Bilirubin Encephalopathy Research Articles

Usefulness of the unbound serum bilirubin for predicting neonatal bilirubin encephalopathy

Bilirubin encephalopathy is still one of the challenges for neonatal society.In recent years, the incidence in Europe and North America is 1/100 000~1/40 000, while it is 1.13‰ in China.The current guideline for neonatal hyperbilirubinemia is based on total serum bilirubin(TSB), combined with gestational age, birth weight, age and risk factors.TSB is used as a main index for phototherapy and exchange transfusion.However, only unbound serum bilirubin(UB)can cross blood brain barrier and neuron membrane to cause neurotoxicity, so it is important to monitor UB.In view of the difficulties to measure UB directly, it has been proposed to measure serum albumin(SA), the TSB/SA ratio, TSB/SA molar ratio and the affinity of SA for TSB in addition to monitor TSB, but their clinical practice value is limited.Previously, the methods for direct detection of UB such as oxidase method, modified peroxidase method and photometric method have not been accepted nor routinely used.Recently Martelanc has piloted to use high performance liquid chromatography to directly measure UB with precision up to pmol/L.This recent progress offers reference for measuring UB in neonates, but the threshold of UB predicting bilirubin encephalopathy needs to be further studied.This article will review the important role of UB in predicting bilirubin encephalopathy, predicting experimental parameters of neonatal bilirubin encephalopathy, current methodologies for direct detection of UB. Key words: Bilirubin encephalopathy; Neonates; Unbound serum bilirubin; Measurement; High performance liquid chromatography

Coordinating Care Across the Perinatal Continuum in Hemolytic Disease of the Fetus and Newborn: The Timely Handoff of a Positive Maternal Anti-Erythrocyte Antibody Screen

Antibody-mediated hemolytic disease of the fetus and newborn, henceforth referred to as hemolytic disease, can pose a significant risk for anemia and severe postnatal hyperbilirubinemia. A positive maternal anti-erythrocyte antibody screen is often the first finding to herald the risk of hemolytic disease and prompt further evaluation including fetal surveillance for anemia and, if indicated, in utero red blood cell transfusion. 1 Liley H.G. Gardener G. Lopriore E. Smits-Wintjens V. Immune hemolytic disease. in: Orkin S. Nathan D. Ginsburg D. Look A.T. Fisher D. Lux S. Nathan and Oski's hematology and oncology of infancy and childhood. Elsevier Saunders, Philadelphia2015: 76-100 Google Scholar A positive maternal anti-erythrocyte antibody screen may also signal a risk for severe hyperbilirubinemia in the neonate, even in the absence of fetal anemia. In this regard, hemolytic disease remains an important cause of marked neonatal hyperbilirubinemia, acute bilirubin encephalopathy, and kernicterus. 2 Johnson L. Bhutani V.K. Karp K. Sivieri E.M. Shapiro S.M. Clinical report from the Pilot US Kernicterus Registry (1992 to 2004). J Perinatol. 2009; 29: S25-S45 Crossref Scopus (232) Google Scholar , 3 Christensen R.D. Agarwal A.M. George T.I. Bhutani V.K. Yaish H.M. Acute neonatal bilirubin encephalopathy in the State of Utah 2009-2018. Blood Cells Mol Dis. 2018; 72: 10-13 Crossref PubMed Scopus (24) Google Scholar , 4 Helal N.F. Ghany E.A. Abuelhamd W.A. Alradem A.Y. Characteristics and outcome of newborn admitted with acute bilirubin encephalopathy to a tertiary neonatal intensive care unit. World J Pediatr. 2019; 15: 42-48 Google Scholar , 5 Rennie J.M. Beer J. Upton M. Learning from claims: hyperbilirubinemia and kernicterus. Arch Dis Child Fetal Neonatal Ed. 2019; 104: F202-F204 Google Scholar Whether a positive maternal anti-erythrocyte antibody screen is detected at pregnancy registration, during gestation, or perinatally at the time of delivery hospitalization, it is incumbent on the newborn caretakers to be aware of the result. 6 Watchko J.F. Common hematologic problems in the newborn nursery. Pediatr Clin N Am. 2015; 62: 509-524 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar , 7 Intermountain Healthcare. Prenatal care for maternal anti-erythrocyte antibodies. 2017 Update. Intermountain Healthcare Patient and Provider Publications CPM043 – 07/17. https://intermountainhealthcare.org/ckr-ext/Dcmnt?ncid=521363279. Accessed December 1, 2018. Google Scholar We review the critical importance of a successful handoff of a positive maternal anti-erythrocyte antibody screen across the perinatal continuum to ensure the timely evaluation and management of the neonate. Although symptomatic ABO hemolytic disease is also an important cause of neonatal hyperbilirubinemia, maternal anti-A and anti-B antibodies are innately produced, that is, immune competent individuals who do not express the A or B protein produce antibody to the antigen. As such, anti-A and anti-B are not included in the maternal anti-erythrocyte antibody screen and ABO hemolytic disease is not addressed. Two case reports underscore the importance of the timely handoff of a positive maternal anti-erythrocyte antibody screen.

