Comparison of prognosis between hyperbilirubinemic infants with and without hypernatremia.

OBJECTIVES: Hypernatremia may facilitate the diffusion of bilirubin through the blood-brain barrier and increase the risk of bilirubin encephalopathy. This study was conducted to compare the prognosis of jaundice infants with those with jaundice and hypernatremia. METHODS: A total of 615 term infants with idiopathic jaundice with or without hypernatremia were enrolled in this cohort study with 24-months follow-up at Ghaem Hospital, Mashhad, Iran, between 2010 and 2022. An in-house questionnaire including the laboratory evaluation and neonatal characteristics was used as the data collection tool. The follow-up of neonatal development status was performed using the Denver test II at 6, 12, 18, and 24 months after discharging from hospital. RESULTS: Normal outcomes were seen in 555 (90.2%) out of 615 studied infants, while 60 cases (9.8%) showed abnormal outcomes. Serum levels of sodium (P = 0.017), bilirubin (P = 0.001), urea (P = 0.024), and creatinine (P = 0.011) as well as hyperthermia (P = 0.046) and unconsciousness (P = 0.005) showed significant differences between the two groups. Approximately 16% of the newborns with both jaundice and hypernatremia, and 9% of those with only jaundice had unfavorable prognoses. Also, bilirubin level had the most predictive power (91.3%). CONCLUSIONS: Our results suggest that hypernatremia or jaundice alone, may affect the prognosis of infants aged 2 years; but jaundice and hypernatremia together, will intensify the developmental problems in jaundice infants. However, the role of hyperbilirubinemia in the incidence of complications is more than hypernatremia.

Evaluating the relationship between aEEG findings and two-year prognosis in neonates with severe hyperbilirubinemia.

OBJECTIVE: Identifying factors that can better predict the prognosis of neonates with hyperbilirubinemia is important. In this study, we aimed to evaluate the relationship between electroencephalography (EEG) findings and two-year prognosis in neonates with severe hyperbilirubinemia. METHODS & MATERIALS: In a cohort prospective study, we studied neonates with a total serum bilirubin level of higher than 18 mg/dL, who were admitted to the neonatal intensive care unit (NICU) of Ghaem hospital, Mashhad, Iran. EEG was recorded upon admission, for all neonates. Patients' data, including demographic characteristics, admission information, and pregnancy and birth data were gathered by obtaining history from parents and studying case files. Also, the relationship between initial EEG findings and final developmental status was assessed. RESULTS: Mean and standard deviation age of patients were 5.46 ± 3.13 days and average serum total bilirubin level was 23.97 ± 4.34 mg/dL at admission. Our findings revealed a significant correlation between the presence of trace alternant on EEG and developmental delay (P = .001). Presence of trace alternant waves on initial EEG at admission was significantly associated with developmental delay in the two year (P = .005). CONCLUSION: These results indicate a relationship between developmental prognosis and the severity of hyper bilirubinemia in neonates. Also, our findings show that the presence of trace alternate waves on the initial EEG is significantly associated with developmental delay of the neonate in the future.

The Effect of Abdominal Massage on Bilirubin Levels in Term Infants Receiving Phototherapy: A Randomized Controlled Trial.

BACKGROUND: The incidence of neonatal hyperbilirubinemia in Europe and the United States is estimated to be 3.2 and 4.4 per 10,000 live births, respectively. Abdominal massage for hyperbilirubinemia is considered a safe complementary treatment for infants that may increase number of defecations and decrease bilirubin levels. PURPOSE: This study was designed as a randomized controlled trial to determine the effect of abdominal massage on bilirubin levels in term infants receiving phototherapy. METHODS: The sample consisted of 43 term newborns (intervention group: 23; control group: 20) who received phototherapy in a university hospital between June 2019 and February 2021. Information and observation forms were used for data collection. The intervention group received 6 abdominal massages over 2 days, performed 3 times a day, 6 hours apart, and lasting 5 minutes each. RESULTS: Transcutaneous bilirubin levels and heart rate were significantly lower in the intervention group than in the control group at 48 hours (P = .015 and P = .033, respectively). Number of defecations was higher in the intervention group at 24 hours (P = .007) but there was no significant difference at 48 hours. The decrease in serum bilirubin between 24 and 48 hours was significantly greater in the intervention group (P = .005). IMPLICATION FOR PRACTICE AND RESEARCH: Abdominal massage was effective in reducing bilirubin levels and may increase the number of defecations. Providing massage training to the parents of infants who are discharged early could be a protective approach to prevent the rise in bilirubin levels.

Comparing Outcomes Between Direct and ED Admissions for Neonatal Hyperbilirubinemia.

