Anne Kennard

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.

Empirical validation of risk screening for Down's syndrome.

Objective— To validate individual risk estimates in antenatal serum screening for Downs syndrome. Methods— Women screened for Downs syndrome using maternal serum a fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophs (hCG) with maternal age (the triple test) or AFP, uE3, free β subunit and free a subunit of hCG with maternal age (the quadruple test) were grouped according to their predicted risk of having an affected pregnancy. The mean predicted risk in each category was then compared with the observed prevalence based on the number of affected and unaffected pregnancies in each category. Subjects— About 100 000 pregnant women screened for Downs syndrome from 1989 to 1995. Results— There was close agreement between the predicted term risk and the prevalence at birth for both the triple test and the quadruple test. For example, with the quadruple test the predicted risk in the highest risk group was 1 in 3.3 and the prevalence was 1 in 2.6; in the lowest risk group these were 1 in 3000 and 1 in 2300 respectively. Conclusion— Risk estimates based on multiple marker screening for Downs syndrome are accurate. The technique used to demonstrate this is simple and offers a useful empirical check on screening performance.

Prenatal biochemical screening for Down??s syndrome and neural tube defects

Antenatal serum screening for Downs syndrome is now becoming established in many centers throughout the world. The screening method is based on the measurement of α-fetoprotein, unconjugated estriol, and human chorionic gonadotropin between 15 and 22 weeks of pregnancy. These measurements, used in conjunction with a womans age, provide risk estimates of having a pregnancy with Downs syndrome for every woman screened. By identifying the 5% of women with highest risk and offering them an amniocentesis, about 60% of Downs syndrome pregnancies can be identified. If an ultrasound scan examination is used routinely to estimate gestational age, the detection rate can be increased by 5% to 10%. Recent information on the distribution of the three serum markers in twin pregnancies and pregnancies with insulin-dependent diabetes mellitus now means that screening can be carried out in such pregnancies. Various other serum markers of Downs syndrome have been reported, but at present they do not have a place in routine antenatal screening for Downs syndrome. The role of amniotic fluid acetylcholinesterase measurement, alone and in combination with amniotic fluid α-fetoprotein measurement, in the antenatal diagnosis of open neural tube defects has recently been clarified. The best policy is to perform an amniotic fluid α-fetoprotein measurement as the primary test and an acetylcholinesterase determination for those women who have an amniotic fluid α-fetoprotein measurement of two times the normal median or greater. The acetylcholinesterase can be measured either by the standard method (gel electrophoresis) or by a new quantitative monoclonal antibody method.

FIRST TRIMESTER BIOCHEMICAL SCREENING FOR DOWN'S SYNDROME

A number of biochemical markers in maternal serum have been proposed for first trimester screening for Downs syndrome. The most promising four are pregnancy associated plasma protein A (PAPP-A), the free beta sub-unit of human chorionic gonadotrophin (hCG) (free beta glycoprotein sub-unit), unconjugated oestriol (uE3) and alpha-fetoprotein (AFP). An analysis of the published literature suggests that 70% of affected pregnancies could be detected for a 5% false-positive rate if the four markers are used in combination with maternal age and assumed to be independent measures of risk. This is a level of performance that is similar to second trimester screening. It is, however, a tentative estimate because of the assumption of independence and the possibility that the effect may be exaggerated by publication bias. Further research is needed before such screening is introduced. Other first trimester markers which have been studied include total hCG, free alpha-hCG, CA125, PLAP and SP1 but they either look unpromising or there are too few data available to determine their value. The timing of antenatal diagnosis by means of chorion villus sampling should be delayed until after 10 weeks of pregnancy because of the risk of causing limb defects. Screening need not, therefore, be performed before about 9 or 10 weeks of pregnancy.

Biparietal diameter and crown‐rump length in fetuses with Down's syndrome: implications for antenatal serum screening for Down's syndrome

Objectives 1. To compare the ultrasound biparietal diameter and crown‐rump length of fetuses with and without Downs syndrome in the first half of pregnancy; 2. To investigate the effect of estimation of gestational age using either measure on the detection rate of serum screening for Downs syndrome.

Recent advances in obstetrics. Figures on screening for Down's syndrome are inaccurate.

EDITOR,—Philip Steers comments about serum screening for Downs syndrome1 should not go unchallenged. Firstly, it is inappropriate to cite a 48% detection rate. For a 5% false positive rate the estimated detection rate is 59% when dates are used to estimate gestational age and 65% if an estimate based on an ultrasound scan is used.2 …

Decision analysis and screening for Down's syndrome. Testing should be in all women.

EDITOR,--The paper by J Fletcher and colleagues1 was incorrect to conclude that restricting serum screening for Downs syndrome to women aged 30 or over is preferable to screening all women. Firstly, using a 58% detection rate and a 5% false positive rate for all pregnant women instead of estimates applicable to women aged 30 or over (72% and 12%2 3), and, secondly, not comparing screening policies appropriately introduces important errors. Screening tests involve a trade off between detection rate and false positive rate. To compare screening policies, cut off levels must be set such that among all pregnancies in …