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Physiologic cholestasis: Elevation of the primary serum bile acid concentrations in normal infants
GASTROENTEROLOGY
1983:80:1037-41
Physiologic Cholestasis: Elevation of the Primary Serum Bile Acid Concentrations in Normal Infants FREDERICK J. SUCHY, WILLIAM F. BALISTRERI, JAMES E. HEUBI, JOHN E. SEARCY, and RON S. LEVIN Division of Gastroenterology, Children’s Hospital Research Foundation, Cincinnati, Ohio: and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
Immaturity of hepatic excretory function resulting in a period of “physiologic cholestasis” may occur during early life. Serum bile acids should accurately reflect maturation of the enterohepatic circulation; we therefore determined serum concentrations of the primary bile acids in normal infants to define age-related changes. There was a striking rise in serum cholylglycine and conjugates of chenodeoxycholate during the first few days of life over JeveJs detected in cord sera; the values attained were significantly greater than maximal postprandial concentrations found in children over 1 yr of age (p < 0.02). There was a gradual decline in bile acid concentration; however cholylglycine remained higher than the postprandial values of older children until 4 mo and chenodeoxycholate until 6 mo of age. In 12 infants a liquid feeding stimulated a greater maximal postprandial cholylglycine concentration and integrated area under the meal curve than that achieved in children (p < 0.01). There was no diflerence in the postprandial response in chenodeoxycholate in these infants compared with the older subjects. We conclude that serum bile acids are eleReceived August 1980. Accepted December 30, 1980. Address requests for reprints to: William F. Balistreri, M.D., Children’s Hospital Research Foundation, Elland and Bethesda Avenues, Cincinnati, Ohio 45229. This study was supported in part by a grant from the Pediatric Liver Research Foundation, Collingswood, New Jersey and by the United States Public Health Service Grant RR-96123 from the General Clinical Research Centers Branch, National Institutes of Health. This paper was presented in part at the Annual Meeting of the American Association for the Study of Liver Disease, Chicago, lllinois, November 8,1966 and has been published in abstract form (Pediatric Research 1980;14:511, and Gastroenterology 1980; 79:1059). The authors gratefully acknowledge the help of Ms. Linda Jonas for the statistical analysis. 0 1981 by the American Gastroenterological Association OOlS-5085/81/051037-05$02.50
vated in normal infants and that the subsequent decline to levels of the child and adult demonstrates the evolving maturation of liver function during infancy. Bile acids are major synthetic and excretory products of the liver. Efficient transport of these compounds is central to the biliary elimination of many endogenous and exogenous compounds since bile acids are the main determinant of bile flow in the mature mammal (1). At birth the newborn can no longer depend on placental excretory function, and progressive maturation must occur in both the liver and gastrointestinal tract during the transition from a fetal to an extrauterine environment. Failure to adequately adapt to these new demands will lead to inefficiency of normal physiologic events such as bile secretion and fat digestion (2,3). In this study, to further define maturational changes in hepatic excretory function, we measured the serum concentrations of the primary bile acids, cholylglycine and conjugates of chenodeoxycholate, in normal newborns and in infants during the first year of life. Methods Subjects Seventy-five mother-infant pairs from the pediatric practice of two of the authors (J. E. Searcy and R. S. Levin) were enrolled in the study over a period of 1 yr. Maternal and cord sera were obtained at the time of delivery. Blood was drawn from infants by heel puncture during the first 3-4 days of life at the time of routine clinical sampling during their stay in the nursery. All infants were well, and their availability for serial study was dependent on the time of discharge. Samples were also obtained from normal infants <12 mo of age during well child care visits. Samples were drawn just before a feeding whenever pos-
1983:80:1037-41
Physiologic Cholestasis: Elevation of the Primary Serum Bile Acid Concentrations in Normal Infants FREDERICK J. SUCHY, WILLIAM F. BALISTRERI, JAMES E. HEUBI, JOHN E. SEARCY, and RON S. LEVIN Division of Gastroenterology, Children’s Hospital Research Foundation, Cincinnati, Ohio: and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
Immaturity of hepatic excretory function resulting in a period of “physiologic cholestasis” may occur during early life. Serum bile acids should accurately reflect maturation of the enterohepatic circulation; we therefore determined serum concentrations of the primary bile acids in normal infants to define age-related changes. There was a striking rise in serum cholylglycine and conjugates of chenodeoxycholate during the first few days of life over JeveJs detected in cord sera; the values attained were significantly greater than maximal postprandial concentrations found in children over 1 yr of age (p < 0.02). There was a gradual decline in bile acid concentration; however cholylglycine remained higher than the postprandial values of older children until 4 mo and chenodeoxycholate until 6 mo of age. In 12 infants a liquid feeding stimulated a greater maximal postprandial cholylglycine concentration and integrated area under the meal curve than that achieved in children (p < 0.01). There was no diflerence in the postprandial response in chenodeoxycholate in these infants compared with the older subjects. We conclude that serum bile acids are eleReceived August 1980. Accepted December 30, 1980. Address requests for reprints to: William F. Balistreri, M.D., Children’s Hospital Research Foundation, Elland and Bethesda Avenues, Cincinnati, Ohio 45229. This study was supported in part by a grant from the Pediatric Liver Research Foundation, Collingswood, New Jersey and by the United States Public Health Service Grant RR-96123 from the General Clinical Research Centers Branch, National Institutes of Health. This paper was presented in part at the Annual Meeting of the American Association for the Study of Liver Disease, Chicago, lllinois, November 8,1966 and has been published in abstract form (Pediatric Research 1980;14:511, and Gastroenterology 1980; 79:1059). The authors gratefully acknowledge the help of Ms. Linda Jonas for the statistical analysis. 0 1981 by the American Gastroenterological Association OOlS-5085/81/051037-05$02.50
vated in normal infants and that the subsequent decline to levels of the child and adult demonstrates the evolving maturation of liver function during infancy. Bile acids are major synthetic and excretory products of the liver. Efficient transport of these compounds is central to the biliary elimination of many endogenous and exogenous compounds since bile acids are the main determinant of bile flow in the mature mammal (1). At birth the newborn can no longer depend on placental excretory function, and progressive maturation must occur in both the liver and gastrointestinal tract during the transition from a fetal to an extrauterine environment. Failure to adequately adapt to these new demands will lead to inefficiency of normal physiologic events such as bile secretion and fat digestion (2,3). In this study, to further define maturational changes in hepatic excretory function, we measured the serum concentrations of the primary bile acids, cholylglycine and conjugates of chenodeoxycholate, in normal newborns and in infants during the first year of life. Methods Subjects Seventy-five mother-infant pairs from the pediatric practice of two of the authors (J. E. Searcy and R. S. Levin) were enrolled in the study over a period of 1 yr. Maternal and cord sera were obtained at the time of delivery. Blood was drawn from infants by heel puncture during the first 3-4 days of life at the time of routine clinical sampling during their stay in the nursery. All infants were well, and their availability for serial study was dependent on the time of discharge. Samples were also obtained from normal infants <12 mo of age during well child care visits. Samples were drawn just before a feeding whenever pos-