OBJECTIVES: Pediatric direct admissions (DA) have multiple benefits including reduced emergency department (ED) volumes, greater patient and provider satisfaction, and decreased costs without compromising patient safety. We sought to compare resource utilization and outcomes between patients with a primary diagnosis of neonatal hyperbilirubinemia directly admitted with those admitted from the ED. METHODS: Single-center, retrospective study at a large, academic, free-standing children's hospital (2017-2021). Patients were between 24 hours and 14 days old with a gestational age of ≥35 weeks, admitted with a primary diagnosis of neonatal hyperbilirubinemia. Outcomes included length of stay (LOS), time to clinical care, resource utilization, NICU transfer, and 7-day readmission for phototherapy. RESULTS: A total of 1098 patients were included, with 276 (25.1%) ED admissions and 822 (74.9%) DAs. DAs experienced a shorter median time to bilirubin level collection (1.9 vs 2.1 hours, P = .003), received less intravenous fluids (8.9% vs 51.4%, P < .001), had less bilirubin levels collected (median of 3.0 vs 4.0, P < .001), received phototherapy sooner (median of 0.8 vs 4.2 hours, P < .001), and had a shorter LOS (median of 21 vs 23 hours, P = .002). One patient who was directly admitted required transfer to the NICU. No differences were observed in the 7-day readmission rates for phototherapy. CONCLUSIONS: Directly admitting patients for the management of neonatal hyperbilirubinemia is a preferred alternative to ED admission as our study demonstrated that DAs had a shorter time to clinical care, shorter LOS, and less unnecessary resource utilization with no difference in 7-day readmissions for phototherapy.

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

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Comparative analysis of the quantitative point-of-care CareSTART™ total bilirubin with central laboratory total bilirubin assays in neonatal blood samples.

This study aimed to assess and compare the accuracy of point-of-care CareSTART™ S1 Total Bilirubin test with a central laboratory total bilirubin assay using neonatal samples. This study was conducted using 152 paired measurements obtained from 122 neonates admitted to the neonatal intensive care unit. Total serum bilirubin (TSB) levels assayed with the central laboratory assay, laboratory bilirubinomter, trancutaneous bliribubin (TcB) instrument and CareSTART were compared using Bland-Altman analysis. The mean difference between the CareSTART and TSB values was -1.43 mg/dL and the 95% limit of agreement (LoA) was -4.25 to 1.39 mg/dL. CareSTART tended to underestimate total bilirubin concentrations compared with TcB, however, the LoA was narrower due to the smaller SD of mean difference for CareSTART. The CareSTART Total Bilirubin test provides an accurate alternative to TcB for total serum bilirubin measurement. Given its low-cost, ease-of-use, and portability, the use of CareSTART is expected to provide point-of-care measurements, especially in low-resource settings.

[Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia].

Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) µmol/L, with a range of 23.7-717.0 µmol/L. The JCard level was (221.4±77.0) µmol/L and the TcB level was (252.5±76.0) µmol/L. Both the JCard and TcB values showed good correlation (r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 µmol/L. The TcB value of 205.2 µmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 µmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 µmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 µmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 µmol/L (both P<0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 µmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 µmol/L).

Innovative approaches to neonatal jaundice diagnosis and management in low-resourced settings.

Persistent challenges in addressing severe neonatal hyperbilirubinaemia in resource-constrained settings have led to ongoing and often unacceptable rates of morbidity, disability and mortality. These challenges stem from limitations such as inadequate, inefficient or financially inaccessible diagnostic and therapeutic options. However, over the past decade, noteworthy innovations have emerged to address some of these hurdles, and these innovations are increasingly poised for broader implementation. This review provides a concise summary of these novel, economically viable diagnostic solutions, encompassing point-of-care assays and smartphone applications, as well as treatment modalities, notably more effective phototherapy and filtered sunlight. These advancements hold promise and have the potential to meaningfully reduce the burden of neonatal hyperbilirubinaemia, signifying a promising shift in the landscape of neonatal healthcare.

Bilirubin Measurement and Phototherapy Use After the AAP 2022 Newborn Hyperbilirubinemia Guideline.

BACKGROUND AND OBJECTIVES: Guidelines for the management of neonatal hyperbilirubinemia have helped to reduce rates of significant hyperbilirubinemia. However, recent evidence suggesting overtreatment and potential harms of phototherapy have informed the American Academy of Pediatrics clinical practice guideline revision and the accompanying increase in phototherapy thresholds. These changes are predicted to safely reduce overuse; however, to date, the exact effect of these guidelines has not been established. METHODS: We conducted a retrospective study of newborns born at ≥35 weeks' gestation across a network of 8 hospitals between January 2022 and June 2023. Outcomes included rates of phototherapy and total serum bilirubin (TSB) measurements before and after guideline publication, as well as clinical outcomes, including length of stay, readmissions, and duration of phototherapy. RESULTS: In our cohort of >22 000 newborns, we observed a 47% decrease in phototherapy utilization, from 3.9% to 2.1% (P < .001). TSB measurements were reduced by 23%, from 712 to 551 measurements per 1000 newborns (P < .001), without an increase in outpatient TSB measurements. We did not observe an increase in readmissions receiving phototherapy, and length of stay increased by only 1 hour (P < .001). CONCLUSIONS: Our study reveals that the publication of the updated American Academy of Pediatrics 2022 hyperbilirubinemia guidelines has likely yielded a significant reduction in phototherapy use and serum bilirubin measurement. Dedicated quality improvement initiatives may help determine which implementation strategies are most effective. Further population-level studies are needed to confirm safety with ongoing guideline uptake.

