British Journal of Obstetrics and Gynaecology February 1992,Vol. 99,pp. 144-149
FETAL AND NEONATAL MEDICINE
Maternal serum screening for Down’s syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight N. J. WALD H. S . C U C K L E ” J . W. D E N S E M A. KENNARD D. S M I T H Department of Environmental and Preventive Medicine Wolfson Institute of Preventive Medicine St. Bartholomew’s Hospital Medical College Charterhouse Square London EC IM 6BQ
ABSTRACT Objective To investigate the effect of using a routine ultrasound estimate of gestational age and maternal weight adjustment on maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE,) and human chorionic gonadotrophin (hCG) levels in antenatal screening for Down’s syndrome. Design Women with a singleton pregnancy without Down’s syndrome were screened using the three serum markers and an estimate of gestational age based on ‘dates’ (time since first day of the last menstrual period) and one based on an ultrasound scan examination was recorded together with maternal weight. Setting Women attending the Homerton Hospital, Hackney, for their antenatal care between February 1989 and January 1990. Subjects 21 13 women with a singleton pregnancy without Down’s syndrome. Results The use of ultrasound to estimate gestational age (usually based on the biparietal diameter of the fetal skull) led to a significant reduction in the variance of each marker at a given week of pregnancy. The level of each marker was negatively associated with maternal weight, so that adjustment for weight also led to a reduction in variance. These data on gestational age and maternal weight, taken together with published data on pregnancies associated with Down’s syndrome, indicate that the routine use of ultrasound to estimate gestational age will increase the detection rate from 58% to 67% while maintaining the false-positive rate at 5%, or reduce the falsepositive rate from 5.7% to 3.1% while maintaining the detection rate at 60%. Routine maternal weight adjustment for the serum marker levels was much less useful, increasing the detection rate by about 0.5% for a given false-positive rate, or reducing the false-positive rate about 0.1% for a given detection rate. Conclusion An ultrasound gestational age estimate available at the time of Down’s syndrome screening confers a substantial advantage to screening performance with a further small benefit resulting from maternal weight adjustment, which is worth adopting if it can be done without difficulty or extra cost.
Antenatal screening for Down’s syndrome using maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (LIE?), and human chorionic gonadotrophin (hCG) can detect about 60% of affected pregnancies with a false-positive rate of 5% (Wald etal. 1988a). This performance can be achieved without using an ultrasound examination to estimate gestational age and without adjusting the values of the three serum markers for maternal weight. These refinements improve the performance of screening using maternal serum AFP alone (Cuckle et a/. 1987) and they are likely to confer a similar benefit on screening using the three serum markers together. We performed a study to investigate this and to estimate the size of any benefit that may arise. Correspondence: Professor N. J. Wald. *Present Address Academic Unit of Obstetrics and Gynaecology, Institute of Epidemiology and Health Services Research, St. James’s University Hospital, Leeds LS9 7TE
144
Subjects and methods Among women who attended the Homerton Hospital, Hackney, for their antenatal care between February 1989 and January 1990, 2113 had a singleton pregnancy without Down’s syndrome or a neural tube defect. All had been screened for Down’s syndrome using the three serum markers, AFP, uE, and hCG. Of these, 2028 women (96%) had an estimate of gestational age based on ‘dates’ (time since the first day of the last menstrual period) and an estimate based on an ultrasound scan examination. In this paper, when a biparietal diameter was available (1865) this was used; otherwise a crown-rump length (61) or an abdominal circumference (102) was used. In each pregnancy gestational age was estimated from a log-linear regression of gestational age based on dates against the ultrasound measure. The log-linear fit was at least as satisfactory a fit to the data as other simple models. A maternal weight measurement was available for 2050 women (97%).
