Minocycline attenuates the bilirubin-induced developmental neurotoxicity through the regulation of innate immunity and oxidative stress in zebrafish embryos.

When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic organisms. Firstly, our results suggested that bilirubin exposure markedly decreased the survival rate, induced the developmental toxicity and increased the yellow pigment deposited in the zebrafish tail. Meanwhile, the number of macrophages and neutrophils was substantially reduced in a concentration-dependent manner. Besides, the antioxidant enzyme activities were greatly elevated while the inflammatory genes were significantly decreased after bilirubin exposure. Secondly, transcriptome analysis identified 708 genes were differentially expressed after bilirubin exposure, which animal organ morphogenesis, chemical synaptic transmission, and MAPK / mTOR signaling pathways were significantly enriched. Thirdly, bilirubin exposure leads to a significant decrease in the motility of zebrafish, including a dose-dependent decrease in the travelled distance, movement time, and average velocity. Moreover, the innate immune genes and apoptosis-related genes such as TLR4, NF-κB p65, STAT3 and p53 were elevated at a concentration of 10 µg/mL of bilirubin. Finally, our results further revealed that the anti-inflammatory and neuroprotective minocycline could partially rescue the bilirubin-induced neurobehavioral disorders in zebrafish embryos. In conclusion, our study explored the bilirubin-induced immunotoxicity and neurotoxicity in aquatic organisms, which will provide a theoretical basis for the treatment of neonatal jaundice in clinical practice.

Neonatal jaundice incidence, risk factors and outcomes in referral-level facilities in Nigeria.

OBJECTIVE: To determine the incidence, risk factors and outcomes of babies with neonatal jaundice in a network of referral-level hospitals in Nigeria. DESIGN: A cross-sectional analysis of perinatal data collected over a 1-year period. SETTING: Fifty-four referral-level hospitals (48 public and 6 private) across the six geopolitical zones of Nigeria. POPULATION: A total of 77 026 babies born at or admitted to the participating facilities (67 697 hospital live births; plus 9329 out-born babies), with information on jaundice between 1 September 2019 and 31 August 2020. METHODS: Data were extracted and analysed to calculate incidence and sociodemographic and clinical risk factors for neonatal jaundice. MAIN OUTCOME MEASURES: Incidence and risk factors of neonatal jaundice in the 54-referral hospitals in Nigeria. RESULTS: Of 77 026 babies born in or admitted to the participating facilities, 3228 had jaundice (41.92 per 1000 live births). Of the 67 697 hospital live births, 845 babies had jaundice (12.48 per 1000 live births). The risk factors associated with neonatal jaundice were no formal education (adjusted odds ratio [aOR] 1.68, 95% CI 1.11-2.52) or post-secondary education (aOR 1.17, 95% CI 0.99-1.38), previous caesarean section (aOR 1.68, 95% CI 1.40-2.03), booked antenatal care at <13 weeks or 13-26 weeks of gestation (aOR 1.58, 95% CI 1.20-2.08; aOR 1.15, 95% CI 0.93-1.42, respectively), preterm birth (aOR 1.43, 95% CI 1.14-1.78) and labour more than 18 hours (aOR 2.14, 95% CI 1.74-2.63). CONCLUSIONS: Hospital-level and regional-level strategies are needed to address newborn jaundice, which include a focus on management and discharge counselling on signs of jaundice.

Continuous versus intermittent phototherapy in treatment of neonatal jaundice: a randomized controlled trial.

