Prenatal Diagnosis and Genetic Testing


Testing is a procedure that (in most cases) provides a definitive answer to the question that is being asked. Tests that have low false positives and negatives are considered diagnostic. In the case of prenatal testing there is a risk of miscarriage associated with all the currently available diagnostic invasive tests.

Human genome project has brought inherited health factors to the forefront and genetic risk assessment, screening and testing are now part of primary care. Prenatal diagnosis is very important and useful in this regard, main purposes being:

  • to enable timely medical or surgical treatment of a condition before or after birth,
  • to give the parents the chance to abort a fetus with the diagnosed condition, and
  • to give parents the chance to “prepare” psychologically, socially, financially, and medically for a baby with a health problem or disability, or for the likelihood of a stillbirth.

Reproductive genetic risk assessment may occur as part of preconception or prenatal care. 4 key assessment areas include:

Maternal age
Family medical history
Current pregnancy history
Ethnic background

Qualifying Risk Factors

  • Women over the age of 35
  • Women who have previously had premature babies or babies with a birth defect, especially heart or genetic problems
  • Women who have high blood pressure, lupus, diabetes, asthma or epilepsy
  • Women who have family histories or ethnic backgrounds prone to genetic disorders, or whose partners have these
  • Women who are pregnant with multiples (twins or more)
  • Women who have previously had miscarriages

Risk Assessment

Maternal Age

Risk for chromosome abnormalities increases with maternal age

Family Medical History

If a family history of a diagnosed genetic condition or birth defect is identified, referral for genetic counseling is appropriate. Examples include

Prior child with spina bifida
Niece with cystic fibrosis
Nephew with Duchenne Muscular Dystorphy
Brother with Fragile X syndrome

For a non-specific, but concerning history, referral for counseling is also appropriate. Examples include

Close family member with mental retardation of unknown etiology
Multiple family members with “kidney disease”
Previous child with seizure disorder and developmental delay

Pregnancy History

During a pregnancy, any reported exposures or maternal condition may prompt genetic counseling referral.

Known/potential teratogens include Accutane, seizure medications, lithium, coumadin, “street drugs”.

Other reasons include high fever, viral infections and maternal diabetes.

Ethnicity Based Carrier Screening

The purpose of ethnicity based carrier screening is to detect couples at risk for prenatally diagnosable genetic disease. Tests offered are based on ethnic background and should be offered to patients seeking preconception counseling or seeking infertility care or in first or early second trimester of pregnancy.

Principles of Counseling

Pre-screening counseling should include:

Purpose, voluntary nature
Range of symptoms/severity of each disease
Risk of carrier status & affect on offspring
Meaning of positive and negative results
Factors to consider in decision-making
Further testing necessary for prenatal diagnosis

methods of prenatal screening

Screening for Fetal Chromosomal Abnormalities

First Trimester

NT (Nuchal translucency)
PAPP-A (pregnancy associated plasma protein-A)
hCG (human chorionic gonadotropin)

Nuchal Translucency

It is performed between 11-14 weeks gestation. Nuchal translucency measurements greater than 3.5 mm are associated with increased risk of

Chromosomal abnormalities
Structural anomalies
SAB, SGA, stillbirth

Down syndrome detection rate is between 64-70%.

1st Trimester Serum Screening

It is performed between 9 to 13+6 EGA. Analytes used (with maternal age) for hCG or Free b-hCG and PAPP-A.

Detection rates with 5% false positive rate are for trisomy 21, 68 % and trisomy 18, 90%.

Combined 1st Trimester Serum + NT

Performed between 11-14 weeks gestation. NT is best visualized @ CRL = 45-84 mm. NT and maternal serum analyses is performed.

Second Trimester Options

Triple screen
Quadruple screen
Genetic sonogram
Extended sonogram: serum + ultrasound markers

Quad Screen

Analytes used (with maternal age) for

Alpha-fetoprotein (AFP)
Unconjugated estriol (uE3)
Beta-human chorionic gonadotropin (b-HCG)
Dimeric inhibin-A

Detection rates with 5% false positive rate are

Trisomy 21: 75-80% (vs 60-70 % with triple screen)
Trisomy 18: 60 %
NTD: 75-80 %

Genetic Ultrasound

Performed at 18-20 weeks for evaluation of major structural anomalies and minor markers for aneuploidy. Conflicting views surround use as independent or adjunct screening test.

Prenatal Diagnostic Procedures

Chorionic villus sampling
Percutaneous umbilical cord sampling


It is performed routinely between 16-20 weeks of gestation. Chromosome analysis may be done. AF-AFP levels may be found.

Risk of miscarriage associated with procedure 1/100 to 1/400.

Chorionic Villus Sampling

It is performed between 10 and 13 weeks of gestation. Risk being 1/100 to 1/200. Benefits include:

  • Can be performed earlier in gestation
  • Rapidly growing cell cultures practically free of maternal cell contamination
  • An efficient direct method to obtain high quality metaphases from the of the syncitiotrophoblasts tissue which the fetal karyotype is defined within a few hours of chorionic villi sampling (specialty cyto techinque)
  • Is suitable for a rapid, direct diagnosis of the related metabolic diseases.
  • Placental mosaicism (trisomic rescue in fetus) can increase the risks of genetic abnormalities such as uniparental disomy

Disadvantages include:

Placental mosaicism 1% of CVS
LRD risk prior to 70 days gestation (10 weeks)
Higher loss rate
Less access to procedure
Higher chance of insufficient sample
Early test=risk of sampling a fetus potentially destined to miscarry
No ONTD testing
More risk of vaginal bleeding

Percutaneous Umbilical Cord Sampling (PUBS) or Cordocentesis

There is approximately 2% risk of loss of fetus. Technically it is difficult to be performed prior to 20 weeks. Blood disorders such as hemophilia and anemia may be detected. Also useful for detection of Rh isoimmunization of the fetus. Chromosomal abnormalities may be found and fetal karyotyping within 48 hours. Infections such as toxoplasmosis and rubella may be diagnosed. The procedure is also used to perform blood transfusions to the fetus and to administer medication directly into the fetal blood supply.

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The writer enjoys medical education and has special interest in community medicine.