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Hereditary TTP (hTTP), termed Upshaw–Schulman syndrome, is an ultra-rare disorder caused by a severe deficiency of plasma ADAMTS13 activity that allows circulation of ultra-large von Willebrand factor (UL-VWF) multimers. The greatest risk for hTTP is in their first days after birth, when 35–50% of patients will have severe hemolysis, jaundice, and thrombocytopenia. It is often fatal without effective treatment. In utero, fetal blood flowing from the pulmonary artery through the ductus arteriosus (DA) to the aorta is under low-shear-force. At birth, blood flow through the DA reverses to a left-to-right shunt, and the diameter of the DA begins to decrease due to hyper-oxygenated blood and decreased plasma prostaglandin E2. This causes turbulent circulation that unfolds UL-VWF, allowing platelet aggregation. If the DA closes promptly, hTTP newborns survive, but if it remains patent, turbulent circulation persists, triggering microvascular thrombosis. hTTP is commonly diagnosed as hemolytic disease of the fetus and newborn (HDFN) caused by anti-red cell antibodies and treated with exchange blood transfusion, which prevents kernicterus even when the diagnosis of hTTP is missed. The diagnosis of newborn-onset hTTP should be considered because HDFN does not cause severe thrombocytopenia, which might be effectively treated with recombinant ADAMTS13. [ABSTRACT FROM AUTHOR]

Background: Neonatal jaundice is a prevalent disease that causes many complications, including kernicterus and even death. Previous studies have shown that clofibrate as an aryloxy isobutyric acid derivate can be effectively applied for the treatment of neonatal jaundice. Thus, this review was carried out to investigate the effects and mechanism of action of clofibrate on neonatal jaundice. Methods: The keywords such as “Clofibrate” in combination with “Neonatal jaundice” or “Neonatal hyperbilirubinemia” or “Newborn Jaundice” were used to search for relevant publications indexed in the Institute for Scientific Information (ISI), Scopus, PubMed, and Google Scholar databases. Finally, after reviewing the studies, 24 papers were included in this study. Results: Results showed that the processes of albumin-bound bilirubin transfer to the hepatocytes, hepatic uptake, and storage via ligandin, hepatic conjugation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), conjugation into the bile via MRP2 represent the main action mechanism of clofibrate that turns it into the bilirubin conjugates and expels it from the bile. Besides, clofibrate has been shown to reduce the level of Total Serum Bilirubin (TSB) in infants even at a dosage of 25 mg/kg without leaving side effects. Conclusions: The results of this review revealed that clofibrate effectively reduces TSB in short-term usage and can even have a promising effect at the dosage of 25 mg/kg in full-term infants. Most studies have shown this property over a short period in term infants, and there is no evidence about long-term usage in this regard.

Context: Phototherapy is the mainstay of treatment for about 3% of neonates in India who develop significant jaundice in phototherapy range. New devices have been introduced in the market over the past few years. Aims: To compare the efficacy of three types of phototherapy machines, namely Blue and White, Compact Fluorescent Lamp, and Light Emitting Diode type. Settings and Design: A non-randomized prospective interventional study conducted in a tertiary care hospital of Western India. Material and Methods: Ninety neonates with phototherapy range hyperbilirubinemia were assigned into three groups of 30 neonates each to receive phototherapy using one of the three types of phototherapy machines. Need for exchange transfusion, total serum bilirubin (TSB) at 24 hours post-phototherapy and side effect profile were recorded. Decision to stop phototherapy was based on acceptable reduction of serum bilirubin to below phototherapy range. Statistical analysis used: Medcalc® Version 11.4.2.0 Software was utilised. Comparison of mean TSB was done using one way ANOVA. P-value of

This comprehensive review thoroughly examines the historical evolution, physiological foundations, and contemporary advancements in the application of phototherapy for neonatal hyperbilirubinemia. Neonatal hyperbilirubinemia, a common condition resulting from the immature hepatic processes in newborns, poses potential risks, including neurotoxicity, if left untreated. The review traces the historical progression from early recognition of neonatal jaundice to the development of various phototherapy modalities, showcasing the dynamic landscape of neonatal care. Emphasizing the physiological intricacies of bilirubin metabolism in neonates, the study underscores the vulnerability of newborns to hyperbilirubinemia due to delayed hepatic maturation. Phototherapy is a cornerstone in managing hyperbilirubinemia, demonstrating consistent efficacy in reducing unconjugated bilirubin levels. The implications for clinical practice are significant, offering healthcare professionals insights into tailoring treatment strategies based on individual neonatal characteristics and the severity of jaundice. Integrating advanced monitoring and control systems enhances the precision and safety of phototherapy. Recommendations for future research emphasize the need to investigate long-term outcomes, explore adjunctive therapies, and address resource limitations to ensure global access to effective neonatal care. Overall, this review contributes to the ongoing refinement of neonatal care practices, offering a comprehensive understanding of neonatal hyperbilirubinemia and its evolving treatment landscape., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Patel et al.)