Phototherapy (PT) is a widely used treatment for neonatal jaundice, yet the ideal model of application remains controversial. In this study, the effects of continuous phototherapy (CPT) and intermittent phototherapy (IPT) models were compared in the treatment of neonatal indirect hyperbilirubinemia (IHB) and whether IPT is a superior modality is investigated. Single-centre parallel randomized controlled open label trial. A computer-based table of random numbers was used to allocate treatments. Newborns ≥ 34 weeks' gestation who received phototherapy in our neonatal intensive care unit (NICU) between July 2022 and April 2023 were included. CPT was applied continuously for 6 h, and IPT was applied as 2 cycles of 1 h on and 2 h off in a 6-h session. Rebound TSB was measured 8 h after phototherapy was stopped in both groups. Phototherapy duration, TSB reduction rate and rebound bilirubin rate were compared between intervention groups. One hundered and four neonates met the inclusion criteria during the study period. CPT and IPT were each used in 52 newborns. Demographic characteristics of the study groups, including sex, mode of delivery, birth weight, admission weight, age at postnatal presentation, diet, discharge weight, and history of PT in siblings, were similar (p > 0.05). The most common cause of IHB in both groups was ABO incompatibility. The median phototherapy time was 12 h (6-15) in the CPT group and 4 h (2-4) in the IPT group (p < 0.001). The mean rate of bilirubin decrease was 1.12 ± 0.73 mg/dl/h in those who underwent IPT and 0.51 ± 0.33 mg/dl/h in those who underwent CPT (p < 0.001). The mean rebound bilirubin rate 8 h after phototherapy was 0.08 ± 0.28 mg/dl/h in the CPT group, and -0.01 ± 0.17 mg/dl/h in the IPT group (p = 0.039). The length of hospital stay was longer in the CPT group (p = 0.032). Skin rash, diarrhoea and increased body temperature were less frequent in the IPT group (p < 0.001). CONCLUSIONS: In this study, IPT was found to be at least as effective as CPT in reducing total serum bilirubin. Even though the duration of PT is shorter in IPT, the slower rate of rebound bilirubin, shorter hospital stays and lower incidence of side effects indicated that intermittent phototherapy is superior to continuous phototherapy. Choosing IPT over CPT is a more rational approach in neonatal jaundice. CLINICALTRIALS: gov Identifier: NCT06386731 (registered retrospectively on 23/04/2024) What is Known: • PT is common used in the treatment of neonatal jaundice. • There is no standard model of application for PT. WHAT IS NEW: • The IPT model is as effective as CPT. • Newborns are discharged faster with IPT.

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.

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 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: - probably reduces readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - may have little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - probably increases the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - may have 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 probably reduces hospital readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening may have little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening probably increases the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening may have 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.

Factors associated with neonatal jaundice among neonates admitted at referral hospitals in northeast Ethiopia: a facility-based unmatched case-control study.

BACKGROUND: Neonatal jaundice is a significant contributor to illness and death in newborns, leading to frequent admissions to neonatal intensive care units. To better understand this issue, a study was conducted to identify the factors contributing to neonatal jaundice among newborns admitted to Dessie and Woldia comprehensive specialized hospitals in northeast Ethiopia. METHODS: The study took place from April 1 to May 30, 2022, using unmatched case-control design. A total of 320 neonates paired with their mothers were involved, including 64 cases and 256 controls. Data were collected through a structured interviewer-administered questionnaire and a review of medical records. The collected data were analyzed using SPSS Version 23, and a multivariate logistic regression model was employed to understand the relationship between independent factors and the occurrence of neonatal jaundice. Statistical significance was determined at a threshold of P value less than 0.05. RESULTS: The study findings revealed that maternal age over 35 years, residing in urban areas [adjusted odds ratio (AOR) = 2.4, 95% confidence interval (CI): 1.23, 4.82], male gender (AOR = 4.3, 95% CI: 1.90, 9.74), prematurity (AOR = 3.9, 95% CI: 1.88, 8.09), and ABO incompatibility (AOR = 2.6, 95% CI: 1.16, 5.96) were significant determinants of neonatal jaundice. Conversely, the study indicated that cesarean birth was associated with a 76% lower likelihood of infant jaundice compared to vaginal delivery (AOR = 0.24, 95% CI: 0.08, 0.72). CONCLUSION: To prevent, diagnose, and treat neonatal jaundice effectively, efforts should primarily focus on managing ABO incompatibility and early detection of prematurity. Additionally, special attention should be given to neonates born through vaginal delivery, those with mothers over 35 years old, and those residing in urban areas, as they are at higher risk of developing newborn jaundice. Close monitoring of high-risk mother-infant pairs during the antenatal and postnatal periods, along with early intervention, is crucial for reducing the severity of neonatal jaundice in this study setting.

Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses.

