Hyperbilirubinemia In Newborns Research Articles

Transcutaneous bilirubinometry for detecting jaundice in term or late preterm neonates.

The American Academy of Pediatrics and the Canadian Paediatric Society both advise that all newborns should undergo bilirubin screening before leaving the hospital, and this has become the standard practice in both countries. However, the US Preventive Task Force has found no strong evidence to suggest that this practice of universal screening for bilirubin reduces the occurrence of significant outcomes such as bilirubin-induced neurologic dysfunction or kernicterus. To evaluate the effectiveness of transcutaneous screening compared to visual inspection for hyperbilirubinemia to prevent the readmission of newborns (infants greater than 35 weeks' gestation) for phototherapy. We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, ICTRP, and ISRCTN in June 2023. We also searched conference proceedings, and the reference lists of included studies. We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, or prospective cohort studies with control arm that evaluated the use of transcutaneous bilirubin (TcB) screening for hyperbilirubinemia in newborns before hospital discharge. We used standard methodologic procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) and 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to evaluate the certainty of evidence. We identified one RCT (1858 participants) that met our inclusion criteria. The study included 1858 African newborns at 35 weeks' gestation or greater who were receiving routine care at a well-baby nursery, and were randomly recruited prior to discharge to undergo TcB screening. The study had good methodologic quality. TcB screening versus visual assessment of hyperbilirubinemia in newborns: - may reduce readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - probably has little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - may increase the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - probably has little or no effect on the rate of acute bilirubin encephalopathy (RR 0.33, 95% CI 0.01 to 8.18; low-certainty evidence). The study did not evaluate or report cost of care. Moderate-certainty evidence suggests that TcB screening may reduce readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening probably has little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening may increase the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening probably has little or no effect on the rate of acute bilirubin encephalopathy compared to visual inspection. Given that we have only identified one RCT, further studies are necessary to determine whether TcB screening can help to reduce readmission and complications related to neonatal hyperbilirubinemia. In settings with limited newborn follow-up after hospital discharge, identifying newborns at risk of severe hyperbilirubinemia before hospital discharge will be important to plan targeted follow-up of these infants.

Dynamic whole-transcriptome landscape of acute bilirubin encephalopathy in newborns

Hyperbilirubinemia in newborns may progress to acute bilirubin encephalopathy (ABE), posing short- and long-term health risks. Despite extensive research identifying numerous mRNAs, lncRNAs, circRNAs, and miRNAs associated with brain injury, their roles in neonatal bilirubin-induced brain injury remain elusive. This study employed whole-transcriptome sequencing to ascertain the differentially expressed (DE) RNA profiles in a newborn ABE rat model, followed by bioinformatic analysis. A time-series competing endogenous RNA (ceRNA) regulatory network was established, and the expression trends of 9 arbitrarily chosen RNAs were verified through quantitative real-time polymerase chain reaction(qRT-PCR). In comparison with the control group, we identified 595, 888, and 1448 DE mRNAs; 22, 37, and 37 DE miRNAs; 1945, 1869, and 1997 DE lncRNAs; and 31, 28, and 36 DE circRNAs at 6 h, 12 h, and 24 h, respectively. Predominantly, these DERNAs contribute to biological functions and pathways associated with inflammation, immunity, metabolism, cell death, and neurodevelopmental regulation. Moreover, we constructed ceRNA networks of DE lncRNA/circRNA-DE miRNA-DE mRNA based on time series. The qRT-PCR expression trends for the selected 9 RNAs were generally similar to the RNA-seq outcomes. This investigation uniquely delineated the temporal expression patterns of mRNA and non-coding RNA in ABE, establishing ceRNA networks and identifying potential molecular mechanisms underlying bilirubin-induced hippocampal damage. Nonetheless, further studies are warranted to corroborate these findings in humans.

Is it time for a precision health approach to the management of newborn hyperbilirubinemia?

