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The purpose of the study was to investigate correlation and concordance between total serum bilirubin (TSB) and transcutaneous bilirubin measured at covered (TcBC) and uncovered (TcBU) skin during and after discontinuation of phototherapy. A cross-sectional study included ≥ 34 weeks gestation infants requiring phototherapy for neonatal hyperbilirubinemia. In-house, photo-opaque patches were placed on infants' sternums before phototherapy initiation. Simultaneous blood sampling for TSB, TcBC, and TcBU measurements were performed. Among 103 infants included in the final analysis, 70% were full-term. Covering skin during phototherapy resulted in strong TcBC-TSB correlation (r = 0.91, 95% CI 0.87–0.94, P < 0.001) compared to TcBU (r = 0.53, 95% CI 0.37–0.65, P < 0.001), persisting post-phototherapy (r = 0.88, 95% CI 0.82–0.91, P < 0.001). Bland–Altman analysis showed a higher mean difference and wider 95% limits of agreement for TcBU-TSB during phototherapy (-6.3 mg/dL and -11.1 to -1.6) vs TcBC-TSB (0.9 mg/dL and -1.2 to 2.9). Passing-Bablok regression analysis confirmed good agreement between TcBC and TSB. Conclusions: The application of in-house, photo-opaque patches enhanced the correlation and agreement between TcBC and TSB during and after discontinuation of phototherapy. This may prove particularly useful in resource-limited settings where commercial devices are unavailable. What is Known: • Transcutaneous bilirubin measurement has been widely used as a screening method for neonatal hyperbilirubinemia. • The accuracy of transcutaneous bilirubin measurements during and after phototherapy in infants with hyperbilirubinemia has been debated. What is New: • Our study demonstrated that utilizing carefully designed photo-opaque patches enhanced the accuracy of transcutaneous bilirubin measurement during and after phototherapy. • Effective in-house alternatives are crucial in resource-limited settings where commercial opaque patches are not always accessible or affordable. [ABSTRACT FROM AUTHOR]

Neonatal hyperbilirubinemia (NH) is a common condition in newborns, with elevated bilirubin levels potentially causing neurological damage or death. Accurate and timely measurements of total serum bilirubin are essential to prevent these outcomes. Direct spectrophotometry, a reliable method for measuring bilirubin, is particularly useful in constrained settings due to its potential for portable low-cost instrumentation. However, this method is susceptible to interference from hemoglobin, often present due to hemolysis. Typically, this interference is reduced using complex optical filters, reagents, multiple wavelengths, or combinations thereof, which increase costs and complexity while reducing usability. This study presents a hemoglobin compensation algorithm applied to a simple, portable, two-wavelength (465 and 590 nm) reflectance photometer designed to receive 30 µL of plasma or whole blood samples and perform the measurement without any reagents. Testing across five bilirubin and hemoglobin levels (4.96 to 28 mg/dL and 0.06 to 0.99 g/dL, respectively) demonstrated that the algorithm effectively reduces hemoglobin interference and overestimation errors. The overall root mean square error was reduced from 4.86 to 1.45 mg/dL, while the measurement bias decreased from −4.46 to −0.10 mg/dL. This substantial reduction in overestimation errors supports future clinical trials with neonatal blood samples. [ABSTRACT FROM AUTHOR]

Most neonates have neonatal jaundice, with 5–15% requiring phototherapy. Although phototherapy is beneficial, it can potentially extend hospital stays and cause harm. This study’s purpose was to analyze the effects of fenofibrate and phototherapy on total serum bilirubin (TSB) levels at 24 and 48 hours (primary outcome) after intervention. Furthermore, the phototherapy duration and adverse events were also of interest (secondary outcome).The study protocol was registered in the PROSPERO database. Articles were searched on EMBASE, PubMed, Cochrane Library, and Google Scholar. Study selection was done following PRISMA and risk of bias studies were conducted. The Review Manager 5.4 was used for the meta-analysis.Nine studies, including 610 newborns, were identified and included in the meta-analysis. This meta-analysis discovered a significant change in TSB levels at 24 hours after intervention (mean difference (MD) –0.96 (95% CI –1.09, –0.83), p <  0.00001) with low heterogeneity and at 48 hours after intervention (MD –1.75 (95% CI –2.26, –1.24), p <  0.00001) with high heterogeneity. Significant shortening of phototherapy duration was observed in the interventional group (MD –15.28 (95% CI –20.65, –9.90), p <  0.00001) with high heterogeneities. One of the nine studies reported a non-significant occurrence of abdominal distension and diarrhea in the fenofibrate group.Fenofibrate might be applied as an adjuvant in unconjugated neonatal hyperbilirubinemia to reduce the average total serum bilirubin and shorten the length of phototherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Neonatal hyperbilirubinemia maybe complicated by severe neurologic disability including hearing impairment (HI). There is no agreement on the precise bilirubin level that may cause auditory affection. Aim of the work: to study the frequency of HI in neonates with indirect hyperbilirubinemia threshold for exchange transfusion (ET). Patients and Methods: This cross-sectional analytical study enrolled full-term neonates whose bilirubin levels were at the ET threshold managed by intensive phototherapy (IP) or ET. Automated auditory brainstem response (AABR) was performed within 24 hours of admission using audiometer among both groups. Results: This study included 98 full-term neonates. Forty-eight (49 %) were males and 50 (51%) were females. Their mean gestational age was 37.78±0.74 weeks. Forty-six (46.9%) neonates underwent ET while 52 (53%) improved on IP with the rapid decline of their bilirubin levels and did not undergo ET. The mean IP group bilirubin-induced neurologic dysfunction (BIND) score was 0, and reticulocyte count was 7.12±6.49% compared to 1.89±2.16 and 11.47±9.82% of ET group (p=0.001) and (p=0.004) respectively. Abnormal AABR was detected in 23 (23.5%) neonates; 8 had unilateral hearing impairment while 15 had bilateral hearing impairment. IP was associated with less HI in both ears in 3 (5.7%) compared to 12 (26.1%) who underwent ET (p=0.005).Neonates with any HI had higher total serum bilirubin (TSB) levels (p= 0.002) and BIND scores (p= 0.002). IP was associated with less (one or both ears) HI in 8 (15.3%) neonates compared to 15 (32.6%) who underwent ET (p=0.045). A TSB cut-off value of 24.5 mg/dl showed a sensitivity of 60.9% and a specificity of 81.3% while a BIND score cut-off value of ≥ 2 showed a sensitivity of 47.8% and a specificity of 86.7% for detecting any hearing impairment. Males had a higher risk for bilateral hearing impairment (p= 0.040). Conclusion: Neonates with higher bilirubin levels and BIND scores are at risk for HI. TSB and BIND score have modest sensitivity and specificity in predicting HI. IP is mandatory in all those with ET threshold bilirubin until procurement of blood to prevent HI. HI may occur despite normal BIND scores in the absence of bilirubin encephalopathy. Those who responded to IP for ET level of TSB had less frequency of HI. Males were more at risk for bilateral HI. Screening for HI among neonates who sustain hyperbilirubinemia is a necessity.

