Transcutaneous bilirubin reliability during and after phototherapy depending on skin color.

Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic populations during and after phototherapy is still controversial even in covered skin. The aim of this study was to determine the reliability of TcB in covered (cTcB) and exposed (eTcB) skin during and after phototherapy in a multiethnic population of term and preterm neonates according to Neomar's neonatal skin color scale. Prospective, observational study comparing SB and TcB. We determined SB when clinically indicated and, at the same time, measured cTcB under a photo-opaque patch and eTcB next to it with a jaundice meter (Dräger JM-105TM). All dyads TcB-SB were compared, both globally and according to skin color. We obtained data from 200 newborns (color1: 44, color2: 111, color3: 41, color4: 4) and compared 296 dyads TcB/SB. Correlation between cTcB and SB is strong during (0.74-0.83) and after (0.79-0.88) phototherapy, both globally and by color group. The SB-cTcB bias depends on gestational age during phototherapy and on skin color following phototherapy. The correlation between eTcB and SB during phototherapy is not strong (0.54), but becomes so 12 h after discontinuing phototherapy (0.78).  Conclusions: Our study supports the reliability of cTcB to assess SB during and after phototherapy, with differences among skin tones after the treatment. The use of cTcB and Neomar's scale during and mainly after phototherapy may help reduce the number of blood samples required. What is Known: • Controversies exist on the reliability of jaundice meters during and after phototherapy in covered skin. Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in covered skin in a multiethnic population depending on skin color based on our own validated neonatal skin color scale during and after phototherapy.

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.

Magnitude and its associated factors of neonatal jaundice among neonates admitted to the neonatal intensive care unit of Dessie Town public hospitals, Amhara region, Ethiopia, 2020: a multicenter cross-sectional study.

Background: Neonatal jaundice is a prevalent illness affecting approximately 60%-80% of newborns. In severe cases, it can result in severe neurological distress. Approximately 1.1 million neonates are affected annually on a global scale, with the vast majority living in sub-Saharan Africa and southern Asia. It is common in newborns in the first week of life. This study aims to assess the magnitude and determinants of jaundice in newborns admitted to the neonatal intensive care unit (NICU) of public hospitals in the city of Dessie in northern Ethiopia. Methods: An institutional cross-sectional study was conducted at the NICU at Dessie town public hospitals from 30 March to 30 April 2020. A systematic random sampling procedure was used to select the study participants. Data were collected through face-to-face interviews with mothers using a structured questionnaire and by reviewing neonatal medical records using a checklist. Binary logistic regression analysis was used to identify the determinants of neonatal jaundice. A significance level of less than 0.05 was used to declare the statistical significance in the final model. Results: A total of 218 neonates with their mothers were included in the study. The prevalence rate of neonatal jaundice was found to be 28.4%. The major associated factors for neonatal jaundice were sepsis [adjusted odds ratio (AOR): 10.13, 95% confidence interval (CI) = 2.36, 43.56], preterm < 37 weeks (AOR: 6.03, 95% CI = 1.41, 25.79) low APGAR score < 7 (AOR: 7.34, 95% CI = 1.34, 39.65), ABO incompatibility (AOR: 24.55 95% CI = 1.58, 68.83), prolonged labor (AOR 9.03, 95% CI = 1.67, 48.33), and Rh incompatibility (AOR = 30.40, 95% CI = 2.01, 66.20). Conclusion: The magnitude of neonatal jaundice among neonates was determined to be high. Therefore, both maternal and neonatal factors contributed significantly to the management of neonatal jaundice and also influenced the use of phototherapy treatment. Proper consideration of these factors is crucial for the prevention and treatment of neonatal jaundice.

Validity of BiliDx as a point-of-care bilirubin measurement device to diagnose and monitor neonatal jaundice at Muhimbili National Hospital, an observational study.

