Search Results (73)

Background: Chlorodontia is a rare condition characterized by intrinsic green discoloration of teeth. It is most often reported in association with bilirubin pigment deposition during teeth development, in cases of severe and/or prolonged neonatal hyperbilirubinemia. In extremely preterm infants, this condition may be complicated by other developmental enamel defects (DDE), such as hypoplasia or hypomineralization, linked to prematurity, systemic diseases, nutritional disturbances, and intensive care exposures. That overlap of enamel abnormalities can make diagnosis more difficult, necessitate a complex treatment plan, and increase the unpredictability of dental treatment efficacy. Case Presentation: This report presents the case of a child born at 25 weeks’ gestation with a birth weight of 910 g. Her neonatal course was complicated by, among others, recurrent episodes of hyperbilirubinemia, first neonatal (treated with phototherapy between the second and fifth day of life), and afterwards due to cholestasis from day 30 of life, with coexisting bacterial sepsis and metabolic disturbances. The available neonatal medical documentation indicated that total bilirubin level peak took place on the 40th day of life with levels approaching approximately 30 mg/dL, as well as levels of conjugated bilirubin being 19.0 mg/dL, but the exact peak values, duration, and bilirubin fractionation were not given in the patient’s discharge form. At 15 months of chronological age (11.5 months corrected age), she was referred for an assessment of abnormal morphology and green discoloration of the erupted primary incisors. Clinical examination revealed intrinsic green discoloration of the teeth, rough incisal edges and enamel breakdown on the incisal third. During follow-up, less intensity of the green pigmentation in the subsequent groups of erupted teeth was noticed. Despite excellent oral hygiene and adherence to a low-cariogenic diet, the primary first molars probably developed post-eruptive enamel loss with exposed dentin tissue. Minimally invasive management was introduced using atraumatic restorative treatment with glass-ionomer cement, combined with intensive preventive care. Conclusions: Despite the fact that, in the presented case, the diagnosis of presumptive bilirubin-related green pigmentation relies exclusively on the clinical picture and the complex neonatal medical history, it shows that, in extremely preterm infants, chlorodontia may coexist with hypomineralization or hypoplasia. This requires the introduction of dental treatment and prophylaxis, adjusted to the child’s age, to lower the risk of further complications of DDEs. Full article

Background/Objectives: Exclusive breastfeeding improves infant health and development, while suboptimal breastfeeding increases risks of hyperbilirubinemia and neonatal hypernatremic dehydration (NHD). This study aims to estimate the prevalence of NHD associated with exclusive breastfeeding and to identify maternal and neonatal risk factors through a systematic review and meta-analysis. Methods: This systematic review followed PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Scopus, Web of Science, LILACS, and the Cochrane Central Register of Controlled Trials from February to March 2025 without language or publication year restrictions. Observational studies evaluating healthy term neonates exclusively breastfed and diagnosed with NHD within the first 28 days of life were included. Two independent meta-analyses were performed to estimate pooled prevalence and associated risk factors using random-effects models. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) tool. Results: A total of 97 studies were identified, and 13 met the inclusion criteria. Ten studies were included in the prevalence meta-analysis and seven in the risk factor meta-analysis. The pooled prevalence of NHD was 1.4% (95% CI: 0.0–5.0%), with high heterogeneity (I² = 99.6%). Delayed initiation of breastfeeding (OR 6.02; 95% CI: 2.85–12.73), excessive neonatal weight loss > 10% (OR 69.28; 95% CI: 0.00–1.87 × 10¹²), low urine output (OR 8.51; 95% CI: 2.86–25.29), and maternal primiparity (OR 3.66; 95% CI: 1.67–8.02) were identified as the main risk factors. Poor breastfeeding technique, inadequate latch, and lack of early postnatal follow-up were consistently associated with NHD. Conclusions: NHD is a clinically relevant condition among exclusively breastfed term newborns. Early breastfeeding assessment, monitoring of neonatal weight loss and hydration status, and strengthened maternal support are essential to prevent severe complications. Full article

