Neonatal phototherapy and risk of epilepsy-A Danish population based study.

To evaluate the risk of epilepsy in children who received neonatal phototherapy. A cohort of live singletons born at a Danish hospital (2002-2016) with a gestational age ≥ 35 weeks. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of epilepsy in children treated with neonatal phototherapy compared to children not treated with neonatal phototherapy in the general population, and in a subpopulation of children who had serum bilirubin measurement. Adjusted HRs (aHR) were computed using multivariable and propensity score matching models to take maternal and neonatal factors into consideration. Children were followed from day 29 after birth to diagnosis of epilepsy, death, emigration, or December 31, 2016. Among 65,365 children, 958 (1.5%) received neonatal phototherapy. Seven children (incidence rates (IRs): 10.8 /10,000 person-years) who received neonatal phototherapy and 354 children (IR: 7.7) who did not receive neonatal phototherapy were diagnosed with epilepsy. Neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 0.95, 95% CI: 0.43-2.09) and propensity score matched (aHR 0.94, 95% CI: 0.39-2.28) models. In the subpopulation of 9,378 children with bilirubin measurement, 928 (9.9%) received neonatal phototherapy. In the analysis of the subpopulation in which bilirubin level and age at the time of bilirubin measurement were further taking into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 1.26, 95% CI: 0.54-2.97) and propensity score matched (aHR 1.24, 95% CI: 0.47-3.25) models,Conclusions: Neonatal phototherapy was not associated with an increased risk of epilepsy after taking maternal and neonatal factors into consideration. What is known: • A few studies have suggested that neonatal phototherapy for hyperbilirubinemia may increase the risk of childhood epilepsy. • Whether the observed associations contribute to hyperbilirubinemia, phototherapy, or underlying factors requires further investigation. What is new: • This study revealed no increased risk of epilepsy in children treated with neonatal phototherapy compared to children not treated with phototherapy after taking maternal and neonatal factors into consideration. • After further taking bilirubin level and age at the time of bilirubin measurement into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy.

Midwifery continuity of care, breastfeeding and neonatal hyperbilirubinemia: A retrospective cohort study.

AIM: To examine the association between Midwifery Continuity of Care (MCoC) and exclusive breastfeeding at hospital discharge and neonatal hyperbilirubinemia. METHODS: A matched cohort design was employed using data from the Swedish Pregnancy Register. The study included 12,096 women who gave birth at a university hospital in Stockholm, Sweden from January 2019 to August 2021. Women and newborns cared for in a MCoC model were compared with a propensity-score matched set receiving standard care. Risk ratios (RR) were determined with 95 % confidence intervals (CI) based on the matched cohort through modified Poisson regressions with robust standard error. A mediation analysis assessed the direct and indirect effects of MCoC on exclusive breastfeeding at hospital discharge and neonatal hyperbilirubinemia and to what extent the association was mediated by preterm birth. FINDING: Findings showed that MCoC was associated with a higher chance of exclusive breastfeeding rate (RR: 1.06, 95 % CI: 1.01-1.12) and lower risk of neonatal hyperbilirubinemia (RR: 0.51, 95 % CI: 0.32-0.82) compared with standard care. Mediation analysis demonstrated that lower preterm birth accounted for approximately 28 % of total effect on the reduced risk of neonatal hyperbilirubinemia. DISCUSSION/CONCLUSION: This matched cohort study provided preliminary evidence that MCoC models could be an intervention for improving exclusive breastfeeding rates at hospital discharge and reducing the risk of neonatal hyperbilirubinemia.

Beneficial changes in gut microbiota after phototherapy for neonatal hyperbilirubinemia.

Phototherapy is the most commonly used treatment for neonatal hyperbilirubinemia (NH). Gut microbiota is involved in bilirubin metabolism; however, it is uncertain whether this is affected by phototherapy. The present study included 43 newborns with hyperbilirubinemia and collected fecal samples for high-throughput sequencing before and after phototherapy. Selection α diversity analysis was used to determine the differences in diversity and abundance between the two groups, whereas similarity was determined using ß diversity analysis. Linear discriminant analysis effect size analysis was used to screen for markedly different bacteria. The structure of the gut microbiota in newborns with hyperbilirubinemia changed after phototherapy, with a significant decrease in abundance and diversity. The changes in the key bacterial species were characterized by an increase in the abundance of Streptococcus salivarius and a decrease in the abundance of Escherichia, Klebsiella pneumoniae, Rothia mucilaginosa and Streptococcus oralis. These changes mainly manifested as an increase in beneficial bacteria and a decrease in opportunistic bacteria, which may not be related to the side effects of phototherapy. These results can provide theoretical assistance for microbiological research on the later stages of NH.

