Duo test / Combined test » Amnio and CVS give certainty?
The first trimester scan was introduced with the primary purpose of dating pregnancies by measuring the exact length of the fetus. In the last ten years, improved quality in the resolution of scanning equipments, have allowed us to describe normal fetal anatomy and diagnose or predict most of the main fetal defects between 11 and 13 weeks of pregnancy.
When a complex structure, such as an organism, or a simple form such as a house is being built, we can expect some imperfections, which can be due to a supply of the wrong materials (in which case the chromosomes) or the erroneous assembly of materials that have been provided correctly (this would be the most probably occurrence).
An invasive procedure (amnio/villocentesis) does not detect fetal malformations, which for simplicity we can define as irregularities in the building of the fetus’s structures. Invasive procedures would only check whether the bricks (chromosomes) are adequate both in number and quality. Therefore amniocentesis can only identify chromosomal defects, which are produced at the time of conception, when chromosomes are formed in an erroneous qualitative and quantitative manner as in the case of trisomy 21. Amniocentesis does not detect anomalies in the formation of organs, for example a congenital heart disease, which has a higher probability of occurrence than the chromosomal one.
The role of the 20 weeks scan, which is also known as morphology scan, is to identify major structural anomalies. However the study of nuchal translucency has demonstrated that majority of important fetal defects can also be identified with the study of fetal anatomy at 12 weeks.
When opting to have an invasive procedure, it is also preferable to do a villocentesis, which does not carry higher risks than amniocentesis; in fact the possibility of obtaining results early, has very important both physical and psychological advantages. In Italy, amniocentesis is generally performed 10 times more than villocentesis.(cvs)
MATERNAL FETAL COMPLICATIOSN OF AMNIOCENTESIS
LOSS OF HEALTHY FETUSES
In order to establish the safety of amniocentesis in the second trimester, many studies, which involved the reporting of various miscarriage risks in percentages were conducted. The only controlled study (the procedure was offered to a group of people and not to another group of the same number of people), was conducted in Denmark and involved a total of 4606 women with low risk (<35 of age). In this study, the percentage of fetal death was higher in the group who were offered amniocentesis (1.7) than the other group (0.7). However given the many technological advancements (for example thinner niddles) available today, this number may be seen as an overestimation of the actual risk.
More recent studies, by using a similar statistical method have concluded that the percentage of fetal death associated with the procedure is approximately 0.5%, but there is still no agreement on this figure.
To conclude, although the exact risk of fetal death following an amniocentesis remains controversial, the procedure is not harmless and can add to the risk of fetal miscarriage by 1% (the British national guideline of 2005 gives a risk of 0.9%)
(expected in 1 for every 1000 examinations)
The chorion-amnionitis post-amniocentesis (0.5-1.5 for every 1.000 examinations) occur due to the skin flora or intestinal contamination, more rarely due to prolonged loss of amniotic fluid. The initial signs can be underestimated (mild fever, flu like symptoms); however if ignored can be cause for severe infection and maternal sepsis. If a woman who recently had an amniocentesis shows signs of fever, she should undergo a further test, which will involve new extraction of amniotic fluid. Where there is an infection, the pregnancy should be immediately terminated and the uterus emptied.
LOSS OF AMNIOTIC FLUID
The loss of amniotic fluid, following an amniocentesis in the second trimester, occurs in 0.8-2% with an additional risk of 1% to pregnancies. Compared to the spontaneous membrane rupture the loss of fluid following an amniocentesis has a more benign course and in most cases is resolved within few days.
(Expected 2 %)
Vaginal bleeding is experienced by 2-3% of patients and is almost always spontaneously resolved.
HOW ACCURATE IS AMNIOCENTESIS?
THE FAILURE OF CULTURES
Failure (0.2-0.6%) is mostly due to insufficient number of cells, the inability of cells to grow in culture or contamination by infectious agents. Most culture failures can be avoided by extracting enough amniotic fluid during the procedure.
(false negatives 1/20.000) (examinations that need to be repeated 244 = 0.2%)
False negatives can be estimated as 1 in twenty thousand and can occur due to maternal cell contamination or wrong interpretation of the mosaicism. When there is a prenatal mosaicism (0.1-0.3% of cases), the chromosomal defect can either involve the fetus or be confined to the area surrounding the embryo. Therefore, in order to clarify the clinical significance of the result, further investigation, which includes fetal tissues (e.g. blood) will need to be conducted. By mosaicism we refer to the presence of two or more cells of two genetically different types in the same individual (if this anomaly is found on culture alone, it can be considered as an error). A true fetal mosaicism is found in ony 60-70% of cases.
The possibility of transplacental hemorrhage (2-3 cases) following an amnio, makes the test a cause for rhesus immunization. Anti-D prophylaxis is therefore advised to all women with Rh negative who had an invasive procedure and that have not previously been sensitized.
Amniocentesis and CVS in twins
It is possible to chariotype and obtain reliable results from amniocentesis done on twin pregnancy with a risk of miscarriage of approximately 2%. villocentesis in twin pregnancy also carries 2% risk of miscarriage, however in almost 1% of cases it is possible to find a diagnostic error due to double sampling from the same placenta or cross-contamination of samples. Therefore amniocentesis is preferred.
However, in twin pregnancies in which one of the fetuses has a chromosomal anomaly while the second is normal, the patient has the option of having a selective termination of the affected fetus, or choose to carry both twins expecting that they will both make it to full term.
With selective termination (just one of the twins) after 16 weeks, the risk of miscarriage becomes three times higher compared to a selective termination before 14 weeks. Subsequently, if the parents decide to do a prenatal diagnostic test, it would be preferable to do a villocentesis. The result in this case will be available within 13 weeks of pregnancy while with amniocentesis results would only be available after 16-17 weeks of pregnancy.
1.Royal College of Obstetricians and Gynaecologists. Amniocentesis and chorionic villus sampling. London: RCOG; 2005 [leggiil testointegrale in PDF, 181 Kb]
2. Dugoff L, Hobbins JC. Invasive procedures to evaluate the fetus.ClinObstetGynecol 2002;45:1039-53
3. Eisenberg B, Wapner RJ. Clinical proceduress in prenatal diagnosis. Best Pract Res ClinObstetGynaecol 2002;16:611-27
4. Alfiveric Z. Amniocentesis and chorionic villus sampling for prenatal diagnosis.The Cochrane Database of Systematic Reviews 2003, Issue 1
For more information please refer to the bibliography.