Cholelithiasis
in Newborns
and Infants
By Dickens St-Vil, Salam Yazbeck, Frarqois I. Luks, B.J. Hancock, Denis Filiatrault, and Sami Youssef Montreal, Quebec l Cholelithiasis in infants is rare, and has usually been associated with hemolysis, ileal disease, congenital anomalies of the biliary tree,
hyperalimentation,
and prolonged
fasting. With the increased use of abdominal phy (US), more cases of cholelithiasis We report abdominal
our experience
with
are being discovered.
13 infants
US to have gallstones.
ultrasonogradiagnosed
on
There were g boys and 4
girls with an average age at diagnosis of 2.6 months (range, 0 to g months). Predisposing factors could be identified in only 6 of the 13 patients. Two patients with obstructive underwent
cholecystectomy
tion. One patient with choledocolithiasis duct dilatation
jaundice
and common bile duct explora-
was observed.
and common
bile
His stone passed spontane-
ously, with resolution of symptoms. Ten patients without cholestasis remained asymptomatic, with disappearance of lithiasis
in five of them.
Neonatal
common than previously suspected;
cholelithiasis
is more
it seems to affect males
more often than females and is usually not associated
with
known predisposing factors. It appears to be a temporary, self-limiting phenomenon, and an aggressive approach is not warranted
in the asymptomatic
infant. Surgical or radiologi-
cal intervention should be reserved for the symptomatic patients or those with underlying lithogenic disorders. Copyright
o 1992 by W.B. Saunders Company
INDEX WORDS: Cholelithiasis,
neonatal.
I
N THE PAST, cholelithiasis in infancy was most frequently caused by hemolytic disease.’ Early cholecystectomy was recommended because of the significant morbidity and mortality associated with this condition.2 With the increased use of abdominal ultrasonography (US), more cases of cholelithiasis are being encountered and the proportion of gallstones associated with hemolytic disorders has decreased to less than 20%.2 Predisposing factors now include congenital anomalies of the biliary tree, furosemide use, prolonged fasting associated with hyperalimentation in premature infants, and ileal disease.3-7 More cases of cholelithiasis in otherwise healthy neonates are also being reported.*,s*9 Jacir et ali0 advocated a conservative approach in asymptomatic patients after noting spontaneous resolution of the gallstones in three of their four patients. We report our experience with cholelithiasis in infants.
RESULTS
There were nine boys and four girls born at a mean gestational age of 38.8 weeks and with a mean birth weight of 2.847 kg. The mean age at diagnosis was 2.6 months (range, 2 days to 9 months). Ten patients were 3 months old or younger. Three infants had received total parenteral hyperalimentation (TPN) for periods of 1, 2, and 8 weeks, respectively. One infant had intestinal malabsorption, one had neonatal septicemia, and another received phototherapy for neonatal hyperbilirubinemia. The other seven infants had no known predisposing factors. Two patients presenting with obstructive jaundice were noted to have a dilated common bile duct (CBD) and choledocholithiasis on US. The stone passed spontaneously, with resolution of symptoms, in one patient, now 4 years old. The other patient underwent cure of malrotation, cholecystectomy, CBD exploration, and T-tube drainage. The postoperative course was complicated by an episode of severe dehydration and electrolytes disturbance secondary to excess biliary loss from an unclamped T-tube. The T-tube was removed, the patient improved and has been doing well for an l&month follow-up. Eleven patients underwent US for investigations unrelated to the biliary tree: postprandial vomiting or regurgitation in 5, chronic diarrhea in 1, growth retardation in 1, and routine examination to rule out renal malformations in 4. The US showed gallstones, with an accoustic shadow, or organized bile sludge in all cases. In one patient, the CBD was noted to be dilated, but no choledocholithiasis could be demonstrated. Associated diagnoses were gastroesophageal reflex in 3 patients and pyloric stenosis, coeliac disease, trisomy 21 and intestinal malrotation each in 1 patient. The infant with concomittant pyloric stenosis underwent pyloromyotomy and cholecystotomy without complication. The other 10 patients were observed and closely followed with ultrasonography. They remained asymptomatic, with disappearance of stones in five patients (one patient is awaiting follow-up US). Four patients
All cases of cholelithiasis diagnosed by US since January 1986 in infants younger than 12 months were reviewed for age, sex, predisposing factors, clinical presentation, management, and outcome. Follow-up clinical and US examinations were performed at regular intervals as long as cholelithiasis persisted.