Aim: To identify neonates at risk of haemolytic hyperbilirubinaemia through near-concurrent measurements of total serum/plasma bilirubin (TB) or transcutaneous bilirubin (TcB) and end-tidal breath carbon monoxide (CO), corrected for ambient CO (ETCOc), an index of bilirubin production and haemolysis.Methods: Paired TB/TcB (mg/dL) and ETCOc (ppm) measurements were obtained in newborns (n = 283) at 20 to <60 hours of age in five nurseries. TB/TcB values were assigned TB/TcB percentile risk values using the Bhutani hour-specific nomogram. In infants having two serial TB/TcB measurements (n = 76), TB rate of rise (ROR, mg/dL/h) was calculated.Results: For the entire cohort (n = 283), 67.1% and 32.9% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.79 ± 1.84 vs 9.14 ± 2.25 mg/dL) and ETCOc (1.61 ± 0.45 vs 2.02 ± 1.35 ppm, p = 0.0002) were different between the groups. About 36.6% of infants with TB/TcB ≥75th percentile had ETCOc ≥ 2.0 ppm. In the subcohort of infants with serial TB/TcB measurements (n = 76), 44.7% and 55.3% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.28 ± 1.97 vs 9.53 ± 2.78 mg/dL), ETCOc (1.72 ± 0.48 vs 2.38 ± 1.89 ppm, p = 0.05) and TB ROR (0.011 ± 0.440 vs 0.172 ± 0.471 mg/dL/h) were different between the groups.Conclusion: The combined use of TB/TcB percentile risk assessments and ETCOc measurements can identify infants with haemolytic hyperbilirubinaemia. The addition of TB ROR can identify those infants with elimination disorders. [ABSTRACT FROM AUTHOR]

Jaundice and pale stools are major indicators of neonatal liver disease. Prognosis depends on timely diagnosis and management. We evaluated the clinical practices among healthcare professionals concerning jaundiced newborns and their ability to recognize pale stools. We supplied a questionnaire and a panel with eight photographs of stools, both locally validated, to physicians and nurses of the National Healthcare Service. Analysis was conducted according to professional status, specialization and years of experience of professionals and level of healthcare. Questionnaires were administered to 266 participants (100 physicians, 166 nurses). The decision to send patients to medical observation depended on the intensity of jaundice for a significant percentage of nurses. Concerning jaundiced newborns breastfed and otherwise healthy, 28.9% of physicians would never request a conjugated bilirubin assay, and only 43.3% would request it after 14 days old; for those with other signs/symptoms of disease, only 69.1% of physicians would request it immediately. Multiple linear regression analysis identified specialization as an independent variable significantly associated with the ability to recognize pale stools.Conclusion: A significant percentage of healthcare professionals assumed clinical practices that preclude the timely recognition of cholestasis/pale stools, reinforcing the idea of educational needs. Specialization, rather than years of experience of professionals, was associated with better skills and practices. What is Known: • Neonatal cholestasis is a condition with some rare underlying entities having high mortality and morbidity. Early diagnosis is crucial to improve prognosis. Yet, many cases remain late recognized and referred. • Studies evaluating the ability of healthcare professionals to recognize neonatal cholestasis are scarce. What is New: • In this study, a significant percentage of professionals assumed clinical practices that preclude timely recognition of neonatal cholestasis and pale stools, reinforcing the idea of educational needs. • Specialization of professionals was associated with better skills and practices. [ABSTRACT FROM AUTHOR]