Background and Clinical Significance: Biliary atresia (BA) and Alagille syndrome (ALGS) represent distinct anatomic and genetic causes of neonatal cholestasis. Their overlapping clinical, biochemical, and early histological features present a formidable diagnostic challenge in early infancy, and their simultaneous coexistence is exceedingly rare. This report documents a unique case of dual diagnosis to highlight the associated diagnostic pitfalls and implications for surgical management. Case Presentation: We present the case of a Taiwanese male neonate who manifested prolonged jaundice and acholic stools. Preoperative imaging and intraoperative cholangiography confirmed biliary atresia, for which the patient underwent a Kasai portoenterostomy. The patient subsequently exhibited an atypical postoperative course characterized by persistent hyperbilirubinemia and intractable pruritus. This atypical trajectory prompted an extensive, multisystem evaluation and molecular genetic analysis, revealing a concurrent genetic diagnosis of Alagille syndrome. To our knowledge, this dual diagnosis is rarely reported in the literature, which creates a significant challenge in determining surgical candidacy and predicting long-term liver health outcomes. Discussions: Early differentiation is complicated by the fact that some ALGS patients can initially mimic BA. Beyond its exceptional rarity, this case holds profound clinical significance for the evaluation of neonatal cholestasis, serving as a stark reminder of the risks of “diagnostic premature closure.” In diagnostically challenging cases of neonatal cholestasis, intraoperative biliary exploration remains the gold standard for the timely diagnosis of BA. Genetic testing should be considered an adjunctive tool when clinical and histological findings are inconclusive. Conclusions: This case highlights a critical clinical caveat in neonatal cholestasis: while a confirmed diagnosis of anatomical BA typically stands alone as a solitary pathology, clinicians should remain mindful of the remote possibility of a concurrent genetic etiology like ALGS in highly atypical presentations. Persistently unexpected postoperative jaundice or the accumulation of multisystem anomalies should prompt an expansion of the differential diagnosis. Recognizing this rare coexistence is crucial for effective multidisciplinary management, informed surgical decision-making, and accurate genetic counseling. Full article

Background: Conjugated hyperbilirubinemia in early infancy is a critical indicator of hepatobiliary dysfunction. Prompt and accurate identification is essential to diagnose cholestatic liver disease (CLD), particularly biliary atresia. Current guidelines define conjugated bilirubin (CB) ≥ 1 mg/dL as abnormal, irrespective of total bilirubin (TB). This study aimed to evaluate whether combining absolute and relative CB thresholds improves diagnostic performance for CLD. Methods: We retrospectively analyzed all infants aged ≤6 months of chronological age with CB ≥ 1 mg/dL admitted to the Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria, between January 2004 and February 2025. During that period, 116,104 infants were born at our hospital catchment area; 3119 of these underwent bilirubin fractionation, and 257 infants (0.2% of total births) had a CB ≥ 1 mg/dL and were included in the analysis. Clinical and biochemical data were extracted. Diagnostic performance of the absolute (CB ≥ 1 mg/dL) and in combination with the relative (CB ≥ 20% of TB) thresholds was assessed using receiver operating characteristic (ROC) analysis for the detection of CLD. Results: Among 257 infants, 47 (18%) were diagnosed with CLD. The median age at the time of blood sampling was 18 days (IQR 9–31). The combined criterion (CB ≥ 1 mg/dL and ≥20% of TB) achieved 100% sensitivity and 61.2% specificity (AUC = 0.82, 95% CI 0.79–0.92; p < 0.001). Implementation of the combined cut-off reduced the number needed to screen from 5.5 to 2.7, representing nearly a twofold improvement in diagnostic efficiency. Conclusions: Applying both absolute (≥1 mg/dL) and relative (≥20% of total bilirubin) CB thresholds substantially improves detection of neonatal CLD in early infancy. This combined approach maintains full sensitivity while reducing false positives and unnecessary investigations, thereby enhancing diagnostic efficiency in early infancy. Full article

