Severe Neonatal Hyperbilirubinemia Research Articles

Severe neonatal hyperbilirubinemia secondary to combined RhC hemolytic disease, congenital hypothyroidism and large adrenal hematoma: a case report

BackgroundABO blood group incompatibility, neonatal sepsis, G-6-PD deficiency, thyroid dysfunction, and hereditary spherocytosis are all probable causes of neonatal hyperbilirubinemia. However, the etiology of some hyperbilirubinemia is extremely complicated, which may be caused by multiple factors, resulting in severe jaundice. We report a case of severe jaundice due to three causes, showing the significance for the investigation of the etiology of neonatal hyperbilirubinemia.Case presentationAt 96 h of life, a full-term and vaginal delivery male infant with yellowish discoloration of body was transferred to our hospital. When he entered neonatal intensive care unit on the fourth day after birth, he developed jaundice and the transcutaneous bilirubin was 28 mg/dl. Total bilirubin was 540.2 μmol/L, while the indirect bilirubin was 516.7 μmol/L. Both parents and the baby’s blood types were O Rh(D +), and direct coomb’s test was negative. But mother’s indirect coomb’s test was positive. Investigating for minor blood group revealed that the father’s blood type of Rh was CCDee, the mather’s was ccDEE, and CcDEe for the baby. After intensive phototherapy and double volume exchange transfusion, the total bilirubin remained at 303 μmol/L. At day 10, the bilirubin level was 303.5 μmol/L, intensive phototherapy was continued, and intravenous immunoglobulin was used again. The test for thyroid hormones at day 10, the TSH was 13.334mIU/L. And the screening for congenital hypothyroidism showed the TSH was 33mIU/L. Because of the palpable abdominal mass, ultrasound and MRI was done, showed a huge mass in the right adrenal gland. Brainstem auditory evoked potential was performed at day 7, which indicated hearing impairment (65db for left ear and 70db for the right). Euthyrox and intermittent phototherapy were given as following treatment. The jaundice did not subside until the 12th day.ConclusionEven if their parents' ABO blood group and Rh (d) are consistent, a Coomb test is required for newborns with hyperbilirubinemia since they may have minor blood group incompatibilities. When bilirubin rises rapidly or the clinical treatment effect is inadequate, additional causes should be aggressively screened. Adrenal ultrasound should be performed on newborns with palpable abdominal mass, anemia and jaundice to determine whether there is adrenal hemorrhage.

Chemoprevention of bilirubin encephalopathy with a nanoceutical agent.

Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. We investigated a novel spinel-structured citrate-functionalized trimanganese tetroxide nanoparticle (C-Mn3O4 NP, the nanodrug) to degrade both systemic and neural bilirubin loads. Severe neonatal unconjugated hyperbilirubinemia (SNH) was induced in neonatal C57BL/6j mice model with phenylhydrazine(PHz) intoxication. Efficiency of the nanodrug on both in vivo bilirubin degradation and amelioration of bilirubin encephalopathy and associated neurobehavioral sequelae were evaluated. Single oral dose (0.25 mg kg-1 bodyweight) of the nanodrug reduced both total serum bilirubin (TSB) and unconjugated bilirubin (UCB) in SNH rodents. Significant (p < 0.0001) UCB and TSB-degradation rates were reported within 4-8 h at 1.84 ± 0.26 and 2.19 ± 0.31 mg dL-1 h-1, respectively. Neural bilirubin load was decreased by 5.6 nmol g-1 (p = 0.0002) along with improved measures of neurobehavior, neuromotor movements, learning, and memory. Histopathological studies confirm that the nanodrug prevented neural cell reduction in Purkinje and substantia nigra regions, eosinophilic neurons, spongiosis, and cell shrinkage in SNH brain parenchyma. Brain oxidative status was maintained in nanodrug-treated SNH cohort. Pharmacokinetic data corroborated the bilirubin degradation rate with plasma nanodrug concentrations. This study demonstrates the in vivo capacity of this novel nanodrug to reduce systemic and neural bilirubin load and reverse bilirubin-induced neurotoxicity. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemopreventive approach to clinical settings. None of the current pharmacotherapeutics treat severe neonatal hyperbilirubinemia (SNH) to prevent risks of neurotoxicity. In this preclinical study, a newly investigated nano-formulation, citrate-functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs), exhibits bilirubin reduction properties in rodents. Chemopreventive properties of this nano-formulation demonstrate an efficacious, efficient agent that appears to be safe in these early studies. Translation of C-Mn3O4 NPs to prospective preclinical and clinical trials in appropriate in vivo models should be explored as a potential novel pharmacotherapy for SNH.