Prebiotics for the prevention of hyperbilirubinaemia in neonates.

Hyperbilirubinaemia occurs in approximately two-thirds of all newborns during the first days of life and is frequently treated with phototherapy. Although generally seen as safe, there is rising concern regarding phototherapy and its potentially damaging effects on DNA and increased side effects particularly for preterm infants. Other methods, such as enteral feeding supplementation with prebiotics, may have an effective use in the management of hyperbilirubinaemia in neonates. To determine whether administration of prebiotics reduces the incidence of hyperbilirubinaemia among term and preterm infants compared with enteral supplementation of milk with distilled water/placebo or no supplementation. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 14 June 2018), Embase (1980 to 14 June 2018), and CINAHL (1982 to 14 June 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. We considered all RCTs that studied neonates comparing enteral feeding supplementation with prebiotics versus distilled water/placebo or no supplementation. Two reviewers screened papers and extracted data from selected papers. We used a fixed-effect method in combining the effects of studies that were sufficiently similar. We then used the GRADE approach to assess the quality of the evidence. Three small studies evaluating 154 infants were included in this review. One study reported a significant reduction in the risk of hyperbilirubinaemia and rate of treatment with phototherapy associated with enteral supplementation with prebiotics (risk ratio (RR) 0.75, 95% confidence interval (95% CI) 0.58 to 0.97; one study, 50 infants; low-quality evidence). Meta-analyses of two studies showed no significant difference in maximum plasma unconjugated bilirubin levels in infants with prebiotic supplementation (mean difference (MD) 0.14 mg/dL, 95% CI -0.91 to 1.20, I² = 81%, P = 0.79; two studies, 78 infants; low-quality evidence). There was no evidence of a significant difference in duration of phototherapy between the prebiotic and control groups, which was only reported by one study (MD 0.10 days, 95% CI -2.00 to 2.20; one study, 50 infants; low-quality evidence). The meta-analyses of two studies demonstrated a significant reduction in the length of hospital stay (MD -10.57 days, 95% CI -17.81 to -3.33; 2 studies, 78 infants; I² = 0%, P = 0.004; low-quality evidence). Meta-analysis of the three studies showed a significant increase in stool frequency in the prebiotic groups (MD 1.18, 95% CI 0.90 to 1.46, I² = 90%; 3 studies, 154 infants; high-quality evidence). No significant difference in mortality during hospital stay after enteral supplementation with prebiotics was reported (typical RR 0.94, 95% CI 0.14 to 6.19; I² = 6%, P = 0.95; 2 studies; 78 infants; low-quality evidence). There were no reports of the need for exchange transfusion and incidence of acute bilirubin encephalopathy, chronic bilirubin encephalopathy, and major neurodevelopmental disability in the included studies. None of the included studies reported any side effects. Current studies are unable to provide reliable evidence about the effectiveness of prebiotics on hyperbilirubinaemia. Additional large, well-designed RCTs should be undertaken in neonates that compare effects of enteral supplementation with prebiotics on neonatal hyperbilirubinaemia with supplementation of milk with any other placebo (particularly distilled water) or no supplementation.