Aim: Relative contributions of increased production [by end-tidal carbon monoxide concentrations (ETCOc)] and decreased elimination of bilirubin to predischarge hour-specific total bilirubin (TB) levels were assessed in healthy late-preterm and term newborns. Secondly, we report predischarge ETCOc ranges to guide clinical management of hyperbilirubinemia.Methods: TB and ETCOc (≤3 timepoints) determinations of newborns aged between six hours and <6 days (n = 79) were stratified by postnatal age epochs. Hyperbilirubinemia risk was assessed by plotting TB values as a function of ETCOc.Results: Stratifications of ETCOc (in ppm, mean, median and interquartile ranges) by postnatal age epochs (0-24, 24-48 and 48-72) were as follows: 2.0, 1.9, 1.8-2.2 (n = 11); 1.6, 1.5, 1.1-2.0 (n = 58); and 2.0, 1.8, 1.6-2.3 (n = 9), respectively. Infants with ETCOc ≥ 2.5 were at high risk, between 1.5 and 2.5 at moderate risk and ≤1.5 were at low risk. Risk due to haemolysis alone was not independent (p < 0.01). For infants with TB >75th percentile (n = 31), 23% had ETCO ≤1.5, and 77% had ETCOc > 1.5 (p < 0.00003).Conclusion: Near-simultaneous ETCOc and TB measurements in infants with TB >75th percentile accurately identify haemolytic hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Background: Newborn jaundice has remained one of the leading causes of neonatal morbidity and mortality in sub-Saharan Africa. It is believed that delays in detection and/or inappropriate treatment may largely be responsible for this. Given that most mothers are now discharged home 24 hours after a normal delivery, the responsibility to detect jaundice in the new-born and take appropriate decision now rest with the mothers. This study therefore sought to evaluate the knowledge and perception of newborn jaundice among parturient mothers. Method: This study was a descriptive cross-sectional study carried out among 255 parturient mothers at the lying-in ward of Mariere Memorial Central Hospital. A structured, pre-tested, interviewer administered questionnaire was used to obtain information from the mothers. SPSS version 16 was employed in the analysis of the data. Results: Of the 255 parturient mothers interviewed, only 156 (61.2%) affirmed their awareness of newborn jaundice and only these mothers were further analysed. Their mean age was 30.2±5.4 and a median parity of 2. Thirty-seven (23.7%) of the mothers had tertiary education and just about half (50.6%) of the mothers knew that newborn jaundice presents with yellowish discoloration of the body and sclera. Three (1.9%) of the mothers knew that haemolysis is an underlying cause of jaundice and four (2.6%) mothers each correctly mentioned phototherapy and exchange blood transfusion as treatment modalities. Health talk given at the antenatal clinic was the source of information by 81 (51.9%) of the mothers. Conclusion: This study showed that the knowledge of risk factors/causes, treatment and complication of newborn jaundice by mothers is unsatisfactory. [ABSTRACT FROM AUTHOR]

We aimed to determine the role of exchange transfusion related complications, treatment, and etiology as well as subgroup incompatibility in patients subject to ET (exchange transfusion) due to newborn jaundice. 82 patients hospitalized due to newborn jaundice and exposed to exchange transfusion between August 2007 and August 2011 were retrospectively studied. Before ET mean total serum bilirubin was 29,2±9,83. The most frequent cause of ET was ABO incompatibility (31%) followed by Rh incompatibility (19%) and subgroup incompatibility (17%), respectively. In 46% of all patients and in 71% of the patients presenting with subgroup incompatibility , direct combs test was detected to be (+). 49% of the patients were administrated with intravenous immunoglobulin. 5 of the patients who were exposed to ET presented with hydrops fetalis. Of these patients 3 had Rh, 1 had ABO while the other had subgroup incompatibility. Although ABO and Rh incompatibility are substantial underlying reasons of severe jaundice requiring exchange transfusion, particularly widespread use of RhoGAM thereby enabling the prior identification and precautions, ET need was reduced compared to previous cases. On the contrary, SGU related severe hemolytic jaundice relatively enhanced, however. [ABSTRACT FROM AUTHOR]