Newborn hyperbilirubinemia during the first two weeks of lifeis one of most common problems requiring management decisions by a pediatrician. However, high bilirubin levels in the circulation have been associated with neurologic injury under a variety of conditions encountered in the newborn infant, such as hemolysis. The risk for developing dangerous hyperbilirubinemia is multifactorial and is determined by a complex set of factors related to a newborn infant's genetic capacities as well as intra- and extrauterine exposures. To this end, a precision health approach based on the integration of prenatal genetic and postnatal diagnostic measures might improve the management of neonatal hyperbilirubinemia.

The Diagnostic Potential of the L Score for ABO Hemolytic Disease of the Newborn: Insights from a Cross-Sectional Study

Abstract Purpose This study aimed to evaluate the diagnostic efficacy of the L score, a novel scoring system, in distinguishing between ABO hemolytic disease of the newborn (ABO-HDN) and non-hemolytic disease of newborn hyperbilirubinemia (NHDNH). Methods A cross-sectional prospective study was conducted to assess the effectiveness of the L score in distinguishing between ABO-HDN (n = 118) and NHDNH (n = 213). Blood routine examination results were collected, and relevant statistical analyses were performed to identify clinically significant parameters. Binary logistic regression analysis was employed to assess the relationship between the L score and the development of these conditions, considering relevant variables. Results Our study identified the red blood cell count, mean corpuscular volume, red blood cell distribution width—coefficient of variation, and red blood cell distribution width—standard deviation as independent risk factors for distinguishing ABO-HDN from other high bilirubinemia conditions (P &lt; 0.001). The L score demonstrated superior predictive performance for ABO-HDN, exhibiting an area under the curve (AUC) of 0.746, with an optimal cutoff value of − 3.0816. The RBC-L score exhibited superior predictive performance (z: 5.596, P &lt; 0.0001) compared to the single-factor RBC indicator, indicating its efficacy in accurately identifying the desired outcome. Conclusion The L score represents a valuable tool for predicting neonatal hyperbilirubinemia and hemolytic disease, facilitating differentiation, and guiding early intervention for improved outcomes. Further research is warranted to validate and expand the applicability of the L score in clinical practice.

Prevalence and association of early onset severe hyperbilirubinemia in newborn in the East China region: Retrospective medical record analyses.

Research on the prevalence and association of hyperbilirubinemia is controversial because of different cultures, demographics, and clinical conditions. The etiology of hyperbilirubinemia is affected by the environment and other factors in the newborn. The World Health Organization recommended a 1-day hospital stay after uncomplicated delivery, jaundice assessment before discharge, and screening on 3rd and 7th days after birth for hyperbilirubinemia. However, the implementation of these recommendations is difficult in China. The objective of this study was to evaluate the prevalence and association of early onset severe hyperbilirubinemia in newborns in East China. Retrospective medical record analyses for 250 cesarean sections or vaginal deliveries, ≥2 kg body weight, and negative for Hepatitis B surface antigen by birth newborns were performed. A biochemical analyzer, quantitative assay, and quantitative polymerase chain reaction were used to evaluate total serum bilirubin, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and gene variant phenotyping, respectively. A total in 33 (13%) newborns were reported with early onset severe hyperbilirubinemia (according to the American Academy of Pediatrics, total serum bilirubin ≥ 342 μmol/L within 6 hours of birth). All newborns with severe hyperbilirubinemia were hospitalized and underwent phototherapy. The mothers of all newborns had a gestational age ≥ 35 weeks. Hospitalization included artificial feeding, and breastfeeding was rare (P < .0001). ABO incompatibility ("O" blood type for mother and either "A" or "AB" or "B" blood type for newborn, P = .0411), G6PD deficiency (G6PD/6-phosphogluconate dehydrogenase ≤ 1.0 in quantitative assay, P = .0422), Rh incompatibility (the mother's blood type was Rh negative and newborn blood type was Rh positive, P = .0416), fewer genotype rs4149056 frequencies (P = .0452), higher genotype rs2306283 frequencies (P = .0461), and higher genotype rs1805173 frequencies (P = .0471) were independent parameter for early onset severe hyperbilirubinemia of newborns. The prevalence of early onset severe hyperbilirubinemia in Chinese newborns is 13% in the East China region. Blood incompatibility, G6PD deficiency, fewer genotype rs4149056 frequencies, higher genotype rs2306283 frequencies, and higher genotype rs1805173 frequencies were independent predictors of early onset severe hyperbilirubinemia among newborns in the East China region (Level of Evidence: IV; Technical Efficacy: Stage 5).