Background: Neonatal hyperbilirubinemia is a common neonatal condition requiring immediate diagnosis and treatment to prevent severe hyperbilirubinemia that can cause brain damage known as kernicterus. Identifying risk factors and monitoring at-risk infants can help reduce the incidence of severe hyperbilirubinemia. Materials and Methods: The present study was a retrospective cohort study analyzed medical records of infants with gestational age (GA) of more than 35 weeks born at Naresuan University Hospital between January 2019 and December 2020. One thousand fifteen infants were enrolled and divided into two groups: the hyperbilirubinemia group comprising 287 infants (28.3%), and the non-hyperbilirubinemia group consisting of 728 infants (71.7%). Results: The incidence of neonatal hyperbilirubinemia in infants with GA of more than 35 weeks was 30.7% (345 out of 1,122). Compared to vaginal delivery, cesarean section reduced the risk of neonatal hyperbilirubinemia by 32% (adjusted odds ratio 0.68). Sepsis increased the risk of neonatal hyperbilirubinemia by 73% (adjusted odds ratio 1.73). Infants in the hyperbilirubinemia group had a longer hospital stay, averaging approximately 28 hours. Conclusion: Vaginal delivery and neonatal sepsis were identified as significant risk factors for neonatal hyperbilirubinemia. Close monitoring of infants identified as at-risk may aid in the prevention of severe hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Background Presently, transcutaneous determination of bilirubin has become a valuable method for the early detection of neonatal hyperbilirubinemia. This study aims to determine the correlation of transcutaneous bilirubin with serum bilirubin levels and assess the factors affecting transcutaneous bilirubin measurement in term and late preterm neonates. Materials and Methods The study included 100 newborns born at a gestational age of 35 to 41 weeks, with a birth weight of 2100 to 3500 g. Simultaneous measurement of bilirubin by traditional (invasive) and transcutaneous (non-invasive) methods was carried out within 15 minutes of admission in the neonatal intensive care unit. Parallel transcutaneous measurements were taken in the forehead and sternum. Statistical analysis was done to determine the correlation of transcutaneous (forehead and sternal) bilirubin with serum bilirubin levels and assess the factors affecting transcutaneous bilirubin measurement. Results In the range of serum bilirubin concentrations till 15 mg/ dl, a close correlation was observed between serum bilirubin (TSB) estimated by direct spectrophotometric method and transcutaneous bilirubin (TcB) estimated by “Bilitest 2000”. TcB estimation on the sternum was better correlated than that on the forehead (r-value: 0.962 vs. 0.935). TcB had a good correlation with TSB across the range of 12.5 - 20.5 mg/dl. Neonatal hypothermia significantly decreased TcB estimation (p =0.021, F=4.227). Respiratory distress, convulsion, sclerema and shock in neonates did not affect TcB estimation. Conclusion TcB has a good correlation with TSB in term and late preterm neonates. Thus TcB readings can be u [ABSTRACT FROM AUTHOR]

Introduction: The perinatal mortality rate of Neonates of Diabetic Mothers (NDMs) over the years showed a reducing trend. Polycythaemia is common in NDMs, and such neonates have a risk of hyperviscosity, renal vein thrombosis, cardiac failure, metabolic abnormalities, and necrotising enterocolitis. Aim: To assess the association between cord blood haematocrit and neonatal outcomes among NDMs. Materials and Methods: The present study was a cohort study that included 130 neonates, which was conducted at Amala Institute of Medical Sciences (AIMS), Thrissur, Kerala, India, from December 2019 to June 2021. The primary inclusion criteria were singleton neonates of Gestational Diabetic Mothers (GDM) (diabetes detected after 20 weeks of gestation) and Overt Diabetes Mellitus (ODM) defined under White's classification (known to be diabetic before the onset of pregnancy or detected in the initial visits). The parameters assessed were the frequency of distribution of hypoglycaemia, hypocalcaemia, and hyperbilirubinemia among the neonates of DM. Statistical analysis was done using Fisher's exact test and Student's t-test. Results: Among the 130 neonates, the majority of the mothers had GDM 111 (85.4%) than ODM 19 (14.6%). The majority were delivered by normal vaginal delivery 67 (51.5%). 10 (7.7%) of NDMs had a birth weight > 4000 g. Significant associations were noted between cord Packed Cell Volume (PCV) and the presence of hypoglycaemia (p-value=0.003), hypocalcaemia (p-value=0.0001), and Neonatal Hyperbilirubinemia (NNH) (p-value=0.0001) among NDMs. Conclusion: Hypoglycaemia, hyperbilirubinemia, and hypocalcaemia were common complications noted in NDMs. [ABSTRACT FROM AUTHOR]