Objectives: Neonatal hyperbilirubinemia is a common disease in the neonatal period. In this meta-analysis, we aim to evaluate the efficacy of adjuvant drugs combined with phototherapy in the treatment of neonatal hyperbilirubinemia. Methods: Randomized controlled trials (RCTs) published before September 2025 were searched from PubMed, Embase, Web of Science, and the Cochrane Library. A Bayesian random-effects network meta-analysis was performed to calculate mean differences and 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) and probability of being the best treatment (PbBT). Results: Thirty-five RCTs involving 4060 neonates were included. Compared with phototherapy alone, clofibrate, ursodeoxycholic acid, fenofibrate, and calcium phosphate significantly reduced bilirubin levels and shortened admission duration. Clofibrate showed the greatest efficacy in bilirubin reduction within 48 h (SUCRA = 0.91, PbBT = 60.9%) and in shortening hospitalization (SUCRA = 0.84, PbBT = 40.83%). Probiotics, zinc, and agar exhibited relatively modest effects, while phenobarbital showed no significant benefit. Conclusions: Adjunctive therapies were associated with greater reductions in bilirubin levels compared with phototherapy alone. Future high-quality RCTs are needed to confirm the long-term efficacy and safety of these adjuvant therapies. Full article

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is among the most common inherited enzymatic disorders worldwide and is an important risk factor for neonatal hyperbilirubinemia. Regional data from Western Saudi Arabia based on universal newborn screening remain limited. Objectives: To determine the prevalence of G6PD deficiency among newborns delivered at a tertiary center in Jeddah, Saudi Arabia, and to evaluate its association with clinically relevant outcomes, including early-onset jaundice (<24 h), need for phototherapy, admission for hyperbilirubinemia management, and readmission after discharge. Methods: We conducted a retrospective cohort study at King Abdulaziz Medical City, Western Region, Jeddah, Saudi Arabia, between January 2020 and May 2025. Cord blood samples from live-born infants were screened using a qualitative fluorescent spot test. Demographic variables (sex, gestational age, birth weight) and jaundice-related outcomes were extracted from the electronic medical record. Categorical variables were compared using chi-square testing, with p < 0.05 considered statistically significant. Results: Among 14,964 screened newborns, 489 were identified as G6PD deficient, yielding a prevalence of 3.3%. Prevalence was higher in males than in females (5.6% vs. 0.9%). Among the G6PD-deficient infants, early-onset jaundice occurred in 17.2%, phototherapy was required in 36.0%, and 16.5% were admitted for hyperbilirubinemia management. Readmission for worsening jaundice requiring phototherapy occurred in 11.0%, and no exchange transfusions were required. Compared with term infants, late preterm infants had higher rates of early-onset jaundice (11/49, 22.4% vs. 73/440, 16.6%) and phototherapy use (22/49, 45.0% vs. 154/440, 35.0%) (p < 0.01). Conclusions: G6PD deficiency was identified in a substantial proportion of newborns in this large screened cohort and was associated with clinically significant jaundice-related outcomes, particularly among late preterm infants. These findings underscore the importance of universal screening and structured postnatal follow-up to reduce the risk of severe hyperbilirubinemia and its complications. Early identification of G6PD-deficient infants should be accompanied by careful bilirubin monitoring, clear discharge planning, and timely post-discharge follow-up, especially for those born late preterm. Full article

