Significant advances in perinatology and neonatology in the last decade have resulted in increased survival of extremely premature infants.' Survival rates at 25 and 26 weeks of gestation age ranging from 60% to 82% and from 75% to 93%, respectively, have been reported.' In Malaysia, the survival rates among premature very low birth weight infants (< 1500 g) were reported to be between 69% and 78%.2,3 Such improvements of survival have been attributed to the advances in the management of respiratory disease and intra-ventricular haemorrahge in the premature infants.',2 Thus, attention have recently been focused on the need to secure adequate nutrient intake of these premature infants. Parenteral nutrition has often been used to manage the transition between transplacental nutrition in-utero and post-natal enteral nutrition, but is associated with cholestasis and sepsis.4 However, the ability to deliver nutrition is limited not only by immature absorptive or digestive function but by inadequate motor activity. Gastroesophageal efflux (GER) and feeding intolerance are the major gastro-enterological problems of the premature neonates.
The liver is an important organ of the human body, playing a major role in the metabolism and storage of nutrients, synthesis of protein and other nutrients, as well as detoxifying many metabolic by-products. The response of the foetal and newborn liver to external insult and injury is limited. This is because the ability of the closely interdependent structures of a developing liver of expressing in the face of a variety of insults is limited as well. Thus most infants with insults to the liver present as cholestatic jaundice with variable degree of pale stools, enlarged liver and conjugated hyperbilirubinaemia. Biliary atresia, an idiopathic condition characterized by progressive fibrosing obliteration of both intra- and extrahepatic bile ducts, is the most important cause of neonatal cholestasis worldwide, including Malaysia. It is also the most important indication for childhood liver transplantation the world over. Challenges facing infants with biliary atresia include a delay in the diagnosis and late surgery, leading to a poor outcome. This often results from a failure to recognise the potential serious nature of an infant with prolonged cholestatic jaundice and pale stools among health care professionals.
A 46 day old female Chinese infant was referred for fail-ure to thrive, jaundice, hepatomegaly and bilateral cataracts. She had vomiting,blood stained stools and severe unconjugated hyperbilirubinaemia soon after birth. The jaundice persisted. At one month of age, pale stools, firm hepatomegaly and bilateral cataracts were noted. Radionuclide hepatobiliary scintigraphy per-formed at another hospital excluded biliary atresia. Investigations showed cholestasis but a negative sero-logical screening for congenital infections. A presump-tive diagnosis of galactosaemia was made and the infant was started on lactose free formula. A deficient red blood cell galactose- 1 -phosphate uridyltransferase (GALT) activity was demonstrated later. Review eight months after the initial diagnosis showed a thriving infant with no jaundice, but persisting cataracts and firm enlarged liver. A high index of clinical suspicion, labo-ratory confirmation of a deficient GALT activity and prompt withdrawal of lactose from diet are necessary to avoid any delay in diagnosis and management of this condition.
From November 1996 to December 1997, 24 infants with neonatal cholestasis were referred to the Department of Paediatrics, University of Malaya Medical Center, Kuala Lumpur for further investigations. Nineteen had neonatal hepatitis. There was considerable delay in referral of infants with cholestasis; the mean age of referral was 63.7 days. None had a positive family history of neonatal hepatitis. All infant had hepatomegaly and ten had splenomegaly. The stools were slightly pale in thirteen, persistently acholic in three and normally pigmented in three infants. Liver synthetic functions were normal in most of the infants. Cytomegalovirus (CMV) IgM antibodies were positive in seven but none were positive for toxoplasma or rubella. al - antitrypsin deficiency, hypothyroidism, and galactosaemia were excluded in all infants. DISIDA scans were performed in seventeen infants, being non-excretory in eight. Liver biopsies were performed in fifteen infants, showing neonatal hepatitis in fourteen, while histological features of large duct obstruction was seen in one. In majority of infants (eight out of ten) the jaundice disappeared by six months. Two infants had progressive jaundice and liver function impairment.