American Journal of Medical Genetics 42:801-806 (1992)
Maternal Serum a-Fetoprotein Screening and Fetal Chromosome Anomalies: Is Lowering Maternal Age for Amniocentesis Preferable? Sara Kaffe and Lillian Y. F. Hsu Prenatal Diagnosis Laboratory of New York City, Medical and Health Research Association of NYC, Znc. (S.K., L.YE.H.), Department of Pediatrics, Mount Sinai School of Medicine (S.K.), and Department of Pediatrics, New York University School of Medicine (L.Y.F.H.), New York, New York
We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098patients referred for amniocentesis because of low maternal serum a-fetoprotein (MSAFP)to those of 445 patients whose indication was elevated MSAFP and those of 361 patients who had amniocentesis for “maternal anxiety.” Autosomal trisomies, sex chromosome aberrations, and various structural rearrangements were detected in all 3 groups and actually exceeded the age-related incidence estimates. The frequency of chromosome anomalies in cases studied because of “maternal anxiety” with no prior screening was similar to that in the group referred for low MSAFP (1.38and 1.27%,respectively). A relatively higher frequency (2.02%)was detected in the group whose indication was elevated MSAFP. Maternal serum screening is designed primarily to recalculate risk figures for Down syndrome, but not for other major chromosome abnormalities. The concept of prenatal screening for chromosome aberrations must therefore be reevaluated. We think that efforts should be directed at making amniocenteses more accessible to patients who request it. “Lowering” maternal age limits to 30 would encompass a greater proportion of pregnancies at risk and would be a step toward more effective prenatal diagnosis for chromosome abnormalities.
KEY WORDS: maternal serum a-fetoprotein, prenatal screening, risk assessment, Down syndrome, chromosome anomalies
Received for publication March 22,1991; revision received June 13, 1991. Address reprint requests to Sara Kaffe, M.D., Prenatal Diagnosis Laboratory of New York City, 455 First Avenue, Room 027, New York, NY 10016.
0 1992 Wiley-Liss, Inc.
INTRODUCTION An association between low MSAFP and fetal Down syndrome has been documented repeatedly [Merkatz et al., 1984; Cuckle et al., 1984; Palomaki and Haddow, 1987; Di Maio et al., 1987; Lustig et al., 1988, New England Regional Genetics group, 19891. MSAFP screening is now offered routinely as a way to select “younger” women who may be at an increased risk for Down syndrome, in order to recommend diagnostic amniocentesis. The current approach to defining an increased risk for Down syndrome in the “younger” mother is to use the accepted arbitrary age related risk at 35 (1:270) as a cut-off guideline, and to recommend amniocentesis to these patients when their recalculated individual risk is equal to or greater than 1:270[Knight et al., 19881. Such screening has increased the detection rate of pregnancies affected with Down syndrome by approximately 20%. In an effort to increase the sensitivity of screening for Down syndrome it was suggested to use a combination of maternal serum AFP, unconjugated estriol (uE,) [Canick et al., 19881, and human chorionic gonadotropin (hCG)levels [Bogart et al., 1989; Wald et al., 19881,or human chorionic gonadotropin free P-protein alone [Macri, 19901. Neither of these screening methods establishes the presence or absence of a chromosome abnormality. Their purpose is to revise the probability of a pregnancy being affected by recalculating risk figures rather than providing an actual diagnosis. In order to assess the usefulness of low MSAFP screening, and whether the concept of screening is appropriate for chromosome abnormalities, we have compared the cytogenetic anomalies diagnosed prenatally in patients referred for low MSAFP to those with an indication of high MSAFP and a “control” group in whom amniocentesis was performed for “maternal anxiety” with no other specific indication. MATERIAL AND METHODS During the period from October 1985 through April 1990 our laboratory received 15,000 amniotic fluids for chromosome analysis. Of those, 1,098 analyses were
802
Kaffe and Hsu TABLE I. Number and Age Distribution of Patients in Our Three Study Groups
Group A Low MSAFP Maternal Number of age Number of chromosome (vears) patients abnormalities