BACKGROUND: Neonatal jaundice is a condition caused by elevated levels of bilirubin in the bloodstream. Laboratory determination of serum bilirubin concentration by total serum bilirubin (TSB) test is still considered as gold standard for clinical guidance and practice. In developed countries, diagnosis of neonatal jaundice is shifting towards point-of-care medical devices. BiliDx is a device developed to allow a fast, blood-based determination of bilirubin levels at the point of care. This study aimed to determine the accuracy of the BiliDx device relative to a standard laboratory total serum bilirubin to diagnose and monitor jaundice among neonates admitted at Muhimbili National Hospital (MNH). MATERIAL AND METHODOLOGY: This was a prospective hospital-based observational study conducted at the Neonatal Ward - MNH, Dar-es-Salaam, Tanzania from November 2022 to January 2023. A total of 180 neonates admitted at the neonatal ward with jaundice and whose parents consented were enrolled in the study. Blood samples were collected; 2 ml of venous blood into the vacutainer bottle for standard laboratory measurement of total serum bilirubin (TSB) and 25µL blood collected into a transfer pipette tube and applied to BiliDx. STATA version 15.1 was used for data analysis. RESULTS: Out of 180 neonates, 39.4% (71/180) had birth weight between 1500 - 2499.9 g, approximately 2/3rd (120/180) were preterm, 92/180 (51.1%) were males and 100/180 (55.6%) were undergoing phototherapy treatment the moment sample taken. The mean bilirubin concentration was 92 mmol/l for BiliDx and 118 mmol/l for standard laboratory TSB. The minimum and maximum values obtained with BiliDx were, 3.4 and 427.5 mmol/l respectively, compared with 10.7 and 382.1 mmol/l using standard laboratory TSB. A linear relationship and correlation coefficient of 0.8408 (p = 0.000) between BiliDx and standard laboratory TSB was found. The regression analysis showed the presence of constant error [coefficient of BiliDx/slope = 0.91, 95% CI (0.82-0.99), p = 0.000] and random error exclusively [coefficient of constant/y-intercept = 48.52, 95%CI (37.70-59.34), p = 0.000]. The Bland-Altman plot showed an acceptable mean difference of 39.1mmol/l, limits of agreement of -48.3mmol/l to 126.4mmol/l, and 179 points (179/180 = 99.4%) lying inside the limits of agreement. CONCLUSION: The results support the use of BiliDx for rapid and accurate testing of elevated levels of bilirubin in the bloodstream among neonates since 99.4% of the differences between BiliDx and standard laboratory TSB lie between the lines of agreement.

Determinants of Jaundice Among Neonates Admitted to Neonatal Intensive Care Unit of Mizan Tepi University Teaching Hospital, Southwest Ethiopia, 2021: Unmatched Case Control Study.

Background. Jaundice is a common problem in the neonatal period, and it is one of multiple factors found in children who die. Despite the majority of pathological jaundice public health consequences, there is no evidence on risk factors of pathological jaundice among neonates in Southwest Ethiopia. Therefore, this study aimed to identify factors associated with jaundice requiring phototherapy management in neonates admitted to the neonatal unit of a university teaching hospital in Southwest Ethiopia (Mizan-Tepi). Methods. Facility-based, unmatched case-control study was conducted among 240 (80 cases and 160 controls) in the Neonatal Intensive Care Unit of Mizan-Tepi University Teaching Hospital. Neonates with pathological jaundice and neonates without pathological jaundice were considered as cases and controls, respectively. Data were collected using a structured questionnaire, and extraction checklist, including information on maternal demographics, obstetrics, and neonatal factors. Simple random sampling techniques were used to select respondents. Bivariate and multivariable analyses were used to examine the association. Finally, statistical significance was declared at a P-value < .05. Results. In this study, 237 mothers with their neonates were included, making a response rate of 98.7%. The mean birth weight of cases and controls was 2330.3 ± 698.9 and 2699.3 ± 686.7 g, respectively. Hypothermia (AOR = 4.28; 95% CI: [1.72-10.67], cesarean delivery (AOR = 4.09; 95% CI: [1.69-9.93]), breast milk feeding (AOR = 2.97; 95% CI: [1.04-8.47]) and being male (AOR = 2.67; 95% CI: [1.17-6.13]) were significantly associated with jaundice. Conclusion. Most of the risk factors of neonatal jaundice were found to be modifiable. Therefore, early prevention and recognition of identified factors are recommended.

