Magnetic resonance spectroscopy and auditory brain-stem response audiometry as predictors of bilirubin-induced neurologic dysfunction in full-term jaundiced neonates.

The purpose of this research was to define the functions of MRS and ABR as predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy and/or exchange transfusion). This prospective cohort study was done at the NICU of Tanta University Hospitals over a 2-year duration. Fifty-six full-term neonates with pathological unconjugated hyperbilirubinemia were divided according to MRS and ABR findings into 2 groups: group (1) included 26 cases with mild acute bilirubin encephalopathy (BIND-M score 1-4). Group (2) included 30 cases with neonatal hyperbilirubinemia only. In addition, 20 healthy neonates with similar ages were employed as the controls. When compared to group 2 and the control group, group 1's peak-area ratios of NAA/Cr and NAA/Cho were found to be significantly reduced (P < 0.05). As compared to group 2 and the control group, group 1's Lac/Cr ratio was significantly greater (P < 0.05), but the differences were not significant for group 2 when compared to the control group. Waves III and V peak latencies, I-III, and I-V interpeak intervals were significantly prolonged in group 1 in comparison to group 2 and controls (P < 0.05) with no significant difference between group 2 and control group.   Conclusion: When the symptoms of ABE are mild and MRI does not show any evident abnormalities, MRS and ABR are helpful in differentiating individuals with ABE from patients with neonatal hyperbilirubinemia.    Trial registration:  ClinicalTrials.gov , Identifier: NCT06018012. What is Known: • MRS can be used as a diagnostic and prognostic tool for the differential diagnosis of patients with acute bilirubin encephalopathy, from patients with neonatal hyperbilirubinemia What is New: • ABR is a useful diagnostic and prognostic tool in the care and management of neonates with significantly raised bilirubin. It can be used as early predictor of acute bilirubin encephalopathy in the earliest stage of auditory damage caused by bilirubin.

Risk Factors of Onset Time and Persistence of Atopic Dermatitis in Children Under Age 5 Years: A Cross-Sectional Study.

Background: The prevalence of atopic dermatitis (AD) is high among children, with development of AD occurring during early childhood in most affected children and some having a chronic disease course. Risk factors for AD in this group remain undefined. Objectives: We analyzed the medical records of children with AD under 5 years of age. We summarized characteristics of the natural course of AD in these children and explored relevant risk factors of AD in infancy and early childhood. Methods: Using a self-developed questionnaire, we investigated 716 children under 5 years of age who were treated for AD at the Dermatology Department of the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China. We conducted the study from October 2021 to September 2022 using telephone and on-site interviews with the children's parents. In parental interviews, data were gathered on neonatal diseases, comorbidities, parental allergy history, maternal history of tobacco and alcohol use, and basic infant information at birth. Some children were tested for serum total immunoglobulin E (IgE) before this study. Results: Neonatal hyperbilirubinemia, neonatal respiratory distress syndrome (NRDS), neonatal infection, and infection during childhood had a significant impact on persistent symptoms and the onset of first symptoms in children with AD (P < 0.05). Allergic diseases as common comorbidities with AD, which had earlier onset of AD related to more obvious disease activity (P < 0.05). Parental history of allergy was also significant in AD (P < 0.05). Serum total iIgE levels in children with AD showed an impact on the clinical course of AD; neonatal hyperbilirubinemia and NRDS may affect IgE levels (P < 0.05). Persistent AD had a significant effect on the physical growth of children with height/length for age Z score ≤3 and weight for height/length Z score ≤3 (P < 0.05). Conclusions: Early adverse events in infants, infection before onset, and susceptibility to infection may affect the onset and clinical course of childhood AD. Serum total IgE levels affect the progression of AD. Persistent AD in childhood may have a slight impact on children's physical growth.

Neonatal Hyperbilirubinemia: Evaluation and Treatment.

