Prenatal Diagnosis in Italy | European Journal of Human Genetics

ABSTRACT In Italy, there are about 560,000 births per year. The number of prenatal diagnoses (PND) performed is estimated at 80,000 examinations per year, but no official data are available

regarding the distribution of the different procedures. There are no official registers, either at a national or at a regional level, concerning PND and particularly the invasive procedures

(as amniocentesis, chorionic villus sampling, chordocentesis). Thanks to the direct interest of some scientific societies, such as the Italian Association of Medical Cytogenetics, the

Italian Association of Medical Genetics, the Italian Society for the Study of Metabolic Hereditary Diseases and the Italian Society of Gynaecology and Obstetrics, it has been possible to

identify the number and distribution of public and private structures interested in genetic counselling and prenatal diagnosis during the last decades. As to the congenital malformations,

there is a regional epidemiological system of surveys (started in 1982) co-ordinated by the Epidemiological and Biostatistical Laboratory of the ‘Istituto Superiore di Sanità’ (National

Board of Health). This institution has published data for the period between 1986 and 1990 concerning the trend of incidence for the most important malformations at birth. 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 the ultrasound examinations. Current methods in use consist in echography, amniocentesis, chorionic villus sampling, fetal blood sampling and maternal serum screening.

At the moment, new approaches to the fetal tissue sampling are, as follows: amniotic fluid filtration, transcervical cell sampling and isolation of fetal cells from maternal blood.

Furthermore, areas under development are 3D sonography and first-trimester anatomic survey sonography. PND is financed by regional laws, the National Health Service and private funds. There

is a current legislation on termination of pregnancy (Law 194/1978). This law permits voluntary interruption of pregnancy within the first 90 days, while it is permitted between 90 and 180

days only in cases of severe fetal anomalies and over 180 days for serious risks for the woman’s life: but it is necessary to do everything to save the fetal life. No law has been issued yet

on pre-implantation diagnosis. Presently, the major problems are: the unbalanced distribution of financial resources among the different regions, the irrational number and distribution of

centres for PND, inadequate prenatal counselling, especially in central/southern Italy, where counselling is somehow lacking. Therefore, guidelines for appropriate prenatal counselling

should be established. For the future, we believe that the best results in this field are probably related to the advances of research (there is a target programme of the Italian National

Research Council called ‘Genetic Engineering’, which is in its fourth year of financing). This programme will hopefully be cost-effective and improve the quality of PND so that more

congenital anomalies can be detected at lower expenses in the future. You have full access to this article via your institution. Download PDF SIMILAR CONTENT BEING VIEWED BY OTHERS DOWN

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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). 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. 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. 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). 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. 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. REFERENCES * Dagna Bricarelli F, Dallapiccola B: Malattie genetiche: Guida ai Servizi

Diagnostici ed alle Associazioni. Ministero della sanità e Associazione Italiana Ricerca, Prevenzione e Cura Handicap (AIRH), 1994. Google Scholar  * Carrera JM, Di Renzo GC: Recommendations

and protocols for prenatal diagnosis. Report of the European Study Group on Prenatal Diagnosis of European Association of Perinatal Medicine, 1993. Google Scholar  * Meli P, DeSpagnolo A e

Gruppo Collaborativo dei Registri Italiani sulle Malformazioni Congenite, Sorveglianza delle malformazioni congenite in Italia (1986–90). Revisione e standardizzazione delle metodologie di

rilevamento e risultati deU’esperienza collaborativa con i Registri italiani. Istituto Superiore di Sanità, 1993. * Associazione di citogenetica medica. Diagnostica citogenetica. Consensus

1995. Analysis 1995;8:3–25. Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Centre of Perinatal Medicine, University of Perugia, Perugia, Italy G. Clerici, 

E. Donti & G. C. Di Renzo * Division of Gynaecology and Obstetrics, Hospital of La Spezia, La Spezia, Italy A. Zacutti Authors * G. Clerici View author publications You can also search

for this author inPubMed Google Scholar * E. Donti View author publications You can also search for this author inPubMed Google Scholar * A. Zacutti View author publications You can also

search for this author inPubMed Google Scholar * G. C. Di Renzo View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Clerici, G., Donti, E., Zacutti, A. _et al._ Prenatal Diagnosis in Italy. _Eur J Hum Genet_ 5 (Suppl 1), 42–47 (1997).

https://doi.org/10.1007/BF03405960 Download citation * Issue Date: January 1997 * DOI: https://doi.org/10.1007/BF03405960 SHARE THIS ARTICLE Anyone you share the following link with will be

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initiative KEY WORDS * Prenatal diagnosis * Genetic disorders * Congenital malformations * Genetic counseling * Cytogenetics