Ultrasound Obstet Gynecol 2003; 22: 555–558
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.935
Editorial
Mass screening for fetal malformations:
the Eurofetus study
S. LEVI
Eurofetus Project Leader and Honorary Professor of Gynaecology
and Obstetrics and Honorary Director of the Gynaecology and
Obstetrical Ultrasound Unit, CHU Brugmann, Brussels, Belgium.
Current address: 4 Derby Avenue, B1050 Brussels, Belgium
(e-mail: slevi@belgacom.net)
Obstetric ultrasound has universal use in developed
countries but at different levels of expertise between
the various centers. Because the correct practice of
ultrasound is strongly operator-dependent, education
and training are of paramount importance. Ultrasound
malformation screening is the best example of this need for
education and training. Screening for fetal malformations
is generally regarded as a worthwhile endeavor and is
taken for granted in the field of obstetric ultrasound.
Obviously, the best results in detecting malformations
will be obtained by the most skilled operators. However,
it is unrealistic to consider organizing a screening program
that is dependent on the participation of expert operators
only. Such expert operators are naturally requested for
targeted examinations, however they are not sufficiently
numerous to be able to handle a mass screening
program involving all the pregnant patients attending
their institution of which only some 2% will have a
malformed fetus.
Discussion as to whether antenatal screening for fetal
malformation is justified will not be included here. It
is generally accepted that ultrasound screening is a
useful procedure for a number of important reasons.
Ultrasound screening permits the diagnosis of the majority
of structural abnormalities and a more rational approach
to the diagnosis of chromosomal abnormalities; it allows
termination of pregnancy at the parents’ request for severe
abnormalities, while for operable lesions it permits the
organization of optimal care or surgery for the newborn
and psychological support for the parents. My approach
to the purpose, organization, methods and benefits of
screening have been extensively discussed elsewhere1,2 .
In this Editorial I will address the efficiency of mass
population screening. For this reason it is important to
consider sensitivity studies performed on large population
samples. Only a few papers in the literature have
analyzed routine scanning on samples from more than
100 000 pregnant women. Two papers published prior
to 19963,4 reported a screening sensitivity for major
malformations of 26.7% and 28.5%, respectively, with
Copyright  2003 ISUOG. Published by John Wiley & Sons, Ltd.
a comparable prevalence of malformed fetuses (1.9%
and 2.0%, respectively). Another two studies appeared
in journals in 1999 and 2001, reporting results from the
Eurofetus study5 and the Euroscan study6 .
The Eurofetus project7 was designed to test the effi-
ciency of ultrasound in detecting fetal malformation in
a mass screening program. Eurofetus was conducted
prospectively between 1990 and 1993 in institutions
in which good conditions for fetal examination were
present, and the program was focused on screening for
congenital anomalies in non-selected pregnant women.
The ultrasound units involved included personnel (nurses,
midwives, technicians, physicians) with daily experience
of routine obstetric ultrasound and who practiced malfor-
mation screening on a regular basis as a full- or part-time
occupation. Additional training personnel could be part
of the examiners’ team under the supervision of the expe-
rienced professionals. Although most of the collaborating
units included at least one individual with average to high
expertise in fetal ultrasound, the staff members in gen-
eral were not expert in fetal malformation assessment at
tertiary level experience.
All the patients with an indication for ultrasound exam-
ination were systematically removed from the Eurofetus
study in order to comply with the non-selection principle
and to retain the average frequency of anomalies found
in a normal population, i.e. 2%8 . We have commented
previously on the relationship between the frequency of
the important group of congenital heart defects and the
sensitivity of fetal malformation screening2,9 .
In 2001 the Editorial in the October issue of this
Journal was dedicated to the Euroscan study6 . The
Eurofetus and Euroscan studies had similar aims and
the European Union sponsored both studies. Fortunately
these studies were not duplicative but complementary,
therefore making appropriate use of the European Union
funding. In addition to sharing certain similarities, the
two projects also exhibited fundamental differences.
EDITORIAL
556
Let us examine the similarities first. The aims of the
two projects were similar, i.e. evaluation of the prenatal
detection by ultrasound of all congenital malformations
in unselected populations. Both studies adopted the
same endpoints, such as excluding identical minor
malformations together with anatomical ‘peculiarities’
regarded as ultrasound markers of a potential genetic
malformation.
