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American Family Physician Feb 2017Jaundice in adults can be an indicator of significant underlying disease. It is caused by elevated serum bilirubin levels in the unconjugated or conjugated form. The... (Review)
Review
Jaundice in adults can be an indicator of significant underlying disease. It is caused by elevated serum bilirubin levels in the unconjugated or conjugated form. The evaluation of jaundice relies on the history and physical examination. The initial laboratory evaluation should include fractionated bilirubin, a complete blood count, alanine transaminase, aspartate transaminase, alkaline phosphatase, ?-glutamyltransferase, prothrombin time and/or international normalized ratio, albumin, and protein. Imaging with ultrasonography or computed tomography can differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders. Ultrasonography is the least invasive and least expensive imaging method. A more extensive evaluation may include additional cancer screening, biliary imaging, autoimmune antibody assays, and liver biopsy. Unconjugated hyperbilirubinemia occurs with increased bilirubin production caused by red blood cell destruction, such as hemolytic disorders, and disorders of impaired bilirubin conjugation, such as Gilbert syndrome. Conjugated hyperbilirubinemia occurs in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree.
Topics: Cholestasis; Diagnosis, Differential; Humans; Hyperbilirubinemia; Jaundice; Liver Diseases
PubMed: 28145671
DOI: No ID Found -
American Family Physician Jun 2014Although neonatal jaundice is common, acute bilirubin encephalopathy and kernicterus (i.e., chronic bilirubin encephalopathy) are rare. Universal screening for neonatal... (Review)
Review
Although neonatal jaundice is common, acute bilirubin encephalopathy and kernicterus (i.e., chronic bilirubin encephalopathy) are rare. Universal screening for neonatal hyperbilirubinemia is controversial. The American Academy of Pediatrics recommends universal screening with bilirubin levels or targeted screening based on risk factors. However, the U.S. Preventive Services Task Force and the American Academy of Family Physicians found insufficient evidence that screening improves outcomes. Universal screening may also increase rates of phototherapy, sometimes inappropriately. Younger gestational age and exclusive breastfeeding are the strongest risk factors for the development of hyperbilirubinemia. Infants who appear jaundiced should be evaluated by a risk score or by measurement of total serum or transcutaneous bilirubin. Phototherapy is an effective treatment for hyperbilirubinemia, but the number needed to treat varies widely depending on sex, gestational age, and time since delivery. If indicated, phototherapy should be initiated based on gestational age and risk factors. Exchange transfusion leads to complications in about 5% of treated infants and has a mortality rate of three or four per 1,000 infants. Infants who breastfeed exclusively-particularly those who consume inadequate calories-are at increased risk of hyperbilirubinemia. However, interrupting breastfeeding for the treatment of jaundice increases the risk of early discontinuation of breastfeeding. Encouragement from health care professionals is important to promote breastfeeding in these situations.
Topics: Bilirubin; Breast Feeding; Exchange Transfusion, Whole Blood; Gestational Age; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Jaundice, Neonatal; Kernicterus; Phototherapy; Practice Guidelines as Topic
PubMed: 25077393
DOI: No ID Found -
BMJ Clinical Evidence May 2015About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks. Jaundice is... (Review)
Review
INTRODUCTION
About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks. Jaundice is caused by bilirubin deposition in the skin. Most jaundice in newborn infants is a result of increased red cell breakdown and decreased bilirubin excretion.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different wavelengths of light in hospital phototherapy as treatment for unconjugated hyperbilirubinaemia in term and preterm infants? What are the effects of different intensities of light in hospital phototherapy as treatment for unconjugated hyperbilirubinaemia in term and preterm infants? What are the effects of different total doses of light in hospital phototherapy as treatment for unconjugated hyperbilirubinaemia in term and preterm infants? What are the effects of starting hospital phototherapy at different thresholds in term and preterm infants? We searched Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
Fourteen studies were included. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of different wavelengths, intensities, total doses, and threshold for commencement of the following intervention: hospital phototherapy.