Clinical characteristics and treatment options of hearing impairment caused by hyperbilirubinemia

SummaryNeonatal hyperbilirubinemia is the most common clinical symptom in neonates. When the concentration of free bilirubin in blood is too high, it crosses through the blood-brain barrier and selectively deposits in specific brain nuclei to cause neurotoxicity and bilirubin neurological dysfunction. The auditory nervous system is highly sensitive to bilirubin. Therefore, auditory neuropathy is the most important or even the only clinical symptom of bilirubin neurological dysfunction. Chronic bilirubin encephalopathy can be classified to three types as mild, moderate and severe，according to the audiological manifestations and other neurological sequelae. Early recognition and intervention of bilirubin-induced hearing impairment is of great significance to improve the speech recognition rate of the referred children. This article reviews the most important studies about the clinical characteristics, pathogenesis and treatment of bilirubin-induced hearing impairment.

A-50 A Comprehensive Neuropsychological Case Study of a Child with Perinatal Hyperbilirubinemia

Abstract Objective Neonatal jaundice (hyperbilirubinemia) remains present in 60% of births in the United States1. Current literature links hyperbilirubinemia with neurodevelopmental problems, particularly with attention deficit hyperactivity disorder (ADHD), general learning difficulties, and non-progressive developmental delays. Moderate elevations in bilirubin are also suggested to increase the risk for cognitive, perceptual, motor, and auditory disorders. Imaging studies have shown selective patterns of injury to specific brain regions associated with deficits in executive function, including impulse control and working memory as well as different subtypes of attention problems grounded in reward circuitry system dysfunction in children with bilirubin encephalopathy. Method Neuropsychological functioning of a 12-year old Hispanic female with a history of high levels of perinatal bilirubin, and subsequent developmental and cognitive difficulties in speech, learning, attention and memory as well as problems with socialization and anxiety is presented with the purpose of adding to existing literature. Comprehensive neuropsychiatric interview and neuropsychological testing was completed. Results Results revealed several areas of neurocognitive weaknesses with deficits in areas of intellectual functioning, learning (reading and mathematics), expressive language, visual memory, attention, and auditory processing. Emotional and behavioral measures evidenced significant deficits in social-emotional functioning, particularly with interpersonal skills, sense of adequacy, and self-reliance, which resulted in increased anxiety contributing to cognitive and academic deficits. Conclusions Neuropsychological profile was consistent with cognitive, academic, behavioral and emotional manifestations theoretically associated with neuropathological findings in hyperbilirubinemia. Furthermore, similar to existing literature, cognitive deficits were observed in the absence of a clear cause of neonatal jaundice following a full-term, uncomplicated pregnancy.

Short Term Exposure to Bilirubin Induces Encephalopathy Similar to Alzheimer's Disease in Late Life

Background: Hyperbilirubinemia may increase the risk of Alzheimer's disease (AD) but its mechanistic role in AD pathogenesis remains obscure. Methods: Three animal models and primary hippocampal cells were used to explore in this study: (1) acute bilirubin treatment; (2) lateral ventricle injection; (3) long term observation. Results: Three days exposure to bilirubin in newborn rats could induce AD-like pathological changes in late life, including tau protein hyperphosphorylation at multiple sites, increased Aβ production in brain tissues, and spatial learning and memory injury. Bilirubin activated the activities of several protein kinases (GSK-3β, CDK5 and JNK), which were positively correlated with hyperphosphorylated tau; simultaneously increased the expression of APP γ-secretase PS2 and decreased the expression of α-secretase ADAM17, which were positively correlated with Aβ production. The above results were well replicated in primary hippocampal cells. Conclusions: Bilirubin may be an upstream activator to induce AD, and bilirubin encephalopathy is an AD-like disease. Funding Statement: The study was supported in part by the National High Technology Research and Development Program of China (2006AA02Z4B5); the National Natural Science Foundation of China(81170608, 81570278, 81602427, 81600089, 81670156); the Science and Technology Program of Guangzhou (201707010046, 201604020001); The National Funds for Developing Local Colleges and Universities (B16056001); Natural Science Foundation research team of Guangdong Province (2018B030312001); Guangzhou Education System (1201610014, 1201620494); Natural Science Foundation of Guangdong Province (2017A030313662). Declaration of Interests: All authors declare that there are no conflicts of interest. Ethics Approval Statement: The protocol for the care and use of all animals in this study was in accordance with the Guangdong Animal Center for the ethical treatment of animals and approved by the Institutional Animal Care and Use Committee of Guangzhou Medical University (SYXK2016-0168, Guangzhou, China).