Objectives: To assess the correlation between total serum bilirubin (TSB) and transcutaneous bilirubin (TcB) values in Malawian newborn infants, and to investigate whether TcB can be used safely to guide phototherapy treatment in the absence of TSB results. Methods: 128 newborn jaundiced infants were studied in the neonatal nursery at Queen Elizabeth Central Hospital, Blantyre. Paired TSB and TcB measurements (from forehead and sternum) were compared using the linear regression and Bland–Altman methods. Clinical decisions based on TcB results were compared with those based on 'gold standard' TSB results. Results: For infants not under phototherapy, the lowest TcB reading (from forehead or sternum) gave the strongest correlation with TSB: r = 0·83 for term infants and r = 0·71 for premature infants. For infants undergoing phototherapy, the highest TcB reading gave the strongest correlation with TSB: r = 0·66 for term infants and r = 0·71 for premature infants. TcB values overestimated the degree of jaundice. For infants not under phototherapy, the mean (SD) bias and imprecision of TcB was 25 (72) μmol/L for term infants and 37 (73) μmol/L for premature infants. For infants under phototherapy, the mean bias and imprecision was 30 (79) μmol/L for term infants and 44 (77) μmol/L for premature infants. For infants not under phototherapy, using the lowest TcB reading to guide treatment decisions (n = 167) had good sensitivity (91%) and specificity (90%). For infants undergoing phototherapy, using the highest TcB reading to guide treatment decisions (n = 129) had good sensitivity (94%), but lower specificity (36%). Conclusions: TcB can be used to safely guide phototherapy treatment in a resource-poor setting. [ABSTRACT FROM AUTHOR]

This study investigated the effectiveness of simple-to-implement adjustments of phototherapy devices on irradiance levels in a cross-section of Nigerian hospitals. A total of 76 phototherapy devices were evaluated in 16 hospitals while adjustments were implemented for a subset of 25 devices for which consent was obtained. The mean irradiance level was 7.6 ± 5.9 µW/cm2/nm for all devices prior to adjustments. The average irradiance level improved from 9.0 µW/cm2/nm to 27.3 µW/cm2/nm for the adjusted group (n = 25) compared with 6.8 ± 5.4 µW/cm2/nm for the unadjusted group (n = 51). Simple, inexpensive adjustments to phototherapy devices with sub-optimal irradiance levels can significantly improve their effectiveness to acceptable international standards and should be widely promoted in resource-constrained settings. [ABSTRACT FROM AUTHOR]

We believe that the syndrome of bilirubin-induced neurologic dysfunction [BIND] represents a spectrum of neurologic manifestations among vulnerable infants who have experienced an exposure to bilirubin of lesser degree than generally described in previous publications. Clinical neuro-motor manifestations extend to a range of subtle processing disorders with objective disturbances of visual-motor, auditory, speech, cognition, and language among infants with a previous history of moderate-to-severe hyperbilirubinemia of varied duration. Confounding effects include prematurity, hemolysis, perinatal-neonatal complications, altered bilirubin-albumin binding, severity and duration of bilirubin exposure, and the individual vulnerability of the infant related to genetic, family, social, and educational predilection, regardless of the cause of neonatal jaundice. Tools to better assess BIND specific domains of multisensory processing disorders, identified by pyschometric, audiologic, speech, language and visual-motor, and neuromotor examination would allow for prospective surveillance of infants at risk for the syndrome. [Copyright &y& Elsevier]

Dramatic improvements in the overall socioeconomic conditions have yet to impact the unacceptably high maternal (approximately 1500 maternal deaths daily, worldwide) and neonatal morbidity and mortality (more than 10,000 deaths per daily 200,000 live-births, worldwide) in the developing nations. Thus, nations with emerging markets have unique health-societal needs. All infants require a safer transition from a birthing facility to home during the first week after birth and providing for a nurturing environment to prevent neonatal illnesses is integral to “good clinical practice.” The unmonitored occurrence of severe hyperbilirubinemia and kernicterus are emblematic of a fractured maternal child healthcare system. The “know-do” gaps that span private versus public health care systems in the emerging markets have led us to conclude that building an interdisciplinary leadership approach to provide innovative strategies and affordable technologies will help bridge and access existing social barriers in the micro- and macro-health environments. Thus, unfettered access, global benchmarks, and culturally relevant strategies are dependent on evidence-based affordable technologies to successfully transform societal health care practices. Implementation of jaundice-related technologies should serve as a template for other affordable newborn health products. [Copyright &y& Elsevier]