Neonatal jaundice due to hyperbilirubinemia is common, and most cases are benign. The irreversible outcome of brain damage from kernicterus is rare (1 out of 100,000 infants) in high-income countries such as the United States, and there is increasing evidence that kernicterus occurs at much higher bilirubin levels than previously thought. However, newborns who are premature or have hemolytic diseases are at higher risk of kernicterus. It is important to evaluate all newborns for risk factors for bilirubin-related neurotoxicity, and it is reasonable to obtain screening bilirubin levels in newborns with risk factors. All newborns should be examined regularly, and bilirubin levels should be measured in those who appear jaundiced. The American Academy of Pediatrics (AAP) revised its clinical practice guideline in 2022 and reconfirmed its recommendation for universal neonatal hyperbilirubinemia screening in newborns 35 weeks' gestational age or greater. Although universal screening is commonly performed, it increases unnecessary phototherapy use without sufficient evidence that it decreases the incidence of kernicterus. The AAP also released new nomograms for initiating phototherapy based on gestational age at birth and the presence of neurotoxicity risk factors, with higher thresholds than in previous guidelines. Phototherapy decreases the need for an exchange transfusion but has the potential for short- and long-term adverse effects, including diarrhea and increased risk of seizures. Mothers of infants who develop jaundice are also more likely to stop breastfeeding, even though discontinuation is not necessary. Phototherapy should be used only for newborns who exceed thresholds recommended by the current AAP hour-specific phototherapy nomograms.

Models of bilirubin neurological damage: lessons learned and new challenges.

OBJECTIVE: Jaundice (icterus) is the visible manifestation of the accumulation of bilirubin in the tissue and is indicative of potential toxicity to the brain. Since its very first description more than 2000 years ago, many efforts have been undertaken to understand the molecular determinants of bilirubin toxicity to neuronal cells to reduce the risk of neurological sequelae through the use of available chemicals and in vitro, ex vivo, in vivo, and clinical models. Although several studies have been performed, important questions remain unanswered, such as the reasons for regional sensitivity and the interplay with brain development. The number of new molecular effects identified has increased further, which has added even more complexity to the understanding of the condition. As new research challenges emerged, so does the need to establish solid models of prematurity. METHODS: This review critically summarizes the key mechanisms of severe neonatal hyperbilirubinemia and the use of the available models and technologies for translational research. IMPACT: We critically review the conceptual dogmas and models used for studying bilirubin-induced neurotoxicity. We point out the pitfalls and translational gaps, and suggest new clinical research challenges. We hope to inform researchers on the pro and cons of the models used, and to help direct their experimental focus in a most translational research.

Association between neonatal hyperbilirubinemia and hypoglycemia in Chinese women with diabetes in pregnancy and influence factors.

This retrospective study aimed to investigate the correlation between neonatal hyperbilirubinemia (NHB) and hypoglycemia (NH) in Chinese women with diabetes in pregnancy (DIP), and the influencing factors. All the data were collected July 1, 2017 and June 30, 2020, and 10,558 Chinese women with DIP and live births were included. Two separate multivariate binary stepwise forward logistic regression analysis calculated OR with 95% CI. The prevalence rates of NHB and NH was respectively 3.65% and 5.82% among women with DIP. The comorbidity of both diseases was 0.59%. NH were 1.81 times (OR 1.81, 1.19-2.76) more likely to have hyperbilirubinemia. NHB is positively correlated with NH (OR 1.93, 1.27-2.92). Increased gestational age has a protective effect on both NH (OR 0.76, 0.68-0.85) and NHB (OR 0.80, 0.69-0.92). Abnormal placental morphology is related to NH (OR 1.55, 1.16-2.08) and NHB (OR 1.64, 1.10-2.45). Regarding neonatal outcomes, congenital heart disease (CHD) (OR 2.16, 1.25-3.73; and OR 10.14, 6.47-15.90) was a risk factor for NH and NHB. NHB and NH were significantly correlated in women with DIP. The offspring of DIP with multiple risk factors have a significantly increased risk of neonatal hyperbilirubinemia.

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

BACKGROUND: ABO 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 PRESENTATION: At 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. CONCLUSION: Even 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.

Discharge of newborns with risk factors of severe hyperbilirubinemia: description of a hospital at home-based care monitoring and phototherapy.