Topics: Humans; Infant; Infant, Newborn; Infant, Premature; Jaundice, Neonatal; Phototherapy
PubMed: 25998618
DOI: No ID Found -
American Family Physician Jan 2004Jaundice in an adult patient can be caused by a wide variety of benign or life-threatening disorders. Organizing the differential diagnosis by prehepatic, intrahepatic,... (Review)
Review
Jaundice in an adult patient can be caused by a wide variety of benign or life-threatening disorders. Organizing the differential diagnosis by prehepatic, intrahepatic, and posthepatic causes may help make the work-up more manageable. Prehepatic causes of jaundice include hemolysis and hematoma resorption, which lead to elevated levels of unconjugated (indirect) bilirubin. Intrahepatic disorders can lead to unconjugated or conjugated hyperbilirubinemia. The conjugated (direct) bilirubin level is often elevated by alcohol, infectious hepatitis, drug reactions, and autoimmune disorders. Posthepatic disorders also can cause conjugated hyperbilirubinemia. Gallstone formation is the most common and benign posthepatic process that causes jaundice; however, the differential diagnosis also includes serious conditions such as biliary tract infection, pancreatitis, and malignancies. The laboratory work-up should begin with a urine test for bilirubin, which indicates that conjugated hyperbilirubinemia is present. If the complete blood count and initial tests for liver function and infectious hepatitis are unrevealing, the work-up typically proceeds to abdominal imaging by ultrasonography or computed tomographic scanning. In a few instances, more invasive procedures such as cholangiography or liver biopsy may be needed to arrive at a diagnosis.
Topics: Adult; Humans; Jaundice
PubMed: 14765767
DOI: No ID Found -
American Journal of Physiology.... Feb 2021Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene... (Review)
Review
Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene transcription by nuclear receptors. Studies are now revealing that low plasma bilirubin levels, defined as "hypobilirubinemia," are a possible new pathology analogous to the other end of the spectrum of extreme hyperbilirubinemia seen in patients with jaundice and liver dysfunction. Hypobilirubinemia is most commonly seen in patients with metabolic dysfunction, which may lead to cardiovascular complications and possibly stroke. We address the clinical significance of low bilirubin levels. A better understanding of bilirubin's hormonal function may explain why hypobilirubinemia might be deleterious. We present mechanisms by which bilirubin may be protective at mildly elevated levels and research directions that could generate treatment possibilities for patients with hypobilirubinemia, such as targeting of pathways that regulate its production or turnover or the newly designed bilirubin nanoparticles. Our review here calls for a shift in the perspective of an old molecule that could benefit millions of patients with hypobilirubinemia.
Topics: Animals; Bilirubin; Energy Metabolism; Gene Expression Regulation; Gilbert Disease; Heme; Hormones; Humans; Hyperbilirubinemia; Metabolic Networks and Pathways; PPAR alpha
PubMed: 33284088
DOI: 10.1152/ajpendo.00405.2020 -
The Cochrane Database of Systematic... Jul 2021Acute bilirubin encephalopathy (ABE) and the other serious complications of severe hyperbilirubinemia in the neonate occur far more frequently in low- and middle-income... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute bilirubin encephalopathy (ABE) and the other serious complications of severe hyperbilirubinemia in the neonate occur far more frequently in low- and middle-income countries (LMIC). This is due to several factors that place babies in LMIC at greater risk for hyperbilirubinemia, including increased prevalence of hematologic disorders leading to hemolysis, increased sepsis, less prenatal or postnatal care, and a lack of resources to treat jaundiced babies. Hospitals and clinics face frequent shortages of functioning phototherapy machines and inconsistent access to electricity to run the machines. Sunlight has the potential to treat hyperbilirubinemia: it contains the wavelengths of light that are produced by phototherapy machines. However, it contains harmful ultraviolet light and infrared radiation, and prolonged exposure has the potential to lead to sunburn, skin damage, and hyperthermia or hypothermia.
OBJECTIVES
To evaluate the efficacy of sunlight administered alone or with filtering or amplifying devices for the prevention and treatment of clinical jaundice or laboratory-diagnosed hyperbilirubinemia in term and late preterm neonates.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 5), MEDLINE, Embase, and CINAHL on 2 May 2019. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster RCTs. We updated the searches on 1 June 2020.
SELECTION CRITERIA
We included RCTs, quasi-RCTs, and cluster RCTs. We excluded crossover RCTs. Included studies must have evaluated sunlight (with or without filters or amplification) for the prevention and treatment of hyperbilirubinemia or jaundice in term or late preterm neonates. Neonates must have been enrolled in the study by one-week postnatal age.
DATA COLLECTION AND ANALYSIS
We used standard methodologic procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were: use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, chronic bilirubin encephalopathy, and death.
