OBJECTIVES: To evaluate the clinical utility and translational potential of a remote jaundice monitoring system for home-based screening of neonatal hyperbilirubinemia. METHODS: A prospective self-controlled study was conducted, enrolling 538 newborns with gestational age ≥35 weeks, birth weight ≥2 000 g, and postnatal age ≤14 days at the Women's Hospital of Nanjing Medical University from March to October 2023. Four screening protocols with different predictive indicators were developed based on the Chinese Neonatal Transcutaneous Hourly Bilirubin Nomogram. The effectiveness of the system was evaluated, and the feasibility of using the remote jaundice monitoring system in actual home settings was analyzed. RESULTS: A total of 538 paired transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) measurements showed a strong correlation (r=0.85, P<0.001), with 95.0% (511/538) of samples within the 95% limits of agreement. Using TcB ≥ the 95th percentile as the predictive indicator, the system achieved 100% sensitivity, 46.2% specificity, and an area under the receiver operating characteristic curve of 0.731 (95%CI: 0.682-0.780). This approach could reduce unnecessary hospital visits by 41.4% (221/538). CONCLUSIONS The system integrates the QBH-801 transcutaneous bilirubinometer, intelligent early warning, and remote guidance services, establishing a closed-loop "hospital-to-home" management model. It demonstrates high safety and feasibility, with significant clinical translational value.
Humans ; Infant, Newborn ; Female ; Male ; Bilirubin/blood* ; Feasibility Studies ; Prospective Studies ; Hyperbilirubinemia, Neonatal/diagnosis* ; Neonatal Screening/methods* ; Jaundice, Neonatal/diagnosis*

OBJECTIVES: To examine the global, regional, and national disease burden of neonatal jaundice. METHODS: The 2019 Global Burden of Disease database was searched to collect incident cases/incidence and deaths/mortality of neonatal jaundice, as well as global socio-demographic index (SDI) and universal health coverage index (UHCI). The epidemiological trend of neonatal jaundice from 1990 to 2019 was analyzed. The correlations between incidence/mortality of neonatal jaundice and SDI and UHCI were evaluated. RESULTS: From 601 681 in 1990 to 626 005 in 2019, with a 4.04% increase in global incident cases of neonatal jaundice. The overall age-standardized incidence rate exhibited an increase [estimated annual percent change=0.13 (95%CI: 0.03 to 0.23)] during this period. Additionally, deaths due to neonatal jaundice decreased by 58.83%, from 128 119 in 1990 to 52 742 in 2019. The overall age-standardized mortality rate showed a decrease [estimated annual percent change=-2.78 (95%CI: -3.00 to -2.57)] over the same period. Countries with lower SDI, such as India, Pakistan, and Nigeria, reported a higher proportion of neonatal morbidity and mortality. In 2019, a negative correlation was observed between estimated annual percent change in age-standardized mortality rate and SDI (ρ=-0.320, P<0.05) or UHCI (ρ=-0.252, P<0.05). CONCLUSIONS The global incidence of neonatal jaundice is on the rise, while the mortality rate is declining. The burden of neonatal jaundice is influenced by social development, economic factors, and the level of medical care.
Infant, Newborn ; Humans ; Global Burden of Disease ; Jaundice, Neonatal/epidemiology* ; Incidence

OBJECTIVE: To explore the genetic etiology and differential diagnosis for a patient with jaundice. METHODS: Clinical data of the patient and his parents were collected. Genes associated with metabolic liver diseases were subjected to high-throughput sequencing. The pathogenicity of the candidate variants was predicted by using bioinformatics software. RESULTS: High-throughput sequencing revealed that the proband has harbored two variants of the ABCC2 gene (NM_000392) including c.3011C>T (p.T1004I) and c.3541C>T (p.R1181X), which were respectively inherited from his father and mother. Both variants have been previously unreported and predicted to be pathogenic by bioinformatics analysis. CONCLUSION The proband was diagnosed with Dubin-Johnson syndrome due to the compound heterozygous variants of the ABCC2 gene. Genetic testing has enabled accurate differential diagnosis of Dubin-Johnson syndrome in this patient.
Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Jaundice, Chronic Idiopathic/pathology* ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Mutation