M A T E R N A L S E R U M S C R E E N I N G FOR D O W N ’ S S Y N D R O M E
145
Table 1. Median maternal serum AFP, uE,, and hCG levels according to maternal weight Median (MOM)
Maternal weight (kg)
Group
Median
No. of women
FETAL AND NEONATAL MEDICINE
Maternal serum screening for Down’s syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight N. J. WALD H. S . C U C K L E ” J . W. D E N S E M A. KENNARD D. S M I T H Department of Environmental and Preventive Medicine Wolfson Institute of Preventive Medicine St. Bartholomew’s Hospital Medical College Charterhouse Square London EC IM 6BQ
ABSTRACT Objective To investigate the effect of using a routine ultrasound estimate of gestational age and maternal weight adjustment on maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE,) and human chorionic gonadotrophin (hCG) levels in antenatal screening for Down’s syndrome. Design Women with a singleton pregnancy without Down’s syndrome were screened using the three serum markers and an estimate of gestational age based on ‘dates’ (time since first day of the last menstrual period) and one based on an ultrasound scan examination was recorded together with maternal weight. Setting Women attending the Homerton Hospital, Hackney, for their antenatal care between February 1989 and January 1990. Subjects 21 13 women with a singleton pregnancy without Down’s syndrome. Results The use of ultrasound to estimate gestational age (usually based on the biparietal diameter of the fetal skull) led to a significant reduction in the variance of each marker at a given week of pregnancy. The level of each marker was negatively associated with maternal weight, so that adjustment for weight also led to a reduction in variance. These data on gestational age and maternal weight, taken together with published data on pregnancies associated with Down’s syndrome, indicate that the routine use of ultrasound to estimate gestational age will increase the detection rate from 58% to 67% while maintaining the false-positive rate at 5%, or reduce the falsepositive rate from 5.7% to 3.1% while maintaining the detection rate at 60%. Routine maternal weight adjustment for the serum marker levels was much less useful, increasing the detection rate by about 0.5% for a given false-positive rate, or reducing the false-positive rate about 0.1% for a given detection rate. Conclusion An ultrasound gestational age estimate available at the time of Down’s syndrome screening confers a substantial advantage to screening performance with a further small benefit resulting from maternal weight adjustment, which is worth adopting if it can be done without difficulty or extra cost.
Antenatal screening for Down’s syndrome using maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (LIE?), and human chorionic gonadotrophin (hCG) can detect about 60% of affected pregnancies with a false-positive rate of 5% (Wald etal. 1988a). This performance can be achieved without using an ultrasound examination to estimate gestational age and without adjusting the values of the three serum markers for maternal weight. These refinements improve the performance of screening using maternal serum AFP alone (Cuckle et a/. 1987) and they are likely to confer a similar benefit on screening using the three serum markers together. We performed a study to investigate this and to estimate the size of any benefit that may arise. Correspondence: Professor N. J. Wald. *Present Address Academic Unit of Obstetrics and Gynaecology, Institute of Epidemiology and Health Services Research, St. James’s University Hospital, Leeds LS9 7TE
144
Subjects and methods Among women who attended the Homerton Hospital, Hackney, for their antenatal care between February 1989 and January 1990, 2113 had a singleton pregnancy without Down’s syndrome or a neural tube defect. All had been screened for Down’s syndrome using the three serum markers, AFP, uE, and hCG. Of these, 2028 women (96%) had an estimate of gestational age based on ‘dates’ (time since the first day of the last menstrual period) and an estimate based on an ultrasound scan examination. In this paper, when a biparietal diameter was available (1865) this was used; otherwise a crown-rump length (61) or an abdominal circumference (102) was used. In each pregnancy gestational age was estimated from a log-linear regression of gestational age based on dates against the ultrasound measure. The log-linear fit was at least as satisfactory a fit to the data as other simple models. A maternal weight measurement was available for 2050 women (97%).
M A T E R N A L S E R U M S C R E E N I N G FOR D O W N ’ S S Y N D R O M E
145
Table 1. Median maternal serum AFP, uE,, and hCG levels according to maternal weight Median (MOM)
Maternal weight (kg)
Group
Median
No. of women
