Biliary atresia: Indications and timing of liver transplantation and optimization of pretransplant care

Shikha S Sundaram, Cara L Mack, Amy G Feldman, Ronald J Sokol, Shikha S Sundaram, Cara L Mack, Amy G Feldman, Ronald J Sokol

Abstract

Biliary atresia (BA) is a progressive, fibro-obliterative disorder of the intrahepatic and extrahepatic bile ducts in infancy. The majority of affected children will eventually develop end-stage liver disease and require liver transplantation (LT). Indications for LT in BA include failed Kasai portoenterostomy, significant and recalcitrant malnutrition, recurrent cholangitis, and the progressive manifestations of portal hypertension. Extrahepatic complications of this disease, such as hepatopulmonary syndrome and portopulmonary hypertension, are also indications for LT. Optimal pretransplant management of these potentially life-threatening complications and maximizing nutrition and growth require the expertise of a multidisciplinary team with experience caring for BA. The timing of transplant for BA requires careful consideration of the potential risk of transplant versus the survival benefit at any given stage of disease. Children with BA often experience long wait times for transplant unless exception points are granted to reflect severity of disease. Family preparedness for this arduous process is therefore critical. Liver Transplantation 23:96-109 2017 AASLD.

© 2016 by the American Association for the Study of Liver Diseases.

References

    1. Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 2007;46:566–581.
    1. Hitch DC, Shikes RH, Lilly JR. Determinants of survival after Kasai’s operation for biliary atresia using actuarial analysis. J Pediatr Surg. 1979;14:310–314.
    1. Lilly JR, Karrer FM, Hall RJ, Stellin GP, Vasquez-Estevez JJ, Greenholz SK, Wanek EA, et al. The surgery of biliary atresia. Ann Surg. 1989;210:289–294. discussion 294-286.
    1. Altman RP, Lilly JR, Greenfeld J, Weinberg A, van Leeuwen K, Flanigan L. A multivariable risk factor analysis of the portoenterostomy (Kasai) procedure for biliary atresia: twenty-five years of experience from two centers. Ann Surg. 1997;226:348–353. discussion 353-345.
    1. Shneider BL, Brown MB, Haber B, Whitington PF, Schwarz K, Squires R, Bezerra J, et al. A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr. 2006;148:467–474.
    1. Schreiber RA, Barker CC, Roberts EA, Martin SR, Alvarez F, Smith L, Butzner JD, et al. Biliary atresia: the Canadian experience. J Pediatr. 2007;151:659–665. 665 e651.
    1. Chardot C, Carton M, Spire-Bendelac N, Le Pommelet C, Golmard J, Reding R, Auvert B. Is the Kasai operation still indicated in children older than 3 months diagnosed with biliary atresia? J Pediatr. 2001;138:224–228.
    1. Alexopoulos SP, Merrill M, Kin C, Matsuoka L, Dorey F, Concepcion W, Esquivel C, et al. The impact of hepatic portoenterostomy on liver transplantation for the treatment of biliary atresia: early failure adversely affects outcome. Pediatr Transplant. 2012;16:373–378.
    1. Davenport M, Puricelli V, Farrant P, Hadzic N, Mieli-Vergani G, Portmann B, Howard ER. The outcome of the older (> or =100 days) infant with biliary atresia. J Pediatr Surg. 2004;39:575–581.
    1. Serinet MO, Wildhaber BE, Broue P, Lachaux A, Sarles J, Jacquemin E, Gauthier F, et al. Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics. 2009;123:1280–1286.
    1. Superina R, Magee JC, Brandt ML, Healey PJ, Tiao G, Ryckman F, Karrer FM, et al. The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplant-free survival. Ann Surg. 2011;254:577–585.
    1. Salzedas-Netto AA, Chinen E, de Oliveira DF, Pasquetti AF, Azevedo RA, da Silva Patricio FF, Cury EK, et al. Grade IV fibrosis interferes in biliary drainage after Kasai procedure. Transplant Proc. 2014;46:1781–1783.
