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Prenatal diagnosis Dr Neda Bogari.

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1 Prenatal diagnosis Dr Neda Bogari

2 Prenatal diagnosis It’s the ability to detect abnormalities in an unborn child. Prenatal diagnosis is an option which is chosen by many couples at high risk of having a child with a serious hereditary disorder.

3 Techniques used in prenatal diagnosis
Non-invasive Maternal serum screening Α-fetoprotein Triplet Test Ultrasound Invasive Amniocentesis Chorionic villus sampling (CVS) Fetoscopy

4 Invasive techniques

5 amniocentesis It involves the aspiration of 10-20ml of amniotic fluid through the abdominal wall under ultrasound guidance. It usually performed around the 16th week of gestation. The sample is spun down to yield a pellet of cells and supernatant fluid. The fluid can be used in the prenatal diagnosis of neural tube defects by assay of α-fetoprotein.

6 amniocentesis The pellet is cultured to stimulate cell growth.
~ 14 days are usually sufficient for having reasonable number of cells for chromosome analysis. The availability of PCR has mad the direct DNA analysis possible without the need for culture.

7 Complications of amniocentesis
There is a 0.5-1% risk of miscarriage associated with the procedure. If the result is abnormal the couple will facing the possibility of having to consider a late mid- trimester termination of pregnancy. 12-14 week gestation have yielded comparable rate of miscarriage. Early amniocentesis has the advantage of allowing a result to be given earlier in the pregnancy ALTHGOUH It will require a mid-trimester termination of pregnancy if the fetus is found to be affected.


9 amniocentesis

10 amniocentesis

11 Chorionic villus sampling (CVS)
Diagnosis can be done during the first trimester. This procedure is carried out at 9-10 weeks gestation under ultrasound guidance by either transcervical or transabdominal aspiration of CV These are fetal in origin being derived from the outer cell layer of the blastocyte, i.e. the trophoblast.

12 Chorionic villus sampling (CVS)
Chromosomal analysis can be undertaken on CV either directly, looking at metaphase spreads from activity dividing cells, or following culture Direct analysis usually allows a provisional result to be given within 24h. Confirmation by analysis of cultured CV is required in order to obtain good quality banded chromosomal analysis.

13 Chorionic villus sampling (CVS)
For single gene disorders, sufficient tissue is usually obtained to allow prenatal diagnosis by biochemical assay or DNA analysis using uncultured villi. Even in experienced hands this procedure conveys a 2-3% risk of causing miscarriage. There is also evidence that this technique can cause limb abnormalities in the embryo if carried out before 9 weeks gestation.



16 Non invasive techniques

17 Ultrasound It can diagnose structural abnormalities which are not associated with known chromosomal, biochemical or molecular defects. Over 280 different congenital malformations may be diagnosed by an experienced ultrasonographer. it conveys no known risk to the fetus or to the mother.

18 Ultrasound It requires specialized expensive equipment and a skilled and experienced operator. It can be used around 18 weeks of gestation as screening procedure for structural abnormalities such as neural tube defects or cardiac anomalies. this technique can also identify features which suggest the presence of chromosomal abnormality. Such a finding would lead to an offer of amniocentesis or placental biopsy for definitive chromosome analysis.



21 Maternal serum screening
use of fetal markers, proteins made by the fetus during early gestation that are present in predictable levels in maternal serum throughout pregnancy. in this way up to 75% of all cases of open neural tube defects and 60-70% of all cases of Down syndrome can be detected.

22 Maternal serum screening: AFP
α-Fetoprotein: is the principal plasma protein in early fetal life, and is gradually replaced by albumin. Levels of AFP can be measured in fetal blood, amniotic fluid, and maternal serum. Maternal serum levels increase during pregnancy, whereas amniotic fluid levels fall. Level must be correlated with gestational age.

23 Maternal serum screening: AFP
Neural tube and abdominal wall defects in the fetus allow leakage of fetal serum into amniotic fluid which can be used as diagnostic test for these abnormalities. Low levels of maternal serum AFP are associated with an increased risk of Down syndrome in the fetus.

24 Maternal serum screening: uE3
Unconjugated estriol (uE3): concentration in maternal serum increase throughout pregnancy. Pregnancies with fetal Down syndrome have significantly lower uE3 levels in the second trimester.

