One of the most common problems many babies encounter is neonatal jaundice. The symptoms are yellowing of the skin or eyes because of bilirubin (from above 2.0 to 2.5 mg/dL in the blood). If left untreated, it can lead to serious neurological complications. Traditionally, jaundice detection has relied on invasive blood tests, but developing non-invasive biosensors has provided an alternative approach. This systematic review aims to assess the advancement of these biosensors. This review discusses the many known invasive and non-invasive diagnostic modalities for detecting neonatal jaundice and their limitations. It also notes that the recent research and development on non-invasive biosensors for neonatal jaundice diagnosis is still in its early stages, with the majority of investigations being in vitro or at the pre-clinical level. Non-invasive biosensors could revolutionize neonatal jaundice detection; however, a number of issues still need to be solved before this can happen. These consist of in-depth validation studies, affordable and user-friendly gadgets, and regulatory authority approval. To create biosensors that meet regulatory requirements, additional research is required to make them more precise and affordable.

Background Physiological neonatal hyperbilirubinemia is a normal transitional phenomenon, however bilirubin encephalopathy can develop due to exposure to very high bilirubin levels. A systematic approach to early detection of high levels can prevent this outcome. Methods We designed a questionnaire to assess local jaundice management practices in Irish maternity units. Results All 19 units responded to our clinical questionnaire. Early discharge (<48 hours) occurs in 12 units (63%). Six units universally screen all babies with a transcutaneous bilirubinometer (TCB) (32%) while 12 units only do so if clinically jaundiced (83%). 12 units follow up <5% of their babies for jaundice monitoring after discharge (67%), which is lower than expected for optimal jaundice management. Conclusion Our survey responses show a high degree of variability in jaundice identification and follow up practices around the country. As maternity units trend towards earlier discharge of mothers due to resource constraints, we need to develop national systems to stratify risk before discharge and monitor jaundice in the out-patient setting. Introduction

UNASSIGNED: Neonatal hyperbilirubinemia is one of the most common conditions for neonate inpatients. Indonesia faces a major challenge in which different guidelines regarding the management of this condition were present. This study aimed to compare the existing guidelines regarding prevention, diagnosis, treatment and monitoring in order to create the best recommendation for a new hyperbilirubinemia guideline in Indonesia.
UNASSIGNED: Through an earlier survey regarding adherence to the neonatal hyperbilirubinemia guideline, we identified that three main guidelines are being used in Indonesia. These were developed by the Indonesian Pediatric Society (IPS), the Ministry of Health (MoH), and World Health Organization (WHO). In this study, we compared factors such as prevention, monitoring, methods for identifying, risk factors in the development of neonatal jaundice, risk factors that increase brain damage, and intervention treatment threshold in the existing guidelines to determine the best recommendations for a new guideline.
UNASSIGNED: The MoH and WHO guidelines allow screening and treatment of hyperbilirubinemia based on visual examination (VE) only. Compared with the MoH and WHO guidelines, risk assessment is comprehensively discussed in the IPS guideline. The MoH guideline recommends further examination of an icteric baby to ensure that the mother has enough milk without measuring the bilirubin level. The MoH guideline recommends referring the baby when it looks yellow on the soles and palms. The WHO and IPS guidelines recommend combining VE with an objective measurement of transcutaneous or serum bilirubin. The threshold to begin phototherapy in the WHO guideline is lower than the IPS guideline while the exchange transfusion threshold in both guidelines are comparably equal.
UNASSIGNED: The MoH guideline is outdated. MoH and IPS guidelines are causing differences in approaches to the management hyperbilirubinemia. A new, uniform guideline is required.

BACKGROUND: JKb antibody rarely causes severe hemolytic disease in the newborn except in 1 case, required blood exchange transfusion but later died of intractable seizure and renal failure. Here we describe 2 cases of JKb-induced severe neonatal jaundice requiring blood exchange transfusion with good neurological outcome.
METHODS: Two female Chinese, ethnic Han, term infants with severe jaundice were transferred to us at the age of 5- and 4-day with a total bilirubin of 30.9 and 25.9 mg/dL while reticulocyte counts were 3.2% and 2.2%, respectively. Both infants were not the firstborn to their corresponding mothers. Direct and indirect Coombs\' tests were positive, and JKb antibody titers were 1:64 (+) for both mothers. Phototherapy was immediately administered, and a blood exchange transfusion was performed within 5 hours of admission. Magnet resonance image showed no evidence of bilirubin-induced brain damage, and no abnormal neurological finding was detected at 6 months of life.
CONCLUSIONS: JKb antibody-induced hemolytic disease of the newborn usually leads to a benign course, but severe jaundice requiring blood exchange transfusion may occur. Our cases suggest good outcomes can be achieved in this minor blood group-induced hemolytic disease of the newborn if identified and managed early enough.

Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ is a type of prolonged unconjugated hyperbilirubinemia that is often late onset in otherwise healthy-appearing newborns, and its occurrence might be related to breast milk itself. This review aims to systematically evaluate evidence regarding breast milk composition and the development of BMJ in healthy neonates. PubMed, Scopus and Embase were searched up to 13 February 2023 with key search terms, including neonates, hyperbilirubinemia, and breastfeeding. A total of 678 unique studies were identified and 12 were ultimately included in the systematic review with narrative synthesis. These included studies covered both nutritional compositions (e.g., fats and proteins) and bioactive factors (e.g., enzymes and growth factors) of breast milk and formally assessed the difference in the concentration (or presence) of various endogenous components of breast milk collected from mothers of BMJ infants and healthy infants. The results were inconsistent and inconclusive for most of the substances of interest, and there was only a single study available (e.g., total energy and mineral content, bile salts and cytokines); conflicting or even contradictory results arose when there were two or more studies on the subject matter (e.g., fats and free fatty acids contents and epidermal growth factor). The etiology of BMJ is likely multifactorial, and no single constituent of breast milk could explain all the BMJ cases observed. Further well-designed studies are warranted to investigate the complex interaction between maternal physiology, the breast milk system and infant physiology before this field could be progressed to uncover the etiology of BMJ.

Phototherapy is the main treatment of neonatal hyperbilirubinemia to prevent encephalopathy. It is generally believed to be safe; however, some studies have shown it might be associated with cancer development. In this systematic review and meta-analysis, we aimed to assess the effect of neonatal phototherapy on future cancer risk. A systematic search in 13 databases was conducted in December 2018 and updated in August 2022 to identify studies that report cancer development after exposure to phototherapy. Throughout the study period, regular manual searches were also conducted to include new studies. A meta-analysis using R programming language was done in which the odds ratios (ORs) with 95% confidence intervals (CIs) were estimated and pooled using the reported adjusted and unadjusted data. Fifteen studies were included. A statistically significant association was detected between neonatal phototherapy and any type of cancer (OR 1.24; 95% CI 1.1, 1.4), any hematopoietic cancer (OR 1.49; 95% CI 1.17, 1.91), any leukemia (OR 1.35; 95% CI 1.08, 1.67), and myeloid leukemia (OR 2.86; 95% CI 1.4, 5.84). The other investigated cancers (lymphoid leukemia, Hodgkin\'s lymphoma, kidney cancer, nervous system cancer, and skin cancer) were not associated with phototherapy.  Conclusions: Phototherapy may carry a possible risk of future cancers. Future research is needed to quantify the magnitude of the cancer risk. These future studies should consider predictors of preterm birth or exclude premature babies from their analysis. What is Known • There were various reports about the possible association between phototherapy in neonates and the increased risk of cancer in the future. What is New • A statistically significant association between phototherapy and various hematopoietic cancers (especially myeloid leukemia) was recorded. • The effect of the duration of phototherapy on the increased risk of hematopoietic cancers is yet unclear.

BACKGROUND: Neonatal jaundice is a transitional phenomenon affecting three out of five full-term newborns globally. Ursodeoxycholic acid could be beneficial in neonatal jaundice needing phototherapy.  METHODS: We searched PubMed, EBSCO, ProQuest, and Cochrane Library up to August 21st, 2021, for articles to be reviewed. Meta-analysis using random-effects model was performed.
RESULTS: Eight studies involving 1116 neonates were chosen in this review; however, only five studies were included for meta-analysis. Phototherapy duration was significantly lower in the interventional group with high heterogeneities. Subgroup analysis of the phototherapy duration based on the risk of bias resulted in a shorter duration (mean difference (MD) = -17.82; 95% CI = -20.17 to -15.47; p =  < 0.001) with low heterogeneity in the treatment group. Secondary outcome focusing on mean total serum bilirubin showed a lower mean total serum bilirubin in 48 h post-treatment (MD = -0.43; 95% CI = -0.64 to -0.22; p =  < 0.0001) with low heterogeneities in Asian countries.\"
CONCLUSIONS: Ursodeoxycholic acid might be considered as a novel adjuvant therapy in neonatal indirect hyperbilirubinemia to shorten the phototherapy duration and lower the mean total serum bilirubin.