Illuminating Progress: A Comprehensive Review of the Evolution of Phototherapy for Neonatal Hyperbilirubinemia.

This comprehensive review thoroughly examines the historical evolution, physiological foundations, and contemporary advancements in the application of phototherapy for neonatal hyperbilirubinemia. Neonatal hyperbilirubinemia, a common condition resulting from the immature hepatic processes in newborns, poses potential risks, including neurotoxicity, if left untreated. The review traces the historical progression from early recognition of neonatal jaundice to the development of various phototherapy modalities, showcasing the dynamic landscape of neonatal care. Emphasizing the physiological intricacies of bilirubin metabolism in neonates, the study underscores the vulnerability of newborns to hyperbilirubinemia due to delayed hepatic maturation. Phototherapy is a cornerstone in managing hyperbilirubinemia, demonstrating consistent efficacy in reducing unconjugated bilirubin levels. The implications for clinical practice are significant, offering healthcare professionals insights into tailoring treatment strategies based on individual neonatal characteristics and the severity of jaundice. Integrating advanced monitoring and control systems enhances the precision and safety of phototherapy. Recommendations for future research emphasize the need to investigate long-term outcomes, explore adjunctive therapies, and address resource limitations to ensure global access to effective neonatal care. Overall, this review contributes to the ongoing refinement of neonatal care practices, offering a comprehensive understanding of neonatal hyperbilirubinemia and its evolving treatment landscape.

Forgoing Exchange Transfusion in Neonatal Hyperbilirubinemia: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Unconjugated hyperbilirubinemia is part of the everyday life of the neonatal period as it reflects the adaptation of the metabolism of bilirubin. The neonatal hyperbilirubinemia usually resolves spontaneously, but it can also be the cause of an acute or chronic encephalopathy known as kernicterus. Regardless of the cause, the goal of therapy is to prevent this neurotoxicity while not causing undue harm. Phototherapy and, if it is unsuccessful, exchange transfusion (ECT) remain the primary treatment modalities used to keep the maximal total serum bilirubin (TSB) below pathologic levels. MATERIALS AND METHODS: This is a descriptive retrospective cohort study of 69 live neonates hospitalized in the Department of Neonatology and Neonatal Resuscitation of Mohammed VI University Hospital with unconjugated hyperbilirubinemia requiring ECT and treated with intensive phototherapy instead, spanning five years from March 2016 to March 2021. We aim to demonstrate the effectiveness of phototherapy in achieving prolonged reduction of bilirubin levels and the prevention of neurological complications and to compare our results with those in the literature. RESULTS: The use of intensive phototherapy in the treatment of neonatal unconjugated hyperbilirubinemia is very effective in lowering total serum bilirubin when its level is in the range of exchange transfusion, and it has succeeded in preventing the neurological complications of severe hyperbilirubinemia. CONCLUSION: Through this study, it can be seen that phototherapy is an efficacious, simpler, and less hazardous alternative to exchange transfusion in achieving a sustained reduction of bilirubin levels and preventing neurological complications.

Novel Two-Infusion Pump Technique for Exchange Transfusion in a Hyperbilirubinemic Neonate.

