CLINICAL REVIEW

Testing for fetal abnormality in routine antenatal care

Josephine Green and Helen Statham

The detection of fetal abnormality is a major component of routine antenatal care. A variety of techniques are now in use, although these are constantly being modified in the pursuit of more accurate and earlier detection. In this paper we draw attention to the distinction between screening and diagnostic tests, and describe the techniques which have been most commonly used in the UK: serum- screening for neural tube defects; screening for Down’s syndrome; ultrasound scanning; amniocentesis and chorionic villus sampling.

INTRODUCTION Diagnosis vs screening -. . . . .

The detection of fetal abnormality has become a major part of antenatal care. A variety of tech- niques are now in use, although these are con- stantly being modified in the pursuit of more accurate and earlier detection. In this paper we describe the techniques which have been most commonly used in the UK, and present informa- tion on what is currently known of their benefits and hazards. Further information about women’s experiences of these techniques can be found in Green (1990), Statham (1992), Green et al (1992) and Green (1993).

Josephine Green PhD, Senior Research Associate, Helen Statham WC, Research Associate, Centre for Family Research, University of Cambridge, Free School Lane, Cambridge CB2 3RF.

Requests for offprints to JG

Diagnostrc tests are those that can tell us, with

reasonable certainty, whether or not the person being tested is affected by a particular disorder. If we had cheap, accurate, risk-free diagnostic tests, we could apply them to everybody. Because we do not, we need to find a basis for selecting a subgroup of people for whom the risks and costs are felt to be justified. This is why we have screening. Thus, pregnant women are screened in various ways to identify a sub-group who are more likely to be carrying an abnormal fetus than the rest of the pregnant population. These women, once defined as ‘at-risk’, can be offered diagnostic tests. A ‘risk factor’ can be anything that has been observed to have a higher than average association with fetal abnormality. Those that are identifiable at the ‘booking’ interview include maternal age, race and family history. However, as the Royal College of Physi- cians (1989) Report on Prenatal Diagnosis and

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MII)WIFEKY 125

Genetic Screening observed: ‘Most infants with

congenital malformations and chromosomal dis- orders are born to healthy young women with no identifiable risk factor’. Conversely, the majority of women who are identified as being ‘at risk’, for example on account of their age, give birth to healthy babies. Indeed, we should remember that we are talking about just 2% of full-term births that have some form of congenital abnor- mality. The vast majority of women who reach the beginning of the second trimester do go on to have healthy babies.

Containers and contents

The routine tests and examinations that preg- nant women experience may be thought of as falling into two categories. The first category monitors maternal variables, e.g. weight, haemo- globin, blood pressure. These tests are to see whether the mother is a healthy container for her unborn child. If test results indicate deviance from what is considered to be the ideal then action can be taken, for example iron tablets or advice about rest and diet can be given. The second category of tests focuses on the contents rather than the container i.e. they are tests of fetal well-being. This paper is concerned with this second category. For both categories of test the aim is stated to be the delivery of a healthy baby, but the big difference is that the first category of test is intended to maintain a benign environment for a fetus that is (assumed to be) healthy, the second is intended to detect fetuses that are non healthy. These tests can only detect

fetal anomalies, they cannot correct them. Unlike the first category of tests, there is rarely any action that can be taken on the basis of the test results which will increase the chances that the baby will be born healthy.

Sometimes a single investigative procedure can be a source of information about both container and contents. Ultrasound scanning is the most obvious example of this. However the point still holds: action can often be taken to correct an imperfect container, but only rarely can anything be done to change anomalies in the contents. The only ‘positive’ action that can be

taken in most cases is termination of the pregnancy.

ALPHA FETO-PROTEIN SCREENING FOR NEURAL TUBE DEFECTS

Alpha feto-protein (AFP) is a substance pro- duced by all human fetuses. Where there is an open neural tube defect the AFP leaks and higher levels are therefore found in both amnio- tic fluid and maternal blood in such pregnancies. The extent of this is sufficient to identify all cases of anencephaly and approximately 85% of cases of spina bifida. AFP is not, however, useful for screening for closed lesions. AFP may be measured in maternal blood (known as maternal serum AFP or MSAFP), or in amniotic fluid. Maternal blood is clearly the more accessible.