Phototherapy is the standard treatment for neonatal jaundice. We aimed to review the efficacy and safety of fenofibrate as an adjunct therapy. Twelve databases were searched and a systematic review and meta-analysis were conducted. Mean change (MC), mean difference (MD), and risk ratios (RR) with a 95% confidence interval (CI) were calculated using a random effects model. The GRADE approach was used to evaluate the evidence's certainty. Nine randomized trials were included. The MC of total serum bilirubin (mg/dL) was significant at 12, 24, 36, 48, and 72 h with respective MC (95% CI) values of -0.46 (-0.61, -0.310), -1.10 (-1.68, -0.52), -2.06 (-2.20, -1.91), -2.15 (-2.74, -1.56), and -1.13 (-1.71, -0.55). The FEN + PT group had a shorter duration of phototherapy (MD: -14.36 h; 95% CI: -23.67, -5.06) and a shorter hospital stay (MD: -1.40 days; 95% CI: -2.14, -0.66). There was no significant difference in the risk of complications (RR: 0.89; 95% CI: 0.54, 1.46) or the need for exchange transfusion (RR: 0.58; 95% CI: 0.12, 2.81). The certainty of the evidence was very low for all outcomes. In conclusion, fenofibrate might be a safe adjunct to neonatal phototherapy. Larger randomized controlled trials are needed for the confirmation of these results.

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.

Comparison of Transcutaneous and Total Serum Bilirubin Measurements at Five Different Sites in Newborns before and after Phototherapy.

OBJECTIVE: This study aims to examine the accuracy of transcutaneous bilirubin (TcB) in estimating the total serum bilirubin (TSB) level at five different sites before and immediately after phototherapy. METHODS: This study prospectively enrolled infants with a gestational age of 34 to 416/7 weeks who were clinically diagnosed with neonatal jaundice and required phototherapy within 28 days after birth. TcB levels were measured on the uncovered four areas (forehead, mid-sternum, abdomen, and interscapular site) and covered hipbone by using the Dräger JM-103 Jaundice Meter before phototherapy and at 0 min after discontinuing phototherapy. Correlation and agreement between TcB and TSB levels were assessed before and after phototherapy. RESULTS: We included 108 infants with a mean gestational age of 37.6±1.5 weeks and birth weight of 3108±548 g. A strong significant correlation was found between TSB and TcB measurements at all five sites before phototherapy with the strongest correlation at the interscapular site (r=0.768, p=0.001). The correlation was weakened between TSB and TcB at all five sites after phototherapy; however, the strongest correlation was at the covered hipbone (r=0.619, p=0.001). TcB measurements at all five sites tended to underestimate TSB levels before and after phototherapy. The difference (TcB - TSB) tended to increase with increasing TSB levels. CONCLUSIONS: TcB levels were most accurately measured at the interscapular site and covered hipbone before and immediately after phototherapy, respectively.

Neonatal jaundice detection in low-resource Mexican settings: possibilities and barriers for innovation with mobile health.

BACKGROUND: Neonatal jaundice is a common condition that can lead to brain damage and disabilities when severe cases go undetected. Low- and middle-income countries often lack accurate methods for detecting neonatal jaundice and rely on visual assessment, resulting in a higher incidence of adverse consequences. Picterus Jaundice Pro (Picterus JP), an easy-to-use and affordable smartphone-based screening device for the condition, has demonstrated higher accuracy than visual assessment in Norwegian, Philippine and Mexican newborns. This study aimed to identify the barriers and facilitators to implementing Picterus JP in public health services in low-income settings in Mexico by exploring the current process of neonatal jaundice detection and stakeholders' perspectives in that context. METHODS: Qualitative data collection techniques, including one focus group, 15 semi-structured interviews and four observations, were employed in urban and rural health facilities in Oaxaca, Mexico. The participants included medical doctors, nurses and health administrators. The data were analysed by thematic analysis guided by the Consolidated Framework for Implementation Research. RESULTS: The analysis yielded four main themes: (I) the current state of neonatal care and NNJ detection, (II) the needs and desires for enhancing NNJ detection, (III) the barriers and facilitators to implementing Picterus JP in the health system and (IV) HCWs' expectations of Picterus JP. The findings identify deficiencies in the current neonatal jaundice detection process and the participants' desire for a more accurate method. Picterus JP was perceived as easy to use, useful and compatible with the work routine, but barriers to adoption were identified, including internet deficiencies and costs. CONCLUSIONS: The introduction of Picterus JP as a supporting tool to screen for neonatal jaundice is promising but contextual barriers in the setting must be addressed for successful implementation. There is also an opportunity to optimise visual assessment to improve detection of neonatal jaundice.