Background: Clinical management of neonatal indirect hyperbilirubinemia is guided by threshold-based recommendations for phototherapy and exchange transfusion. This retrospective, single-center study compared phototherapy and exchange transfusion thresholds according to the Turkish Neonatology Society and the 2022 American Academy of Pediatrics guidelines in neonates hospitalized for indirect hyperbilirubinemia. Methods: This single-center, retrospective cross-sectional study included neonates born at ≥35 weeks of gestation who were admitted to a neonatal intensive care unit solely due to indirect hyperbilirubinemia. Phototherapy and exchange transfusion thresholds were calculated according to both the TNS guideline and the 2022 AAP guideline. Eligibility according to guideline thresholds and admission indications were compared between the two guidelines. Statistical analyses were performed using appropriate non-parametric tests. Results: A total of 344 neonates were included in the analysis. Mean phototherapy and exchange transfusion thresholds were significantly higher according to the AAP 2022 guideline compared with the TNS guideline (p < 0.001 for both). While 89.2% of admissions met eligibility according to the national guideline thresholds, only 36.6% met admission criteria according to the AAP 2022 guideline. Conclusions: Substantial differences exist between national and international guidelines for the management of neonatal indirect hyperbilirubinemia. These differences significantly influence treatment thresholds and hospitalization practices. Real-life comparative data may contribute to future evaluations of guideline-based management strategies. Full article

Pediatric (neonatal and infantile) jaundice resulting from underlying cholestasis (caused by conjugated hyperbilirubinemia) is always pathological and requires prompt evaluation. Pediatric cholestasis can be caused by medical or surgical factors and, if left untreated, can lead to irreversible liver damage. Timely recognition of pediatric cholestasis and identification of the underlying etiology are paramount to improve outcomes. The broad spectrum of causes potentially underlying pediatric cholestasis requires a multidisciplinary diagnostic approach, and each aspect must be interpreted in the concomitant clinical picture. A liver biopsy is one component of a complex diagnostic puzzle. However, interpreting a liver biopsy performed on a newborn/infant with conjugated/direct hyperbilirubinemia can be a challenging task, as these biopsies are rarely encountered in general hospitals. The aim of this review is to provide a practical and simplified approach to pediatric cholestasis with examples of real clinical cases we have encountered and discuss key features, both histological and clinical, that can help narrow the differential diagnosis and identify treatable causes. Full article

Background: Pyruvate kinase deficiency (PKD) is the most prevalent enzymatic defect of the glycolytic pathway, causing chronic congenital non-spherocytic hemolytic anemia. Clinical severity ranges from mild anemia to transfusion-dependent diseases. Severe neonatal presentations, including liver failure, have rarely been reported. Case presentation: We report a preterm female neonate with PKD who developed early-onset hemolytic anemia, conjugated hyperbilirubinemia, hepatosplenomegaly, coagulopathy, and progressive transaminitis. Imaging demonstrated hepatomegaly with diffuse parenchymal involvement. Whole-genome sequencing identified compound heterozygous pathogenic mutations in the PKLR gene, confirming the diagnosis of PKD. The patient required continuous transfusion support and was discharged following clinical stabilization. Discussion: Although PKD most often manifests as isolated hemolytic anemia, this case illustrates a rare neonatal phenotype with concurrent liver dysfunction. We investigated the potential underlying mechanism. Recognition of hepatic involvement in PKD is essential because liver failure is associated with considerable morbidity and mortality, and it may necessitate interventions such as liver transplantation. Conclusions: This case highlights the importance of considering PKD in neonates presenting with hemolysis and liver failure. Early genetic confirmation enables timely management, including transfusion support, iron overload surveillance, and anticipatory guidance for potential hepatic complications. Full article

Phototherapy is the standard treatment for neonatal hyperbilirubinemia. During phototherapy, the highly lipophilic bilirubin is converted into more hydrophilic photoisomers, which can be more easily excreted from the body. This process typically lowers bilirubin levels to non-harmful concentrations. However, despite decades of research into the formation and role of bilirubin photoisomers, methodological limitations and the compound’s complex biochemistry have hindered comprehensive understanding. This review provides an updated overview of current knowledge on bilirubin photoisomers, including their basic chemistry, analytical quantification, clinical relevance, and future research directions. Improved insight into the mechanism of photoisomer formation and kinetics may inform optimization of phototherapy parameters, including light intensity and wavelength, and offer additional indicators of treatment efficacy beyond total bilirubin concentration. Advances in sensitive and standardized mass spectrometry techniques now enable more accurate measurement of different bilirubin isomers and serve as a first step towards a deeper insight into the clinical relevance of photoisomers. Full article

