Prenatal Diagnosis: Screening and Diagnostic Tools

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Key points

  • Aneuploidy screening should be offered to all women at their first prenatal visit.

  • Cell-free fetal DNA screening is currently recommended for high-risk populations only and should be considered a screening test rather than a diagnostic test.

  • Chorionic villus sampling and amniocentesis carry a small but potential risk of pregnancy loss but remain the only diagnostic methodologies available presently.

  • Women should receive thorough pretest counseling regarding the risks and benefits of available

History of screening

Initial screening for birth defects was developed in the 1950s with ultrasound and has become increasingly prominent in obstetric care. Real-time gray-scale imaging became available in the 1970s and improved prenatal diagnosis by allowing for evaluation of pregnancies earlier in gestation. Aims of ultrasonography include determination of gestational age and fetal number, evaluation for malformations, testing of fetal well-being, and assistance with invasive diagnostic and therapeutic procedures.

Screening tests

Most prenatal testing is intended for screening. These tests include serum screening, carrier screening, and ultrasound; the goals of these tests are to identify women with pregnancies at high risk of chromosomal abnormalities or birth defects. Although ultrasound can be diagnostic, such as in the case of open neural tube defect, serum screening is intended only to identify women with pregnancies at an increased risk. Numerous options for serum screening are available with varying test criteria

First-trimester screen

The first-trimester screen is a commonly used screening test that includes a combination of serum screening and ultrasonographic examination of the nuchal translucency performed between 10 and 13 weeks 6 days’ gestation. Serum markers, including free beta–human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A, are collected with a capillary blood sample between 9 and 13 weeks 6 days’ gestation. A risk estimate is then developed that incorporates maternal age, past

Quadruple marker screen

The quadruple marker screen, or the quad screen, is the initial serum screening test that became available in the 1990s. It is still commonly used today, particularly in patients who present for care after the first trimester, which comprises more than 25% of patients using public health clinics.16 The quad screen may be performed between 15 and 22 weeks’ gestation and involves serum measurements of proteins secreted by the pregnancy, including hCG, alpha-fetoprotein (AFP), inhibin A, and

Integrated, stepwise sequential, and contingent screening

Numerous screening modalities incorporate both a first-trimester screen and the quad screen. These modalities included integrated screening, the stepwise sequential screen, and the contingent screening. Integrated screening involves performing a first trimester screen, of which the results are not providing to the patient or provider, and subsequently performing a quad screen. All of these values are then incorporated into a single risk estimate to provide patient a comprehensive risk of her

Cell-free fetal DNA

Cell-free DNA, commonly referred to as noninvasive prenatal screening, became commercially available in 2011. This relatively new technology involves collecting a maternal serum sample, from which cell-free fragments of DNA from the pregnancy are isolated. This cell-free DNA is primarily placental in origin and is released from apoptotic trophoblasts. Fetal fraction increases with gestational age but is reliably greater than 10% as early as 10 weeks’ gestation. Notably, fetal fraction of

Ultrasound only

Ultrasound is now ubiquitous in pregnancy management. Nearly all women receive at least one ultrasonographic examination of their pregnancy during a routine obstetric care, and many receive more than one. The primary function of ultrasound and obstetric care is for confirmation of dating as well as surveillance for birth defects.

Many patients choose to pursue ultrasound screening only for evaluation of malformations or markers for aneuploidy, as second-trimester transabdominal ultrasonography

Diagnostic testing

Diagnostic testing allows patients to know with as much certainty as possible whether their pregnancy may be affected by a particular genetic condition. The most common indication for diagnostic testing in the United States currently is advanced maternal age or maternal age of 35 years or older on the estimated date of delivery. Other common indications include positive aneuploidy screening results, known family history of genetic disorders, or anomalies identified on ultrasound. Although

Chorionic villus sampling

CVS has decreased in frequency with the recent increased uptake of cell-free DNA screening. It remains the only diagnostic test available in the first trimester and allows for diagnostic analyses, including fluorescence in situ hybridization (FISH), karyotype, microarray, molecular testing, and gene sequencing. CVS is performed between 10 and 14 weeks’ gestation. CVS has been performed before 9 weeks in the past, though this has shown to increase the risk of limb deformities and, therefore, is

Amniocentesis

Amniocentesis, similar to CVS, has decreased in frequency with increased utilization of cell-free fetal DNA screening. It remains the only diagnostic test available in the second or third trimesters of pregnancy and may be performed at any gestational age after 15 weeks. Using this technique, a sterile needle is introduced into the amniotic sac under ultrasound guidance, and amniotic fluid is obtained and sent for testing. In addition to evaluation for genetic disorders, amniocentesis may also

Cytogenetic evaluations

Chromosome analysis from CVS and amniocentesis samples is the most reliably predictive method of identifying pregnancies affected by chromosomal disorders. However, some issues with cytogenetic testing have been identified that may limit the clinical utility of these methods.

Mosaicism refers to tissue that contains 2 or more distinct cell lines. It is thought to reflect true mosaicism when multiple colonies from multiple cultures reveal the same results. Pseudomosaicism refers to a single cell

Preimplantation genetic diagnosis

Preimplantation genetic diagnosis (PGD) is now widely available and may allow for even earlier detection of chromosomal abnormalities. This procedure is performed after in vitro fertilization (IVF) by manipulation of the embryo to either remove a polar body or to remove a single cell from the blastocyst. This procedure allows for detection of the abnormality before embryo transfer so that only unaffected embryos are transferred back. It is recommended that all pregnancies conceived with IVF/PGD

Summary

All women should be offered aneuploidy screening or diagnostic testing during pregnancy. Just as importantly, available options should be explained to patients and families in depth, most notably including the risks and benefits of each option, and how results might be reported. Patients who choose cell-free fetal DNA technology should be counseled that the test remains a screening test for aneuploidy at this time and that microdeletion testing continues to have poor positive predictive values

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  • Cited by (0)

    Disclosure: The authors have no conflicts of interest to report.

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