Establishment and Evaluation of Influencing Factors and Risk Prediction Model of Severe Neonatal Hyperbilirubinemia Complicated with Acute Bilirubin Encephalopathy.

Objective To explore the influencing factors of severe hyperbilirubinemia in neonates complicated with acute bilirubin encephalopathy (ABE) and then build relevant prediction models and evaluate the prediction performance of the models. Methods The data of 120 neonates with severe hyperbilirubinemia were collected by retrospective analysis. Univariate and multivariate analysis methods were used to analyze the data of 120 children. R software was used to visualize the results of multivariate analysis, and a nomogram model was obtained. The receiver operating characteristic curve (ROC), calibration curve, and decision-making curve (DC) were used to evaluate the discrimination, accuracy, and clinical net profit rate of the model. Results Multivariate analysis showed that nonfull breastfeeding, high-risk symptoms, and pregnancy complications were independent risk factors for ABE in neonates with severe hyperbilirubinemia. At the same time, the risk of ABE in neonates with severe hyperbilirubinemia increased with the increase of B/A and Hb levels. The ROC curve showed that the area under the curve for the model was 0.908 (95% CI: 0.839–0.960). The calibration curve shows that the actual prediction curve of the model is in good agreement with the corrected prediction curve. Using the cutoff value of the ROC curve as the diagnostic criterion, the threshold probability of the model was calculated to be 38%. The decision curve shows that when 38% is used as the basis for judging whether to take measures to intervene, the profit rate is 61%. Conclusion The occurrence of ABE in neonates with severe hyperbilirubinemia is affected by many factors, and there is a certain degree of interaction between these factors. Combining multiple factors to construct a risk nomogram model can provide a reference for early clinical detection of high-risk neonates.

Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation

To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

Risk Factors Predicting the Need for Phototherapy in Glucose 6 Phosphate Dehydrogenase-Deficient Infants in a Large Retrospective Cohort Study

Introduction: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of severe neonatal hyperbilirubinemia. This study evaluates the risk factors predicting the need for phototherapy in G6PD-deficient neonates after 72 h of age and assesses the safety of early discharge. Methods: A retrospective cohort study of 681 full-term G6PD-deficient infants with a birth weight ≥2,500 g over 4 years was conducted. We compared the baseline characteristics, bilirubin level on day 4 (after 72 h of life), day of peak bilirubin, G6PD levels, and concomitant ABO incompatibility between the group that required phototherapy (Group A) and those who did not (Group B). Results: 396 infants (58%), predominantly males, required phototherapy in the first week of life. The infants who required phototherapy had a lower median gestational age (38.3 vs. 38.7 weeks, p < 0.01) and had lower G6PD levels (2.3 ± 2.5 vs. 3 ± 3.4 IU, p < 0.05) compared to the controls. The mean day-four total serum bilirubin (TSB) levels were higher (213 ± 32 vs. 151 ± 37 µmol/L, p < 0.01), with bilirubin level peaking earlier (3 vs. 4 days of life, p < 0.01) in group A. Regression analysis identified TSB levels on day 4, Chinese race, lower gestation, and concomitant ABO incompatibility as the significant predictors for the need for phototherapy in the study population. In particular, coexisting ABO blood group incompatibility increased the risk of jaundice requiring phototherapy (OR 4.27, 95% CI: 1.98–121, p < 0.01). Day four TSB values above 180 µmol/L predicted the need for phototherapy with 86% sensitivity and 80% specificity. The findings were similar across both male and female infants with G6PD deficiency. Conclusion: G6PD-deficient infants with day four TSB levels of >180 µmol/L (10.5 mg/dL) and associated ABO blood group incompatibility have a higher risk of requiring phototherapy in the first week of life and should be closely monitored.