From the Departments of Surgery and Radiology, Ste-Justine Hospital, University of Montreal, Montreal, Quebec. Presented at the 23rd Annual Meeting of the Canadian Association of Paediatrik Surgeons, Quebec City, Quebec, September 19-22, 1991. Address reprint requests to Salam Yazbeck, MD, Ste-Justine Hospital, 3175 Ste-Catherine Rd, Montreal, Quebec H3T IC5. Canada. Copyright o 1992 by W B. Saunders Company 0022-3468/92/2710-0013$03.00/0
Journalof Pediatric Surgery, Vol27, No 10 (October), 1992: pp 1361307
1305
MATERIALS AND METHODS
ST-VIL ET AL
1306
have persistent calcified gallstones low-up of 1.8 years.
at a mean fol-
DISCUSSION
Cholelithiasis in infancy was mainly associated with congenital anomalies of the biliary tree and hemolytic diseases such as sickle cell anemia and hereditary spherocytosis,“-is and was often complicated by gallbladder or CBD perforation8 More recently, TPN, prolonged fasting, furosemide therapy, and phototherapy have become the most probable etiologic factors.3 In children receiving TPN, duration of hyperalimentation, aberrant eating patterns, and prior ileal resection significantly increase the incidence of gallstones.16-*0 These stones consist mostly of calcium billirubinate and result from bile stasis within the gallbladder. *I A surveillance program and early cholecystectomy have been recommended.3 In 1941, Spence9 reported the presence of multiple gallstones at autopsy in a newborn who died of intracranial hemorrhage; no explanation for the cholelithiasis was found. Since then, several incidental cases of neonatal cholelithiasis have been described, usually at laparotomy, and cholecystotomy has been proposed. ls2With increasing use of abdominal US, more cases of cholelithiasis are being diagnosed in otherwise healthy infants.22s23The etiology of this condition is unclear. Recent studies in the composition of human fetal bile24 and the ultrasonographic identification of the human gallbladder in utero25 are first steps in the antenatal detection of altered lithogenicity of the bile and congenital anomalies of the gallbladder which could predispose to congenital cholelithiasis. The present review illustrates several features of idiopathic cholelithiasis. It is now the most common form of cholelithiasis in the neonatal period, as 7 of 13 infants had no known predisposing factors. Bile stasis secondary to prolonged fasting and hyperalimen-
tation represent the second largest group, while hemolytic disease has become a less predominant cause of cholelithiasis in infants. Males are affected more often (70%) than female, which is in sharp contrast with the female preponderance in adults and adolescents.*~2~8In most cases, the condition is initially diagnosed by US. In addition, plain abdominal radiographs may show right upper quadrant calcifications, as was the case on follow-up in three of the present patients. Transcholecystic cholangiography (TCC) identified a distal CBD obstruction in one patient in this series. Recent studies have proposed the therapeutic use of TCC with lavage in the management of CBD stones26,27in infants. Of 10 patients with gallstones followed prospectively, five had spontaneous resolution within 6 months of diagnosis. All five patients were asymptomatic, and none had an identifiable risk factor for the development of gallstones. In all, five of the seven patients with asymptomatic, idiopathic cholelithiasis experienced complete resolution of their stones with one patient awaiting follow-up US. Only one of the four patients with persistent, calcified gallstones belongs to the idiopathic group. This has led us to believe that cholelithiasis in infants in the absence of known lithogenic factors is a transient and self-limiting condition that does not behave like its adult counterpart. Based on these observations, we recommend that asymptomatic infants with idiopathic cholelithiasis be observed for spontaneous resolution of their stones, as already suggested by Jacir et aLi0 Cholelithiasis associated with known risk factors does not tend to resolve spontaneously, and treatment is indicated. Treatment is also indicated for symptomatic cholelithiasis or choledocholithiasis, regardless of its etiology. Although cholecystectomy would appear to be indicated if gallstones persist or calcify, the exact timing of the operation is not as yet clearly established.
REFERENCES 1. Hugues
RG, Mayell MJ: Cholelithiasis
in a neonate.