The Effect of Probiotics on Phototherapy for Bilirubin Reduction in Term Neonates: A Randomized Controlled Trial.

BACKGROUND: This interventional study aimed to assess the impact of combining probiotics with phototherapy compared to using phototherapy alone on bilirubin reduction in term neonates hospitalized in neonatal wards in hospitals of western Iran. METHODS: This clinical trial study included 150 term neonates with a gestational age of 37 to 42 weeks, birth weight of more than 2500 g, and diagnosed with neonatal jaundice. Patients were equally assigned to two groups of phototherapy (wavelength 420-450 nm) with oral probiotics (PediLact drop, 10 drops daily) and phototherapy alone through a simple random sampling method. Serum bilirubin levels (SBL) at the time of intervention, and 24, 48, and 72 hours later, duration of phototherapy, duration of hospitalization, and the need for blood transfusion were compared in the two groups. We used t-test and repeated analysis of variance to compare continuous variables. SPSS24 software was used to analyze the data. The significance level was set as 0.05. RESULTS: There was no statistically significant difference found between the two groups regarding basic variables, gender, birth weight, gestational age, maternal age, and neonatal age at hospitalization time. On the first day of hospitalization, the mean serum bilirubin level (SBL) in the combinatory therapy group was 15.6 ± 1.7 mg/dl, while in the monotherapy group, it was 15.8 ± 1.6 mg/dl (p=0.584). On the second day, the mean SBL in the combinatory therapy group was 11.2 ± 2.2, whereas in the monotherapy group, it was 12.4 ± 2.1. By the third day, these levels were 7.2 ± 0.9 and 7.8 ± 0.7, respectively, with a statistically significant difference between the two groups. Repeated analysis of variance testing confirmed a statistically significant decrease in serum bilirubin levels in both groups. The average length of hospital stay for the combinatory therapy group was 2.4 ± 0.5 days, compared to 2.8 ± 0.6 days in the phototherapy group (p = 0.001). In terms of phototherapy duration, the combinatory therapy group received treatment for 26.2 ± 9.9 hours, while the phototherapy group received it for 31.4 ± 10.3 hours (p = 0.001). CONCLUSION: The findings of the present study indicate that incorporating oral probiotics into phototherapy for neonatal jaundice (icterus) treatment is associated with a reduction in phototherapy duration and hospital stay.

Current status of neonatal jaundice management in Japan.

BACKGROUND: This nationwide survey aimed to determine the status of jaundice management in Japan. METHODS: A questionnaire about bilirubin level measurements and neonatal jaundice treatment was sent to 330 institutions providing neonatal care. The responses were analyzed according to institution level. RESULTS: Of 330 institutions, 172 responded (52.1% response rate). Total bilirubin levels were measured in the central laboratory using spectrophotometry at 134 institutions and a blood gas analyzer at 81 institutions. Unbound bilirubin (UB) levels were measured by 79 institutions, while transcutaneous bilirubin measurements were taken at 63 institutions. There was no association between institution level and UB or transcutaneous bilirubin measurement. For phototherapy criteria, the Murata-Imura criteria were adopted by 67 institutions, Nakamura criteria by 36, and Morioka criteria by 39. Light-emitting diodes (LED) were used by 160 institutions versus fluorescent lights by 31. When a blue LED was used, 119 institutions used the high mode. There is no standard for increasing light intensity. No association was found between institution level and phototherapy criteria. UB was measured in 14 of 63 institutions using the Murata-Imura criteria. CONCLUSIONS: There is a large variation in the management and treatment of neonatal jaundice among institutes in Japan.

