Determination of Levels of Carcinoembryonic Antigen and Nonspecific Cross-Reacting Antigen in the Sera of Neonatallnfants: Brief Communication 1
s. von Kleist, 2 S. Troupel, 2 M. King, 2 and P. Burtin 2 ABSTRACT-Seventy-eight sera from neonatal infants, born at full term or prematurely, were studied for their carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) concentrations, which were compared to the normal adult concentrations. The levels of CEA in the sera were significantly higher in newborns than inadults: 9.05 ng CEA/ml in newborns as compared to 2.5 ng CEA/ml in adults (P=O.001). The levels of NCA in the sera were also higher in newborns: 164 ng NCA/ml in newborns as compared to 130 ng NCA/ml in adults. This difference in NCA levels was not significant, although 80% of the newborns had increased values (>130 ng/ml). Whether the infant was born at full term or prematurely and whether the infant was a boy or girl had no statistically significant influence on the concentration of the CEA and the NCA in the infant.-J Natl Cancer In5t59: 1621-1623, 1977.
Literature on levels of circulating CEA found in the sera of both cancer and noncancer patients, as co mpared with those of healthy adults, is abundant and increases steadily. The first published report on this subject was that of Thomson et al. (1). [For recent reviews, see Martin et al. (2), Laurence and Neville (3), and Lamerz and Fateh-Moghadam (4)]. Surprisingly, among the numerous clinical investigations, only a few were concerned with the CEA assay in children (5). Moreover, we know of no systematic study being done to determine whether the normal levels of CEA in the sera of newborns are the same as those of adults. RIA has definite medical application in the postoperative follow-up and therapy monitoring of adult patients with cancer; consequently, it will be used more and more routinely in the surveillance of cancers in infants. Therefore, we wanted to determine whether the normal values of CEA and NCA differ significantly in the sera of adults and infants. This is important, because the evolution of the malignant condition is evaluated principally on the basis of areturn or the absence of a return of elevated and, therefore, pathologic serum levels to what have been defined as normal levels. So far, for healthy adults, the upper limit for CEA has been generally accepted to be 2.5 ng/rnl or less (1, 6). For NCA, the principal antigen cross-reacting with CEA (7), this value is less known, but we determined it to be 130 ng/rnl (8).
MATERIALS AND METHODS Sera.-Seventy-eight sera were studied simultaneously for both CEA and NCA. Forty-four sera came from infants born at full term and 34 sera were obtained from prematurely born VOL. 59,
NO. 6, DECEMBER 1977
infants. Following international standards, we considered "at-terrn" newborns born after 36-42 weeks of gestation and having a birth weight above 2,500 g. Infants born before this time and/or weighing less than 2,500 g were considered premature. Seventy-eight sera from adult donors (Centre National de Transfusion Sanguine, Paris, France) served as the control group. The sera of the infants came from the maternity ward of St. Antoine Hospital, Paris. Reagents.-Specific immune sera directed against CEA and NCA were prepared in sheep, and immune sera directed against the sheep y-globulins were prepared in rabbits; the immunization procedures followed established schedules. The antigens were purified according to procedures described in (7, 9) and recently summarized in (10). Techniques.-RIA was used as a microassay on whole sera. The antigen-antibody complex was precipitated by a second antibody in a technique adapted from the method of Laurence and Neville (3). The antigens were labeled by 125 1 with the use of the chloramine-T method (11).
