Better assessment of neonatal jaundice at home (BEAT Jaundice @home): protocol for a prospective, multicentre diagnostic study.

INTRODUCTION: Severe neonatal hyperbilirubinaemia can place a neonate at risk for acute bilirubin encephalopathy and kernicterus spectrum disorder. Early diagnosis is essential to prevent these deleterious sequelae. Currently, screening by visual inspection followed by laboratory-based bilirubin (LBB) quantification is used to identify hyperbilirubinaemia in neonates cared for at home in the Netherlands. However, the reliability of visual inspection is limited. We aim to evaluate the effectiveness of universal transcutaneous bilirubin (TcB) screening as compared with visual inspection to: (1) increase the detection of hyperbilirubinaemia necessitating treatment, and (2) reduce the need for heel pricks to quantify bilirubin levels. In parallel, we will evaluate a smartphone app (Picterus), and a point-of-care device for quantifying total bilirubin (Bilistick) as compared with LBB. METHODS AND ANALYSIS: We will undertake a multicentre prospective cohort study in nine midwifery practices across the Netherlands. Neonates born at a gestational age of 35 weeks or more are eligible if they: (1) are at home at any time between days 2 and 8 of life; (2) have their first midwife visit prior to postnatal day 6 and (3) did not previously receive phototherapy. TcB and the Picterus app will be used after visual inspection. When LBB is deemed necessary based on visual inspection and/or TcB reading, Bilistick will be used in parallel. The coprimary endpoints of the study are: (1) hyperbilirubinaemia necessitating treatment; (2) the number of heel pricks performed to quantify LBB. We aim to include 2310 neonates in a 2-year period. Using a decision tree model, a cost-effectiveness analysis will be performed. ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethical Committee of the Erasmus MC Rotterdam, Netherlands (MEC-2020-0618). Parents will provide written informed consent. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NL9545).

Feasibility for SERS-based discrimination of gallbladder cancer from polyp by indirect recognition of components in bile.

The aqueous solution extracted from raw bile juice is composed primarily of bile salts, with lower levels of bilirubin and its derivatives. Among them, the bilirubin and bilirubin-derived metabolites are the only surface-enhanced Raman scattering (SERS)-active components. An analytical scheme indirectly responsive and able to utilize all bile components, including SERS-inactive bile salts, was explored for SERS-based discrimination of gallbladder (GB) polyp and GB cancer. Initially, the surface of a SERS substrate (Au nanodendrite on Ni foil (AuND@NiF)) was covered with an alkanethiol molecule to generate a SERS signal and attract bile components by mutual interaction. For more effective recognition of bile components, 4 independent substrates covered with 4 different alkanethiols with various functional groups (SH(CH2)2CH3, SH(CH2)2NH2, SH(CH2)2COOH, and SH(CH2)2OH) were prepared. The SERS peaks of each substrate clearly varied on interaction with pure bile components as well as aqueous bile samples, and the SERS peaks in each substrate were individually characteristic. When the principal component (PC) scores of spectra obtained using the SH(CH2)2CH3- and SH(CH2)2OH-covered substrates were combined, the k-Nearest Neighbor-based discrimination accuracy was 100%, superior to those (90.6-96.9%) using individual substrates. The use of complementary bile component-induced spectral information provided by the two substrates was responsible for accurate discrimination. On the other hand, when bare AuND@NiF recognizing only SERS-active bilirubin derivatives was used, discrimination was unsatisfactory (accuracy: 75.0%).

Which Is More Accurate: Transcutaneous Bilirubin Measurement on the Forehead or Sternum?