Caspase-1 involves in bilirubin-induced injury of cultured rat cortical neurons.

Bilirubin encephalopathy, the most serious complication of hyperbilirubinemia during the neonatal period, with high mortality and morbidity, often causes irreversible neurological damage. Currently, caspase-1, a member of the cysteinyl aspartate-specific protease caspase family, is regarded as a key mediator of inflammatory processes, attracting widespread attention. The purpose of this study was to investigate whether caspase-1 is involved in bilirubin-induced neuronal injury. VX-765, a highly potent and selective inhibitor of caspase-1, was used to investigate the effects of unconjugated bilirubin (UCB) on rat cortical neurons, including cell viability, morphological changes in the cell membrane, and nuclear factor-kappa B (NF-κB) activation. Neurons treated with UCB showed increased caspase-1 activity without the secretion of interleukin (IL)-1β and IL-18, and caspase-1 was significantly inhibited by pretreatment with VX-765. The cell viability of the VX-765-pretreated neurons was improved, and cell membrane rupture was prevented, as detected by lactate dehydrogenase release and ethidium bromide uptake. Moreover, NF-κB activation by UCB exposure, was attenuated by VX-765 pretreatment. Bilirubin-induced neuronal injury involves the activation of caspase-1 and NF-κB, leading to membrane leakage, independently of IL-1β and IL-18.

141 Total bilirubin rate of rise of in moderate preterm neonates: impact of gestational age

Abstract Background As compared to term neonates, those < 35 weeks gestation (wks GA) are at greater risk for both acute and chronic bilirubin encephalopathy (ABE, CBE). Among these with postnatal total bilirubin rate of rise, (TB ROR) at age 0 to 72 hours has been observed because of either loss placental elimination system or increased postnatal production due to hemolysis. The ranges are known to vary > 8.5 umol/L/h in neonates with Rh disease to >3.4 umol/L/h at the 95th percentile track of the hour-specific nomogram. TB ROR in healthy term neonates is <3.4 umol/L/h. Objectives To determine the GA ranges on TB ROR to explore predictive TB ROR in preterm neonates who are more vulnerable with each <35 wks GA. Design/Methods A multi-site observational study to quantify TB ROR in preterm infants between 28 to 35 weeks. 1804 infants born between January 2013- March 2018 at 28–35 wks GA from three canadian perinatal centres were included and those with Rh disease were excluded. Analysis included infants >27 weeks with at least one TB prior to the initiation of treatment for severe hyperbilirubinemia treatment. Feeding patterns, birth history and maternal health conditions were documented. Results The TB ROR were compared by two prematurity GA groups (28–31 weeks and 32–35 weeks) then per individual gestational age in four time periods in hours, 0–24, 24–48, 48–96, and 96 -120 in 1049 preterm infants using 3065 TB samples. Infants <28 weeks GA were excluded since they represented a more diverse population. TB ROR by prematurity groups over all was higher in 32–35 weeks group at 0–12 hours (3.85 umol/L/h) and 25–36 hours (2.81umol/L/h) and decreased at 49–72 hours (0.24umol/L/h) time period as compared to the less mature group. Conclusion Though TB ROR were of similar patterns between prematurity groups (28–31 weeks and 32–35 weeks) it was at higher rate of rise between 13–36 hours and decreasing from 36–72 hours, with a plateau after 72 hours of age. There was a significant difference in the magnitude of TB ROR between prematurity groups at 0–24 hours. Additional research into the clinical care impact on the TB ROR should be conducted to study impact of production and elimination.

A Novel Icterometer for Hyperbilirubinemia Screening in Low-Resource Settings.