Arch Dis
Child 50:815-816,1975 2. Holcomb GW Jr: Gallbladder disease, in Welch KJ, Randolph JG, Ravitch MM, et al (eds): Pediatric Surgery (ed 4). Chicago, IL, Year Book, 1986, pp 1060-1067 3. Roslyn JJ, Berquist WE, Pitt HA, et al: Increased risk of gallstone in children receiving total parenteral nutrition. Pediatrics 71:784-789,1983 4. Callahan J, Haller JO, Cacciarelli AA: Cholelithiasis in infants: Association with total parenteral nutrition and furosemide. Pediatr Radio1 143:437-439,1982 5. Boyle RJ, Sumner TE, Volberg FM: Cholelithiasis in a 3-week-old small premature infant. Pediatrics 71:967-969,1983 6. Manginello FP, Javitt MB: Parenteral nutrition and neonatal cholestasis. J Pediatr 94:296-298,1979 7. Schlechter RD, Laberge JM, Youssef S: Cholelithiasis in
infancy. Presented ation of Paediatric
at the Annual Meeting of the Canadian AssociSurgeons, Montreal, Quebec, September 1984
8. Brill PW, Winchester P, Rosen Pediatr Radio1 12:285-288,1982 9. Spence GR: Cholelithiasis 58479-481, 1941
MS: Neonatal
in newborn
cholelithiasis.
infants.
Arch Pediatr
10. Jacir NN, Anderson KD, Eichelberger M, et al: Cholelithiasis in infancy: Resolution of gallstones in three of four infants. J Pediatr Surg 21:567-569, 1986 11. Graivier L, Dorman GW, Votteler TP: Gallbladder in infants and children. Surgery 63:690-696,1968 12. Forshall I, Rickham Br J Surg 42:161-164,1955
PP: Gallbladder
13. Hamkins PE, Grahn FB, Holliday children. Am J Surg 11:741-744.1966
disease
disease
in childhood.
P: Gallbladder
disease
in
CHOLELITHIASIS IN NEWBORNSANED INFANTS 14. Seiler I: Gallbladder disease in children. Am J Dis Child 99:662-666, 1960 15. Walker CHM: Etiology of cholelithiasis in childhood. Arch Dis Child 32:293-297, 1951 16. Roslyn JJ, Pitt HA, Mann L, et al: Long term total parenteral nutrition induces gallbladder disease. Gastroenterology 80:1264, 1981 (abstr) 17. Whitington PF. Black DD: Cholelithiasis in premature infants treated with parenteral nutrition and furosemide. J Pediatr 971647-649, 1980 18. Petersen SR, Sheldon GF: Acute acalculous cholecystitis: A complication of hyperalimentation. Am J Surg 138:814-817,1979 19. Hill GL, Mair WSG, Goligher JC: Gallstones after ileostomy and ileal resection. Gut 16:932-936, 1975 20. Pellerin D, Bertin P, Nihoul-FCkCte C, et al: Cholelithiasis and heal pathology in childhood. J Pediatr Surg lo:%-41, 1975 21. Alien B, Bernhoft R, Blanckaert N, et al: Sludge is calcium bilirubinate associated with bile stasis. Am J Surg 141:51-56,198l
1307 22. Avni EF, Matos C, Van Gansbeke D, et al: Atypical gallbladder content in neonates, ultrasonographic demonstration. Ann Radio1 29:267-273,1986 23. Greenberg M, Kangarloo H, Cochran ST, et al: The ultrasonographic diagnosis of cholecystitis and cholelithiasis in children. Radiology 137:745-749, 1980 24. Setchell KDR, DuMaswala R, Colombo C, et al: Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. J Biol Chem 263:1663716644,1988 25. Kata K, Aoki S, Hata T, et al: Ultrasonographic identification of the human fetal gallbladder in utero. Gynecol Obstet Invest 23:79-83,1987 26. Brunelle F, Descos B, Bernard 0, et al: Lithiase de la voie biliaire principale du nourrisson. Ann Radio1 26:147-153, 1983 27. Pariente D, Bernard 0, Gauthier F, et al: Radiological treatment of common bile duct lithiasis in infancy. Pediatr Radio1 19:104-107, 1989
in Newborns
and Infants
By Dickens St-Vil, Salam Yazbeck, Frarqois I. Luks, B.J. Hancock, Denis Filiatrault, and Sami Youssef Montreal, Quebec l Cholelithiasis in infants is rare, and has usually been associated with hemolysis, ileal disease, congenital anomalies of the biliary tree,
hyperalimentation,
and prolonged
fasting. With the increased use of abdominal phy (US), more cases of cholelithiasis We report abdominal
our experience
with
are being discovered.
