Testing for fetal abnormality in routine antenatal care

CLINICAL REVIEW

Testing for fetal abnormality care

in routine antenatal

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: serumscreening for neural tube defects; screening for Down’s syndrome; ultrasound scanning; amniocentesis and chorionic villus sampling.

Diagnosis -.

INTRODUCTION The detection of fetal abnormality has become a major

part of antenatal

care. A variety of tech-

niques are now in use, although stantly

being

modified

these are con-

in the pursuit

accurate

and earlier detection.

describe

the techniques

of more

In this paper we

which have been most

commonly used in the UK, and present information on what is currently known of their benefits Further information about and hazards.

vs screening ..

tests are those that can tell us, with

reasonable

certainty,

being tested is affected If we had cheap,

whether

accurate,

subgroup

124

Because a

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

Requests for offprints to JG

disorder. diagnostic

tests, we could apply them to everybody.

women,

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

risk-free

we do not, we need to find a basis for selecting

al (1992)

(1993).

or not the person

by a particular

women’s experiences of these techniques can be found in Green (1990), Statham (1992), Green et and Green

..

Diagnostrc

once defined

population.

These

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 Physicians (1989) Report on Prenatal Diagnosis and

125

MII)WIFEKY

Genetic

Screening

congenital

observed:

malformations

‘Most infants

and chromosomal

with dis-

taken

in

most

cases

is

termination

of

the

pregnancy.

orders are born to healthy young women with no identifiable

risk factor’. Conversely,

of women who are identified

the majority

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 mality. The vast majority the beginning

ALPHA FETO-PROTEIN SCREENING FOR NEURAL TUBE DEFECTS

abnor-

of women who reach

of the second trimester

do go on to

Alpha

feto-protein

(AFP)

duced by all human open

neural

tube

is a substance

fetuses. defect

the

higher levels are therefore

have healthy babies.

tic fluid and maternal

Where

Containers The

routine

nant women falling

and contents experience

monitors

maternal

leaks

that preg-

may be thought The

of as

first category

variables, e.g. weight, haemo-

screening measured serum

for

to identify all cases

and approximately closed

in maternal

AFP

Maternal

and

blood in such pregnancies. 85% of cases

of spina bifida. AFP is not, however,

tests and examinations

into two categories.

AFP

found in both amnio-

The extent of this is sufficient of anencephaly

pro-

there is an

lesions.

useful for

AFP

may

be

blood (known as maternal

or MSAFP),

or in amniotic

fluid.

blood is clearly the more accessible.

globin, blood pressure. These tests are to see whether the mother is a healthy container for

The optimum timing for the blood test is 1618 weeks; sensitivity is lower at other stages

her unborn child. If test results indicate deviance

of pregnancy.

from

gestation

is known because

the level of AFP in

maternal

blood rises during

the course of preg-

what is considered

to be the ideal then

action can be taken, for example advice

about

iron tablets or

rest and diet can be given.

The

nancy. about

It is important

In the second

every 4 weeks (Wald

fetal well-being.

tation

paper

is concerned

with

trimester

it increases

19% per week, approximately

second category of tests focuses on the contents rather than the container i.e. they are tests of This

that the correct

is not

& Cuckle,

accurately

1984).

known

by

doubling

then

If gesMSAFP

the aim is stated to be the delivery of a healthy

cannot be properly interpreted because the judgement that it is ‘elevated’ is made in terms of

baby,

the first

multiples

a benign

tation. The other common benign for elevated MSAFP is multiple

this second category.

For both categories

but the big difference

category

of test is intended

environment healthy,

is that

to maintain

of test

for a fetus that is (assumed

the second is intended

that are non healthy.

These

to be)

to detect fetuses

tests can only detect

fetal anomalies, they cannot correct them. Unlike the first category of tests, there is rarely

of the median

Inaccurate

dating

and

(MOM’S) for that ges-

multiple

explanation pregnancy. pregnancy

between them explain about one quarter raised MSAFP results (Robinson et al, 1989).

of

any action that can be taken on the basis of the

There are two major problems associated with MSAFP testing. One is that it does not detect all

test results which will increase

neural tube defects,

the chances

that

the baby will be born healthy. Sometimes a single investigative

procedure

can be a source of information container and contents. Ultrasound

about both 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

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

126

MIDWIFERY

is judged

to be abnormal

what is abnormal

is a pragmatic

one, but

for one group of women might

not be for others. Thus,

MSAFP

has been found

be made of this forewarning,

but the discovery

that high AFP may be linked to chromosomal abnormalities is leading to a trend towards

to vary with race (Cuckle et al, 1987; Macri et al,

amniocentesis

1987;

age, and

regardless

into

ment, which has more obvious implications

Johnson

maternal

1990a), maternal (Johnson et al, 1990b)

weight

diabetic

status,

consideration. boys having ences

et al,

which are often It is also related

higher

al, 1990).