MAIN RESULTS
We included three RCTs (1103 infants). All three studies had small sample sizes, were unblinded, and were at high risk of bias. We planned to undertake four comparisons, but only found studies reporting on two. Sunlight with or without filters or amplification compared to no treatment for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates One study of twice-daily sunlight exposure (30 to 60 minutes) compared to no treatment reported the incidence of jaundice may be reduced (risk ratio [RR] 0.61, 95% confidence interval [CI] 0.45 to 0.82; risk difference [RD] -0.14, 95% CI -0.22 to -0.06; number needed to treat for an additional beneficial outcome [NNTB] 7, 95% CI 5 to 17; 1 study, 482 infants; very low-certainty evidence) and the number of days that an infant was jaundiced may be reduced (mean difference [MD] -2.20 days, 95% CI -2.60 to -1.80; 1 study, 482 infants; very low-certainty evidence). There were no data on safety or potential harmful effects of the intervention. The study did not assess use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, and long-term consequences of hyperbilirubinemia. The study showed that sunlight therapy may reduce rehospitalization rates within seven days of discharge for treatment for hyperbilirubinemia, but the evidence was very uncertain (RR 0.55, 95% CI 0.27 to 1.11; RD -0.04, -0.08 to 0.01; 1 study, 482 infants; very low-certainty evidence). Sunlight with or without filters or amplification compared to other sources of phototherapy for the treatment of hyperbilirubinemia in infants with confirmed hyperbilirubinemia Two studies (621 infants) compared the effect of filtered-sunlight exposure to other sources of phototherapy in infants with confirmed hyperbilirubinemia. Filtered-sunlight phototherapy (FSPT) and conventional or intensive electric phototherapy led to a similar number of days of effective treatment (broadly defined as a minimal increase of total serum bilirubin in infants less than 72 hours old and a decrease in total serum bilirubin in infants more than 72 hours old on any day that at least four to five hours of sunlight therapy was available). There may be little or no difference in treatment failure requiring exchange transfusion (typical RR 1.00, 95% CI 0.06 to 15.73; typical RD 0.00, 95% CI -0.01 to 0.01; 2 studies, 621 infants; low-certainty evidence). One study reported ABE, and no infants developed this outcome (RR not estimable; RD 0.00, 95% CI -0.02 to 0.02; 1 study, 174 infants; low-certainty evidence). One study reported death as a reason for study withdrawal; no infants were withdrawn due to death (RR not estimable; typical RD 0.00, 95% CI -0.01 to 0.01; 1 study, 447 infants; low-certainty evidence). Neither study assessed long-term outcomes. Possible harms: both studies showed a probable increased risk for hyperthermia (body temperature greater than 37.5 °C) with FSPT (typical RR 4.39, 95% CI 2.98 to 6.47; typical RD 0.30, 95% CI 0.23 to 0.36; number needed to treat for an additional harmful outcome [NNTH] 3, 95% CI 2 to 4; 2 studies, 621 infants; moderate-certainty evidence). There was probably no difference in hypothermia (body temperature less than 35.5 °C) (typical RR 1.06, 95% CI 0.55 to 2.03; typical RD 0.00, 95% CI -0.03 to 0.04; 2 studies, 621 infants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Sunlight may be an effective adjunct to conventional phototherapy in LMIC settings, may allow for rotational use of limited phototherapy machines, and may be preferable to families as it can allow for increased bonding. Filtration of sunlight to block harmful ultraviolet light and frequent temperature checks for babies under sunlight may be warranted for safety. Sunlight may be effective in preventing hyperbilirubinemia in some cases, but these studies have not demonstrated that sunlight alone is effective for the treatment of hyperbilirubinemia given its sporadic availability and the low or very low certainty of the evidence in these studies.
Topics: Bias; Exchange Transfusion, Whole Blood; Heliotherapy; Humans; Hyperbilirubinemia, Neonatal; Hyperthermia; Hypothermia; Incidence; Infant, Newborn; Infant, Premature; Jaundice, Neonatal; Patient Readmission; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 34228352
DOI: 10.1002/14651858.CD013277.pub2 -
JAMA Network Open Mar 2019Neonatal hyperbilirubinemia can cause lifelong neurodevelopmental impairment (kernicterus) even in high-resource settings. A better understanding of the incidence and...
IMPORTANCE
Neonatal hyperbilirubinemia can cause lifelong neurodevelopmental impairment (kernicterus) even in high-resource settings. A better understanding of the incidence and processes leading to kernicterus may help in the design of preventive measures.
