: Newborn Jaundice". Science-Based Medicine.
  28. 1 2 Wolkoff, Allan W. (2012). "Chapter 303: The Hyperbilirubinemias". In Longo, Dan L.; Kasper, Dennis L. (eds.). Harrison's principles of internal medicine (18th ed.). New York: McGraw-Hill. ISBN   978-0071748896.
  29. ↑ CREMER, RJ; PERRYMAN, PW; RICHARDS, DH (24 May 1958). "Influence of light on the hyperbilirubinaemia of infants". Lancet. 1 (7030): 1094–7. doi:10.1016/s0140-6736(58)91849-x. PMID   13550936.
  30. ↑ Lucey, J; Ferriero, M; Hewitt, J (June 1968). "Prevention of hyperbilirubinemia of prematurity by phototherapy". Pediatrics. 41 (6): 1047–54. doi:10.1542/peds.41.6.1047. PMID   5652916. S2CID   41816888.
  31. ↑ Abdellatif, Mohammed (February 2020). "Massage therapy for the treatment of neonatal jaundice: A systematic review and network meta-analysis". Journal of Neonatal Nursing. 26 (1): 17–24. doi: 10.1016/j.jnn.2019.09.002 .
  32. ↑ Anderson, Candice Megan; Kandasamy, Yogavijayan; Kilcullen, Meegan (August 2021). "The efficacy of home phototherapy for physiological and non-physiological neonatal jaundice: A systematic review". Journal of Neonatal Nursing. 28 (5): 312–326. doi:10.1016/j.jnn.2021.08.010. S2CID   238646014.
  33. ↑ Pettersson, M.; Eriksson, M.; Albinsson, E.; Ohlin, A. (1 May 2021). "Home phototherapy for hyperbilirubinemia in term neonates—an unblinded multicentre randomized controlled trial". European Journal of Pediatrics. 180 (5): 1603–1610. doi:10.1007/s00431-021-03932-4. ISSN   1432-1076. PMC   8032579 . PMID   33469713.
  34. ↑ Kemper, A. R.; Newman, T. B.; Slaughter, J. L.; Maisels, M. J.; Watchko, J. F.; Downs, S. M.; Grout, R. W.; Bundy, D. G.; Stark, A. R.; Bogen, D. L.; Holmes, A. V.; Feldman-Winter, L. B.; Bhutani, V. K.; Brown, S. R.; Maradiaga Panayotti, G. M.; Okechukwu, K.; Rappo, P. D.; Russell, T. L. (2022). "Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation". Pediatrics. 150 (3). doi: 10.1542/peds.2022-058859 . PMID   35927462 . Retrieved 20 September 2022.
  35. ↑ Abdellatif, Mohammed, et al. "Association between neonatal phototherapy and future cancer: an updated systematic review and meta-analysis." European Journal of Pediatrics (2022): 1-13
  36. 1 2 3 4 Mancuso, Cesare (15 May 2017). "Bilirubin and brain: A pharmacological approach". Neuropharmacology. 118: 113–123. doi:10.1016/j.neuropharm.2017.03.013. PMID   28315352. S2CID   21001248.
  37. ↑ Gholitabar, M; McGuire, H; Rennie, J; Manning, D; Lai, R (12 December 2012). "Clofibrate in combination with phototherapy for unconjugated neonatal hyperbilirubinaemia". The Cochrane Database of Systematic Reviews. 12 (3): CD009017. doi:10.1002/14651858.CD009017.pub2. PMC   6426433 . PMID   23235669.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.