J. W. Densem

Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Downs syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Downs syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Downs syndrome in the United Kingdom from about 900 a year to about 350 a year.

PRENATAL SCREENING FOR DOWN'S SYNDROME USING INHIBIN-A AS A SERUM MARKER

The value of measuring inhibin‐A (αβA dimer) with human chorionic gonadotrophin (total or the sub‐units free α‐hCG and free β‐hCG separately), alpha‐fetoprotein (AFP), and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Downs syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples from 77 Downs syndrome singleton pregnancies and 385 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the sample, supplemented by data from 970 white women with unaffected pregnancies. Inhibin‐A was elevated in the serum of women with Downs syndrome pregnancies with a median of 1·79 multiples of the median (MOM). Using the four serum markers AFP, uE3, total hCG, and inhibin‐A, in addition to maternal age, 70 per cent of Downs syndrome pregnancies were detected for a 5 per cent false‐positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, and total hCG with maternal age). If the estimate of gestational age were based on an ultrasound scan examination, the detection rate would be 77 per cent [95 per cent confidence interval (CI) 69–85 per cent] using the four serum markers including inhibin‐A, compared with 67 per cent with the triple test or 79 per cent (95 per cent CI 71–87 per cent) if marker values were adjusted for maternal weight. If the detection rate were kept at 70 per cent and the gestational age were estimated by an ultrasound scan examination, the four‐marker test would reduce the false‐positive rate from 6·1 per cent using the triple test to 2·9 per cent. The results were virtually the same if free β‐hCG was used instead of total hCG. The inhibin‐A‐based four‐marker test is the most effective method of prenatal screening for Downs syndrome suitable for routine use. If the extra cost required to carry out the inhibin‐A test were less than about £3 per woman screened, the four‐marker test including inhibin‐A would be financially cost‐effective.

Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy

Objective To determine the value of serum screening for Downs syndrome at 8–14 weeks of pregnancy using seven potential serum markers (alpha‐fetoprotein, unconjugated oestriol, total human chorionic gonadotrophin (hCG), free α‐hCG, free P‐hCG, pregnancy associated plasma protein A (PAPP‐A), and dimeric inhibin A).

Maternal serum screening for Down's syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight.

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 (uE3) and human chorionic gonadotrophin (hCG) levels in antenatal screening for Downs syndrome.

Maternal serum unconjugated oestriol as an antenatal screening test for Down's syndrome

Summary. The median maternal serum unconjugated oestriol level between 13 and 27 weeks gestation in 77 pregnancies associated with Downs syndrome was lower than the median level in 385 unaffected control pregnancies matched for maternal age, gestational age, and duration of serum sample storage (P<0·001). The median level for the affected pregnancies was 73% of that in the controls. Low unconjugated oestriol levels can be used to detect fetal Downs syndrome; at cut‐off levels selected to detect at least 35% of affected pregnancies, unconjugated serum oestriol was a better screening test than either maternal age or serum alpha‐fetoprotein (AFP). The use of all three variables in combination to select women with a 1:250 or greater risk of a Downs syndrome term pregnancy would yield a 45% detection rate with a falsepositive rate of 5.2%. The same detection rate using maternal age alone or using age and serum AFP in combination would yield higher falsepositive rates, 15% and 9.8% respectively. The addition of unconjugated oestriol to a Downs syndrome screening programme would therefore be more efficient than the use of age and AFP alone; for a given detection rate fewer women would need an amniocentesis or, for a given percentage of women having an amniocentesis, more pregnancies with Downs syndrome would be detected.

Maternal Serum Screening for Down Syndrome in Early Pregnancy

The possibility of improving the effectiveness of antenatal screening for Downs syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Downs syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Downs syndrome in the United Kingdom from about 900 a year to about 350 a year.

The use of free β‐hCG in antenatal screening for Down's syndrome

Objective To investigate the value of the measurement of free β human chorionic gonadotrophin (hCG) as a serum marker of Downs syndrome in the second trimester of pregnancy.

The effect of smoking in pregnancy on maternal serum alpha-fetoprotein, unconjugated oestriol, human chorionic gonadotrophin, progesterone and dehydroepiandrosterone sulphate levels

H. S. Cuckle, N. J. Wald, J. W. Densem, P. Royston Department of Environmentaland Preventive Medicine, St Bartholomew’s Hospital Medical College, Charterhouse Square, London EClM6BQ. G. J. Knight, J. E. Haddow, G. E. Palomaki Foundation fo r Blood Research, P O Box 190, Scarborough, Maine 04074, USA & J. A. Canick. Department of Pathology and Laboratory Medicine, Brown University, Women and Infants’ Hospital, 120 Dudley Street, Providence, RI 0290-5-2401, USA

Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in pregnancies with insulin-dependent diabetes: implications for screening for Down's syndrome.

Objective To investigate maternal serum unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in pregnant women with insulin‐dependent diabetes mellitus and to consider the implications of the results for antenatal screening for Downs syndrome.

Detection of hydatidiform mole in maternal serum screening programmes for Down's syndrome

Objective To determine how frequently hydatidiform mole will be detected in a maternal serum Downs syndrome screening programme.