Insights into Risk: Exploring Retinopathy of Prematurity and Short-term Comorbidities in Moderate-to-Late Preterm Infants.

BACKGROUND: Retinopathy of prematurity (ROP) and short-term comorbidity data moderate-to-late preterm (MLP) infants in Saudi Arabia are limited. AIM: The present study mainly aimed to identify ROP incidence and severity in MLP infants. The secondary objective was to explore whether moderate preterm infants are more prone to systemic short-term comorbidities compared to late preterm infants. MATERIALS AND METHODS: This retrospective study was conducted at King Abdulaziz University Hospital, a tertiary center in Jeddah, Saudi Arabia. Two-hundred and sixty-eight MLP infants born with gestational ages (GAs) of 32 to 36 + 6 weeks were included. Births were classified as moderate preterm (GA 32 to 33 + 6 weeks) and late preterm (GA 34 to 36 + 6 weeks) and the two groups were compared with an independent t-test. RESULTS: ROP incidence was 1.5%; all cases were stage 1 and involved zone II or III. No patient had type 1 ROP requiring treatment. The short-term comorbidity incidence was high (76.1%) and included hyperbilirubinemia (n = 206, 76.7%), respiratory distress syndrome (n = 178, 66.4%), hypoglycemia (n = 32, 11.9%,), and transient tachypnea of newborn (n = 25, 9.3%). Moderate preterm infants were more likely to have lower birth weight (P < 0.001), any-stage ROP (P = 0.032), respiratory distress syndrome (P = 0.031), intraventricular hemorrhage (P = 0.038), and hyperbilirubinemia (P < 0.001) compared to the late preterm infants. CONCLUSIONS: Any-stage ROP incidence among MLP infants was low, with no type 1 ROP cases requiring treatment. Short-term comorbidity incidence was relatively high among the moderate preterm infants. Despite the low non-type 1 ROP incidence at our center, MLP infants require proper surveillance of systemic short-term comorbidities.

Jaundice in a Child with Sickle Cell Anemia: A Case Based Approach.

Sickle cell anemia (SCA) is an autosomal recessive disorder caused by a mutation in beta globin gene. Hepatobiliary system is affected in 10-40% of patients with SCA and has a multifactorial etiology. The authors present a child with SCA and conjugated hyperbilirubinemia due to biliary obstruction. He underwent endoscopic retrograde cholangiopancreatography (ERCP) and biliary stenting, had complications of post sphincterotomy bleed, retroperitoneal hematoma and post laparoscopic cholecystectomy sepsis with acute sickle hepatic crisis. He was managed successfully and is doing well on follow-up. Here authors discuss a stepwise approach in management of jaundice in a patient with SCA. Patients with SCA are prone to develop vaso-occlusive crisis (VOC) during periods of stress. VOC affects the liver as acute sickle hepatic crisis, acute hepatic sequestration or sickle cell intrahepatic cholestasis and is collectively termed as sickle cell hepatopathy. Hemolysis due to sickling results in cholelithiasis with its associated complications. These patients are vulnerable to viral hepatitis and hemochromatosis due to multiple blood transfusions. There may be a concomitant acute viral hepatitis, drug induced liver injury, Budd-Chiari syndrome or other chronic liver diseases. These conditions have considerable clinical overlap and may coexist, making the evaluation more challenging. Detailed history, examination and investigations are required for differentiation of etiology. Periods of stress must be tackled with proper hydration, oxygen supplementation, maintaining hemoglobin >10 g/dL, and a low hemoglobin S fraction. Patients with SCA and conjugated hyperbilirubinemia are "high-risk" and best managed by a multidisciplinary team. Preventive strategies like timely vaccinations, chelation, etc. must be practised.

Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia.

OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

Prevalence and association of early onset severe hyperbilirubinemia in newborn in the East China region: Retrospective medical record analyses.