13 infants
US to have gallstones.
ultrasonogradiagnosed
on
There were g boys and 4
girls with an average age at diagnosis of 2.6 months (range, 0 to g months). Predisposing factors could be identified in only 6 of the 13 patients. Two patients with obstructive underwent
cholecystectomy
tion. One patient with choledocolithiasis duct dilatation
jaundice
and common bile duct explora-
was observed.
and common
bile
His stone passed spontane-
ously, with resolution of symptoms. Ten patients without cholestasis remained asymptomatic, with disappearance of lithiasis
in five of them.
Neonatal
common than previously suspected;
cholelithiasis
is more
it seems to affect males
more often than females and is usually not associated
with
known predisposing factors. It appears to be a temporary, self-limiting phenomenon, and an aggressive approach is not warranted
in the asymptomatic
infant. Surgical or radiologi-
cal intervention should be reserved for the symptomatic patients or those with underlying lithogenic disorders. Copyright
o 1992 by W.B. Saunders Company
INDEX WORDS: Cholelithiasis,
neonatal.
I
N THE PAST, cholelithiasis in infancy was most frequently caused by hemolytic disease.’ Early cholecystectomy was recommended because of the significant morbidity and mortality associated with this condition.2 With the increased use of abdominal ultrasonography (US), more cases of cholelithiasis are being encountered and the proportion of gallstones associated with hemolytic disorders has decreased to less than 20%.2 Predisposing factors now include congenital anomalies of the biliary tree, furosemide use, prolonged fasting associated with hyperalimentation in premature infants, and ileal disease.3-7 More cases of cholelithiasis in otherwise healthy neonates are also being reported.*,s*9 Jacir et ali0 advocated a conservative approach in asymptomatic patients after noting spontaneous resolution of the gallstones in three of their four patients. We report our experience with cholelithiasis in infants.
RESULTS
There were nine boys and four girls born at a mean gestational age of 38.8 weeks and with a mean birth weight of 2.847 kg. The mean age at diagnosis was 2.6 months (range, 2 days to 9 months). Ten patients were 3 months old or younger. Three infants had received total parenteral hyperalimentation (TPN) for periods of 1, 2, and 8 weeks, respectively. One infant had intestinal malabsorption, one had neonatal septicemia, and another received phototherapy for neonatal hyperbilirubinemia. The other seven infants had no known predisposing factors. Two patients presenting with obstructive jaundice were noted to have a dilated common bile duct (CBD) and choledocholithiasis on US. The stone passed spontaneously, with resolution of symptoms, in one patient, now 4 years old. The other patient underwent cure of malrotation, cholecystectomy, CBD exploration, and T-tube drainage. The postoperative course was complicated by an episode of severe dehydration and electrolytes disturbance secondary to excess biliary loss from an unclamped T-tube. The T-tube was removed, the patient improved and has been doing well for an l&month follow-up. Eleven patients underwent US for investigations unrelated to the biliary tree: postprandial vomiting or regurgitation in 5, chronic diarrhea in 1, growth retardation in 1, and routine examination to rule out renal malformations in 4. The US showed gallstones, with an accoustic shadow, or organized bile sludge in all cases. In one patient, the CBD was noted to be dilated, but no choledocholithiasis could be demonstrated. Associated diagnoses were gastroesophageal reflex in 3 patients and pyloric stenosis, coeliac disease, trisomy 21 and intestinal malrotation each in 1 patient. The infant with concomittant pyloric stenosis underwent pyloromyotomy and cholecystotomy without complication. The other 10 patients were observed and closely followed with ultrasonography. They remained asymptomatic, with disappearance of stones in five patients (one patient is awaiting follow-up US). Four patients
All cases of cholelithiasis diagnosed by US since January 1986 in infants younger than 12 months were reviewed for age, sex, predisposing factors, clinical presentation, management, and outcome. Follow-up clinical and US examinations were performed at regular intervals as long as cholelithiasis persisted.
