Guideline for the Evaluation of Cholestatic Jaundice in Infants

Abstract

Cholestatic jaundice in infancy affects approximately 1 in every 2500 term infants and is infrequently recognized by primary providers in the setting of physiologic jaundice. Cholestatic jaundice is always pathologic and indicates hepatobiliary dysfunction. Early detection by the primary care physician and timely referrals to the pediatric gastroenterologist/hepatologist are important contributors to optimal treatment and prognosis. The most common causes of cholestatic jaundice in the first months of life are biliary atresia (25%-40%) followed by an expanding list of monogenic disorders (25%), along with many unknown or multifactorial (eg, parenteral nutrition-related) causes, each of which may have time-sensitive and distinct treatment plans. Thus, these guidelines can have an essential role for the evaluation of neonatal cholestasis to optimize care. The recommendations from this clinical practice guideline are based upon review and analysis of published literature and the combined experience of the authors. The committee recommends that any infant noted to be jaundiced after 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin, and that an elevated serum direct bilirubin level (direct bilirubin levels >1.0 mg/dL or >17 μmol/L) warrants timely consideration for evaluation and referral to a pediatric gastroenterologist or hepatologist. Of note, current differential diagnostic plans now incorporate consideration of modern broad-based next-generation DNA sequencing technologies in the proper clinical context. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all infants with cholestasis. Broad implementation of these recommendations is expected to reduce the time to the diagnosis of pediatric liver diseases, including biliary atresia, leading to improved outcomes.

Diagnosis of monogenic liver diseases in childhood by next‐generation sequencing

“…Pediatric cholestatic diseases often present with overlapping phenotypes making accurate diagnosis challenging. The underlying conditions for the clinical phenotype “neonatal cholestasis” encompass infection, immaturity and biliary atresia as well as numerous orphan diseases . The most frequent are the entity of progressive familial intrahepatic cholestasis, a heterogeneous group of bile acid transporter defects and related conditions (PFIC) or benign recurrent intrahepatic cholestasis (BRIC), congenital bile acid synthesis defects, citrin deficiency or Alagille syndrome (ALGS).…”

Evolução laboratorial da colestase multifatorial em pacientes pediátricos

“…É importante ressaltar que o valor de BD como critério diagnóstico diverge na literatura, sendo considerado icterícia colestática BD > 1; 1,5 ou 2 mg/dl, como verificado nos estudos de Lane et al 10 , Albers et al 17 , Satrom et al 18 . O consenso mais recente de colestase elaborado pelas Sociedades Norte Americana e Europeia de Gastroenterologia, Hepatologia e Nutrição Pediátrica (NASPGHAN e ESPGHAN), conceitua colestase como valores de BD maior que 1mg/ dl independente do valor da bilirrubina total 5 . Logo, este foi o valor levado em consideração para elaboração do nosso estudo.…”

“…Existem múltiplas causas de colestase neonatal, muitas vezes relacionadas à resposta do recém-nascido (RN) a agentes endógenos ou condições patológicas específicas 4 . As mais comuns são atresia de vias biliares (25%-40%), distúrbios genéticos (25%) e causas desconhecidas ou multifatoriais 5 .…”

Cholestasis caused by panhypopituitarism and acquired cytomegalovirus infection in a 2-month-old male infant

“…[5] The most common causes of infantile cholestasis are biliary atresia (25.89%) and idiopathic neonatal hepatitis (26%). CMV is the most common infection identified (31.51%).…”

“…The infants with hypopituitarism usually present with elevation of both direct and total bilirubin. [5,8–11] …”