Neonatal hyperbilirubinemia is a common concern in newborns, with ABO blood group incompatibility serving as a significant risk factor for severe jaundice. This case report outlines the successful management of a 2.5 kg female infant born to a primigravida mother with ABO incompatibility-induced hyperbilirubinemia. The neonate, born at 38.4 weeks via lower segment cesarean section, exhibited signs of jaundice at 91 hours of life, prompting screening and subsequent confirmation of serum bilirubin levels 26.4. The decision was made using the American Academy of Pediatrics (AAP) and categorized the child under high risk according to age and bilirubin level to implement a complete exchange transfusion using a novel approach with two infusion pumps. The unique aspect of this case lies in introducing a two-infusion pump technique, one to infuse and one to extract blood by inserting the IV set in opposite directions in the infusion pump to perform the exchange transfusion, aiming to minimize complications associated with traditional methods. Careful handling of umbilical venous and arterial lines, coupled with aseptic precautions, sought to mitigate the risk of sepsis. The procedure, conducted over two hours, demonstrated stability in vital signs and was monitored with a transcutaneous bilirubinometer. Post-transfusion, repeat serum bilirubin tests showed a decrease in bilirubin of 10.1, indicating the success of the novel exchange transfusion method. The infant was discharged after a five-day hospital stay, showcasing this innovative approach's potential efficacy and safety. This case contributes to the evolving strategies in neonatal care and emphasizes the importance of tailored interventions in managing hyperbilirubinemia associated with ABO incompatibility.

Prospective Evaluation of Hearing Status in Neonatal Hyperbilirubinemia.

Elevated bilirubin levels in neonates are commonly seen both physiologically and in pathological conditions. There are few articles describing the effects of elevated bilirubin levels on the auditory system. The objectives of this paper was to study the prevalence of hearing impairment in neonates with hyperbilirubinemia and assess outcome/reversibility of hearing impairment in these neonates with follow-up hearing evaluation. This was a prospective single centre, case control study. Cases: neonates, total bilirubin levels >15 mg/dl. Controls: <15 mg/dl. Exclusion criteria included neonates with neonatal hypoxia, intrauterine infections, sepsis or meningitis, infants with a family history of hearing loss, low birth weight, ototoxic medications, external and middle ear pathology. Otoacoustic emission testing (OAE) was done at birth. Neonates who fail OAE were advised follow up with Brainstem Evoked Response Audiometry (BERA) after 2 months. Neonates having abnormal BERA waves were called for follow up at 6 months. Out of 57 cases, 3 had failed OAE and had normal BERA waves on follow up at 2 months. Out of 60 controls, 5 had failed OAE and follow up BERA for 3 patients were normal and 2 babies were lost to follow up. No statistical significance in hearing impairment in hyperbilirubinemia v/s normal babies was noted. Elevated bilirubin levels in the absence of any other risk factors may not show significant changes in the hearing screening. Some effect owing to the p value close to being significant in cases has been noted. The same may not contribute to permanent hearing impairment as first OAE changes may be transient and seem to revert with age. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04181-7.

Efficacy of home phototherapy versus inpatient phototherapy for neonatal hyperbilirubinemia: a systematic review and meta-analysis.

BACKGROUND: Home phototherapy (HPT) remains a contentious alternative to inpatient phototherapy (IPT) for neonatal hyperbilirubinemia. To guide evidence-based clinical decision-making, we conducted a meta-analysis of randomized clinical trials (RCTs) and cohort studies and assessed the comparative risks and benefits of HPT and IPT. METHODS: PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technique Journals Database, ClinicalTrials.gov, and International Clinical Trial Registry Platform trial were searched from inception until June 2, 2023. We included RCTs and cohort studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Cochrane Collaboration Risk of Bias tool and the Newcastle-Ottawa scale. The outcome measures were phototherapy duration, daily bilirubin level reduction, exchange transfusion, hospital readmission, parental stress scale, and complications. We used fixed- or random-effects meta-analysis models, assessed heterogeneity (I2), conducted subgroup analyses, evaluated publication bias, and graded evidence quality. RESULTS: Nine studies (998 patients) were included (four RCTs, five cohort studies). HPT was associated with longer phototherapy duration (SMD = 0.55, 95% CI: 0.06-1.04, P = 0.03). Cohort study subgroup analysis yielded consistent results (SMD = 0.90; 95% CI: 0.69 to 1.11, P < 0.001, I2 = 39%); the RCTs were not significantly different (SMD = -0.04; 95% CI: -0.15 to 0.08, P = 0.54, I2 = 0%). Hospital readmission was higher with HPT (RR = 4.61; 95% CI: 1.43-14.86, P = 0.01). Daily bilirubin reduction (WMD = -0.12, 95% CI: -0.68 to 0.44, P = 0.68) or complications were not significantly different (RR = 2.29; 95% CI: 0.31-16.60, P = 0.41). The evidence quality was very low. HPT was associated with lower parental stress (SMD = -0.44, 95% CI: -0.71 to -0.16, P = 0.002). None of three included studies reported exchange transfusion. CONCLUSIONS: The current evidence does not strongly support HPT efficacy for neonatal hyperbilirubinemia, as high-quality data on long-term outcomes are scarce. Future research should prioritize well-designed, large-scale, high-quality RCTs to comprehensively assess HPT risks and benefits.