From the Departments of Surgery and Radiology, Ste-Justine Hospital, University of Montreal, Montreal, Quebec. Presented at the 23rd Annual Meeting of the Canadian Association of Paediatrik Surgeons, Quebec City, Quebec, September 19-22, 1991. Address reprint requests to Salam Yazbeck, MD, Ste-Justine Hospital, 3175 Ste-Catherine Rd, Montreal, Quebec H3T IC5. Canada. Copyright o 1992 by W B. Saunders Company 0022-3468/92/2710-0013$03.00/0
Journalof Pediatric Surgery, Vol27, No 10 (October), 1992: pp 1361307
1305
MATERIALS AND METHODS
ST-VIL ET AL
1306
have persistent calcified gallstones low-up of 1.8 years.
at a mean fol-
DISCUSSION
Cholelithiasis in infancy was mainly associated with congenital anomalies of the biliary tree and hemolytic diseases such as sickle cell anemia and hereditary spherocytosis,“-is and was often complicated by gallbladder or CBD perforation8 More recently, TPN, prolonged fasting, furosemide therapy, and phototherapy have become the most probable etiologic factors.3 In children receiving TPN, duration of hyperalimentation, aberrant eating patterns, and prior ileal resection significantly increase the incidence of gallstones.16-*0 These stones consist mostly of calcium billirubinate and result from bile stasis within the gallbladder. *I A surveillance program and early cholecystectomy have been recommended.3 In 1941, Spence9 reported the presence of multiple gallstones at autopsy in a newborn who died of intracranial hemorrhage; no explanation for the cholelithiasis was found. Since then, several incidental cases of neonatal cholelithiasis have been described, usually at laparotomy, and cholecystotomy has been proposed. ls2With increasing use of abdominal US, more cases of cholelithiasis are being diagnosed in otherwise healthy infants.22s23The etiology of this condition is unclear. Recent studies in the composition of human fetal bile24 and the ultrasonographic identification of the human gallbladder in utero25 are first steps in the antenatal detection of altered lithogenicity of the bile and congenital anomalies of the gallbladder which could predispose to congenital cholelithiasis. The present review illustrates several features of idiopathic cholelithiasis. It is now the most common form of cholelithiasis in the neonatal period, as 7 of 13 infants had no known predisposing factors. Bile stasis secondary to prolonged fasting and hyperalimen-
tation represent the second largest group, while hemolytic disease has become a less predominant cause of cholelithiasis in infants. Males are affected more often (70%) than female, which is in sharp contrast with the female preponderance in adults and adolescents.*~2~8In most cases, the condition is initially diagnosed by US. In addition, plain abdominal radiographs may show right upper quadrant calcifications, as was the case on follow-up in three of the present patients. Transcholecystic cholangiography (TCC) identified a distal CBD obstruction in one patient in this series. Recent studies have proposed the therapeutic use of TCC with lavage in the management of CBD stones26,27in infants. Of 10 patients with gallstones followed prospectively, five had spontaneous resolution within 6 months of diagnosis. All five patients were asymptomatic, and none had an identifiable risk factor for the development of gallstones. In all, five of the seven patients with asymptomatic, idiopathic cholelithiasis experienced complete resolution of their stones with one patient awaiting follow-up US. Only one of the four patients with persistent, calcified gallstones belongs to the idiopathic group. This has led us to believe that cholelithiasis in infants in the absence of known lithogenic factors is a transient and self-limiting condition that does not behave like its adult counterpart. Based on these observations, we recommend that asymptomatic infants with idiopathic cholelithiasis be observed for spontaneous resolution of their stones, as already suggested by Jacir et aLi0 Cholelithiasis associated with known risk factors does not tend to resolve spontaneously, and treatment is indicated. Treatment is also indicated for symptomatic cholelithiasis or choledocholithiasis, regardless of its etiology. Although cholecystectomy would appear to be indicated if gallstones persist or calcify, the exact timing of the operation is not as yet clearly established.
REFERENCES 1. Hugues
RG, Mayell MJ: Cholelithiasis
in a neonate.
