Prenatal Diagnosis

Prenatal Diagnosis (PND) cover the entire investigation performed in the pregnancy period focusing on identifying the presence of fetal anomalies, if any risk factor is present. There are several investigation techniques that are prescribed according to what must be investigated, the pregnancy time, or any other technical or anatomic characteristic that might make a procedure unfeasible, leading to the choice of another.

Prenatal diagnosis indications
1 – Pregnant women of 35 years old or older (with increased risk of fetal chromosomal anomaly);
2 – Couples in whose previous pregnancies presented fetal or newborn chromosomal anomalies;
3 – At least one member of the couple bearing balanced chromosomal rearrangement;
4 – Couples with history of diseases related to the “X” chromosome (Muscular Dystrophy, Hemophilia);
5 - Couples with family history of Mental Retardation related to the “X” chromosome (X-fragile);
6 - Couples with previous children bearing innate metabolism error (related to X or recessive autossomic);
7 – Pregnant women with child (fetus) that present(ed) multiple malformations;
8 – Pregnancies in which are diagnosed fetal anatomic anomalies, amniotic fluid amount changes, placenta anomalies or intra-uterine growth retardation in routine prenatal ultrasonometry;
9 - Pregnant women with suspect of infection during the pregnancy (toxoplasmosis, rubella or cytomegalovirus);
10- Pregnant women exposed to drugs;
11- Consanguineous couples;
12- Alloimmunizated pregnant women (Rh negative exposed to Rh positive blood).

Prenatal trials that can diagnose or exclude genetic fetal anomalies.

- Chorionic villus sampling (CVS);
- Amniotic fluid sampling (AMNIOCENTESIS).

Chorionic Villus Sampling (CVS)

What are Chorionic Villus?
CHORIONIC VILLI (or chorionic villus) is the denomination given to the placenta up to 12 weeks of pregnancy. It is also called trophoblast, it is derived from the trophectoderm, genetically representing the fetus.

What is Chorionic Villus Sampling (CVS)?
Chorionic Villi Sampling is the collection of a placenta tissue under ultrasonometric view for prenatal genetic analysis. The sample can be collected through TRANSABDOMINAL duct (from 11 weeks of pregnancy, including second and third quarters of pregnancy). The procedure is standardized and was introduced in Brazil in 1985 by Dr. Gollop. In this period, about 6,000 samples have been analyzed successfully in our clinic, proving the efficiency and safety of those early procedures used for fetal genetic analysis.

To whom is this test prescribed?
CVS must be prescribed when there is an increased risk of chromosomal anomalies or genetic defects to the birth (see indications), and couples who need the earliest diagnose possible. Another prenatal trial, amniocentesis, may diagnose the same anomalies, but is performed in later pregnancy stages.

What is the material used in the analysis?
The Trial is performed with a small fragment of fetal villi (a few milligrams), that are part of the tissue that unites the gestational sac to the womb walls. The lab will analyze the cells that compose the villi, which normally have the same genetic and biochemical construction of the embryo.

Which tests can be performed?
The villus sample collected allows for a fetal chromosomal examination (karyotype), as well as DNA analysis in cases of hereditary genetic diseases (Mental Retardation related to the X chromosome, Muscular Dystrophies, Cystic Fibrosis and, currently, through partner centers, a series of molecular analyses involving numerous diseases), and biochemical analyses for innate metabolism errors.  The karyotype obtained in the chorionic villus represents the fetal karyotype; false-positives and false-negatives are rare. In about 1.5% of the cases an ambivalent result is found, that is, cells with normal karyotype next to cells with abnormal karyotype; this finding is named chromosomal mosaicism. In these cases, an additional test is prescribed,  amniocentesis, for diagnosis confirmation, and a more rigorous Ultrasonometric control, since the implications of such mosaicisms in the fetal development are being discussed, for example its association with retardation and intra-uterine growth. It is also possible the use of chorionic villus sampling to determine intra-uterine paternity. The delivery time for the karyotype result varies between 7 and 10 days (when necessary, preliminary results can be provided before this period). The delivery times of other tests will be provided to the patient when they are performed.

How is the sample removed?
After asepsis and under Ultrasonometric view, for transabdominal samples, a 20-gauge needle is inserted. Once the chorionic plate is reached, the material is sucked to a syringe containing culture medium. There is no need for anesthesia. Generally, the sample removal can generate a slight discomfort to the patients.

Is it a safe procedure?
About 200,000 women around the world have been subjected to the Chorionic Villus Sampling since its introduction, in 1983. Studies correlating risk of fetal loss after test and the CVS have shown that operator experience is one of the most important factors.

Papers released until 2007 show that the risk of gestational loss related to chorionic villus sampling is 0.5 to 1%, maximum.
Given the precocity of the test and the quick access to results, several countries in the world, such as Japan and the United States, have given preference to tests such as the CVS (Evans, personal communication, 2005).

Amniotic Fluid Sampling (AMNIOCENTESIS)

What is amniocentesis (Amniotic Fluid Sampling)?
AMNIOCENTESIS is a medical procedure that consists in an abdominal puncture in the patient for collecting a Amniotic Fluid (AF) sample, contained inside the chorionic-amniotic cavity, in which the fetus is completely submerse since the beginning of pregnancy. Amniocentesis is a well known and standardized test, but it has the disadvantage of being performed in a later stage of the pregnancy, that is, after 15 weeks, and takes an average 20 days to show results.

To whom is this test prescribed?
AMNIOCENTESIS must be prescribed when there is an increased risk for chromosomal anomalies or genetic defects in birth (see indications). Women who prefer amniocentesis are generally those who are less concerned with early diagnosis.

What is the material used in the analysis?
Cells found in the Amniotic Fluid, in suspension, come from fetal skin, mucous membranes, urinary tract and upper respiratory ducts, and, therefore, represent the fetal genetic construction.

Which tests can be performed?
When cultivated in appropriate media, cells allow the evaluation of the fetal karyotype. This prenatal test detects, with 99.9% accuracy, fetal chromosomal anomalies. In couples bearing genetic diseases, the test can also be performed with the purpose to investigate abnormal genes, proteins or biochemical levels. Diseases that can be investigated include Tay-Sachs disease, Cystic Fibrosis, etc. Congenital infections can be diagnosed by the analysis of this fluid through the PCR technique. The delivery time of the resulting karyotype varies between 15 and 20 days (when needed, preliminary results can be delivered earlier through a specific technique called FISH). The delivery times of other tests will be provided to the patient when they are performed.

How is the sample removed?
After asepsis and under Ultrasonometric view, an abdominal puncture is made with a 22-gauge needle and the amniotic fluid sample is removed (about 1ml per gestation week). There is no need for anesthesia. Generally, the sample removal can generate a slight discomfort to the patients.

Is it a safe procedure?
Amniocentesis is a very safe procedure, with estimated risk of spontaneous miscarriage of less than 0.5%, when performed by expert hands. It seems not to have statistically proved increased risk of fetal loss when comparing women that undergone traditional amniocentesis to the ones that didn’t undergo any prenatal fetal tests.