Principles of Screening

Definition and Brief History

Screening was first formally defined in 1951 by the United States Commission of Chronic Illness as:

. . . the presumptive identification of unrecognised disease or defect by the application of tests, examinations, or other procedures which can be applied rapidly. Screening tests sort out apparently well persons who probably have a disease from those who probably do not. A screening test is not intended to be diagnostic. Persons with positive or suspicious findings must be referred to their physicians for diagnosis and necessary treatment.

Put simply, the purpose of screening is to identify patients at high risk for a specific condition within a group of apparently healthy and asymptomatic people. Prenatal screening should be differentiated from prenatal diagnosis, in which a definitive diagnosis is made.

Prenatal diagnosis first became available in the 1960s with the introduction of amniocentesis for Down syndrome. At that time, the only screen was maternal age; patients with advanced maternal age were offered amniocentesis as a diagnostic test. In the 1970s, the first maternal serum screen became available with the discovery of differences in maternal serum alpha-fetoprotein (AFP) with neural tube defects. In 1984, associations between reduced serum AFP and Down syndrome were recognised, and screening with this test was introduced shortly thereafter. Since then, the field has progressed rapidly to include advanced ultrasound and noninvasive prenatal testing (NIPT) using cell-free fetal DNA.

Goal and Scope of Prenatal Screening

The goal of prenatal screening is to detect conditions that can be deleterious to the mother, fetus or both. Prenatal screening includes both maternal (and occasionally paternal) and fetal screening. In the course of routine prenatal care, mothers are screened for a number of conditions such as sexually transmitted diseases and gestational diabetes that can affect both the mother and fetus. Patients can be screened for carrying genetic diseases such as cystic fibrosis, haemoglobin S trait and Tay Sachs disease. Based on these results, further testing such as invasive fetal testing or paternal genetic testing can be recommended. Finally, fetal screening focuses on screening the fetus for conditions such as aneuploidy or congenital defects, and this can be accomplished either through maternal blood testing or fetal ultrasound. The results of prenatal screening and subsequent diagnostic testing may be used to make a decision to terminate a pregnancy, to prepare for the birth of a child with chronic or fatal illness or to use advanced reproductive technology to avoid carrying a fetus with the disease in question in a subsequent pregnancy. The purpose of this chapter is to explore the basic principles underlying all of these screening tests.

Basic Parameters of Diagnostic and Screening Tests

To be useful, a screening test must be valid . The validity of a screening test is defined as its ability to distinguish between those who have a disease and those who do not. This is further broken down into sensitivity and specificity . Sensitivity is the ability of a test to correctly identify those who have a disease. Specificity is the ability of the test to identify those who do not have the disease in question. Accuracy is another important aspect of a test and refers to the ‘closeness of the measured value to the correct value’.

Imagine a population of 1000 gravidas. One hundred of them are carrying a fetus with Down syndrome, and the rest are not. Table 16.1 illustrates the four possibilities of a screening test in this population. Sensitivity is defined as True positives/(True positives + False negatives). Specificity is defined as True negatives/(True negatives + False positives). If we put numbers into our table ( Table 16.2 ), we can calculate the sensitivity and specificity of the screening test. In this case, the sensitivity is 70/(70 + 30) = 70%, and the specificity is 800/(800 + 100) = 88.9%.