to fetal sex, with

levels, although

are not large

explanation

not taken

enough

the differ-

to be used as an

in cases of raised MSAFP Yet a further

element

lies in the fact that MSAFP

(Calvas et

MSAFP

neural

of women found to have

will actually

tube defect.

are very variable,

The

(Campbell,

1987),

In practice,

have a fetus with a

proportions

for example:

al, 1979), 1 in 30 (Lilford

1 in 15 (Wald et

& Chard,

1985), 1 in 67

1 in 18 (Robinson

false positive

reported

et al, 1989).

rates will depend

the cut off level used to assess MSAFP incidence

of neural

tion being screening

screened.

tube defects The

condition

on

and the

in the popula-

predictive

power

of a

test (i.e. how likely it is that someone

with a positive screening

result actually has the

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 tion (Office of Population 1983; Stone et al, 1988). because

ultrasound

powerful

tool, a number

starting

to abandon

and selective aborCensuses & Surveys, For this reason, and

was

a

more

of UK hospitals

becoming

were

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 approximately one third of pregnancies with raised levels of MSAFP will have a problem of some kind. Unfortunately

et al, 1990).

The other

developfor

action, is the finding that LOW levels of MSAFP are associated

with Down’s syndrome

al 1984;

Merkatz

discussed

below.

et al,

1984),

(Cuckle et

which

will be

levels may vary from

within 30% of the true mean (Carter et al, 1988). Thus only a minority

Warner

of uncertainty

day to day and a single sample is likely only to fall

raised

1989;

following raised MSAFP, of other indications (Cowan et al,

it is not clear what use can

SCREENING SYNDROME

FOR DOWN’S

Down’s syndrome somal

is the most common

chromo-

abnormality,

accounting for approximately 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 for others, particularly

sex chromosome

lies, the consequences

are uncertain.

little

mentioned

chromosomal

hazard

disorders:

found whose prognosis

of

with life; anomaThis

anomalies

for

may

be

is not known. Parents are

rarely told in advance about this possibility. probability

is a

screening

The

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 screening

recently,

maternal

age

was the

test for Down’s syndrome

sole

and other

chromosomal abnormalities. In the UK the precise age at which a diagnostic test would be offered Table 1 Estimated

varies between

different

incidence of chromosomal

Health Service

abnormalities

Maternal age

Liveborn babies Down’s syndrome All chromosomal

21 27 35 37 40 45

l/l 500 1/1000 l/400 11220 l/l00 l/30

l/500 II450 II200 l/l25 l/60 l/20

From: Berini R Y & Kahn E (1987) p 59. Reprinted by permission of Blackwell Scientific Publications, Inc.

MIDWIFERY

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 procedure (this is of course, a curious piece of algebra assuming as it does that having a child with Down’s syndrome and experiencing a miscarriage 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. Originally 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 markers to increase the screen’s sensitivity and specificity 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 35-year old woman will be the same as that rziven to any other 35-year old woman. With &urn screening, age is still taken into account, but in addition there is information about this particular pregnancy. This means that everyone will be assigned their own particular risk figure which is

127

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: maximising 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 probability 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 group (years) under 25 25-29 3Q-34

35-39 40-44 45 and over

All

Probability of screen positive

Proportion of DS detected

I/45 l/32 If15 l/5 l/2 > l/2

35% 40% 54% 76% 93%

> 99%

l/20

58%

Table courtesy of Wald 81 Kennard, personal communication (derived from parameters in Wald et al (1992c).

128 to

MIDWIFERY

1989

(Robinson,

1991),

women are having children

perhaps

of Down’s babies were detected

antenatally

this rose to 38% in 1991 (Mutton This

represented

women 1991.

