Prenatal Diagnosis in Switzerland

Switzerland, with a population of slightly over 7 million, has about 83,000 births per year. There is no comprehensive national registry for prenatal diagnosis (PND) or congenital

malformations. Health care is largely organised within each of the 23 counties. Whereas ultrasound screening is available to all pregnant women, the availability of other types of PND is

largely determined by proximity to the university medical centres or specialised clinics. Maternal biochemical serum screening is offered by some 15–20 laboratories, and cytogenetic analyses

are performed in 8. DNA-based diagnosis is essentially limited to the medical genetics departments/divisions of the 5 university medical schools. It can be estimated that slightly over 10%

of gestations are monitored by invasive prenatal diagnostic techniques. The greatest challenge for the future will be the training of the medical and paramedical personnel necessary for the

current and future pre- and postnatal diagnostic testing.

Switzerland, with a population of 7,019,000, had 82,890 births in 1994 (Bevölkerungsbewegung in der Schweiz 1994, Bundesamt für Statistik, Bern, 1995), a figure which has varied little over

the past 3–5 years. Switzerland is a federalistic democracy, in which primary obstetrical care is provided on an extremely decentralised basis; the majority of hospitals with obstetrics

divisions deliver fever than 500 babies annually and at least 25 hospitals perform less than 100 deliveries annually [1]. There are 23 counties (‘cantons’), which vary considerably in

geographical availability of specialised medical services such as prenatal diagnosis (PND). The interpretation and application of regulations concerning assisted procreation, PND and

abortion also differ between counties.

In this paper we consider three categories of prenatal diagnostic techniques: ultrasound screening, biochemical analysis and invasive procedures; amniocentesis, chorionic villus sampling

(CVS) and cordocentesis. Whereas the majority of pregnancies are evaluated at least once by ultrasound, the exact proportion of pregnancies monitored and the median number of scans per

pregnancy cannot be calculated, since echography is performed by doctors in private practice, in regional public or private clinics and in tertiary-referral university hospitals. The

proportion of pregnancies monitored by biochemical screening (maternal serum α-fetoprotein, AFP, for example), although on the rise, varies from a few percent to over 50%, depending mainly

on the geographical situation and the organisation of services in that county. Currently, 15–20 private and university-linked laboratories perform biochemical screening of maternal serum

with the goal of identifying pregnancies at risk for chromosomal disorders and other malformations.

Map of Switzerland showing location of the 5 university (*) and 3 commercial (•) cytogenetics laboratories.

Although most regional and/or university hospitals maintain their own registries of congenital anomalies and of PND, no comprehensive national registry appropriate for epidemiological

studies exists. The two principal sources of information in these areas are the federal Invalidity Insurance (AI) system and the Swiss EUROCAT (European Registry of Congenital Anomalies and

Twins) malformation registry [2, 3].

The federal AI system covers medical expenses occasioned by congenital malformations; most infants with serious birth defects are thus registered with the AI at birth (or time of diagnosis).

Although only limited data from the AI are accessible to the public, some published statistics from this source will be cited in the section on the impact of PND. Switzerland has

participated in EUROCAT since 1987, when the country joined thanks to a joint initiative of the Swiss Academic Medical Society and the Swiss Society of Paediatrics [2–4]. The registry is

centralised in Lausanne (county of Vaud), and this county has had the most complete coverage. In 1988, it was estimated that 40% of all deliveries (on a national scale) were monitored under

the system. Participation grew progressively so that since 1991 over 85% of births have been included in EUROCAT coverage. As of 1994, only three counties (representing less than 10% of

births) did not yet have a EUROCAT neonatologist. Participation and coverage are, however, quite variable from one county to the other, depending on the type of population (e.g. rural or

urban), the organisation of the registry and the source of funding. The proportion of births monitored can be estimated by comparing the reported rate of malformation in Switzerland to the

overall EUROCAT rates. For all EUROCAT registries (1980–1992), the malformations prevalence was 23.1 per thousand births; Switzerland reported 13.8 malformations per 1,000 births between

1988 and 1992 [2–5].

Swiss EUROCAT collaborates closely with the Swiss Teratogen Information System, a Lausanne-based but nationwide service created to benefit counselling and pregnancy management in

reproductive toxicology.

— the Swiss Society of Medical Genetics counts paediatricians and obstetricians as well as clinical and laboratory geneticists among its over 700 members. The Society publishes a bi-annual

bulletin which includes practical information (e.g., lists of books and conferences, addresses of laboratories and lay associations) as well as scientific articles [6];

— the Swiss Society of Gynaecology and Obstetrics has recently proposed a protocol for monitoring spontaneous abortions occurring between 8 and 11 weeks.

Other groups having an impact on PND and which meet at least annually are the Swiss Society of Ultrasound in Medicine and Biology (SGUMB) and the Swiss Perinatal Society.

A number of lay organisations, created principally over the past 10–15 years in Switzerland, are an increasingly important source of information on specific genetic disorders.

No databases or information systems concerning PND or congenital malformations in Switzerland are accessible by Internet.

