Long-Term Effects of Biliverdin Reductase a Deficiency in Ugt1−/− Mice: Impact on Redox Status and Metabolism

Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of Bvra deficiency in neonatal and aged mice, in a background of unconjugated hyperbilirubinemia, by abolishing bilirubin production. We also investigated the disposal of biliverdin during fetal development. In Ugt1−/− mice, Bvra deficiency appeared sufficient to prevent lethality and to normalize bilirubin level in adults. Although biliverdin accumulated in Bvra-deficient fetuses, both Bvra−/− and Bvra−/−Ugt1−/− pups were healthy and reached adulthood having normal liver, brain, and spleen histology, albeit with increased iron levels in the latter. During aging, both Bvra−/− and Bvra−/−Ugt1−/− mice presented normal levels of relevant hematological and metabolic parameters. Interestingly, the oxidative status in erythrocytes from 9-months-old Bvra−/− and Bvra−/−Ugt1−/− mice was significantly reduced. In addition, triglycerides levels in these 9-months-old Bvra−/− mice were significantly higher than WT controls, while Bvra−/−Ugt1−/− tested normal. The normal parameters observed in Bvra−/−Ugt1−/− mice fed chow diet indicate that Bvra inhibition to treat unconjugated hyperbilirubinemia seems safe and effective.

Role of Short Duration Double Phototherapy in The Treatment of Unconjugated Hyperbilirubinemia

Objective: To determine the role of short duration double phototherapy in the treatment of unconjugated hyperbilirubinemia. Materials and Methods: This prospective cases series study was conducted at pediatric department of CMH hospital at Malir Karachi. All the neonates diagnosed with unconjugated hyperbilirubinemia admitted to the neonatal ward were included. All the cases underwent short duration double phototherapy. Babies were observed for side-effects of phototherapy, like skin reaction and dehydration. Serum bilirubin was checked by bilirubinometre after 6 hourly of the treatment. Al the data was collected via study proforma. Data was analyzed by using SPSS version 20 Results: Total 74 neonates were studied, most of the neonates presented within 48-72 hours after birth. Majority of the term babies as 59.5% had history of 37-40 weeks of gestation and 28.4% had gestational age history >40 weeks. Out of all, males’ babies were 58.1% and female babies were 41.9%. Neonatal bilirubin level was significantly decreased from bassline 18.35+0.97 after 6 hours of double phototherapy as 14.66+1.18 with mean difference of 3.68+1.37 (p-value 0.001). Conclusion: Short duration double phototherapy found to be the effective, reliable and safe for skin reaction in the treatment of unconjugated hyperbilirubinemia. Key words: Hyperbilirubinemia, double phototherapy, six hours

Irradiance footprint of phototherapy devices: a comparative study

Background Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. The irradiance footprint, i.e., the illuminated area by the PT device with sufficient spectral irradiance, is essential for PT to be effective. Irradiance footprint measurements are not performed in current clinical practice. We describe a user-friendly method to systematically evaluate the high spectral irradiance (HSI) footprint (illuminated area with spectral irradiance of ≥30 μW cm−2 nm−1) of PT devices in clinical practice. Materials and methods Six commercially available LED-based overhead PT devices were evaluated in overhead configuration with an incubator. Spectral irradiance (µW cm−2 nm−1) and HSI footprint were measured with a radiospectrometer (BiliBlanket Meter II). Results The average measured spectral irradiance ranged between 27 and 52 μW cm−2 nm−1 and HSI footprint ranged between 67 and 1465 cm2, respectively. Three, two, and one PT devices out of six covered the average BSA of an infant born at 22, 26–32, and 40 weeks of gestation, respectively. Conclusion Spectral irradiance of LED-based overhead PT devices is often lower than manufacturer’s specifications, and HSI footprints not always cover the average BSA of a newborn infant. The proposed measurement method will contribute to awareness of the importance of irradiance level as well as footprint measurements in the management of neonatal jaundice. Impact While a sufficient spectral irradiance footprint is essential for PT to be effective, some PT devices have spectral irradiance footprints that are too small to cover the entire body surface area (BSA) of a newborn infant. This study introduces a user-friendly, accessible method to systematically evaluate the spectral irradiance level and footprint of PT devices. This study supports awareness on the role of the spectral irradiance footprint in the efficacy of PT devices. Irradiance footprint can be easily measured during phototherapy with the proposed method.