Arch Dis
Child 50:815-816,1975 2. Holcomb GW Jr: Gallbladder disease, in Welch KJ, Randolph JG, Ravitch MM, et al (eds): Pediatric Surgery (ed 4). Chicago, IL, Year Book, 1986, pp 1060-1067 3. Roslyn JJ, Berquist WE, Pitt HA, et al: Increased risk of gallstone in children receiving total parenteral nutrition. Pediatrics 71:784-789,1983 4. Callahan J, Haller JO, Cacciarelli AA: Cholelithiasis in infants: Association with total parenteral nutrition and furosemide. Pediatr Radio1 143:437-439,1982 5. Boyle RJ, Sumner TE, Volberg FM: Cholelithiasis in a 3-week-old small premature infant. Pediatrics 71:967-969,1983 6. Manginello FP, Javitt MB: Parenteral nutrition and neonatal cholestasis. J Pediatr 94:296-298,1979 7. Schlechter RD, Laberge JM, Youssef S: Cholelithiasis in
infancy. Presented ation of Paediatric
at the Annual Meeting of the Canadian AssociSurgeons, Montreal, Quebec, September 1984
8. Brill PW, Winchester P, Rosen Pediatr Radio1 12:285-288,1982 9. Spence GR: Cholelithiasis 58479-481, 1941
MS: Neonatal
in newborn
cholelithiasis.
infants.
Arch Pediatr
10. Jacir NN, Anderson KD, Eichelberger M, et al: Cholelithiasis in infancy: Resolution of gallstones in three of four infants. J Pediatr Surg 21:567-569, 1986 11. Graivier L, Dorman GW, Votteler TP: Gallbladder in infants and children. Surgery 63:690-696,1968 12. Forshall I, Rickham Br J Surg 42:161-164,1955
PP: Gallbladder
13. Hamkins PE, Grahn FB, Holliday children. Am J Surg 11:741-744.1966
disease
disease
in childhood.
P: Gallbladder
disease
in
CHOLELITHIASIS IN NEWBORNSANED INFANTS 14. Seiler I: Gallbladder disease in children. Am J Dis Child 99:662-666, 1960 15. Walker CHM: Etiology of cholelithiasis in childhood. Arch Dis Child 32:293-297, 1951 16. Roslyn JJ, Pitt HA, Mann L, et al: Long term total parenteral nutrition induces gallbladder disease. Gastroenterology 80:1264, 1981 (abstr) 17. Whitington PF. Black DD: Cholelithiasis in premature infants treated with parenteral nutrition and furosemide. J Pediatr 971647-649, 1980 18. Petersen SR, Sheldon GF: Acute acalculous cholecystitis: A complication of hyperalimentation. Am J Surg 138:814-817,1979 19. Hill GL, Mair WSG, Goligher JC: Gallstones after ileostomy and ileal resection. Gut 16:932-936, 1975 20. Pellerin D, Bertin P, Nihoul-FCkCte C, et al: Cholelithiasis and heal pathology in childhood. J Pediatr Surg lo:%-41, 1975 21. Alien B, Bernhoft R, Blanckaert N, et al: Sludge is calcium bilirubinate associated with bile stasis. Am J Surg 141:51-56,198l
1307 22. Avni EF, Matos C, Van Gansbeke D, et al: Atypical gallbladder content in neonates, ultrasonographic demonstration. Ann Radio1 29:267-273,1986 23. Greenberg M, Kangarloo H, Cochran ST, et al: The ultrasonographic diagnosis of cholecystitis and cholelithiasis in children. Radiology 137:745-749, 1980 24. Setchell KDR, DuMaswala R, Colombo C, et al: Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. J Biol Chem 263:1663716644,1988 25. Kata K, Aoki S, Hata T, et al: Ultrasonographic identification of the human fetal gallbladder in utero. Gynecol Obstet Invest 23:79-83,1987 26. Brunelle F, Descos B, Bernard 0, et al: Lithiase de la voie biliaire principale du nourrisson. Ann Radio1 26:147-153, 1983 27. Pariente D, Bernard 0, Gauthier F, et al: Radiological treatment of common bile duct lithiasis in infancy. Pediatr Radio1 19:104-107, 1989