Most university hospitals have registers of congenital anomalies which include those detected prenatally. For example, in 1995 at the University of Zurich, a tertiary-referral centre,

malformations were diagnosed prenatally in 175 gestations. Such information is, however, of little epidemiological utility.

Published in Geneva four times a year is the French-language Bulletin de Périnatalogie [4, 7]; the Bulletin, offered free of charge, enjoys a wide distribution among French-speaking health

professionals.

The impact of PND on the prevalence of severe congenital malformations and chromosomal disorders has not been evaluated on a national level, but some trends can be deduced from EUROCAT data

or from regional studies. The 1996 EUROCAT-CH information bulletin reports [3] that 25% of the malformations reported to the system are diagnosed prenatally.

Another idea of the impact which PND has had on the incidence of chromosomal anomalies can be obtained from a study of the epidemiology and prevention of trisomy 21 in the county of Vaud

from 1980 to 1994 [10]. If the prenatal detection rate of trisomy 21 for mothers 35 years and older has remained stable (77–78%), the proportion of prenatally diagnosed fetuses conceived by

younger mothers has increased from 9.8% in the period 1980–1989 to 48.0% for the period 1990–1994 [10, and M.C. Addor, pers. commun.].

The EUROCAT subproject on congenital heart disease [2, 3, 5] was coordinated in Switzerland and included data from the 5 Swiss university centres. According to this study, the proportion of

cases of congenital heart disease detected prenatally has more than tripled over the past 10 years.

The increasing availability of PND has also had an important psycho-social impact on the population in general and on couples of child-bearing age in particular. If 15 years ago, over 60% of

amniocenteses studied at the Geneva University Hospital were done for advanced maternal age and 30% for ‘anxiety’ [7], the proportion of patients presenting today for those reasons is

approximately equal, e.g. about 40%. This reflects the higher knowledge level of a population which is confronted with an increasing number of choices abut which they (and their doctors) are

not always well informed. One of the greatest challenges for the future will be to provide adequate information and follow-up counselling for pre- and postnatal detection of genetic

disease.

Increasing awareness of PND and of genetics in general has certainly also played a role in the increasing number of lay organisations available to serve individuals and families with genetic

disorders.

A public increasingly aware (and wary) of genetic diagnosis and research has also placed legislative restrictions on PND (see below).

In Switzerland routine ultrasound screening is offered to all pregnant women at 10 and at 20 weeks of gestation, the costs being covered by their health insurance. Additional scans are

covered if the pregnancy is classified as high risk on the basis of history, clinical or ultrasound examination. Goals of the initial ultrasound exam are dating and detection of multiple

pregnancies. The 20-week ultrasound is a detailed screening for malformations, placenta praevia and other pathologies.

Second-trimester maternal serum screening is not performed routinely but is available on request in all regions of the country. The proportion of pregnancies screened is variable, being

about 16% in the Zurich region (large county, with numerous physicians and laboratories involved in PND) [11, 12] and nearly 60% in Geneva (small, urban county with established collaboration

between private and university laboratories) [P. Bischof, pers. commun.]. Biochemical serum screening is offered to most pregnant women, depending on the policy of their obstetricians.

Laboratory testing for AFP, β-hCG and free oestriol levels is performed in 15–20 university and commercial laboratories. The costs are generally defrayed by the expectant mother’s health

insurance.

Amniocentesis, performed by numerous obstetricians both in private practice and in specialised clinics, is the most readily available of the invasive techniques. Chorionic villus sampling

(CVS) is done mainly in the university obstetrics departments, although some practitioners, particularly in the German-speaking part of the country, do the sampling in their offices.

Cordocentesis is available only in university medical centres, none of which are located in the Italian-speaking part of Switzerland. The laboratories which carry out the analysis of these

three types of fetal samples are located in the 5 counties shown in figure 1.

— parent or previous child with a chromosomal anomaly, neural tube defect or genetic disorder for which diagnostic testing is available;

— increased risk of chromosomal anomaly or malformation following maternal serum screening.

At least 75% of the obstetricians and general practitioners who care for pregnant women are involved in PND, as they perform level 1 ultrasound examinations. For all doctors, backup level 2

ultrasound is available, mostly in regional hospitals (where it may be performed by obstetricians, radiologists or experienced ultrasound technicians) or by specialists in private practice.

In general, obstetricians are well trained to detect sonographic markers and well equipped to perform this ultrasound screening. In Switzerland there are 5 level 3 referral centres at the 5

university hospitals, with highly experienced examiners and high-standard technical equipment for sonomorphological diagnosis.

There exists no nationwide programme on quality control of prenatal sonographic diagnosis in Switzerland. A monitoring system to evaluate the diagnostic efficiency of prenatal ultrasound

examinations at the main referral centres was initiated by the gynaecology subgroup of the Swiss Society of Ultrasound in Medicine and Biology (SGUMB) in August 1996. Currently, 1995 data

have been collected from referring centres and are being analysed.

Comparison of utilisation of the three invasive techniques of PND in counties with diagnostic laboratories. The population of each county is given below the respective bar graph, which

compares the numbers of the three procedure types performed each year. Counties marked with an asterisk have two cytogenetics laboratories.