BACKGROUND: The accuracy and reliability of noninvasive methods of neonatal jaundice assessment are not completely obvious, including which area of the body is more suitable to estimate actual bilirubin with transcutaneous bilirubinometry (TCB). METHODS: This cross-sectional study compares the accuracy of three noninvasive methods for neonatal jaundice estimation included visual estimation, TCB on the forehead, and TCB on the sternum. The mean and standard deviation describe quantitative variables. In addition to analytical analysis, we used the linear regression test to evaluate the association of different variables with the accuracy of TCB as well as paired t test for comparing the TCB results on the sternum with the forehead before and after phototherapy. For all statistical tests, a P value less than 0.05 was considered as significant. RESULTS: We enrolled 100 neonates with a mean age (±SD, standard deviation) of 6.5±1.9 days (range 2-11 days) in our study. The mean gestational age (GA) of the participants was 38.94 weeks±1.00 w SD, and their mean (±SD) weight was 3302 g (±315.60). The mean (mg/dL)±SD for bilirubin level by clinical estimation of jaundice, TCB on the forehead and TCB on the sternum were 17.35±2.88, 17.23±1.63, and 17.77±1.58, respectively. Also, comparing mean differences before and after phototherapy showed that TCB on the sternum is a good predictor for neonatal jaundice before phototherapy (0.539 vs. 0.348). CONCLUSION: TCB on the sternum is more predictive than the forehead, especially before phototherapy, to assess the need for treatment in outpatient settings.

Liver biomarkers in adults: Evaluation of associations with reported green tea consumption and use of green tea supplements in U.S. NHANES.

Some events of hepatotoxicity have been linked to consumption of green tea supplements. The association between consumption of green tea or green tea supplements and abnormal liver biomarkers in adults was investigated using cross-sectional data from the 2009-2014 United States National Health and Nutrition Examination Survey (U.S. NHANES). Individuals with levels of either bilirubin or GGT, ALT, AST, and/or ALP in excess of the age- and gender-specific upper limits of normal ranges were classified as having abnormal liver biomarkers. Associations between green tea or green tea supplement use (consumption vs. not) and liver function were determined using multiple logistic regression modelling. 12,289 persons were included in the green tea analyses and 12,274 in the green tea supplement analyses. The odds of having one or more abnormal liver biomarkers were significantly reduced (p = 0.01) with consumption of green tea (OR: 0.49; 95% CI: 0.28, 0.85), while no significant association (p = 0.78) was determined for consumption of green tea supplements (OR: 0.92; 95% CI: 0.52, 1.64). Based on data from the 2009-2014 U.S. NHANES, green tea consumption was associated with reduced odds of having one or more abnormal liver biomarkers; whereas, no significant association was determined with consumption of green tea supplements.

Biliary Atresia/Neonatal Cholestasis: What is in the Horizon?

"Biliary atresia (BA) is a common cause of jaundice in infancy. There is increasing evidence that newborn screening with direct or conjugated bilirubin leads to earlier diagnosis. Although the Kasai portoenterostomy is the primary treatment, there are scientific advances in adjuvant therapies. As pediatric patients transition to adult care, multidisciplinary care is essential, given the complexity of this patient population."

Transient deterioration of albumin-bilirubin scores in early post-dose period of molecular targeted therapies in advanced hepatocellular carcinoma with 50% or higher liver occupation: A STROBE-compliant retrospective observational study.

ABSTRACT: Real-world clinical cases of molecularly targeted agent (MTA) administration to patients with advanced hepatocellular carcinoma (HCC) with ≥50% liver occupation have been reported, but treatment outcomes have rarely been described. We have encountered several cases in which albumin-bilirubin (ALBI) scores deteriorated markedly and C-reactive protein (CRP) levels elevated in the early post-dose period. The present study therefore investigated early clinical changes in ALBI score and CRP levels after initiating MTA in advanced HCC patients with ≥50% liver occupation, focusing on antitumor response at 6 weeks.This retrospective study included 46 HCC patients with liver occupation ≥50% and 191 patients with <50%, Child-Pugh score ≤7, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1, who were treated with sorafenib or lenvatinib as first-line systemic therapy at our hospital between June 2011 and January 2020. We analyzed their medical records up to March 2020 and investigated the outcomes and changes in CRP and ALBI scores classified according to antitumor response at 6 weeks.Overall survival was significantly longer in patients with partial response (PR) + stable disease (SD) (13.7 months) than in patients with progressive disease (PD) (1.7 months, P < .001) in the ≥50% group. Patients with antitumor response of PR + SD at 6 weeks in the ≥50% group showed more marked deterioration of ALBI score at 2 weeks than those in the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. Focusing on patients with PD at 6 weeks, ALBI score deteriorated over time in both groups. Regarding CRP, on 6-week PR + SD patients, a significant increase in CRP levels at 1 and 2 weeks was evident in the >50% group compared to the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. In PD patients, no difference between groups in CRP elevation occurred at 1 and 2 weeks.In MTA treatment for patients with ≥50% liver occupation, to obtain an antitumor response of PR + SD, adequate management might be important considering transient deteriorated ALBI scores and elevated CRP levels.