Neonatal jaundice is common and associated with delay in hospital discharge and risk of neurological sequelae if not treated. The objectives of the study were to report on our experience of the monitoring and treatment of neonatal jaundice in a home care setting and its feasibility and safety for neonates with high risk of severe hyperbilirubinemia. The 2-year study has been led in the greater Paris University Hospital At Home (Assistance Publique-Hôpitaux de Paris). The device of the intervention was the Bilicocoon® Bag, a light-emitting diode sleeping bag worn by the neonate when the total serum bilirubin value exceeds intensive phototherapy threshold, according to the guidelines from the American Academy of Pediatrics. One hundred and thirty-nine neonates had participated in the intervention and 39 (28%) were treated by phototherapy at home, as continuation of inpatient phototherapy or started at home. Seventy-five percent of the sample had more than two risk factors for development of severe hyperbilirubinemia. Twenty five percent of the cohort who received phototherapy at home had lower gestational age (p < 0.014) and had younger age at discharge from maternity (p < 0.09). Median length of stay in hospital at home was 5 days. Two patients needed readmission in conventional hospital (1%) for less than 24 h. In multivariate model, the length of stay decreased with the higher gestational age (p < 0.001) and increased significantly with the older age at discharge, the birth weight < 10th percentile, and a treatment by phototherapy at home.    Conclusion: Hospital at home, which is a whole strategy using an effective and convenient phototherapy device combined with a specialized medical follow-up, could be an alternative to conventional hospitalization for neonates at high risk of severe jaundice. The maternity discharge is facilitated, the mother-infant bonding can be promoted, and the risk of conventional rehospitalization is minimal, while guaranteeing the safety of this specific care. What is Known: • Managing neonatal jaundice is provided in conventional hospital with phototherapy. • Neonatal jaundice increases the risk of prolonged hospitalization or readmission. What is New: • Phototherapy is feasible in hospital at home for neonates with high risk of severe hyperbilirubinemia. • The care pathway of neonates from conventional hospital to hospital at home is described.

Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study.

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS: In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Outcome Analysis of Severe Hyperbilirubinemia in Neonates Undergoing Exchange Transfusion.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Neonatal hyperbilirubinemia and bilirubin neurotoxicity in hospitalized neonates: analysis of the US Database.

OBJECTIVE: The objective of this study was to assess the prevalence and trends for neonatal hyperbilirubinemia, and the development of bilirubin neurotoxicity in the USA. STUDY DESIGN: We used a de-identified national dataset for the years 2002-2017. The study included all newborn inpatients with postnatal age ≤28 days. Cochran-Armitage trend test was used for trend analyses. Regression analyses were performed and adjusted odds ratios (aOR) were reported. RESULTS: The study included 57,989,476 infants; of them 53,259,758 (91.8%) were term infants and 4,725,178 (8.2%) were preterm infants. Bilirubin neurotoxicity decreased over the years in term infants (Z = 0.36, p = 0.03) without change in preterm infants (Z = 42.5, p = 0.12). Black neonates were less likely to be diagnosed with hyperbilirubinemia than White neonates (aOR = 0.77, 95% confidence interval (CI): 0.77-0.78, p < 0.001) and more likely to develop bilirubin neurotoxicity than White neonates (aOR = 3.0.5, 95% CI: 2.13-4.36, p < 0.001). Bilirubin neurotoxicity rate in the overall population was 2.4 per 100,000 live births. CONCLUSIONS: Bilirubin neurotoxicity has significantly decreased in term infants and did not change in preterm infants. Despite the less diagnosis of hyperbilirubinemia in Black newborns, they are disproportionately at increased risk of developing bilirubin neurotoxicity when compared to White newborns. IMPACT: In this article, we analyzed the National Inpatient Database. This is the largest study of its kind using data on 57,989,476 neonates. The article has multiple novel findings: (1) it demonstrated that utilization of phototherapy has increased significantly over the years, (2) the rate of kernicterus for neonates decreased in term infants and did not change in preterm babies, (3) kernicterus was mostly encountered in infants without isoimmunization jaundice, and (4) there is a clear racial disparity in neonatal jaundice; although Black newborns have less neonatal jaundice, they are at increased risk of developing kernicterus.

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

BACKGROUND: Neonatal 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. METHODS: 3 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. RESULTS: The 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. CONCLUSION: Our 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.

Changes in amplitude-integrated electroencephalography, neuron-specific enolase, and S100B in neonates with brain injury induced by neonatal hyperbilirubinemia and their significance.