Developing and evaluating a predictive model for neonatal hyperbilirubinemia based on UGT1A1 gene polymorphism and clinical risk factors.

Background: Neonatal hyperbilirubinemia (NHB) is one of the most common diseases in the neonatal period. Without timely diagnosis and treatment, it can lead to long-term complications. In severe cases, it may even result in fatality. The UGT1A1 gene and clinical risk factors play important roles in the development and progression of NHB. Methods: In this study, we conducted a cohort study and analyzed 3258 newborns from the Jilin Women And Children Health Hospital in northern China, including 372 children with hyperbilirubinemia. We established a predictive model using a logistic regression model based on clinical risk factors and the polymorphism of the G211A locus in the UGT1A1 gene of newborns. Furthermore, the performance of the prediction model was evaluated using the ROC curve. Results: The logistic regression model indicates that the following factors are associated with an increased risk of NHB: the time when stool turns yellow [P ≤ 0.001, OR 1.266 (95% CI: 1.125-1.425)]; neonatal cephalohematoma [P ≤ 0.001, OR 33.642 (95% CI: 21.823-51.861)]; hemolytic disease of newborn [P ≤ 0.001, OR 33.849 (95% CI: 18.589-61.636)]; neonatal weight loss [P ≤ 0.001, OR 11.275 (95% CI: 7.842-16.209)]; neonatal premature rupture of membranes (PROM) history [P = 0.021, OR 1.422 (95% CI: 1.056-1.917)]; genetic polymorphism at the UGT1A1 gene G211A locus. Gestational age is a protective factor [P ≤ 0.001, OR 0.766 (95% CI: 0.686-0.855)]. Compared to natural labor, cesarean section is a protective factor [P = 0.011, OR 0.711 (95% CI: 0.546-0.926)], while assisted delivery is a risk factor [P = 0.022, OR 2.207 (95% CI: 1.121-4.346)]. The area under the curve (AUC) of this prediction model is 0.804 (95% CI: 0.777-0.831), indicating good discrimination ability and value for predicting the risk of NHB after birth. Conclusion: We have developed and evaluated a predictive model that combines UGT1A1 gene polymorphism and clinical risk factors for the first time. By using this nomogram and taking into account the results of serum total bilirubin measurement or transcutaneous bilirubin measurement, early prediction of the risk of neonatal hyperbilirubinemia can be achieved.

Neonatal jaundice and associated factors in public hospitals of southern Ethiopia: A multi-center cross-sectional study.

Background: Neonatal jaundice is one of the most prevalent problems, affecting over a million newborns globally every year. It increases the likelihood of hospitalization, lifetime disability, and death, particularly in low and middle-income countries. Despite its impact and diverse risk factors, neonatal jaundice remains underappreciated in developing nations such as Ethiopia. As a result, this study aimed to determine the magnitude and associated factors of jaundice in newborns admitted to public hospitals in south Ethiopia. Methods: A facility-based cross-sectional study was conducted among 417 newborns from October 1, 2020, to April 30, 2021. The data was collected using pretested interviewer-administered questionnaire and checklist. Jaundice and its severity were assessed using the physician's diagnosis and the Kramer scale. Open data kit tools and Stata version 16.0 were used for data collection and analysis, respectively. Bivariable and multivariable analyses were used to identify factors associated with neonatal jaundice. An odds ratio with a 95 % confidence interval was used to assess the direction and strength of the association. Results: Out of the newborns, 24.46 % [95 % CI: 20.42-28.88] encountered neonatal jaundice. Being male [AOR: 1.81, 95 % CI: 1.06, 3.12], birth injuries [AOR: 3.01, 95 % CI: 1.27, 7.12], perinatal asphyxia [AOR: 2.10, 95 % CI: 1.18, 3.76], hyaline membrane disease [AOR: 2.16, 95 % CI: 1.16, 4.00], sepsis [AOR: 3.30, (95 % CI: 1.67, 6.54], the combined effect of low birth weight and prematurity [AOR: 1.88, 95 % CI: 1.06, 3.35], and maternal alcohol abuse during pregnancy [AOR: 2.46, 95 % CI: 1.02, 5.94] were significantly associated with neonatal jaundice. Conclusion: The burden of neonatal jaundice was high in the hospitals studied. Early detection and treatment of neonatal problems, counseling pregnant women to avoid consuming any level of alcohol, strict monitoring of labor and delivery, improving antenatal care utilization, and pre-discharge universal bilirubin screening of newborns are essential to reduce the incidence and complications of jaundice. The findings of this study will be used as input to initiate interventions and conduct further studies.

