Taking account of vaginal bleeding in screening for Down's syndrome.

Objective: To derive a method for revising the risk of Down's syndrome in maternal serum marker screening when there is vaginal bleeding. The effect on screening performance of routinely allowing for the presence or absence of bleeding in all women is also assessed.

Design: Overview of published studies on the rate of reported vaginal bleeding in pregnancies with Down's syndrome, on the rate according to maternal age and on the association of bleeding with alpha-fetoprotein (AFP) level.

Urinary beta-core human chorionic gonadotrophin: a new approach to Down's syndrome screening.

Human chorionic gonadotrophin (hCG) is the most discriminatory maternal serum marker of Down's syndrome. We have carried out a study to establish whether urinary beta-core-hCG, a major metabolic product of hCG, might be an even better marker. Urine samples were available from seven singleton pregnancies with Down's syndrome, and one each of Edwards' syndrome, triploidy, and twins discordant for Down's syndrome.

Maternal age-specific risks for trisomies at 9-14 weeks' gestation.

This study provides data on the incidence of fetal trisomies 21, 18, and 13 at 9-14 weeks' gestation in women aged 35-45 years and estimates of maternal age-specific risks in women aged 20-45 years. Our data from 5814 singleton pregnancies undergoing first-trimester karyotyping for the sole indication of maternal age > or = 35 years were combined with those from two previous reports and the incidence of the trisomies was calculated from a total of 15,793 pregnancies. Comparison of incidences at 9-14 weeks' gestation with published data at 15-20 weeks' gestation and in livebirths demonstrated that at birth the maternal age-specific incidence of trisomy 21 is 33 per cent lower than at 15-20 weeks' gestation and 54 per cent lower than at 9-14 weeks' gestation.

Repeat maternal serum testing in multiple marker Down's syndrome screening programmes.

The effect of repeat testing in maternal serum multiple marker screening for Down's syndrome was estimated using samples stored in an antenatal serum bank. Human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) levels were determined in 142 pairs of routinely collected samples which had already been tested for alpha-fetoprotein (AFP). For each marker, about two-thirds of the pairs of values were within 20 per cent of each other and most were within 40 per cent.

Maternal serum inhibin levels in second-trimester Down's syndrome pregnancies.

Maternal serum inhibin levels were measured in 19 second-trimester pregnancies affected by fetal Down's syndrome and 95 unaffected control pregnancies matched for gestational age. A statistically significant elevation was found in the affected pregnancies compared with the controls (Wilcoxon rank sum test: one-tail P = 0.02).

Screening for neural tube defects.

The birth prevalence of neural tube defects fell by 95% in England and Wales between 1970 and 1990 largely as a result of antenatal screening, subsequent diagnosis and selective abortion of affected pregnancies. Anencephaly can be diagnosed using ultrasound, whereas both amniotic fluid biochemistry and ultrasound are required for the diagnosis of spina bifida. Both methods have a false-positive rate of about two per 1000 when carried out in high-risk pregnancies.

Cystic fibrosis screening strategies.

Cystic fibrosis is the most common single gene disorder in Western populations. With the discovery of the principal genetic mutations responsible for the disease, screening has become feasible. The challenge is now to devise an effective screening strategy.

Expanding multiple marker screening for Down's syndrome to include Edward's syndrome.

Information on maternal age and maternal serum alpha-fetoprotein, unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi-marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10-12 (67-80 per cent) cases with a false-positive rate of 0.

Serum PAPP-A levels are depressed in women with fetal Down syndrome in early pregnancy.

The value of maternal serum pregnancy-associated plasma protein (PAPP)-A in screening for Down syndrome in early pregnancy was assessed using stored samples. Seventeen cases of Down syndrome and 66 unaffected control pregnancies were studied. The median PAPP-A level in the cases was 0.

Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

Objectives: To assess the implementation of antenatal screening for Down's syndrome in practice, using individual risk estimates based on maternal age and the three serum markers: alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin.

Design: Demonstration project of Down's syndrome screening; women with a risk estimate at term of 1 in 250 or greater were classified as "screen positive" and offered diagnostic amniocentesis.

Setting: Hospital and community antenatal clinics in four health districts in London.