The importance of quality control in maternal screening

Aug. 18, 2014

Screening for fetal anomalies in a pregnant patient is a unique process within clinical diagnostics. In most diagnostic processes, clinicians start with a sick patient who is presenting certain physical symptoms. When diagnosis is made, the results from the laboratory are just part of a package of information which is considered alongside the patient’s physical symptoms.

Maternal screening is very different—in that screening is designed to detect a disorder before physical symptoms appear.

Maternal screening tests 

Maternal screening practices vary across the world, but the first screening is usually carried out between weeks 11 and 14 of pregnancy. It is a combination of two blood tests and a special ultrasound that are used to assess a pregnant women’s risk of carrying a baby with chromosomal abnormalities such as Down syndrome (trisomy 21) or Edwards syndrome (trisomy 18).

The first screening tests for abnormal levels of pregnancy-associated plasma protein (PAPP-A) and human chorionic gonadotrophin (hCG) in the patient’s blood, while the ultrasound measures nuchal translucency. If the results are a cause for concern, then further tests such as amniocentesis or chorionic villus sampling (CVS) may be recommended.

Second trimester screening (either triple or quad screening) usually takes place between weeks 15 and 20 of pregnancy. These tests assess the risk of the fetus having a chromosomal abnormality or neural tube defects such as spina bifida.

When alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated estriol (uE3) are measured together, it’s called a triple screen; when inhibin A is added, it’s called a quad screen. Including the fourth marker increases both the sensitivity and specificity of the screen for Down syndrome. According to ACOG (American College of Obstetricians and Gynecologists), the triple screen detects Down syndrome in 69% of the cases, while the quad screen detects it in 81% of cases.

It is important to remember, however, that screening tests are not diagnostic of a fetal abnormality; they merely indicate a normal or increased risk. A result showing an increased risk could lead to further, more invasive, tests being conducted. Therefore it’s crucially important that screening results are accurate. 

Any undetected errors in the testing process could result in false negatives being reported, leading to the unacceptable situation in which a pregnant patient could think she is carrying a healthy fetus but in fact is carrying a fetus that has an undetected abnormality.

False positives also carry a real risk to the patient, as they could result in further, more invasive testing being carried out unnecessarily, such as amniocentesis. While the risks are small, amniocentesis carries the risk of miscarriage, and therefore it should only be carried out where screening indicates an increased risk of abnormality. It is therefore vital that clinicians have total confidence in the maternal screening results produced by the laboratory to minimize both false negatives and false positives.

Functions and options in quality control 

Quality control (QC) is a crucial part of any clinical testing program to ensure the accuracy and reliability of patient test results. QC is designed to detect, reduce, and correct deficiencies in the laboratory’s analytical process prior to the release of patient results and to improve the quality of the results reported by the lab. 

Quality controls are designed to mimic a patient sample and contain one or more analytes of known concentration. They are made using a base material of bovine serum, urine, spinal fluid, or, ideally 100% human serum. Controls manufactured from 100% human serum provide a matrix which mirrors the patient sample, and this reduces the possibility of cross-reactivity and shifting QC values.

 Laboratories use quality controls to validate the patient’s samples. If QC results are within their target range, then the lab can be confident that the patient results are accurate. These results can then be used for patient diagnosis, prognosis, and treatment planning, if appropriate. If QC values are outside the target range, it may indicate a number of issues, including inaccurate calibration, instrument failure, operator error or reagent issue. Any of those issues could contribute to false-negative or false-positive results being reported. 

It is therefore important to ensure that frequent and stringent quality control procedures are undertaken in maternal screening. To facilitate the increased screening for Down syndrome, trisomy 18 and neural tube defects, QC manufacturers are helping streamline the process by developing multi-analyte, tri-level controls. These are designed to cover both first and second trimester prenatal screening of inhibin A and PAPP-A, AFP, total hCG, free B-hCG, and uE3, helping laboratories reduce the need to purchase individual, and often costly, single controls. 

To further assess the performance of maternal screening tests, laboratories should also be involved in a proficiency testing (PT) scheme. PT provides a means of assessing the analytical performance of a laboratory compared to other laboratories utilizing the same methods and instruments. Participation in a PT scheme, as recommended in ISO15189, will help produce reliable and accurate reporting of patient results. Quality results will reduce time and labor costs, and most importantly provide accurate results in maternal screening. 

Sarah Kee, BSc, PGCE, serves as Quality Control Scientific Consultant for Randox laboratories.