Acceptability and operational feasibility of community health worker-led home phototherapy treatment for neonatal hyperbilirubinemia in rural Bangladesh.

There is an unmet need for phototherapy treatment in low- and middle-income countries (LMICs) to prevent disability and death of newborns with neonatal hyperbilirubinemia. Home phototherapy deployed by community health workers (CHWs) in LMICs may help increase access to essential newborn postnatal care in a more acceptable way for families and lead to an increase in indicated treatment rates for newborns with hyperbilirubinemia. We aimed to investigate the operational feasibility and acceptability of a CHW-led home phototherapy intervention in a rural sub-district of Bangladesh for families and CHWs where home delivery was common and a treatment facility for neonatal hyperbilirubinemia was often more than two hours from households. We enrolled 23 newborns who were ≥ 2 kg in weight and ≥ 35 weeks gestational age, without clinical danger signs, and met the American Academy of Pediatric treatment criteria for phototherapy for hyperbilirubinemia. We employed a mixed-method investigation to evaluate the feasibility and acceptability of home phototherapy through surveys, in-depth interviews and focus group discussions with CHWs, mothers, and grandparents. Mothers and family members found home phototherapy worked well, saved them money, and was convenient and easy to operate. CHWs found it feasible to deploy home phototherapy and identified hands-on training, mHealth job aids, a manageable workload, and prenatal education as facilitating factors for implementation. Feasibility and acceptability concerns were limited amongst parents and included: a lack of confidence in CHWs' skills, fear of putting newborn infants in a phototherapy device, and unreliable home power supply. CHW-led home phototherapy was acceptable to families and CHWs in rural Bangladesh. Further investigation should be done to determine the impact of home phototherapy on treatment rates and on preventing morbidity associated with neonatal hyperbilirubinemia. Clinical Trial (CT) registration ID: NCT03933423, full protocol can be accessed at https://doi.org/10.1186/s13102-024-00824-6 . Name of the trial registry: clinicaltrials.gov. Clinical Trial (CT) registration Date: 01/05/2019.

Neurodevelopmental outcome at 6 months of age of full-term neonates with hyperbilirubinemia necessitating exchange transfusion.

BACKGROUND: Bilirubin neurotoxicity involves a spectrum of varying severity that could result in adverse long-term sequelae. AIMS: To compare the neurodevelopmental outcome of full-term neonates who underwent exchange transfusion with those who did not. STUDY DESIGN: A retrospective cohort study. SUBJECTS: This study included a retrospective review of records of sixty neonates who were matched in admission ages and serum bilirubin levels and the comparison groups were those who received an exchange transfusion (n = 30) versus those where exchange transfusion was planned, but the bilirubin levels dropped sufficiently during the period where the exchange blood was being prepared (n = 30). History, clinical examination, and laboratory investigations were documented. OUTCOME MEASURES: Neurodevelopmental outcome, at 6 months of age, using Bayley scales of infant development was assessed. RESULTS: The exchange group had statistically significant lower cognitive scores (p-value 0.005). The higher the rate of bilirubin decline, the better the language and motor scores in the phototherapy group (p-values 0.020 and 0.024 respectively). Infants with longer duration to exchange transfusion had lower cognitive, language, and motor scores (p-values 0.01, 0.001, and 0.003 respectively). CONCLUSIONS: Slower rates of bilirubin decline and longer duration before intervention increase the chances of adverse neurodevelopmental outcomes.

Risk factors for urinary tract infection in infants with unexplained hyperbilirubinemia: a single center case-control study.