Polymorphisms of the uridine-diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene, hepatic solute carrier organic anion transporter 1B1/B3 (SLCO1B1/3) gene, and glutathione S-transferase (GST) gene have been associated with significant hyperbilirubinemia in some populations. This study aims to determine whether the variation of UGT1A1, SLCO1B1/3 and GST genes play an important role in neonatal hyperbilirubinemia in Turkish newborn infants.

Abstract 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 (I 2 ), 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

Background: Neonatal hyperbilirubinemia is a common neonatal problem. Although benign in the majority of the cases, few neonates develop bilirubin-induced neurological dysfunction further progressing to kernicterus. Due to early hospital discharge of healthy-term neonates, there is need of a reliable tool for early prediction of significant hyperbilirubinemia in them. Aim: The aim of this study is to determine the utility of cord total serum bilirubin/albumin ratio as an early predictor of significant neonatal hyperbilirubinemia in healthy-term newborns. Settings and Design: This is a tertiary care hospital-based prospective cohort study. Subjects and Methods: The study was conducted on 100 sequentially born healthy-term neonates. Cord bilirubin/albumin ratio was calculated and neonates were divided into two groups on the basis of 50th percentile value. Serum bilirubin was also measured at 72 h of life in all neonates and value ≥17 mg/dl was taken as significant requiring intervention. Statistical Analysis Used: Continuous variables were summarized as mean and standard deviation while nominal/categorical variables as percentage. Association between total serum bilirubin at 72 h of life and cord bilirubin/albumin ratio was assessed using two-sample independent t-test and Pearson correlation coefficient formula. Cutoff value of the ratio was derived using receiver operating characteristics (ROC) curve analysis. Results: Statistically significant association was observed between cord bilirubin/albumin ratio with the development of neonatal hyperbilirubinemia. On ROC analysis, cutoff point to predict significant hyperbilirubinemia was found to be >0.66 (92.9% sensitivity, 60.5% specificity, and PPV 79.61%). Conclusions: Cord total serum bilirubin/albumin ratio is a good parameter to predict significant neonatal hyperbilirubinemia in healthy-term neonates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to investigate whether there are differences in carboxyhemoglobin, bilirubin and hemoglobin values of neonates born by normal spontaneous vaginal birth (NSVD) (without anesthesia) and elective spinal cesarean section (CS) and its effect on neonatal jaundice. Materials and Methods: A total of 110 healthy neonates without any risk factors for neonatal hyperbilirubinemia were included in the study. There were fifty-five neonates in both NVSD and spinal CS groups. COHb, bilirubin and Hb values which were measured from umbilical cord blood (as cord) and capillary blood taken from the heel 4-6 hours after birth (as post cord) were recorded. Results: No statistically significant difference was found between the groups in terms of birthweight, maternal age, APGAR scores, and gender (p>0.05). There was a statistical difference between the groups according to the mean of gestational age, and it was observed that the mean of gestational age in spinal CS group was lower than in NSVD group (38.30±1.2 and 39.16±1.39 respectively) (p=0.001). Umbilical cord COHb levels in spinal CS group were higher than in NSVD group, but there was no statistically significant difference between groups (1.01±0.15 and 0.99±0.20 respectively, p=0.22). Furthermore, the differences between groups in term of mean of bilirubin and Hb levels in cord and post cord were not statistically significant (>0.05). But, it was determined that post cord COHb levels were higher than in NVSD group, and this difference was statistically significant (p=0.028). Additionally, it was found that the mean rank of COHb, bilirubin, and Hb in cord and post cord values were statistically significantly different between the groups (p < 0.05). Conclusion: It should be kept in mind of that the anesthetic agent may also be a factor in bilirubin increases that occurs in neonatal hyperbilirubinemia without an underlying risk factor. [ABSTRACT FROM AUTHOR]

Introduction: The perinatal mortality rate of Neonates of Diabetic Mothers (NDMs) over the years showed a reducing trend. Polycythaemia is common in NDMs, and such neonates have a risk of hyperviscosity, renal vein thrombosis, cardiac failure, metabolic abnormalities, and necrotising enterocolitis. Aim: To assess the association between cord blood haematocrit and neonatal outcomes among NDMs. Materials and Methods: The present study was a cohort study that included 130 neonates, which was conducted at Amala Institute of Medical Sciences (AIMS), Thrissur, Kerala, India, from December 2019 to June 2021. The primary inclusion criteria were singleton neonates of Gestational Diabetic Mothers (GDM) (diabetes detected after 20 weeks of gestation) and Overt Diabetes Mellitus (ODM) defined under White’s classification (known to be diabetic before the onset of pregnancy or detected in the initial visits). The parameters assessed were the frequency of distribution of hypoglycaemia, hypocalcaemia, and hyperbilirubinemia among the neonates of DM. Statistical analysis was done using Fisher’s exact test and Student’s t-test. Results: Among the 130 neonates, the majority of the mothers had GDM 111 (85.4%) than ODM 19 (14.6%). The majority were delivered by normal vaginal delivery 67 (51.5%). 10 (7.7%) of NDMs had a birth weight > 4000 g. Significant associations were noted between cord Packed Cell Volume (PCV) and the presence of hypoglycaemia (p-value=0.003), hypocalcaemia (p-value=0.0001), and Neonatal Hyperbilirubinemia (NNH) (p-value=0.0001) among NDMs. Conclusion: Hypoglycaemia, hyperbilirubinemia, and hypocalcaemia were common complications noted in NDMs.