Gilbert or Crigler\u2013Najjar syndrome? Neonatal severe unconjugated hyperbilirubinemia with P364L UGT1A1 homozygosity

BackgroundSeveral mutations of bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) have been reported in patients with unconjugated hyperbilirubinemia. Few reports are available about the p.Pro364Leu mutation (P364L, c.1091C > T) in homozygous newborns. We describe the clinical, laboratory and therapeutic approach in two Chinese neonates with severe jaundice, homozygous for the P364L mutation.Case presentationTwo Chinese breastfed female infants presented prolonged unconjugated hyperbilirubinemia at the age of 1 month. Total bilirubin was higher than 15 mg/dl (D < 1). An exhaustive etiological work-up to detect possible causes of hyperbilirubinemia (notably hemolytic ones) was negative.The promoter and coding regions of UGT1A1 were amplified by polymerase chain reaction (PCR) from genomic DNA isolated from leukocytes. Both patients resulted homozygous for a variant site within the coding region of the gene in the 4 exon, c.1091C > T, p.Pro364Leu.In front of the persistently high level of unconjugated bilirubin, phototherapy was performed without persistent results. A treatment with phenobarbital was then begun and bilirubin level progressively decreased, with a complete and persistent normalization. The therapy was stopped.ConclusionUGT1A1 enzyme activity associated with the P364L mutation has been described as 35.6% of the wild-type enzyme activity. Photo-therapy and phenobarbital can be useful in front of persistently high level of unconjugated bilirubin.Our cases presented high bilirubin values, overlapping between Gilbert syndrome (GS) and Crigler-Najjar syndrome type II (CNS), but the complete normalization of bilirubin makes GS more likely. Homozygous P364L variant can be associated with severe neonatal unconjugated hyperbilirubinemia in Chinese infants, but jaundice can completely resolve in a few months, contrary to what happens in Crigler-Najjar syndrome type II.

COVID-19 DILEMMA: EARLY SEVERE HEMOLYTIC JAUNDICE IN NEWBORN BORN TO MOTHER WITH SARS-COV-2 INFECTION IN PREGNANCY

COVID-19 has been associated with hemolytic anemia in pediatric as well as adult age group. However, very little is known about the clinical course and immune responses in newborn born to a mother who contracted SARS-CoV-2 infection during pregnancy. Previously, few cases of autoimmune hemolytic anemia with SARS-CoV-2 infection due to the cytokine storm or through molecular mimicry has been found. Through this report, we would discuss about the SARS-COV-2 reactive antibodies as a potential etiology of severe early hemolysis leading to severe neonatal hyperbilirubinemia in a neonate born to a mother with SARS-CoV-2 infection.

Study on the application value of red blood cell distribution width and platelet distribution width in neonatal exchange transfusion with hyperbilirubinemia

Purpose The study aimed to evaluate the application of Red Blood Cell Distribution Width (RDW) and Platelet Distribution Width (PDW) in the treatment of neonatal exchange transfusion (ET) with hyperbilirubinemia as well as to provide relevant reference materials for clinical diagnosis and treatment. Patients and methods This was a retrospective study in a single center. Between January 2011 and December 2020, a total of 198 neonates, who were admitted to Fujian Maternity and Child Health Hospital for hyperbilirubinemia and treated with ET therapy were selected. They were divided into blood group antibody negative (BGAbN) ET (n = 92) and blood group antibody positive (BGAbP) ET (n = 106) groups. We analyzed changes in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet count(PLT) before and after ET; The clinical data of the neonates with hyperbilirubinemia were collected, and RDW and PDW were compared in the two groups before ET.. Results The concentrations of STB, SIB, and platelet count were much higher before ET and decreased significantly after ET; the difference was statistically significant (p<.001); There were significant differences between the two groups in RDW and PDW before ET. Conclusion ET therapy is the most timely and effective treatment method for severe hyperbilirubinemia in neonates clinically; RDW and PDW can help determine neonatal hemolysis caused by blood group antibodies.