Globally, health care providers worldwide recognize that severe neonatal jaundice is a “silent” cause of significant neonatal morbidity and mortality. Untreated neonatal jaundice can lead to death in the neonatal period and to kernicterus, a major cause of neurologic disability (choreo-athetoid cerebral palsy, deafness, language difficulty) in children who survive this largely preventable neonatal tragedy. Appropriate technologies are urgently needed. These include tools to promote and enhance visual assessment of the degree of jaundice, such as simpler transcutaneous bilirubin measurements and readily available serum bilirubin measurements that could be incorporated into routine treatment and follow-up. Widespread screening for glucose-6-phoshate dehydrogenase deficiency is needed because this is often a major cause of neonatal jaundice and kernicterus worldwide. Recognition and treatment of Rh hemolytic disease, another known preventable cause of kernicterus, is critical. In addition, effective phototherapy is crucial if we are to make kernicterus a “never-event.” Finally it is essential that we conduct appropriate population-based studies to accurately elucidate the magnitude of the problem. However, knowledge alone is not sufficient. If we are to implement these and other programs and technologies to relegate severe neonatal jaundice and its sequelae to the history books, screening and interventions must be low cost and technologically appropriate for low and middle income nations. [Copyright &y& Elsevier]

Phototherapy is the treatment of choice to reduce the severity of neonatal unconjugated hyperbilirubinemia regardless of its etiology. Its implementation requires a technical framework that conforms to existing evidence-based guidelines that promote its safer and effective use worldwide. Optimal use of phototherapy has been defined by specific ranges of total serum bilirubin thresholds configured to an infant''s postnatal age (in hours) and potential risk for bilirubin neurotoxicity. Effective phototherapy implies its use at specific blue light wavelengths (peak emission, 450 ± 20 nm) and emission spectrum (range, 400-520 nm), preferably in a narrow bandwidth that is delivered at an irradiance of ≥30 μW/cm2/nm to up to 80% of an infant''s body surface area. However, this is often not feasible in clinical settings with limited or constrained resources. To identify and bridge implementation barriers, we propose minimum criteria for device performance for safe and practical use of phototherapy as a prophylactic intervention to prevent severe hyperbilirubinemia. [Copyright &y& Elsevier]

Background: Severe neonatal hyperbilirubinemia, when unmonitored or untreated, can progress to acute bilirubin encephalopathy (ABE). Initiatives to prevent and eliminate post-icteric sequelae (kernicterus) are being implemented to allow for timely interventions for bilirubin reduction. Objectives: We report an observational study to determine the clinical risk factors and short-term outcomes of infants admitted for severe neonatal jaundice. Methods: A post-discharge medical chart review was performed for a cohort of infants admitted for management of newborn jaundice to the Children Welfare Teaching Hospital during a 4-month period in 2007 and 2008. Immediate outcomes included severity of hyperbilirubinemia, association of ABE, need and impact of exchange transfusion, and survival. Short-term post-discharge follow-up assessed for post-icteric sequelae. Results: A total of 162 infants were admitted for management of severe jaundice. Incidences of severe sequelae were: advanced ABE (22%), neonatal mortality within 48 h of admission (12%) and post-icteric sequelae (21%). Among the cohort, 85% were <10 days of age (median 6 days, IQR 4-7 days). Readmission total serum bilirubin ranged from 197 to 770 μM; mean 386 ± 108 SD μM (mean 22.6 ± 6.3 SD mg/dl; median 360, IQR 310-445 μM). The major contributory risk factor for the adverse outcome of kernicterus/death was admission with advanced ABE (OR 8.03; 95% CI 3.44-18.7). Other contributory factors to this outcome, usually significant, but not so for this cohort, included home delivery, sepsis, ABO or Rh disease. Absence of any detectable signs of ABE on admission and treatment of severe hyperbilirubinemia was associated with no adverse outcome (OR 0.34; 95% CI 0.16-0.68). Conclusions: Risks of mortality and irreversible brain injury among healthy infants admitted for newborn jaundice are urgent reminders to promote education of communities, families and primary health care providers, especially in a fractured health system. Known risk factors for severe hyperbilirubinemia were overwhelmed by the effect of advanced ABE. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To reduce the incidence of severe neonatal hyperbilirubinemia affecting newborns with jaundice in the United States and to prevent kernicterus, there is a need to implement proven prevention strategies for severe neonatal hyperbilirubinemia as recommended in the 2004 American Academy of Pediatrics Guidelines for newborns >35 weeks gestational age. The purpose of universal predischarge bilirubin screening is to identify infants with bilirubin levels >75th percentile for age in hours and track those with rapid rates of bilirubin rise (>0.2 mg per 100 ml per h). Early identification has been reported to predict severe hyperbilirubinemia and allow for evidence-based targeted interventions. A systems approach is likely to reduce the preventable causes of acute bilirubin encephalopathy. To do so, highest priority should be given to (i) designating extreme hyperbilirubinemia (total serum bilirubin >427 μmol l−1 or >25 mg per 100 ml) as a reportable condition by laboratories and health-care providers through public health mandates; (ii) implementation of Joint Commission's Sentinel Report for kernicterus; (iii) nursing outreach to communities for education of prospective parents; (iv) development of clinical pathways to monitor, evaluate and track infants with extreme hyperbilirubinemia; and (v) societal awareness. These efforts should be monitored by a state and national surveillance system in order to critically improve the timeliness and completeness of notifications and to allow evaluation and interventions at the policy and individual family level. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the performance of the Konica Minolta/Air-Shields® JM-103 jaundice meter on the basis of infant skin tone during the early neonatal period. Methods: Infants were prospectively categorized into light, medium and dark skin tone groups relative to two reference colours. Transcutaneous bilirubin readings were taken at predetermined intervals through the early neonatal period on a convenience sample of 938 healthy infants ≥37 weeks gestation. Serum bilirubin measurements were drawn routinely with metabolic studies and repeated in the presence of an elevated transcutaneous reading or clinically significant jaundice. Results: Multivariate linear regression analysis showed a significant impact on serum and transcutaneous bilirubin agreement by skin tone. Highest precision and lowest bias were observed for medium skin toned infants. Greater disagreement between serum and transcutaneous measurements was noted at serum bilirubin concentrations >200 μmol/L. Insufficient numbers of dark skin toned infants were enroled to evaluate fully the performance of the jaundice meter for this group. Conclusion: The JM-103 jaundice meter displayed good correlation with serum bilirubin concentrations in light and medium skin tone infants, although it showed a tendency to under-read in the lighter skin tone group and to over-read in the darker skin tone group. The device shows excellent performance characteristics for use as a screening device. [ABSTRACT FROM AUTHOR]