Severe neonatal hyperbilirubinemia (>20 mg/dL) affects ∼1 million infants annually. Improved jaundice screening in low-income countries is needed to prevent bilirubin encephalopathy and mortality. The Bili-ruler is an icterometer for the assessment of neonatal jaundice that was designed by using advanced digital color processing. A total of 790 newborns were enrolled in a validation study at Brigham and Women's Hospital (Boston) and Sylhet Osmani Medical College Hospital (Sylhet, Bangladesh). Independent Bili-ruler measurements were made and compared with reference standard transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) concentrations. Bili-ruler scores on the nose were correlated with TcB and TSB levels (r = 0.76 and 0.78, respectively). The Bili-ruler distinguished different clinical thresholds of hyperbilirubinemia, defined by TcB, with high sensitivity and specificity (score ≥3.5: 90.1% [95% confidence interval (CI): 84.8%-95.4%] and 85.9% [95% CI: 83.2%-88.6%], respectively, for TcB ≥13 mg/dL). The Bili-ruler also performed reasonably well compared to TSB (score ≥3.5: sensitivity 84.5% [95% CI: 79.1%-90.3%] and specificity 83.2% [95% CI: 76.1%-90.3%] for TSB ≥11 mg/dL). Areas under the receiver operating characteristic curve for identifying TcB ≥11, ≥13, and ≥15 were 0.92, 0.93, and 0.94, respectively, and 0.90, 0.87, and 0.86 for identifying TSB ≥11, ≥13, and ≥15. Interrater reliability was high; 97% of scores by independent readers fell within 1 score of one another (N = 88). The Bili-ruler is a low-cost, noninvasive tool with high diagnostic accuracy for neonatal jaundice screening. This device may be used to improve referrals from community or peripheral health centers to higher-level facilities with capacity for bilirubin testing and/or phototherapy.

Early Amplitude-Integrated Electroencephalography Predicts Long-Term Outcomes in Term and Near-Term Newborns With Severe Hyperbilirubinemia

BackgroundWe aimed to determine the predictive neurological prognostic value of early amplitude-integrated electroencephalography (aEEG) in term and near-term neonates with severe hyperbilirubinemia compared with cranial magnetic resonance imaging (MRI) and auditory brainstem response (ABR). MethodsInfants of ≥35 weeks of gestation with severe hyperbilirubinemia (total serum bilirubin [TSB] ≥340 μmol/L) or with hyperbilirubinemia (TSB ≥257 μmol/L) in association with bilirubin-induced neurological dysfunction were recruited. All the subjects had an aEEG after being admitted to the neonatal intensive care unit, whereas cranial MRI and ABR were performed when TSB had come down to the normal range. All the infants were followed up to 12 months. ResultsDuring the study period, 77 of 83 infants were eligible, of which 71 had severe hyperbilirubinemia and six had hyperbilirubinemia in association with bilirubin-induced neurological dysfunction. Thirty-three infants were diagnosed with acute bilirubin encephalopathy (ABE), two of whom died of ABE, and 62 completed the follow-up, of which 12 infants had adverse outcomes. Sixty-four infants underwent aEEG, 40 infants had cranial MRI, and 39 infants had ABR. Logistic regression and the receiver-operator characteristic curve analysis showed that the ability of severely abnormal aEEG to predict adverse neurological outcomes in severe hyperbilirubinemia was no better than abnormal ABR, with a sensitivity of 35.7% versus 83.3%, a specificity of 92.0% versus 74.1%, a positive predictive value of 55.6% versus 58.8%, and a negative predictive value of 83.6% versus 90.9%. ConclusionsEarly aEEG could predict adverse neurodevelopmental outcomes in neonates with severe hyperbilirubinemia, although the sensitivity was lower than ABR.

A Study of Cord Blood Albumin as a Predictor of Significant Neonatal Jaundice

Background: Neonatal hyperbilirubinemia is the commonest abnormal physical finding during the first week of life and its early detection is essential for prevention of bilirubin encephalopathy. Early discharge of healthy term neonates is a com-mon practice due to various reasons. The commonest cause for readmission of a normal neonate during early neonatal peri-od is neonatal hyperbilirubinemia. Readmission causes considerable stress to the family members. Aims: To assess whether cord blood albumin level could be used to predict the occurrence of significant jaundice requiring intervention. Settings and Design: It is a prospective study undertaken in postnatal wards of a teaching hospital. Material and Methods: Cord blood albumin was estimated in 130 healthy term neonates and they were divided into 3 groups based on cord blood albumin levels as follows: Group 1 with albumin levels <2.8g/dl; Group 2 with albumin levels between 2.8 and 3.3 g/dl and Group 3 with albumin levels of > 3.3g/dl. All the enrolled neonates were followed up for 72 hours and observed for clinical jaundice based on yellowish discoloration of skin. Neonates with evidence of clinical jaun-dice were subjected to total serum bilirubin estimation and hour specific values were plotted on Bhutani’s charts. Results: Clinical jaundice was present in 100 neonates for whom serum bilirubin estimation was done. There was a signifi-cant negative correlation between cord blood albumin levels and total serum bilirubin. Out of 100 neonates with clinical jaundice, 19 received phototherapy for significant hyperbilirubinemia. While all neonates in Group 1 received phototherapy none in Group 3 received intervention which was highly significant (p value <0.0001). Conclusion: Cord blood albumin estimation helps in predicting the possibility of hyperbilirubinemia in healthy term neo-nates. Key words: Cord blood albumin, Neonatal hyperbilirubinemia, Phototherapy