Congenital cerebral malaria: a masquerader in a neonate

BackgroundCongenital malaria, which is caused by vertical transmission of malaria parasites, is a potentially fatal condition. Despite Africa’s high malaria burden, congenital malaria is not routinely screened for, and thus may go undiagnosed. Malaria, if not treated promptly, can quickly progress to severe forms and result in death. Severe congenital malaria is believed to be uncommon in neonates due to maternal antibodies, fetal haemoglobin, and the placenta’s sieving effect. The majority of reported cases were classified as having severe anaemia. Following a thorough review of the literature, only one case of congenital cerebral malaria (CCM) has been reported, and it was misdiagnosed.Case presentationA 5-day-old Nigerian neonate born to an apparently healthy mother initially displayed characteristics consistent with neonatal sepsis and severe neonatal hyperbilirubinaemia. He quickly developed characteristics consistent with meningitis. Surprisingly, the peripheral blood film revealed evidence of malaria parasites, which was immediately confirmed by Giemsa-stained thick and thin blood film microscopy for malaria. The patient was diagnosed with congenital cerebral malaria. The medication was modified to parenteral artesunate followed by oral artemisinin combination therapy. The neonate recovered fully and had no neurological deficits on follow up.ConclusionBecause CCM and infant meningitis have similar clinical presentations, CCM could be misdiagnosed and lead to death if there isn’t a high index of suspicion.

Severe neonatal hyperbilirubinaemia: lessons learnt from a national perinatal audit

ObjectivesTo describe characteristics of neonates with severe neonatal hyperbilirubinaemia (SNH) and to gain more insight in improvable factors that may have contributed to the development of SNH.Design and settingDescriptive study,...

Outcome Analysis of Severe Hyperbilirubinemia in Neonates Undergoing Exchange Transfusion.

Severe neonatal hyperbilirubinemia can cause neurological disability or mortality if not effectively managed. Exchange transfusion (ET) is an efficient treatment to prevent bilirubin neurotoxicity. The purpose of this study was to evaluate outcomes in severe neonatal hyperbilirubinemia with ET and to identify the potential risk factors for poor outcomes. Newborns of ≥28 weeks of gestational age with severe hyperbilirubinemia who underwent ET from January 2015 to August 2019 were included. Demographic data were recorded and analyzed according to follow-up outcomes at 12 months of corrected age. Poor outcomes were defined as death due to bilirubin encephalopathy or survival with at least one of the following complications: cerebral palsy, psychomotor retardation (psychomotor developmental index < 70), mental retardation (mental developmental index < 70), or hearing impairment. A total of 524 infants were eligible for recruitment to the study, and 62 infants were lost to follow-up. The outcome data from 462 infants were used for grouping analysis, of which 398 cases (86.1%) had normal outcomes and 64 cases (13.9%) suffered poor outcomes. Bivariate logistic regression analysis showed that peak total serum bilirubin (TSB) (odds ratio [OR] = 1.011, 95% confidence interval [CI] = 1.008-1.015, p = 0.000) and sepsis (OR = 4.352, 95% CI = 2.013-9.409, p < 0.001) were associated with poor outcomes of hyperbilirubinemia. Receiver operator characteristic curve analysis showed that peak TSB ≥452.9 µmol/L could predict poor outcomes of severe hyperbilirubinemia. Peak TSB and sepsis were associated with poor outcomes in infants with severe hyperbilirubinemia, and peak TSB ≥452.9 µmol/L could predict poor outcomes.

Increased prevalence of severe neonatal hyperbilirubinaemia during social distancing.