OBJECTIVE: To explore the changes in amplitude-integrated electroencephalography (aEEG), neuron-specific enolase (NSE), and S100B in neonates with brain injury induced by neonatal hyperbilirubinemia (NHB). METHODS: 67 neonates with brain injury induced by NHB admitted to our hospital from March 2016 to October 2018 were included in a brain injury group (BIG), and 82 neonates with NHB but without brain injury in our hospital during the same period were included in a non-BIG. The two groups were compared regarding the rates of normal and abnormal aEEG results. RESULTS: The proportion of normal aEEG results in the BIG was significantly lower than that in the non-BIG, and the proportion of moderately and severely abnormal aEEG results in the BIG were both significantly higher than those in the non-BIG. The BIG showed significantly higher NSE and S100B levels than those of the non-BIG. The ROC curve for predicting prognosis showed that the AUC of aEEG, NSE, S100B, and the combined detection are 0.780, 0.754, 0.743, 0.788. The AUC > 0.700 indicated a good predictive value for the prognosis. CONCLUSION: The combination of aEEG, NSE, and S100B has good value in diagnosing injury induced by NHB and can predict prognosis moderately well.

Correlation between neonatal hyperbilirubinemia and vitamin D levels: A meta-analysis.

OBJECTIVE: Hyperbilirubinemia is a common disease in the neonatal period, and hyperbilirubinemia may cause brain damage. Therefore, prevention and diagnosis and management of hyperbilirubinemia is very important, and vitamin D may affect bilirubin levels. To evaluate the relationship between neonatal hyperbilirubinemia and vitamin D levels. METHOD: The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and Embase databases as well as clinical trial registries in China and the United States were searched for relevant studies from inception to September 2020 without restrictions on language, population, or year. The studies was screened by two reviewers independently, the data were extracted, and the risk of bias of the included studies was evaluated using the NOS. A meta-analysis was conducted on the included studies using Stata11 software. RESULTS: Six case-control studies were included, and the methodological quality of the studies was high (grade A). The studies included 690 newborns; more than 409 were diagnosed with hyperbilirubinemia. The means and standard deviations were calculated. Meta-analysis results showed that neonatal vitamin D levels were 7.1 ng/ml lower among infants with hyperbilirubinemia than among healthy newborn levels (z = 6.95, 95% CI 9.10 ~ 5.09, P < 0.05). Subgroup analysis was conducted based on whether the bilirubin levels were concentrated in the 15 to 20 mg/dl range. Vitamin D level of infants with hyperbilirubinemia (the bilirubin levels were concentrated in the 15 to 20 mg/dl range) was 9.52 ng/ml (Z = 15.55, 95% CI-10.72~-8.32, P<0.05) lower than that of healthy infants. The bilirubin levels in four cases were not concentrated in the 15-20 mg/dl range. The results showed that the vitamin D level of hyperbilirubinemia (The bilirubin levels were not concentrated in the 15-20 mg/dl range) neonates were 5.35 ng/ml lower than that of healthy neonates (Z = 6.43, 95% CI-6.98~-3.72, P<0.05). CONCLUSION: Vitamin D levels were observed to be lower in neonates with hyperbilirubinemia as compared to term neonates without hyperbilirubinemia in this study. This can possibly suggest that neonates with lower vitamin D levels are at higher risk for developing hyperbilirubinemia.

Incidence of urinary tract infection in neonates with significant indirect Hyperbilirubinemia of unknown etiology: case-control study.

BACKGROUND: Indirect hyperbilirubinemia is frequently encountered during neonatal period. Although it has different causes, in some cases it can't be explained. Previous studies have illustrated that jaundice could be a major sign of urinary tract infection (UTI) in neonates. AIM OF THE WORK: We aimed to determine the association between UTI and significant unexplained neonatal indirect hyperbilirubinemia. METHODS: This prospective controlled study was performed on 150 neonates divided in two groups (100 as cases and 50 as controls) to investigate the incidence of UTI in neonates with significant unexplained hyperbilirubinemia. Urine sample was obtained using urine catheterization technique from neonates and full urine analysis was done and cases with pyuria had urine culture to confirm UTI. Immediate renal ultrasonography (USG) was performed for neonates with UTI. RESULTS: UTI incidence was 11% in cases while none of neonates in control group had UTI with statistical significance between cases and controls (P value < 0.05). The most common (36.4%) pathogen was Escherichia coli. Posterior urethral valve with mild hydronephrosis was diagnosed in 18.2% of UTI positive patients by renal ultrasonography. CONCLUSION: In neonates with unexplained indirect hyperbilirubinemia, UTI should be considered as a pathological cause.