    1. Neto JS, Feier FH, Bierrenbach AL, Toscano CM, Fonseca EA, Pugliese R, Candido HL, et al. Impact of Kasai portoenterostomy on liver transplantation outcomes: A retrospective cohort study of 347 children with biliary atresia. Liver Transpl. 2015;21:922–927.
    1. Sandler AD, Azarow KS, Superina RA. The impact of a previous Kasai procedure on liver transplantation for biliary atresia. J Pediatr Surg. 1997;32:416–419.
    1. Urahashi T, Ihara Y, Sanada Y, Wakiya T, Yamada N, Okada N, Mizuta K. Effect of repeat Kasai hepatic portoenterostomy on pediatric live-donor liver graft for biliary atresia. Exp Clin Transplant. 2013;11:259–263.
    1. Meister RK, Esquivel CO, Cox KL, Concepcion W, Berquist W, Nakazato P, deVries PA. The influence of portoenterostomy with stoma on morbidity in pediatric patients with biliary atresia undergoing orthotopic liver transplantation. J Pediatr Surg. 1993;28:387–390.
    1. Millis JM, Brems JJ, Hiatt JR, Klein AS, Ashizawa T, Ramming KP, Quinones-Baldrich WJ, et al. Orthotopic liver transplantation for biliary atresia. Evolution of management. Arch Surg. 1988;123:1237–1239.
    1. Visser BC, Suh I, Hirose S, Rosenthal P, Lee H, Roberts JP, Hirose R. The influence of portoenterostomy on transplantation for biliary atresia. Liver Transpl. 2004;10:1279–1286.
    1. DeRusso PA, Ye W, Shepherd R, Haber BA, Shneider BL, Whitington PF, Schwarz KB, et al. Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research Consortium. Hepatology. 2007;46:1632–1638.
    1. Sokol RJ, Stall C. Anthropometric evaluation of children with chronic liver disease. Am J Clin Nutr. 1990;52:203–208.
    1. Feranchak ASFJ, Sokol RJ. Medical and Nutrtional Management of Cholestasis in the Infant and Child. In: Suchy FJ SR, Balistereri WF, editors. Liver Disease in Children. 4th. Cambridge University Press; pp. 419–434.
    1. Rothenberg SS, Schroter GP, Karrer FM, Lilly JR. Cholangitis after the Kasai operation for biliary atresia. J Pediatr Surg. 1989;24:729–732.
    1. Davenport M, Kerkar N, Mieli-Vergani G, Mowat AP, Howard ER. Biliary atresia: the King’s College Hospital experience (1974–1995) J Pediatr Surg. 1997;32:479–485.
    1. Qiao G, Li L, Cheng W, Zhang Z, Ge J, Wang C. Conditional probability of survival in patients with biliary atresia after Kasai portoenterostomy: a Chinese population-based study. J Pediatr Surg. 2015;50:1310–1315.
    1. Chung PH, Wong KK, Tam PK. Predictors for failure after Kasai operation. J Pediatr Surg. 2015;50:293–296.
    1. Kumagi T, Drenth JP, Guttman O, Ng V, Lilly L, Therapondos G, Hiasa Y, et al. Biliary atresia and survival into adulthood without transplantation: a collaborative multicentre clinic review. Liver Int. 2012;32:510–518.
    1. Lykavieris P, Chardot C, Sokhn M, Gauthier F, Valayer J, Bernard O. Outcome in adulthood of biliary atresia: a study of 63 patients who survived for over 20 years with their native liver. Hepatology. 2005;41:366–371.
    1. Weisshaar E, Diepgen TL, Luger TA, Seeliger S, Witteler R, Stander S. Pruritus in pregnancy and childhood--do we really consider all relevant differential diagnoses? Eur J Dermatol. 2005;15:320–331.
    1. Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease. Hepatology. 2014;59:1627–1637.
