National Organisation

Italy has 58 million inhabitants with about 560,000 births per year. The birth rate is 9.6 per thousand and the fertility rate 1.26 per woman. The median maternal age at delivery is 29.4 years.

The first Italian cytogenetic laboratories were created in the early sixties, while the prenatal diagnosis (PND) services date back to about the mid-seventies, often in association with the organisation of genetic counselling centres. Molecular genetics laboratories were set up starting about in 1985. All these experiences were initiated by researchers employed in biological or clinical institutes of public universities where most scientific research is done in our country. As soon as the results of basic research could be utilised for clinical (mainly diagnostic) applications, a number of laboratories arose initially in the public care services and subsequently in private structures, with a different distribution in various parts of Italy, probably because of territorial and historic conditions, often creating situations poorly controlled by organisms responsible for public health. Medical genetics is also an independent medical speciality since 1980.

On the basis of the observation that about 9–10% of the Italian women are older than 35 years at the time of delivery, we can roughly estimate a request of 55,000–60,000 prenatal cytogenetic analyses per year for pregnancies at risk for fetal chromosomal disorders; 60–70% of these requests are covered by PND public services, especially in some northern areas. Actually, the number of PND performed in Italy is certainly much higher, probably reaching 80,000 examinations per year because a number of non-high-risk-pregnancies are investigated in private laboratories.

Sources of Information

Until 1985, there were no data regarding cytogenetic laboratories in Italy. Thanks to the direct interest of some scientific societies, such as the Italian Association of Medical Cytogenetics, the Italian Association of Medical Genetics (AIGM), the Italian Society for the Study of Metabolic Hereditary Diseases, and the Italian Society of Gynaecology and Obstetrics, it was possible to identify public and private structures interested in genetic counselling and pre- and postnatal diagnosis of genetic disorders. Particularly in the cytogenetic field, periodic surveys by AICM have enabled one to evaluate the cytogenetic examinations carried out in 1985, 1989 and 1991 (fig. 1, table 1).

Fig. 1.
figure 1

Prenatal cytogenetic examinations in Italy (1985–1991).

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Table 1 Genetic investigations
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Results from extensive inquiries concerning not only the cytogenetic but also the biochemical and molecular biology laboratories have been published thereafter [1]; they refer to 1992 (table 2); an update made in 1995 is being elaborated and will be available in Internet as soon as possible. The above-mentioned volume lists the public and voluntary associations which operate in the scientific research field and/or in the care of subjects affected by specific genetic disorders which have brought about the creation of these associations due to their frequency and social impact.

Table 2 Italy (1992)
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Concerning congenital malformations, there is an epidemiological system of survey that has been created in 1978 as regional registers (fig. 2). A national integration of these registers started in 1982–1983 with the co-ordination of the Epidemiological and Biostatistical Laboratory of the ‘Istituto Superiore di Sanità’, which founded a national archive of malformations. In 1989–1990 a coverage of 30.6% of the total number of newborns registered by ISTAT was reached, with the regional distribution shown in figure 3. Some of these registers including that of Umbria (Umbrian Investigation of Congenital Malformations) participate in the project of European Registration of Congenital Anomalies of Twins (Eurocat), which has access to 25 European registers. The Italian Multicentric Investigation for Congenital Malformations and the Emilia-Romagna Investigation for Congenital Malformations registers participate in the International Clearinghouse for Birth Defects Monitoring System, affiliated to WHO from 1986. However, there are no organised registers, at the regional or national level, concerning PND.

Fig. 2.
figure 2

Italian registers of congenital malformations (1992). IMER = Emilia-Romagna Investigation for Congenital Malformations; IUMC = Umbrian Investigation for Congenital Malformations; IPIMC = Italian Multicentric Investigation for Congenital Malformations; ISMAC = Sicilian Investigation for Congenital Malformation.

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Fig. 3.
figure 3

Regional coverage (%) (1989–1990).

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Concerning the incidence of the various chromosome syndromes, there have been multicentre retrospective or prospective studies, performed for limited periods of time, because of lack of funding. One of the most important studies was carried out by the Italian Group of Embryo-Fetal Diagnosis (table 3).

Table 3 Study of the Italian group of Embryo-Fetal Diagnosis on 6,858 PND
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In 1993, the Study Group on Prenatal Diagnosis of the European Association of Perinatal Medicine published a booklet on Recommendations and protocols for prenatal diagnosis [2, now under second revision].

