Neonatal Bilirubin Encephalopathy Research Articles

Globus pallidus/putamen T1WI signal intensity ratio in grading and predicting prognosis of neonatal acute bilirubin encephalopathy.

This study sought to investigate the relationship between the globus pallidus/putamen T1 weighted image (T1WI) signal intensity ratio (G/P ratio) and the acute bilirubin encephalopathy (ABE) in neonates, and to develop a new strategy for the grading and prognosis of ABE based on the G/P ratio. A total of 77 full-term neonates with ABE were scored according to bilirubin-induced neurological dysfunction and divided into mild, moderate, and severe groups. Cranial magnetic resonance imaging examinations were performed and the G/P ratio was recorded. The follow-up reexaminations were carried out at 6 months, 1 year, and 2 years after the initial examination. The neonates were then divided into two groups, the good prognosis group and the kernicterus spectrum disorder (KSD) group, according to the evaluation of Gesell Developmental Schedules and Brainstem Audio Electric Potential at 6 months. The differences of G/P ratios were statistically significant, not only among the mild, moderate, and severe ABE groups for the initial examinations but also between the KSD and the good prognosis groups for the follow-up reexaminations. Therefore, the ABE grading model and prognosis predicting model could be established based on the G/P ratio. In the KSD group, the area under the receiver operating characteristic curve of the G/P ratio-based predicting model was 93.5%, the optimal critical point was 1.29, the sensitivity was 88.2%, and the specificity was 93.3%. The G/P ratio can be used as an indicating parameter for both the clinical grading of neonatal ABE and the assessment of neonatal ABE prognosis. Specifically, the G/P ratio greater than 1.29 indicates a KSD of neonatal ABE.

The differential value of radiomics based on traditional T1-weighted sequences in newborns with hyperbilirubinemia

BackgroundOn the basis of visual-dependent reading method, radiological recognition and assessment of neonatal hyperbilirubinemia (NH) or acute bilirubin encephalopathy (ABE) on conventional magnetic resonance imaging (MRI) sequences are challenging. Prior studies had shown that radiomics was possible to characterize ABE-induced intensity and morphological changes on MRI sequences, and it has emerged as a desirable and promising future in quantitative and objective MRI data extraction. To investigate the utility of radiomics based on T1-weighted sequences for identifying neonatal ABE in patients with hyperbilirubinemia and differentiating between those with NH and the normal controls.MethodsA total of 88 patients with NH were enrolled, including 50 patients with ABE and 38 ABE-negative individuals, and 70 age-matched normal neonates were included as controls. All participants were divided into training and validation cohorts in a 7:3 ratio. Radiomics features extracted from the basal ganglia of T1-weighted sequences on magnetic resonance imaging were evaluated and selected to set up the prediction model using the K-nearest neighbour-based bagging algorithm. A receiver operating characteristic curve was plotted to assess the differentiating performance of the radiomics-based model.ResultsFour of 744 radiomics features were selected for the diagnostic model of ABE. The radiomics model yielded an area under the curve (AUC) of 0.81 and 0.82 in the training and test cohorts, with accuracy, precision, sensitivity, and specificity of 0.82, 0.80, 0.91, and 0.69 and 0.78, 0.8, 0.8, and 0.75, respectively. Six radiomics features were selected in this model to distinguish those with NH from the normal controls. The AUC for the training cohort was 0.97, with an accuracy of 0.92, a precision of 0.92, a sensitivity of 0.93, and a specificity of 0.90. The performance of the radiomics model was confirmed by testing the test cohort, and the AUC, accuracy, precision, sensitivity, and specificity were 0.97, 0.92, 0.96, 0.89, and 0.95, respectively.ConclusionsThe proposed radiomics model based on traditional TI-weighted sequences may be used effectively for identifying ABE and even differentiating patients with NH from the normal controls, which can provide microcosmic information beyond experience-dependent vision and potentially assist in clinical diagnosis and treatment.

Diagnostics Value of Quantitative Magnetic Resonance Imaging (MRI) in Neonatal Acute Bilirubin Encephalopathy.