Phototherapy causing a purpuric eruption in a neonate.

Neonatal jaundice is a frequent condition in newborns and is commonly treated with phototherapy. We describe the case of a neonate with hemolytic disease of the newborn who developed a rarely described purpuric eruption. Laboratory testing revealed elevated porphyrins.

Signal Quality in Continuous Transcutaneous Bilirubinometry.

Bilirubin is a product of the metabolism of hemoglobin from red blood cells. Higher levels of bilirubin are a sign that either there is an unusual breaking down rate of red blood cells or the liver is not able to eliminate bilirubin, through bile, into the gastrointestinal tract. For adults, bilirubin is occasionally monitored through urine or invasive blood sampling, whilst all newborns are routinely monitored visually, or non-invasively with transcutaneous measurements (TcBs), due to their biological immaturity to conjugate bilirubin. Neonatal jaundice is a common condition, with higher levels of unconjugated bilirubin concentration having neurotoxic effects. Actual devices used in TcBs are focused on newborn populations, are hand-held, and, in some cases, operate in only two wavelengths, which does not necessarily guarantee reliable results over all skin tones. The same occurs with visual inspections. Based on that, a continuous bilirubin monitoring device for newborns is being developed to overcome visual inspection errors and to reduce invasive procedures. This device, operating optically with a mini-spectrometer in the visible range, is susceptible to patient movements and, consequently, to situations with a lower signal quality for reliable bilirubin concentration estimates on different types of skin. Therefore, as an intermediate development step and, based on skin spectra measurements from adults, this work addresses the device's placement status prediction as a signal quality indication index. This was implemented by using machine learning (ML), with the best performances being achieved by support vector machine (SVM) models, based on the spectra acquired on the arm and forehead areas.

What Happens in the Gut during the Formation of Neonatal Jaundice-Underhand Manipulation of Gut Microbiota?

Jaundice is a symptom of high blood bilirubin levels affecting about 80% of neonates. In neonates fed with breast milk, jaundice is particularly prevalent and severe, which is likely multifactorial. With the development of genomics and metagenomics, a deeper understanding of the neonatal gut microbiota has been achieved. We find there are accumulating evidence to indicate the importance of the gut microbiota in the mechanism of jaundice. In this paper, we present new comprehensive insight into the relationship between the microbiota and jaundice. In the new perspective, the gut is a crucial crossroad of bilirubin excretion, and bacteria colonizing the gut could play different roles in the excretion of bilirubin, including Escherichia coli as the main traffic jam causers, some Clostridium and Bacteroides strains as the traffic police, and most probiotic Bifidobacterium and Lactobacillus strains as bystanders with no effect or only a secondary indirect effect on the metabolism of bilirubin. This insight could explain why breast milk jaundice causes a longer duration of blood bilirubin and why most probiotics have limited effects on neonatal jaundice. With the encouragement of breastmilk feeding, our perspective could guide the development of new therapy methods to prevent this side effect of breastfeeding.

The Effect of Tub Bathing on the Skin and Bilirubin Levels of Babies Receiving Tunnel and Light-Emitting Diode Phototherapies: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of tub bathing on the skin and bilirubin levels of newborns receiving tunnel and light-emitting diode phototherapy. METHODS: In this randomized controlled trial, hospitalized newborns diagnosed with hyperbilirubinemia treated with a tunnel or light-emitting diode device were randomly assigned to either the experimental (bath) or control (no bath) groups using a computer program. The skin integrity moisture balance of all groups was recorded using the Newborn Skin Condition Score at 6, 12, and 24 hours after phototherapy, and their total serum bilirubin measurements were evaluated. RESULTS: A statistically significant difference was observed in the babies' total serum bilirubin levels; this decrease was the highest in the experimental groups. Further, the skin integrity-moisture balance was higher in the experimental groups than in the control groups; it was highest in the tunnel-experimental group and lowest in the tunnel control group. CONCLUSIONS: These results show that bathing is effective in reducing total bilirubin levels. This study adds to the evidence on skin integrity and moisture balance in newborns who were bathed during phototherapy.

Evaluation of Glucose 6-Phosphate Dehydrogenase, Pyruvate Kinase, and New Generation Inflammation Biomarkers in Prolonged Neonatal Jaundice.