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

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

Hyperbilirubinemia screening and treatment in neonates born prior to 35 weeks of gestation.

BACKGROUND: Guidelines on when to screen for neonatal hyperbilirubinemia apply to infants born at 35 weeks or later of gestation. It is unknown whether infants born earlier would benefit from similar guidelines. Our objective was to examine hyperbilirubinemia screening and phototherapy prescription among early preterm infants during the first 6 days of life. METHODS: We reviewed the charts of 193 infants born prior to 35 weeks of gestation who were admitted to a tertiary care NICU in Southeastern Ontario in 2018-2019. Information on total serum bilirubin (TSB) measurements over each 12-hour interval during the first six days of life and the treatment decision (no treatment, initiate, continue, or stop phototherapy) was extracted. We also examined what proportion of infants were prescribed phototherapy during each 12-hour interval. RESULTS: Of 1006 TSB measurements performed over the first 6 days of life, 605 were done to determine whether phototherapy should be initiated. Treatment was prescribed in 275 instances (45%). A higher proportion of infants born prior to 28 weeks of gestation required phototherapy in the first 12 hours of life (37%) compared to those born at 28-32 weeks (20%) and 33-34 weeks (5.7%). CONCLUSIONS: Our results suggest that TSB measurements are often poorly timed to detect treatment need in infants born prior to 35 weeks of gestation. This unnecessarily increases the risk of complications from phlebotomy and is an ineffective use of health care resources. There is a need to develop guidelines to optimize hyperbilirubinemia screening among early preterm infants.

Effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates: a randomised controlled trial.

INTRODUCTION: Raised serum bilirubin levels can cause kernicterus, and premature infants are at increased risk owing to metabolic immaturity. The standard treatment for neonatal jaundice is phototherapy, but probiotics alone can reduce the duration of phototherapy and hospitalisation. OBJECTIVES: To determine the effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates. PATIENTS AND METHODS: The open-labelled randomised controlled trial was conducted from January 2022 to January 2023 in the neonatal unit of the University of Lahore Teaching Hospital, Pakistan. A total of 76 preterm neonates who fulfilled the selection criteria were included and divided into two groups. Both groups received standard phototherapy. In Group B, a probiotic (Saccharomyces boulardii) 125 mg, twice daily, orally (in 5 cc of whichever milk the infant was receiving) was given until discharge from hospital. The primary outcome measurements were the duration of phototherapy and the length of hospitalisation. RESULTS: The mean (SD) duration of phototherapy was 36.55 (14.25) hours in Group A and 24.61 (9.25) hours in Group B (p <0.05). The mean (SD) duration of hospital stay was 47.36 (16.51) hours in Group A and 33.13 (8.93) hours in Group B (p <0.05). CONCLUSION: Oral probiotics (Saccharomyces boulardii) have a significant effect on the duration of phototherapy for neonatal hyperbilirubinaemia, and they decrease the chances of nosocomial infection. Exploration of clinical outcomes by investigating faecal flora and undertaking large randomised controlled trials of various probiotics are needed. ABBREVIATIONS: ABE: acute bilirubin encephalopathy; CNS: central nervous system; GA: gestational age; IVIG: intravenous immunoglobulin; KSD: kernicterus; NNU: neonatal unit; RCT: randomised controlled trial; S. boulardii: Saccharomyces boulardii.

Application of machine learning algorithms for accurate determination of bilirubin level on in vitro engineered tissue phantom images.

Neonatal Jaundice is a common occurrence in neonates. High excess bilirubin would lead to hyperbilirubinemia, leading to irreversible adverse damage such as kernicterus. Therefore, it is necessary and important to monitor neonates' bilirubin levels in real-time for immediate intervention. However, current screening protocols have their inherent limitations, necessitating more convenient measurements. In this proof-of-concept study, we evaluated the feasibility of using machine learning for the screening of hyperbilirubinemia in neonates from smartphone-acquired photographs. Different machine learning models were compared and evaluated to gain a better understanding of feature selection and model performance in bilirubin determination. An in vitro study was conducted with a bilirubin-containing tissue phantom to identify potential biological and environmental confounding factors. The findings of this study present a systematic characterization of the confounding effect of various factors through separate parametric tests. These tests uncover potential techniques in image pre-processing, highlighting important biological features (light scattering property and skin thickness) and external features (ISO, lighting conditions and white balance), which together contribute to robust model approaches for accurately determining bilirubin concentrations. By obtaining an accuracy of 0.848 in classification and 0.812 in regression, these findings indicate strong potential in aiding in the design of clinical studies using patient-derived images.

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

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

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

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

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

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