Inter-device reproducibility of transcutaneous bilirubin meters.

BACKGROUND: Transcutaneous bilirubinometry is a widely used screening method for neonatal hyperbilirubinemia. Deviation of the transcutaneous bilirubin concentration (TcB) from the total serum bilirubin concentration (TSB) is often ascribed to biological variation between patients, but variations between TcB meters may also have a role. This study aims to provide a systematic evaluation of the inter-device reproducibility of TcB meters. MATERIALS AND METHODS: Thirteen commercially available TcB meters (JM-105 and JM-103) were evaluated in vitro on phantoms that optically mimic neonatal skin. The mimicked TcB was varied within the clinical range (0.5-181.3 µmol/L). RESULTS: Absolute differences between TcB meter outcomes increased with the measured TcB, from a difference of 5.0 µmol/L (TcB = 0.5 µmol/L phantom) up to 65.0 µmol/L (TcB = 181.3 µmol/L phantom). CONCLUSION: The inter-device reproducibility of the examined TcB meters is substantial and exceeds the specified accuracy of the device (±25.5 µmol/L), as well as the clinically used TcB safety margins (>50 µmol/L below phototherapy threshold). Healthcare providers should be well aware of this additional uncertainty in the TcB determination, especially when multiple TcB meters are employed in the same clinic. We strongly advise using a single TcB meter per patient to evaluate the TcB over time. IMPACT: Key message: The inter-device reproducibility of TcB meters is substantial and exceeds the clinically used TcB safety margins. What this study adds to existing literature: The inter-device reproducibility of transcutaneous bilirubin (TcB) meters has not been reported in the existing literature. This in vitro study systematically evaluates this inter-device reproducibility. IMPACT: This study aids in a better interpretation of the measured TcB value from a patient and is of particular importance during patient monitoring when using multiple TcB meters within the same clinical department. We strongly advise using a single TcB meter per patient to evaluate the TcB over time.

Predictive effects of a combined indicator in patients with hepatocellular carcinoma after thermal ablation.

AIM: This study aimed to investigate the predictive power of the combination of Systemic Immune-Inflammation Index (SII) and albumin-bilirubin (ALBI) grade in prognosis outcomes of early-stage hepatocellular carcinoma (HCC) after thermal ablation. MATERIALS AND METHODS: This retrospective study was reviewed and approved by our institutional review board, and written informed consent was obtained from each patient. According to the Milan criteria, a total of 405 treatment-naïve patients with clinicopathologically confirmed HCC were enrolled who subsequently underwent thermal ablation from 2011 to 2016. The outcomes of overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were statistically analyzed. RESULTS: The median follow-up time of this study was 45.1 months (range, 1.3-83.2 months). After thermal ablation in patients with SII-ALBI Grades 1, 2, and 3, the cumulative 5-year OS rates were 81.7%, 63.2%, and 26.9%; the 5-year CSS rates were 82.4%, 67.5%, and 26.9%; and the 5-year RFS rates were 49.3%, 44.6%, and 25.3%, respectively (all P < 0.001). On multivariate Cox regression analyses, SII-ALBI was independently associated with the three outcomes after adjustment for various confounders (all P < 0.05). In addition, SII-ALBI played a predictive role in OS, CSS, and RFS for patients with negative alpha-fetoprotein (AFP) (P < 0.05). Compared with SII and ALBI, the AUCs for the prediction of OS and CSS using SII-ALBI were superior to single indicator (bothP < 0.05). CONCLUSION: Elevated preablation SII-ALBI is associated with shorter OS, CSS, and RFS in patients with early-stage HCC. Our indicator showed the potential to be a supplement tool for patients with negative AFP during follow-up.

Predischarge transcutaneous bilirubin screening reduces readmission rate for hyperbilirubinaemia in diverse South African newborns: A randomised controlled trial.