However, the material selection for the two stud-
ies differed. Indeed, Eurofetus was a prospective
institution-based study while Euroscan was a retrospective
population-based study (the data were collected from mal-
formation registries covering several defined geographical
areas).
Thus the comparability of the studies might be altered
by subtle bias as follows:
• The expertise of examiners from a geographical
area-based study can be very heterogeneous, reflect-
ing the totality of ultrasound practice from basic
office to tertiary ultrasound units. Basic office prac-
tice – characterized by relatively few patients and a rare
occurrence of malformation – is usually linked with
low expertise. Specialized units usually have a high
throughput of malformations and are usually run by
expert personnel.
• Low-risk and documented high-risk pregnant women
are mixed in a population-based study although
an excessive number of high-risk patients might be
included in samples from areas characterized by a high
concentration of obstetric tertiary centers.
Although a standard region should have a full range
of ultrasound skills and an average number of fetal
malformations, the weight of each of these very different
practices in making up the totality is not known.
Conversely, Eurofetus had a more homogeneous practice,
thus making it easier to evaluate the overall and the
individual unit performance.
We have tracked down samples exceeding 30 000 preg-
nant women and observed that the sensitivity observed in
population-based studies (24% to 38%)4,10 – 12 was lower
than in the Eurofetus institution-based (61%) study5 .
Some methodological differences are observed also:
• The proportion of false-positives is not available for the
Euroscan study.
• Major malformations not detectable by ultrasound
were excluded from the Euroscan study.
• Unlike the Euroscan project, all the Eurofetus centers
have a routine screening policy: at least one scan around
the 20th week for nearly all the pregnant women
attending the institutions.
• The frequency of malformed fetuses or babies in the
Euroscan study is 1.15%. This is considerably lower
than the mean frequency disclosed in the Eurocat
Registry of malformations (2.27%)8 , which includes
most of the registries covered by the Euroscan study,
and also much lower than the frequency disclosed by
Eurofetus (2.0%). (NB. Extrapolation from available
Copyright  2003 ISUOG. Published by John Wiley & Sons, Ltd.
Levi
data concerning 76% or 2600 out of the 3400 of the
Eurofetus malformed fetuses).
• The Euroscan detection rate was not given as a whole
but only for specific classes of anomalies.
I will now illustrate some rarely considered facts and
misconceptions by considering the Eurofetus study. The
severity of the anomalies and the outcome for malformed
fetuses are rarely considered in screening studies. I will
illustrate this with reference to congenital heart defects
(CHD) to show the influence of severity on the outcome
of screened fetuses. CHD are chosen for two reasons:
• CHD can be equally distributed into serious and
relatively benign lesions.
• Antenatal diagnosis of CHD is difficult, unlike other
severe lesions such as those affecting the central nervous
system (CNS), and the number of detected cases of CHD
does not greatly exceed the non-detected cases. Hence,
comparison between missed and detected anomalies
becomes statistically assessable13 .
Eurofetus has shown that the global sensitivity of CHD
detection (34%) is significantly lower when compared to
CNS (88%) and to urogenital malformations (89%). This
observation would appear to support some of the reserva-
tions expressed with regard to CHD screening. However,
the study also demonstrated that there are large differences
in sensitivities between isolated and associated CHD sensi-
tivity, 23% vs. 67% respectively, and between severe and
benign isolated lesions, i.e. 56% vs. 5%, respectively. It is
therefore obvious that a shift in the proportion between
the subgroups can alter significantly the sensitivity figures.
Conversely, let us reflect on what we can expect from
antenatal detection. Although discussed on several occa-
sions, it remains paradoxical that the fetuses that are
diagnosed antenatally have a poorer outcome. This can
be explained by the fact that the majority of the detected
abnormalities are severe malformations compared with
those not diagnosed (85% vs. 36%, respectively).
The detection of fetal malformation reduces signif-
icantly the number of affected newborns. Among the
pregnancies with the most severe CHD (68 cases), 52%
of the detected cases were terminated, while an addi-
tional 12% died in utero and 24% died before day 6.
Conversely, all of the missed abnormal fetuses were born
alive but 51% died before day 6. It is possible to rule out
the effect of pregnancy termination by examining the less
severely affected fetuses (297 cases) since none of these
was terminated. The total spontaneous loss was 19% in
the detected group vs. 3% of the missed cases. Obviously,
the set of detected anomalies included more severe lesions
than the set of non-detected anomalies.