EVALUATION OF THE EFFECTS OF PHOTOTHERAPY ON VARIOUS BIOCHEMICAL PARAMETERS IN NEONATAL HYPERBILIRUBINEMIA

BACKGROUND: Neonatal jaundice has been the most common physical nding during the earlier week of life. High values of unconjugated bilirubin can develop encephalopathy and later kernicterus. The aims of phototherapy are to avoid the occurrence of encephalopathy or kernicterus. Phototherapy has many side effects like dehydration, temperature instability, skin rashes, retinal damage, hypocalcemia, electrolyte imbalance. AIM: Aim is to investigate the effect of phototherapy in full term neonate with unconjugated hyper bilirubinemia on various biochemical parameters before and after >48 hr phototherapy. MATERIAL AND METHODS: The study was conducted in the department of pediatrics, S.P.M.C.H.I. (J.K. Lon Hospital) and hospitals attached to SMS Medical College, Jaipur, Rajasthan from June 2019 – July 2020. It was a Hospital based prospective comparative observational study. The required sample size was at least 154 Full term neonates (37 completed weeks to 42 weeks) with unconjugated Hyperbilirubinemia receiving phototherapy ≥ 48 hr. All data were collected and analyzed with the help of suitable statistical parameters. RESULTS: Present study found that all parameters ( Serum Bilirubin, Urea, Creatinine, Calcium, Total Protein, And Albumin except Serum Electrolyte) has shown similar trends i.e. statistically signicant ndings in both groups before and after phototherapy. Whereas serum electrolyte has different pattern in both groups, it showed statistically signicant results only in group-I. CONCLUSION: our study concluded that phototherapy is benecial modality with judicious calculation of the risk benet ratio.

Oral Manifestations of a Patient Suffering from a Rare Gilbert’s Syndrome: A Case Report

Gilbert's syndrome is a rare genetic disorder characterized by abnormal glucuronidation of bilirubin in the liver, presenting as unconjugated hyperbilirubinemia in the absence of hepatocellular injury or hemolysis. Diagnosis of this pathology is primarily made during routine examination described as the presence of a yellowish tinge in the eyes and skin in general. Normally, the oral manifestations of Gilbert's syndrome are present but mostly go unnoticed as the teeth are minimally affected which are visible to the patient and surrounding mucosa in the oral cavity, where yellow discoloration can be appreciated. Dental treatments are smoothly carried out for such patients like extractions, root canal treatment, cleaning prophylaxis. The patient in this case safely underwent the root canal treatment after being diagnosed with irreversible pulpitis without any unusual discomfort. Local anesthesia can also be safely administered to such patients such as infiltration and inferior alveolar block anesthesia.

Severe Presentation of Congenital Hemolytic Anemias in the Neonatal Age: Diagnostic and Therapeutic Issues

Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells abnormalities. Suggestive features of CHAs are anemia and hemolysis, with high reticulocyte count, unconjugated hyperbilirubinemia, increased lactate dehydrogenase (LDH), and reduced haptoglobin. The peripheral blood smear can help the differential diagnosis. In this review, we discuss the clinical management of severe CHAs presenting early on in the neonatal period. Appropriate knowledge and a high index of suspicion are crucial for a timely differential diagnosis and management. Here, we provide an overview of the most common conditions, such as glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and hereditary spherocytosis. Although rare, congenital dyserythropoietic anemias are included as they may be suspected in early life, while hemoglobinopathies will not be discussed, as they usually manifest at a later age, when fetal hemoglobin (HbF) is replaced by the adult form (HbA).