Hyperbilirubinemia, commonly known as jaundice, is a prevalent condition in newborns, primarily arising from alterations in red blood cell metabolism during the first week of life. While conventional diagnostic methods, such as serum analysis and transcutaneous bilirubinometry, are effective, there remains a critical need for robust, non-invasive, image-based diagnostic tools. In this study, we propose a custom-designed convolutional neural network for classifying jaundice in neonatal images. Image preprocessing and segmentation techniques were systematically evaluated. The optimal workflow, which incorporated contrast enhancement and the extraction of regular skin patches of 144 × 144 pixels from regions of interest segmented using the Segment Anything Model, achieved a testing F1-score of 0.80. Beyond performance, this study addresses numerous shortcomings in the existing literature in this area relating to trust, replicability, and transparency. To this end, we employ fair performance metrics that are more robust to class imbalance, a transparent workflow, share source code, and use Gradient-weighted Class Activation Mapping to visualise and quantify the image regions that influence the classifier’s predictions in pursuit of epistemic justification. Full article

Severe neonatal hyperbilirubinemia (SNH) (jaundice) is responsible for over 114,000 preventable neonatal deaths annually, as the technology that can treat the condition is cost-prohibitive for low- and middle-income countries. In this study an open-source neonatal phototherapy device (NPTD) to treat SNH was designed, built, and validated against the phototherapy technical specifications set by the American Academy of Pediatrics and UNICEF. The open-source device can be built for a tenth of the cost of the least expensive proprietary one on the market, with treatment metrics equivalent to or exceeding commercial devices available in developed nations. This device, whose material costs are USD 93.00, was shown to deliver an irradiance up to 80 µW/cm²/nm, within the acceptable wavelength range of 420–500 nm. It was further demonstrated that the unit could deliver a uniform distribution of irradiance (34.5 ± 4.3 µW/cm²/nm) over a surface area exceeding 3200 cm². These findings show that the open-source NPTD is capable of delivering accurate, consistent, and reliable irradiances for the management of SNH. By releasing full documentation in an open-source manner, the device may be broadly used to ensure affordable and consistent low-cost means of improving the quality of care for SNH. Full article

Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of clinically stable preterm neonates by Rotational Thromboelastometry [ROTEM; (EXTEM, INTEM, FIBTEM assays)], (b) establishing reference ranges, and (c) investigating potential differences in comparison to healthy term neonates. We also evaluated the impact of clinical and perinatal factors on the haemostatic status of this vulnerable population. Materials and Methods: 69 premature neonates with no underlying morbidity and 226 healthy term neonates were the study subjects. In term neonates, blood was collected on the 2nd-3rd day of life, if sampling was required for any other reason (hyperbilirubinemia, ABO blood group incompatibility screening, maternal thyroid antibodies, or insufficient prenatal care), whereas in premature neonates, blood was collected between the 4nd-10th day after stabilisation. The parameters measured for each ROTEM assay included Clotting Time (CT), Clot Formation Time (CFT), Alpha angle (α, degrees), Clot Amplitude at 5 and 10 min (A5, A10), Maximal Clot Firmness (MCF), and Lysis Index at 30, 45 and 60 min (Li30, Li45, and Li60 respectively). Results: The data analysis demonstrated a prothrombotic profile in preterm neonates, characterized by increased values of A5, A10, (MCF), and α-angle, and shortened CT and CFT across all assays (EXTEM, INTEM, FIBTEM), when compared to term neonates. A statistically significant inverse correlation was observed between gestational age and clot lysis parameters (INTEM Li45, Li60). Additionally, hematocrit levels were negatively correlated with clot amplitude and kinetics of clot development, while platelet count was positively associated with clot firmness parameters (A5, A10, MCF) and α-angle. Mode of delivery and the presence of gestational diabetes did not significantly affect ROTEM assay values. Preterm neonates with a history of respiratory distress syndrome (RDS) exhibited a more pronounced hypercoagulable profile compared to those without RDS, as reflected by the enhanced clot strength and reduced CT, findings that may be attributed to postnatal pulmonary inflammation and its systemic effects on coagulation. Conclusions: This study introduces for the first time reference values for the parameters of ROTEM assays (EXTEM, INTEM, FIBTEM) in clinically stable preterm neonates—a highly vulnerable patient group with a distinct need for accurate and individualized monitoring of their haemostatic status. The combined assessment of these assays enhances diagnostic precision, and offers a more comprehensive evaluation of neonatal haemostasis. By defining reference ranges in whole blood, this work provides novel data that support the integration of ROTEM into clinical transfusion algorithms. Full article