A zebrafish model for studying the mechanisms of newborn hyperbilirubinemia and bilirubin-induced neurological damage.

Unresolved neonatal hyperbilirubinemia may lead to the accumulation of excess bilirubin in the body, and bilirubin in neural tissues may induce toxicity. Bilirubin-induced neurological damage (BIND) can result in acute or chronic bilirubin encephalopathy, causing temporary or lasting neurological dysfunction or severe damage resulting in infant death. Although serum bilirubin levels are used as an indication of severity, known and unknown individual differences affect the severity of the symptoms. The mechanisms of BIND are not yet fully understood. Here, a zebrafish newborn hyperbilirubinemia model is developed and characterized. Direct exposure to excess bilirubin induced dose- and time-dependent toxicity linked to the accumulation of bilirubin in the body and brain. Introduced bilirubin was processed by the liver, which increased the tolerance of larvae. BIND in larvae was demonstrated by morphometric measurements, histopathological analyses and functional tests. The larvae that survived hyperbilirubinemia displayed mild or severe morphologies associated with defects in eye movements, body posture and swimming problems. Interestingly, a plethora of mild to severe clinical symptoms were reproduced in the zebrafish model.

Coagulation profile of neonates with hyperbilirubinaemia in full-term newborns.

To determine the relationship between coagulation system markers and hyperbilirubinaemia in full-term neonates. This retrospective case-control study enrolled full-term neonates with hyperbilirubinaemia and healthy control full-term neonates. Prothrombin time (PT), thrombin time (TT), fibrinogen (Fbg), activated partial thromboplastin time (APTT) and international normalized ratio (INR) were recorded. The correlation between INR and total bilirubin and between INR and indirect bilirubin was analysed by linear regression analysis. Receiver operating characteristic curve analysis was used to assess the efficacy of INR to identify neonates with hyperbilirubinaemia. This study enrolled 40 full-term neonates with hyperbilirubinaemia and 30 healthy controls. PT, INR and APTT were significantly higher in the neonates with hyperbilirubinaemia compared with the healthy controls. There was a significant positive correlation between INR and the level of total bilirubin in neonates with hyperbilirubinaemia (R = 0.3327). There was also a significant positive correlation between INR and the level of indirect bilirubin in neonates with hyperbilirubinaemia (R = 0.3406). INR in neonates with hyperbilirubinaemia significantly achieved an area under the curve of 0.800 (95% confidence interval, 0.6288, 0.9712; cut-off value, 1.060; specificity, 71.43%; sensitivity, 80.00%). These findings suggest that INR is a novel biomarker for the diagnosis of neonatal hyperbilirubinaemia in full-term neonates.