Acute kernicterus remains a clinical emergency and its delayed management represents an easily preventable neonatal brain injury. Yet, practitioners encounter recurrent questions regarding the risk and timing of bilirubin-related neurotoxicity. These include the following: does bilirubin damage the brain of healthy infants? Is there a re-emergence of kernicterus in the United States? Was kernicterus previously prevented in the United States? What was the public health impact of 1994 American Academy of Pediatrics Guidelines? What is the current incidence of kernicterus and severe neonatal hyperbilirubinemia? What is the estimated risk of kernicterus in infants with excessive hyperbilirubinemia? Is there a specific bilirubin threshold total serum bilirubin (TSB) value for neurotoxicity? Are there sequelae of severe or prolonged moderate hyperbilirubinemia in the absence of recognized acute bilirubin encephalopathy? Can we define a bilirubin level that is safe in newborns? We address these questions in the context of available data and evidence, and estimate the current risk of chronic kernicterus is about one in seven in infants with TSB >30 mg per 100 ml (513 μmol l−1).Journal of Perinatology (2009) 29, S20–S24. doi:10.1038/jp.2008.212 [ABSTRACT FROM AUTHOR]

To identify antecedent clinical and health services events in infants (35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants 35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 μmol l−1; range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age 1 week. Along with a rapid rise of TSB (>0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age 5 days in 81 of 118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were 35 mg per 100 ml (598 μmol l−1) in 46 (39%) infants, of whom one died before exchange transfusion, one was untreated and one was lost to follow-up. Timely and efficacious bilirubin reduction interventions defined by ‘crash-cart’ initiation of immediate intensive phototherapy and urgent exchange transfusion were accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in whom a timely exchange sometimes could not be accomplished. No overt sequelae were found in 8 of 11 infants (73%) treated with a ‘crash-cart’ approach compared with none without sequelae when exchange was delayed by pre-admission delays, technical factors or need to transfer to a tertiary facility. None of the remaining 20 of 43 infants treated only with phototherapy escaped sequelae. Regardless of age at readmission and intervention, infants with peak measured TSB >35 mg per 100 ml had post-icteric sequelae (n=73). There was a narrow margin of safety between birthing hospital discharge or home birth and readmission to a tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to hazardous levels and onset of neurological signs were often not identified as infant's care and medical supervision transitioned during the first week after birth. The major underlying root cause for kernicterus was systems failure of services by multiple providers at multiple sites and inability to identify the at-risk infant and manage severe hyperbilirubinemia in a timely manner.Journal of Perinatology (2009) 29, S25–S45; doi:10.1038/jp.2008.211 [ABSTRACT FROM AUTHOR]

