of Prenatal Diagnosis

Figure 17-1 A, Amniocentesis. A needle is inserted transabdominally into the amniotic cavity, and a sample of amniotic fluid (usually approximately 20 mL) is withdrawn by syringe for diagnostic studies (e.g., chromosome studies, enzyme measurements, or DNA analysis). Ultrasonography is routinely performed before or during the procedure. B, Chorionic villus sampling (CVS). Two alternative approaches are drawn: transcervical (by means of a flexible cannula) and transabdominal (with a spinal needle). In both approaches, success and safety depend on use of ultrasound imaging (scanner). C, Preimplantation genetic diagnosis (PGD). Eggs are removed and used for in vitro fertilization. For blastomere biopsy, the fertilized embryos are incubated for 3 days, to the 8- to 16-cell stage, and a single blastomere is removed and undergoes genetic testing for a chromosomal abnormality or mendelian disorder. In this example, the embryo is affected (“X”) and after testing would not be implanted. In the blastocyst biopsy, approximately five trophectoderm cells (which will go to make the placenta and not the embryo proper) are removed and tested. Only those embryos that are unaffected will be implanted in the patient’s uterus to establish a pregnancy.

In addition to fetal chromosome and genome analysis, the concentration of alpha-fetoprotein (AFP) can be assayed in amniotic fluid to detect open neural tube defects (NTDs) (see Chapters 8 and 14). AFP is a fetal glycoprotein produced mainly in the liver, secreted into the fetal circulation, and excreted through the kidneys into the amniotic fluid. AFP enters the maternal bloodstream through the placenta, amniotic membranes, and maternal-fetal circulation. It can therefore be assayed either in amniotic fluid (amniotic fluid AFP [AFAFP]) or in maternal serum (maternal serum AFP [MSAFP]). Both assays are extremely useful for assessing the risk for an open NTD but also for other reasons (see later discussion).

AFP concentration is measured by an immunoassay, a relatively simple and inexpensive method that can be applied to all amniotic fluid samples, regardless of the specific indication for the amniocentesis. To interpret an AFAFP, one compares the level to the normal range for each gestational age. If the AFAFP level is elevated (relative to the normal range for that particular gestational age), one must look for an open NTD as well as for causes other than an open NTD. Factors potentially leading to abnormally high concentrations of AFP in amniotic fluid are shown in Table 17-1. When the AFAFP assay is used in conjunction with ultrasonographic scanning at 18 to 19 weeks’ gestation, approximately 99% of fetuses with open spina bifida and virtually all fetuses with anencephaly can be identified.

TABLE 17-1

Causes of Elevated Amniotic Fluid Alpha-Fetoprotein Other Than Neural Tube Defect


Note: Some of these causes of an elevated amniotic fluid AFP level can be confirmed or ruled out by ultrasonographic examination.

AFP, Alpha-fetoprotein.

If amniocentesis is performed for any reason, both the concentration of AFP in the amniotic fluid and a chromosome analysis of amniotic fluid cells are determined to screen for open NTDs and chromosomal and other genomic abnormalities, respectively. Other tests are performed only for specific indications.


Chorionic Villus Sampling


Figure 17-2 Development of the tertiary chorionic villi and placenta. A, Cross section of an implanted embryo and placenta at approximately 21 days. B, Cross section of a tertiary villus showing establishment of circulation in mesenchymal core, cytotrophoblast, and syncytiotrophoblast. See Sources & Acknowledgments.

The major advantage of CVS compared with midtrimester amniocentesis is that CVS allows the results to be available at an early stage of pregnancy, thus reducing the period of uncertainty and allowing termination, if it is elected, to be performed in the first trimester. However, unlike after amniocentesis, AFAFP cannot be assayed at this stage. Evaluation for a possible open NTD thus must be done by other methods, including MSAFP screening, amniocentesis for AFAFP, and ultrasonography.

The success of chromosome analysis by karyotype or CMA is the same as with amniocentesis (i.e., more than 99%). However, approximately 1% of CVS samplings yield ambiguous results because of chromosomal mosaicism (including true mosaicism and pseudomosaicism; see later); in these situations, follow-up with amniocentesis is recommended to establish whether the fetus has a chromosomal abnormality.


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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on of Prenatal Diagnosis
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