Proceedings of the EUCROMIC Workshop on Prenatal Diagnosis

Registration of prenatal diagnostic (PND) procedures, abnormal and ambiguous diagnoses, and outcome of pregnancy is of importance to genetic centres as well as policy-makers. In European countries, this registration varies considerably: some countries compile detailed data from all centres each year, while in others there is no central registration. Within these extremes, there are various levels of registration.

One of EUCROMIC goals is to obtain an overview of the PND activity in Europe for the project period 1993–1995. The data reported from the participating 78 centres represent, but do not cover the entire activity. Consistent with the EUCROMIC goals, the intentions for a workshop on PND in Europe was (1) to increase the level of information on PND between the EU countries; (2) to create a forum for exchange of experience with national registers; (3) to unveil the present state: what are we actually doing? and (4) to support the start of new registers, revive prior registers and increase the efficiency of existing registers; could we do better?

In Amsterdam, November 6, 1995, an organising committee consisting of Segolène Aymé, Nico J. Leschot, Gordon Lowther and Lars O. Vejerslev decided to pursue the goals through a closed workshop in Paris, May 23–24, 1996. The invited participants, selected according to scientific criteria and active involvement in PND, were one geneticist and one gynaecologist/obstetrician from each of the EU countries. Besides, observers from non-EU European countries and related concerted actions were encouraged to participate and contribute. The delegates (table 1) were asked to prepare a paper addressing the following questions at the workshop and in the proceedings:

Table 1 Participants in EUCROMIC workshop on PND, Paris 1996

• (1) What sources of information are available at the local, regional, or national level? What data relevant to PND are systematically collected?

• (2) What is the impact of prenatal diagnosis on the prevalence of chromosomal disorders and severe malformations?

• (3) Which diagnostic procedures are available for fetal karyotyping, biochemical serum screening, ultrasound screening/diagnosis, and molecular diagnosis?

• (4) What are the current methods in use for PND (amniocentesis, chorionic villus sampling, cordocentesis), and what are the professional guidelines?

• (5) What areas are under development (interphase cytogenetics, fetal cells in maternal circulation, first-trimester biochemical screening, others)?

• (6) What are the funding arrangements for PND?

• (7) What is the current legislation surrounding PND for termination of pregnancy and for pre-implantation diagnosis?

• (8) What are the problems you have to face in the future in your own country, and how do you see the future?

For the proceedings, the authors were furthermore asked to include an introduction on the national organisation of PND, a list of indications for PND, the psychosocial impact of PND, and the topic of counselling. They were also asked to give the name of a third person, who could act as independent reviewer of the information given in the paper.

Evidently, it has been a tremendous task for the authors to collect this amount of data on a nation-wide scale. None of the papers provide complete information on all topics, which is mainly due to lack of central registration or considerable variation between countries and regions.

After reviewing all manuscripts, we have designed a number of tables in order to summarise some of the many data. These tables were sent to the authors for corrections/completion. Unfortunately, Austria though present at the workshop, was unable to prepare a formal manuscript.

Table 2 illustrates the great variety of the number of genetic centres in relation to the total population in each country. Since the definition of a ‘genetic centre’ differs between the different countries, this is only a very rough estimate. At the extreme ends of the spectrum are Finland/Luxembourg each with 1 centre for every 400,000 people and the Netherlands with 1 centre for every 1,900,000 people. In 9 countries there are only public genetic centres, in the other 6 countries private laboratories exist in addition to public centres.

Table 2 Population and number of public and private genetic centres

Some form of central data collection of diagnostic prenatal chromosome studies exists in 8 countries (table 3). For prenatal molecular studies such a registration exists in only 5 countries. The registration of the invasive obstetrical procedures and of ultrasound screening is only carried out in a minority of the 15 countries. Biochemical maternal serum screening seems not to be registered at a national level at all.

Table 3 Central registration of PND and screening

In table 4, the number of pregnancies that were actually examined by an invasive obstetrical procedure (i.e. amniocentesis and chorionic villus sampling) is compared with the total number of pregnancies in each country for the years 1993–1995. Again, great difference among the 15 countries are evident. This time, the extreme ends of the spectrum are Norway/Portugal each with 2.3% invasive procedures and Italy with 14.2% invasive procedures (including a number of cordocenteses). In all countries, the annual number of amniocenteses that was carried out exceeded the number of chorionic villus sampling.

Table 4 PND by amniocentesis (AC) or chorionic villus sampling (CVS) related to births per year a, b

The national screening strategies are summarised in table 5. Even for the almost ‘classical’ maternal age indication for the detection of fetal Down syndrome, there are differences between the 15 countries, varying from ≥ 35 years to >38 years in most countries to an unspecified ‘advanced’ maternal age in the UK. Maternal serum screening is organised as a local programme in 3 countries, and widely (but not universally) available in the UK, France and Italy. The number of ultrasound examinations per pregnancy is listed in this table too and varies from 0 to 3 to ‘unlimited’.

Table 5 National screening strategies in each country

There is more or less consensus over the indications for PND by an invasive procedure as is illustrated in table 6. It is interesting to note that in 12 of the 15 countries an abnormal result after maternal serum screening is an indication for invasive prenatal chromosome studies. In 14 of the 15 countries, an indication for prenatal chromosome studies exists if ultrasound examination has revealed a fetal anomaly. In some countries, a chromosomal or monogenic disease among close relatives is an indication for PND. In other countries, additional examinations are indicated in the first place to reveal whether or not the pregnant woman is really at risk for that particular disease.

Table 6 Indications for prenatal diagnosis by invasive procedure

Quality assessment is summarised in table 7. Only 2 countries have developed criteria for the quality control of ultrasound diagnosis in pregnancy. In 5 countries professional and technical guidelines exist for the application of invasive obstetrical procedures. For the control of the quality of the work in the laboratories, guidelines (or more sophisticated control systems) have been developed in 8 countries. In 10 of the 15 countries Medical Genetics or Clinical Genetics is recognised as an official medical (sub)-speciality. Standard psychological support for women who undergo termination of pregnancy on a genetic indication is available in only 5 of the 15 countries.

Table 7 Quality assessment or demands at the national level

The present legislation for termination of pregnancy in the 15 countries is listed in table 8. The application of PND is seriously hampered by the legislation for termination of pregnancy in only one country. In Portugal termination of pregnancy is not allowed after 16 weeks. This is a problem when an abnormal test result is found after second-trimester amniocentesis. Legislation for pre-implantation diagnosis exists in 7 of the 15 countries.

Table 8 Legislation for termination of pregnancy and for pre-implantation diagnosis

Finally, the funding of PND in the 15 countries is summarised in table 9.

Table 9 Funding of PND

It is the hope of the organisers of the workshop in Paris that the detailed overview of the situation for PND in Europe, as presented in this supplement issue, can have the function of a basis. This basis can be used as a starting point, both by geneticists and gynaecologists and by the responsible policy-makers, when recommendations are being formulated for this rapidly developing diagnostic field.