Background: Urinary tract infection (UTI) is a potential cause of neonatal jaundice. Nevertheless, there remains a lack of consensus regarding appropriate screening practices for UTI in infants with hyperbilirubinemia. This study aimed to analyze a group of jaundiced infants to assess the prevalence of UTI, explore potential risk factors, and examine the impact of UTI on the course and severity of neonatal jaundice. Methods: This retrospective case-control study was conducted on 150 jaundiced infants (aged < 8 weeks) without a known etiology in the hyperbilirubinemia work-up. All subjects underwent phototherapy treatment and UTI screening by catheterization. They were then classified into UTI and non-UTI groups based on urine culture results, with a positive urine culture indicating the growth of ≥10,000 colony-forming units. The clinical characteristics and jaundice-related parameters of both groups were analyzed. Results: Among the 150 jaundiced patients, the prevalence of UTI was 29%. There was a significantly higher male predominance in the UTI group, and patients with UTI also had a significantly longer duration of hospitalization compared to those without UTI. Significant risk factors associated with UTI in jaundiced infants included male gender and a peak total bilirubin level higher than 18 mg/dl during hospitalization. The most common pathogens identified in urine culture were Escherichia coli (41.9%) and Enterococcus faecalis (30.2%). Conclusion: In cases of neonatal jaundice where the underlying cause is not evident, screening for UTI should be performed, particularly when associated risk factors or inadequate response to phototherapy is present.

Modified Kramer's versus Kramer's Method for Clinical Assessment of Jaundice in Term and Near-Term Neonates.

OBJECTIVES: To compare the performance of Modified Kramer's and Kramer's methods in terms of agreement with total serum bilirubin (TSB). METHODS: This cross-sectional study was done in Level-III neonatal unit in New Delhi. Visibly jaundiced neonates born at ≥35 wk of gestation were enrolled and examined by (i) conventional Kramer's, (ii) Modified Kramer's in artificial (MK-A) and (iii) natural daylight (MK-N), and finally sampled for estimation of TSB by point-of-care spectrophotometry. The primary outcomes were agreement of Kramer's and Modified Kramer's with TSB and accuracy in terms of proportion of bilirubin estimates lying within ±2 mg/dL of TSB; secondary outcome was agreement of MK-A and MK-N with TSB. RESULTS: A total of 144 neonates with median gestation of 37 wk and mean birth weight of 2788 g were enrolled. Bland Altman analysis between Kramer's and TSB yielded mean difference of 1.7 mg/dL, 95% limits of agreement (LOA) -3.1 to 6.6 mg/dL. For Modified Kramer's and TSB, mean difference was -0.02 mg/dL, 95% LOA -4.7 to 4.7 mg/dL under artificial light; 0.02 mg/dL, 95% LOA -4.2 to 4.2 mg/dL under natural daylight. MK-N had highest proportion of bilirubin estimates lying within ±2 mg/dL of TSB (68.7%) as compared to MK-A (59.7%) [OR, 1.77; 95% CI, 1.09 to 2.86] and Kramer's (45.8%) [OR, 1.65; 95% CI, 1.27 to 2.15]. CONCLUSIONS: Though all the three methods had poor agreement with TSB, Modified Kramer's method when performed in natural light had reasonable accuracy, however limited clinical utility, in evaluation of clinical jaundice.

Associations between UGT1A1, SLCO1B1, SLCO1B3, BLVRA and HMOX1 polymorphisms and susceptibility to neonatal severe hyperbilirubinemia in Chinese Han population.