Abstract 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.

Abstract 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

Abstract 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

The results of modern studies on breast milk jaundice pathogenesis, that is common form of neonatal jaundice, are presented. The major risk factors and diagnostic methods (excluding other forms of jaundice syndrome at recurrent and lingering jaundice in newborns) were defined. The main therapy approaches for breast milk jaundice were presented. Issues of phototherapy indications were discussed. The feasibility of maintaining breastfeeding in case of breast milk jaundice development was proved. This condition requires the attention of pediatricians despite the relatively favorable course and outcomes. The need to continue studies on pathogenetic therapy of such patients was noted.

Neonatal hyperbilirubinemia (NH) is a common condition in newborns, with elevated bilirubin levels potentially causing neurological damage or death. Accurate and timely measurements of total serum bilirubin are essential to prevent these outcomes. Direct spectrophotometry, a reliable method for measuring bilirubin, is particularly useful in constrained settings due to its potential for portable low-cost instrumentation. However, this method is susceptible to interference from hemoglobin, often present due to hemolysis. Typically, this interference is reduced using complex optical filters, reagents, multiple wavelengths, or combinations thereof, which increase costs and complexity while reducing usability. This study presents a hemoglobin compensation algorithm applied to a simple, portable, two-wavelength (465 and 590 nm) reflectance photometer designed to receive 30 µL of plasma or whole blood samples and perform the measurement without any reagents. Testing across five bilirubin and hemoglobin levels (4.96 to 28 mg/dL and 0.06 to 0.99 g/dL, respectively) demonstrated that the algorithm effectively reduces hemoglobin interference and overestimation errors. The overall root mean square error was reduced from 4.86 to 1.45 mg/dL, while the measurement bias decreased from −4.46 to −0.10 mg/dL. This substantial reduction in overestimation errors supports future clinical trials with neonatal blood samples.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Neonatal hyperbilirubinemia remains a common clinical challenge. Phototherapy is a primary intervention, but its impact on bilirubin and electrolyte levels, as well as its safety profile, needs ongoing evaluation. Objective: To assess the changes in bilirubin and electrolyte levels in neonates undergoing phototherapy and to evaluate its safety profile. Methods: A prospective study involving 100 term neonates subjected to phototherapy. Bilirubin and electrolyte levels were measured at various durations, and adverse effects were monitored. Results: A significant reduction in total bilirubin was observed, especially beyond 48 hours of phototherapy, from a baseline of 17.5 ± 2.1 mg/dl to 11.0 ± 2.1 mg/dl. Electrolyte assessments post-phototherapy indicated subtle declines, with sodium decreasing from 140 ± 3 mEq/L to 135 ± 4.5 mEq/L after >48 hours. The adverse effect profile was reassuring, with 90% of neonates displaying no negative outcomes, though dehydration was observed in 5% of the cohort. Conclusion: Phototherapy effectively reduced bilirubin levels in neonates. Concurrently, changes in electrolyte levels and a low incidence of dehydration highlight the need for vigilant monitoring. These insights stress the importance of individualized therapeutic strategies in neonatal hyperbilirubinemia management. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal hyperbilirubinemia (NH) affects nearly 60% of term and 80% of preterm neonates during the first week of their life. Because of the potential toxicity of bilirubin, newborn infants must be monitored to identify those who might develop severe hyperbilirubinemia and, in rare cases, acute bilirubin encephalopathy or kernicterus. Neonatal hyperbilirubinemia is the most common reason for readmission after early hospital discharge. Objective: To find out critical value of Cord Serum albumin in predicting the subsequent development of significant neonatal hyperbilirubinemia requiring interventions like phototherapy or exchange transfusion. Methodology: It is a Hospital based prospective observational studying a sample of 100 per term babies with birth weight <2.5 kg selected by simple random sampling. Cord blood was collected from the placental side at the time of delivery. Cord blood Albumin estimation was done by using auto-analyser while Serum bilirubin estimation (Total and direct) was done using venous blood of children having jaundice involving palms and soles on any day of follow up, using Diazotized Sulfanilic test by spectrometry. Results: In our study out of hundred patients 71 patients had hyper bilirubinemia requiring either phototherapy (PT) or Exchange transfusion (ET). They were divided in three groups according to Cord blood albumin in group 1, 2, 3 with CBA <2.8,2.8-3.1,>3.1 g/dl. Statistical analysis was conducted and it showed <2.8 g/dl CBA is critical and associated with higher relation with hyperbilirubinemia requiring phototherapy (95.65%) and also requiring Exchange transfusions 47.83%. CBA >3.1 g/dl is less association with Hyperbilirubinemia, that is about in 9.52% cases. Conclusion: Cord blood albumin can be considered as a risk indicator rather than diagnostic tool, which can give a clue to the possibility of severe jaundice during neonatal period. It may help treating doctors and the parents stay alert to take action at the earliest. [ABSTRACT FROM AUTHOR]