Background and Objectives: To evaluate the clinical findings of glucose 6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiency in prolonged jaundice and to determine whether the systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) can be used in the diagnosis of neonatal prolonged jaundice. Materials and Methods: Among full-term neonates with hyperbilirubinemia who were admitted to Medicine Hospital between January 2019 and January 2024 with the complaint of jaundice, 167 infants with a serum bilirubin level above 10 mg/dL, whose jaundice persisted after the 10th day, were included in this study. Results: G6PD activity was negatively correlated with NLR, SII, age, and hematocrit (Hct). There was a weak negative correlation between G6PD and NLR and a moderate negative correlation between G6PD activity and SII when adjusted for age and Hct. PK activity showed no significant correlation with G6PD, NLR, PLR, SII, age, and Hct. A linear relationship was observed between G6PD activity and SII and NLR. Conclusions: NLR and SII can be easily calculated in the evaluation of prolonged jaundice in G6PD deficiency has a considerable advantage. NLR and SII levels may contribute by preventing further tests for prolonged jaundice and regulating its treatment. It may be useful to form an opinion in emergencies and in early diagnostic period.

The effect of phototherapy treatment on serum melatonin levels in term newborns.

Background/aim: The aim of this study was to investigate the effect of phototherapy treatment on serum melatonin levels in term newborn infants. Material and methods: This study was planned as a single-center, prospective, observational, case-control study. Term infants (gestation week ≥37 weeks) who received at least 6 h of phototherapy due to jaundice constitute the phototherapy group, while the term infants without jaundice and who were exclusively breastfed constitute the control group. Melatonin levels were examined by taking blood samples from babies in both groups at 02:00 at night. Melatonin values were compared between groups. The effect of phototherapy on serum melatonin levels was investigated. The relationship between the duration of phototherapy and maximum serum bilirubin values on melatonin values was investigated. Results: Seventy term infants (64.3% girls) were included in the study. Mean gestational week was 38.3 ± 1.1 weeks, mean birth weight was 3295 ± 434 g. There was no statistically significant difference between the phototherapy group and the control group in terms of sex, type of delivery, gestational week, birth weight, height, and head circumference (all p > 0.05). Serum melatonin level was 20.3 ± 5.9 pg/mL (range: 8.7-36.6 pg/mL) in the phototherapy group and 19.9 ± 4.38 pg/mL (range: 9.9-26.3 pg/mL) in the control group. There was no significant difference between the two groups in terms of serum melatonin levels (p = 0.155). The mean total bilirubin value was 17.65 ± 1.48 mg/dL, and the average duration of phototherapy application was 13.94 ± 7.64 h in the babies in the phototherapy group. No correlation was found between the duration of phototherapy application and serum melatonin levels (p = 0.791). Conclusion: It was determined that there was no significant difference in serum melatonin levels in term newborn babies who received phototherapy for at least 6 h due to jaundice. No correlation was found between the duration of phototherapy application and the serum melatonin level of the maximum bilirubin values.

Evidence Suggests a Decrease in the Incidence of Kernicterus in California.

We identified children diagnosed with kernicterus in the California Department of Developmental Services and estimated an incidence of 0.42 per 100 000 births from 1988 to 2014, significantly decreasing to 0.04 per 100 000 births after 2009. We also examined national infant kernicterus mortality from 1979 to 2016 using CDC data. It did not decrease significantly.

Maternal and neonatal safety of COVID-19 vaccination during the peri-pregnancy period: A prospective study.

