Introductory Remarks

In Norway, genetic prenatal diagnosis (PND) is at present conducted in three laboratories. These are located in Oslo, Bergen and Tromsø. According to decisions of the Norwegian Parliament (‘Stortinget’), the costs of PND in these laboratories are covered by the Government of Norway. The laboratory in Oslo has been manned and equipped for 750–800 annual analyses whereas the laboratories in Bergen and Tromsø, respectively, have been manned and equipped for 500 analyses each. Approximately 80% (about 1,100) of the cases accepted for PND each year are examined in our Department of Medical Genetics, Ullevål University Hospital, which together with the Institute of Medical Genetics, University of Oslo, forms a World Health Organization Collaborating Centre. Norway is diveded into 5 ‘health regions’ and 3 of these regions are served by the Department of Medical Genetics, Ullevål University Hospital (until 1989 this department served the whole of Norway). The remaining approximately 20% of PND are conducted in the laboratories in Bergen and Troms0, the former laboratory conducting about 160 analyses per year and the latter, about 110 analyses per year. These figures refer only to genetic PND where a laboratory analysis is carried out on fetal material. Ultrasonography, primarily to date the pregnancy, is conducted in about 98% of pregnancies in Norway.

PND in Norway is regulated by the law on ‘Medical Use of Biotechnology’ of August 5, 1994. This law requires genetic counselling in connection with genetic tests. Medical genetics is officially recognized as a medical specialty since 1971.

Sources of Information

The indications for genetic PND in Norway are stated in a letter to all Norwegian physicians from the government’s Director of Health, dated December 30, 1983. The indications stated in the letter are: (1) couples with a previous child with a chromosomal disorder; (2) couples with a previous child with a neural tube defect; (3) couples with a previous child with a metabolic disorder where prenatal diagnosis is possible; (4) couples with a previous child with an X-linked disease or where it is known that the woman has a high risk of being a carrier for an X-linked disease; (5) couples where the man or woman is a carrier of a balanced chromosomal anomaly, and (6) couples at increased risk of a chromosomal disorder in the fetus, due to maternal age (age above 38 years at delivery). Since the letter stating the indications dates back to 1983, the new indication of ‘findings at ultrasonography suggesting a genetic disorder or malformation in the fetus’ is not included.

Data on PND are as yet not systematically registered in Norway. However, the three national/regional laboratories will report on their activities every year. Since 80% of genetic PND are conducted in our centre, the annual report from our centre will adequately reflect trends or changes in PND in Norway.

Since the 1960s, an obligatory national register of newborns’ health including any malformation has been in operation (‘Medisinsk Fødselsregister’). In this register, information on any disease or malformation diagnosed at birth or immediately thereafter is recorded. One aim with this register was to be able to detect any changes in the frequency of disorders or malformations detectable at birth.

A general register of persons with monogenic disorders was introduced by the health authorities at the Institute of Medical Genetics, University of Oslo, in the 1950s. Reporting to this registry was strongly recommended by the government’s Director of Health but reporting was not made mandatory, so registration was never complete. Over the last 15 years or so, the legal basis for the registry has become unclear because of application to medical registries of data protection laws primarily created for other purposes. Some unfortunate consequences of present laws and practices are at present under consideration.

As yet there is no single register for PND. Each of the three laboratories involved does report annually and previously those reports were amalgamated into a joint report by a governmental commission (‘Etterprøvingsutvalget for medisinsk-genetiske servicefunksjoner’) which was recently abolished. Plans are now being developed to provide national registration of outcome of pregnancies where PND were conducted, probably to be implemented by the same registry that handles obligatory records on the medical condition of newborns in Norway.

Whereas there is a yet no single database for the whole of Norway, the annual reports from our centre account for 80% of all genetic PND conducted in Norway. Couples’ choices with respect to continuation of pregnancies or otherwise if an affected fetus has been detected are not adequately recorded, since there is no obligation on departments of obstetrics and gynaecology to report back to us the outcome of pregnancy once an affected fetus has been detected.

There is no information available on Internet.

There are a number of lay groups in Norway and one outstanding example is the lay group for families with Huntington’s chorea (‘Landsforeningen for Huntingtons sykdom’). These and other organisations (for example concerning muscular diseases, haemophilia or growth retardation) may keep registers and do an important job in informing the public, physicians and paramedical personnel as well as institutions.