Background: This study was designed to investigate the diagnostic value of relative signal intensity of globus pallidus on T1-weighted magnetic resonance imaging (MRI) in neonatal acute bilirubin encephalopathy (ABE). Methods: Participants who were recruited in hospital from April 2019 to May 2020 were grouped into mildly increased total serum bilirubin (TSB) group (n = 30), severely increased TSB group (n = 25), or extremely increased TSB group (n = 10) based on the total serum bilirubin level. Bilirubin-induced neurologic dysfunction scale score was used to determine if participants had acute bilirubin encephalopathy. All neonates underwent conventional brain MRI and the relative signal intensity of globus pallidus was measured on T1-weighted images. The diagnostic value of these 3 indices was assessed by receiver operating characteristic curve analysis. Results: There was a significant correlation between relative signal intensity of globus pallidus and total serum bilirubin level in neonates with hyperbilirubinemia (r = 0.551, P < .001). Relative signal intensity of globus pallidus in the extremely increased TSB group was significantly higher than that in severely increased TSB, mildly increased TSB, and healthy control groups. Relative signal intensity of globus pallidus in the acute bilirubin encephalopathy group was significantly higher than that in the non-acute bilirubin encephalopathy group (P < .01). The area under the receiver operating characteristic curve of the relative signal intensity of globus pallidus was 0.765 (P < .01), with sensitivity of 0.655 and specificity of 0.861. The area under the curve of the total serum bilirubin and visual inspection of globus pallidus signal was 0.621 and 0.579, respectively. The area under the curve of relative signal intensity was significantly greater than that of total serum bilirubin and visual inspection (P = .04 for both). Conclusion: Relative signal intensity of globus pallidus, which is an objective assessment, has the potential to be used as a diagnostic tool for acute bilirubin encephalopathy.

Incidence and risk factors of acute bilirubin encephalopathy in neonates with hyperbilirubinemia presenting at secondary care hospital.

In neonates, hyperbilirubinemia is the most common problem. Acute bilirubin encephalopathy is serious problem in less developed nations and their incidence varies with geographical location. Our objective was to find out the incidence and risk factors of acute bilirubin encephalopathy in neonates with hyperbilirubinemia. This was a prospective cross sectional study carried out at the department of pediatrics, THQ Hospital, Pindigheb in Punjab from October 2020 to October 2021. The inclusion criterion for our study was all the neonates of both the gender diagnosed with hyperbilirubinemia. Blood samples were collected from all the neonates and were sent to hospital laboratory for total serum bilirubin (TSB) measurement. The risk factors like delivery place, Rh/ABO incompatibility and preterm delivery were recorded. SPSS version 23 was used to input and analyze all of the data. In this study, a total of 350 neonates were included. The prevalence of acute bilirubin encephalopathy in our study was 16% (n=56). Seven (12.5%) neonates with acute bilirubin encephalopathy were preterm which was the major significant risk factor for acute bilirubin encephalopathy in hyperbilirubinemia neonates (p<0.05). The other risk factors such as hospital delivery, birth weight, Rh and ABO incompatibility were also observed but were non-significant (p>0.05). Our study observed 16% prevalence of acute bilirubin encephalopathy in neonates with hyperbilirubinemia. The preterm birth was a significant risk factor associated with the acute bilirubin encephalopathy in neonates with hyperbilirubinemia.

Development and evaluation clinical-radiomics analysis based on T1-weighted imaging for diagnosing neonatal acute bilirubin encephalopathy.

To investigate the value of clinical-radiomics analysis based on T1-weighted imaging (T1WI) for predicting acute bilirubin encephalopathy (ABE) in neonates. In this retrospective study, sixty-one neonates with clinically confirmed ABE and 50 healthy control neonates were recruited between October 2014 and March 2019. Two radiologists' visual diagnoses for all subjects were independently based on T1WI. Eleven clinical and 216 radiomics features were obtained and analyzed. Seventy percent of samples were randomly selected as the training group and were used to establish a clinical-radiomics model to predict ABE; the remaining samples were used to validate the performance of the models. The discrimination performance was assessed by receiver operating characteristic (ROC) curve analysis. Seventy-eight neonates were selected for training (median age, 9 days; interquartile range, 7-20 days; 49 males) and 33 neonates for validation (median age, 10 days; interquartile range, 6-13 days; 24 males). Two clinical features and ten radiomics features were finally selected to construct the clinical-radiomics model. In the training group, the area under the ROC curve (AUC) was 0.90 (sensitivity: 0.814; specificity: 0.914); in the validation group, the AUC was 0.93 (sensitivity: 0.944; specificity: 0.800). The AUCs of two radiologists' and the radiologists' final visual diagnosis results based on T1WI were 0.57, 0.63, and 0.66, respectively. The discriminative performance of the clinical-radiomics model in the training and validation groups was increased compared to the radiologists' visual diagnosis (P < 0.001). A combined clinical-radiomics model based on T1WI has the potential to predict ABE. The application of the nomogram could potentially provide a visualized and precise clinical support tool.

