The term prenatal diagnostics or prenatal diagnostics (abbreviation PND ; composed of the Latin prae “before” and natal “birth”, see prenatal and diagnostics ) denotes examinations on fetuses and pregnant women (see also early detection of diseases ).
Common methods are, on the one hand, the non-invasive examinations carried out only from outside the body, such as ultrasound examinations (sonography), which include measurement of the neck transparency , measurement of the nasal bone (in the 12th to 14th week of pregnancy), fetometry , fine ultrasound , and Doppler -Sonography , which includes 3D ultrasound and the 4D ultrasound . Tests of hormone concentrations in maternal blood ( serological tests ) such as the triple test , the quadruple test and, as a combination of both methods, first trimester screening (ETS, an examination in the first trimester of pregnancy) and integrated screening (combined examination the biochemical serum parameters to determine the risk of fetal chromosome and occlusion disorders) belong to the non-invasive methods. The non-invasive diagnosis also includes the prenatal paternity test , which is possible from the 9th week of pregnancy , in which fetal DNA is isolated and analyzed using a blood sample from the mother. Invasive examinations of prenatal diagnosis, i.e. examinations carried out inside the body, are chorionic villus sampling (CVS), amniocentesis (AC) and umbilical cord puncture . An earlier method of prenatal diagnosis was amnioscopy .
|Research in reproductive medicine|
Prefertilization diagnosis :
examination of the egg cell before fertilization
Pre-implantation diagnosis :
Prenatal diagnosis :
The first amniocentesis for prenatal diagnosis was carried out in 1930 by Thomas Menees and others. The basis of modern prenatal diagnostics was laid by the British obstetrician Ian Donald in 1958 with the first sonographic representation of an unborn child. The technical advancement of the ultrasound devices enabled a high resolution of details and thus the detection of structural malformations of fetal organs with high diagnostic reliability. The diagnosis was of abdominal wall breakthroughs, diaphragmatic hernias, displacements of the heart axis, malformation of organs such. B. the lungs or kidneys , cyst kidneys , malformations of the extremities , obstructions in the gastrointestinal tract, etc. possible.
The non-invasive ultrasound technology has been expanded with the development of invasive techniques. In 1966, Steele and Breg demonstrated the possibility of taking and chromosomal examination of fetal cells contained in the amniotic fluid ( amniocentesis ) during the second trimester of pregnancy. The publication of the chorionic villus sampling followed in the early 1980s . In this procedure, cells are removed from the villi of the egg membrane ( chorion ) during the first trimester of pregnancy , which later forms the placenta . These cells are cultivated and subjected to genetic analysis. Later, with the early amniocentesis, 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 followed.
More recently (as of 2006), fetal MRI has also increasingly been available as a non-invasive diagnostic tool. The basis for the assignment is often suspected sonographic diagnoses . The clarification of rare syndromes is possible with high diagnostic certainty using MRI.
So far, invasive examination procedures with different risks depending on different factors, e.g. B. that of a miscarriage burdened. As a result, in addition to the global basic need of prospective parents to have a physically and cognitively healthy, non-disabled child and the desire to know about the child's state of health, the weighing up between the risks of the examination and the likelihood of a certain disability plays a role plays an important role in the decision about whether to use an invasive examination.
However, this can have far-reaching social and legal consequences: those doctors who advise against invasive examinations such as amniocentesis or chorionic villus sampling are sometimes faced with claims for damages when a child is born with a disability that can be identified through the examination . This is one of the reasons why a nationwide range of prenatal examinations with a high level of diagnostic certainty has now been established in Germany, which sometimes gives the impression of "avoidability" of children with disabilities due to the high level of awareness of various examination methods.
Search tests such as the double test , triple test and the measurement of the nuchal transparency as part of the first trimester screening are currently popular as risk-free but non-diagnostic examinations . They provide information about a possible chromosome peculiarity or certain physical malformations , e.g. B. in the area of the spinal canal , the abdominal wall and the kidneys. The extent to which these procedures are to be applied across Germany as part of maternity care is still the subject of controversial ethical and health policy discussions.