A wireless physiological parameter monitoring system with a treatment feedback function during neonatal phototherapy.

Objective. Neonatal jaundice is a common condition in the early stages of newborns, and phototherapy is a fast, safe and effective method that is used to treat it. However, recent studies have shown that phototherapy may elicit side effects in infants, such as hypothermia, hyperthermia and dehydration. To improve the quality of phototherapy and the prognosis of patients, the changes in neonatal physiological parameters during phototherapy should be monitored to give better feedback to pediatricians or the phototherapy system. However, the current standard of clinical care during neonatal phototherapy with hard-wired devices limits this realization.Approach. Here, we developed a prototype of a neonatal wearable device, which can wirelessly potentially monitor the jaundice value, transepidermal water loss, skin wettedness factor and body orientation during phototherapy, and conducted prototype validation experiments. We also set up user-friendly interfaces and an analysis system on custom software, all designed to make the future addition of data interfaces for treatment feedback functions easier.Main results. The preliminaryin vitroexperiment demonstrated the effectiveness of simultaneous monitoring of the required physiological parameters. And further suggestions and specific operations are discussed in terms of optimization of the treatment of neonatal jaundice.Significance. It is believed that the established system has the potential to provide a basis for future phototherapy nursing guidelines and physiological monitoring standards.

The Accuracy of Transcutaneous Bilirubin as a Screening Test in Preterm Infants.

OBJECTIVE: To determine the accuracy of transcutaneous bilirubin (TcB) to predict total serum bilirubin (TSB) in preterm infants across gestational age (GA) ranges and to calculate the cost-effectiveness of TcB as the primary screening test of choice for neonatal jaundice in neonatal intensive care unit (NICU) settings. METHODS: Single-center retrospective study of infants aged ≤ seven days admitted to the NICU over a six-month period with a paired TSB and TcB, with or without phototherapy as part of their routine clinical care. Infants were divided into GA-specific groups as term, late preterm, moderate preterm, and very preterm. Measurement bias (bias=TSB-TcB) was calculated on the paired TSB and TcB values, and a Bland-Altman analysis was carried out. The impacts of additional infant-specific variables on the bias were assessed with univariate and multivariate linear regression techniques. The potential direct cost savings associated with the use of TcB as the primary screening test were calculated. RESULTS: A total of 263 paired TSB and TcB samples from 95 patients were included (130 paired samples from term (n=60), 75 from late preterm (n=21), 27 from moderate preterm (n=7), and 31 from very preterm (n=7)). The mean paired measurement bias across all the GA groups was -0.9 ± 2.9 mg/dL. The sensitivity and specificity of TcB in GA < 35 weeks were 92% and 62%, respectively. A conservative estimate of a one-third reduction in TSB measurement by using TcB as the primary screening test will have a direct cost saving of $3,148 over a six-month period. CONCLUSION: Our data suggest that TcB is a safe and potentially cost-effective screening test for jaundice across GA groups.

Effectiveness and safety of prophylactic phototherapy to prevent jaundice in premature newborns: Systematic review and meta-analysis.

To determine the effectiveness and safety of prophylactic phototherapy compared with conventional phototherapy for the prevention of neonatal jaundice. We included clinical trials comparing prophylactic phototherapy to conventional phototherapy to prevent jaundice in premature newborns. We searched Embase, MEDLINE, LILACS, Central, and others. The statistical analysis was performed in RevMan (Review Manager 5.3). Outcomes were analyzed according to the type of variable: risk difference (RD) and mean difference (MD). A random effects model was used due to heterogeneity. We reported results in forest plots. Risk of bias was evaluated, and a sensitivity analysis was made. 1127 articles were found, and six studies (2332 patients) were included in the meta-analysis. Five studies evaluated the need for exchange transfusion as the primary outcome RD -0.01, 95% CI [-0.05 to 0.03]. One study evaluated bilirubin encephalopathy RD -0.04, 95% CI [-0.09 to 0.00]. Five studies evaluated the duration of phototherapy, MD 38.47, 95% CI [1.28 to 55.67]. Four studies evaluated levels of bilirubin (MD -1.23, 95% CI [-2.25 to -0.21]. Two studies evaluated mortality, RD 0.01, 95% CI [-0.03 to 0.04]. As a conclusion, compared to conventional phototherapy, prophylactic phototherapy decreases the last measured level of bilirubin, as well as the probability of neurodevelopmental disturbances. However, it increases phototherapy duration.