The optimum timing for the blood test is 1618 weeks; sensitivity is lower at other stages of pregnancy. It is important that the correct gestation is known because the level of AFP in maternal blood rises during the course of preg- nancy. In the second trimester it increases by about 19% per week, approximately doubling every 4 weeks (Wald & Cuckle, 1984). If ges- tation is not accurately known then MSAFP cannot be properly interpreted because the judgement that it is ‘elevated’ is made in terms of multiples of the median (MOM’S) for that ges- tation. The other common benign explanation for elevated MSAFP is multiple pregnancy. Inaccurate dating and multiple pregnancy between them explain about one quarter of raised MSAFP results (Robinson et al, 1989).

There are two major problems associated with MSAFP testing. One is that it does not detect all neural tube defects, especially ‘closed’ ones, and these are also the ones least likely to be spotted by ultrasound scanning. The other is that there is a high rate of false positives, i.e. pregnancies

where MSAFP is elevated but where there is no neural tube defect. Some of the explanation for this, as we have seen, lies with inaccurate dating and multiple pregnancy, but there is also the problem that there is a wide range of ‘normal’ levels. The choice of cut off beyond which a level

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is judged to be abnormal is a pragmatic one, but what is abnormal for one group of women might not be for others. Thus, MSAFP has been found to vary with race (Cuckle et al, 1987; Macri et al, 1987; Johnson et al, 1990a), maternal age, maternal weight (Johnson et al, 1990b) and diabetic status, which are often not taken into consideration. It is also related to fetal sex, with boys having higher levels, although the differ- ences are not large enough to be used as an explanation in cases of raised MSAFP (Calvas et al, 1990). Yet a further element of uncertainty lies in the fact that MSAFP levels may vary from day to day and a single sample is likely only to fall within 30% of the true mean (Carter et al, 1988).

Thus only a minority of women found to have raised MSAFP will actually have a fetus with a neural tube defect. The proportions reported are very variable, for example: 1 in 15 (Wald et al, 1979), 1 in 30 (Lilford & Chard, 1985), 1 in 67 (Campbell, 1987), 1 in 18 (Robinson et al, 1989). In practice, false positive rates will depend on the cut off level used to assess MSAFP and the incidence of neural tube defects in the popula- tion being screened. The predictive power of a screening test (i.e. how likely it is that someone with a positive screening result actually has the condition being sought) is strongly related to the prevalence of the disorder being screened for. The incidence of neural tube defects in the UK has, in fact, been falling, even in places where there has been no screening and selective abor- tion (Office of Population Censuses & Surveys, 1983; Stone et al, 1988). For this reason, and because ultrasound was becoming a more powerful tool, a number of UK hospitals were starting to abandon mass MSAFP screening during the late 1980s especially in places with a low incidence of neural tube defects. There have, however, been two developments which have changed attitudes recently. One is the publication of data suggesting that raised AFP levels indicate a raised risk for a wide range of other fetal problems including fetal/neonatal death (Burton, 1988; Milunsky et al, 1989; Robinson et al, 1989). It appears that approxi- mately one third of pregnancies with raised levels of MSAFP will have a problem of some

be made of this forewarning, but the discovery that high AFP may be linked to chromosomal abnormalities is leading to a trend towards amniocentesis following raised MSAFP, regardless of other indications (Cowan et al, 1989; Warner et al, 1990). The other develop- ment, which has more obvious implications for action, is the finding that LOW levels of MSAFP are associated with Down’s syndrome (Cuckle et al 1984; Merkatz et al, 1984), which will be discussed below.

SCREENING FOR DOWN’S SYNDROME

Down’s syndrome is the most common chromo- somal abnormality, accounting for approxi- mately 50% of those that can be detected. There is an exceedingly wide range of other chromoso- ma1 defects that make up the other 50%, most of them very rare. Many are incompatible with life; for others, particularly sex chromosome anoma- lies, the consequences are uncertain. This is a little mentioned hazard of screening for chromosomal disorders: anomalies may be found whose prognosis is not known. Parents are rarely told in advance about this possibility. The probability of having a child with a chromosomal disorder rises with maternal age. As shown in Table 1, this relationship is stronger for Down’s syndrome than for other chromosomal abnor- malities.