Diagnostic Accuracy of Cord Blood Bilirubin in Predicting Neonatal Hyperbilirubinemia, Taking Neonatal Hyperbilirubinemia within One Week of Birth as Gold Standard

Objective: To determine the diagnostic accuracy of cord blood bilirubin in predicting neonatalhyperbilirubinemia, taking neonatal hyperbilirubinemia within one week of birth as the gold standard.Study Design: Across-sectional study.Place and Duration of Study: The Study was conducted at the Department of Pediatric Medicine, Sheikh Zayed Hospital, Rahim Yar Khan, Pakistan from 7 September 2020 to 6 March 2021.Methods: A total of 366 term neonates of both gendersgenders were included. Neonates with congenital hypothyroidism, neonatal hepatitis, biliary atresia, and sepsis were excluded. After getting informed consent from parents, a cord blood sample was taken and sent to the institutional laboratory for measuring total bilirubin levels, and neonatal hyperbilirubinemia (yes/no) was noted. All neonates were followed by the researcher for one week and neonatal hyperbilirubinemia was noted.Results: The study yielded 193 true positive and 14 false positive cases, along with 7 false negative and 152 true negative cases, with a statistically significant p-value of 0.0001. Overall, the diagnostic accuracy of cord blood bilirubin in predicting neonatal hyperbilirubinemia, using neonatal hyperbilirubinemia within one week of birth as the gold standard, was found to be 96.50% for sensitivity, 91.57% for specificity, 93.24% for positive predictive value, 95.60% for negative predictive value, and 94.26% for diagnostic accuracy.Conclusion: This study has shown that cord blood bilirubin has a rather good diagnostic accuracy for predicting newborn hyperbilirubinemia.&#x0D; How to cite this: Majeed M, Ahmed D, Hanif D, Khaliq H, Ahmad A, Khan ZA. Diagnostic Accuracy of Cord Blood Bilirubin in Predicting Neonatal Hyperbilirubinemia, Taking Neonatal Hyperbilirubinemia within One Week of Birth as Gold Standard. Life and Science. 2023; 4(4): 401-409. doi: http://doi.org/10.37185/LnS.1.1.347

Immunoglobulin G Levels in Neonates After Receiving Phototherapy

Background: Most cases of newborn hyperbilirubinemia are physiologic; however, excessive unconjugated bilirubin is a potential neurotoxin. Phototherapy treats moderate to severe hyperbilirubinemia. If phototherapy increases immunoglobulin G (IgG) clearance, there is a chance of humoral immune disorders. Objectives: The purpose of the study was to investigate the effect of phototherapy on the level of IgG in neonates. Methods: This study investigated 40 full-term newborns with hyperbilirubinemia. Blood samples were taken before and 72 hours after phototherapy. The IgG level was measured by calorimetry tests. Results: Phototherapy resulted in a decrease in IgG levels. The IgG level significantly decreased from 833.135 to 720.185 mg/dL. Before phototherapy, 12.5% of the population had low IgG levels; however, 32.5% had low IgG levels after the treatment. Conclusions: According to the results of the study, intensive phototherapy caused a reduction in IgG levels. Since there was no significant decrease in IgG levels in neonates who received conventional phototherapy, it can be concluded that this treatment is safe in terms of IgG levels.

What is the diagnostic test accuracy of non-invasive transcutaneous bilirubin measurement devices for detecting hyperbilirubinemia in newborns?

What is the diagnostic test accuracy of non-invasive transcutaneous bilirubin measurement devices for detecting hyperbilirubinemia in newborns?

A Randomized Trial Comparing NeoLight Skylife and Blanket Phototherapy in Newborn Indirect Hyperbilirubinemia.

This investigation aimed to assess the safety and efficacy of NeoLight's Skylife phototherapy device for the treatment of hyperbilirubinemia. A prospective, two-arm, randomized, unblinded controlled investigation compared total serum bilirubin (TSB) levels at baseline and discharge for a new phototherapy device (Skylife) with an existing phototherapy treatment in newborn infants. The repeated-measures analysis of variance (RM-ANOVA) indicated a significant main effect for the treatment condition, F(1, 54) = 4.041, P = .049. Post hoc findings showed that the Skylife group had significantly lower TSB levels following treatment (n = 28, Mean = 11.36, SD = 1.69) compared with the standard of care group (n = 28, Mean = 12.37, SD = 2.08), t(54) = 2.01, P = .049). The Skylife phototherapy device was as effective as the currently used therapy, with a shift toward a more rapid decline in bilirubin levels. Using this device may potentially decrease the length of therapy and hospitalization.Clinical Trial Registration Comparison of Phototherapy Using Neolight Skylife Versus Standardized Phototherapy for Hyperbilirubinemia in Newborns is registered at clinicaltrials.gov as NCT03599258.