OBJECTIVE: To explore the genetic etiology in four patients with hyperbilirubinemia, and discuss the correlation between clinical characteristics and molecular basis. METHODS: The data of clinical manifestation and auxiliary examinations were collected. Genomic DNA of the four patients was extracted and analyzed by next-generation sequencing using the panel including genes involved in hereditary metabolic liver diseases. Suspected variants were verified by Sanger sequencing. RESULTS: All of the four patients were males with normal liver enzymes. It was revealed that all the patients had heterozygous variants, among which c.3011C>T, c.2443C>T and c.2556del were the variants which have not been reported previously. CONCLUSION All of the patients were diagnosed as Dubin-Johnson syndrome (DJS) caused by ABCC2 gene variants. The novel variants add to the spectrum of genetic variants of the disease. Because of the favorite prognosis, precise diagnosis can greatly reduce the psychological pressure of patients and avoid excessive treatments. At the same time, it could provide pertinent genetic counseling for the families.
DNA ; Female ; Heterozygote ; Humans ; Jaundice, Chronic Idiopathic/genetics* ; Male ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Phenotype

OBJECTIVE: To study the association of fatty acid composition in human milk with breast milk jaundice (BMJ) in neonates. METHODS: A total of 30 full-term neonates who were admitted to the neonatal intensive care unit from October 2016 to October 2017 and were diagnosed with late-onset BMJ were enrolled as the BMJ group. Thirty healthy neonates without jaundice or pathological jaundice who were admitted to the confinement center during the same period of time were enrolled as the control group. Related clinical data were collected, including sex, mode of birth, feeding pattern, gestational age, birth weight, gravida, parity, and peak level of total serum bilirubin. Breast milk was collected from the mothers, and the MIRIS human milk analyzer was used to measure macronutrients (fat, protein, and carbohydrate) and calorie. Gas chromatography was used to analyze the content of different fatty acids in breast milk. RESULTS: The control group had higher levels of macronutrients in human milk than the BMJ group, with significant differences in fat, dry matter, and calorie ( CONCLUSIONS Some macronutrients and fatty acid composition in human milk may be associated with the pathogenesis of BMJ in neonates.
Case-Control Studies ; Fatty Acids/analysis* ; Female ; Humans ; Infant, Newborn ; Jaundice, Neonatal/etiology* ; Milk, Human/chemistry* ; Nutrients/analysis* ; Pregnancy

OBJECTIVE: To explore the feasibility of remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease. METHODS: Forty six neonates of gestational age >35 weeks with ABO hemolytic disease admitted to Women's Hospital, Zhejiang University School of Medicine from January 20th, 2020 to February 29th, 2020 were enrolled in the study (study group). The newborns were followed up at home after discharge, the transcutaneous bilirubin (TCB) levels were measured by parents using the provided device and the results were sent to the doctor by smart phone using the installed APP. Fifty six newborns with ABO hemolytic disease admitted in 2018 who received conventional outpatient follow-up after discharge served as the control group. The demographic characteristics, total serum bilirubin (TSB) level during hospitalization, number of outpatient visit and rate of re-admission due to rebound hyperbilirubinemia were compared between the two groups. RESULTS: There were no significant differences between the two groups in gestational age, birth weight, delivery mode, gender, length of the first hospitalization, TSB level before phototherapy and before discharge, and the managements during the first hospitalization (all CONCLUSIONS The remote follow-up for neonatal jaundice at home can effectively reduce the number of outpatient visits without increasing the risk of readmission and severe neonatal hyperbilirubinemia for newborns with ABO hemolytic disease.
Bilirubin ; Erythroblastosis, Fetal/diagnosis* ; Female ; Humans ; Hyperbilirubinemia, Neonatal/diagnosis* ; Infant, Newborn ; Jaundice, Neonatal/diagnosis* ; Monitoring, Physiologic/methods* ; Phototherapy

OBJECTIVE: To explore the clinical characteristics and molecular basis for a Chinese boy affected with jaundiced skin and liver disease. METHODS: The patient was subjected to clinical examination and laboratory tests. Genomic DNA of the patient and his parents was extracted and analyzed by using next generation sequencing (NGS). Suspected mutations were analyzed with bioinformatic software and verified by Sanger sequencing. RESULTS: The patient had jaundice in his eyes and skin. Serum bilirubin was elevated along with hepatomegaly. Next generation sequencing showed that the patient has carried c.18C>A(p.C6X) and c.2556delA mutations in the MRP2 gene, which were respectively inherited from his father and mother. CONCLUSION The missense mutation c.18C>A and frameshift mutation c.2556delA probably account for the disease. NGS has provided a powerful tool for the diagnosis of rare genetic diseases including Dubin-Johnson syndrome.
Asian Continental Ancestry Group ; DNA ; High-Throughput Nucleotide Sequencing ; Humans ; Jaundice, Chronic Idiopathic ; Male ; Mutation