Implementation of neonatal phototherapy with the BiliCocoon Bag® device in the maternity ward and impact on mother-infant separation.

BACKGROUND: Free bilirubin jaundice is a frequent pathology in the neonatal period. The major complication is neurological toxicity, the most severe form of which is kernicterus. Overall, 5%-10% of jaundiced neonates require treatment. The first-line treatment is phototherapy, with intensive phototherapy being the gold standard. Other equipment is also available, including the BiliCocoon Bag®. It is a safe and controlled therapy that can be performed in the mother's room in the maternity ward, thereby avoiding separation and allowing for breast- or bottle-feeding during treatment. It is easy to install and does not require protective glasses, thus no scope or hospitalization. In our maternity ward, all neonates requiring intensive phototherapy are hospitalized in the neonatology ward. OBJECTIVE: The objective of our study was to evaluate the number of avoided hospitalizations in neonatology for free bilirubin jaundice since the introduction, according to a strict protocol, of the BiliCocoon Bag® device. MATERIAL AND METHOD: This was a single-center retrospective cohort study using data of newborns usually collected as part of standard care. Children born in our maternity ward during an 18-month period (August 1, 2020 to January 31, 2022) were included. Causes of jaundice, age at the beginning and mode of treatment, number of sessions for each device, and length of stay were compared. Results are presented as number and percentage with median (25th-75th) or mean (extremes) values for categorical and continuous variables, respectively. A t-test was used to compare the means of the independent groups. RESULTS: A total of 316 newborns were included. Physiological jaundice was the main cause of jaundice. The median age for the first phototherapy treatment was 54.5 h (30-68). The 316 neonates needed 438 phototherapy sessions: 235 (74%) neonates required only one phototherapy session, 85 (36%) of them were treated with the BiliCocoon Bag®. For the 81 children who needed two or more phototherapy sessions, 19 children (23.5%) were treated by tunnel phototherapy and then the BiliCocoon Bag®, and eight children (10%) by BiliCocoon Bag® alone. The BiliCocoon Bag® enabled a relative reduction in the hospitalization rate of 38% and avoided hospitalization for approximately one third of the newborns treated. The BiliCocoon Bag® failure rate was 3.6% and the average length of stay was comparable between the two types of treatment. CONCLUSION: Following a strict protocol of use, the BiliCocoon Bag® is a reliable method and a good alternative to intensive phototherapy for newborns in the maternity ward, as it avoids hospitalization and mother-infant separation.

Oral fenofibrate for hyperbilirubinemia in term neonates: A single-blind randomized controlled trial.

Background: Hyperbilirubinemia is common in the neonatal period; however, delayed diagnosis or inadequate treatment can cause irreparable damage to the neonates. We aimed to evaluate the efficacy of oral fenofibrate for hyperbilirubinemia in term neonates. Methods: This single-blind randomized controlled trial included 86 term neonates aged 3-7 days, with birth weight ≥2500 g, admitted to Bandar Abbas Children's Hospital, Bandar Abbas Iran, from July 23, 2019, to July 22, 2020. The fenofibrate group received 10 mg/kg oral fenofibrate and phototherapy, while controls only received phototherapy. Serum total bilirubin was measured at 24 and 48 h and at the time of discharge. Hospital length of stay was also noted. Results: The two study groups were comparable regarding age, gender, gestational age, birth weight, and baseline total serum bilirubin levels. Serum total bilirubin levels at 48 h (P < 0.001) and at discharge (P < 0.001) were significantly lower in the fenofibrate group compared to controls. Although hospital length of stay was lower in the fenofibrate group compared to controls, the difference was not statistically significant (P = 0.612). Fenofibrate was more effective on the reduction of serum bilirubin in neonates aged 3-4.5 days starting at the 24th hour. Moreover, it was more effective in female neonates compared to males starting at the 48th hour. Conclusions: A single dose of oral fenofibrate reduced total serum bilirubin in term neonates with hyperbilirubinemia without any side effects; however, this effect was more prominent after 48 h.