Impact of PND

The Italian Policentric Investigations on Congenital Malformations published data concerning the impact of PND on chromosomal diseases, particularly on Down’s syndrome, from 1978 to 1992. According to this investigation, the maternal distribution curve shifts toward older ages, observed in this period, that may have produced an increase (16.4%) of Down’s syndrome among life-births. At the present time, an opposite effect is observed due to the increasing use of PND and thus selective pregnancy interruptions. The latter would have produced a decrease of 15%, while associated with the shift of maternal age at delivery; in reality it has had an increased effect (29.1%). Because this phenomenon does not involve women less than 35 years old, but only women between 35 and 39 years, the decrease can be estimated at 36 and 76.1% in women more than 39 years old.

The Istituto Superiore di Sanità, as the co-ordinator for the regional registers, published data concerning the trend of incidence for the most important malformations at birth from 1986 to 1990 [3]. As may be seen in figures 4a, b, this evaluation shows a substantial decrease in the incidence of most of the listed anomalies due to the impact of PND, particularly when associated with other malformations.

Fig. 4a,b.
figure 4

Trend of incidence for the most important malformations at birth (1986–1990). ○ = Multiple; ■ = single; △ = total.

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In Umbria, with the increasing number of intra-uterine malformations, the implementation of PND during the last decade has resulted in a decrease in the birth rate of malformed newborns.

Available Diagnostic Procedures and Current Methods

In Italy there are 780 maternity care units, 161 (21%) perform level 2 and 3 echography and 117 (15%) carry out invasive procedures for prenatal diagnosis. Whereas all these centres can perform amniocentesis (AC), only 24% offer chorionic villus sampling (CVS) and 15% fetal blood sampling (FBS). One hundred and eighteen cytogenetic laboratories, 27 of which are private, are involved in fetal karyotyping. For the invasive procedures there is an imbalance in the regional distribution: the percentage is high in the north (52%), low in the south and islands (32%) and even lower in the centre (16%).

Cytogenetic PND in public services is allowed for the following indications: maternal age 35 and over, previous child with a chromosomal anomaly, parent with a constitutional chromosomal abnormality and abnormal findings at ultrasound examinations. Guidelines for the different parts of cytogenetic diagnostic investigations have been recently published by AICM in Analysis [4].

Biochemical marker screening on maternal blood has been approved by a recent law for women at the 15th–16th week of gestation; however the criteria for the administration of the so-called triple test and the related invasive PND in the Public Service are still under discussion at the regional level.

Areas under Development

As regards the new approach to fetal tissue sampling, apart from the classical methods (AC, CVS and FBS), we (at the Centre of Perinatal Medicine, University of Perugia) are starting to evaluate the new amniotic fluid sampling technique with amniotic fluid filtration and re-injection into the amniotic cavity, from 12 to 14 weeks of gestation. There are other centres (Rome, Dallapiccola) in which some researchers are testing the sampling of transcervical cells, while others (Perugia, Milan) are trying to test the possibility of isolating fetal cells from maternal blood. New diagnostic techniques are beginning to be used such as 3D sonography and first-trimester sonography.

As these procedures are still experimental, the results have not been codified.

Funding and Legislation

The PND centres are financed by Regional law, the National Health Service and private funds, especially if experiments on new technologies are being applied. All the tests are reimbursed (including serum marker screening, but excluding fetal karyotype after serum marker screening). Three ultrasound examinations are reimbursed: one per trimester (in complicated pregnancies, the number is not limited).

There is a current law surrounding PND as far as termination of pregnancy is concerned (Law 194/1978). This law permits voluntary interruption of pregnancy within the first 90 days, while after 90 days (till 25 weeks) it permits it only for severe fetal anomalies and over 25 weeks, in case of serious risk for the woman’s life.

There is no law for pre-implantation diagnosis, but there are some Italian centres which are trying to apply pre-implantation diagnosis (Milan, Bologna and Turin). A law issued in 1984 has established rules for private but not for public genetic services.

Problems and the Future

Presently, the major problem is financing, secondly, correct prenatal counselling, especially in central/southern Italy, where counselling is lacking and where most pregnant women are invited to undergo prenatal diagnostic procedures more for implementing private funding or for reasons such as the anxiety of the patients, than for a correct genetic counselling. Therefore we have to solve the problem of the unbalanced distribution of financial resources, and also to create guidelines for an adequate prenatal counselling.

For the future, we believe that the best results in this field are probably related to the advances of research (we have a target programme of the Italian National Research Council called ‘Genetic Engineering’, which is in its 4th year of financing) and which aims at improving the capacity of the PND centres to detect more congenital anomalies with good quality control and less expenses.