Modulation of Cav2.3 channels by unconjugated bilirubin (UCB) – Candidate mechanism for UCB-induced neuromodulation and neurotoxicity

Elevated levels of unbound unconjugated bilirubin (UCB) can lead to bilirubin encephalopathy and kernicterus. In spite of a large number of studies demonstrating UCB-induced changes in central neurotransmission, it is still unclear whether these effects involve alterations in the function of specific ion channels. To assess how different UCB concentrations and UCB:albumin (U/A) molar ratios affect neuronal R-type voltage-gated Ca2+ channels, we evaluated their effects on whole-cell currents through recombinant Cav2.3 + β3 channel complexes and ex-vivo electroretinograms (ERGs) from wildtype and Cav2.3-deficient mice. Our findings show that modestly elevated levels of unbound UCB (U/A = 0.5) produce subtle but significant changes in the voltage-dependence of activation and prepulse inactivation, resulting in a stimulation of currents activated by weak depolarization and inhibition at potentials on the plateau of the activation curve. Saturation of the albumin binding capacity (U/A = 1) produced additional suppression that became significant when albumin was omitted completely and might involve a complete loss of channel function.Acutely administered UCB (U/A = 0.5) has recently been shown to affect transsynaptic signaling in the isolated vertebrate retina. The present report reveals that sustained exposure of the murine retina to UCB significantly suppresses also late responses of the inner retina (b-wave) from wildtype compared to Cav2.3-deficient mice. In addition, recovery during washout was significantly more complete and faster in retinae lacking Cav2.3 channels.Together, these findings show that UCB affects cloned and native Cav2.3 channels at clinically relevant U/A molar ratios and indicate that supersaturation of albumin is not required for modulation but associated with a loss of channel functional that could contribute to chronic neuronal dysfunction.

The effect on Bilirubin levels of massage, tub bath, and sponge bath in newborns with hyperbilirubinemia: A randomized controlled trial

IntroductionNeonatal jaundice is a common condition in newborns. Neonatal jaundice is usually treatable, but it may cause kernicterus that leads to bilirubin encephalopathy The aim of this study was to examine the effect of massage, tub bath and sponge bath on bilirubin levels of newborn infants with hyperbilirubinemia. MethodsThis is a randomized controlled experimental study. This study was conducted with 140 newborns in the 34th and following weeks of gestation who were receiving phototherapy in the neonatal intensive care unit of a university hospital in eastern Turkey. The newborns were given a either massage (n = 35), a tub bath (n = 35) or a sponge bath (n = 35) by the researcher. Except for routine clinical procedures, no other procedures were administered to the newborns in the control group (n = 35). The total bilirubin values of the newborns were measured using non-invasive bilirubin device before the procedures, and six hours and 12 h after. ResultsThis study found that there was a significant difference between the bilirubin levels in massage (3.82 ± 1.78; p = 0.000), sponge bath (4.42 ± 1.30; p = 0.000), tub bath (3.63 ± 1.50; p = 0.000) and control groups (7.62 ± 2.54; p = 0.000). A similar case was observed in the duration of receiving phototherapy mean scores in massage (13.60 ± 2.45; p = 0.000), sponge bath (20.05 ± 0.72; p = 0.000), tub bath (16.97 ± 1.75; p = 0.000) and control groups (32.05 ± 9.03; p = 0.000). ConclusionsIn this study, the bilirubin levels and the duration of phototherapy treatment of newborns decreased most rapidly in the massage group, followed by tub bath group and sponge bath group.

Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus.