Corrigendum: Management challenges in the treatment of severe hyperbilirubinemia in low-and middle-income countries: encouraging advancements, remaining gaps, and future opportunities.

[This corrects the article DOI: 10.3389/fped.2023.1001141.].

Jaundice and its associated factors among neonates admitted to selected referral hospitals in southwest oromia, Ethiopia: Multi-center cross-sectional study.

Background: Jaundice is a common clinical problem during the first month of birth throughout the world. Mainly, it is the leading cause of neonatal morbidity and mortality in developing countries. Objectives: The aimed of this studied was to assess predictors of jaundice among neonates admitted to selected referral hospitals in southwest Oromia, Ethiopia, 2021. Methods: An Institutional based cross-sectional study was implemented among 205 admitted neonates at selected referral hospitals in southwest Oromia, Ethiopia from October 05 to November 5, 2021. Jimma medical center (JMC), Wollega University referral hospital (WURH), and Ambo University Referral hospital (AURH) were selected by simple random sampling technique. A pretested structured interviewer-administered questionnaire and medical record review was used to collect data. Both binary and multivariable logistic regression analyses were performed to identify factors associated with neonatal jaundice. Logistic regression analyses were performed to identify factors associated with neonatal jaundice. Statistical Significance was declared at P-value less than 0.05 in the final model, and if the confidence interval does not include the null hypothesis value. Results: The prevalence of neonatal jaundice was 20.5% (95%CI: 1.74-1.85). The mean age of neonates was 8.6 ± 7.8 days. Traditional medicine use during current pregnancy (AOR: 5.62, 95%CI: 1.07, 9.52), Rh incompatibility (AOR: 0.045, 95%CI: 0.01, 0.21), gestational age (AOR: 4.61, 95%CI: 1.05, 10.3), premature rupture of membrane (AOR: 3.76, 95%CI: 1.58, 8.93) and hypertension (mother) (AOR: 3.99, 95%CI: 1.13, 14.02) were factors significantly associated with neonatal jaundice. Conclusion: Neonatal jaundice was relatively higher in the current study. Traditional medicine use, Rh incompatibility, premature ruptures of membrane, hypertension, and preterm gestational age were factors associated with neonatal jaundice.

Associations between neonatal jaundice and autism spectrum disorder or attention deficit hyperactivity disorder: Nationwide population based cohort study.

BACKGROUND/PURPOSE: Neonatal jaundice might result brain insults. Both autistic spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are developmental disorders, which might result from early brain injury at neonatal period. We aimed to explore the association between neonatal jaundice treated with phototherapy and the ASD or ADHD. METHODS: This retrospective nationwide population cohort study was based on a nationally representative database of Taiwan, and neonates born from 2004 to 2010 were enrolled. All eligible infants were divided into 4 groups, without jaundice, jaundice with no treatment, jaundice with simple phototherapy only and jaundice with intensive phototherapy or blood exchange transfusion (BET). Each infant was follow-up until the date of incident primary outcomes, death, or 7-year-old, whichever occurred first. Primary outcomes were ASD, ADHD. Using cox proportional hazard model to analyze their associations. RESULTS: In total, 118,222 infants with neonatal jaundice were enrolled, including diagnosed only (7260), simple phototherapy (82,990), intensive phototherapy or BET (27,972 infants). The cumulative incidences of ASD in each group was 0.57%, 0.81%, 0.77%, and 0.83%, respectively. The cumulative incidences of ADHD in each group was 2.83%, 4.04%, 3.52% and 3.48%, respectively. Jaundice groups were significantly associated with ASD, ADHD, or either one, even after all other extraneous maternal and neonatal variables were adjusted. After stratification, the associations were still existed in subgroup with birth weights ≥2500 grams and in male subgroup. CONCLUSION: Neonatal jaundice correlated with the ASD and ADHD. The associations were significant in infants of both sexes and with birth weights larger than 2500 grams.