Neonatal jaundice is a common condition characterized by a yellowish discoloration of the skin, conjunctiva, and sclera caused by elevated serum or plasma bilirubin levels during the newborn period. The condition is usually not dangerous, but it can progress to severe hyperbilirubinemia, which can lead to acute bilirubin encephalopathy and kernicterus, a bilirubin-induced neurological damage. Therefore, this study aimed to assess the pooled prevalence of neonatal jaundice and its determinants in Ethiopia.
Scopus, PubMed, Google Scholar, Embase, and CINAHL databases were searched for studies published between January 1, 2010 and July 30, 2021. A weighted DerSimonian Laird random-effects model was used to estimate the pooled prevalence of neonatal jaundice and its associated factors. The I2 was used to calculate the degree of heterogeneity. The funnel plot and Egger\'s regression test were used to assess publication bias.
Totally 697 articles were generated from various databases, and the review included a total of eight articles. The pooled prevalence of neonatal jaundice was 30.96% [95% confidence interval (CI) 16.61%-45.31%)] in Ethiopia. This review showed that prolonged labor [adjusted odd ratio (AOR) = 3.39; 95% CI 2.41-4.77), low birth weight (AOR = 5.12; 95% CI 3.11-8.72), birth asphyxia (AOR = 3.75; 95% CI 2.11-6.66), cephalohematoma (AOR = 7.07; 95% CI 2.72-18.38), ABO incompatibility (AOR = 6.05; 95% CI 2.95-12.42), Rhesus (RH) incompatibility (AOR = 3.77; 95% CI 2.04-6.96), male sex (AOR = 4.53; 95% CI 3.39-6.07), and neonatal sepsis (AOR = 2.47; 95% CI 1.49-4.08) were identified as a determining factor for neonatal jaundice in Ethiopia.
In low- and middle-income countries, neonatal jaundice is a significant healthcare burden, accounting for a significant portion of global childhood mortality and morbidity. However, some low-cost, effective, practical, and dependable solutions have been implemented. Prolonged labor, ABO incompatibility, RH incompatibility, birth asphyxia, neonatal sepsis, low birth weight, cephalohematoma, and male sex were identified as risk factors for neonatal jaundice in Ethiopia.

BACKGROUND: Neonatal hyperbilirubinemia is observed in most newborns, and 5-15% of neonates require phototherapy. Phototherapy is effective but often prolongs hospitalization and has both short-term and potential long-term harms. The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid (UDCA) combined with phototherapy in neonatal hyperbilirubinemia.
METHODS: A literature search was conducted on September 1, 2021; 590 studies were screened, and 17 full texts were assessed by two authors. We included randomized controlled trials with or without placebo intervention. Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration. We calculated mean differences with 95% confidence intervals (CI).
RESULTS: Six studies with 880 neonates were included. Of these studies, only two used a placebo-controlled double-blinded design. The overall risk of bias was high in one and moderate in four of the included studies. The mean decrease in the total bilirubin level during the first 24 hours was 2.06 mg/dL (95% CI 0.82-3.30; six studies) greater in the UDCA treatment group. The phototherapy duration was 19.7 hours (95% CI 10.4-29.1; five studies) shorter in the UDCA treatment group.
CONCLUSIONS: We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment. Further studies are needed to confirm the efficacy, acute and long-term outcomes, and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.

BACKGROUND: Yinzhihuang granule, consisting of extracts of Artemisia capillaris Thunb., Gardenia jasminoides Ellis, Lonicera japonica Thunb., and Scutellaria baicalensis Georgi is a well-known traditional Chinese patent medicine for patients with liver injury in China. However, the effects and safety of its use for pathologic jaundice in newborns require further systematic evaluation.
OBJECTIVE: To systematically evaluate the efficacy and safety of Yinzhihuang granules for the treatment of neonatal pathologic jaundice and to provide clinical evidence.
METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database, and VIP Database) and English databases (PubMed, EmBase, and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on Yinzhihuang granules for neonatal pathologic jaundice from the establishment of all databases to November 18, 2021. A meta-analysis was performed for selected data using STATA software. TSA software was used for trial sequential analyses of the total effective rate and adverse reactions.
RESULTS: A total of 19 trials and 2,221 newborns with pathologic jaundice were included in this study. Outcome measures of clinical efficacy in the experimental group were higher than in controls, including total bilirubin (WMD = -30.34, 95% CI = -35.44 to -25.23, p < 0.001), direct bilirubin (WMD = -15.03, 95% CI = -23.54 to -6.52, p < 0.001), indirect bilirubin (WMD = -11.22, 95% CI = -17.50 to -4.95, p < 0.001), recovery time (WMD = -2.96, 95% CI = -3.92 to -2.00, p < 0.001), hospitalization time (WMD = -3.83, 95% CI = -4.89 to -2.76, p < 0.001), and liver function indices. There were statistically significant differences between the two groups. Likewise, the incidence of adverse reactions, including diarrhea, erythra, and fever decreased remarkably in the trial group (RR = 0.44, 95% CI =  0.33 to 0.59, p < 0.001). Publication bias did not exist. We verified the efficacy and safety of Yinzhihuang granules with phototherapy for pathologic jaundice in newborns according using TSA analysis.
CONCLUSIONS: Yinzhihuang granules with phototherapy for neonatal pathologic jaundice are more effective than phototherapy alone. The incidence of ADRs does not increase with the application of Yinzhihuang granules. Due to the heterogeneity across the included studies, additional multicenter clinical trials with follow-ups are needed to confirm our findings.