Until recently, maternal age was the sole screening test for Down’s syndrome and other chromosomal abnormalities. In the UK the pre- cise age at which a diagnostic test would be offered varies between different Health Service

Table 1 Estimated incidence of chromosomal abnormalities

Liveborn babies Maternal age Down’s syndrome All chromosomal

21 l/l 500 l/500 27 1/1000 II450 35 l/400 II200 37 11220 l/l25 40 l/l00 l/60 45 l/30 l/20

From: Berini R Y & Kahn E (1987) p 59. Reprinted by kind. Unfortunately it is not clear what use can permission of Blackwell Scientific Publications, Inc.

MIDWIFERY 127

Kegions. It is usually between 35 and 38 years. It is around this age that the probability of having an affected pregnancy is greater than that of

spontaneous abortion as a result of the pro- cedure (this is of course, a curious piece of algebra assuming as it does that having a child

with Down’s syndrome and experiencing a mis- carriage are equivalent events).

A number of Health Districts are now using

various biochemical markers in maternal blood as an additional screening method. These tests are focused on Down’s syndrome, rather than chromosome abnormalities in general. Origin- ally low levels of AFP were measured in the same samples that were used to test for neural tube defects, and this is still the case in some areas.

Subsequently unconjugated oestriol and human chorionic gonadotrophin (hCG) have also been shown to be linked to Down’s syndrome (Wald et al, 1988). It is the use of these three together, plus age, that is known as the ‘Bart’s test’, or ‘triple test’. There continues to be considerable

debate about the relative usefulness of these different parameters (e.g. Macri et al, 1990a; 1990b; Suchy & Yeager, 1990; Dawson & Keynolds, 1992; Spencer, 1992) and it seems that the search for additional maternal serum mark- ers to increase the screen’s sensitivity and speci- ficity will continue. In Britain the use of serum

screening in conjunction with maternal age is increasing rapidly, although in a very piecemeal way (Wald et al, 1992a). Wald et al (1992a) estimated that by the end of 1992,69% of Health

Districts would be providing some form of serum screening to pregnant women of all ages.

The princ$rle of serum screening is the same as using maternal age: every woman is assigned a risk figure which says how likely it is that she is carrying a baby with Down’s syndrome. Where age is the screening method, this risk figure is

based on the observed frequency with which women of a given age have Down’s syndrome babies. Thus the risk assigned to a particular

likely to be different from other women’s.

However, in the same way as with age, a cut off is still chosen and risks higher than this are called

‘high’ or ‘screen positive’ and those below ‘low’or ‘screen negative’. The usual cut-off in the UK is 1 in 250, but it varies. The higher the cut-off the

fewer women will go on to have amniocentesis, but the more likely it is that babies with Down’s syndrome will be missed. This is an inherent dilemma for any screening programme: max-

imising the number of affected pregnancies detected while minimising the number of false positives.

The chances of a woman having a screen positive result, and the probability that a true positive will actually be detected, both increase with maternal age, as shown in Table 2. The

positive predictive value of the test also increases with age, i.e. the probability that a woman with a screen positive result is, in fact, carrying a

Down’s syndrome child (Reynolds et al, 1993). Thus, a 16-year-old who screens positive on the triple test has only a l/l 11 chance of having a Down’s baby, while for a 44-year-old the prob- ability is l/26. Knowledge of the relationship

between serum screening results and age should be of benefit to midwives counselling pregnant women.

The aim of serum screening is to provide a better screening test than age alone. Age as a screening method has not had a substantial impact on the number of Down’s babies born, and there was, in fact, a slight increase in the

birth incidence of Down’s syndrome from 1988

Table 2 Probability of a screen positive result and proportion of Down’s pregnancies detected for women of different ages using a 1 in 250 cut-off

Maternal age Probability of group (years) screen positive

Proportion of DS detected

under 25 25-29 3Q-34

I/45 35% l/32 40% If15 54%

35-year old woman will be the same as that rziven 35-39 l/5 76%

to any other 35-year old woman. With &urn 40-44 l/2 93%

screening, age is still taken into account, but in 45 and over > l/2 > 99%

addition there is information about this particu- All l/20 58%

lar pregnancy. This means that everyone will be Table courtesy of Wald 81 Kennard, personal

assigned their own particular risk figure which is communication (derived from parameters in Wald et al (1992c).

128 MIDWIFERY

to 1989 (Robinson, 1991), perhaps because women are having children later. In 1989,30% of Down’s babies were detected antenatally and this rose to 38% in 1991 (Mutton et al, 1993). This represented 59% of those carried by women aged 35 and over in 1989 and 62% in 1991. In the under 35-year age group the proportions detected were 8% and 17%. The proportion of diagnoses that followed a positive serum screen rose from 5% to 21% in that period.