Integrated analysis of microbiota with bile acids for the phototherapy treatment of neonatal jaundice.

Introduction: Infant jaundice is a common condition which results from a high concentration of serum bilirubin. Phototherapy is a widely used treatment for bilirubin clearance. We analyzed the effect of phototherapy on intestinal flora and metabolism of newborns. The aim was to assess the benefit of treatment for hyperbilirubinemia with phototherapy. Material and methods: Fifty-three jaundiced infants hospitalized at our neonatal intensive care unit were treated with phototherapy. Of them, 29 were prescribed antibiotics during the hospitalization. Fecal samples were collected before and 24 h and 48 h after phototherapy. The bacterial species and relative abundance were identified with Macrogene sequencing. The bile acids in feces were identified using liquid chromatography-mass spectroscopy (LC-MS). Results: Differential microbial species/genera and secondary bile acids were found after phototherapy. There are significant differences in the changes of the microbial species/genera between infants who did not receive antibiotic treatment and those who were given antibiotic treatment. Secondary bile acids were also significantly altered. At the same time, the differential microbial species/genera and the differential secondary bile acids interacted with each other. Conclusions: This study identified several differential intestinal microbial species and secondary bile acids in fecal samples from infants with jaundice before and after phototherapy. Phototherapy can change the flora and its metabolism and its long-term impact needs further observation.

Management challenges in the treatment of severe hyperbilirubinemia in low- and middle-income countries: Encouraging advancements, remaining gaps, and future opportunities.

Neonatal jaundice (NJ) is common in newborn infants. Severe NJ (SNJ) has potentially negative neurological sequelae that are largely preventable in high resource settings if timely diagnosis and treatment are provided. Advancements in NJ care in low- and middle-income countries (LMIC) have been made over recent years, especially with respect to an emphasis on parental education about the disease and technological advancements for improved diagnosis and treatment. Challenges remain, however, due to lack of routine screening for SNJ risk factors, fragmented medical infrastructure, and lack of culturally appropriate and regionally specific treatment guidelines. This article highlights both encouraging advancements in NJ care as well as remaining gaps. Opportunities are identified for future work in eliminating the gaps in NJ care and preventing death and disability related to SNJ around the globe.

Intrapartum Maternal Prophylactic Antimicrobial Treatment and Neonatal Jaundice.

Intrapartum antibiotics are widely used and may potentially affect bilirubin levels and neurotoxicity in the newborn. The aim of this study was to examine the effect of intrapartum antibiotic exposure on neonatal jaundice. We retrospectively collected data from 972 neonates born to 963 mothers. Five hundred forty-five mothers (56.6%) received intrapartum antibiotics. There were no statistically significant differences in maximum bilirubin level (7.82 ± 3.65 vs 7.63 ± 3.71, P = .43) or need for phototherapy (9 [1.62%] vs 4 [0.94%], P = .52) between exposed and non-exposed newborns. The rate of phototherapy was significantly higher only in the group of infants born to mothers who received broad-spectrum antibiotics at 2 to 3.9 hours prior to delivery (χ2 = 10.453, P = .015) and was not higher in the group of exposure >4 hours, which may represent a short transient effect of antibiotics exposure on bilirubin turnover. Further studies are needed to validate this finding.