Research on the prevalence and association of hyperbilirubinemia is controversial because of different cultures, demographics, and clinical conditions. The etiology of hyperbilirubinemia is affected by the environment and other factors in the newborn. The World Health Organization recommended a 1-day hospital stay after uncomplicated delivery, jaundice assessment before discharge, and screening on 3rd and 7th days after birth for hyperbilirubinemia. However, the implementation of these recommendations is difficult in China. The objective of this study was to evaluate the prevalence and association of early onset severe hyperbilirubinemia in newborns in East China. Retrospective medical record analyses for 250 cesarean sections or vaginal deliveries, ≥2 kg body weight, and negative for Hepatitis B surface antigen by birth newborns were performed. A biochemical analyzer, quantitative assay, and quantitative polymerase chain reaction were used to evaluate total serum bilirubin, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and gene variant phenotyping, respectively. A total in 33 (13%) newborns were reported with early onset severe hyperbilirubinemia (according to the American Academy of Pediatrics, total serum bilirubin ≥ 342 µmol/L within 6 hours of birth). All newborns with severe hyperbilirubinemia were hospitalized and underwent phototherapy. The mothers of all newborns had a gestational age ≥ 35 weeks. Hospitalization included artificial feeding, and breastfeeding was rare (P < .0001). ABO incompatibility ("O" blood type for mother and either "A" or "AB" or "B" blood type for newborn, P = .0411), G6PD deficiency (G6PD/6-phosphogluconate dehydrogenase ≤ 1.0 in quantitative assay, P = .0422), Rh incompatibility (the mother's blood type was Rh negative and newborn blood type was Rh positive, P = .0416), fewer genotype rs4149056 frequencies (P = .0452), higher genotype rs2306283 frequencies (P = .0461), and higher genotype rs1805173 frequencies (P = .0471) were independent parameter for early onset severe hyperbilirubinemia of newborns. The prevalence of early onset severe hyperbilirubinemia in Chinese newborns is 13% in the East China region. Blood incompatibility, G6PD deficiency, fewer genotype rs4149056 frequencies, higher genotype rs2306283 frequencies, and higher genotype rs1805173 frequencies were independent predictors of early onset severe hyperbilirubinemia among newborns in the East China region (Level of Evidence: IV; Technical Efficacy: Stage 5).

An evaluation of ursodeoxycholic acid treatment in prolonged unconjugated hyperbilirubinemia due to breast milk.

Background/Aim: Prolonged jaundice is one of the most common problems during neonatal period. The aim of this study was to evaluate the efficiency of ursodeoxycholic acid (UDCA) treatment in newborn infants with prolonged unconjugated hyperbilirubinemia. Materials and Methods: The present study included 27 patients who were fed by breast milk and followed up in the outpatient clinic due to prolonged jaundice without any underlying etiological factor; 10 mg/kg/day UDCA was administrated in two doses for 7 days. Furthermore, 20 newborns diagnosed with prolonged jaundice with same characteristics were enrolled as the control group. The control group was also given a placebo; demographic characteristics, liver functions tests before and after the treatment, bilirubin decrease rates, and hemogram parameters of groups were compared. Results: Total bilirubin levels in the study and control groups before the treatment were 16.02 ± 1.41 mg/dL and 15.93 ± 1.66 mg/dL, respectively (P = 0.84). Total bilirubin levels in the study and control groups at day 7 after UDCA treatment were detected 8.18 ± 2.31 mg/dL and 13.92 ± 2.66 mg/dL, respectively (P < 0.001), and at day 14 after the treatment were 5.45 ± 2.59 mg/dL and 11.91 ± 2.83 mg/dL, respectively (P < 0.001). Furthermore, serum aspartate aminotransferase (AST) was detected <21 U/L in the ROC analysis after UDCA treatment (P = 0.04). Conclusion: The study outcomes indicated that an efficient reduction in total bilirubin levels may be achieved, and outpatient clinic follow-up period may be reduced in patients whom UDCA was administrated. Moreover, it may be speculated that AST can be used to evaluate the efficacy after treatment. However, studies with larger sample sizes are needed for the routine use of UDCA in the treatment of prolonged jaundice.

Cardiovascular and metabolic effects of hyperbilirubinemia in a cohort of Italian Olympic athletes.