Impact of Prenatal Diagnosis

The number of newborns in Norway is slowly increasing and was 60,092 in 1994. All available information from the period before PND was started suggested that the prevalence of chromosomal disorders or neural tube defects in newborns was the same in Norway as in most other Western European countries.

Because there is as yet no central registry of PND or their outcome in Norway, it is not possible to precisely answer the question of the impact of PND on the prevalence of chromosomal disorders. However, the centre conducting 80% of PND in Norway (on 1,151 fetuses in 1995), has detected about 50 fetuses with a chromosomal anomaly per year over the last several years, the figures being 57 and 52 in 1994 and 1995, respectively. The number of fetuses detected with trisomy 21 was 17 in 1994 and 19 in 1995. Although it is not obligatory for departments of gynaecology and obstetrics to report back to our centre, such information as we have (on the majority of cases) indicates that nearly all women carrying a fetus with an anomaly of the autosomal chromosomes opt for abortion.

The impact of genetic PND on the frequency of severe malformations is modest. Neural tube disorders are not frequent anomalies in Norway, occurring about once in 1,000 births. Spina bifida and anencephaly are about equally frequent, each condition having a frequency of about 1 in 2,000 births. Since there is no maternal screening in Norway, an effect of PND on the prevalence of neural tube disorders could only result from PND in women who have already given birth to a child with a neural tube disorder, from random findings where the indication for PND was not related to risk of neural tube disorder (we conduct α-fetoprotein determination on all amniotic fluids received for prenatal diagnosis) or from ultrasonography conducted at a handful of centres specialising in detecting malformations. In the centre conducting 80% of PND in Norway, 1–3 cases of neural tube disorder in the fetus have been discovered per year over the last several years.

The impact of PND in terms of frequency of other disorders is by necessity very low (since the risk situation will only rarely be known prior to the birth of an affected child).

PND with selective abortion is accepted with respect to Huntington’s disease but also in this area, the impact in terms of frequency of birth of children with a mutant genotype is very small.

Available Diagnostic Procedures

Fetal karyotyping and α-fetoprotein determination have been available since 1971, and both procedures are carried out on any samples received. The age criterion for genetic PND is strict. Thus, PND based on maternal age is only offered to women who will be 38 years or older at the time of delivery. There is a trend towards conducting amniocentesis (AC) early in pregnancy and at present a great number of AC are carried out at around 13 weeks of pregnancy. Placental biopsies are carried out in approximately 40 women per year, women at particularly high risk being preferentially offered this procedure.

Fluorescence in situ hybridisation (FISH) analyses are available for a number of disorders as are diagnostic procedures using DNA technologies.

Biochemical screening with respect to neural tube disorders or chromosomal anomalies in the fetus is not conducted in Norway at present, because of an ambivalent attitude towards such studies (the resources and the knowledge to conduct such studies would obviously be available).

Ninety-eight percent of pregnant women in Norway undergo ultrasound examination whose main purpose is to correctly date the pregnancy. However, to an increasing degree, the National Ultrasound Centre as well as some of the other centres are detecting anomalies or malformations that could be genetic or chromosomal in nature. This development is reflected in the fact that over the last several years our centre, which conducts 80% of the PND in Norway, has annually examined from 40 to 50 cord blood samples from pregnancies where the indication had been that suspicion of a genetic anomaly had arisen at ultrasonography.

Resources are adequate for molecular diagnosis at the level of DNA and PND is conducted for cystic fibrosis, Duchenne muscular dystrophy, fragile X, Prader-Willi-Angelmann syndromes and several other disorders.

In principle, any woman at risk of having a fetus with a known mutation causing a serious disorder may be examined today in one of the three centres conducting PND, as long as the specific mutation is known. Enzymatic analyses are conducted for only a handful of disorders.

Current Methods in Use for PND

All traditional methods are available. The quality of laboratory analyses is believed to be adequate.

The centre conducting 80% of genetic PND in Norway analyses samples from AC from 4 different departments of obstetrics and gynaecology, from chorion biopsies from one department and from chordocentesis from two departments of obstetrics and gynaecology.

No specific professional guidelines with respect to sampling techniques exist, as yet. The involved departments are, however, working according to well-established international practices, but there is a need to establish minimum standards for annual numbers of examinations to be conducted, for a department to maintain the capacity to adequately conduct the procedure in question. The need for European guidelines would be obvious here as well as with respect to acceptable indications for PND.

Areas under Development

FISH methodologies are being actively pursued and interphase cytogenetics is being conducted at an experimental level.