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.

Predischarge Transcutaneous Bilirubin and Total Serum Bilirubin in Predicting Readmission Due to Significant Hyperbilirubinemia in Near-Term and Term Neonates

Background: Prevention of bilirubin encephalopathy in healthy near-term and term neonates is the primary focus of newborn care. This study aims to assess the predictive accuracy of transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) measured before discharge for subsequent readmission because of significant hyperbilirubinemia in near-term and term neonates during the first postnatal week and to analyze the risk factors associated with readmission because of significant hyperbilirubinemia. Methods: TcB with BiliChek device and TSB measurements with bilirubinometer were obtained prior to discharge in all healthy near-term and term neonates delivered and admitted in the postnatal wards during the study period. Postnatal age (in hours) was recorded during bilirubin measurement. Results: The predictive ability of predischarge TcB measurement for the optimum cutoff of 104 µmol/L derived from the area under the receiver operating characteristic curve has a negative predictive value of 99.3% with a negative likelihood ratio (LR) of 0.15 and sensitivity of 91.7%, whereas the predictive ability of predischarge TSB measurement for the optimum cutoff of 109 µmol/L derived from the area under the receiver operating characteristic curve has 100% sensitivity and 100% negative predictive value with a negative LR of 0.0 for no readmission because of significant hyperbilirubinemia. The predischarge TSB level of those readmitted neonates had a very high odds for high-risk zone [OR (95% CI) 358.4 (96.39, 1332.59)] and 7.8 folds higher odds for intermediate-risk zone compared to those neonates who did not require readmission in Bhutani’s predischarge nomogram. Conclusion: The result of our study showed that both TcB obtained by using BiliChek device and TSB measurements obtained by bilirubinometer for the optimum cutoffs of 104 µmol/L and 109 µmol/L, respectively, and with negative LR of 0.15 and 0.0, respectively, can be used as a safe predischarge tool for no readmission because of significant hyperbilirubinemia after 24 h of postnatal age. The existing Bhutani’s predischarge nomogram for predicting significant hyperbilirubinemia should be an additional screening tool to reduce the rate of subsequent readmission because of hyperbilirubinemia.

STUDY OF CORRELATION OF ABO AND RH INCOMPATIBILITY WITH RISK OF NEONATAL HYPERBILIRUBINEMIA IN A TERTIARY CARE HOSPITAL

Background: Hyperbilirubinemia in a neonate is one of the most common problems that may occur in 60-70 % of term and 80% of preterm babies. It is known to be associated with signicant morbidity like neonatal bilirubin encephalopathy and even death. Clinically, and almost exclusively ABO incompatibility occurs in 'A' and 'B' blood group babies of O '+ve' mothers. These babies are reported to be at high risk of severe hyperbilirubinemia. So early intervention, at proper time, is mandatory to prevent these sequelae Methods: The aim is to determine the frequency of ABO and Rh blood group incompatibilities and associated incidence of hyperbilirubinemia for the purpose of instituting intervention for better neonatal outcomes. It was a descriptive cross-sectional study that includes 102 neonates born to mother with O or Rh-negative blood group admitted in the post-natal ward for routine newborn care. Serum bilirubin was documented in icteric neonates. Results: The incidence of ABO incompatibility in our study was 33.33% and of Rh incompatibility was 4.9%. In ABO and Rh incompatibility group, 41.17% and 20% new born respectively developed clinical jaundice. In ABO incompatibility group, majority, 64.28% did not require treatment, whereas in Rh incompatibility group 100% required treatment. In both ABO and Rh incompatibility exchange transfusion was not required. In ABO and Rh incompatibility, all new-born treated well and no kernicterus was seen. Conclusions: In ABO incompatibility, if jaundice develops, it remains in physiological limits. In presence of some aggravating conditions may present as pathological jaundice. It results in signicant morbidity but no mortality, so prevention of aggravating factors is very important, in case of ABO and Rh incompatibility.