BACKGROUND: To investigate the safety of inactivated COVID-19 vaccine in Chinese pregnant women and their fetuses when inoculated during the peri-pregnancy period. METHODS: Eligible pregnant women were prospectively collected and divided into a vaccine group (n = 93) and control group (n = 160) according to whether they had been vaccinated against COVID-19 within 3 months before their last menstruation period (LMP) and after pregnancy. Demographic data of couples, complications during pregnancy and delivery of pregnant women, and data of newborns at birth were collected. RESULTS: Sixty-six women were vaccinated with a median time of 35.5 (range = 0-91) days before LMP, and 27 women were vaccinated with a median time of 17 (range = 1-72) days after LMP. The incidence of premature rupture of membrane (PROM) in the vaccine group was significantly higher than that in the control group (16.13% vs. 6.88%, p = 0.019). Multivariate logistic regression analysis revealed that maternal peri-pregnancy COVID-19 vaccination was not an independent risk factor for PROM (odds ratio: 2.407, 95% confidence interval: 0.932-6.216, p = 0.069). There was no difference in the incidence of other complications during pregnancy and delivery between the two groups. A total of 253 neonates were delivered, including two cases with congenital abnormalities in each group. The incidence of congenital abnormalities between the two groups was similar (2.15% vs. 1.25%, p = 0.626). There was no difference in neonatal length, weight, head circumference, and Apgar score between the two groups (p > 0.05), but the incidence of neonatal jaundice in the vaccine group was significantly higher than that in the control group (20.43% vs. 7.5%, p = 0.002). Multivariate logistic regression analysis revealed that maternal peri-pregnancy vaccination, postpartum blood loss, cesarean section, 1-min Apgar score, and paternal smoking were independent risk factors for neonatal jaundice. CONCLUSIONS: It is safe for pregnant women and their fetuses to be inoculated the inactivated COVID-19 vaccine during the peri-pregnancy period, but attention should be paid to neonatal jaundice.

Models of bilirubin neurological damage: lessons learned and new challenges.

OBJECTIVE: Jaundice (icterus) is the visible manifestation of the accumulation of bilirubin in the tissue and is indicative of potential toxicity to the brain. Since its very first description more than 2000 years ago, many efforts have been undertaken to understand the molecular determinants of bilirubin toxicity to neuronal cells to reduce the risk of neurological sequelae through the use of available chemicals and in vitro, ex vivo, in vivo, and clinical models. Although several studies have been performed, important questions remain unanswered, such as the reasons for regional sensitivity and the interplay with brain development. The number of new molecular effects identified has increased further, which has added even more complexity to the understanding of the condition. As new research challenges emerged, so does the need to establish solid models of prematurity. METHODS: This review critically summarizes the key mechanisms of severe neonatal hyperbilirubinemia and the use of the available models and technologies for translational research. IMPACT: We critically review the conceptual dogmas and models used for studying bilirubin-induced neurotoxicity. We point out the pitfalls and translational gaps, and suggest new clinical research challenges. We hope to inform researchers on the pro and cons of the models used, and to help direct their experimental focus in a most translational research.

Quantification of cephalocaudal progression of jaundice in preterm infants.

BACKGROUND: The cephalocaudal progression (CCP) of neonatal jaundice is a well-known phenomenon, but quantitative information on CCP in preterm infants is absent. In this study, CCP was quantified in preterm infants as a function of postnatal age and body location. METHODS: 5.693 transcutaneous bilirubin (TcB) measurements were performed in 101 preterm infants from birth until postnatal day seven at five body locations (forehead, sternum, hipbone, tibia, ankle). Multi-level linear regression analysis was performed to evaluate the CCP as a function of body location and postnatal age. TcB measurements at all body locations and postnatal days were compared to total serum bilirubin (TSB) levels (N = 1.113). RESULTS: The overall average change in ratio of TcB compared to forehead was for sternum +0.04 [95% CI -0.02;0.09]; hipbone +0.05 [0.00;0.01]; tibia -0.33 [-0.38;-0.27] and ankle -0.62 [-0.68;-0.57]. No effect modification of CCP by sex, gestational age, birthweight, phototherapy, and TSB was found. The TcB maximally underestimated the TSB at the ankle -79.5 µmol [-0.1;159.2]. CONCLUSIONS: CCP is present in preterm infants and is relatively stable over time. Since TcB measurements on the tibia and ankle underestimate TSB significantly, we advise to use only measurement locations cephalic from the tibia; i.e., hipbone, sternum, and forehead. IMPACT: Cephalocaudal progression (CCP) of jaundice in preterm infants, assessed by transcutaneous bilirubin (TcB) measurements, is substantial and rather stable over postnatal day 0 to 7. To the best of our knowledge, this study is the first to investigate CCP of jaundice in preterm infants as a function of postnatal age in preterm infants. Our results demonstrate that TcB measurements at the tibia and ankle differ from the TSB beyond the clinically used TcB safety margins. We advise to perform TcB measurements only at locations cephalic from the tibia; i.e., hipbone, forehead, and sternum.