HEREDITARY UNCONJUGATED HYPERBILIRUBINEMIA (COMBINATION OF CRIGLER-NAJJAR SYNDROME TYPE II AND GILBERT'S SYNDROME)

Background. Enzymopathic jaundices are manifested by intermittent hyperbilirubinemia, no changes in the structure of the liver, no hemolysis, Rh-conflict as well as cholestasis being noted. These jaundices include Crigler-Najjar syndrome type I, Crigler-Najjar syndrome type II and Gilbert's syndrome. They are characterized by an autosomal recessive inheritance due to the presence of mutations and polymorphisms in uridine 5'-diphosphate-glucuronosyltransferase gene (UGT1A1) leading to a decrease of the enzyme activity or to its complete loss. Objective. To demonstrate the peculiarities of diagnosis and treatment of a rare case of hereditary unconjugated hyperbilirubinemia - a combination of Crigler-Najjar syndrome type II and Gilbert's syndrome. Material and methods. Clinical observation of a patient G. aged 19, who was examined and treated at the Department of gastroenterology of a multidisciplinary hospital in Moscow in January 2021. Results. The patient G. has had icteric sclerae and skin since birth; he occasionally suffers from easy fatigability and general malaise. Physical examination revealed no changes (except for icteric discoloration). An increase in unconjugated bilirubin up to 270 μmol/L (median - 170 μmol/L) was detected. The molecular genetic study of UGT1A1 gene identified mutations in exon 4 Val378Asp (2002) and Arg108Cys as well as polymorphism 6/7TA in the promoter region, confirming the diagnosis of autosomal recessive inherited disease – a combination of Crigler Najjar syndrome type II and Gilbert's syndrome (heterozygous state), complicated by the development of hepatic encephalopathy stage 2. There was noted a significant decrease in unconjugated bilirubin up to 170.5 μmol/L, as well as improvement in general condition – reduced fatigue and weakness during the treatment with microsomal enzyme inducer (phenobarbital) and hyperammonemia corrector (ornithine aspartate). Conclusions. The use of molecular genetic analysis allows tailoring strategies for patient-specific disease diagnostics, treatment and prevention. The preservation of quality of life within satisfactory level is achieved through elimination of adverse effects provoking the development of this syndrome and through control of risk factors.

UGT1A1 mutation association with increased bilirubin levels and severity of unconjugated hyperbilirubinemia in ABO incompatible newborns of China

Background Neonatal hyperbilirubinemia causing jaundice is common in East Asian population. Uridine diphosphate glucuronosyltransferase isoenzyme (UGT1A1) glucuronidates bilirubin and converts the toxic form of bilirubin to its nontoxic form. Method A retrospective study was conducted to review clinical information of ABO hemolysis neonates (ABO HDN) admitted to the Department of Neonatology, referred for neonatal hyperbilirubinemia, in a large general hospital of southern China from 2011 to 2017. Variation status of UGT1A1 was determined by direct sequencing or genotype assays. Result Sixty-nine ABO HDNs were included into the final analysis. UGT1A1 c.211 G > A mutation (UGT1A1*6, p.Arg71Gly, rs4148323) was significantly associated with the increased bilirubin level in ABO HDNs, after adjusted by age, sex and feeding method (P = 0.019 for TBIL, P = 0.02 for IBIL). Moreover, heterozygous and/or homozygous UGT1A1 mutations in the coding sequence region were significantly associated with the increased risk of developing hazardous hyperbilirubinemia (as defined by TSB > 427 umol/L) as compared those with a normal UGT1A1 genotype (ORadj = 9.16, 95%CI 1.99–42.08, P = 0.002) in the study cohort. Conclusion UGT1A1 variant in coding region is actively involved in the pathogenesis of ABO hemolysis related neonatal hyperbilirubinemia. Genetic assessment of UGT1A1 may be useful for clinical diagnosis of neonatal unconjugated hyperbilirubinemia.