BACKGROUND: Severe neonatal hyperbilirubinemia could lead to kernicterus and neonatal death. This study aimed to analyze the association between single nucleotide polymorphisms in genes involved in bilirubin metabolism and the incidence of severe hyperbilirubinemia. METHODS: A total of 144 neonates with severe hyperbilirubinemia and 50 neonates without or mild hyperbilirubinemia were enrolled in 3 institutions between 2019 and 2020. Twelve polymorphisms of 5 genes (UGT1A1, SLCO1B1, SLCO1B3, BLVRA, and HMOX1) were analyzed by PCR amplification of genomic DNA. Genotyping was performed using an improved multiplex ligation detection reaction technique based on ligase detection reaction. RESULTS: The frequencies of the A allele in UGT1A1-rs4148323 and the C allele in SLCO1B3-rs2417940 in the severe hyperbilirubinemia group (30.2% and 90.6%, respectively) were significantly higher than those in the controls (30.2% vs.13.0%, 90.6% vs. 78.0%, respectively, both p < 0.05). Haplotype analysis showed the ACG haplotype of UGT1A1 were associated with an increased hyperbilirubinemia risk (OR 3.122, p = 0.001), whereas the GCG haplotype was related to a reduced risk (OR 0.523, p = 0.018). CONCLUSION: The frequencies of the A allele in rs4148323 and the C allele in rs2417940 are highly associated with the incidence of severe hyperbilirubinemia in Chinese Han neonates. TRIAL REGISTRATION: Trial registration number:ChiCTR1800020424; Date of registration:2018-12-29.

The correlation between serum total bile acid and alanine aminotransferase of pregnant women and the disorders of neonatal hyperbilirubinemia-related amino acid metabolism.

BACKGROUND: To explore the association between liver metabolism-related indicators in maternal serum and neonatal hyperbilirubinemia (NHB), and further investigate the predictive value of these indicators in NHB-related amino acid metabolism disorders. METHODS: 51 NHB and 182 No-NHB newborns and their mothers who treated in the Fourth Hospital of Shijiazhuang from 2018 to 2022 were participated in the study. The differences in clinical data were compared by the Mann-Whitney U test and Chi-square test. Multivariate logistic regression was used to analyze the relationship between maternal serum indicators and the occurrence of NHB. The correlation analysis and risk factor assessment of maternal serum indicators with NHB-related amino acid metabolic disorders were performed using Spearman correlation analysis and multivariate logistic regression. RESULTS: Compared to the non NHB group, the NHB group had higher maternal serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, and total bile acid (TBA), while lower levels of serum albumin (ALB), total cholesterol (TC) and high-density lipoprotein (HDL). The levels of alanine (ALA), valine (VAL), ornithine (ORN), and proline (PRO) in the newborns were reduced in NHB group, while arginine (ARG) showed a tendency to be elevated. Multiple logistic regression analysis showed that maternal ALT, AST, ALT/AST, and TBA levels were all at higher risk with the development of NHB, whereas ALB, TC, and HDL levels were negatively associated with NHB development. Increasing maternal TBA level was associated with lower ALA (r=-0.167, p = 0.011), VAL (r=-0.214, p = 0.001), ORN (r=-0.196, p = 0.003), and PRO in the newborns (r=-0.131, p = 0.045). Maternal ALT level was negatively associated with ALA (r=-0.135, p = 0.039), VAL (r=-0.177, p = 0.007), ORN (r=-0.257, p < 0.001), while ALT/AST was positively correlated with ARG (r = 0.133, p = 0.013). After adjustment for confounding factors, maternal serum TBA and ALT were the independent risk factor for neonatal ORN metabolic disorders [(adjusted odds ratio (AOR) = 0.379, 95%CI = 0.188-0.762, p = 0.006), (AOR = 0.441, 95%CI = 0.211-0.922, p = 0.030)]. Maternal ALT level was an independent risk factor for neonatal VAL metabolic disorders (AOR = 0.454, 95%CI = 0.218-0.949, p = 0.036). CONCLUSIONS: The levels of high TBA, ALT, AST, and low HDL, TC of maternal were associated with the risk of NHB. Maternal TBA and ALT levels were independent risk factors for NHB-related amino acid disturbances which have value as predictive makers.

Neonatal hyperbilirubinemia and repercussions on neurodevelopment: A systematic review.