Hearing screening in neonates with hyperbilirubinemia.

BACKGROUND: Hyperbilirubinemia is toxic to the auditory pathways and to the central nervous system, leaving sequelae such as hearing loss and encephalopathy. The damage to the auditory system occurs primarily within the brainstem and cranial nerve VIII, and manifests clinically as auditory neuropathy spectrum disorder. AIM: to establish the relationship that exists between hyperbilirubinemia at birth as a risk factor of neonatal hearing loss in children born in ABOU-EL-REISH hospital. MATERIALS AND METHODS: we carried out of 60 neonates categorized into two groups: Group (A n = 30), neonates with hyperbilirubinemia; Group (B n = 30), neonates without hyperbilirubinemia. RESULTS: Ten neonates were boys and twenty were girls from group A and eleven boys and nigh-teen girls from group B.There was significant statistical difference between group A and group B regarding ABR (P-value = 0.001) and a statistical difference regarding OAE (P-value = 0.103 in the right ear and 0.028 in the left ear). Also, our study shows the area under the curve and the diagnostic accuracy of total serum bilirubin (TSB) level for detection of hearing screening results (ABR) at a cut-off point 21 mg/dl (P-value = 0.008 and 0.009 in the right and left ears respectively.) CONCLUSIONS: Our study showed a relevant association between bilirubin levels and abnormal hearing screening results and the importance of combined screening with OAE and ABR tests.

Is Neonatal Hyperbilirubinemia Exposure Associated with a Risk of Autism Spectrum Disorder? A Nationwide Cohort Study.

OBJECTIVE: This study aimed to determine whether neonatal hyperbilirubinemia is associated with a risk of autism spectrum disorder (ASD) using a large population-based cohort. STUDY DESIGN: This retrospective cohort study used data from the children's database (2000-2012) of the National Health Insurance Research Database (1996-2012) in Taiwan. We included neonates who were born between 2000 and 2004 and aged <1 month diagnosed with and without hyperbilirubinemia. The primary outcome was physician-diagnosed ASD. At the end of 2012, multivariate Cox's regression analysis was used to estimate hazard ratios (HRs). RESULTS: A total of 67,017 neonates were included. The neonates with hyperbilirubinemia were associated with 1.28-fold increased risk of ASD (HR = 1.28, 95% confidence interval [CI]: 1.05-1.57) compared with those without hyperbilirubinemia. In subanalysis to determine how phototherapy and exchange transfusion treatment for hyperbilirubinemia were associated with ASD showed no association between treatment and ASD, suggesting the lack of a dose-response effect of hyperbilirubinemia on the risk of ASD. Boys had a nearly six-fold higher risk of ASD than girls (HR = 5.89, 95% CI: 4.41-7.86). Additionally, neonates born with preterm birth and low birth weight were associated with a risk of ASD (HR = 1.46, 95% CI: 1.00-2.13). CONCLUSION: We did not observe a dose-response effect of hyperbilirubinemia on ASD, but neonatal hyperbilirubinemia may be an independent risk factor for ASD if there is a residual confounding by other perinatal complications. Therefore, this study does not support a causal link between neonatal hyperbilirubinemia exposure and the risk of ASD.

Does riboflavin depletion cause auditory neuropathy spectrum disorder in at risk neonates?

We present a new hypothesis for the pathogenesis of auditory neuropathy spectrum disorder (ANSD) in at risk neonates involving depletion of riboflavin. The association between neonatal hyperbilirubinemia and ANSD is well recognized, yet causation has not been proven. The risk of ANSD does not correlate clearly with severity of hyperbilirubinemia and ASND only occurs in a small proportion of hyperbilirubinemic neonates. Additional, perhaps co-dependent, factors are therefore likely to be involved in pathogenesis. The metabolism of bilirubin consumes riboflavin and levels of riboflavin are depleted further by phototherapy. The neonate may also be deficient in riboflavin secondary to maternal deficiency, and reduced intake or impaired absorption. We propose that riboflavin depletion may be a significant contributor to development of ANSD in at risk neonates. The basis of this hypothesis is the recent recognition that impairment of riboflavin metabolism caused by genetic mutations (SLC52A2 or AIMF1) also causes ANSD.