American Journal of Medical Genetics 41:52-53 (1991)
Human Chorionic Gonadotrophin and Trisomy 18 G. Barkai, R. Chaki, M. Sochat, and B. Goldman Institute o f Human Genetics. The Sheba Medical Center. Tel Hashomer (G.B., R.C., B.G.); Beilinson Medical Center i M . S J ,ISA Estimation of maternal serum p-hCG is used in conjunction with a-fetoprotein (AFP) and estriol (EJ for estimating the risk of Down syndrome (DS)affected fetuses. However, low hCG levels have not been regarded as having clinical significance. We report on 2 patients with trisomy 18 fetuses in whom antenatal screening showed extremely low hCG levels (0.05 and 0.15 MOM). Low hCG levels might indicate increased risk for trisomy 18 despite low estimated risk for DS.
KEY WORDS: trisomy 18, maternal serum, low P-hCG INTRODUCTION Screening for neural tube defects (NTD) and Down syndrome (DS) by measurement of maternal serum a-fetoprotein (AFP) level is undertaken in many centers. A marked improvement in the detection rate of DS has been achieved by the measurement of 2 additional biochemical markers, human chorionic gonadotrophin (hCG) and unconjugated estriol (E3). hCG levels are raised and E, levels reduced in affected pregnancies. Occasionally when screening for DS, other chromosome aberrations, in particular trisomy 18, are detected because of a low AFP level. It is possible that the introduction of the additional markers will enable improved detection of trisomy 18, the second most common aneuploidy with a n incidence of approximately 0.3 per 1000 newborns. We report on 2 cases of trisomy 18 in which markedly reduced maternal serum hCG levels were found in conjunction with normal AFP levels. CLINICAL REPORTS Case No. 1 G.M., a 41-year-old woman, was referred for serum AFP and hCG measurement at 16 weeks of pregnancy. The patient had refused diagnostic amniocentesis. Received for publication August 13,1990; revision received January 7, 1991. Address reprint requests to Dr. G. Barkai, Deputy Director, Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel.
0 1991 Wiley-Liss, Inc.
On the basis of AFP level of 0.91 multiples of the normal median (MOM) and a n hCG level of 0.05 MOM, the risk of a DS affected fetus was regarded as low. Contact was lost until 34 weeks gestation when she was hospitalized because of polyhydramnios and premature contractions. While under investigation, including thorough ultrasonography to rule out fetal malformations, evidence of severe fetal distress was noted and a n emergency cesarean section was performed. A female infant weighing 1400 g was delivered. Apgar scores were 1and 4, at 1 and 5 min, respectively. Physical examination and radiological investigation showed typical findings of trisomy 18, including growth retardation, micrognathia, cleft palate, small oral opening, apparently low-set auricles, and overlap of fifth finger over fourth. Chromosome analysis confirmed the diagnosis of47,XX, + 18.The baby died a t age 14hr. Permission for postmortem examination was not granted.
Case No. 2 M.S., a 36-year-old healthy woman, was referred for amniocentesis a t 18 weeks of pregnancy because of age. The amniotic fluid AFP level was moderately elevated (2.68 MOM) while maternal serum AFP was 2.00 MOM (normal).The maternal serum hCG level was extremely low (0.15 MOM). Karyotype was 47,XX,+18. Unexpectedly, an open spina bifida was found which may explain the increased AFP levels in both amniotic fluid and maternal serum. DISCUSSION Maternal serum hCG level above the upper limit of normal (>2.0 MOM) is a useful marker for the prediction of DS fetuses. However, low levels of hCG have not been reported as being of clinical significance. We report on 2 patients in whom a routine screening test for the detection of DS showed extremely low levels of P-hCG (0.05 and 0.15 MOM), with a subsequent diagnosis of trisomy 18 fetuses. These results corroborate previous reports of low p-hCG levels in individual cases of trisomy 18 [Arab et al., 1988; Bogart et al., 19891. Since trisomy 18 fetuses are usually of low birth weight, it is possible that the small placental size may explain the reduced hCG levels in these patients. The optimal results in screening programs for estimating the risk of DS are based on maternal age together with serum levels of biochemical markers. Low hCG levels reduce the estimated risk of DS, but does not account for
Low p-hCG and Trisomy 18
the potential presence of other aneuploidies such as trisomy 18. we suggest that low SerumhCG levels might indicate an increased risk for trisomy 18, and amniocentesis should be considered despite a low estimated risk for DS.
REFERENCES Arab H, Siegel-Bartelt J, Wong PY, Doran T 11988):Maternal serum beta human chorionic gonadotrophin (MSHCG)combined with ma-
53
ternal serum alpha fetoprotein (MSAFP) appears superior for prenatal screening for Down syndrome (DS)than either test alone. Am J Hum Genet 43:A225. Bogart MH, Golbus MS, Sorg ND, Jones OW (1989):Human chorionic gonadotrophin levels in pregnancies with aneuploid fetuses. h e n a t Diagn 9379-384.