OBJECTIVES
To determine incidence rates of hazardous hyperbilirubinemia and kernicterus among near-term to term newborns and to evaluate health care professional adherence to best practices.
DESIGN, SETTING, AND PARTICIPANTS
This population-based nationwide cohort study used prospectively collected data on the highest serum bilirubin level for all infants born alive at 35 weeks' gestation or longer and admitted to neonatal care at all 46 delivery and 37 neonatal units in Sweden from 2008 to 2016. Medical records for newborns with hazardous hyperbilirubinemia were evaluated for best neonatal practices and for a diagnosis of kernicterus up to 2 years of age. Data analyses were performed between September 2017 and February 2018.
EXPOSURES
Extreme (serum bilirubin levels, 25.0-29.9 mg/dL [425-509 μmol/L]) and hazardous (serum bilirubin levels, ≥30.0 mg/dL [≥510 μmol/L]) neonatal hyperbilirubinemia.
MAIN OUTCOMES AND MEASURES
The primary outcome was kernicterus, defined as hazardous neonatal hyperbilirubinemia followed by cerebral palsy, sensorineural hearing loss, gaze paralysis, or neurodevelopmental retardation. Secondary outcomes were health care professional adherence to national guidelines using a predefined protocol with 10 key performance indicators for diagnosis and treatment as well as assessment of whether bilirubin-associated brain damage might have been avoidable.
RESULTS
Among 992 378 live-born infants (958 051 term births and 34 327 near-term births), 494 (320 boys; mean [SD] birth weight, 3505 [527] g) developed extreme hyperbilirubinemia (50 per 100 000 infants), 6.8 per 100 000 infants developed hazardous hyperbilirubinemia, and 1.3 per 100 000 infants developed kernicterus. Among 13 children developing kernicterus, brain injury was assessed as potentially avoidable for 11 children based on the presence of 1 or several of the following possible causes: untimely or lack of predischarge bilirubin screening (n = 6), misinterpretation of bilirubin values (n = 2), untimely or delayed initiation of treatment with intensive phototherapy (n = 1), untimely or no treatment with exchange transfusion (n = 6), or lack of repeated exchange transfusions despite indication (n = 1).
CONCLUSIONS AND RELEVANCE
Hazardous hyperbilirubinemia in near-term or term newborns still occurs in Sweden and was associated with disabling brain damage in 13 per million births. For most of these cases, health care professional noncompliance with best practices was identified, suggesting that a substantial proportion of these cases might have been avoided.
Topics: Female; Guideline Adherence; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Kernicterus; Male; Prospective Studies; Sweden
PubMed: 30901042
DOI: 10.1001/jamanetworkopen.2019.0858 -
The Cochrane Database of Systematic... May 2023Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by increased bilirubin in the blood from the breakdown of red blood cells. The gold standard for measuring bilirubin levels is obtaining a blood sample and processing it in a laboratory. However, noninvasive transcutaneous bilirubin (TcB) measurement devices are widely available and used in many settings to estimate total serum bilirubin (TSB) levels.
OBJECTIVES
To determine the diagnostic accuracy of transcutaneous bilirubin measurement for detecting hyperbilirubinaemia in newborns.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries up to 18 August 2022. We also checked the reference lists of all included studies and relevant systematic reviews for other potentially eligible studies.
SELECTION CRITERIA
We included cross-sectional and prospective cohort studies that evaluated the accuracy of any TcB device compared to TSB measurement in term or preterm newborn infants (0 to 28 days postnatal age). All included studies provided sufficient data and information to create a 2 × 2 table for the calculation of measures of diagnostic accuracy, including sensitivities and specificities. We excluded studies that only reported correlation coefficients.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the eligibility criteria to all citations from the search and extracted data from the included studies using a standard data extraction form. We summarised the available results narratively and, where possible, we combined study data in a meta-analysis.
MAIN RESULTS
We included 23 studies, involving 5058 participants. All studies had low risk of bias as measured by the QUADAS 2 tool. The studies were conducted in different countries and settings, included newborns of different gestational and postnatal ages, compared various TcB devices (including the JM 101, JM 102, JM 103, BiliChek, Bilitest and JH20-1C) and used different cutoff values for a positive result. In most studies, the TcB measurement was taken from the forehead, sternum, or both. The sensitivity of various TcB cutoff values to detect significant hyperbilirubinaemia ranged from 74% to 100%, and specificity ranged from 18% to 89%.