59%

because

later. In 1989,30%

of

and

et al, 1993).

those

carried

by

aged 35 and over in 1989 and 62% in 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%

should

be possible

pregnancies women

that using the triple to detect

while needing

to amniocentesis.

age alone

detects,

involves 7-S%

at best,

60%

test it

of Down’s

screening

subsequent

based

of cases

on and

(i.e. all women published

(or about

even if they were found

ULTRASOUND method virtually

every

fetus;

is the most widely used for fetal abnormality,

pregnant

woman

obtained

from

gestations.

beginning

1992; Herrou

to et al,

Wald et al, 1992c).

sorts

of

scans

This

performed

paper

to consider alone.

measuring

is primarily

ultrasound

scanning

While these indicate that the test is not perform-

fore

three

ultrasound

detecting

about

syndrome

with a false positive rate of approxim-

50%

of fetuses

tely 5%, a more recent 9 1% detection

publication

with Down’s has shown a

rate for a 4.1% amniocentesis

(Cheng et al, 1993). Serum screening for Down’s syndrome mean

fewer

diagnostic detected.

women testing

However,

subjected and

more

anxiety

to the stress of affected

fetuses

to some

is causing consider-

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) predicted, 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

and localisof the

We will therehow useful

apart from detecting

is

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

sound on low risk populations other

should

it is evident that, at least in its

early days, serum screening able

rate

questions:

in this

counting,

even if the main function

ing quite as well in practice

consider

be

concerned

Any scan will involve

for abnormalities.

but is

can

it is not possible,

scan is looking

as in theory,

and the

at different

and dating the baby(ies)

ing the placenta,

UK

is a source

information

with tests for fetal abnormality;

with

in the

about both the mother

different

context

et al, 1992;

SCANNING

scanning

for testing

however,

of the use of serum now

in a

still want amniocentesis,

rates has been based on retrospective

appear (Dawson 8c Reynolds,

would want

syndrome

to be ‘low risk’.

However

Phillips

Down’s

but 76% of them would

analyses.

are

for

of information

35%

diagnostic

pregnancy,

detection

practice

to

Screening

Most of what has been

in

‘right’

having at least one scan. Ultrasound

aged 35 years or over) having amniocentesis

screening

their

et al (1993) found that 55% of

to subject only 5% of

of the population

reports

lose

155 older women in the Netherlands serum

Ultrasound

It was estimated

1992;

to

in that

period.

CVS).

unwilling

testing. Roelofsen

than the detection

ultra-

for investigations

of fetal abnormalities

(assessment of gestational age, identification of multiple pregnancies, detection of intrauterine growth

retardation

(IUGR)

and placenta

via) provide little evidence of improved

prae-

perinatal

outcomes. From an initial sample of 2 17 1 pregnant women Ewigman et al (1990) randomised 915 women who were less than 18 weeks pregnant 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

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 gestat&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 pregnancies, 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 evidence of growth retardation in some Down’s syndrome fetuses (Nyberg et al, 1990). Ultrasound scanning is also used as an adjunct to amniocentesis and CVS; localisation of the fetus and placenta minimise the risks of these procedures. 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 8cKivinen (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-

129

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 abnormality 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 sensitivity of detecting heart anomalies was 36%. Fourthly, not all women in whom serious anomalies are detected go on to terminate the pregnancy, as also shown in an American study by Pryde et al (1992). The fifth point is that there is considerable variation between different maternity 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

sis takes 3 to 4 weeks because

years’

(Northern

cultured.

Croup,

1992). In Luck’s (1992)

accuracy

Regional

increased

radiographer. Journal

Survey

Steering

study diagnostic

with the experience

of the

A recent special issue of the AIMS

(1993) on ultrasound

comments

that we

do not know how many of those carrying obstetric

scans

are

qualified

in

out

medical

ultrasound. campaign

ultrasound ordinary

against

the

in pregnancy.

routine

should

so little is known

about

effects.

A recent

(Reece

logical

review

that there

effects,

but

wholesale

exposure

ultrasound

scanning

were the

be so widely of its

the long term et al,

1990)

no confirmed

problem

of a whole

of

extra-

given the shortness

history,

concluded

use

It is indeed

that a‘technique

used when, necessarily,

the Associ-

bio-

is that

the

generation

to

has made it virtually impos-

Given

is unlikely

the cervix or through abdominal

problems extremely

scanning

such as reading difficult

major

advantage

In addition

(e.g.

et al, 1990).

The

of CVS over amniocentesis

that it can be performed of pregnancy,

usually between results

9 and 11 weeks.

are available results

can be obtained

without

the need for cells to be cultured.

that this was

ways of teaching

children

to

whose risk status is established and it is therefore

to screening

erally agreed amniocentesis, reasons that

which CVS

take

is gen-

than that following

but there is a lack of consensus is. There

for this (Goldberg

base

to

early in

not of use as an

programmes

to be higher

to what this rate

read.