High levels of unbound bilirubin are associated with acute bilirubin encephalopathy in post-exchange transfusion neonates

BackgroundAlthough it is known that unbound bilirubin can enter the brain, there is little evidence of its association with the development of acute bilirubin encephalopathy. Here, we investigated this potential relationship in neonates who had undergone exchange transfusion.MethodsData from 46 newborns who underwent exchange transfusion between 2016 and 1-1 to 2018-12-31 at the First People’s Hospital of Changde City in China were analyzed. The unbound bilirubin level was taken as the independent variable and the development of the acute bilirubin encephalopathy as the dependent variable. The covariates were age, birth weight, sex, red blood cell count, blood glucose, hemolytic disease, and whether the infant had received phototherapy.ResultsThe mean age and gestational age of the neonates were 146.5 ± 86.9 h and 38.6 ± 1.3 weeks [38.7(34.6–41.1) weeks] old, respectively; 52.17% were male. Binary logistic regression analysis after adjustment for covariates showed a positive association between the levels of unbound bilirubin and the development of acute bilirubin encephalopathy (odds ratio = 1.41, 95% confidence intervals 1.05–1.91, P = < 0.05).ConclusionThere is a significant association between unbound bilirubin levels and the development of acute bilirubin encephalopathy in neonates. Further investigations are required to explore the mechanisms.

Magnetic Resonance Image of Neonatal Acute Bilirubin Encephalopathy: A Diffusion Kurtosis Imaging Study.

Background and Objective: The abnormal T1-weighted imaging of MRI can be used to characterize neonatal acute bilirubin encephalopathy (ABE) in newborns, but has limited use in evaluating the severity and prognosis of ABE. This study aims to assess the value of diffusion kurtosis imaging (DKI) in detecting ABE and understanding its pathogenesis.Method: Seventy-six newborns with hyperbilirubinemia were grouped into three groups (mild group, moderate group, and severe group) based on serum bilirubin levels. All the patients underwent conventional MRI and DKI serial, as well as 40 healthy full-term infants (control group). The regions of interest (ROIs) were the bilateral globus pallidus, dorsal thalamus, frontal lobe, auditory radiation, superior temporal gyrus, substantia nigra, hippocampus, putamen, and inferior olivary nucleus. The values of mean diffusivity (MD), axial kurtosis (AK), radial kurtosis (RK), and mean kurtosis (MK), and fractional anisotropy (FA), radial diffusivity (RD), and axis diffusivity (AD) of the ROIs were evaluated. All newborns were followed up and evaluated using the Denver Development Screening Test (DDST). According to the follow-up results, the patients were divided into the normal group, the suspicious abnormal group, and the abnormal group.Result: Compared with the control group, significant differences were observed with the increased MK of dorsal thalamus, AD of globus pallidus in the moderate group, and increased RD, MK, AK, and RK value of globus pallidus, dorsal thalamus, auditory radiation, superior temporal gyrus, and hippocampus in the severe group. The peak value of total serum bilirubin was moderately correlated with the MK of globus pallidus, dorsal thalamus, and auditory radiation and was positively correlated with the other kurtosis value. Out of 76 patients, 40 finished the DDST, and only 9 patients showed an abnormality. Compared with the normal group, the AK value of inferior olivary nucleus showed significant differences (p < 0.05) in the suspicious abnormal group, and the MK of globus pallidus, temporal gyrus, and auditory radiation; RK of globus pallidus, dorsal thalamus, and auditory radiation; and MD of globus pallidus showed significant differences (p < 0.05) in the abnormal group.Conclusion: DKI can reflect the subtle structural changes of neonatal ABE, and MK is a sensitive indicator to indicate the severity of brain damage.