It was estimated that using the triple test it should be possible to detect 60% of Down’s pregnancies while needing to subject only 5% of women to amniocentesis. Screening based on age alone detects, at best, 35% of cases and involves 7-S% of the population (i.e. all women aged 35 years or over) having amniocentesis (or CVS). Most of what has been published about detection rates has been based on retrospective analyses. However reports of the use of serum screening in practice are now beginning to appear (Dawson 8c Reynolds, 1992; Herrou et al, 1992; Phillips et al, 1992; Wald et al, 1992c). While these indicate that the test is not perform- ing quite as well in practice as in theory, but is detecting about 50% of fetuses with Down’s syndrome with a false positive rate of approxim- tely 5%, a more recent publication has shown a 9 1% detection rate for a 4.1% amniocentesis rate (Cheng et al, 1993).

Serum screening for Down’s syndrome should mean fewer women subjected to the stress of diagnostic testing and more affected fetuses detected. However, it is evident that, at least in its early days, serum screening is causing consider- able anxiety to some women (Marteau et al, 1988; Abuelo et al, 1991; Keenan et al, 1991; Green, 1993; Statham & Green, 1993). It is also apparent that a higher proportion of screen

positive women elect to have amniocentesis than women offered it on grounds of age. This means that in some places the number of amniocenteses being carried out has increased, even though the number of women identified as eligible has decreased. As Donnai and Andrews (1988) pre- dicted, the idea that being over 35 years puts a woman at risk for Down’s syndrome is now so well established that these older women are

unwilling to lose their ‘right’ to diagnostic testing. Roelofsen et al (1993) found that 55% of 155 older women in the Netherlands would want serum screening for Down’s syndrome in a subsequent pregnancy, but 76% of them would still want amniocentesis, even if they were found to be ‘low risk’.

ULTRASOUND SCANNING

Ultrasound scanning is the most widely used method for testing for fetal abnormality, with virtually every pregnant woman in the UK having at least one scan. Ultrasound is a source of information about both the mother and the fetus; different sorts of information can be obtained from scans performed at different gestations. This paper is primarily concerned with tests for fetal abnormality; it is not possible, however, to consider ultrasound scanning in this context alone. Any scan will involve counting, measuring and dating the baby(ies) and localis- ing the placenta, even if the main function of the scan is looking for abnormalities. We will there- fore consider three questions: how useful is ultrasound apart from detecting fetal abnormali- ties; how useful is it for detecting fetal abnorma- lities; and what are the long term risks?

The data concerning uses of routine ultra- sound on low risk populations for investigations other than the detection of fetal abnormalities (assessment of gestational age, identification of multiple pregnancies, detection of intrauterine growth retardation (IUGR) and placenta prae- via) provide little evidence of improved perinatal outcomes. From an initial sample of 2 17 1 preg- nant women Ewigman et al (1990) randomised 915 women who were less than 18 weeks preg- nant into groups receiving ‘routine ultrasound’ or ‘usual prenatal care’; 24% of those in the usual-care group received an ultrasound scan. No differences were found between the groups in induction of labour or adverse perinatal outcomes. One of seven sets of twins in the usual-care group was not diagnosed until delivery at 36 weeks, but this did not affect the outcome. Similar findings were reported from a much larger trial in Finland (Saari-Kemppainen et al, 1990). Although perinatal mortality was

MIDWIFERY 129

lower in screened women, this was because they

were more likely to have terminated a pregnancy following detection of a fetal abnormality. A number of other studies which have considered the reliability of ultrasound in assessing ges- tat&al age and IUGK have recently been reviewed by Kinga et al (1989) and by Breart and Ringa (1990). These authors concluded that as a routine examination for the general population

any benefits were marginal, although the value for women for whom it was clinically indicated

was clear. Ultrasound is of use as an aid to dating the

pregnancy and for detecting multiple pregnan- cies, both of which are necessary for the accurate interpretation of maternal serum test results. In some hospitals the two forms of screening are deliberately co-ordinated with a dating scan preceding the blood test and an anomaly scan performed after the results are known. Wald et al (1992b) have calculated that the routine use of a dating scan before serum screening will increase the detection rate from 58-67% while maintaining the same false positive rate, or could be used to reduce the false positive rate while

maintaining the same detection rate. The use of dating scans only after a positive screening test is

not recommended, especially since there is evi- dence of growth retardation in some Down’s

syndrome fetuses (Nyberg et al, 1990). Ultra- sound scanning is also used as an adjunct to

amniocentesis and CVS; localisation of the fetus and placenta minimise the risks of these pro- cedures.