INTRODUCTION: Bilirubin was supposed to have cardio-metabolic protective role by signaling functions. Indeed, mild hyperbilirubinemia has immunosuppressive and endocrine activities and may offer protection against oxidative stress-mediated diseases. Gilbert syndrome (GS) has been hypothesized to provide cardio-metabolic benefits. OBJECTIVE: To investigate the prevalence of hyperbilirubinemia and its cardio-metabolic effects in a cohort of elite Italian athletes engaged in different sports disciplines. METHODS: We enrolled 1492 elite athletes (age 25.8 ± 5.1) practising different disciplines (power, skills, endurance, and mixed) underwent blood, echocardiographic, and exercise tests. GS was diagnosed per exclusionem in athletes with isolated asymptomatic unconjugated hyperbilirubinemia. RESULTS: GS was highlighted in 91 athletes (6%; globally 9% male and 2.4% female); 82% were males (p < 0.0001) showing higher indirect bilirubin (0.53 ± 0.4 vs. 0.36 ± 0.24 mg/dL in females, p < 0.0001). GS athletes had fewer platelets (201 ± 35 vs. 214 ± 41, p = 0.01), higher iron (male: 124 ± 44 vs. 100.9 ± 34 mcg/dL, p < 0.0001; female: 143.3 ± 35 vs. 99.9 ± 42 mcg/dL, p < 0.0001), and lower erythrocyte sedimentation rate, (1.93 ± 0.9 vs. 2.80 ± 2.7 mm/H, p = 0.03). At multivariate analysis, male (OR 3.89, p = 0.001) and iron (OR 3.47, p = 0.001) were independently associated with GS. No significant differences were found in cardiac remodeling, heart rate, blood pressure, arrhythmias, or power capacity at stress test. Endurance athletes (313) presented higher total (p = 0.003) and indirect bilirubin (p = 0.001). CONCLUSION: Bilirubin has several metabolic effects (including immunosuppressive and endocrine) and plays a role in regulating antioxidant pathways exercise-related with hematological consequences but seems not to affect significantly cardiovascular remodeling. Endurance athletes present higher bilirubin concentrations, likely as an adaptive mechanism to counteract increased oxidative stress.

Serum metabolomics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau has unique characteristics.

Few studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.

Intravenous immunoglobulin G therapy for neonatal hyperbilirubinemia.

BACKGROUND: Neonatal hyperbilirubinemia (NHb) results from increased total serum bilirubin and is a common reason for admission and readmission amongst newborn infants born in North America. The use of intravenous immunoglobulin (IVIG) therapy for treating NHb has been widely debated, and the current incidence of NHb and its therapies remain unknown. METHODS: Using national and provincial databases, a population-based retrospective cohort study of infants born in Ontario from April 2014 to March 2018 was conducted. RESULTS: Of the 533,084 infants born in Ontario at ≥35 weeks gestation, 29,756 (5.6%) presented with NHb. Among these infants, 80.1-88.2% received phototherapy, 1.1-2.0% received IVIG therapy and 0.1-0.2% received exchange transfusion (ET) over the study period. Although phototherapy was administered (83.0%) for NHb, its use decreased from 2014 to 2018 (88.2-80.1%) (P < 0.01). Similarly, the incidence of IVIG therapy increased from 71 to 156 infants (1.1-2.0%) (P < 0.01) and a small change in the incidence of ET (0.2-0.1%) was noted. CONCLUSION: IVIG therapy is increasingly being used in Ontario despite limited studies evaluating its use. The results of this study could inform treatment and management protocols for NHb. IMPACTS: Clinically significant neonatal hyperbilirubinemia still occurs in Ontario, with an increasing number of infants receiving Intravenous Immunoglobulin G (IVIG) therapy. IVIG continues to be used at increasing rates despite inconclusive evidence to recommend its use. This study highlights the necessity of a future prospective study to better determine the effectiveness of IVIG use in treating neonatal hyperbilirubinemia, especially given the recent shortage in IVIG supply in Ontario. The results of this study could inform treatment and management protocols for neonatal hyperbilirubinemia.

HYPERBILIRUBINEMIA AGGRAVATES RENAL ISCHEMIA REPERFUSION INJURY BY EXACERBATING PINK1-PARKIN-MEDIATED MITOPHAGY.

ABSTRACT: Background: Hyperbilirubinemia is a common perioperative complication, which is associated with acute kidney injury. Bilirubin permeabilizes mitochondrial membranes leading to mitochondrial swelling and dysfunction. In this study, we aimed to determine the association between PINK1-PARKIN-mediated mitophagy and renal ischemia-reperfusion (IR) injury aggravated by hyperbilirubinemia. Methods: A C57BL/6 mouse hyperbilirubinemia model was induced via intraperitoneal injection of bilirubin solution. In addition, a hypoxia/reoxygenation (H/R) injury model of TCMK-1 cells was established. In these models, we determined the effects of hyperbilirubinemia on oxidative stress, apoptosis, mitochondrial damage, and fibrosis. Results:In vitro , colocalization of GFP-LC3 puncta and Mito-Tracker Red showed that the number of mitophagosomes increased in TCMK-1 cells under H/R and bilirubin condition. Silencing of PINK1 or inhibition of autophagy alleviated mitochondrial damage, oxidative stress, and apoptosis in H/R injury aggravated by bilirubin and decreased cell death detected by methyl-thiazolyl-tetrazolium. In vivo , hyperbilirubinemia increased serum creatinine level in the renal IR injury mice model. Hyperbilirubinemia enhanced apoptosis induced by renal IR. In addition, hyperbilirubinemia increased mitophagosomes and autophagosomes and disrupted mitochondrial cristae in the IR kidney. Inhibition of PINK1 or autophagy reduced histological damages by alleviating apoptosis in renal IR injury, aggravated by hyperbilirubinemia. 3-MA or PINK1-shRNA-AAV9 treatment decreased the area of collagen and proteins related to fibrosis in renal IR injury, aggravated by hyperbilirubinemia. Conclusions: We have demonstrated that hyperbilirubinemia aggravated oxidative stress, apoptosis, mitochondrial damage, and fibrosis in renal IR injury by exacerbating PINK1-PARKIN-mediated mitophagy.