Bilirubin encephalopathy/kernicterus is relatively rare, but continues to occur despite universal newborn screening. What is more interesting is the spectrum of clinical and even neuropathological findings that have been reported in the literature to be associated with bilirubin encephalopathy and kernicterus. In this review, the authors discuss the array of clinicopathological findings reported in the context of bilirubin encephalopathy and kernicterus, as well as the types of diagnostic testing used in patients suspected of having bilirubin encephalopathy or kernicterus. The authors aim to raise the awareness of these features among both pediatric neurologists and neuropathologists.

Turkish Neonatal Society guideline to the approach, follow-up, and treatment of neonatal jaundice.

Jaundice is one of the most common problems in the newborn. It is generally accepted as a physiologic condition; most cases are benign and transient. However, in a small portion of jaundiced newborn infants, serum bilirubin concentrations increase to a level at which irreversible brain damage can occur. The timely diagnosis and management of severe hyperbilirubinemia is essential to prevent acute bilirubin encephalopathy and kernicterus. Kernicterus still occurs although it is almost always preventable. The focus of this guideline is to reduce the incidence of severe hyperbilirubinemia and bilirubin encephalopathy. Therefore, a system-based approach using the recommendations of this guideline should be implemented in all birthing facilities and continued in ambulatory care of the newborn infants.

A Novel Whole Spectrum-Based Non-Invasive Screening Device for Neonatal Hyperbilirubinemia.

Careful screening of bilirubin level in newborns is mandatory as per American Academy of Pediatrics (2004), to reduce incidents of kernicterus and acute bilirubin encephalopathy. Although, invasive capillary collection of blood and subsequent biochemical test is considered a gold standard for jaundice detection in neonates, transcutaneous bilirubin measurement using various non-invasive instruments is also used sporadically across the globe. The major aim of this study was to develop a non-invasive spectrometry-based technique for measurement of neonatal bilirubin level as an alternative of total serum bilirubin (TSB) test without limitations of other available bilirubinometers. The instrument comprises of a light source and a spectroscopic detector. A light beam from source incident on the neonatal nail plate through optical fibers. The retro reflected light is acquired using the detector. An indigenously developed software is used to acquire and analyze the optical signal and to calculate the bilirubin value. The instrument was calibrated and validated in reference to TSB on 1033 subjects. The result (r = 0.95 and P < 0.001) indicates a strong correlation between the bilirubin value obtained from our method and TSB. Time variant analysis of the subjects undergoing phototherapy provided a good correlation (r = 0.98). The repeatability test result shows the mean coefficient of variation is less than 5.0%. The indigenously developed non-invasive technique successfully detects the bilirubin level in newborns under various physiological conditions with high accuracy and precision.

Jaundice in the Newborn at the Teaching Hospital of Brazzaville

Introduction: Jaundice is a major symptom during neonatal time. It is defined by a bilirubin ≥ 50 mg/l. Objectives: To determine the frequency of neonatal jaundice at the Brazzaville University Hospital, to determine the main etiologies, to evaluate the management, to specify the evolution. Patients and Method: It was a prospective and descriptive study that was conducted in the Neonatology Department and Biochemistry Laboratory of the University Hospital of Brazzaville, from 1st August 2015 to 31st July 2016. It included newborn children admitted into the neonatal unit for treatment of jaundice. The variables studied were epidemiological, clinical, etiological therapy and outcome. Results: The frequency of the neonatal jaundice is 7.2%. The hyperbilirubinemia as not conjugated was found in 99.1% of cases. The main causes are bacterial neonatal infection n = 102 (47.9%), the physiological icterus n = 46 (21.6%) and the ABO incompatibility n = 40 (18.8%). The treatment consists of the phototherapy in all cases. Each phototherapy session lasts 3 hours n = 99 (56.9%), 6 hours n = 58 (33.3%) and 12 hours n = 17 (9.8%). The average duration of the administering of the therapy is of 3 ± 2 days. Hyperbilirubinemia encephalopathy occurred in 62 (29.1%) cases, including 49 cases of kernicterus. The death occurred in 70 (32.9%) children. Conclusion: The importance and the gravity of the neonatal jaundice require primary preventive means based on proper care in pregnancy and the birth. While the secondary prevention includes high index of suspicion, comprehensive diagnostic equipment availability to prevent acute bilirubin encephalopathy.