    1. Condino AA, Ivy DD, O’Connor JA, Narkewicz MR, Mengshol S, Whitworth JR, Claussen L, et al. Portopulmonary hypertension in pediatric patients. J Pediatr. 2005;147:20–26.
    1. Whitworth JR, Ivy DD, Gralla J, Narkewicz MR, Sokol RJ. Pulmonary vascular complications in asymptomatic children with portal hypertension. J Pediatr Gastroenterol Nutr. 2009;49:607–612.
    1. Ecochard-Dugelay E, Lambert V, Schleich JM, Duche M, Jacquemin E, Bernard O. Portopulmonary Hypertension in Liver Disease Presenting in Childhood. J Pediatr Gastroenterol Nutr. 2015;61:346–354.
    1. Noli K, Solomon M, Golding F, Charron M, Ling SC. Prevalence of hepatopulmonary syndrome in children. Pediatrics. 2008;121:e522–e527.
    1. Krowka MJ, Wiesner RH, Heimbach JK. Pulmonary contraindications, indications and MELD exceptions for liver transplantation: a contemporary view and look forward. J Hepatol. 2013;59:367–374.
    1. Yousef N, Habes D, Ackermann O, Durand P, Bernard O, Jacquemin E. Hepatorenal syndrome: diagnosis and effect of terlipressin therapy in 4 pediatric patients. J Pediatr Gastroenterol Nutr. 2010;51:100–102.
    1. Shusterman B, McHedishvili G, Rosner MH. Outcomes for hepatorenal syndrome and acute kidney injury in patients undergoing liver transplantation: a single-center experience. Transplant Proc. 2007;39:1496–1500.
    1. Hadzic N, Quaglia A, Portmann B, Paramalingam S, Heaton ND, Rela M, Mieli-Vergani G, et al. Hepatocellular carcinoma in biliary atresia: King’s College Hospital experience. J Pediatr. 2011;159:617–622. e611.
    1. Brunati A, Feruzi Z, Sokal E, Smets F, Fervaille C, Gosseye S, Clapuyt P, et al. Early occurrence of hepatocellular carcinoma in biliary atresia treated by liver transplantation. Pediatr Transplant. 2007;11:117–119.
    1. Yu SB, Kim HY, Eo H, Won JK, Jung SE, Park KW, Kim WK. Clinical characteristics and prognosis of pediatric hepatocellular carcinoma. World J Surg. 2006;30:43–50.
    1. Romano F, Stroppa P, Bravi M, Casotti V, Lucianetti A, Guizzetti M, Sonzogni A, et al. Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma. Pediatr Transplant. 2011;15:573–579.
    1. Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, Mazariegos GV. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Hepatology. 2014;60:362–398.
    1. Utterson EC, Shepherd RW, Sokol RJ, Bucuvalas J, Magee JC, McDiarmid SV, Anand R, et al. Biliary atresia: clinical profiles, risk factors, and outcomes of 755 patients listed for liver transplantation. J Pediatr. 2005;147:180–185.
    1. Smith J, Horowitz J, Henderson JM, Heymsfield S. Enteral hyperalimentation in undernourished patients with cirrhosis and ascites. Am J Clin Nutr. 1982;35:56–72.
    1. Moreno LA, Gottrand F, Hoden S, Turck D, Loeuille GA, Farriaux JP. Improvement of nutritional status in cholestatic children with supplemental nocturnal enteral nutrition. J Pediatr Gastroenterol Nutr. 1991;12:213–216.
    1. Charlton CP, Buchanan E, Holden CE, Preece MA, Green A, Booth IW, Tarlow MJ. Intensive enteral feeding in advanced cirrhosis: reversal of malnutrition without precipitation of hepatic encephalopathy. Arch Dis Child. 1992;67:603–607.
    1. Macias-Rosales R, Larrosa-Haro A, Ortiz-Gabriel G, Trujillo-Hernandez B. Effectiveness of Enteral Versus Oral Nutrition With a Medium-Chain Triglyceride Formula to Prevent Malnutrition and Growth Impairment in Infants With Biliary Atresia. J Pediatr Gastroenterol Nutr. 2016;62:101–109.
