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Prenatal testing

Main reasons for the changes in number and structure of the chromosomes are radiation, UV lighting and toxic chemical exposure. Negative environmental effects could alter genetic material in the gametes (before fertilization) or in the fertilized egg (called de novo). Substantial errors in genetic material would prevent fetus from normal development and miscarriage will happen (usually at the beginning of the pregnancy). Some alterations in the structure and number of chromosomes are carried to the next generation; lifespan of those individuals will depend on the importance of altered chromosome(s) or gene(s).

Fetal health could be detected non-invasively (using ultrasound and maternal blood testing techniques) or by screening fetal genetic material. All methods that are dealing with fetal DNA material are considered aggressive and potentially harmful for the baby. Amniocentesis is one of those methods. Needle inserted in the uterus during amniotic fluid sampling could result in fetal damage or trigger series of events that will lead to spontaneous miscarriage. Chorionic villus sampling can be performed earlier than amniocentesis and it is another aggressive method focused on placental tissue sampling. Although those methods are risky, both amniotic fluid and placental tissue contain more than enough fetal genetic material and testing will provide precise evidence of fetal genetic health.

Less invasive methods that could provide more details about fetal health can be conducted on maternally derived samples. Fetal DNA could be obtained from the mother's blood because it contains fetal cells and free fetal DNA (2-10% of total DNA in the blood). During in vitro fertilization, embryos could be tested prior implantation (to prevent implanting genetically altered embryos).

Proteins in the blood could be good indicators of potential genetic defects. Human chorionic gonadotropin (hCG) level is typical marker of pregnancy (home tests are designed to register pregnancy by detecting beta hCG in the urine sample). It’s produced by placenta from the moment women become pregnant and its level keep on rising during pregnancy. hCG influence yellow body (corpus luteum) by promoting its progesterone secretion. Triple test (known as Kettering test or the Bart's test) is screening beta hCG, AFP and estriol levels to detect any chromosomal aberration during second trimester of pregnancy. Impaired hormone level could indicate neural tube defect and couple other genetic conditions. For example, if all three hormones are present in lower than expected level, there is high chance that baby has Edward’s syndrome (trisomy 18). If AFP and estriol levels are low, and beta hCG level is high – there is high chance that baby with Down syndrome (trisomy 21) will be born. Down syndrome could be detected with ~80% sensitivity and 5% false positive rate.

Pregnancy-associated plasma protein A (pappalysin 1 or PAPPA) is another protein used in prenatal screening. Low PAPPA plasma level suggests that women is probably carrying aneuploid fetus.
Alpha-fetal protein (alpha-1-fetoprotein) is produced by the yolk sac and liver during pregnancy. It’s fetal form of serum albumin and this is the most abundant fetal protein. It’s used as clinical marker for couple of genetic disorders. When alpha-1-fetoprotein level is increased, open neural tube defects and omphalocele are suspected. Decreased hormone levels points to the Down syndrome.

When serious genetic disorder is suspected after maternal testing or ultrasound check – extraction and screening of fetal genetic material is needed to confirm or discard initially obtained results.

Karyotype (set of chromosomes) is prepared when cells are in the metaphase stage of division. That’s when chromosomes are condensed, duplicated and easily recognized after staining. Photomicrographs of stained chromosomes (karyogram) allow further examinations of their number and structure. Karyogram could show if some chromosomes are missing or are present abundantly. Staining of the chromosomes will show if deviation such as deletions, duplications or translocations are present. PCR analysis of the fetal DNA sample is used to provide more information on the altered genes.

Prenatal testing is especially important if there are suspected genetic disorders in the family or if parents already have a child with genetic abnormalities. Women that are older than 35 years are at increased risk of giving birth to babies with Down syndrome (1 out of 400 babies) and genetic testing is strongly advised. Information on the disorder could prevent parents from having a baby with impaired genetic material or prepare them (economically and physically) to nurture a child that needs special heath care and unique social environment.