Since the beginning of the 1990s, intensive research has been carried out worldwide into non-invasive examination methods (NIPT), in which the genetic material of the fetus can be extracted from cells in the blood of the pregnant woman and examined for genetic deviations without risk in order to use invasive procedures with a risk of miscarriage To avoid chromosome extraction. According to Hepp, this method was in clinical testing in 1999.
Researchers at Stanford University in California , according to their own statements, succeeded in 2008 in enriching the fetal cells that were present in the mother's blood, subjecting them to a DNA analysis and thus making many invasive examinations carried out for this purpose superfluous. The NIPT procedure was successful in detecting 12 different chromosomal disorders.
In the case of non-invasive (= not penetrating the pregnant woman's body) examinations, such as a maternal blood examination ( NIPT ) and an ultrasound examination such as According to the current state of knowledge (2014), e.g. when measuring the neck transparency, there are no risks for the unborn child or its mother.
In various medical textbooks with a research status of 2000, 2005 and 2007, the amniocentesis (amniotic fluid puncture ) and the chorionic villus sampling are each assumed to have an abortion risk of around 1%.
According to more recent studies, invasive (penetrating into the body of the pregnant woman) diagnostic interventions such as amniocentesis, chorionic villus sampling or umbilical cord puncture hardly pose any risks to the fetus.
In a study in 2006, 35,003 unselected pregnant patients from the normal population were examined. It found that the risk of miscarriage in patients who did not undergo amniocentesis was 0.94%, while the risk of miscarriage in the women in the study group only increased to 1.0%. Amniocentesis showed no statistically significant effect on the risk of miscarriage in this study .
Another study from 2006, in which 9,886 chorionic villus sampling and 39,893 amniocentesis were evaluated, shows that there is no significant difference in the risks between the two examination methods.
Until a meaningful test result is obtained, there is sometimes a restricted mother-child relationship due to the socially and personally at least latently assessed as “pregnancy on trial”. An emotionally strong bond is sometimes only permitted if the findings are normal, which means that the option of terminating the pregnancy in the event of an abnormal finding is kept as open as possible emotionally. Sometimes the time until then is psychologically difficult for the pregnant woman; "Most guilty feelings arise from the feeling of having put the child up for discussion", since the health of the fetus is seen as the decisive criterion for its acceptance or rejection. On the other hand, an inconspicuous finding helps reassure the parents. Expectant parents are advised to take advantage of counseling services before using prenatal diagnostics. It is advisable to go to a genetic counseling center, especially if there is a family history .
Maternity guidelines in Germany
The examinations to be used during pregnancy are described in the so-called “ maternity guidelines” (guidelines of the Federal Committee of Doctors and Health Insurance Funds, 1999; see also illustration). These examinations include the medical history interview , a general medical examination, various serological examinations such as tests for infectious diseases such as rubella , HIV , hepatitis B and toxoplasmosis (if there is justified suspicion) and for the presence of maternal blood group antibodies that could lead to a lesion of fetal erythrocytes, three ultrasound examinations , one of which is used explicitly to detect physical malformations ( fine ultrasound ), and so on. If there are any indications of a high-risk pregnancy due to the check- ups , e.g. B. arise due to malformations of the child, the doctor is required to inform the pregnant woman about the possibilities of a human genetic counseling and a human genetic examination by chorionic villus sampling , amniocentesis or the like. to enlighten.
Possibilities, limits and social impact
Parents-to-be face various questions and decisions. The first question that arises is whether a prenantal examination should be carried out and which factors speak for or against an examination. If a prenatal examination is to be carried out, a personal assessment of the examination results obtained and a weighing up for or against further measures follow in addition to the medical advice. Doctors and prenatal diagnosticians are also challenged in prenatal diagnostics with regard to professional and ethical issues.
The result of a prenatal examination obtained can provide information on possible complications during childbirth or a possible illness. For example, information about a possibly difficult birth and / or immediately necessary postnatal treatment can be obtained. In another case, indications of chromosomally caused disabilities or diseases can be obtained. As a rule, the examinations provide results in the form of probabilities ; an example: a couple has a first trimester screening carried out. The result provides a probability of 1: 300 that you could have a child with trisomy 21 . Based on the test results obtained, the genetic history of the parents, the age of the mother and the confidence in the test procedure (keywords true positive rate and false positive rate ), the parents - possibly in combination with the attending doctor - can make a decision about further measures .