Umbilical Cord Blood Hemoglobin as a Predictor of Significant Neonatal Hyperbilirubinemia in Term Newborns in a Tertiary Care Centre in North Kerala

Aims: Neonatal hyperbilirubinemia is one of the most common problems during first week of life and is the most common cause of readmission in early neonatal period. The present study aimed to predict the development of significant hyperbilirubinemia in term neonates using cord blood hemoglobin.&#x0D; Study Design: Prospective study.&#x0D; Place and Duration of Study: Department of Paediatrics, MMCH &amp; RC, Kozhikode, Kerala from March 2021 to July 2022.&#x0D; Methodology: The prospective study enrolled 162 appropriate for gestational age term newborns, delivered at MMCH &amp; RC. Cord blood hemoglobin was measured and bilirubin estimation was done at 48-72 hours of life. Hyperbilirubinemia was considered significant if serum bilirubin value was above standard as per American Academy of Pediatrics guidelines. Data was entered in Microsoft Excel and analysed using SPSS 20.0 version. The relationship between cord hemoglobin in predicting significant neonatal hyperbilirubinemia was studied using appropriate statistical tests. Sensitivity and specificity of the variables were defined using ROC curve and Pearson correlation coefficient to determine the correlation between the variables.&#x0D; Results: Out of the total 162 neonates enrolled, 86 were boys (53.1%) and 76 were girls (46.9%). The mean cord hemoglobin value was 15.3g/dl. 20 neonates (12.3%) had developed significant hyperbilirubinemia and required phototherapy while none of them needed exchange transfusion. Correlation between cord hemoglobin with serum bilirubin showed weak correlation (r=0.194) but the correlation was statistically significant (p&lt;0.05). On ROC curve analysis, cord hemoglobin cut off value ≥14.9g/dl showed 75% sensitivity and 39.4% specificity to predict significant neonatal hyperbilirubinemia.&#x0D; Conclusion: There is significant correlation between umbilical cord blood hemoglobin level and neonatal hyperbilirubinemia. Cord hemoglobin ≥14.9g/dl can predict future development of significant neonatal hyperbilirubinemia. This will be useful in very low resource centres to plan early discharge of newborns without fear of hyperbilirubinemia.

Overdiagnosis of Newborn Hyperbilirubinemia: A Natural Experiment in Quality Improvement Fundamentals.

In January 2020, 2 hospitals (A and B) transitioned to a new method of measuring TSB using a new clinical chemistry analyzer (Siemens Atellica CH), which measured TSB by vanadate oxidase assay instead of the previous diazo assay. Five affiliated hospitals (C-G) continued to utilize the diazo assay. This natural experiment led to a comparison of data across the 7 hospitals. We analyzed: (1) TSB levels, (2) hospital hyperbilirubinemia readmissions, and (3) paired TSB measurements comparing the diazo assay and vanadate oxidase method. Compared to the 2019 baseline, Hospitals A and B had a significant increase in TSBs ≥17.0 mg/dl and TSBs ≥20 mg/dl in 2020; Hospitals C-G did not. Readmissions for phototherapy significantly increased in hospitals A and B in 2020 compared to 2019. Paired blood samples showed bias-elevated TSBs by vanadate assay compared to the diazo method. By 2021, the laboratory resumed processing TSB samples by diazo assay, and the frequency of elevated TSBs and hyperbilirubinemia readmissions returned to 2019 levels. Factitious TSB elevation related to an assay change significantly increased newborn hyperbilirubinemia evaluations and phototherapy readmissions. Imbedded quality improvement methodologies of careful structure, process, and outcomes review hastened resolution.