25 Maternal serum screening: hcg
Human chorionic gonadotropin (hcg): originates from the placenta, and levels decreased sharply between 10 and 20 weeks of pregnancy. Down syndrome pregnancies have higher hcg levels, and hcg levels may be the best single marker for Down syndrome.

26 New prenatal diagnostic techniques under development
The development of non-invasive techniques which minimise the risk of pregnancy loss would offer an ideal means of prenatal diagnosis.

27 Preimplantation genetic diagnosis (PGD)
In this procedure, an egg is removed from the female and fertilised in vitro using in vitro fertilising technique (IVF). The fertilised oocyte is cultured up to the eight-cell stage of the early blastocyst. A single cell is removed and analysed by PCR to see if the zygote is affected by the disorder for which the couple is at risk. Then unaffected blastocyst is implemented in the mother uterus

28 Preimplantation genetic diagnosis (PGD)
With the PGD the couple will avoids having to consider the possibility of termination of pregnancy. PGD has been used diagnostically in very limited instances (Duchenne muscular dystrophy, cystic fibrosis, and myotonic dystrophy.

29 Preimplantation genetic diagnosis (PGD)
In PGD we are doing a PCR for a single cell and as a result of this we got a risk of a false-negative result due to contamination with extraneous DNA.

30 Indication for prenatal diagnosis
There are numerous indications for offering prenatal diagnosis. Ideally couples at high risk of having a baby with abnormalities should be identified and assessed before embarking upon a pregnancy so that they can be counselled and come to decisions. Many couples at high risk are still not referred until mid-pregnancy, when it can be too late to offer the most appropriate forms of prenatal diagnosis.

31 Indication for prenatal diagnosis: Parental age
This has been the most common indication for offering prenatal diagnosis. Prenatal karyotyping by CVS or amniocentesis should be offered to women 35 years of age and older at the time of delivery. There is an association between advance maternal age and a risk of having a child with Down syndrome and the other autosomal trisomy syndromes. Paternal age older than 55 years is associated with an increased risk of dominant mutations. It may be appropriate to offer detailed ultrasound scanning to such patients.


33 Indication for prenatal diagnosis:
Previous child with a chromosomal abnormalities In Down syndrome, the risk in a subsequent pregnancy is usually given as the mother’s age-related risk plus approximately 0.5%. The precise risk will depend on the nature of the parental rearrangement and the specific segments of the individual chromosomes involved .

34 Indication for prenatal diagnosis:
Family history of a chromosome abnormality no increase in risk since most cases have arisen as a result of non-disjunction rather than as a result of a familial chromosomal rearrangement. Each situation should carefully evaluated, either by confirming the nature of the chromosome abnormality in the affected individual or, if this is not possible, by chromosomal analysis of blood from the relevant parent at risk. If the result is normal then invasive prenatal diagnostic procedure is not then appropriate since the risk is no greater than that for the general population.

35 Indication for prenatal diagnosis:
Family history of a single gene disorder If prospective parents have already had an affected child or if one of the parents is affected or has a positive family history of a single gene disorder which conveys a significant risk to offspring, then the option of prenatal diagnosis should be discussed with them.

36 Indication for prenatal diagnosis:
Family history of a neural tube defect Careful evaluation of the pedigree is necessary to determine the risk which applies to each pregnancy. Ultrasound examination in conjunction with assay of maternal serum protein are usually done as prenatal diagnosis procedure for these cases.

37 Indication for prenatal diagnosis:
Other high risk factors Parental consanguinity. Poor obstetric history (abortion& stillbirth). Maternal illnesses (epilepsy, diabetes).

38 Problems in prenatal diagnosis
Failure to obtain a sample or culture failure. An ambiguous chromosome result. An expected chromosome results A different numerical chromosomal abnormalities A structural chromosomal abnormalities The presence of marker chromosomes

39 Termination of pregnancy
It is essential that all couples undergoing any form of prenatal diagnosis investigation be provided with information about the practical aspects of termination of pregnancy before the prenatal diagnostic procedure is carries out. This should include a practical explanation that termination in the first trimester is carried out by surgical means under general anaesthetic, whereas a women undergoing a mid-trimester termination will have to experience labour and delivery.

40 The End

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