To address systems failures and promote a safer management of newborn jaundice, we propose an ‘aviation safety standard’ for newborn health-care services during the first week after birth. Systems failure in newborn jaundice management has been characterized by lapses in concern, loss of continuity, and delays in care by multiple providers at multiple sites. Components for a six-step national strategy to prevent severe neonatal hyperbilirubinemia and possibly kernicterus are being implemented as delineated in the 2004 AAP guidelines. The clinical guidelines for safer and evidence-based practice have been characterized by both healthcare and societal communities. Professional and community organizations are optimizing outreach resources and facilitating institutionalization of these practices. Nationwide implementation at individual birthing hospitals concurrent with surveillance feedback needs to be initiated. Implementation of a ‘six-sigma’ approach, as proposed to the current Center for Disease Control and Prevention-initiated partnership (health-care providers, public health and community advocates) may be achieved through collaboration with state and national agencies.Journal of Perinatology (2009) 29, S61–S67; doi:10.1038/jp.2008.213 [ABSTRACT FROM AUTHOR]

Background: Neonatal jaundice is a prevalent disease that causes many complications, including kernicterus and even death. Previous studies have shown that clofibrate as an aryloxy isobutyric acid derivate can be effectively applied for the treatment of neonatal jaundice. Thus, this review was carried out to investigate the effects and mechanism of action of clofibrate on neonatal jaundice. Methods: The keywords such as "Clofibrate" in combination with "Neonatal jaundice" or "Neonatal hyperbilirubinemia" or "Newborn Jaundice" were used to search for relevant publications indexed in the Institute for Scientific Information (ISI), Scopus, PubMed, and Google Scholar databases. Finally, after reviewing the studies, 24 papers were included in this study. Results: Results showed that the processes of albumin-bound bilirubin transfer to the hepatocytes, hepatic uptake, and storage via ligandin, hepatic conjugation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), conjugation into the bile via MRP2 represent the main action mechanism of clofibrate that turns it into the bilirubin conjugates and expels it from the bile. Besides, clofibrate has been shown to reduce the level of Total Serum Bilirubin (TSB) in infants even at a dosage of 25 mg/kg without leaving side effects. Conclusions: The results of this review revealed that clofibrate effectively reduces TSB in short-term usage and can even have a promising effect at the dosage of 25 mg/kg in full-term infants. Most studies have shown this property over a short period in term infants, and there is no evidence about long-term usage in this regard. [ABSTRACT FROM AUTHOR]

A jaundiced neonate in an emergency department can be a catastrophic emergency that necessitates expeditious care. Progressive and irreversible bilirubin neurotoxicity may be minimized by rapid reduction of serum bilirubin concentrations through a “crash-cart” approach: immediate administration of intensive phototherapy and preparation for a possible exchange transfusion. Onset of acute bilirubin encephalopathy (ABE) is initially nonspecific and insidious and may progress to irritability, painful tonic spasms, apnea, seizures, obtundation, coma, respiratory failure, and death. Early recognition of hyperbilirubinemia severity can facilitate rapid transition to treatment and overcome the major barriers to timely therapy. Emergency department personnel need to develop policies that define access to intensive phototherapy either on site or immediate access to a neonatal/pediatric critical care facility. This article reviews a systems strategy for a crash-cart approach that may be initiated in the emergency department for a safer transition to alternative facilities to manage and prevent ABE. [Copyright &y& Elsevier]