BACKGROUND: In South Africa (SA), healthy term newborns are usually discharged ˂72 hours after delivery. Discharged babies remain at risk for severe hyperbilirubinaemia if it is not identified early. Hyperbilirubinaemia is an important cause of readmission, and also leads to neonatal mortality and morbidity. Use of transcutaneous bilirubin (TcB) screening before hospital discharge has been controversial. OBJECTIVES: To test the clinical benefits of TcB screening of healthy newborns before discharge for the outcomes of readmission for jaundice and severe hyperbilirubinaemia in a randomised controlled trial (RCT). METHODS: This was a RCT. We compared predischarge TcB screening with visual assessment (alone) for jaundice in apparently healthy newborns at a public tertiary hospital in Cape Town, SA. Patients or study participants were not involved in the study design and implementation. RESULTS: Of the 1 858 infants, 63% were black, 35% of mixed race and 1% white. There was a significant reduction in the rate of readmission for jaundice (risk ratio (RR) 0.25; 95% confidence interval (CI) 0.14 - 0.46; p<0.0001) and in the incidence of severe hyperbilirubinaemia (RR 0.27; 95% CI 0.08 - 0.97; p=0.05) with the use of TcB screening compared with visual inspection. CONCLUSIONS: Predischarge TcB screening is superior in identifying newborns at risk of severe hyperbilirubinaemia compared with visual inspection. We recommend that every newborn, regardless of skin pigmentation, should receive objective bilirubin screening before hospital discharge. Universal bilirubin screening in newborns could potentially reduce hyperbilirubinaemia-related morbidity and mortality.

Benefits and harms of ginseng supplementation on liver function? A systematic review and meta-analysis.

OBJECTIVE: Existing evidence on the possible effects of ginseng on liver function has not been fully established. Therefore, the present review was undertaken to evaluate the overall effects of ginseng supplementation on liver enzymes in adults. METHODS: A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google scholar databases was conducted up to May 2019. All RCTs using ginseng supplements in adults were included in this systematic review and meta-analysis. RESULTS: Overall, 14 randomized trials (with 20 arms) including 992 subjects were identified. Pooled analysis did not illustrate any significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin (ALB) levels, however, it showed a minor significant increase in bilirubin (BIL) levels. Subgroup analysis by dosage and study population revealed significant increase of bilirubin after ginseng supplementation ≥3 g/day or in unhealthy individuals. CONCLUSION: Ginseng appears to have neither hepatoprotective nor hepatotoxic effects in conventional doses and duration. It is noteworthy that this seems applicable only for individuals with healthy liver function. Further largescale studies are warranted to confirm present findings.

Transcutaneous bilirubin nomogram for the first 144 hours in Thai neonates.

Objectives: To develop an hour-specific transcutaneous bilirubin (TcB) nomogram for Thai neonates and to compare the ability of this nomogram with that of Bhutani's total serum bilirubin (TSB) nomogram for prediction of significant hyperbilirubinemia requiring phototherapy.Methods: Healthy Thai neonates, gestational age ≥35-week-gestation and birth weight ≥2000 grams were enrolled. Neonates who could not attend the postdischarge follow-up at our center were excluded. TcB measurements were routinely performed at 6 am and 6 pm using JM103 transcutaneous bilirubinometer until the neonates were discharged or received phototherapy. TcB levels were also measured at least once during 24-72 hours after discharge and thereafter depending on the pediatricians' decision. The nomogram was developed from the TcB data during age 12-144 hours of neonates who did not require phototherapy. The TcB values that obtained predischarge or before receiving phototherapy of all neonates were used to determine the predictive ability of this nomogram and Bhutani's TSB nomogram.Results: A total of 1071 neonates were included. Two hundred forty-one neonates (22.5%) required phototherapy. The nomogram was constructed using 4834 hour-specific TcB values. It provided a good prediction with the area under curve (AUC) of 0.89. The 75th percentile tract revealed sensitivity and negative predictive value (NPV) of 87.1 and 95.4% while that of the 40th percentile tract were 97.9 and 98.5% respectively. When Bhutani's nomogram was used, the AUC was 0.84. The sensitivity and NPV of the 75th percentile tract were 56.4 and 88.2%, and for the 40th percentile tract were 97.1 and 98.0% respectively.Conclusion: The newly developed TcB nomogram revealed slightly better predictive ability than Bhutani's TSB nomogram for term and late preterm Thai neonates who were the population with high prevalence of significant hyperbilirubinemia. The 40th percentile curve of both nomograms should be considered as an appropriate cut-off level for prediction.