Polymorphisms of the uridine-diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene, hepatic solute carrier organic anion transporter 1B1/B3 (SLCO1B1/3) gene, and glutathione S-transferase (GST) gene have been associated with significant hyperbilirubinemia in some populations. This study aims to determine whether the variation of UGT1A1, SLCO1B1/3 and GST genes play an important role in neonatal hyperbilirubinemia in Turkish newborn infants. The study included 61 idiopathic hyperbilirubinemia cases, 28 prolonged jaundice cases, and 41 controls. Ten common polymorphisms in four genes involved in bilirubin metabolism were examined. Polymerase chain reaction-restriction fragment length polymorphism method was used to detect variants of those genes. No association was found between the variants of UGT1A1 at nt 211, the SLCO1B1 gene at nt 388, 463, 521, 1463, the SLCO1B3 gene at nt 334, 727+118, 1865+19721, and the GST gene at nt 313, 341, and neonatal hyperbilirubinemia. There was no difference between the case and control groups in terms of allele frequencies of these genes (except SLCO1B3 at nt 334) (p>0.05 in all comparisons). The presence of the G allele of the SLCO1B3 at nt 334 variant gene seemed to protect from jaundice in infants with idiopathic hyperbilirubinemia. These gene polymorphisms currently studied do not seem to modulate the risk of hyperbilirubinemia in Turkish newborn infants. [ABSTRACT FROM AUTHOR]

Background: Neonatal hyperbilirubinemia is a common neonatal problem. Although benign in the majority of the cases, few neonates develop bilirubin-induced neurological dysfunction further progressing to kernicterus. Due to early hospital discharge of healthy-term neonates, there is need of a reliable tool for early prediction of significant hyperbilirubinemia in them. Aim: The aim of this study is to determine the utility of cord total serum bilirubin/albumin ratio as an early predictor of significant neonatal hyperbilirubinemia in healthy-term newborns. Settings and Design: This is a tertiary care hospital-based prospective cohort study. Subjects and Methods: The study was conducted on 100 sequentially born healthy-term neonates. Cord bilirubin/albumin ratio was calculated and neonates were divided into two groups on the basis of 50th percentile value. Serum bilirubin was also measured at 72 h of life in all neonates and value ≥17 mg/dl was taken as significant requiring intervention. Statistical Analysis Used: Continuous variables were summarized as mean and standard deviation while nominal/categorical variables as percentage. Association between total serum bilirubin at 72 h of life and cord bilirubin/albumin ratio was assessed using two-sample independent t-test and Pearson correlation coefficient formula. Cutoff value of the ratio was derived using receiver operating characteristics (ROC) curve analysis. Results: Statistically significant association was observed between cord bilirubin/albumin ratio with the development of neonatal hyperbilirubinemia. On ROC analysis, cutoff point to predict significant hyperbilirubinemia was found to be >0.66 (92.9% sensitivity, 60.5% specificity, and PPV 79.61%). Conclusions: Cord total serum bilirubin/albumin ratio is a good parameter to predict significant neonatal hyperbilirubinemia in healthy-term neonates.

BackgroundNeonatal 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.MethodsIn 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.ResultsThe 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.ConclusionWe 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.

Background Extreme hyperbilirubinemia leading to neurologic disability and death is disproportionately higher in low- and middle-income countries (LMIC) such as Bangladesh, and is largely preventable through timely treatment. In LMICs, an estimated half of all newborns are born at home and few receive screening or treatment for hyperbilirubinemia, leading to 6 million newborns per year who need phototherapy treatment for hyperbilirubinemia but are untreated. Household screening and treatment for neonatal hyperbilirubinemia with phototherapy administered by a trained community health worker (CHW) may increase indicated treatment for neonatal hyperbilirubinemia in comparison to the existing care system in Bangladesh. Methods 530 Bangladeshi women in their second or third trimester of pregnancy from the rural community of Sakhipur, Bangladesh will be recruited for a cluster randomized trial and randomized to the intervention arm — home screening and treatment for neonatal hyperbilirubinemia — or the comparison arm to receive usual care. In the intervention arm, CHWs will provide mothers with two prenatal visits, visit newborns by 2 days of age and then daily for 3 days to measure transcutaneous bilirubin (TcB) and monitor for clinical danger signs. Newborns without danger signs but with a TcB above the treatment threshold, but >15 mg/dL will be treated with light-emitting diode (LED) phototherapy at home. Newborns with danger signs or TcB ≥15 mg/dL will be referred to a hospital for treatment. Treatment rates for neonatal hyperbilirubinemia in each arm will be compared. Conclusion This study will evaluate the effectiveness of CHW-led home phototherapy to increase neonatal hyperbilirubinemia treatment rates in rural Bangladesh. LMICs are expanding access to postnatal care by using CHWs, and our work will give CHWs a curative treatment option for neonatal hyperbilirubinemia. Similar projects in other LMICs can be pursued to dramatically extend healthcare access to vulnerable newborns with hyperbilirubinemia.

BackgroundUrinary 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.MethodsThis retrospective case-control study was conducted on 150 jaundiced infants (aged

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.