Detecting neonatal acute bilirubin encephalopathy based on T1-weighted MRI images and learning-based approaches

BackgroundNeonatal hyperbilirubinemia is a common clinical condition that requires medical attention in newborns, which may develop into acute bilirubin encephalopathy with a significant risk of long-term neurological deficits. The current clinical challenge lies in the separation of acute bilirubin encephalopathy and non-acute bilirubin encephalopathy neonates both with hyperbilirubinemia condition since both of them demonstrated similar T1 hyperintensity and lead to difficulties in clinical diagnosis based on the conventional radiological reading. This study aims to investigate the utility of T1-weighted MRI images for differentiating acute bilirubin encephalopathy and non-acute bilirubin encephalopathy neonates with hyperbilirubinemia.Methods3 diagnostic approaches, including a visual inspection, a semi-quantitative method based on normalized the T1-weighted intensities of the globus pallidus and subthalamic nuclei, and a deep learning method with ResNet18 framework were applied to classify 47 acute bilirubin encephalopathy neonates and 32 non-acute bilirubin encephalopathy neonates with hyperbilirubinemia based on T1-weighted images. Chi-squared test and t-test were used to test the significant difference of clinical features between the 2 groups.ResultsThe visual inspection got a poor diagnostic accuracy of 53.58 ± 5.71% indicating the difficulty of the challenge in real clinical practice. However, the semi-quantitative approach and ResNet18 achieved a classification accuracy of 62.11 ± 8.03% and 72.15%, respectively, which outperformed visual inspection significantly.ConclusionOur study indicates that it is not sufficient to only use T1-weighted MRI images to detect neonates with acute bilirubin encephalopathy. Other more MRI multimodal images combined with T1-weighted MRI images are expected to use to improve the accuracy in future work. However, this study demonstrates that the semi-quantitative measurement based on T1-weighted MRI images is a simple and compromised way to discriminate acute bilirubin encephalopathy and non-acute bilirubin encephalopathy neonates with hyperbilirubinemia, which may be helpful in improving the current manual diagnosis.

Detecting acute bilirubin encephalopathy in neonates based on multimodal MRI with deep learning

Differentiating acute bilirubin encephalopathy (ABE) from non-ABE in neonates with hyperbilirubinemia (HB) from routine magnetic resonance imaging (MRI) is extremely challenging since both conditions demonstrate similar T1 hyperintensities. To this end, we investigated whether the integration of multimodal MRI from routine clinical scans with deep-learning approaches could improve diagnostic performance. A total of 75 neonates with ABE and 75 neonates with HB (non-ABE) were included in the study. Each patient had three types of multimodal images taken, i.e., a T1-weighted image (T1WI), a T2-weighted image (T2WI), and an apparent diffusion coefficient (ADC) map. The three types of MRI contrasts and their combination were fed into two deep convolutional neural networks (CNNs), i.e., ResNet18 and DenseNet201. The performance of CNNs was compared with a traditional statistical method named logistic regression. We demonstrated that diagnostic methods with the multimodal data were better than any of the single-modal data. Both CNN models outperformed the logistic regression method. The best performance was achieved by DenseNet201 with the combination of three modalities of T1WI, T2WI, and ADC, with an accuracy of 0.929 ± 0.042 and an area under the curve (AUC) of 0.991 ± 0.007. Our study demonstrated that CNN models with multimodal MRI significantly improve the accuracy of diagnosing ABE. We proposed an efficient strategy of detecting ABE in neonates based on multimodal MRI with deep learning, which achieved an accuracy of 0.929 ± 0.042 and an AUC of 0.991 ± 0.007. We demonstrated the advantage of integrating multimodal MRI in detecting ABE in neonates with HB, using deep-learning models. Our strategy of diagnosing ABE using deep-learning techniques with multimodal MRI from routine clinical scans is potentially applicable to clinical practice.

Pattern of serum bilirubin changes following double volume exchange blood transfusion in neonates at a tertiary health facility in Nigeria.

Introductionexchange blood transfusion (EBT) is a form of massive transfusion useful in rapidly reducing serum bilirubin levels, but serum bilirubin levels frequently rebound within hours of completing the procedure, due to equilibration of extravascular bilirubin as well as on-going hemolysis. The study was carried out to determine the pattern of reduction in serum bilirubin levels following EBT among neonates with severe hyperbilirubinemia, as well as the factors contributing to this pattern, so as to establish evidence-based expectations following EBT.Methodsa retrospective descriptive study covering a two-year period in a Nigerian tertiary hospital. Details of the EBT procedures, including serial serum bilirubin levels, were obtained from the hospital records of all newborn babies who had double volume EBT done for severe hyperbilirubinaemia during the study period. Data was analyzed using the statistical software SPSS version 21.0.Resultsthe mean total serum bilirubin (TSB) before EBT in the 36 babies was 17.9 ± 6.3 mg/dl. The mean percentage decrease in TSB immediately following EBT was 44.3 ± 10.2%. Six hours after EBT, TSB levels had increased from the immediate post-EBT values by an average of 57.5 ± 32.2%. Twenty-four hours after the procedure, TSB values in most (87.1%) cases were still higher than the immediate post-EBT values, but lower than the pre-EBT values. Post-EBT anemia was recorded among 33.3% of the babies.ConclusionEBT is effective in rapidly reducing serum bilirubin levels and preventing acute bilirubin encephalopathy in neonates with severe hyperbilirubinemia, despite the rebound increase that occurs in TSB values after the procedure.