In 1994, one can estimate the number of amniocenteses analysed nationwide at about 7,900, CVS at 2,500 and fetal blood sampling at less than 100. The total and the proportion of tests done

in each of the 5 counties reflects various factors such as total population accommodated and policy of referring obstetricians. In general, CVS is currently more popular among the

German-speaking population than it is in Romandy (French-speaking).

Biochemical analyses for a number of genetic disorders, including lysosomal storage disorders, haemoglobinopathies and collagen (connective tissue) diseases are available in some of the

university hospitals.

First-trimester biochemical screening: research protocols, in some centres as part of an international collaboration, are underway in all 5 university hospitals to evaluate the utility of

biochemical markers such as PAPP-A and free β-hCG in screening for chromosomal disorders.

Early amniocentesis: all 5 university centres are evaluating cytogenetic and clinical aspects of amniocentesis performed between 10 and 14 weeks.

Interphase cytogenetics: FISH is being applied to uncultured amniotic fluid cells under a research protocol in several university centres, with the goal of detecting aneuploidies for

selected chromosomes (13),18,21, X and Y).

Separation of fetal cells from the maternal circulation is done only on a research basis, as part of an international collaboration in which the Basel University Hospital participates. Data

concerning the efficiency of the method became available in late 1996.

On a clinical level, health insurance (compulsory in Switzerland) pays for at least two ultrasound examinations per pregnancy and generally covers maternal biochemical serum screening. When

invasive prenatal techniques are warranted on medical grounds (e.g. maternal age of at least 35, previous child with a chromosomal anomaly, increased risk on maternal serum screening), the

costs of the procedure, including counselling and genetic testing, are equally covered by most health insurance companies. In most other situations invasive prenatal diagnosis is not

reimbursed.

— Longitudinal Measurements of Pregnancy-Associated Proteins and Hormones (University of Zurich, FNSRS 32-40391.94);

— Nature and Role of Cytogenetic Anomalies in Fetoplacental Interactions (University of Geneva; FNSRS 32-40864.94);

— European Collaborative Study on Mosaicism in Chorionic Villus Sampling (EUCROMIC), EU Concerted Action BMH1-CT93-1673 (OFES grant 93.0337, University of Geneva).

Other projects are partially subsidised by university funding as some costs for technical development and improvement are absorbed in the operating budget of the university centres. Some

private subsidies (from pharmaceutical companies, for example) are equally available, but none, to our knowledge, currently funds research in the area of PND.

Interpretations of the Swiss National Abortion Law (Art. 120 StGB) in 1970 (a) and 1996 (b). The map shows counties with a liberal (white), intermediate (shaded) and strict (black)

interpretation of the law. From Dondénaz et al. [9], with permission.

A law limiting assisted procreation, voted by a majority of the Swiss people in 1992 (article 24 novies) specifically forbids pre-implantation diagnosis in either clinical or research

settings.

In early 1995, a federally commissioned study group on human gene research recommended that research directly related to PND and treatment be permitted on unimplanted human embryos

(resulting from in vitro fertilisation) throughout the blastocyst stage (14-day equivalent) [13].

On a short-term basis, a major lack is that of a comprehensive national registry for congenital anomalies and genetic diseases, including those detected prenatally. The absence of such a

tool seriously limits attempts at quality control of prenatal diagnostic procedures. Along the same line are the lack of political initiatives and of funding for the development and

improvement of prenatal diagnostic techniques.

One of the problems with a decentralised system of hospital care is that of education; only a small number of individuals can be trained in the few existing university centres. There is a

need for centralisation in the care of high-risk cases and the development of additional centres for perinatal medicine [1]. In our opinion, the greatest challenge we face — which will

become even more critical with the development of additional and more efficient methods of pre- and postnatal diagnosis — is the dearth of trained individuals working in the various fields

touching prenatal diagnosis. Specifically, no recognised medical training programme exists in human genetics: clinical genetics is not recognised as a medical subspecialty and those who

practice it are either trained on the job or in foreign centres. This is also true for cytogenetic and molecular genetic laboratory personnel; criteria have been recommended by the SSGM for

their training and quality control of the services, but have not yet been recognised and implemented.

Just as serious on a long-term basis is the complete lack of paramedical specialists such as genetic counsellors and genetics nurses. Education of the medical public and genetic counselling

for the lay public will be such a pervasive need that development of paramedical degrees in medical genetics should have a high priority.

We would like to thank numerous colleagues from the Medical Genetics and Obstetrics and Gynaecology Departments of the University Hospitals for their devotion to developing prenatal

diagnostic techniques in Switzerland. Several of these individuals, as well as those from the commercial cytogenetics laboratories, provided information cited in this article. We would like

to thank the OFES (grant No. 93-0337 to C.D.B.) for funding our participation in the workshop on PND in Europe, organised by the concerted action project EUCROMIC (BMH1-CT93-1673) and held

in Paris in May 1996; this article was written as an extension of that workshop.

Division of Medical Genetics, University of Geneva Hospital, Geneva, Switzerland, CMU, I, rue Michel-Serve!, CH-1211

Department of Obstetrics and Gynaecology, Zurich University Hospital, Zurich, Switzerland

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