The

is that it is only of relevance

place during the second trimester. The miscarriage rate following

and not the result

quickly

chromosome

difficulties,

to demonstrate

more

because

pregnancy,

is

at a much earlier stage

adjunct

it would be

through the trans-

to be preferred

Brambati

caused relatively subtle

indeed an effect of ultrasound of, say, different

it were the case

means of obtain-

the abdomen;

route is tending

Elias et al, 1989;

women

Thus, if, for example,

(CVS) is an alterna-

ing fetal cells. The villi can be sampled

other

influences.

of serious fetal abnor-

villus sampling

results

that ultrasound

the 20th week.

tive, and less widely available,

scanning

of

are

to English law mean that there is

on grounds

disadvantage

the

amniocenteses

mality.

from

are

most

now no longer a legal time limit for performing terminations

may result

what

that

amniocente-

cells have to be

to take place before

Recent changes

sible to know what problems and

analysis following

carried out at 16 weeks or later, any termination

Chorionic

The AIMS special issue continues ation’s

Chromosome

loss rates

are

are a number et al, 1990).

difficult

the risk of spontaneous

as of

One is

to establish

DIAGNOSING CHROMOSOMAL ABNORMALITIES: AMNIOCENTESIS AND CVS

because

confirmed

at 8 weeks will abort

To detect chromosomal abnormalities it is necessary to have a sample of fetal cells. This is most commonly obtained from amniotic fluid from

(Simpson,

1990), this figure may be less than 2%

with maternal

age. Thus,

that overall approximately

abortion

although

rises

it is agreed

3% of all pregnancies spontaneously

for women under 36 years of age, but more than 10% for women over 40 (Cohen-Overbeek et al,

which fetal cells may be cultured. This procedure - amniocentesis - is usually carried out between 16 and 20 weeks of pregnancy. The

1990). Jahoda women under

et al (1989) found 3% losses in 36 years and 6% over, following

CVS. Another

confounding

removal of amniotic

ators get better with time (Breed

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.

factor is that operet 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

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 compared 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-termination karyotyping was not always carried out. Neither, of course, were they able to say how many true positives would have aborted spontaneously 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 multicentre trial, which reported its results in 1989, also found that 10% of women having CVS went on to have amniocentesis as well. Another problem 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

13 1

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 miscarriage 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 randomised 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

gestation

because

amniotic

fluid.

are

now

However,

reporting

between

out before

9 and

16 weeks

there would not be sufficient a number

successful

14 weeks (Elejalde

Nevin et al, 1990; Kebello

of centres

amniocentesis et al, 1990;

et al, 1991;

Parker

et

prenatal

diagnosis

England

and Wales

shows

that

of

Down’s

(Mutton

the increase

syndrome

in

et al, 1993)

also

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

al, 1991). This is not yet widely available and no

years 1989,

randomised

nancies in women under 35 years were detected

control

trials of early amniocentesis

via ultrasound

have yet been published. A recent development is the transvaginal examination technique

1988). It is suggested the prenatal

abnormalities

(Lancet

editorial,

although,

in

1989;

early

Cullen

of

1990),

as the Lancet points out, it will be some

before

detected

the

implications

of

anomalies

at this stage can be understood.

who have experienced

the procedure

women is that, unlike traditional ultrasound, fortably that

the fetus

ultrasound,

fold

syndrome thickness positive therefore

with and

Down’s

without

such as the thickness

and

the

BPD/femur

et al, 1987;

rate in a prospective is likely

ratio

et al, 1989).

75% of Down’s a nuchal skin for a 1% false study.

that ultrasound

syndrome

of the

length

Brumfield

pregnancies with of 6 mm or greater appear

Even

abnorma-

to be other measurable

babies

Crane and Gray (1991) identified

Women

It would

screening

to become

for

a major

area of investigation.

transabdominal

The disadvantages

is exposed

ever earlier

to higher

in pregnancy;

may be levels of there

no available data on any possible miscarriage The

screening.

they do not need to have an uncom-

full bladder.

associated

nuchal

as part of

IVF treatment are reported to find it acceptable (Lavy et al, 1987). A particular advantage for

between

Down’s syndrome (Benecerrdf

pregnancy

et al,

lities, there are thought differences

that this

diagnosis

than via serum

when there are not obvious structural

ultrasound

probe which enables detailed

will enable

structural

while

in obstetric

of the fetus in the first trimester

(Green & Hobbins,

1990 and 199 1 more Down’s preg-

is

risk

with this more invasive procedure.

other

ultrasound

new development in

abnormalities. abnormalities

screening A

number

are associated

is the use of

for

chromosomal

of

chromosomal

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 indicators for amniocentesis. The French study found a considerably higher proportion of chromosoma1 abnormalities detected in women who had amniocentesis because of anomalies picked up on scan than amongst those having amniocentesis 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

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