    1. Sullivan JS, Sundaram SS, Pan Z, Sokol RJ. Parenteral nutrition supplementation in biliary atresia patients listed for liver transplantation. Liver Transpl. 2012;18:120–128.
    1. Shneider BL, Magee JC, Bezerra JA, Haber B, Karpen SJ, Raghunathan T, Rosenthal P, et al. Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia. Pediatrics. 2012;130:e607–e614.
    1. Alatas FS, Hayashida M, Matsuura T, Saeki I, Yanagi Y, Taguchi T. Intracranial hemorrhage associated with vitamin K-deficiency bleeding in patients with biliary atresia: focus on long-term outcomes. J Pediatr Gastroenterol Nutr. 2012;54:552–557.
    1. Shneider BL, Abel B, Haber B, Karpen SJ, Magee JC, Romero R, Schwarz K, et al. Portal hypertension in children and young adults with biliary atresia. J Pediatr Gastroenterol Nutr. 2012;55:567–573.
    1. Shneider BL, Bosch J, de Franchis R, Emre SH, Groszmann RJ, Ling SC, Lorenz JM, et al. Portal hypertension in children: expert pediatric opinion on the report of the Baveno v Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension. Pediatr Transplant. 2012;16:426–437.
    1. Duche M, Ducot B, Ackermann O, Jacquemin E, Bernard O. Progression to high-risk gastroesophageal varices in children with biliary atresia with low-risk signs at first endoscopy. J Pediatr Gastroenterol Nutr. 2015;60:664–668.
    1. Wanty C, Helleputte T, Smets F, Sokal EM, Stephenne X. Assessment of risk of bleeding from esophageal varices during management of biliary atresia in children. J Pediatr Gastroenterol Nutr. 2013;56:537–543.
    1. Molleston JP, Shneider BL. Preventing variceal bleeding in infants and children: is less more? Gastroenterology. 2013;145:719–722.
    1. Wang X, Xu Z, Miao CH. Current clinical evidence on the effect of general anesthesia on neurodevelopment in children: an updated systematic review with meta-regression. PLoS One. 2014;9:e85760.
    1. Wagner M, Ryu YK, Smith SC, Patel P, Mintz CD. Review: effects of anesthetics on brain circuit formation. J Neurosurg Anesthesiol. 2014;26:358–362.
    1. Duche M, Ducot B, Ackermann O, Baujard C, Chevret L, Frank-Soltysiak M, Jacquemin E, et al. Experience with endoscopic management of high-risk gastroesophageal varices, with and without bleeding, in children with biliary atresia. Gastroenterology. 2013;145:801–807.
    1. Eroglu Y, Emerick KM, Whitingon PF, Alonso EM. Octreotide therapy for control of acute gastrointestinal bleeding in children. J Pediatr Gastroenterol Nutr. 2004;38:41–47.
    1. Stringer MD, Howard ER, Mowat AP. Endoscopic sclerotherapy in the management of esophageal varices in 61 children with biliary atresia. J Pediatr Surg. 1989;24:438–442.
    1. Bernard B, Grange JD, Khac EN, Amiot X, Opolon P, Poynard T. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology. 1999;29:1655–1661.
    1. Zargar SA, Javid G, Khan BA, Yattoo GN, Shah AH, Gulzar GM, Singh J, et al. Endoscopic ligation compared with sclerotherapy for bleeding esophageal varices in children with extrahepatic portal venous obstruction. Hepatology. 2002;36:666–672.
    1. Satapathy SK, Sanyal AJ. Nonendoscopic management strategies for acute esophagogastric variceal bleeding. Gastroenterol Clin North Am. 2014;43:819–833.
    1. Ling SC. Advances in the evaluation and management of children with portal hypertension. Semin Liver Dis. 2012;32:288–297.
    1. Boyer TD, Haskal ZJ. American Association for the Study of Liver D. The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in the Management of Portal Hypertension: update 2009. Hepatology. 2010;51:306.