Neonatal Phototherapy and Clinical Characteristics: The Danish National Patient Registry 2000-2016.

Purpose: Phototherapy is the standard treatment for neonatal hyperbilirubinemia. It is important to collect data on phototherapy to support research related to the efficacy and safety of phototherapy. We explored the registration of phototherapy in the Danish National Patient Registry (DNPR) and the clinical characteristics of neonates treated with phototherapy. Methods: We identified children born alive in Denmark from 1 January 2000 through 30 November 2016 from the DNPR (N=1,044,502). We calculated the proportion of children registered that received phototherapy during the neonatal period and examined temporal trends, both nationwide and at the level of individual hospitals. In a sub-cohort of children born at Aarhus University Hospital (AUH) in 2002-2016 (N=71,781), we analyzed the proportions of children registered that received phototherapy, according to sex, gestational age, birth weight, and neonatal characteristics, like Apgar score, birth asphyxia, and infections. Results: We identified 11,295 (1.1%) registered that received phototherapy. The proportions of children registered that received phototherapy differed among hospitals (range: 0 to 4.1%). Nationwide registration was low during the study period, but it increased to 1.8% in 2016. For the AUH sub-cohort the proportion of children registered with phototherapy averaged 4.4% (N=3182, range:3.9-5.1%). The proportion of children registered with phototherapy was inversely correlated with gestational age and birth weight, and positively correlated with neonatal characteristics, including low Apgar score, birth asphyxia, and infections. Conclusion: Phototherapy was under-reported in the DNPR and the proportions of children registered that received phototherapy differed among hospitals. The non-compulsory policy for reporting treatment and care in hospitals to the DNPR might explain the variation. The most consistent reporting was observed among children born in an university hospital, where 4.4% of children registered that received phototherapy, and phototherapy was inversely associated with gestational age, birth weight, and positively associated with clinical characteristics like birth asphyxia, and infections.

Determination of Serum Unbound Bilirubin and Its Clinical Application Value in Neonates / 中山大学学报(医学科学版)

ObjectiveTo investigate the clinical appropriateness and application value of the peroxidase （POD） method for the detection of unbound bilirubin （UB） in neonatal serum. MethodsHydrogen peroxide （0.33 mol/L） and three different final concentrations （0.019， 0.038， 0.075 μg/mL） of horseradish peroxidase （HRP） were added to standard bilirubin solution （1， 2， 3 μmol/L） to obtain a standardized HRP primary rate constant Kp. Then 25 μL of neonatal serum was diluted by 41.6 fold， and measured with 2.4 and 4.8 μg/mL HRP at 37 ℃ under the dark， to determine the UB concentration. The accuracy， precision， and stability of the methodology were validated. The clinical characteristics of 33 jaundiced neonates were collected， including total serum bilirubin （TSB）， indirect bilirubin （IDB）， albumin （ALB）， bilirubin to albumin molar ratio （BAMR）， etc. The experimental data were analyzed by Graphpad Prism 8.0. ResultsA standardized Kp of （7.20±1.08） mL·μg-1·min-1 was determined at pH 7.4±0.2， 37 ℃ in the dark. The HRP activity and UB concentrations remained stable at -20 ℃ for 3 weeks and a week， respectively. The mean intra-day and inter-day coefficients of variation of the serum samples with different UB concentrations were less than 10%. In this study， the UB concentrations in 33 jaundiced neonates （gestational age ≥35 weeks） were measured by the POD method in the range of （0.32～1.20） μg/dL， which was positively correlated with TSB， IDB and BAMR. Of the five infants whose UB concentrations measured more than 1 μg/dL， three received intensive phototherapy （60%）. ConclusionsThe POD method combined with a standard equipment spectrophotometer to detect serum UB concentrations in neonates is easy to operate， rapid to detect， and low cost. This method has good accuracy and precision， which is convenient for clinical implementation. Moreover， the measurement of serum UB may assist us in better management of neonatal jaundice in clinical practice.