Hyperbilirubinemia in hospitalized patients: Etiology and outcomes.

There is little information on the differential diagnosis and prognosis of hospitalized patients with hyperbilirubinemia. Here, we hypothesized that hyperbilirubinemia in hospitalized patients is associated with specific diseases and outcomes. This retrospective cohort analysis included patients admitted to the Medical University of South Carolina with a total bilirubin >3 mg/dL from January 9, 2015 to August 25, 2017. Collected clinical data included demographics, primary diagnosis, Charlson Comorbidity Index (CCI), laboratory data, and clinical outcomes. We separated and analyzed the cohort into seven primary diagnostic groups. We identified 1693 patients with a bilirubin level >3 mg/dL. The cohort was 42% female, had an average age of 54, average CCI of 4.8, and average length of stay of 13 days. The causes of hyperbilirubinemia included the following: primary liver disease (868/1693; 51%) with cirrhosis being most common (385/1693; 23%), benign biliary obstruction (252/1693; 15%), hemolytic anemia (149/1693; 9%), malignant biliary obstruction (121/1693; 7%), unknown etiology (108/1693; 6%), primary liver cancer (74/1693; 4%), and metastatic cancer to the liver (57/1693; 3%). Overall, the mortality/discharge to hospice rate in patients with a bilirubin >3 mg/dL was 30%, and was proportional to the severity of hyperbilirubinemia, including when controlling for the underlying severity of illness. Mortality was highest in patients with primary liver disease and malignancy and was lowest in patients with non-cancerous obstruction or hemolytic jaundice. Hyperbilirubinemia in hospitalized patients is most often due to primary liver disease, and identifies patients with a poor prognosis, particularly when caused by primary liver disease or cancer.

An Exploratory Analysis of Gastrointestinal Morbidities and Feeding Outcomes Associated with Neonatal Hypoxic-Ischemic Encephalopathy With or Without Hypothermia Therapy.

This study investigates the clinical profile and predictors of gastrointestinal/hepatic morbidities and feeding outcomes among neonates with hypoxic-ischemic encephalopathy (HIE). A single-center retrospective chart review of consecutive neonates >35 weeks of gestation admitted with a diagnosis of HIE between January 1, 2015, and December 31, 2020, and treated with therapeutic hypothermia, if met the institutional eligibility criteria. Outcomes assessed included necrotizing enterocolitis (NEC), conjugated hyperbilirubinemia, hepatic dysfunction, assisted feeding at discharge, and time to reach full enteral and oral feeds. Among 240 eligible neonates (gestational age 38.7 [1.7] weeks, birth weight 3279 [551] g), 148 (62%) received hypothermia therapy, and 7 (3%) and 5 (2%) were diagnosed with stage 1 NEC and stage 2-3 NEC, respectively. Twenty-nine (12%) were discharged home with a gastrostomy/gavage tube, conjugated hyperbilirubinemia (first week 22 [9%], at discharge 19 [8%]), and hepatic dysfunction (74 [31%]). Time to reach full oral feeds was significantly longer in hypothermic neonates compared with neonates who did not receive hypothermia (9 [7-12] days vs. 4.5 [3-9] days, p < 0.0001). Factors significantly associated with NEC were renal failure (odds ratio [OR] 9.24, 95% confidence interval [CI] 2.7-33), hepatic dysfunction (OR 5.69, 95% CI 1.6-26), and thrombocytopenia (OR 3.6, 95% CI 1.1-12), but no significant association with hypothermia, severity of brain injury, or stage of encephalopathy. Transient conjugated hyperbilirubinemia, hepatic dysfunction within first week of life, and need for assistive feeding are more common than NEC in HIE. Risk of NEC was associated with the severity of end-organ dysfunction in the first week of life, rather than severity of brain injury and hypothermia therapy per se.