RESULTS CEA Levels Concentrations of CEA in the sera were measured in the at-term infants, premature infants, and adults. Of the 78 neonatal sera, 19 had CEA values below 2 ng/rnl, 16 had values between 2 and 3.9 ng/rnl, 6 had values between 4 and 5 ng/rnl, and the remaining 37 had values above 5 ng/rnl (text-fig. 1). Of the 78 adult sera, only 5 showed this elevated CEA concentration (>5 ng/rnl), which was only 6% in the adult group as compared to 46% in the newborn group (table 1). The normal mean level of CEA in the sera in newborns was 9.5 ng/ml, which was significantly higher than that in adults (P=
s. von Kleist, 2 S. Troupel, 2 M. King, 2 and P. Burtin 2 ABSTRACT-Seventy-eight sera from neonatal infants, born at full term or prematurely, were studied for their carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) concentrations, which were compared to the normal adult concentrations. The levels of CEA in the sera were significantly higher in newborns than inadults: 9.05 ng CEA/ml in newborns as compared to 2.5 ng CEA/ml in adults (P=O.001). The levels of NCA in the sera were also higher in newborns: 164 ng NCA/ml in newborns as compared to 130 ng NCA/ml in adults. This difference in NCA levels was not significant, although 80% of the newborns had increased values (>130 ng/ml). Whether the infant was born at full term or prematurely and whether the infant was a boy or girl had no statistically significant influence on the concentration of the CEA and the NCA in the infant.-J Natl Cancer In5t59: 1621-1623, 1977.
Literature on levels of circulating CEA found in the sera of both cancer and noncancer patients, as co mpared with those of healthy adults, is abundant and increases steadily. The first published report on this subject was that of Thomson et al. (1). [For recent reviews, see Martin et al. (2), Laurence and Neville (3), and Lamerz and Fateh-Moghadam (4)]. Surprisingly, among the numerous clinical investigations, only a few were concerned with the CEA assay in children (5). Moreover, we know of no systematic study being done to determine whether the normal levels of CEA in the sera of newborns are the same as those of adults. RIA has definite medical application in the postoperative follow-up and therapy monitoring of adult patients with cancer; consequently, it will be used more and more routinely in the surveillance of cancers in infants. Therefore, we wanted to determine whether the normal values of CEA and NCA differ significantly in the sera of adults and infants. This is important, because the evolution of the malignant condition is evaluated principally on the basis of areturn or the absence of a return of elevated and, therefore, pathologic serum levels to what have been defined as normal levels. So far, for healthy adults, the upper limit for CEA has been generally accepted to be 2.5 ng/rnl or less (1, 6). For NCA, the principal antigen cross-reacting with CEA (7), this value is less known, but we determined it to be 130 ng/rnl (8).
MATERIALS AND METHODS Sera.-Seventy-eight sera were studied simultaneously for both CEA and NCA. Forty-four sera came from infants born at full term and 34 sera were obtained from prematurely born VOL. 59,
NO. 6, DECEMBER 1977
infants. Following international standards, we considered "at-terrn" newborns born after 36-42 weeks of gestation and having a birth weight above 2,500 g. Infants born before this time and/or weighing less than 2,500 g were considered premature. Seventy-eight sera from adult donors (Centre National de Transfusion Sanguine, Paris, France) served as the control group. The sera of the infants came from the maternity ward of St. Antoine Hospital, Paris. Reagents.-Specific immune sera directed against CEA and NCA were prepared in sheep, and immune sera directed against the sheep y-globulins were prepared in rabbits; the immunization procedures followed established schedules. The antigens were purified according to procedures described in (7, 9) and recently summarized in (10). Techniques.-RIA was used as a microassay on whole sera. The antigen-antibody complex was precipitated by a second antibody in a technique adapted from the method of Laurence and Neville (3). The antigens were labeled by 125 1 with the use of the chloramine-T method (11).
RESULTS CEA Levels Concentrations of CEA in the sera were measured in the at-term infants, premature infants, and adults. Of the 78 neonatal sera, 19 had CEA values below 2 ng/rnl, 16 had values between 2 and 3.9 ng/rnl, 6 had values between 4 and 5 ng/rnl, and the remaining 37 had values above 5 ng/rnl (text-fig. 1). Of the 78 adult sera, only 5 showed this elevated CEA concentration (>5 ng/rnl), which was only 6% in the adult group as compared to 46% in the newborn group (table 1). The normal mean level of CEA in the sera in newborns was 9.5 ng/ml, which was significantly higher than that in adults (P=
