Prenatal diagnosis

The term prenatal diagnosis ( PND abbreviation, composed of Latin prae / before and natal / geburtlich, see prenatally, as well as diagnostics) referred to studies of the unborn child ( fetus ) and pregnant women ( see also early detection of disease ).

Common methods are, firstly, the non-invasive, made ​​only outside the body examinations such as ultrasound ( sonography), to which the nuchal translucency measurement, the nasal bone measurement ( in the 12th to 14th week of pregnancy ), the fetometry, the fine ultrasound, the Doppler ultrasound, 3D ultrasound and 4D ultrasound are. The studies of hormone concentrations in maternal blood ( serological tests ), such as the triple test, the quadruple test and a combination of both methods, the first-trimester screening (ETS, an investigation in the first trimester ) and the integrated screening ( combined study the serum biochemical parameters for determining risks for fetal chromosomal disorders and closure ) are among the non-invasive methods. As well to the non- invasive diagnosis of one possible starting from the 9th week of pregnancy prenatal paternity test, is isolated and analyzed for the fetal DNA based on a maternal blood sample. Invasive, that is within the body of the investigations carried out prenatal diagnosis are chorionic villus sampling (CVS), amniocentesis (AC) and the umbilical cord puncture.

• 4.1 Example: Prevention of thalassemia in Cyprus
• 4.2 General debate
• 4.3 Legal restrictions

• 6.1 guidelines
• 6.2 criticism

• 7.1 criticism
• 7.2 New non- invasive methods ( maternal blood test for fetal DNA )

History

Preimplantation genetic diagnosis: Examination of the embryo prior to implantation in the womb

Prenatal diagnosis: Examination of the fetus before birth

The basis for prenatal diagnosis put the British obstetrician Ian Donald in 1958 with the initial sonographic presentation of an unborn child ( Hepp, 1999; Kowalcek, Bachmann & Mühlhof, 1999). The technical development of ultrasound devices allowed for a high detail resolution and therefore the detection of structural abnormalities of fetal organs with high diagnostic accuracy. Thus, the diagnosis of abdominal wall openings, diaphragmatic hernia, displacements of the heart axis, malformation of organs such as the lung or kidney disease, polycystic kidneys, malformations of the extremities, obstructions in the gastrointestinal tract, etc. have been possible.

The non-invasive ultrasonic technology has been extended by the development of invasive techniques. So Steele and Breg (1966 ) demonstrated the possibility of withdrawal and the chromosomal analysis of fetal cells contained in the amniotic fluid ( amniocentesis ) during the second trimester of pregnancy. The early 1980s was followed by the publication of chorionic villus sampling by Ward et al. (1983 ) and Rodeck et al. (1983). In this method, cells from the villi of the caul are removed ( chorion ) during the first trimester of pregnancy, the placenta is the later. These cells are cultured and subjected to a genetic analysis. Later followed with early amniocentesis ( Hanson et al., 1987), the puncture of fetal vessels and fetal organs as well as the withdrawal of blood from the umbilical cord further measures for the removal of fetal cells ( Hepp, 1999).

More recently (as of 2006) is increasingly on fetal MRI as a non- invasive diagnostics. Often provide a basis for the allocation represents the clarification of rare syndromes is possible using MRI with high diagnostic accuracy sonographic suspected diagnoses.

So far, invasive examination method with different and dependent on various factors risks, such as the miscarriage charged. This caused usually plays alongside the world's existing basic need of prospective parents to get a physically and cognitively healthy, non- disabled child, and the desire for knowledge of the state of health of the child, the balance between the risks of the study and the probability of a certain disability in deciding on the use of invasive investigation an important role.

However, this can have far-reaching social and legal consequences: Those doctors who advise against invasive examination such as amniocentesis, chorionic villus sampling, or, look at the birth of a child with detectable by examining disability occasionally exposed to claims for damages. Also why a comprehensive range of prenatal tests with high diagnostic accuracy has been established in Germany now that sometimes the impression of " preventability " of children with disabilities mediated by the now fairly high level of awareness of different investigation methods ( Honnef Elder, 2000).

As a risk-free, but non- diagnostic section are currently screening tests such as the triple test and the nuchal translucency measurement in the context of first- trimester screening popular. They indicate a possible chromosome specific or certain physical defects, eg in the area of the spinal canal, the abdominal wall and the kidney ( Stengel - Rutkowski, 1997, Sherer et al. 1999). To what extent these practices will be applied nationwide in Germany as part of prenatal care, is still the subject of controversial ethical and health policy discussions ( Winter 2000).

Already controversial, although not yet fully developed, but most intensively researched, is a research method in which can be extracted the genotype of the fetus from cells in the blood of pregnant women and risk examined for genetic variations, so non-invasive methods are applied with a miscarriage risk for chromosome extraction need. This case is by Hepp (1999) is currently in clinical trials and it is not yet clear whether it is possible to adjust the procedures to market.

Researchers at the Stanford University in California has succeeded claims to 2008, isolated to enrich fetal cells in maternal blood known to undergo DNA analysis and so much to do a lot of analysis done for this purpose, invasive investigations unnecessary. The procedure was successful in the detection of 12 different chromosome disorders.

Application risks

Non-invasive investigations

In non-invasive ( = not penetrate into the body of the pregnant woman ) studies, as a study maternal blood and even with an ultrasound examination made ​​according to present knowledge (2005), no risks for the unborn child and its mother.

Invasive investigations

Invasive ( in the body of the pregnant woman penetrating ) tests such as amniocentesis ( amnio ) and chorionic villus sampling or the umbilical cord puncture include according to recent studies, very little risk to the fetus.