The effectiveness of routine ultrasound in the detection of fetal abnormality has been the subject of a number of recent reports, three from the UK. Rosendahl 8c Kivinen (1989) have reported data on nine thousand pregnancies routinely scanned in Finland between 1980 and

1988. Ninety-three babies (1.03%) showed major abnormalities and 54 of these (58%) were detected antenatally. In 85 of the 93 cases there was no indicative family history, and in only 26% of the cases was there any suspicion of fetal abnormality prior to the scan although in a study by Sollie et al (1988) selective scanning of a sample of their population defined as high risk (because of IUGR, polyhydramnios, family his-

tory) resulted in the identification of 60% of the

malformations present. Chitty et al (199 I) and Luck (1992) have both described findings obtained in single district general hospitals while the Northern Regional Survey Steering Group (1992) have described regional results, including mismatches between antenatal and postnatal diagnoses. A number of key points arise from

these studies. Firstly, ultrasound scanning which is primarily directed at the detection of fetal abnormalities is best carried out at around 18-20 weeks gestation. The evidence from the

Northern Region Fetal Abnormality Survey (Scott & Renwick, 1993) shows clearly that detection of urological abnormalities increases from 26% in women scanned at 16 weeks or less to 93% in women scanned between 17 and 20 weeks. Secondly, false positive diagnoses do occur (Atkins & Hey, 1991); in the two single hospital studies no pregnancy was terminated

erroneously because all suspected anomalies were scanned twice. In ten out of 30 cases of suspected major malformation in a Finnish study (Saari-Kemmpainen et al, 1990) the abnor-

mality disappeared spontaneously. Urological problems are particularly susceptible to false positive diagnoses (Rosendahl & Kivinen, 1989; Scott & Renwick, 1993); hydronephrosis is the most common urological abnormality and in the Northern Region 55% were found to be normal postnatally although all those diagnosed in

Luck’s (1992) study were reported to be under the care of a paediatrician. Thirdly, not all detectable abnormalities are detected; overall detection rate was 74% in the study of Chitty et al

(1991) and 85% in that of Luck (1992). In this latter study, the detection of renal and central nervous system anomalies was 100% while sensi- tivity of detecting heart anomalies was 36%. Fourthly, not all women in whom serious anoma- lies are detected go on to terminate the preg- nancy, as also shown in an American study by Pryde et al (1992). The fifth point is that there is considerable variation between different mater- nity units which ‘does not seem to be linked to unit size, to the type of equipment in use, or to the amount of antenatal ultrasound work done’, ‘Had the antenatal diagnostic ability of every unit in the region matched that of the best, a

130 MIDWIFEKY

hundred more significant diagnoses would have been made in the region each year in the last five years’ (Northern Regional Survey Steering Croup, 1992). In Luck’s (1992) study diagnostic accuracy increased with the experience of the radiographer. A recent special issue of the AIMS Journal (1993) on ultrasound comments that we do not know how many of those carrying out obstetric scans are qualified in medical ultrasound.

The AIMS special issue continues the Associ- ation’s campaign against the routine use of ultrasound in pregnancy. It is indeed extra- ordinary that a‘technique should be so widely used when, necessarily, given the shortness of its history, so little is known about the long term effects. A recent review (Reece et al, 1990) concluded that there were no confirmed bio- logical effects, but the problem is that the wholesale exposure of a whole generation to ultrasound scanning has made it virtually impos- sible to know what problems may result from scanning and what are the results of other influences. Thus, if, for example, it were the case that ultrasound scanning caused relatively subtle problems such as reading difficulties, it would be extremely difficult to demonstrate that this was indeed an effect of ultrasound and not the result of, say, different ways of teaching children to read.

