Clinico-etiological Spectrum of Neonatal Cholestasis in the Era of Next Generation Sequencing Spectrum of neonatal cholestasis
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Abstract
Background: Neonatal cholestasis (NC) is a complex condition that poses a diagnostic challenge to paediatricians. A significant proportion of NC patients remain idiopathic even after a detailed evaluation. However, with the availability of next-generation sequencing (NGS), the etiological spectrum is changing through the identification of more genetic and metabolic disorders. This study aimed to identify the aetiology and outcomes of NC using NGS.
Method: A prospective cohort study was conducted at the Department of Pediatrics in a tertiary care centre in central India from April 2021 to September 2023. Infants from birth through 1 year of age presenting with cholestasis were included. Details of their history, clinical examinations, and investigations including NGS were recorded in a study proforma.
Result: A total of 106 infants were included, of whom 62 (58%) were male. Biliary atresia was the most common cause, identified in 33 (31%) children, followed by preterm multifactorial causes in 21 (20%) children. NGS was performed on 16 children, and disease-causing mutations were identified in 13 (81%) of them [homozygous in 10 (62.5%), heterozygous in 3 (18.75%), and no mutation in 3 (18.75%)]. A small proportion of patients were found to have idiopathic NC [18 (17%)] and transient neonatal cholestasis [15 (14%)].
Conclusion: Biliary atresia remains the most common cause of NC. A meticulous workup is required to ascertain other causes of the condition. NGS can help identify the causes of NC, providing a definitive diagnosis that aids in determining treatment and prognosis
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