Social distancing guidelines implemented with the COVID-19 pandemic impacted health-care utilisation and disrupted critical social supports. Resurgence of highly transmissible strains has resulted in revisiting restrictions with potential impacts on newborn health. With concerns for inadequate post-partum support, we sought to determine if social distancing correlated with increased rates of readmission for hyperbilirubinaemia. Retrospective chart review identified all readmissions for hyperbilirubinaemia between 1/18 and 4/20 in Western New York. Infant/maternal demographics and data on hospital course were collected on control (1/1/18-31/1/20) and social distancing (1/2/20-30/4/20) cohorts. Nineteen outpatient clinics were surveyed regarding lactation support. Monthly readmissions for hyperbilirubinaemia nearly tripled during social distancing (0.90 ± 0.91 vs. 2.63 ± 2.29 per 1000 births during early COVID, P=0.015). Comparable severity of disease at readmission was observed with no difference in the need for therapies (phototherapy, intravenous immunoglobulin or exchange transfusion) or length of hospital stay. Mothers were younger (25.8 ± 3.3 vs. 31.3 ± 4.7 years; P=0.005) with higher rates of primiparity and exclusive breastfeeding than national norms, however not significantly higher than controls in our small cohort (62.5 vs. 37.0% for primiparity; 87.5 vs. 81.5% for breastfeeding). Of 19 clinics surveyed, only six confirmed a telemedicine option for lactation support. Rates of readmission for hyperbilirubinaemia increased during social distancing. Younger maternal age with high rates of primiparity and exclusive breastfeeding raise concern for inadequate social and/or lactation support. Proactive identification of mothers at risk and expansion of remote lactation services may be indicated with recurrent waves of the pandemic.

A Metadecomposition of Clinical Value Assessed Using aEEG in Severe Neonatal Hyperbilirubinemia.

Amplitude-integrated electroencephalography (aEEG) is an effective and simple means of continuous EEG monitoring beside the neonatal bed, which can be used to predict the early brain injury and prognosis evaluation of neonatal hyperbilirubinemia. This paper summarized 11 randomized controlled studies to meta-analyze the value of aEEG in evaluating neonatal hyperbilirubinemia and acute bilirubin encephalopathy. Through the literature search of health and interest science engineering and computer in the medical databases such as Wanfang Medicine and PubMed database, the medical information literature of aEEG to evaluate the clinical value in neonatal severe hyperbilirubinemia is used, and RevMan 5.2 software is selected for metadecomposition. The experimental results show that their serum total bilirubin is significantly higher than that of normal newborns, and with the aggravation of the condition, the serum expression is higher and higher. aEEG can effectively enhance the detection rate of such sufferers and help sufferers to receive therapy as soon as possible to ensure the prognosis of children.

Severe neonatal hyperbilirubinemia and the brain: the old but still evolving story

Severe neonatal hyperbilirubinemia and the brain: the old but still evolving story

Study on the Effect of Two Different Transfusion Methods in Neonates with Hyperbilirubinemia Induced by Non-Blood-Group Antibodies.

PurposeThe study aimed to analyse the clinical effect of homotype ET method and compatible ET method in neonates with hyperbilirubinemia caused by non-blood-group antibodies (non-blood-group antibodies refers to due to cause other than blood-group antibodies) as well as to provide relevant reference materials for clinical diagnosis and treatment in Fuzhou city.Patients and MethodsBetween January 2011 and December 2020, a total of 125 neonates, who were admitted to the Sentinel hospital of Fuzhou city, Fujian Provincial Maternity and Children’s Hospital for hyperbilirubinemia and treated with ET therapy were selected. They were divided into homotype ET (n=32) and compatibility ET (n=93) treatment groups. We analysed changes in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet count before and after ET; retrospectively analysed the neonates’ clinical data; and compared findings between the 2 groups.ResultsThe homotype ET group and the compatible ET group showed higher STB, SIB, and platelet levels before ET and decreased levels of the same after ET; the difference was statistically significant (P<0.001). Compared with the compatible ET group, the decreases in STB, SIB, and platelet count in the homotype ET group showed no significant difference (P>0.05).ConclusionET therapy is the most timely and effective treatment method for severe hyperbilirubinemia in neonates clinically, and the effects of homotype and compatible ET are similar.