DIAGNOSING CHROMOSOMAL ABNORMALITIES: AMNIOCENTESIS AND CVS

To detect chromosomal abnormalities it is neces- sary to have a sample of fetal cells. This is most commonly obtained from amniotic fluid from which fetal cells may be cultured. This pro- cedure - amniocentesis - is usually carried out between 16 and 20 weeks of pregnancy. The removal of amniotic fluid carries with it possible risks to the fetus (Turnbull, 1984), including the suggestion that children may be more prone to bilateral middle ear impedance abnormalities (Finegan et al, 1990). The main risk, however, is a probability of spontaneous abortion of about 1 in 200.

Chromosome analysis following amniocente- sis takes 3 to 4 weeks because cells have to be cultured. Given that most amniocenteses are carried out at 16 weeks or later, any termination is unlikely to take place before the 20th week. Recent changes to English law mean that there is now no longer a legal time limit for performing terminations on grounds of serious fetal abnor- mality.

Chorionic villus sampling (CVS) is an alterna- tive, and less widely available, means of obtain- ing fetal cells. The villi can be sampled through the cervix or through the abdomen; the trans- abdominal route is tending to be preferred (e.g. Elias et al, 1989; Brambati et al, 1990). The major advantage of CVS over amniocentesis is that it can be performed at a much earlier stage of pregnancy, usually between 9 and 11 weeks. In addition results are available more quickly because chromosome results can be obtained without the need for cells to be cultured. The disadvantage is that it is only of relevance to women whose risk status is established early in pregnancy, and it is therefore not of use as an adjunct to screening programmes which take place during the second trimester.

The miscarriage rate following CVS is gen- erally agreed to be higher than that following amniocentesis, but there is a lack of consensus as to what this rate is. There are a number of reasons for this (Goldberg et al, 1990). One is that base loss rates are difficult to establish because the risk of spontaneous abortion rises with maternal age. Thus, although it is agreed that overall approximately 3% of all pregnancies confirmed at 8 weeks will abort spontaneously (Simpson, 1990), this figure may be less than 2% for women under 36 years of age, but more than 10% for women over 40 (Cohen-Overbeek et al, 1990). Jahoda et al (1989) found 3% losses in women under 36 years and 6% over, following CVS. Another confounding factor is that oper- ators get better with time (Breed et al, 1990). The

final problem identified by Goldberg et al (1990) is reporting bias. In a table entitled ‘As you like it’ they demonstrate that by reorganising the same data, CVS loss rates can range from 4.3 to 8.2%!

There are still some doubts about the accuracy and safety of CVS and false negative results have

MlDWII;EKY 13 1

been reported (Lilford et al, 1991). The MKC European multi-centre randomised control trial

involving 3248 women published its findings in June 199 1. These showed that women allocated to CVS were significantly less likely to achieve the desired result of a liveborn healthy child than women allocated to amniocentesis: 14% in the CVS group had unsuccessful pregnancies com- pared with 9% in the amniocentesis group. The difference arose from a greater number of spontaneous fetal deaths before 28 weeks, more terminations for chromosomal abnormality, and

more neonatal deaths. The greater number of terminations (43 vs 28) arises partly because

earlier diagnosis (by any method) means that cases will be detected that would otherwise have aborted spontaneously before the 16th week. The other possible explanation for the greater

number of terminations is that some of the results were false positives, i.e. the diagnosis of a chromosomal abnormality was wrong. The MKC working party was, unfortunately, not able to say how many of these occurred, because post-ter- mination karyotyping was not always carried

out. Neither, of course, were they able to say how many true positives would have aborted spon-

taneously before the 16th week. Either way, the higher termination rate is a risk of the procedure that women should be aware of.

Another way in which CVS compared badly

with amniocentesis was in the need for retesting (6% vs 2%). In the CVS group 100 women needed a second test (which often meant waiting until 16 weeks to have amniocentesis), compared with 35 women in the amniocentesis group. The most common reason for retesting was failure to obtain an adequate sample. The Canadian multi- centre trial, which reported its results in 1989, also found that 10% of women having CVS went on to have amniocentesis as well. Another prob- lem that is more common with CVS is ‘mosaicism’, when an abnormality is evident in only some, but not all cultures, from the same specimen. These ambiguous findings are the other main reason for retesting.

