Prenatal Testing: Screening Tests & Diagnostic Tests

July 2nd, 2014
Prenatal Testing: Screening Tests & Diagnostic Tests

Pregnant women should commence prenatal care as soon as they learn they are pregnant. Adequate prenatal care is statistically proven to increase the chances of delivering a healthy baby, reduce the chances of preterm labor and help towards fewer gestational complications. Prenatal care maximizes well-being through consistent fetal monitoring, invaluable expert advice and guidance. Prenatal tests (one important aspect of prenatal care) can be of two types: screening tests and diagnostic tests. Screening tests (one typically example is urine testing) can help detect disease but do not provide the same level of accuracy as diagnostic tests such as amniocentesis or fetal DNA sampling from maternal blood.

Screening tests during pregnancy

Ultrasounds are one type of screening testing as are blood tests or maternal serum tests. An ultrasound is important because it can indicate the presence of certain chromosomal abnormalities such as Down’s syndrome. In such instances, the specialist overseeing the ultrasound may note certain folds and creases in the fetus’s neck region, known as nuchal translucency, which is a possible indication of Down’s syndrome. Maternal serum tests assess the risk of genetic disorders in the unborn baby. Disorders commonly tested for include:

  • Down’s syndrome
  • Turner’s syndrome
  • Spina bifida

Maternal serum testing measures the levels of alpha-feto protein, human chorionic gonadotropin (HCG) and estriol in a sample of maternal blood. High levels of these substances might suggest the fetus is in fact suffering from a genetic disorder. However, diagnosis is far from 100% accurate and thus, should suspicion be aroused following the abnormal results of a screening test, prenatal care specialists might suggest undergoing diagnostic testing. Such tests can more accurately determine whether or not the unborn baby is suffering from any genetic disorder.

Diagnostic tests during pregnancy

Any woman who falls pregnant after the age of 35 or who has had maternal serum testing of which results indicate a genetic disorder may be advised to undergo diagnostic tests. Whilst diagnostic tests, or prenatal care in itself, are important to confirm whether the fetus is in fact entirely healthy and normal, it is simply a matter of choice. With diagnostic testing, some couples do not go ahead with such tests as they are known to have a risk of miscarriage.
Diagnostic tests are done by testing either tissue samples taken from placenta, from the amniotic sac or using maternal blood. The result of diagnostic tests gives a clear indication about any genetic or chromosomal abnormalities present in the fetus. The tests have both pros and cons. Despite the risk of miscarriage and the unpleasant side effects (leakage of amniotic fluid, fevers and chills to mention a few), they are more accurate than screening tests. Diagnostic tests include chorionic villus sampling – a fetal genetic sampling procedure done between the 10th and the 12th week which is carried out in order to collect a tiny tissue sample (a biopsy of chorionic villus) from a pregnant woman’s placenta. As the placenta is formed by the fertilized egg, the cells in the placenta contain DNA from the fetus. Testing this sample may reveal chromosomal disorders such as Down’s syndrome or Trisomy 18.

Amniocentesis is another diagnostic test carried out somewhere between the 15th and the 18th week, although it can in some cases be carried out earlier. During this procedure, a small sample of amniotic fluid (a liquid surrounding the unborn babe composed of fetal urine and dead fetal skin cells) is collected using a syringe. This test may also predict whether a baby has Down ’s syndrome or not. Amniotic fluid is further tested to detect the level of baby’s alpha-fetoprotein found in mother’s blood. A mismatch in the level of alpha-fetoprotein level when compared to normal readings signifies a high risk of the fetus having either Spina bifida or another neural tube defect.

Non Invasive sampling of fetal nucleic acid

Scientists have developed what is termed non invasive prenatal testing using maternal blood samples as a means of determining fetal health; this method is entirely safe, posing no threat whatsoever to the unborn baby or the mother. The test requires a medical blood draw from the expectant mother. Some leading companies such as International Biosciences are offering this non invasive test as a means of determining paternity of the child at around 10 weeks.

Amongst the first to pioneer studies were researchers at Stanford University who succeeded in mapping the entire genome of the unborn child using a simple blood draw. A maternal blood taken from an expecting mother sample will contain fetal DNA in both nucleated and cell-free form. The presence of fetal DNA in the peripheral maternal blood is due to fact that some dead fetal cells are able to penetrate the placenta and enter the blood stream. It in fact through the death of placental cells, a process known as apoptosis, that these DNA fragments make their way into the blood stream.

The first studies were however, stalled by a major challenge: the difficulty of distinguishing the maternal DNA and the fetal DNA in the blood sample. If the fetus was male distinguishing fetal DNA from maternal DNA could be done by identifying Y chromosome-specific genetic markers in the blood. But the issue was made more complex when the fetus was female as the blood sample could only contain X chromosome sequences.

Analysis tends to focus more on cell free fetal nucleic acid than on nucleated cells despite the fact that the former is found in higher volumes at any given time in pregnancy. The reason for choosing cell free DNA is simple: nucleated fetal DNA remains in the blood for long stretches of time (even years). Analysis of a blood sample from a current pregnancy could reveal both DNA from the current pregnancy but also DNA from previous pregnancies. This leads to the possibility of a misdiagnosis which could have very serious repercussions.

Many companies have launched tests which can detect anomalies or abnormalities in the unborn fetus. One of these is Sequenom whose maternal blood analysis can reveal cases of Trisonomy 21. Another US company is Natera, which offers very advanced genetic testing services including pre-implantation Genetic Diagnosis. Their prenatal test is able to diagnose an array of conditions including Down syndrome, Edwards Syndrome, Patau Syndrome and sex chromosome abnormalities. Some studies on prenatal blood sampling have detected increased levels of male DNA in maternal blood samples in cases where the mother was carrying a fetus suffering from an aneuploidy, in this case Trisomy 21.

The future looks indeed very promising and it is highly likely that conventional sampling methods such as amniocentesis or chorionic villus sampling will eventually become a thing of the past.


Conger K., (2012) New method enables sequencing of fetal genomes using only maternal blood sample. Available at []

Dhallan R., Emche X, S., Damewood M., Bayliss P., Cronin M., Barry J., Betz J., Franz K., Gold K., Vallecillo B., Varney J., (2007) A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study, Lancet, 369(9560), pp. 474-81.

Levy, Y. 2008. Fetal DNA Sequenced From Mother’s Blood. Available at []

Wolfberg A., Prenatal diagnosis using cell-free fetal nucleic acids in maternal blood, Available at []

Zhong XY., Bürk MR., Troeger C., Jackson LR., Holzgreve W. ,S. Hahn, 2000. Fetal DNA in maternal plasma is elevated in pregnancies with aneuploid fetuses. Prenatal Diagnosis, 20 (10). p.795-8


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