Short-term outcomes of infants with hyperbilirubinemia-associated auditory neuropathy spectrum disorder in neonatal intensive care unit.

OBJECTIVES: Hyperbilirubinemia is a high-risk factor for auditory neuropathy spectrum disorder (ANSD) as well as hearing loss in general. This study described the outcomes of hyperbilirubinemia-associated ANSD infants diagnosed in hearing screening in the neonatal intensive care unit (NICU). METHODS: A total of 578 children with hyperbilirubinemia admitted to the NICU between October 2020 and October 2021 were included in this study. The distortion product otoacoustic emission (DPOAE) and automatic auditory brainstem response (AABR) were combined for hearing screening, and those who failed the DPOAE or/and AABR underwent an auditory brainstem response (ABR) test. Infants with ANSD were followed up for 12 months. RESULTS: Forty infants (40/578, 6.9%) failed the DPOAE or/and AABR tests, of which, 13 (13/578, 2.2%) were diagnosed as ANSD, and 27 (27/578, 4.7%) were diagnosed as having sensorineural hearing loss (SNHL). Of the 13 ANSD infants followed up for 12 months, 7 recovered, 3 improved, 3 did not recover, and 1 was lost, equating to improved or recovered hearing in 75% (9/12) of ANSD infants at 12 months of age. Moreover, the maximum bilirubin in recovered or improved ANSD infants was 408.6 ± 129.0 µmol/L, while the maximum bilirubin in unrecovered ANSD infants was 749.3 ± 323.0 µmol/L. Furthermore, poorly differentiated and absent ABR waveforms were observed in 6 and 14 ears at 1 month, 2 ears were lost, 6 (6/6, 100.0%) and 6 (6/12, 50.0%) ears were recovered or improved at 12 months of age. CONCLUSION: s: The incidence of hyperbilirubinemia associated-ANSD was 2.2% of infants screened in the NICU. ANSD caused by hyperbilirubinemia may be transient, with most infants improving or recovering hearing by 12 months of age. Infants with poorly differentiated ABR waveforms and low bilirubin concentration are more likely to recover and hearing aids are not recommended in hyperbilirubinemia-associated ANSD below 12 months of age.

Neonatal Hyperbilirubinemia: Evaluation and Treatment.

Neonatal jaundice due to hyperbilirubinemia is common, and most cases are benign. The irreversible outcome of brain damage from kernicterus is rare (1 out of 100,000 infants) in high-income countries such as the United States, and there is increasing evidence that kernicterus occurs at much higher bilirubin levels than previously thought. However, newborns who are premature or have hemolytic diseases are at higher risk of kernicterus. It is important to evaluate all newborns for risk factors for bilirubin-related neurotoxicity, and it is reasonable to obtain screening bilirubin levels in newborns with risk factors. All newborns should be examined regularly, and bilirubin levels should be measured in those who appear jaundiced. The American Academy of Pediatrics (AAP) revised its clinical practice guideline in 2022 and reconfirmed its recommendation for universal neonatal hyperbilirubinemia screening in newborns 35 weeks' gestational age or greater. Although universal screening is commonly performed, it increases unnecessary phototherapy use without sufficient evidence that it decreases the incidence of kernicterus. The AAP also released new nomograms for initiating phototherapy based on gestational age at birth and the presence of neurotoxicity risk factors, with higher thresholds than in previous guidelines. Phototherapy decreases the need for an exchange transfusion but has the potential for short- and long-term adverse effects, including diarrhea and increased risk of seizures. Mothers of infants who develop jaundice are also more likely to stop breastfeeding, even though discontinuation is not necessary. Phototherapy should be used only for newborns who exceed thresholds recommended by the current AAP hour-specific phototherapy nomograms.

Breast Milk Constituents and the Development of Breast Milk Jaundice in Neonates: A Systematic Review.

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.

[HEPATIC MANIFESTATIONS OF CHRONIC LYMPHOCYTIC LEUKEMIA AND CORRELATION WITH PROGNOSIS].