The antenatal detection of cardiac malformation does
not influence the rate of Cesarean section. The complexity
of the defect favors per se the occurrence of premature
birth, as observed in both the antenatal and postnatal
diagnosis groups.
We encountered a cardinal problem in attempting to
complete one aspect of the Eurofetus study. We failed to
Ultrasound Obstet Gynecol 2003; 22: 555–558.
Editorial
achieve a satisfactory analysis of the cost–benefit aspect
of the screening project. Despite the expertise of the
specialized team in charge of the project, it appeared that
the costs of the scanning process and the consequences
of false-positive and false-negative cases were impossible
to calculate. Our health economist experts were unable
to obtain financial data of sufficient quality from the
institutions involved, and in addition the available health
statistical data were often incomplete. The shortage of
records required to calculate the costs with even minimal
accuracy to achieve average scientific standards meant
that the cost–benefit calculation had to be discarded.
However, a few studies on the costs associated with
specific malformation identification can be found in the
literature together with additional references 1,14 – 18 .
The high number of malformed fetuses in the Eurofetus
database provides robust information on the frequency
of particular malformations in the population together
with meaningful statistics on the detection rates of these
malformations.
At the beginning of this article the clear dependence of
ultrasound screening efficiency on education and expertise
was stressed. However, at a similar level of expertise,
screening efficiency might be altered by other often quite
simple factors such as an excess of routine work or
the inclusion of too many scanning staff members. Too
many routine anatomical scans done each day, combined
with the expected low prevalence of anomalies, can
result in lowered operator attention. Too many part-
time scanning staff members could reduce the average
expertise level. Indeed, looking at the overall detection
rate in the Eurofetus study (sensitivity 61%) we noticed
that the highest sensitivity (71%) was reached by 45
centers scanning a population of less than 1500 pregnant
patients per year, while the three centers scanning in excess
of 4000 patients per year achieved a much lower average
sensitivity (47%), thus suggesting that a high throughput
lowers screening efficiency.
CONCLUSIONS
Overall experience gleaned from some 20 years of
screening for fetal malformation supported by data from
studies and analyses such as Eurofetus prompts me to
offer some thoughts and advice on the subject. First, a
few recommendations on the practical aspects of the daily
screening process:
1. The malformation screening at 20 weeks’ gestation
should be left to qualified examiners.
2. It should be remembered that a detected malformation
frequently coexists with others.
3. Any unusual fetal image needs expert ultrasound
examination, usually in a tertiary center.
4. Any malformation identified by this process requires
subsequent karyotyping.
Since ultrasound examination is operator-dependent,
and given that high-level expertise is not generally
Copyright  2003 ISUOG. Published by John Wiley & Sons, Ltd.
557
available for mass screening, ultrasound personnel
involved in moderately busy obstetric ultrasound units
should be trained to recognize deviations from normal
and when these occur to refer cases on for diagnosis or
for substantiation to a tertiary center. We naturally would
advise policy- and decision-makers to adopt the Eurofetus
method of screening practice, i.e. to direct pregnant
patients to ultrasound units familiar with malformation
screening at least for the 20-week detailed anatomical
scan. Some practitioners may need convincing both of the
need for routine screening and the need to refer patients
on to a tertiary center and it is important to present to
such individuals detailed results from the available mass
screening programs. It would be a mistake to consider
only the sensitivity as the main criterion since a variety
of parameters can alter the relevance of a given detection
rate. Some of these factors are:
• The frequency of malformations and of malformed
fetuses in a given sample.
• The incidence of each anomaly and accurate classifica-
tion under the international code.
• The proportion of severe and benign malformation in a
given sample.
• The proportion of isolated and associated malformation
in a given sample.
• The number and timing of ultrasound examinations.
Other important factors are more difficult to quantify
such as:
• The education, training and expertise of the exam-
iner(s).
• The motivation of the examiner(s).
• The quality of the available ultrasound equipment.
These objective and subjective factors have to be taken
into account when evaluating the obvious significance
of ultrasound sensitivity in the detection of fetal
abnormalities.
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Ultrasound Obstet Gynecol 2003; 22: 555–558.