Objective: To analyze the risk factors for the acute bilirubin encephalopathy (ABE) occurrence in severe neonatal hyperbilirubinemia (NHB) and to investigate the predictive value of cranial magnetic resonance pale globule to shell nucleus T1-weighted imaging signal intensity ratio (G/P value) combined with total serum bilirubin (TSB) and neuron-specific enolase (NSE). Methods: 369 children with severe NHB who were admitted to the Tianmen First People's Hospital of Hubei Province from January 2018 to January 2020 were selected, and they were divided into ABE group and non-ABE group according to whether ABE occurred within 1 week after admission. Clinical data of all children were collected, the cranial magnetic resonance G/P value were calculated, and serum TSB and NSE levels were detected. Univariate and multivariate Logistic regression were used to analyze the influencing factors of ABE occurrence in severe NHB. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of cranial magnetic resonance G/P value combined with serum TSB and NSE for ABE occurrence in severe NHB. Results: The incidence of ABE in 369 children with NHB was 12.47% (46/369). Multivariate Logistic regression analysis showed that lower birth weight, shorter hospital admission days, longer hospital stay, non-breastfeeding, increased hemoglobin and G/P value, increased TSB and NSE were independent risk factors for ABE occurrence with severe NHB (P＜0.05). ROC curve analysis showed that the area under curve predicted ABE occurrence of severe NHB by G/P value combined with serum TSB and NSE was larger than that predicted by G/P value combined with serum TSB and NSE alone (P＜0.05). Conclusion: Lower birth weight, shorter hospital admission days, longer hospital stay, non-breastfeeding, increased hemoglobin, increased G/P value, increased TSB and increased NSE are risk factors for ABE occurrence in severe NHB. The value of cranial magnetic resonance G/P value combined with serum TSB and NSE is higher in predicting ABE. [ABSTRACT FROM AUTHOR]

Background: To study the difference in serum total calcium levels during phototherapy with light-emitting diodes (LEDs) in full-term neonates with hyperbilirubinemia. Materials and Methods: In this prospective observational study, 74 term neonates with hyperbilirubinemia who were admitted for phototherapy using LEDs devices were examined. The research was carried out in a tertiary care facility. Before and after the phototherapy treatment, total serum bilirubin levels as well as total serum calcium levels were measured and compared. The symptoms observed with hypocalcemia, such as drowsiness irritability/excitability, lethargy, and convulsions, were also evaluated in full-term neonates during this study. Results: After treatment, the total serum calcium level decreased significantly (P < 0.001) compared to the pretreatment level. Around 5% of the term neonates who participated in the study had hypocalcemia, where the serum calcium level is defined that is lower than 8 mg/dL in term neonates. Conclusions: In the context of the treatment of neonatal jaundice in full-term neonates, LED phototherapy, which is analogous to traditional blue and white light phototherapy, also has hypocalcemia as one of its potential side effects. During their treatment with light-emitting diode phototherapy, we advise checking up on these full-term neonates for signs of hypocalcemia. [ABSTRACT FROM AUTHOR]

Abstract Background Neonatal hyperbilirubinemia (NH) is a major cause of hospitalization after birth. Previous studies indicated that vitamin D deficiency might play an important role in NH susceptibility, but the results were controversial. Meanwhile, there has been limited description of the association between vitamin D related genes single nucleotide polymorphisms (SNP) and NH susceptibility. We aimed to investigate the vitamin D metabolic pathway genes polymorphisms and vitamin D levels with NH susceptibility. Methods We retrospectively analyzed the clinical data, vitamin D levels and its metabolic pathway gene polymorphisms of 187 NH neonates and 149 controls at Tianjin Children’s Hospital/Tianjin University Children’s Hospital between April 2019 and August 2022. Vitamin D levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the genetic polymorphism of NADSYN1/DHCR7, GC, CYP2R1, CYP24A1 and CYP27B1 was detected by high resolution melting (HRM) analysis. Results The frequency of vitamin D deficiency (25(OH)D

Abstract Background Universal screening for neonatal hyperbilirubinemia risk assessment is recommended by the American Academy of Pediatrics to reduce related morbidity. In Bangladesh and in many low- and middle-income countries, there is no screening for neonatal hyperbilirubinemia. Furthermore, neonatal hyperbilirubinemia may not be recognized as a medically significant condition by caregivers and community members. We aimed to evaluate the acceptability and operational feasibility of community health worker (CHW)-led, home-based, non-invasive neonatal hyperbilirubinemia screening using a transcutaneous bilimeter in Shakhipur, a rural subdistrict in Bangladesh. Methods We employed a two-step process. In the formative phase, we conducted eight focus group discussions with parents and grandparents of infants and eight key informant interviews with public and private healthcare providers and managers to explore their current knowledge, perceptions, practices, and challenges regarding identification and management of neonatal hyperbilirubinemia. Next, we piloted a prenatal sensitization intervention and home-based screening by CHWs using transcutaneous bilimeters and evaluated the acceptability and operational feasibility of this approach through focus group discussions and key informant interviews with parents, grandparents and CHWs. Results Formative findings identified misconceptions regarding neonatal hyperbilirubinemia causes and health risks among caregivers in rural Bangladesh. CHWs were comfortable with adoption, maintenance and use of the device in routine home visits. Transcutaneous bilimeter-based screening was also widely accepted by caregivers and family members due to its noninvasive technique and immediate display of findings at home. Prenatal sensitization of caregivers and family members helped to create a supportive environment in the family and empowered mothers as primary caregivers. Conclusion Adopting household neonatal hyperbilirubinemia screening in the postnatal period by CHWs using a transcutaneous bilimeter is an acceptable approach by both CHWs and families and may increase rates of screening to prevent morbidity and mortality.