Effects of Massage Therapy on Indirect Hyperbilirubinemia in Newborns Who Receive Phototherapy.

OBJECTIVE: To evaluate the effects of massage therapy on total serum bilirubin (TSB) levels and frequency of defecation, urination, and feeding in newborns who receive phototherapy for indirect hyperbilirubinemia. DESIGN: A randomized controlled clinical trial. SETTING: Ankara University Cebeci Research and Training Hospital and 29 May State Hospital in Ankara, Turkey. PARTICIPANTS: Fifty full-term newborns with indirect hyperbilirubinemia who underwent phototherapy. METHODS: The newborns were randomly allocated to an intervention group (n = 25) or a control group (n = 25). Newborns in the intervention group received massage therapy throughout the duration of phototherapy for 15 minutes twice per day; newborns in the control group received routine care during phototherapy. Every 24 hours, TSB levels were measured, and the frequencies of defecation, urination, and feeding were also calculated for each newborn. RESULTS: We found no differences in the characteristics of the newborns or in TSB levels between groups at enrollment. After treatment, TSB levels were lower in the intervention group (p < .001). Frequencies of defecation, urination, and feeding were significantly greater in the intervention group than in the control group. CONCLUSION: Massage therapy had significant effects on TSB levels, feeding, breastfeeding, defecation, and urination in newborns who received phototherapy for indirect hyperbilirubinemia. Massage therapy can be added as routine care for full-term newborns with hyperbilirubinemia under phototherapy and may be an effective supplementary intervention.

Accuracy of the Bilicare™ transcutaneous bilirubinometer as the predischarge screening tool for significant hyperbilirubinemia in healthy term and late preterm neonates.

Background: The Bilicare™ is a new device that measures transcutaneous bilirubin (TcB) level at the ear pinna. There are only few studies which have evaluated its accuracy in clinical practice.Objective: This study aims to determine the accuracy of Bilicare™ as a predischarge screening tool in late preterm and term neonates and to define the optimal cutoff point for determining the need to measure total serum bilirubin (TSB).Methods: The 35 weeks' gestation or more and healthy neonates who underwent predischarge TSB measurement were enrolled. Bilicare™ TcB was measured within 30 minutes of blood sampling. Paired TcB and TSB data were analyzed.Results: We collected 214 paired samples. Mean age (SD) at TcB measurement was 57.17 (7.47) hours. Mean TSB (SD) was 9.79 (2.83) mg/dL. TcB showed a significant correlation with TSB (r = 0.84, r2 = 0.7). The mean difference (SD) between TcB and TSB was 0.7 (0.21) mg/dL (95%CI 0.49-0.91). TcB tended to overestimate TSB level at the TSB values of <12 mg/dL but underestimate at the higher TSB level. The accuracy of using TcB values to detect neonates who required phototherapy was 92.5%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 78.3, 94.2, 62.1, and 97.3%, respectively. If TcB +3 mg/dL was applied as a cutoff point, the sensitivity, specificity, PPV, and NPV were 100, 53.9, 20.7, and 100%, respectively.Conclusions: Bilicare™ TcB and TSB measurements were well correlated. The TcB level +3 mg/dL could detect all neonates who had significant hyperbilirubinemia requiring phototherapy during their birth hospitalization.

Accuracy of transcutaneous bilirubin on covered skin in preterm and term newborns receiving phototherapy using a JM-105 bilirubinometer.

OBJECTIVE: Determine the suitability of transcutaneous bilirubin (TCB) as a tool to assess the effectiveness of phototherapy on patched skin. STUDY DESIGN: A prospective observational study was conducted. We covered a fragment of skin (sternum) with a photo-opaque patch. Several simultaneous TCB and TSB measurements were performed with the JM-105 bilirubinometer. Bland and Altman test evaluated the agreement between bilirubin levels. RESULT: A total of 217 patients were studied, 48.8% were preterm. The mean difference between TSB and TCB before the start of treatment was 1.07 mg/dL. During phototherapy, differences on covered skin were 0.52, 0.27, and 0.39 mg/dL at 24, 48, and 72 h of therapy respectively. The best correlation was observed at 48 h in preterm infants. CONCLUSION: The measurement of TCB on patched skin (PTCB) is useful for monitoring the response to phototherapy in term and preterm infants. We use a patch with a removable flap that eases successive measures without disturbing the patients.