Gut–liver axis and the impact of probiotics on neonatal jaundice symptoms: a review

Neonatal jaundice, which can affect up to 60% of term and 80% of preterm babies, can have a serious detrimental effect on their health. The effects of microbiota on neonatal bilirubin are poorly understood, which creates a critical knowledge gap about how they affect the neonate's blood bilirubin levels and how the gut delicately balances close contact with the host. Prebiotics and probiotics have a significant impact on the management of hyperbilirubinemia, but their effectiveness is still being debated. To offer a compelling novel therapeutic approach for newborn hyperbilirubinemia, a thorough understanding of the process is required.

Risk Stratification of Term Neonates for Development of Significant Hyperbilirubinemia by Cord Serum Bilirubin and Albumin Ratio

ABSTRACT 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 &gt;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.

Evaluate of newborn with jaundice at central teaching hospital of pediatrics in Baghdad : descriptive study

Background: - Neonatal jaundice is a frequent condition at newborns, particularly in the first few days after delivery, and it has to be treated well to prevent complications that might have significant, long-lasting complications.&#x0D; Objective: - To assess the outcome of newborn jaundice at the central teaching Hospital of pediatrics in Baghdad using different modality of treatments.&#x0D; Patients and Methods: - A retrospective study is done depending on the medical data of infants have jaundice who were admitted to the neonate units of the central teaching hospital within the period of a year, from May 1st 2020 to May 1st 2021. Blood grouping and total serum bilirubin measurements were taken in each case. Phototherapy, strong phototherapy, and exchange transfusion were utilized to treat the newborn jaundice, depending on its severity.&#x0D; Results: Total neonates admitted from 1st may2020 to1st may 2021 in neonate unit were 2508 and 855 [34%] have jaundice. the male: female rati0 is [1.6:1], males 516[60.3%], females 339[39.6%]. The Physiol0gical jaundice is the often-frequent cause 285[33.3%] patients. The Prematurity seen in 171[20%] patient and the ABO incompatibility seen in 128[1.3%] and the Rh incompatibility 17[2%] patient, the sepsis found in 16[2%] case and the other causes of hyperbilirubinemia seen in 238[27.8%] patient. the Phototherapy is the most frequent kind of management used in 513[55%] and intensive phototherapy is applied for 342[40.3%] patients and just 59[7%] of patients treated with exchange transfusion particularly patients with ABO incompatibility 25 [42%] also Rh incompatibility 34 [57.6%] Good decline in TSB level and not require the exchange transfusion is 812 [95%] of patients. Majority of infants 849 [99.55%] discharge with clinical improvement and only 17 [0.3%] of infant’s patients develops kernicterus and 8 patients is dying [0.1%]&#x0D; Conclusion: Moderate to severe hyperbilirubinemia is still often treated with phototherapy. Intensive phototherapy is beneficial in lowering T.S.B levels, minimizing the need for exchange transfusions, and shortening hospital stays in patients with newborn hyperbilirubinemia.

Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns.

Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by increased bilirubin in the blood from the breakdown of red blood cells. The gold standard for measuring bilirubin levels is obtaining a blood sample and processing it in a laboratory. However, noninvasive transcutaneous bilirubin (TcB) measurement devices are widely available and used in many settings to estimate total serum bilirubin (TSB) levels. To determine the diagnostic accuracy of transcutaneous bilirubin measurementfor detecting hyperbilirubinaemia in newborns. We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries up to 18 August 2022. We also checked the reference lists of all included studies and relevant systematic reviews for other potentially eligible studies. We included cross-sectional and prospective cohort studies that evaluated the accuracy of any TcB device compared to TSB measurement in term or preterm newborn infants (0 to 28 days postnatal age). All included studies provided sufficient data and information to create a 2 × 2 table for the calculation of measures of diagnostic accuracy, including sensitivities and specificities. We excluded studies that only reported correlation coefficients. Two review authors independently applied the eligibility criteria to all citations from the search and extracted data from the included studies using a standard data extraction form. We summarised the available results narratively and, where possible, we combined study data in a meta-analysis. We included 23 studies, involving 5058 participants. All studies had low risk of bias as measured by the QUADAS 2 tool. The studies were conducted in different countries and settings, included newborns of different gestational and postnatal ages, compared various TcB devices (including the JM 101, JM 102, JM 103, BiliChek, Bilitest and JH20-1C) and used different cutoff values for a positive result. In most studies, the TcB measurement was taken from the forehead, sternum, or both. The sensitivity of various TcB cutoff values to detect significant hyperbilirubinaemia ranged from 74% to 100%, and specificity ranged from 18% to 89%. The high sensitivity of TcB to detect hyperbilirubinaemia suggests that TcB devices are reliable screening tests for ruling out hyperbilirubinaemia in newborn infants. Positive test results would require confirmation through serum bilirubin measurement.

Etiology analysis for term newborns with severe hyperbilirubinemia in eastern Guangdong of China

Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin, resulting in sequelaes such as hearing loss, motor and intellectual development disorders, and even death. The pathogenic factors of neonatal hyperbilirubinemia are complex. Different cases of hyperbilirubinemia may have a single or mixed etiology. To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China. Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed. The etiology was determined according to the laboratory results and clinical manifestations. Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China, 32.20% (580/1602) was severe hyperbilirubinemia. Among the causes of severe hyperbilirubinemia, neonatal hemolysis accounted for 15.17%, breast milk jaundice accounted for 12.09%, infection accounted for 10.17%, glucose-6-phosphate dehydrogenase (G6PD) deficiency accounted for 9.14%, and the coexistence of multiple etiologies accounted for 6.55%, unknown etiology accounted for 41.72%. ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy. 94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)*6 variant (rs4148323, c.211G>A, p.Arg71Gly), 9 cases were 211 G to A homozygous variant, 37 cases were 211 G to A heterozygous variant, and 48 cases were wild genotypes. The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns, G6PD deficiency and infection. UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia. Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

Red Blood Cell Membrane-Related Gene Variants and Clinical Risk Factors in Chinese Neonates with Hyperbilirubinemia

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.

A prospective study on correlation of cord blood bilirubin with occurrence of neonatal hyperbilirubinemia

Background: Neonatal hyperbilirubinemia is one of the most common problems that can occur in a healthy new-born. This physiological rise in indirect component of bilirubin resolves gradually without any intervention in majority of cases. But few babies require intervention in the form of phototherapy and exchange transfusion when the bilirubin levels exceed the normal physiological range for gestational age. The study was aimed to evaluate the predictive value of cord blood bilirubin level for identifying newborn for development of significant hyperbilirubinemia. Methods: It was a prospective observational study carried out in Adichunchanagiri Institute of Medical Sciences, B.G. Nagara, Karnataka. The cord blood bilirubin at birth and 48 hrs serum bilirubin levels were measured. Also, blood group, Rh status and DCT (direct coomb’s test) were tested to estimate the risk in development of hyperbilirubinemia. Results: A total of 210 were included in the study, out of which 52 babies required phototherapy, with a sensitivity of 94.23% and specificity of 3.97%, with the mean cord blood bilirubin level of 2.6mg/dl, having sensitivity of 63.46% and specificity of 90.50%. The multivariate analysis showed ABO and Rh incompatibility, cord blood bilirubin level and lower gestational age had an increased the risk of hyperbilirubinemia requiring phototherapy. Conclusions: Cord blood bilirubin may be used as a potential tool to determine hyperbilirubinemia in newborns. And initiation of phototherapy early in at-risk neonates may decrease the hyperbilirubinemia related morbidity and mortality. Keywords: hyperbilirubinemia; cord blood bilirubin; phototherapy; newborn