Background/Objectives: We wished to raise awareness of Hereditary Spherocytosis (HS) as a potential cause of early and significant hemolytic newborn jaundice. Methods: We utilized three recent cases from our experience to discuss hyperbilirubinemia etiologies to be considered when a baby has hemolytic hyperbilirubinemia, including HS, and presented a review of the literature about this disorder including presentation and evaluation in the neonate. Results: We found that ABO hemolytic disease of the newborn (HDN) is often considered as the etiology for presumed hemolytic hyperbilirubinemia even when the direct antiglobulin test (DAT) is negative. When there is a mother-baby ABO mismatch and baby’sDAT is negative, another etiology should be sought. HS should be considered in these cases as the prevalence of HS is as frequent as 1 in 2000 in certain populations, it is the third most common hemolytic disorder after ABO isoimmunization and G6PD deficiency, and it is the most common cause of non-immune hemolytic hyperbilirubinemia in neonates with kernicterus. The indices to look for in the complete blood count that are suggestive for HS are MCHC > 36.5–37 g/dL, an MCHC:MCV ratio (HS Index) > 0.36, and increased RDW. The lack of spherocytes on the newborn peripheral blood smear, family history, initial anemia, and reticulocytosis do not eliminate the diagnosis of HS. Conclusions: HS is common and should be included in the differential diagnosis for hemolytic hyperbilirubinemia. Red blood cell indices can suggest the diagnosis of HS, and eosin 5’ maleimide (EMA) testing can be used to make the diagnosis. If DAT-negative ABO HDN is the leading diagnosis for hyperbilirbinemia, a different etiology should urgently be sought. Full article

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymopathy with significant clinical implications, particularly in malaria-endemic regions and in the management of neonatal hyperbilirubinemia. Timely and accurate detection of G6PD deficiency is critical to prevent life-threatening hemolytic events following oxidative drug administration. This study evaluated the MyG6PD device, a quantitative point-of-care (PoC) tool, for the assessment of hemoglobin concentration and G6PD enzyme activity. Analytical performance was benchmarked against laboratory spectrophotometry and the STANDARD G6PD Analyzer™ (SD Biosensor; Suwon-si, Republic of Korea). MyG6PD demonstrated excellent linearity (R² ≥ 0.99), accuracy (bias < ±15%), and precision (CV < 15%) across normal, intermediate, and deficient activity ranges, including heterozygous females with intermediate phenotypes. The device’s compact, battery-operated design, rapid turnaround, and minimal training requirements support its use in decentralized and resource-limited settings. Furthermore, cost-effective consumables and robust detection of intermediate activity highlight its potential for large-scale deployment. Overall, MyG6PD provides a reliable, accessible, and clinically actionable solution for urgent G6PD deficiency screening, enabling safer administration of oxidative therapies and improving patient outcomes in high-risk populations. Full article