Background: Neonatal hyperbilirubinemia is a widespread and significant clinical problem among neonates worldwide. Globally, every year about 1.1 million babies develop it and the vast majority reside in South Asia and sub-Saharan Africa. Studies on the magnitude and factors associated with neonatal hyperbilirubinemia are limited in Ethiopia. So this study was aimed at assessing the prevalence and associated factors of neonatal hyperbilirubinemia among hospitalized neonates in the neonatal intensive care unit of Jimma Medical Center (JMC), Jimma, South West Ethiopia. Design: Hospital-based cross-sectional study was conducted at JMC from July 24 to October 19, 2020. Methods: A total of 222 neonates with their mothers were included and conveniently selected. Data was collected by interviewing mothers through structured questionnaires and reviewing neonates' medical records using a checklist. Multivariable binary logistic regression analyses were employed to identify factors associated with neonatal hyperbilirubinemia. Results: from a total of neo-maternal pairs included in the studies; the proportion of Neonatal hyperbilirubinemia was found to be 94 (42.3%). Neo-maternal ABO incompatibility 33 (35.1%), prematurity 41 (43.6%), sepsis 35 (37.2%), Neonatal birth asphyxia 20 (21.2%), and Rh isoimmunization 10 (10.6%) was significantly associated with neonatal hyperbilirubinemia. Conclusion: The prevalence of neonatal hyperbilirubinemia in the study setting was high. Antenatal care (including both mother and fetus detail examination and follow-ups) as well as cautions during labor need to focus on since Neonatal hyperbilirubinemia-associated factors were maternal and neonatal. Hence, further assessment, early intervention, and timely treatment are important to mitigate the burdens in neonates due to hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Hemolytic disease of the fetus and newborn is due to maternal IgG antibodies that transport through the placenta and destroy neonatal red cells. A mismatch of antigens between mother and fetus causes isoimmunization resulting in mild anemia, which may progress to fetal hydrops in the intrauterine period and severe hyperbilirubinemia to kernicterus in neonates. The isoimmunization is mainly caused by Rh-D and ABO antibodies. In this case report, we found neonatal hyperbilirubinemia due to the presence of anti-c alloantibody previously developed in a sickle cell disease (SCD) pregnant female. It is an unusual case of fetal hyperbilirubinemia due to minor blood group alloimmunization in a SCD needing exchange transfusion. Multi-transfused patients should be counseled regarding the need to perform antibody screening frequently before pregnancy for better treatment of both mother and child. [ABSTRACT FROM AUTHOR]

Background: One of the most prevalent illnesses in neonates that needs care and treatment is neonatal jaundice. Several drugs are used as pharmacological modalities for treating hyperbilirubinemia, like intravenous immunoglobulin, D-penicillamine, metalloporphyrin, phenobarbital, zinc sulfate and clofibrate. Previous studies suggest the usefulness of fenofibrate in the treatment of hyperbilirubinemia. Objectives: The study aims at assessing the effectiveness of oral fenofibrate in the treatment of indirect neonatal hyperbilirubinemia in full-term neonates. Method: This is a quasi-experimental study that was conducted at Heevi Pediatrics Teaching Hospital in Duhok, which is located in the Kurdistan Region of Iraq. It involved term infants who had jaundice. The neonates who were eligible for the study were randomly assigned to one of two groups: the intervention group or the control group. Both groups were treated with conventional phototherapy. Fenofibrate was administered in a single oral dose of 10 mg/kg to the participants in the intervention group. Throughout the entirety of the treatment, levels of total serum bilirubin were compared and contrasted between the two groups. Results: After 12 h of treatment, a statistically significant difference (p-value = 0.001) was seen in the serum bilirubin levels between the two groups. The difference in serum bilirubin levels became significantly progressively pronounced after 24, 48, and 72 h. The average time of discharge was 63.6 h for the intervention group and 90.9 h for the control group, and this difference was statistically significant (p-value < 0.001). Conclusions: The time it takes to lower high bilirubin levels in neonates may be shortened by combining conventional phototherapy with a single oral dosage of 10 mg/kg fenofibrate. Consequently, these neonates will experience a shorter hospitalization and an accelerated discharge from the hospital. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal hyperbilirubinemia is common and remains a clinical concern in China. Since neonatal hyperbilirubinemia is linked to genetic factors, we aimed to identify the gene variants of the red blood cell membrane (RBCM) and evaluate the clinical risk factors in Chinese neonates with hyperbilirubinemia. Methods: 117 hyperbilirubinemia neonates (33 cases of moderate hyperbilirubinemia and 84 cases of severe hyperbilirubinemia) and 49 controls with normal bilirubin levels were selected as our study subjects. A customized 22-gene panel with next-generation sequencing (NGS) was designed to characterize genetic variations among the neonates. Sanger sequencing was used to verify the accuracy of the NGS. The clinical risk factors and potential effects of genetic variations in neonates with hyperbilirubinemia were subsequently assessed. Results: After data filtering, suspected pathogenic variants of UGT1A1, SLCCO1B1, and RBCM-associated gene were identified in neonates, the combined numbers of RBCM-associated gene variants were found to have differences between the hyperbilirubinemia group and the controls (p = 0.008), they were also different between severe hyperbilirubinemia and moderate hyperbilirubinemia (p = 0.008), and were correlated with an increased risk of hyperbilirubinemia (odds ratio = 9.644, p = 0.006). The UGT1A1-rs4148323 variant in neonates with hyperbilirubinemia was significantly increased as compared with the controls (p < 0.001). However, there was no statistical difference for the SLCO1B1-rs2306283 variant between the hyperbilirubinemia group and the controls. In addition, breastfeeding contributed to an increased risk of hyperbilirubinemia. Conclusion: Our study highlights that the RBCM-related gene variants are an underestimated risk factor, which may play an important role in developing hyperbilirubinemia in Chinese newborns. [ABSTRACT FROM AUTHOR]