Objective: The early discharge of neonates from hospitals makes transcutaneous measurement of total serum bilirubin concentration a useful tool to monitor neonatal jaundice. The objective of this study was to evaluate the Bilitest BB 77™ (Bertocchi SRL Elettromedicali, Cremona, Italy), a new device for noninvasive transcutaneous total bilirubin measurement. Methods: We studied 241 newborn infants ≥32 weeks of gestation admitted to the Neonatal Nursery of Careggi University Hospital, Florence. These infants had total serum bilirubin (TSB) levels measured by a standard laboratory test (group B = 198) as part of their normal care, and transcutaneous bilirubin (TcB) levels were obtained within 10 min after heel pricking. Results: There was a good correlation between TSB and TcB values. The linear regression plot showed a general underestimation of Bilitest BB 77 measurement compared to standard laboratory test; the negative difference between Bilitest BB 77 values and TSB increased at higher bilirubin levels, as confirmed by the Bland-Altman error plot. To visualize the accuracy of the Bilitest BB 77 measurements, ROC curves plot sensitivity versus specificity and the maximum range of difference between Bilitest BB 77 and TSB were considered. Pearson correlation analysis demonstrated that Bilitest BB 77 accuracy was independent of gestational and postnatal age of newborns. Conclusion: We conclude that the Bilitest BB 77, a new device for bilirubin transcutaneous measurement, shows a good correlation with standard laboratory method and has the merit to be quite inexpensive and does not need calibration with consumable or disposable parts. However, because TcB measurements with Bilitest BB 77 underestimated STB levels particularly at STB ≥12 mg/dl, serum bilirubin measurements are still required when treatment with phototherapy or exchange transfusion is being considered. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objectives : To assess the effects of sample dilution, peroxidase concentration, and chloride ion (Cl−) on plasma unbound bilirubin (B f) measurements made using a commercial peroxidase methodology (UB Analyzer) in a study population of ill, premature newborns. Design and methods : B f was measured with a UB Analyzer in 74 samples at the standard 42-fold sample dilution and compared with B f measured at a 2-fold sample dilution using a FloPro Analyzer. B f was measured at two peroxidase concentrations to determine whether the peroxidase steady state B f (B fss) measurements were significantly less than the equilibrium B f (B feq), in which case it was necessary to calculate B feq from the two B fss measurements. B f was also measured before and after adding 100 mmol/L Cl− to the UB Analyzer assay buffer. Results : B feq at the 42-fold dilution was nearly 10-fold less than but it correlated significantly with B feq at the 2-fold dilution (mean 8.2±5.2 nmol/L versus 73.5±70 nmol/L, respectively, p <0.0001; correlation r =0.6). The two UB Analyzer B fss measurements were significantly less than B feq in 42 of 74 (57%) samples, and Cl− increased B feq in 66 of 74 (89%) samples by a mean of 82±67%. Conclusions : B fss measured by the UB Analyzer at the standard 42-fold sample dilution using assay buffer without Cl− and a single peroxidase concentration is significantly less than the B feq in undiluted plasma. Accurate B f measurements can be made only in minimally diluted serum or plasma. [Copyright &y& Elsevier]

Summary: Hyperbilirubinemia and kernicterus are re-emerging as prominent clinical concerns and have been hypothesized to be secondary to increased breast-feeding rates, early hospital discharges and overall lack of concern for the potential impact of severe hyperbilirubinemia on healthy term newborns. Although the clinical symptoms can be non-specific and vague, they could be early, insidious and heralding signs of acute bilirubin encephalopathy (ABE) or acute stage kernicterus. Because it is highly prevalent, evaluation of a jaundiced neonate requires detailed questions about specific signs, review of birth and postnatal histories, evaluation of predischarge data, and possibly an emergency clinical evaluation of the neurological status of the infant. Medical urgency to evaluate, investigate and monitor such a newborn ensues from the possibility of rapid progression that might lead to permanent sequelae of bilirubin-induced neurologic dysfunction (BIND). Early recognition of the urgency and rapid transition to treatment seem to be the major barriers leading to delay in therapy. However, because there is a well-established and relatively safe treatment for neonatal jaundice, there should be zero tolerance for kernicterus, and BIND prevention has become a national priority in the USA. This paper reviews the clinical signs and epidemiology of ABE and BIND and presents a system-based strategy for preventing their occurrence, focusing particularly on the transition from recognition of clinical jaundice to actual treatment. A novel emergency-room-based protocol is presented as an example of how to expedite and facilitate rapid progression to treatment. [Copyright &y& Elsevier]

The plasma glutathione peroxidase (GSH-Px) and selenium (Se) levels were determined in 31 newborns affected by jaundice (NWJ). The GSH-Px levels of both full-term and premature newborns exhibiting jaundice and having a birthweight lower than 2000 g were significantly low ( p<0.05) when compared to controls. No significant differences were found in the corresponding Se levels, which were similar in all groups and independent of the pregnancy period and birthweight. [ABSTRACT FROM AUTHOR]