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder resulting from biallelic mutations of ABCC2 gene, with long-term or intermittent conjugated hyperbilirubinemia being the main clinical manifestation. This paper aims to report the clinical features and ABCC2 genotypes of an infant with DJS. A 9.5-month-old male infant was referred to the hospital due to abnormal liver function discovered over 9 months. The major clinical presentation was prolonged jaundice since neonatal period. A series of biochemistry analysis revealed markedly elevated total bilirubin, conjugated bilirubin and total bile acids. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. Physical examination revealed jaundiced skin and sclera, and a palpable liver 3 cm below the right subcostal margin with medium texture. The spleen was not enlarged. Genetic analysis revealed a splice-site variant c.3988-2A>T and a nonsense variant c.3825C>G (p.Y1275X) in the ABCC2 gene of the infant, which were inherited from his mother and father respectively. The former had not been previously reported. Then ursodeoxycholic acid and phenobarbital were given orally. Half a month later, as a result, his jaundice disappeared and the biochemistry indices improved. However, the long-term outcome needs to be observed. Literature review revealed that neonates/infants with DJS presented with cholestatic jaundice soon after birth as the major clinical feature, and the ABCC2 variants exhibited marked heterogeneity.
Bile Acids and Salts ; Bilirubin ; Humans ; Infant ; Jaundice ; Jaundice, Chronic Idiopathic ; genetics ; Male ; Multidrug Resistance-Associated Proteins ; genetics ; Ursodeoxycholic Acid

We present the case of a patient with biliary and duodenal atresia who showed false-negative hepatobiliary scintigraphy results. The patient was born at 37 weeks and 2 days of gestation. Her mother had undergone amnioreduction after detection of a double-bubble ultrasound sign in the fetal abdomen. At 2 days of age, total serum bilirubin level was elevated. On hepatobiliary scintigraphy 4 days later, the gallbladder was visualized from 30 min and it showed duodeno-gastric reflux at 240 min. After 24 h, the radiotracer was almost washed out in the hepatic parenchyma, but there was retention in the gastroduodenal junction. Because the biliary to duodenal transit was visible, biliary atresia seemed unlikely. Abdominal ultrasonography at 7 days of age showed a small dysmorphic gallbladder, but triangular cord sign was not definite. Magnetic resonance cholangiography revealed atretic gallbladder. Although cystic and common bile ducts were visible, the proximal common hepatic bile duct was not visible. The next day, serum total bilirubin levels remained elevated (17.1 mg/dl) with direct bilirubin level of 1.2 mg/dl. Kasai portoenterostomy with duodeno-duodenostomy was performed at 10 days of age. Histopathological evaluation showed a fibrous obliteration of the common bile duct, consistent with that of biliary atresia.
Abdomen ; Bile Ducts ; Biliary Atresia ; Bilirubin ; Cholangiography ; Common Bile Duct ; Duodenogastric Reflux ; Gallbladder ; Humans ; Infant, Newborn ; Jaundice, Neonatal ; Mothers ; Pregnancy ; Radionuclide Imaging ; Ultrasonography

OBJECTIVES: Herbal remedies such as purgative manna are used to treat neonatal jaundice. In this study Bilineaster drop (purgative manna) and phototherapy, and phototherapy treatment alone were compared by assessing phototherapy duration and number of days in hospital. METHODS: There were 150 consecutive term neonates with jaundice, weighting from 2,500 g to 4,000 g enrolled in this randomized double blind clinical trial. The neonates were randomly assigned to intervention and control groups. The control patients received only phototherapy and the intervention group underwent phototherapy treatment and purgative manna drop (5 drops per kg of body weight, 3 times a day). Direct and total measurements of bilirubin concentration in the serum were measured and the reduction in concentration of bilirubin was calculated. RESULTS: There were 28% of patients whose hospital duration following phototherapy was 2 days, for Bilineaster and phototherapy treatment this was 49.3% of patients. At 48 hours and 72 hours the reduction in the concentration of total bilirubin in the serum was statistically significantly different across groups (p < 0.05) but at 24 hours and 96 hours there were no significant differences between groups (p > 0.05). The reduction in direct bilirubin concentration in the serum was significantly different between groups at 72 hours and 96 hours (p > 0.001). CONCLUSION: Purgative manna and phototherapy, can statistically significantly reduce total bilirubin concentration at 48 hours and 72 hours compared with phototherapy alone, and reduce the length of hospital stay for jaundiced neonates at 2 days compared with phototherapy treatment.
Bilirubin ; Body Weight ; Herbal Medicine ; Humans ; Infant, Newborn ; Jaundice ; Jaundice, Neonatal ; Length of Stay ; Phototherapy