BackgroundPhysiologic neonatal hyperbilirubinemia (jaundice) is common and affects most newborn infants. However, there is a risk for permanent neurological damage if the bilirubin levels rise above a certain threshold. The management of neonatal jaundice includes the assessment of bilirubin laboratory values, consideration of patient-specific risk factors, and plotting on a bilirubin nomogram reference to determine risk and guide therapy. When performed manually, the process can be time consuming and error-prone. Therefore, web-based calculators such as BiliTool have been developed to assist in risk assessment.MethodsTo streamline the risk assessment calculation process further within our electronic health record (EHR), we created a "BiliReport" to display patient bilirubin-related data and automate transmission of deidentified patient data to the BiliTool website (https://bilitool.org). After implementation, we evaluated usage data, provider satisfaction, and accuracy of documentation.ResultsWe demonstrated high provider use of the BiliReport and satisfaction with the workflow. We found a significant improvement in the accuracy of bilirubin risk level documentation, with a reduction in erroneous risk stratification from 4% (15/232) to 0.4% (1/243), P < 0.001. We did not find significant a difference in erroneous documentation of the bilirubin lab value (P = 0.07).ConclusionsIntegrating the neonatal hyperbilirubinemia risk assessment process into the EHR may reduce errors and improve provider documentation and adherence to recommended guidelines.

Objective: This study aimed to describe the effect of prophylactic phototherapy in the treatment of infants with Neonatal Hemolytic Disease. Method: A retrospective cohort study was carried out with 199 RhD-positive infants, born to RhD-negative mothers, alloimmunized for RhD antigen, between January 2009 and December 2018. Results: The incidence of exchange transfusions in the study population was 9.5%, with a mean maximum bilirubin value of 11.3 mg % (± 4.3mg %). Bilirubin's maximum peak was achieved with a mean of 119.2 life hours (± 70.6h). Conclusion: The low incidence of exchange transfusion, the extended maximum bilirubin peak for later ages, and the low mean of the maximum bilirubin values may indicate a positive effect of prophylactic phototherapy in the treatment of this disease. Further studies must be carried out to confirm these findings.

Abstract Background Neonatal jaundice is a transitional phenomenon affecting three out of five full-term newborns globally. Ursodeoxycholic acid could be beneficial in neonatal jaundice needing phototherapy. Methods We searched PubMed, EBSCO, ProQuest, and Cochrane Library up to August 21st, 2021, for articles to be reviewed. Meta-analysis using random-effects model was performed. Results Eight studies involving 1116 neonates were chosen in this review; however, only five studies were included for meta-analysis. Phototherapy duration was significantly lower in the interventional group with high heterogeneities. Subgroup analysis of the phototherapy duration based on the risk of bias resulted in a shorter duration (mean difference (MD) = –17.82; 95% CI = –20.17 to –15.47; p =

Abstract 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.

Background: Neonatal hyperbilirubinemia (NH) is a major cause of hospitalization after birth. Previous studies indicated that vitamin D deficiency might play an important role in NH susceptibility, but the results were controversial. Meanwhile, there has been limited description of the association between vitamin D related genes single nucleotide polymorphisms (SNP) and NH susceptibility. We aimed to investigate the vitamin D metabolic pathway genes polymorphisms and vitamin D levels with NH susceptibility. Methods: We retrospectively analyzed the clinical data, vitamin D levels and its metabolic pathway gene polymorphisms of 187 NH neonates and 149 controls at Tianjin Children's Hospital/Tianjin University Children's Hospital between April 2019 and August 2022. Vitamin D levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the genetic polymorphism of NADSYN1/DHCR7, GC, CYP2R1, CYP24A1 and CYP27B1 was detected by high resolution melting (HRM) analysis. Results: The frequency of vitamin D deficiency (25(OH)D < 15 ng/mL) was significantly increased in the NH group compared to controls. TT genotype of rs12785878 and GT genotype of rs10877012 were protective factors of vitamin D deficiency and NH, and GT genotype and dominant model carriers of rs12785878 had a higher risk of severe NH than the GG genotype carriers (GT genotype: OR: 2.43; 95% CI: 1.22–4.86; P = 0.012, dominant model: OR: 1.97; 95% CI: 1.04–3.73; P = 0.037). GC gene haplotype was associated with vitamin D deficiency. No significant SNP-SNP and SNP-vitamin D levels interaction combinations were found. Conclusions: There were associations among NH, vitamin D deficiency and NADSYN1/DHCR7 and CYP27B1 polymorphisms, TT genotype of rs12785878 and GT genotype of rs10877012 could reduce the risk of vitamin D deficiency and NH. Furthermore, rs12785878 was significantly associated with severe NH. [ABSTRACT FROM AUTHOR]

Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ is a type of prolonged unconjugated hyperbilirubinemia that is often late onset in otherwise healthy-appearing newborns, and its occurrence might be related to breast milk itself. This review aims to systematically evaluate evidence regarding breast milk composition and the development of BMJ in healthy neonates. PubMed, Scopus and Embase were searched up to 13 February 2023 with key search terms, including neonates, hyperbilirubinemia, and breastfeeding. A total of 678 unique studies were identified and 12 were ultimately included in the systematic review with narrative synthesis. These included studies covered both nutritional compositions (e.g., fats and proteins) and bioactive factors (e.g., enzymes and growth factors) of breast milk and formally assessed the difference in the concentration (or presence) of various endogenous components of breast milk collected from mothers of BMJ infants and healthy infants. The results were inconsistent and inconclusive for most of the substances of interest, and there was only a single study available (e.g., total energy and mineral content, bile salts and cytokines); conflicting or even contradictory results arose when there were two or more studies on the subject matter (e.g., fats and free fatty acids contents and epidermal growth factor). The etiology of BMJ is likely multifactorial, and no single constituent of breast milk could explain all the BMJ cases observed. Further well-designed studies are warranted to investigate the complex interaction between maternal physiology, the breast milk system and infant physiology before this field could be progressed to uncover the etiology of BMJ. [ABSTRACT FROM AUTHOR]