Human Chorionic Gonadotrophin and Trisomy 18 G. Barkai, R. Chaki, M. Sochat, and B. Goldman Institute o f Human Genetics. The Sheba Medical Center. Tel Hashomer (G.B., R.C., B.G.); Beilinson Medical Center i M . S J ,ISA Estimation of maternal serum p-hCG is used in conjunction with a-fetoprotein (AFP) and estriol (EJ for estimating the risk of Down syndrome (DS)affected fetuses. However, low hCG levels have not been regarded as having clinical significance. We report on 2 patients with trisomy 18 fetuses in whom antenatal screening showed extremely low hCG levels (0.05 and 0.15 MOM). Low hCG levels might indicate increased risk for trisomy 18 despite low estimated risk for DS.
KEY WORDS: trisomy 18, maternal serum, low P-hCG INTRODUCTION Screening for neural tube defects (NTD) and Down syndrome (DS) by measurement of maternal serum a-fetoprotein (AFP) level is undertaken in many centers. A marked improvement in the detection rate of DS has been achieved by the measurement of 2 additional biochemical markers, human chorionic gonadotrophin (hCG) and unconjugated estriol (E3). hCG levels are raised and E, levels reduced in affected pregnancies. Occasionally when screening for DS, other chromosome aberrations, in particular trisomy 18, are detected because of a low AFP level. It is possible that the introduction of the additional markers will enable improved detection of trisomy 18, the second most common aneuploidy with a n incidence of approximately 0.3 per 1000 newborns. We report on 2 cases of trisomy 18 in which markedly reduced maternal serum hCG levels were found in conjunction with normal AFP levels. CLINICAL REPORTS Case No. 1 G.M., a 41-year-old woman, was referred for serum AFP and hCG measurement at 16 weeks of pregnancy. The patient had refused diagnostic amniocentesis. Received for publication August 13,1990; revision received January 7, 1991. Address reprint requests to Dr. G. Barkai, Deputy Director, Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel.
0 1991 Wiley-Liss, Inc.
On the basis of AFP level of 0.91 multiples of the normal median (MOM) and a n hCG level of 0.05 MOM, the risk of a DS affected fetus was regarded as low. Contact was lost until 34 weeks gestation when she was hospitalized because of polyhydramnios and premature contractions. While under investigation, including thorough ultrasonography to rule out fetal malformations, evidence of severe fetal distress was noted and a n emergency cesarean section was performed. A female infant weighing 1400 g was delivered. Apgar scores were 1and 4, at 1 and 5 min, respectively. Physical examination and radiological investigation showed typical findings of trisomy 18, including growth retardation, micrognathia, cleft palate, small oral opening, apparently low-set auricles, and overlap of fifth finger over fourth. Chromosome analysis confirmed the diagnosis of47,XX, + 18.The baby died a t age 14hr. Permission for postmortem examination was not granted.
Case No. 2 M.S., a 36-year-old healthy woman, was referred for amniocentesis a t 18 weeks of pregnancy because of age. The amniotic fluid AFP level was moderately elevated (2.68 MOM) while maternal serum AFP was 2.00 MOM (normal).The maternal serum hCG level was extremely low (0.15 MOM). Karyotype was 47,XX,+18. Unexpectedly, an open spina bifida was found which may explain the increased AFP levels in both amniotic fluid and maternal serum. DISCUSSION Maternal serum hCG level above the upper limit of normal (>2.0 MOM) is a useful marker for the prediction of DS fetuses. However, low levels of hCG have not been reported as being of clinical significance. We report on 2 patients in whom a routine screening test for the detection of DS showed extremely low levels of P-hCG (0.05 and 0.15 MOM), with a subsequent diagnosis of trisomy 18 fetuses. These results corroborate previous reports of low p-hCG levels in individual cases of trisomy 18 [Arab et al., 1988; Bogart et al., 19891. Since trisomy 18 fetuses are usually of low birth weight, it is possible that the small placental size may explain the reduced hCG levels in these patients. The optimal results in screening programs for estimating the risk of DS are based on maternal age together with serum levels of biochemical markers. Low hCG levels reduce the estimated risk of DS, but does not account for
Low p-hCG and Trisomy 18
the potential presence of other aneuploidies such as trisomy 18. we suggest that low SerumhCG levels might indicate an increased risk for trisomy 18, and amniocentesis should be considered despite a low estimated risk for DS.
REFERENCES Arab H, Siegel-Bartelt J, Wong PY, Doran T 11988):Maternal serum beta human chorionic gonadotrophin (MSHCG)combined with ma-
53
ternal serum alpha fetoprotein (MSAFP) appears superior for prenatal screening for Down syndrome (DS)than either test alone. Am J Hum Genet 43:A225. Bogart MH, Golbus MS, Sorg ND, Jones OW (1989):Human chorionic gonadotrophin levels in pregnancies with aneuploid fetuses. h e n a t Diagn 9379-384.