Maternal Serum a-Fetoprotein Screening and Fetal Chromosome Anomalies: Is Lowering Maternal Age for Amniocentesis Preferable? Sara Kaffe and Lillian Y. F. Hsu Prenatal Diagnosis Laboratory of New York City, Medical and Health Research Association of NYC, Znc. (S.K., L.YE.H.), Department of Pediatrics, Mount Sinai School of Medicine (S.K.), and Department of Pediatrics, New York University School of Medicine (L.Y.F.H.), New York, New York
We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098patients referred for amniocentesis because of low maternal serum a-fetoprotein (MSAFP)to those of 445 patients whose indication was elevated MSAFP and those of 361 patients who had amniocentesis for “maternal anxiety.” Autosomal trisomies, sex chromosome aberrations, and various structural rearrangements were detected in all 3 groups and actually exceeded the age-related incidence estimates. The frequency of chromosome anomalies in cases studied because of “maternal anxiety” with no prior screening was similar to that in the group referred for low MSAFP (1.38and 1.27%,respectively). A relatively higher frequency (2.02%)was detected in the group whose indication was elevated MSAFP. Maternal serum screening is designed primarily to recalculate risk figures for Down syndrome, but not for other major chromosome abnormalities. The concept of prenatal screening for chromosome aberrations must therefore be reevaluated. We think that efforts should be directed at making amniocenteses more accessible to patients who request it. “Lowering” maternal age limits to 30 would encompass a greater proportion of pregnancies at risk and would be a step toward more effective prenatal diagnosis for chromosome abnormalities.
KEY WORDS: maternal serum a-fetoprotein, prenatal screening, risk assessment, Down syndrome, chromosome anomalies
Received for publication March 22,1991; revision received June 13, 1991. Address reprint requests to Sara Kaffe, M.D., Prenatal Diagnosis Laboratory of New York City, 455 First Avenue, Room 027, New York, NY 10016.
0 1992 Wiley-Liss, Inc.
INTRODUCTION An association between low MSAFP and fetal Down syndrome has been documented repeatedly [Merkatz et al., 1984; Cuckle et al., 1984; Palomaki and Haddow, 1987; Di Maio et al., 1987; Lustig et al., 1988, New England Regional Genetics group, 19891. MSAFP screening is now offered routinely as a way to select “younger” women who may be at an increased risk for Down syndrome, in order to recommend diagnostic amniocentesis. The current approach to defining an increased risk for Down syndrome in the “younger” mother is to use the accepted arbitrary age related risk at 35 (1:270) as a cut-off guideline, and to recommend amniocentesis to these patients when their recalculated individual risk is equal to or greater than 1:270[Knight et al., 19881. Such screening has increased the detection rate of pregnancies affected with Down syndrome by approximately 20%. In an effort to increase the sensitivity of screening for Down syndrome it was suggested to use a combination of maternal serum AFP, unconjugated estriol (uE,) [Canick et al., 19881, and human chorionic gonadotropin (hCG)levels [Bogart et al., 1989; Wald et al., 19881,or human chorionic gonadotropin free P-protein alone [Macri, 19901. Neither of these screening methods establishes the presence or absence of a chromosome abnormality. Their purpose is to revise the probability of a pregnancy being affected by recalculating risk figures rather than providing an actual diagnosis. In order to assess the usefulness of low MSAFP screening, and whether the concept of screening is appropriate for chromosome abnormalities, we have compared the cytogenetic anomalies diagnosed prenatally in patients referred for low MSAFP to those with an indication of high MSAFP and a “control” group in whom amniocentesis was performed for “maternal anxiety” with no other specific indication. MATERIAL AND METHODS During the period from October 1985 through April 1990 our laboratory received 15,000 amniotic fluids for chromosome analysis. Of those, 1,098 analyses were
802
Kaffe and Hsu TABLE I. Number and Age Distribution of Patients in Our Three Study Groups
Group A Low MSAFP Maternal Number of age Number of chromosome (vears) patients abnormalities
