Thursday, 20 August 2020

NIPT-Noninvasive prenatal tests

 

Should a day come in 22 nd century where routine amniocentesis followed by preservation of “Amniotic Stem Cells” for later use if warranted??

 

Prenatal   diagnosis is the branch of medicine and in particular of obstetrics that studies and applies the techniques   that reveal the normality or the presence of disease of various   kinds. In the fetus all the techniques   of prenatal   diagnosis   are performed    during pregnancy   and may be invasive or less. Prenatal diagnosis of fetal genetic conditions   is a standard part of modern obstetric care. But unfortunately, many of the current methods rely on invasive   methods (CVS/amniocentesis) and  are associated with an inherent  risk of fetal loss. Consequently there has been   a long term   goal for development   of NIPD(Non Invasive prenatal  diagnois)   . What is cffdna test in maternal blood?  Recently an extremely sensitive test  for the most   common aneuploidies   and in particular.   Down syndrome  has been  proposed to be performed  on maternal blood.  This test   is based  on the count of fragments of specific   chromosomes in maternal   blood  although   not belonging to diagnostic  tests but to probabilistic ones  this test is absolutely the most accurate so far available  with values  around 99.99%   sensitivity and 0.2%   false   positives   . Also   ultrasound  in th second  trimester  of pregnancy      that can  detect  any malformation or fetal abnormality and fetal   echocardiography   which   analyzes sonographically the fetal heart  not only anatomically but also  from the dynamic functional point of view may be  considered   methods of prenatal diagnosis. This technique   cannot  identify  genetic   diseases.

 

Role of Molecular genetics ?? Ans:- The  phenomenal developments  in molecular genetics and technological  refinements which    have occurred  over the past  decades have    revolutionized   the area of prenatal genetics  , state of the  art care   commences  with  comprehensive   preconceptional  counseling  .

 

Conclusion:- Prenatal  diagnosis is now feasible  from the moment   of conception    onward   . Imaging   techniques   have allowed non invasive   diagnosis   while minimally invasive techniques concentrate on sampling   maternal   blood for fetal cells or markers of feto placental metabolism.

Invasive  techniques   have been   rapidly expanding   and becoming safer  comprising   of  A) chorionic   villus  sampling   B) early amniocentesis or C)  midtrimester   amniocentesis  as well as very early  fetoscopy and umbilical vein   sampling Advances in prenatal  diagnostic   techniques   allow for   earlier more   rapid and more   effective detection of congenital  disorders  Recent   advances  in non invasive   detection  methods such as fetal    ultrasound    and the isolation   of fetal cells in the maternal circulation   allow the intrauterine  diagnosis  of congenital infections and chromosomal  and Mendelian disorders  as well as   hematologic disorders.

We   currently have the potential to diagnose a number of others for which the opportunity has not yet arisen. If  A)  biochemical B) morphologic  C)  chromosomal or D) genetic:-deoxyribonucleic acid    alternation is known  for a specific condition   and is likely to be expressed in one of the fetal  tissues or secretions attempt    at prenatal diagnosis    is reasonable .

 

Forget CS /Lap ports!!!! Know what are gene probes???? Development  of specific  gene  probes  ::Diagnosis of inherited   disorders  in utero :--  Our   ability to    detect  the inherited   disorders  in utero   will continue to improve  both in the number of   specific  disorders   successfully diagnosed or excluded  and in the increasingly earlier  stages  of pregnancy  at which    the disorder can be detected. Non invasive  prenatal   testing   and non invasive approach   involves   analysis of   cell  free fetal   DNA  in maternal  plasma   or serum . Another   approach   utilizes fetal cells  within the  maternal circulation   as a source  of fetal DNA.  Advances in instrumentation have decreased the risk   of the invasive    methods of prenatal diagnosis   and improvement   in non invasive methods  such as maternal  serum screening  may eliminate the need  for invasive procedures  altogether   .

 

Detection of   useful DNA   polymorphisms linked to  genes for specific   diseases and development  of specific  gene  probes  have   improved  the accuracy  of diagnosis  and reduced the  need   for specific fetal   tissues. The   entire genome of an individual  is present   in each cell   even though    a specific   gene product  may not be   expressed  in that cell. Thus DNA   restriction  endonuclease studies    can be  performed  on amniotic  fluid  cells chorionic  villi fetal cells  in maternal     circulation  and fetal  tissues    with equal  facility.  The usefulness   of prenatal   diagnosis   will always be limited   by the ability   to detect   pregnancies   at risk. If carrier detection is unavailable   the only way to identify couples     at risk  for offspring  with an autosomal  recessive  condition  is by the birth   of an affected   child. For autosomal dominant and X linked   recessive and dominant conditions new mutations will continue to occur. As  mentioned previously  screening  of all pregnancies for  all defects  is not possible  now and is unlikely  ever to be feasible  either economically or technically . The   reliability of prenatal  diagnosis  will continue   to depend  upon accurate  diagnosis  in the index case  and upon the availability  of a specific and sensitive test  with no overlap in values between heterozygotes and homozygotes  for autosomal  recessive   conditions or between normal and affected fetuses   with autosomal   dominant and X linked  recessive  disorders . Correct  interpretation of test results is subject  to experience recognition  of artifact  and variation  in the expression of a given   disorder in utero.

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