Role of Baseline Albumin-Bilirubin Grade on Predict Overall Survival Among Sorafenib-Treated Patients With Hepatocellular Carcinoma in Vietnam.

INTRODUCTION: Albumin-bilirubin (ALBI) grade has been recently used in evaluation of liver function and prognosis of patients with hepatocellular carcinoma (HCC). However, in Vietnam, the utility of ALBI grade in clinical setting has not been adequately investigated. METHODS: This is a retrospective study of 110 patients with HCC treated with sorafenib from January 2010 to November 2018 at 2 tertiary hospitals in Vietnam. Prognostic value of ALBI grade was evaluated by Kaplan-Meier survival analysis and Cox proportional regression model. RESULTS: Results showed that the majority of ALBI grade 1 were Child-Pugh level A (97.5%); ALBI grade 2 was seen in all Child-Pugh score groups of 5, 6, 7, ≥8, whereas ALBI grade 3 was mostly reported in Child-Pugh score ≥8 group (83.3%). Compared with ALBI grade 3, ALBI grade 1 reduced 66.4% risk of death (hazards ratio [HR] = 0.336, 95% confidence interval [CI]: 0.115-0.981; P = .046). Compared with ALBI grade 3, ALBI grade 2 reduced 67.3% risk of death (HR = 0.327, 95% CI: 0.122-0.875; P = .026). Albumin-bilirubin grade was an independent predictor of survival outcome. CONCLUSION: Baseline ALBI grade is a simple and objective approach in assessing liver functions of patients with HCC. Baseline ALBI grade is an independent predictor of survival in patients treated with sorafenib.

Changes in saliva analytes in equine acute abdominal disease: a sialochemistry approach.

BACKGROUND: The biochemical components of saliva can change in certain pathologies in horses, for example in acute abdominal disease. The aim of this study was (1) to evaluate if a panel of biochemical analytes usually used in serum can be measured in saliva of horses and (2) to study the possible changes of these biochemical analytes in saliva of horses affected by acute abdominal disease. A panel of 23 analytes was analytically validated in saliva of horses and possible changes in these analytes in a pilot study with six healthy horses and six horses with acute abdominal disease were evaluated. The analytes with significant changes were then evaluated in a larger population of 20 healthy and 37 diseased horses. RESULTS: Seven analytes showed significant increases in the pilot study which were confirmed in the larger population. The analytes which showed significant changes, and their median fold increase and significance shown in the larger population were salivary γ-glutamyl transferase (gGT, 2.3 fold, P = 0.001), creatine kinase (CK, 6.2 fold, P < 0.001), urea (2.3 fold, P = 0.001), total bilirubin (2.6 fold, P < 0.001), total proteins (3.2 fold, P < 0.001), phosphorus (P, 4.5 fold, P < 0.001) and alpha-amylase (sAA, 8.5 fold, P < 0.001). Total proteins, P and sAA showed sensitivities higher than 70% at their optimal cut-off points and a specificity of 100% in differentiating between healthy horses and those with acute abdominal disease. CONCLUSIONS: A panel of 23 biochemical analytes can be measured in saliva of horses, where gGT, CK, urea, total bilirubin, total protein, P and sAA levels are raised in horses with acute abdominal disease.

Screening and treatment to reduce severe hyperbilirubinaemia in infants in primary care (STARSHIP): a factorial stepped-wedge cluster randomised controlled trial protocol.