Nomogram for Acute Bilirubin Encephalopathy Risk in Newborns With Extreme Hyperbilirubinemia.

Background and Objectives: This work aimed to develop a predictive model of neonatal acute bilirubin encephalopathy.Methods: We retrospectively analyzed the data on extreme hyperbilirubinemia (EHB) newborns hospitalized in the First Hospital of Jilin University from January 1, 2012 to December 31, 2019. The demographic characteristics, pathological information, and admission examination results of newborns were collected to analyze the factors affecting acute bilirubin encephalopathy and to establish a predictive model.Results: A total of 517 newborns were included in this study, of which 102 (19.7%) had acute bilirubin encephalopathy. T1WI hyperintensity [18.819 (8.838–40.069)], mother's age > 35 years [2.618 (1.096–6.2530)], abnormal white blood cell (WBC) [6.503 (0.226–18.994)], TSB level [1.340 (1.242–1.445)], and albumin level [0.812 (0.726–0.907)] were independently associated with neonatal acute bilirubin encephalopathy (ABE). All independently associated risk factors were used to form an ABE risk estimation nomogram. The bootstrap validation method was used to internally validate the resulting model. The nomogram demonstrated good accuracy in predicting the risk of ABE, with an unadjusted C index of 0.943 (95% CI, 0.919–0.962) and a bootstrap-corrected C index of 0.900.Conclusion: A nomogram was constructed using five risk factors of ABE. This model can help clinicians determine the best treatment for neonatal hyperbilirubinemia.

Advances in studies on the polymorphism of UGT1A1 gene in neonates with unexplained hyperbilirubinemia

Neonatal hyperbilirubinemia is a common clinical symptom in the neonatal period. Severe jaundice can cause neonatal bilirubin encephalopathy. Clinically because severe hyperbilirubinemia more causes, the cause of hemolysis and infection is more common, this also accounted for a certain proportion of unknown reasons. UGT1A1 is a key enzyme for bilirubin metabolism, and unexplained jaundice is associated with a decrease in UGT1A1 activity caused by mutations in UGT1A1 gene, leading to neonatal persistent jaundice. The relationship between neonatal unexplained hyperbilirubinemia and UGT1A1 gene polymorphism was reviewed.

Cord Blood Alkaline Phosphatase and Albumin as Probable Predictors of Significant Neonatal Jaundice in Healthy Full-Term Infants

Background: Hyperbilirubinemia in a neonate may occur in 60 -70 % of term and 80 % of preterm babies. It is known to be associated with significant morbidity like neonatal bilirubin encephalopathy and even death. The concept of prediction of jaundice offers an attractive option to pick up babies at risk of neonatal hyperbilirubinemia. Objective: To assess the predictive value of cord blood alkaline phosphatase (ALP) and cord albumin in development of indirect neonatal hyperbilirubinemia in healthy term infants. Patients and method: This prospective cohort study was conducted at Obstetrics Emergency Department, Menoufia University Hospital and included (100) healthy full-term neonates over a period November 2019 to August 2020. Result: The cord alkaline phosphatase in no jaundice group was (248.63±71.73 U/L) while in jaundice group it was significantly higher (374.98±67.15 U/L, p <0.01). The cord albumin in no jaundice group was (3.72±0.18 g/dl) and in jaundice group it was (2.81±0.31 g/dl) with a highly significant decrease in jaundice group than the no jaundice group (p <0.01). The area under the curve was 0.965, at the cutoff value of alkaline phosphatase more than 315 (U/L), with a sensitivity of diagnosis of jaundice 95.0%, and a specificity 100.0%. Also, the area under the curve was 0.983 at the cutoff value of cord albumin (g/dl) less than 2.82 (g/dl) with sensitivity of diagnosis of jaundice 96.0% and a specificity of 100%. Conclusion: It can be concluded that both cord albumin levels and cord blood alkaline phosphatase in a healthy term neonate can predict the possibility of the neonate who will develop hyperbilirubinemia with a high sensitivity and specificity, with cutoff value less than 2.8 gm/dl for cord albumin and more than 315 U/L for alkaline phosphatase. Hence routine determination of cord albumin along with alkaline phosphatase can be implemented to keep track of at-risk neonates.