Since publication of the MKC trial results,

there has been somewhat less enthusiasm for CVS. This was reinforced by reports of limb and facial abnormalities, which had started to appear

shortly before (Boyd et al, 1990; Firth et al, 1991). These reports led many other groups to

report their own experiences, some claiming

that the numbers could have occurred by chance, others supporting the interpretation that the events were causally linked. The

number of cases now reported makes it quite likely that there is in fact a real effect (Lilford,

1991). It is now recommended that CVS should not be carried out before 9.5 weeks’ gestation, that CVS should be carried out with a minimum

of placental damage, that women who have had CVS should be offered a detailed scan at 18-20 weeks, and that all babies whose mother had an early CVS should be followed up and examined

in detail (Rodeck, 1993). There is one other important point to be made

about CVS vs amniocentesis, which is raised by Robinson et al (199 1) concerning miscarriage after CVS. Compared with amniocentesis, a relatively large number of women will miscarry

after CVS, partly because it does actually cause more fetal losses than amniocentesis and partly because there is a higher rate of spontaneous loss

at the earlier stage of pregnancy. However, no-one can know whether their particular mis-

carriage was a consequence of the procedure or was one that would have happened anyway. Robinson et al (1991) found that women who miscarried after CVS experienced a great deal of guilt and blamed their loss on their selfish desire for an earlier test result. They in fact had even less reason for feeling this way than might be supposed because they were part of the rando- mised trial and had not actually chosen to have CVS. This is an important point which should be taken into account when counselling women for prenatal diagnosis.

THE FUTURE

This paper has described the techniques for detecting fetal abnormalities that are most commonly used in the UK at present. This is, however, a constantly changing held. Most efforts at the moment are being directed towards earlier diagnosis and alternative screening methods. It used to be thought that amniocente-

132 MIDWIFERY

sis could not be carried out before 16 weeks gestation because there would not be sufficient amniotic fluid. However, a number of centres are now reporting successful amniocentesis between 9 and 14 weeks (Elejalde et al, 1990; Nevin et al, 1990; Kebello et al, 1991; Parker et al, 1991). This is not yet widely available and no randomised control trials of early amniocentesis have yet been published.

A recent development in obstetric ultrasound is the transvaginal probe which enables detailed examination of the fetus in the first trimester (Green & Hobbins, 1988). It is suggested that this technique will enable the prenatal diagnosis of structural abnormalities in early pregnancy (Lancet editorial, 1989; Cullen et al, 1990), although, as the Lancet points out, it will be some while before the implications of anomalies detected at this stage can be understood. Women who have experienced the procedure as part of IVF treatment are reported to find it acceptable (Lavy et al, 1987). A particular advantage for women is that, unlike traditional transabdominal ultrasound, they do not need to have an uncom- fortably full bladder. The disadvantages may be that the fetus is exposed to higher levels of ultrasound, ever earlier in pregnancy; there is no available data on any possible miscarriage risk associated with this more invasive procedure.

The other new development is the use of ultrasound in screening for chromosomal abnormalities. A number of chromosomal abnormalities are associated with structural ano- malies (Nyberg et al, 1990) although not all investigators have found this to be the case for Down’s syndrome (Lynch et al, 1989; Marquette et al, 1990). However two large studies in France (Eydoux et al, 1989) and the UK (Nicolaides et al, 1992) have published impressive findings on the use of ultrasound detected anomalies as indica- tors for amniocentesis. The French study found a considerably higher proportion of chromoso- ma1 abnormalities detected in women who had amniocentesis because of anomalies picked up on scan than amongst those having amniocente- sis because oftheir age. The British report found that 14% (i.e. 1 in 7) of those selected on the basis of ultrasound anomalies had chromosomal abnormalities. A recent report on trends in

prenatal diagnosis of Down’s syndrome in England and Wales (Mutton et al, 1993) also shows that the increase in detection rates in women aged under 35 years is the result of improved detection through ultrasound as well as via serum screening. In fact, for each of the years 1989, 1990 and 199 1 more Down’s preg- nancies in women under 35 years were detected via ultrasound than via serum screening. Even when there are not obvious structural abnorma- lities, there are thought to be other measurable differences between babies with and without Down’s syndrome such as the thickness of the nuchal fold and the BPD/femur length ratio (Benecerrdf et al, 1987; Brumfield et al, 1989). Crane and Gray (1991) identified 75% of Down’s syndrome pregnancies with a nuchal skin thickness of 6 mm or greater for a 1% false positive rate in a prospective study. It would therefore appear that ultrasound screening for Down’s syndrome is likely to become a major area of investigation.

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