    1. Wolff M, Hirner A. Current state of portosystemic shunt surgery. Langenbecks Arch Surg. 2003;388:141–149.
    1. Sen Sarma M, Yachha SK, Bhatia V, Srivastava A, Poddar U. Safety, complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease. J Hepatol. 2015;63:1126–1132.
    1. John S, Thuluvath PJ. Hyponatremia in cirrhosis: pathophysiology and management. World J Gastroenterol. 2015;21:3197–3205.
    1. Wong F, Watson H, Gerbes A, Vilstrup H, Badalamenti S, Bernardi M, Gines P, et al. Satavaptan for the management of ascites in cirrhosis: efficacy and safety across the spectrum of ascites severity. Gut. 2012;61:108–116.
    1. Larcher VF, Manolaki N, Vegnente A, Vergani D, Mowat AP. Spontaneous bacterial peritonitis in children with chronic liver disease: clinical features and etiologic factors. J Pediatr. 1985;106:907–912.
    1. de Vries W, de Langen ZJ, Groen H, Scheenstra R, Peeters PM, Hulscher JB, Verkade HJ, et al. Biliary atresia in the Netherlands: outcome of patients diagnosed between 1987 and 2008. J Pediatr. 2012;160:638–644. e632.
    1. Bu LN, Chen HL, Chang CJ, Ni YH, Hsu HY, Lai HS, Hsu WM, et al. Prophylactic oral antibiotics in prevention of recurrent cholangitis after the Kasai portoenterostomy. J Pediatr Surg. 2003;38:590–593.
    1. Mendoza MM, Chiang JH, Lee SY, Kao CY, Chuang JH, Tiao MM, Hsieh CS. Reappraise the effect of redo-Kasai for recurrent jaundice following Kasai operation for biliary atresia in the era of liver transplantation. Pediatr Surg Int. 2012;28:861–864.
    1. Nio M, Sasaki H, Tanaka H, Okamura A. Redo surgery for biliary atresia. Pediatr Surg Int. 2013;29:989–993.
    1. Bondoc AJ, Taylor JA, Alonso MH, Nathan JD, Wang Y, Balistreri WF, Bezerra JA, et al. The beneficial impact of revision of Kasai portoenterostomy for biliary atresia: an institutional study. Ann Surg. 2012;255:570–576.
    1. Kroger AT, Atkinson WL, Marcuse EK, Pickering LK. Advisory Committee on Immunization Practices Centers for Disease C, Prevention General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep. 2006;55:1–48.
    1. Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44–e100.
    1. Feldman AGSS, Beaty B, Kempe A. Hospitalizations for Respiratory Syncitial Virus, Influenza, and other Vaccine Preventable Illnesses in Liver Transplant Recipients at Freestanding Childrens Hospitals. Hepatology. 2015;62:279A.
    1. Feldman AGSS, Beaty B, Kempe A. Immunization Practices Amongst Pediatric Transplant HEpatologists at SPLIT centers. Hepatology. 2015;62:177A.
    1. Barshes NR, Lee TC, Udell IW, O’Mahoney CA, Karpen SJ, Carter BA, Goss JA. The pediatric end-stage liver disease (PELD) model as a predictor of survival benefit and posttransplant survival in pediatric liver transplant recipients. Liver Transpl. 2006;12:475–480.
    1. OPTN-RHSA Final Rule with comment period. Fed Regist. 1998:16296–16338.
    1. Tessier ME, Harpavat S, Shepherd RW, Hiremath GS, Brandt ML, Fisher A, Goss JA. Beyond the Pediatric end-stage liver disease system: solutions for infants with biliary atresia requiring liver transplant. World J Gastroenterol. 2014;20:11062–11068.
    1. Kim WR, Smith JM, Skeans MA, Schladt DP, Schnitzler MA, Edwards EB, Harper AM, et al. OPTN/SRTR 2012 Annual Data Report: liver. Am J Transplant. 2014;(14 Suppl 1):69–96.