At present, there is no specific effort to examine fetal cells in the maternal circulation, but the field is being actively followed and work in it will be started when sufficient evidence of its potential reliability, and technologies useful for practical diagnostic work become available.

The leading fetal ultrasonography team is working actively on developing reliable first-trimester ultrasonography technologies. There is considerable activity towards standardizing early AC in the gynaecological/obstetrical departments collaborating with our centre.

There is no work aiming at establishing first-trimester biochemical screening of maternal serum because of the ambivalent attitude towards screening at large that prevails in Norway at the present time.

Pre-implantation diagnosis will doubtless come, but has as yet not been carried out.

Funding Arrangements for PND

PND on the restrictive indications listed above are paid for by the Government. Women seeking prenatal diagnosis or their families are not being charged at any level.

Prior to 1995, the Government paid for all expenses incurred by the three laboratories conducting PND without negotiations. As of 1995, a lump sum is provided for PND. The formula for dividing the lump sum between three laboratories provides the laboratory that conducts 80% of prenatal diagnosis with only 50% of the funds set aside for this purpose. At our centre, we hope that we will see a percent allocation of available funds that reflects the actual number of analyses conducted at the centre in the near future.

At present, there is some uncertainty as to what the near future will bring with respect to payment for diagnostic procedures. For the last 15–16 years, PND has doubtless been a service that has been offered without any discrimination.

The system for public funding or reimbursement for medical laboratory analyses is presently under examination and it is somewhat uncertain what the preferred solutions will be over the next few years.

Current Legislation Surrounding PND

Assisted procreation, genetic testing and PND are all regulated by the law on ‘Medical Use of Biotechnology’ of August 5, 1994.

Termination of pregnancy is at the woman’s request in the first trimester of pregnancy. Thereafter, decisions about termination of pregnancy are made by a small commission. The risk of a serious genetic disorder in the fetus, as well as the total medico-social condition of the woman are among the criteria that the commissions should evaluate and they are expected to put particular emphasis on the woman’s own evaluation of the situation. With serious genetic disorders, the general experience is that the commissions accept termination of pregnancy up to around the 18th to 21st week of pregnancy. Rejection of application to discontinue pregnancy may be appealed. There is no list of conditions accepted as indications for PND.

Pre-implantation diagnosis is in principle acceptable by law but it is not encouraged by the law-makers, presumably because it is expected to be too expensive. However, there is ambivalence towards ‘manipulating nature’.

The law on ‘Medical Use of Biotechnology’ appears to limit medical uses of biotechnology to diagnostic or therapeutic purposes and this problem area is under reconsideration. The law requires informed consent for genetic tests to be conducted.

Problems and the Future

The Government’s position in Norway until now has been that one should take a restrictive attitude towards PND, for example to accept the maternal age indication only for women who will be 38 years or older at delivery. This strict rule is at variance with rules in countries we usually compare ourselves with and represents a strange deviation from the parallelism that can otherwise be seen between Nordic countries. One strong reason for this difference between Norway and other Nordic countries may be the particular status that the abortion issue has had and has in Norway. This issue has been extremely strongly influenced by Christian fundamentalists who, although limited in number, have a rather strong voice. This issue has been elaborated on by K. Berg and K.E. Tranøy in the book by Wertz and Fletcher: Ethics and Human Genetics (Springer, Berlin, 1989).

One major ethical problem is that with such strict limitations to PND, it is extremely difficult to fulfil the wish in governmental and other quarters of equal access to this service. A reasonable level of ‘distributive justice’ appears to be difficult to achieve if the volume of PND is too small. There is clearly a need for a somewhat more liberal attitude towards PND if ‘distributive justice’ is to be achieved in Norway.

Other problems relate to shortage of highly qualified personnel to conduct the necessary analyses in Norway. Only one centre possesses top academic qualifications in cytogenetics, molecular genetics, biochemical genetics and genetic counselling (the centre that conducts 80% of PND in Norway).

The restrictive attitude towards PND in several quarters in Norway, which is often echoed in the media, constitutes a problem by itself, for people who for their own sake and the sake of their family want PND, but still feel that they may be ‘doing something wrong’ by ‘interfering with nature’.

The future is likely to lead to developments which in the long run will make the conditions in Norway more similar to those in our neighbouring countries. This development should happen soon because it is a significant problem that women who do not qualify for PND with the present strict rules in Norway go abroad to have PND (if they can afford it), a development that violates the principle of equal access to medical genetics services.