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Liver function tests (LFT) revealing impairment are described in 5% of CLL patients. Although these effects are described in the literature, their occurrence at the diagnosis of CLL and correlation with prognostic data have rarely been evaluated. We aimed to evaluate the prevalence of impairment of different LFT at CLL diagnosis and its correlation with prognosis. METHODS: This is a descriptive observational retrospective study. Diagnostic and prognostic data from CLL patients followed at Bnai Zion Medical Center were collected from charts for the period January 1st, 2000 until October 6, 2020. A t-test for continuous variables, Chi-2 and Fisher-exact tests for discrete variables, and log-rank test for survival analysis, were performed to evaluate prognostic correlations of impaired as compared with normal LFT. The significance level was defined as p value < 0.05. RESULTS: Overall, 153 patients with CLL diagnosed from 2000 until 2020 were included. The median age was 66 (42-89) years, and 62 were women (40.5%). Before CLL treatment initiation, mildly elevated cholestatic enzymes were encountered among 12% patients, while hepatocellular enzymes were elevated in only 2%. After excluding patients with hemolysis, hyperbilirubinemia was found among 5% of the patients. Cholestatic impairment was associated with negative prognostic data, especially increased alkaline phosphatase levels which was associated with a shorter overall survival (p=0.001). CONCLUSIONS: Impairment of cholestatic enzymes and hyperbilirubinemia is not rare before CLL treatment. Despite its mild impairment, it seems to be associated with worse prognosis.

The Green Placental Disk: Massive Placental Disk Bilirubin Deposition Due to Maternal Hyperbilirubinemia.

BACKGROUND: Bile staining in the hepatobiliary tree is a well-known phenomenon, but bilirubin can also be deposited in and stain the umbilical cord, amniotic fluid, placental disk and placental membranes. CASE REPORT: We present a placenta with grossly greenish discoloration of the placental disk and microscopic villous bilirubin deposition due to maternal hyperbilirubinemia. Conclusion: Maternal hyperbilirubinemia causes massive bilirubin deposition in villous synctiotrophoblasts and Hofbauer cells leading to grossly green discoloration of the placental disk.

Jaundice in relation to immune activation during Epstein-Barr virus-induced infectious mononucleosis.

BACKGROUND: Liver involvement during infectious mononucleosis is common, but jaundice is considered rare. This study aimed to investigate serum bilirubin concentrations in patients with infectious mononucleosis and immune abnormalities associated with jaundice. METHODS: We report on an adult patient with monoclonal B lymphocytosis and IgM-lambda gammopathy who developed a severe icteric hepatitis during infectious mononucleosis. We then reviewed the clinical records of 389 patients admitted to the hospital with infectious mononucleosis between 1995 and 2018 (51.7% male patients; median age, 19 years; range, 15-87 years) with focus on liver abnormalities and associated factors. RESULTS: Fifty-nine patients (15.1%) had serum bilirubin concentrations between 1.5 and 3 mg/dL, and 47 patients (12.0%) had serum bilirubin >3 mg/dL. Patients with increased bilirubin concentrations had a distinct clinical presentation, with more frequent abdominal pain, nausea and vomiting, and less frequent sore throat than patients with normal bilirubin. Age and sex were not significantly different for the patients with increased and normal serum bilirubin concentrations. The patients with increased serum bilirubin concentrations showed higher levels of immune activation markers than the patients with normal bilirubin, including blood lymphocyte counts, serum IgM, and ß2-microglobulin concentrations. Heterophile antibody-positive patients (88.6%) showed similar bilirubin concentrations but higher aspartate aminotransferase and alkaline phosphatase levels than their heterophile-negative counterparts. Serum bilirubin elevations normalized quickly during follow-up. CONCLUSIONS: Transient hyperbilirubinemia is common during severe (in-hospital) infectious mononucleosis in adult patients. Patients with hyperbilirubinemia have less frequent pharyngitis symptoms and more frequent abdominal symptoms. Hyperbilirubinemia during infectious mononucleosis is associated with immune activation markers.

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.

Indirect hyperbilirubinemia because of eltrombopag in two cases after autologous hematopoetic stem cell transplantation.

ABSTRACT: The oral thrombopoietin receptor agonist eltrombopag has some side effects. One of them is related to bilirubin metabolism. Two patients with neuroblastoma in remission underwent stem cell transplantation with the Busulfan-melphalan regimen. Eltrombopag was started because of platelet engraftment failure. Indirect hyperbilirubinemia was detected after eltrombopag treatment. Laboratory and radiological investigations were all normal. The drugs and their side effects they used were examined. After eltombopag cutting, bilirubin levels of them returned to normal. These cases are presented to emphasize that eltrombopag can cause liver toxicity with hypertransaminesemia and hyperbilirubinemia. Drug side effects should be considered in the differential diagnosis of the patients. The significance of this case is that testing for serum aminotransferase and bilirubin levels should be monitored before and after eltrombopag use.