Were examined in a study of 35 003 unselected pregnant patients from the general population. It turned out that the risk of miscarriage in patients who did not perform amniocentesis was 0.94%, whereas the risk of miscarriage increase with the women of the study group, only 1.0%. Amniocentesis showed in this study no significant effect on the risk of miscarriage. Another study, in which 9,886 Chorionzottenbiopsien and 39 893 amniocenteses were evaluated showing that there is no significant difference in risk between the two methods of investigation. In several medical textbooks, however, intervened conditional risk of abortion are accepted for amniocentesis and chorionic villus sampling for each about 1%.

Mental stress

Up to a meaningful examination result is sometimes a limited parent -child relationship by the socially and personally, at least latently as " tentative pregnancy " rated basis. An emotionally strong bond is partially allowed only when findings are unremarkable, making the termination of pregnancy option will be kept open emotionally as much as possible with abnormal test result. We sometimes until then psychologically difficult for the pregnant woman the time; "From the feeling that you have put the child up for grabs, most adult guilt " because the health of the fetus is regarded as the decisive criterion for the acceptance or rejection ( Ringler, 1994, p 106). Expectant parents is recommended over the use of prenatal diagnosis to take advice offers. Especially with familial predispositions, it is advisable to consult a genetic counseling center.

Maternity policies in Germany

The applicable during the pregnancy tests are in the so-called " maternity Guidelines " ( guidelines of the Federal Committee of Physicians and Sickness Funds, 1999; see also Figure ) described. These studies include the history taking, a general medical examination, various serological tests such as tests for infectious diseases such as rubella, HIV, hepatitis B and toxoplasmosis ( reasonable suspicion ), a test for immunological defense reactions between mother and child, three ultrasound examinations, one of which explicitly for detection of physical abnormalities is (fine ultrasound) etc.. If there is evidence of a high-risk pregnancy, eg due to malformations of the child arise due to the checkups so the doctor is held, the pregnant woman on the possibilities of genetic counseling and a human genetic study by chorionic villus sampling, amniocentesis, or the like. educate.

Possibilities, limitations, social impact

Is a set of parents have no specific probability increase is to get with disabilities with them, the average base risk of about 3 %, a child. This is due to possible birth complications ( 2-3 %) or genetic disorders ( approximately 0.3 to 1%) due. Besides the example of heart defects, spina bifida and cleft lip and cleft palate, there are a variety of other prenatally diagnosable features neither prenatally through therapy in utero or by postnatal therapy treatment options causal or complete healing. A not insignificant part of the identified pathological diagnoses therefore ultimately remains without the possibility of reasonable cause or curative medical and therapeutic intervention, so that the diagnosis of a disability, deformity or disease of the fetus often leads to termination of pregnancy ( medical indication ) [Source desirable ]. This discrepancy is for expectant parents, but not least for the attending physician and Pränataldiagnostiker, a personal and professional challenge.

Apart from a gain of information about a potentially difficult birth and / or immediately necessary postnatal treatment is due to its particular in chromosomally -related disabilities and diseases of the abortion, the most common consequence of which is drawn from the knowledge of the disability or illness of the unborn child. For some parents the postnatal child for adoption or the delivery of the child in a foster family an alternative if they do not wish to accept even the child or can.

Example: Prevention of thalassemia in Cyprus

Cyprus is a country with a particularly high prevalence of β - thalassemia major, an inherited blood disorder that should be treated only with very great effort. In the early 1970s, it became clear that new therapies, the number of patients rose rapidly because they survived longer. It was expected to double the number of sufferers in about 8 years, so it was foreseeable that the cost of care of Thalassämieerkrankten would result in no further action to the collapse of the health system. Since 1976, there are about Cyprus, a program to educate and voluntary genetic screening and prenatal diagnosis was also targeted manner. The genetic testing, prenatal diagnosis, and a possible abortion are free. For several years, preimplantation genetic diagnosis is available as an alternative to Cyprus instead of prenatal diagnosis followed by abortion. About 200 Prenatal tests are performed per year for the presence of thalassemia and run annually in about 50 cases to an abortion. Initial resistance of orthodox church against an imminent expansion of abortions has been made to overcome that since 1983 the church requires all newly wedded couples before marriage a certificate of participation in the screening and appropriate genetic counseling. In fact, apparently forego some couples ( under 3 %) after such consultation on a marriage.

Through all these measures, a reduction in the incidence of 70 per year in the middle of the 1970s could be achieved today about 2 per year. The expenditure for the Thalassämiemedikament deferoxamine decreased by half, the number of patients at about 630 Da to Cyprus almost every family is constantly affected by thalassemia for some time, there are against this voluntary eugenics no significant resistance in the population. Almost every adult population of marriageable age knows due to a genetic testing its own thalassemia status, do so if he is a carrier of the gene defect.

General debate

Be critics of prenatal diagnosis should be noted that the diagnostic possibilities of prenatal examinations in society arises the impression disabilities and deformities are preventable, "It appears, for example, subtly develop that pregnant women are held responsible for a healthy, with all the possibilities to get to the medicine mellow baby " and" "is ignorance .. increasingly seen as a liability or blame. In practice, there are already confirmations of these tendencies: Thus, in a study of Lümkemann was (2001) found that in the meantime the vast majority of parents of a child with Down syndrome (72 % of the mothers interviewed, 100% of the fathers interviewed ) to confronted with the question of birth can see why one would have taken any prenatal diagnostic services.

Legal restrictions

In cultures with the social expectation for women to give birth to sons (eg, various Asian countries such as China, India), an abortion is often initiated as soon as antenatal announce a girl. Reinforced by the one-child policy are, for example in China on 10 newborn girls 12 boys. To prevent lack of women as a resulting societal long-term consequence, in many countries, prenatal diagnosis is only allowed restricted.