Causes of severe neonatal hyperbilirubinemia: a multicenter study of three regions in China.

Available evidence suggests that our country bear great burden of severe hyperbilirubinemia. However, the causes have not been explored recently in different regions of China to guide necessary clinical and public health interventions. This was a prospective, observational study conducted from March 1, 2018, to February 28, 2019. Four hospitals in three regions of China participated in the survey. Data from infants with a gestational age ≥ 35weeks, birth weight ≥ 2000g, and total serum bilirubin (TSB) level ≥ 17mg/dL (342µmol/L) were prospectively collected. A total of 783 cases were reported. Causes were identified in 259 cases. The major causes were ABO incompatibility (n = 101), glucose-6-phosphate dehydrogenase deficiency (n = 76), and intracranial hemorrhage (n = 70). All infants with glucose-6-phosphate dehydrogenase deficiency were from the central south region. Those from the central south region had much higher peak total bilirubin levels [mean, 404μmol/L; standard deviation (SD), 75μmol/L] than those from the other regions (mean, 373μmol/L; SD, 35μmol/L) (P < 0.001). ABO incompatibility was the leading cause in the east and northwest regions, but cases in the central south region were mainly caused by both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency, and infants in this region had a much higher peak total bilirubin level. Intracranial hemorrhage may be another common cause. More thorough assessments and rigorous bilirubin follow-up strategies are needed in the central south region.

Diagnostic methods for neonatal hyperbilirubinemia: benefits, limitations, requirements, and novel developments.

Invasive bilirubin measurements remain the gold standard for the diagnosis and treatment of infants with severe neonatal hyperbilirubinemia. The present paper describes different methods currently available to assess hyperbilirubinemia in newborn infants. Novel point-of-care bilirubin measurement methods, such as the BiliSpec and the Bilistick, would benefit many newborn infants, especially in low-income and middle-income countries where the access to costly multi-analyzer in vitro diagnostic instruments is limited. Total serum bilirubin test results should be accurate within permissible limits of measurement uncertainty to be fit for clinical purposes. This implies correct implementation of internationally endorsed reference measurement systems as well as participation in external quality assessment programs. Novel analytic methods may, apart from bilirubin, include the determination of bilirubin photoisomers and bilirubin oxidation products in blood and even in other biological matrices. IMPACT: Key message: Bilirubin measurements in blood remain the gold standard for diagnosis and treatment of severe neonatal hyperbilirubinemia (SNH). External quality assessment (EQA) plays an important role in revealing inaccuracies in diagnostic bilirubin measurements. What does this article add to the existing literature? We provide analytic performance data on total serum bilirubin (TSB) as measured during recent EQA surveys. We review novel diagnostic point-of-care (POC) bilirubin measurement methods and analytic methods for determining bilirubin levels in biological matrices other than blood. Impact: Manufacturers should make TSB test results traceable to the internationally endorsed total bilirubin reference measurement system and should ensure permissible limits of measurement uncertainty.

Screening methods for neonatal hyperbilirubinemia: benefits, limitations, requirements, and novel developments.

Severe neonatal hyperbilirubinemia (SNH) is a serious condition that occurs worldwide. Timely recognition with bilirubin determination is key in the management of SNH. Visual assessment of jaundice is unreliable. Fortunately, transcutaneous bilirubin measurement for screening newborn infants is routinely available in many hospitals and outpatient settings. Despite a few limitations, the use of transcutaneous devices facilitates early recognition and appropriate management of neonatal jaundice. Unfortunately, however, advanced and often costly screening modalities are not accessible to everyone, while there is an urgent need for inexpensive yet accurate instruments to assess total serum bilirubin (TSB). In the near future, novel icterometers, and in particular optical bilirubin estimates obtained with a smartphone camera and processed with a smartphone application (app), seem promising methods for screening for SNH. If proven reliable, these methods may empower outpatient health workers as well as parents at home to detect jaundice using a simple portable device. Successful implementation of ubiquitous bilirubin screening may contribute substantially to the reduction of the worldwide burden of SNH. The benefits of non-invasive bilirubin screening notwithstanding, any bilirubin determination obtained through non-invasive screening must be confirmed by a diagnostic method before treatment. IMPACT: Key message: Screening methods for neonatal hyperbilirubinemia facilitate early recognition and timely treatment of severe neonatal hyperbilirubinemia (SNH). Any bilirubin screening result obtained must be confirmed by a diagnostic method. What does this article add to the existing literature? Data on optical bilirubin estimation are summarized. Niche research strategies for prevention of SNH are presented. Impact: Transcutaneous screening for neonatal hyperbilirubinemia contributes to the prevention of SNH. A smartphone application with optical bilirubin estimation seems a promising low-cost screening method, especially in low-resource settings or at home.