Severe neonatal hyperbilirubinemia in the southeast region of Turkey

Severe neonatal hyperbilirubinemia is an important cause of morbidity and mortality in developing countries. The aim was to assess etiologic reasons for development of severe hyperbilirubinemia and define risk factors for exchange transfusion and acute bilirubin encephalopathy (ABE) in Şanlıurfa located in the southeast region of Turkey. An observational cohort study included 115 infants with ≥35 weeks of gestation admitted with diagnosis of severe hyperbilirubinemia in a period of 18 months. Potential risk factors associated with exchange transfusion and development of ABE were analyzed. Among 115 infants, 67 (58.3%) received exchange transfusion and 45 (39.1%) developed ABE. Rh isoimmunization (OR: 24.6, 95% CI = 2.2–271, P = 0.009), glucose-6-phosphate dehydrogenase deficiency (G6PD) (OR: 21.1, 95% CI = 1.8–238.4, P = 0.01), early discharge (OR: 14.4, 95% CI = 4.2–48.9, P ≤ 0.001), and male sex (OR: 4.3, 95% CI = 1.3–14.1, P = 0.02) were independently associated with an increased risk for exchange transfusion. Being a refugee (OR: 6.8, 95% CI = 1.8–25.8, P = 0.005) and G6PD deficiency (OR: 9.9, 95% CI = 1.3–71.9, P = 0.02) were associated with development of ABE. Early discharge, Rh isoimmunization, and G6PD deficiency are significant risk factors for severe hyperbilirubinemia and exchange transfusion. Prevention of early hospital discharges, family education to increase awareness for hazardous effects of hyperbilirubinemia, and early follow-up visits after discharge would reduce the disease burden.

Alkaline phosphatase and haptoglobin as predictor of neonatal jaundice

Background: The term kernicterus refers to the clinical features of bilirubin encephalopathy. Its risk is increased in term babies with very high bilirubin levels. Kernicterus is also known to occur at lower levels of bilirubin in term babies who have risk factors and in preterm babies. Objective: The aim of the present study was to investigate whether serum alkaline phosphatse & haptoglobin (Hp) level could be used for the early diagnosis and prediction of hyperbilirubinemia in newborns. Methodology: The study is a prospective clinical study design, which was carried out in Pediatric Department, Faculty of Medicine, Aswan University Hospital. The study included 100 newborns with gestational age more than 35wk delivered in obstetric department. Results: Our study showed no statistically significant difference between jaundiced and non- jaundiced cases regarding the mode of delivery, maternal gravidity and parity. As regards previous sibiling affected, we found a significant relation between clinically appearing jaundice and previous sibling affected with neonatal hyperbillirubinemia, which may reflect genetic susceptibility for hyperbillirubinemia. No significant relationship between gestational age and clinically appearing jaundice. When assessing the relationship between clinically appearing jaundice and birth weight, our results revealed no significant relationship. Conclusion: The cord blood alkaline phosphatase level is not only a useful predictor for severe neonatal jaundice but also can predict the early onset of neonatal hyperbilirubinemia and expected methods of treatment in healthy newborns more than 35 weeks gestational age.

Causes of death in a neonatal intensive care unit in southeast region of Turkey

Aim: Neonatal mortality rate is a good indicator to show the developmental status of a country. The aim was to assess mortality rate and causes of death in a tertiary level neonatal intensive care unit (NICU) at Sanliurfa Training and Research Hospital. Material and Methods: All infant deaths occurred in one year period between 2017 and 2018 at Sanliurfa Training and Research Hospital NICU were retrospectively reviewed and causes of death and mortality rate were examined. A total of 189 (9.4%) infants died in the study period. Most common cause of death was prematurity and associated conditions (49.2%) followed by perinatal asphyxia (16.4%) and congenital anomalies (12.7%). In term infants perinatal asphyxia (36.9%), congenital anomalies (16.9%) and acute bilirubin encephalopathy (12.3%) were the three leading causes of death. The median age of death was 3 (1-240) days. Most of the deaths (73%) occurred in the early neonatal period. Conclusion: Prematurity, perinatal asphyxia, congenital anomalies and severe hyperbilirubinemia are the leading causes of neonatal mortality in Sanliurfa. Measures for antenatal follow-up, diagnosis of antenatal risk factors, early neonatal follow-up and certification of health staff in delivery room would contribute for reduction of neonatal mortality in southeast region of Turkey.