INTRODUCTION: Jaundice caused by hyperbilirubinaemia is a physiological phenomenon in the neonatal period. However, severe hyperbilirubinaemia, when left untreated, may cause kernicterus, a severe condition resulting in lifelong neurological disabilities. Although commonly applied, visual inspection is ineffective in identifying severe hyperbilirubinaemia. We aim to investigate whether among babies cared for in primary care: (1) transcutaneous bilirubin (TcB) screening can help reduce severe hyperbilirubinaemia and (2) primary care-based (versus hospital-based) phototherapy can help reduce hospital admissions. METHODS AND ANALYSIS: A factorial stepped-wedge cluster randomised controlled trial will be conducted in seven Dutch primary care birth centres (PCBC). Neonates born after 35 weeks of gestation and cared for at a participating PCBC for at least 2 days within the first week of life are eligible, provided they have not received phototherapy before. According to the stepped-wedge design, following a phase of 'usual care' (visual assessment and selective total serum bilirubin (TSB) quantification), either daily TcB measurement or, if indicated, phototherapy in the PCBC will be implemented (phase II). In phase III, both interventions will be evaluated in each PCBC. We aim to include 5500 neonates over 3 years.Primary outcomes are assessed at 14 days of life: (1) the proportion of neonates having experienced severe hyperbilirubinaemia (for the TcB screening intervention), defined as a TSB above the mean of the phototherapy and the exchange transfusion threshold and (2) the proportion of neonates having required hospital admission for hyperbilirubinaemia treatment (for the phototherapy intervention in primary care). ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethics Committee of the Erasmus MC Rotterdam, the Netherlands (MEC-2017-473). Written parental informed consent will be obtained. Results from this study will be published in peer-reviewed journals and presented at (inter)national meetings. TRIAL REGISTRATION NUMBER: NTR7187.

Comparison of conventional phototherapy and phototherapy along with Kangaroo mother care on cutaneous bilirubin of neonates with physiological jaundice.

BACKGROUND: One of the adjuvant and desirable therapies is skin contact between mother and baby or Kangaroo mother care (KMC) that is a cheap, accessible, relaxing, noninvasive and easy method. This study aimed to compare the effect of conventional phototherapy method and phototherapy along with KMC on cutaneous bilirubin in neonates with physiological jaundice. MATERIALS AND METHODS: In this randomized clinical trial, all infants with physiological jaundice who referred for phototherapy to Mofid Hospital of Shahid Beheshti University of Medical Sciences, Tehran, Iran were selected by convenience sampling based on inclusion criteria and were randomly assigned into two groups of conventional phototherapy (n = 35) and phototherapy along with KMC (n = 35). RESULTS: The results showed that there was a significant difference in the average volume of skin bilirubin before treatment with cutaneous bilirubin every 24 h after treatment (p < .001). This significant difference was present in both intervention and control groups. Although the average volume of skin bilirubin every 24 h after treatment was lower in the intervention group than the control group, this difference was not statistically significant (p = .236). Mean duration of hospitalization of infants in the intervention group was significantly lower than the control group (2.09 versus 3.03 d, p < .001). CONCLUSION: Although KMC along with phototherapy has a favorable effect on the reduction of cutaneous bilirubin in neonates with physiological jaundice, there are not significant differences in routine care. This may need to do KMC for a longer time (more than 1 h) which must be surveyed in the future studies. KMC was effective in reduction of the duration of hospitalization in jaundiced infants.

Accuracy of transcutaneous bilirubinometry in the preterm infants: a comprehensive meta-analysis.

BACKGROUND: Transcutaneous bilirubin (TcB) measurement is widely used in term babies. But its effectiveness till debated in preterm infants. So, our objective was to pool data to see the accuracy of transcutaneous bilirubinometry in preterm infants. METHOD: MEDLINE, Embase, Cochrane Library database were searched from 2000 to July 2017. The included studies had compared TcB with total serum bilirubin (TSB) in preterm infants before phototherapy and data were presented as correlation coefficients. Data were extracted by two reviewers and checked for accuracy by the third reviewer. The risk bias assessments were done by an assessment quality assessment of diagnostic accuracy studies tool. Pooled correlation coefficient assed after Fisher's z transformation and then converted to r. RESULTS: We included 28 studies; all those studies reported results as correlation coefficients. In combination of both sternal and forehead site measurement, our pooled estimates of r = 0.82 (95% CI: 0.78-0.85) in random effect and r = 0.803 (95% CI: 0.78-0.81) in fixed effect model. For separate sites of measurement of TcB pooled r for forehead and sternum were comparable, r = 0.82 (95% CI: 0.78-0.85), and pooled correlation coefficient for the two devices JM103 and Bilicheck the estimated pooled r were also comparable (Pooled r = 0.83). CONCLUSION: Our study found that TcB measurement is well related with TSB values and can represent a reliable method for evaluating preterm infants with possible hyperbilirubinemia. Our findings support the use of investigated devices at both forehead and sternum sites in preterm infants.