    1. Hsu EK, Shaffer M, Bradford M, Mayer-Hamblett N, Horslen S. Heterogeneity and disparities in the use of exception scores in pediatric liver allocation. Am J Transplant. 2015;15:436–444.
    1. Shneider BL, Neimark E, Frankenberg T, Arnott L, Suchy FJ, Emre S. Critical analysis of the pediatric end-stage liver disease scoring system: a single center experience. Liver Transpl. 2005;11:788–795.
    1. Shneider BL, Suchy FJ, Emre S. National and regional analysis of exceptions to the Pediatric End-Stage Liver Disease scoring system (2003–2004) Liver Transpl. 2006;12:40–45.
    1. Salvalaggio PR, Neighbors K, Kelly S, Emerick KM, Iyer K, Superina RA, Whitington PF, et al. Regional variation and use of exception letters for cadaveric liver allocation in children with chronic liver disease. Am J Transplant. 2005;5:1868–1874.
    1. Lacaille F, Sokal E. Living-related liver transplantation. J Pediatr Gastroenterol Nutr. 2001;33:431–438.
    1. Yang SC, Huang CJ, Chen CL, Wang CH, Wu SC, Shih TH, Juang SE, et al. Living donor liver transplantation with body-weight more or less than 10 kilograms. World J Gastroenterol. 2015;21:7248–7253.
    1. Sokal EM, Veyckemans F, de Ville de Goyet J, Moulin D, Van Hoorebeeck N, Alberti D, Buts JP, et al. Liver transplantation in children less than 1 year of age. J Pediatr. 1990;117:205–210.
    1. Sundaram SS, Alonso EM, Anand R. Study of Pediatric Liver Transplantation Research G. Outcomes after liver transplantation in young infants. J Pediatr Gastroenterol Nutr. 2008;47:486–492.
    1. Arnon R, Leshno M, Annunziato R, Florman S, Iyer K. What is the optimal timing of liver transplantation for children with biliary atresia? A Markov model simulation analysis. J Pediatr Gastroenterol Nutr. 2014;59:398–402.
    1. Mizuta K, Urahashi T, Ihara Y, Sanada Y, Wakiya T, Yamada N, Okada N, et al. Living donor liver transplantation in children with cholestatic liver disease: a single-center experience. Transplant Proc. 2012;44:469–472.
    1. Barshes NR, Lee TC, Balkrishnan R, Karpen SJ, Carter BA, Goss JA. Orthotopic liver transplantation for biliary atresia: the U.S. experience. Liver Transpl. 2005;11:1193–1200.
    1. Bourdeaux C, Darwish A, Jamart J, Tri TT, Janssen M, Lerut J, Otte JB, et al. Living-related versus deceased donor pediatric liver transplantation: a multivariate analysis of technical and immunological complications in 235 recipients. Am J Transplant. 2007;7:440–447.
    1. Gurevich M, Guy-Viterbo V, Janssen M, Stephenne X, Smets F, Sokal E, Lefebvre C, et al. Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Universite Catholique de Louvain. Ann Surg. 2015;262:1141–1149.
    1. Cauley RP, Vakili K, Fullington N, Potanos K, Graham DA, Finkelstein JA, Kim HB. Deceased-donor split-liver transplantation in adult recipients: is the learning curve over? J Am Coll Surg. 2013;217:672–684. e671.
    1. Fung E, Shaw RJ. Pediatric Transplant Rating Instrument - a scale for the pretransplant psychiatric evaluation of pediatric organ transplant recipients. Pediatr Transplant. 2008;12:57–66.
    1. Caudle SE, Katzenstein JM, Karpen S, McLin V. Developmental assessment of infants with biliary atresia: differences between boys and girls. J Pediatr Gastroenterol Nutr. 2012;55:384–389.
    1. Caudle SE, Katzenstein JM, Karpen SJ, McLin VA. Language and motor skills are impaired in infants with biliary atresia before transplantation. J Pediatr. 2010;156:936–940. 940 e931.

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