Translucencia Nucal » DNA en Sangre Materna
Traducción:Dr. Jesús Rodriguez Calvo
Las técnicas no invasivas para la detección de aneuploidías usando ADN fetal libre en sangre materna podrían aportar una serie de ventajas
importantes frente a la obtención del cariotipo a través de amniocentesis biopsia del corion, como menor número de complicaciones del parto, riesg de pérdida fetal y molestias físicas y psíquicas a las embarazadas.
Evitar la realización de pruebas invasivas en los casos en que la existencia de aneuploidías fetales fuese descartable a través de la extracción de
sangre materna, supondría una ganancia en términos personales, temporales y económicos, motivos para evaluar la posibilidad de inclusión de esta nueva
técnica diagnóstica dentro del protocolo de diagnóstico prenatal.
En dicho contexto se justifica la necesidad de revisar la evidencia disponible sobre la seguridad, eficaci y efectividad de las nuevas técnicas
de diagnóstico de aneuploidías usando ADN fetal libre en sangre materna, que hagan posible un diagnóstico acertado, disminución de la ansiedad materna por el procedimiento invasivo y posibilidad de daño fetal.
NIPT is a Non-Invasive Prenatal Test (NIPT) performed on maternal blood to screen pregnancies for the most common fetal chromosome anomalies : trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome), monosomy X (Turner syndrome), XXY (Klinefelter syndrome) and XYY syndrome.
NIPT is performed on a maternal blood sample which contains DNA from the fetus. During pregnancy, there are cell-free DNA fragments (cfDNA) from both the mother and fetus in maternal circulation. It is possible to analyze cell-free DNA to detect fetal trisomies such as Down syndrome (trisomy 21).
Although NIPT can be performed in all pregnancies without specific indication, it might be most appropriate in pregnancies with an increased risk for fetal Down syndrome, trisomy 18, or trisomy 13 based on first trimester screening for Down syndrome. In these cases NIPT is an alternative to chromosome studies after amniocentesis or chorion biopsy (CVS).
NIPT is not a advised when there are:
Fetal anomalies on ultrasound
Severely elevated NT (nuchal translucency)
Known genetic anomalies that cannot be diagnosed by NIPT
During pregnancy, there are fetal cells and cell-free DNA fragments (cfDNA) from the fetus in the maternal circulation. DNA isolated from maternal blood therefore not only contains maternal DNA but also a small amount of fetal DNA : the fetal fraction of cell-free DNA in maternal blood from week 10 on is about 10-15% of all cell-free DNA. It is possible to analyze this cell-free DNA to detect fetal trisomies such as Down syndrome (trisomy 21).
20 ml blood (2 tubes) from the mother has to be taken into specific blood tubes The maternal blood can be taken from week 10 of the pregnancy.NIPT takes 2 weeks to complete from arrival of the sample in the lab to the result report.
Reliability of NIPT results
The reliability of NIPT results is very high.
The sensitivity of NIPT to exclude Down syndrome (trisomy 21) is > 99%, which means that less than 1 pregnancies on 100 with Down syndrome is not detected with NIPT (false negatives).
If NIPT is normal, the residual risk for trisomy 21, trisomy 18, trisomy 13, monosomy X, XXY syndrome and XYY syndrome is < 1 on 10.000.
The specificity of NIPT for the 3 chromosomes tested (chromosomes 21, 18, 13, X and Y) is > 99%, which means that in less than 1 on 100 pregnancies an abnormal NIPT result is obtained although the fetus has normal chromosomes (false positives).
NIPT test failure
In a limited number of pregnancies (< 5%) not enough fetal DNA can be extracted from the maternal blood, and NIPT cannot be performed. This has no implications on the risk of fetal aneuploidies or other fetal anomalies. In these pregnancies NIPT can be repeated at no extra cost on a repeat maternal blood sample.
Limitations of NIPT
Samples are analyzed for aneuploidy of chromosomes 21, 18, 13, X and Y. Aneuploidy of other chromosomes, other chromosome anomalies including mocaicism for chromosomes 21, 18, 13, X and Y, molecular anomalies or congenital anomalies including neural tube defects might be present.
Advantages of NIPT versus amniocentesis or chorion biopsy
Procedures such as amniocentesis or chorion biopsy (cvs) are invasive procedures that carry a slight risk for miscarriage. NIPT is non-invasive as only maternal peripheral blood is necessary, and is therefore a procedure without any risk to the fetus.
NIPT results will be sent to the patient and/or physician who ordered the test and who will explain the test results and recommended follow-up steps if necessary. At that time the patient can also request to reveal the genetic sex of the baby.
Follow up steps after NIPT
1. In case of a normal NIPT result: no specific follow up is necessary unless ultrasound examination of the fetus reveals anomalies and further fetal studies might be indicated.
2. In case of test failure: in a limited number of pregnancies (< 5%) not enough fetal DNA can be extracted from the maternal blood, and NIPT cannot be performed. This has no implications on the risk of fetal aneuploidies or other fetal anomalies. In these pregnancies NIPT can be repeated at no extra cost on a repeat maternal blood sample.
3. In case of an abnormal NIPT result: in case of an abnormal result, the physician or genetic counseler will discuss the implications of such chromosomal anomaly with the patient, who can then decide to confirm the NIPT results with chromosome studies after amniocentesis or chorion biopsy. Fee is around 700$/Euro