BACKGROUND: Accumulation of bilirubin above normal levels is considered a neurological risk factor for both premature and full-term newborns. This systematic review aimed to determine the effect of neonatal hyperbilirubinemia on neurodevelopment in preterm and full-term newborns. METHODS: PubMed, EMBASE, Cochrane Library, CINAHL, PsycINFO, Scopus and Lilacs databases were searched for articles published until 1 June 2022. The quality of cohort and case-control studies was assessed with the Newcastle-Ottawa Scale, and the MINCir scale was used to evaluate the methodological quality of therapy studies or the therapeutic procedures. Premature neonates without neurological conditions and those born at term with hyperbilirubinemia as the sole risk factor were included. Studies reporting one or more neurodevelopmental outcomes were included with an inter-group comparison of a hyperbilirubinemia group versus a non-hyperbilirubinemia or non-pathological hyperbilirubinemia group. The main outcomes were auditory function, visual function, cognitive function, motor function, behavior, global development and neurological risk. RESULTS: The search identified 951 studies, 19 of which (n = 2210 newborns) were finally included. Fifteen of the cohort and case-control studies presented low risk of bias, and six studies showed high methodological quality. Within the preterm population, hyperbilirubinemia as the sole risk factor was not shown to affect neurodevelopment. Auditory, neurological and motor development alterations were found in the population of full-term newborns with hyperbilirubinemia, which were more evident during the first year of life. CONCLUSIONS: Elevated bilirubin levels may be a trigger for the onset of neurodevelopmental disorders in full-term infants during the first year of life. More studies are warranted in the preterm population with hyperbilirubinemia to draw conclusions about its impact on their neurodevelopment.

A novel heterozygous deletion in ABCB4 gene in a Chinese family with intrahepatic cholestasis of pregnancy, neonatal hyperbilirubinemia, and cholelithiasis: Case reports and literature review.

BACKGROUND: ABCB4 gene (OMIM *171060) variant is associated with a wide clinical spectrum of hepatobiliary diseases, including familial intrahepatic cholestasis of pregnancy (ICP), progressive familial intrahepatic cholestasis type 3 (PFIC3), and neonatal hyperbilirubinemia due to impaired protection of the bile duct. The majority of reported cases, however, were missense or nonsense variants, with few deletion variant findings in the Chinese population. METHOD: We performed whole genome sequencing and confirmed it with Sanger sequencing of the proband infant and his families. Clinical courses and laboratory results were documented and collected from the proband infant and his mother. We also reviewed other published cases related to genetic variants in ABCB4 in the Chinese population. RESULTS: A 26-year-old Chinese female (II.2) who had recurrent intrahepatic cholestasis of pregnancy and her 49-day-old son (III.4) who had hyperbilirubinemia, both presented with extremely elevated total bile acid, cholestatic dominant pattern liver function abnormalities. They were able to stay relatively stable with mild pruritus on ursodeoxycholic acid treatment. After ruling out other possibilities, genetic sequencing revealed a diagnosis of heterozygous deletion variant NM_018849.3:c.1452_1454del (NP_061337.1:p.Thr485del) in ABCB4, which was not reported before, in the symptomatic mother (II.2), index patient (III.4), and the symptomatic grandmother (I.2). This variant resulted in clinical spectrums of ICP, neonatal hyperbilirubinemia, and cholelithiasis in our pedigree. CONCLUSION: We reported a novel heterozygous deletion variant of the ABCB4 gene in a Chinese family, as well as a literature review of ABCB4-related disorders. We aim to facilitate healthcare professionals to better understand genetic factors as an uncommon cause of hepatobiliary diseases, as well as improve therapeutic strategies in challenging clinical situations such as pregnancy and neonatal care.

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.

"Light" on Phototherapy-Complications and Strategies for Shortening Its Duration, A Review of the Literature.

Neonatal hyperbilirubinemia is an extremely common metabolic complication of the neonatal period which may be associated with bilirubin encephalopathy and even death. Adverse neurological consequences are preventable if a timely diagnosis and treatment are provided. Phototherapy is usually the preferred option to decrease hyperbilirubinemia. Although considered to be safe, evidence in recent years has shown that this treatment may not be free of side effects and short- and long-term unfavorable outcomes. These are usually mild or rare, but should be decreased or avoided if possible. Many useful complementary measures and treatments have been described that could shorten the duration of exposure to phototherapy. However, there is no current unequivocal recommendation to use any of the methods presented in this review. Our review aims to depict the wide range of possible complementary treatments to phototherapy, and to provide the scientific and clinical evidence available regarding their usefulness. It is essential that, while utilizing the full potential of phototherapy to treat hyperbilirubinemia, caregivers are aware of its side effects and possible inherent dangers, and seek ways to minimize the exposure to phototherapy to what is really needed for the newborn. Further studies are needed to clarify the preferred complementary treatments that could reduce the duration of exposure to phototherapy without impairing its effectiveness.