Parents without specific risk characteristics have an average probability of around 3% [ country, other dependent factors and source desired ] of having a child with a disability. Possible reasons include possible birth complications (approx. 2-3%) or genetic diseases (approx. 0.3 to 1%) [ source desired ]. For prenatal diagnoses such as heart defects , spina bifida and cleft lip and palate, there are treatment options for causal or complete healing . For a large number of other peculiarities that can be diagnosed prenatally, there are neither prenatal treatment options through therapy in utero nor postnatal therapies for causal or complete healing (see also medical indication ). A not insignificant part [ how much concrete and source desired ] of the pathological diagnoses made thus ultimately remains without the possibility of adequate or causally healing medical-therapeutic intervention . Some parents decide to terminate the pregnancy based on the prenatal diagnosis of possible disability, malformation, or disease of the fetus [ country and source desired ]. For some parents, the postnatal release for adoption or the transfer of the child to a foster family is an alternative if they do not want to or cannot adopt the child themselves.
Example: Prevention of Thalassemia in Cyprus
Cyprus is a country with a particularly high prevalence of β-thalassemia major , an inherited blood disease that can only be treated with great effort. At the beginning of the 1970s it became apparent that the number of sick people rose rapidly with new therapies because they survived longer and longer. It was expected that the number of sick people would double in about 8 years, so it was foreseeable that the costs of caring for thalassemia sufferers would lead to the collapse of the health system without further measures.
That is why there has been an education and voluntary genetic screening program in Cyprus since 1976, and prenatal diagnostics have also been systematically expanded. Genetic tests, prenatal diagnostics and an eventual abortion are free. For some years now, pre-implantation diagnostics have been available as an alternative in Cyprus instead of prenatal diagnostics with subsequent abortion . Couples who want to have children and both partners are carriers are advised to have a voluntary prenatal diagnosis in a consultation. About 200 such prenatal examinations are carried out each year for the presence of thalassemia and lead to an abortion in about 50 cases each year.
Initial resistance from the Orthodox Church to the threat of an increase in the number of abortions was overcome to such an extent that, since 1983, the Church has required all bridal couples to certify that they have participated in the screening and receive appropriate human genetic counseling before they marry . In fact, apparently some couples (less than 3%) do not marry after such counseling.
All of these measures made it possible to reduce the number of new cases per year from 70 per year in the mid 1970s to around 2 per year today. Spending on the thalassemia drug deferoxamine has halved , and the number of patients has been constant for some time at around 630. Since almost every family in Cyprus is affected by thalassemia, there is no significant resistance among the population to this voluntary eugenics . Almost every adult resident of marriageable age knows their own thalassemia status based on a genetic test, so they know whether they are the carrier of the genetic defect.
Critics of prenatal diagnostics point out that the diagnostic possibilities of prenatal examinations give society the impression that disabilities and malformations are avoidable: “For example, it seems to be developing subtly that pregnant women are made responsible for a healthy one, with all possibilities medicine to have a clear baby ”and“ ignorance .. increasingly seen as guilt or liability ”. These tendencies have already been confirmed in practice: One study found that the vast majority of parents of a child with Down syndrome (72% of the mothers surveyed, 100% of the fathers surveyed) now answer the question after the birth sees confronted why one would not have used prenatal diagnostics.
In cultures where the society expects women to have sons (e.g. countries like China , India ), an abortion is often initiated as soon as prenatal examinations announce a girl. Reinforced by the one-child policy , z. For example, in China there are 12 boys for every 10 newborn girls. In many countries, prenatal diagnostics are only permitted to a limited extent in order to prevent the lack of women as a resulting long-term social consequence.
- Screening , first trimester screening , double test , triple test , neck transparency (NT screening / neck fold measurement), hygroma colli , dorsonuchal edema , hydrops fetalis , soft marker , chorionic villus sampling , amniocentesis , FISH test (prenatal rapid test ), therapy in utero
- Preimplantation Diagnostics , Prenatal Paternity Test
- Termination of pregnancy
- Reproductive medicine
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