Normalizing hyperactivity of the Gunn rat with bilirubin-induced neurological disorders via ketanserin.

Severe neonatal hyperbilirubinemia has been known to cause the clinical syndrome of kernicterus and a milder one the syndrome of bilirubin-induced neurologic dysfunction (BIND). BIND clinically manifests itself after the neonatal period as developmental delay, cognitive impairment, and related behavioral and psychiatric disorders. The complete picture of BIND is not clear. The Gunn rat is a mutant strain of the Wistar rat with the BIND phenotype, and it demonstrates abnormal behavior. We investigated serotonergic dysfunction in Gunn rats by pharmacological analyses and ex vivo neurochemical analyses. Ketanserin, the 5-HT2AR antagonist, normalizes hyperlocomotion of Gunn rats. Both serotonin and its metabolites in the frontal cortex of Gunn rats were higher in concentrations than in control Wistar rats. The 5-HT2AR mRNA expression was downregulated without alteration of the protein abundance in the Gunn rat frontal cortex. The TPH2 protein level in the Gunn rat raphe region was significantly higher than that in the Wistar rat. It would be of value to be able to postulate that a therapeutic strategy for BIND disorders would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after onset of BIND manifestations. We demonstrated serotonergic dysregulation underlying hyperlocomotion in Gunn rats. This finding suggests that a therapeutic strategy for bilirubin-induced neurologic dysfunction (BIND) would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after the onset of the BIND manifestations. Ketanserin normalizes hyperlocomotion of Gunn rats. To our knowledge, this is the first study to demonstrate a hyperlocomotion link to serotonergic dysregulation in Gunn rats.

Developmental outcome of severe neonatal indirect hyperbilirubinemia

Background: Indirect hyperbilirubinemia is one of the most common causes of hospitalization in the neonatal period and its potential association with brain damage is well established. This study was conducted to determine neurodevelopmental outcome of children who had severe indirect hyperbilirubinemia in neonatal period and received intensive phototherapy with or without double volume exchange transfusion for its management. Material &amp; methods: This descriptive analytical study was performed in healthy infants with the history of severe indirect hyperbilirubinemia and need intensive phototherapy with or without exchange transfusion. We invited the enrolled infants at their 2-3 years age. Neurodevelopmental assessment was performed by a trained nurse using Ages and Stages Questionnaire. Results: The mean total serum bilirubin (TSB) of studied children was 26.4±4.1 mg/dl at their neonatal period. The estimated rate of severe hyperbilirubinemia with the TSB of 25-30 mg/dl was 48.7/100,000 live born infants and 11.4 /100,000 for hyperbilirubinemia higher than 30 mg/dl. The most common cause of jaundice in patients with exchange transfusion was ABO incompatibility. At their follow up examination, the classic form of bilirubin induced encephalopathy (Kernicterus) was diagnosed in 3 neonates. Two of them had sensory neural hearing loss too. Eleven children had low score based on ASQ in at least one area. The score was less than 2SD in 3 patients. Conclusion: Severe hyperbilirubinemia and kernicterus is still occurring in term and late pre-term infants. Early detection and management of severe hyperbilirubinemia may improve the neurodevelopmental outcome in high risk infants.