AUTHORS' CONCLUSIONS
The high sensitivity of TcB to detect hyperbilirubinaemia suggests that TcB devices are reliable screening tests for ruling out hyperbilirubinaemia in newborn infants. Positive test results would require confirmation through serum bilirubin measurement.
Topics: Humans; Infant; Infant, Newborn; Bilirubin; Cross-Sectional Studies; Hyperbilirubinemia; Jaundice, Neonatal; Neonatal Screening; Prospective Studies
PubMed: 37158489
DOI: 10.1002/14651858.CD012660.pub2 -
Nutrients May 2023Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ... (Review)
Review
Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ is a type of prolonged unconjugated hyperbilirubinemia that is often late onset in otherwise healthy-appearing newborns, and its occurrence might be related to breast milk itself. This review aims to systematically evaluate evidence regarding breast milk composition and the development of BMJ in healthy neonates. PubMed, Scopus and Embase were searched up to 13 February 2023 with key search terms, including neonates, hyperbilirubinemia, and breastfeeding. A total of 678 unique studies were identified and 12 were ultimately included in the systematic review with narrative synthesis. These included studies covered both nutritional compositions (e.g., fats and proteins) and bioactive factors (e.g., enzymes and growth factors) of breast milk and formally assessed the difference in the concentration (or presence) of various endogenous components of breast milk collected from mothers of BMJ infants and healthy infants. The results were inconsistent and inconclusive for most of the substances of interest, and there was only a single study available (e.g., total energy and mineral content, bile salts and cytokines); conflicting or even contradictory results arose when there were two or more studies on the subject matter (e.g., fats and free fatty acids contents and epidermal growth factor). The etiology of BMJ is likely multifactorial, and no single constituent of breast milk could explain all the BMJ cases observed. Further well-designed studies are warranted to investigate the complex interaction between maternal physiology, the breast milk system and infant physiology before this field could be progressed to uncover the etiology of BMJ.
Topics: Infant; Female; Humans; Infant, Newborn; Milk, Human; Bilirubin; Jaundice, Neonatal; Breast Feeding; Hyperbilirubinemia; Jaundice
PubMed: 37242142
DOI: 10.3390/nu15102261 -
Scientific Reports Aug 2022Jaundice caused by hyperbilirubinaemia is a common phenomenon during the neonatal period. Population-based studies evaluating assessment, management, and incidence of... (Randomized Controlled Trial)
Randomized Controlled Trial
Jaundice caused by hyperbilirubinaemia is a common phenomenon during the neonatal period. Population-based studies evaluating assessment, management, and incidence of jaundice and need for phototherapy among otherwise healthy neonates are scarce. We prospectively explored these aspects in a primary care setting via assessing care as usual during the control phase of a stepped wedge cluster randomised controlled trial.We conducted a prospective cohort study embedded in the Screening and TreAtment to Reduce Severe Hyperbilirubinaemia in Infants in Primary care (STARSHIP) Trial. Healthy neonates were included in seven primary care birth centres (PCBCs) in the Netherlands between July 2018 and March 2020. Neonates were eligible for inclusion if their gestational age was ≥ 35 weeks, they were admitted in a PCBC for at least 2 days during the first week of life, and if they did not previously receive phototherapy. Outcomes were the findings of visual assessment to detect jaundice, jaundice incidence and management, and the need for phototherapy treatment in the primary care setting.860 neonates were included of whom 608 (71.9%) were visibly jaundiced at some point during admission in the PCBC, with 20 being 'very yellow'. Of the latter, four (20%) did not receive total serum bilirubin (TSB) quantification. TSB levels were not associated with the degree of visible jaundice (p = 0.416). Thirty-one neonates (3.6%) received phototherapy and none received an exchange transfusion. Five neonates did not receive phototherapy despite having a TSB level above phototherapy threshold.Jaundice is common in otherwise healthy neonates cared for in primary care. TSB quantification was not always performed in very jaundiced neonates, and not all neonates received phototherapy when indicated. Quality improvement initiatives are required, including alternative approaches to identifying potentially severe hyperbilirubinaemia.Trial registration: NL6997 (Dutch Trial Register; Old NTR ID 7187), registered 3 May 2018.
Topics: Bilirubin; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Neonatal; Incidence; Infant; Infant, Newborn; Jaundice; Jaundice, Neonatal; Phototherapy; Primary Health Care; Prospective Studies
PubMed: 35999237
DOI: 10.1038/s41598-022-17933-2