Cord Blood Alkaline Phosphatase and Albumin as Probable Predictors of Significant Neonatal Jaundice in Healthy Full-Term Infants

Hyperbilirubinemia in a neonate may occur in 60 -70 % of term and 80 % of preterm babies. It is known to be associated with significant morbidity like neonatal bilirubin encephalopathy and even death

Does heterozygosity for UGT1A1 *28 convey increased risk for severe neonatal jaundice?

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Bilirubin disrupts calcium homeostasis in neonatal hippocampal neurons: a new pathway of neurotoxicity.

Severe hyperbilirubinemia leads to bilirubin encephalopathy in neonates, causing irreversible neurological sequelae. We investigated the nature of neuronal selective vulnerability to unconjugated bilirubin (UCB) toxicity. The maintenance of intracellular calcium homeostasis is crucial for neuron survival. Calcium release from endoplasmic reticulum (ER) during ER-stress can lead to apoptosis trough the activation of Caspase-12. By live calcium imaging we monitored the generation of calcium signals in dissociated hippocampal neurons and glial cells exposed to increasing UCB concentrations. We showed the ability of UCB to alter intracellular calcium homeostasis, inducing the appearance of repetitive intracellular calcium oscillations. The contribution of intracellular calcium stores and the induction and activation of proteins involved in the apoptotic calcium-dependent signaling were also assessed. Thapsigargin, a specific inhibitor of Sarco/endoplasmic reticulum ATPase (SERCA) pumps, significantly reduced the duration of Ca2+ oscillation associated with UCB exposure indicating that UCB strongly interfered with the reticulum calcium stores. On the contrary, in pure astrocyte cultures, spontaneous Ca2+ transient duration was not altered by UCB. The protein content of GRP78, AT6, CHOP, Calpain and Caspase-12 of neuronal cells treated with UCB for 24h was at least twofold higher compared to controls. Calcium-dependent Calpain and Caspase-12 induction by UCB were significantly reduced by 50% and 98%, respectively when cells were pretreated with the ER-stress inhibitor 4-PBA. These results show the strong and direct interference of UCB with neuronal intracellular Ca2+ dynamics, suggesting ER Ca2+ stores as a primary target of UCB toxicity with the activation of the apoptotic ER-stress-dependent pathway.

A clinical prediction rule for acute bilirubin encephalopathy in neonates with extreme hyperbilirubinemia: A retrospective cohort study.

To establish a clinical prediction rule for acute bilirubin encephalopathy (ABE) in term/near-term neonates with extreme hyperbilirubinemia.A retrospective cohort study was conducted between January 2015 and December 2018. Six hundred seventy-three out of 26,369 consecutive neonates with extreme hyperbilirubinemia were enrolled in this study. Data included demographic characteristics, total serum bilirubin (TSB), albumin, bilirubin/albumin ratio (B/A), direct antiglobulin test, glucose-6-phosphate deficiency, asphyxia, sepsis, acidosis. ABE was defined as a bilirubin induced neurological dysfunction score of 4 to 9. We used stepwise logistic regression to select predictors of ABE and devised a prediction score.Of the 673 eligible infants, 10.8% suffered from ABE. Our prediction score consisted of 3 variables: TSB (as a continuous variable; odds ratio [OR] 1.16; 95% confidence interval [CI], 1.02–1.31; logistic coefficient 0.15), B/A (as a continuous variable; OR 1.88; 95% CI, 1.19–2.97; logistic coefficient 0.67), and sepsis (OR 3.78; 95% CI, 1.40–10.21; logistic coefficient 1.19). Multiplying the logistic coefficients by 10 and subtracting 75, resulted in the following equation for the score: Score = 12 × (if sepsis) + 1.5 × (TSB) + 7 × (B/A) − 75. The model performed well with an area under the curve of 0.871.The risk of ABE can be quantified according to TSB, B/A, and sepsis in term/near-term neonates with extreme hyperbilirubinemia.