The Quad Screen is a prenatal blood test that measures four key biomarkers—AFP, hCG, estriol, and inhibin‑A—to estimate the risk of Down syndrome, trisomy 18, and neural tube defects. It supports early screening and informed pregnancy care.
Introduction
Prenatal care is a cornerstone of modern obstetrics, aiming to optimise maternal and fetal health outcomes. Among the array of screening tests available, the Quad Screen stands out as a pivotal tool for assessing the risk of certain fetal chromosomal abnormalities and neural tube defects.
What is the Quad Screen?
Definition
The Quad Screen, also known as the Quadruple Marker Test or Maternal Serum Quadruple Screen, is a prenatal blood test performed during the second trimester of pregnancy. It quantitatively measures four specific serum biomarkers in the maternal blood to estimate the risk of the fetus having certain chromosomal anomalies or neural tube defects.
History and Development
The evolution of prenatal screening has seen significant advancements over the past several decades. Initially, maternal serum alpha-fetoprotein (AFP) was measured alone. The addition of human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) led to the development of the triple screen. Subsequently, the incorporation of inhibin A resulted in the Quad Screen, increasing sensitivity and specificity for detecting fetal anomalies.
Purpose
The primary aim of the Quad Screen is to identify pregnancies at increased risk for:
- Down syndrome (Trisomy 21)
- Trisomy 18 (Edwards syndrome)
- Open neural tube defects (e.g., spina bifida, anencephaly)
- Other, less common chromosomal or structural fetal abnormalities
By stratifying risk, the Quad Screen guides further diagnostic interventions and patient counselling.
Indications for the Quad Screen
Who Should Get It and Why?
The Quad Screen is generally offered to all pregnant individuals as part of routine prenatal care, particularly those who:
- Have not undergone first-trimester combined screening (including nuchal translucency and serum markers)
- Present for prenatal care during the second trimester (typically between 15 and 22 weeks of gestation)
- Have a personal or family history of chromosomal or neural tube defects
- Are of advanced maternal age (≥35 years at delivery)
- Have pre-existing medical conditions that may increase fetal risk
The test is non-invasive, poses minimal risk to the mother and fetus, and serves as a critical risk assessment tool rather than a definitive diagnostic test.
Biomarkers Measured
The Quad Screen derives its predictive value from the quantitative analysis of four maternal serum biomarkers:
- Alpha-Fetoprotein (AFP):
- A glycoprotein produced primarily by the fetal liver and yolk sac.
- Elevated or reduced levels in maternal serum can indicate neural tube defects or chromosomal abnormalities, respectively.
- Human Chorionic Gonadotropin (hCG):
- A hormone produced by the placenta.
- Abnormal levels may be associated with Down syndrome or other chromosomal abnormalities.
- Unconjugated Estriol (uE3):
- An oestrogen produced by the placenta and fetal adrenal glands.
- Low levels may suggest chromosomal abnormalities or impaired fetal well-being.
- Inhibin A:
- A hormone secreted by the placenta and ovaries.
- Elevated levels are often seen in pregnancies affected by Down syndrome.
Each biomarker reflects distinct aspects of placental and fetal physiology, and their combined interpretation enhances risk assessment accuracy.
Step-by-Step Procedure
Timing
The optimal window for the Quad Screen is between 15 and 18 weeks of gestation, though it may be performed as late as 22 weeks. Earlier or later testing may compromise accuracy due to gestational-age-dependent changes in biomarker concentrations.
Patient Preparation
Preparation is minimal; fasting is not required. The healthcare provider should:
- Confirm gestational age (based on last menstrual period and/or ultrasound)
- Gather relevant maternal history (age, weight, ethnicity, diabetes status, multiple gestation)
- Explain the test’s purpose, risks, and implications to obtain informed consent
Accurate demographic and clinical data are essential for reliable risk calculation.
Sample Collection
A standard venipuncture is performed to collect a maternal blood sample (typically 5–10 mL) into a serum separator tube. Proper labelling and prompt transport to the laboratory are necessary to prevent pre-analytical errors.
Laboratory Analysis
In the laboratory:
- The blood sample is centrifuged to separate serum.
- Quantitative immunoassays (e.g., ELISA, chemiluminescence) are used to measure the concentrations of AFP, hCG, uE3, and inhibin A.
- Results are entered into a risk calculation algorithm that incorporates maternal demographic data and gestational age.
The laboratory report provides individual biomarker values, multiples of the median (MoM) for each marker, and calculated risk estimates for specific fetal conditions.
Interpretation of Results
Normal Ranges and MoM Values
Raw biomarker measurements are converted to multiples of the median (MoM) to adjust for gestational age and maternal factors. Reference medians are established for each week of gestation in the laboratory’s population.
- MoM ≈ 1.0: Typical/average value for gestational age
- MoM > 2.0 or < 0.5: Considerably elevated or reduced, respectively
Pattern Recognition
Characteristic patterns of biomarker deviations guide risk assessment:
- Down Syndrome (Trisomy 21):
- ↓ AFP, ↓ uE3, ↑ hCG, ↑ Inhibin A
Trisomy 18 (Edwards Syndrome):
↓ AFP, ↓ uE3, ↓ hCG, (Inhibin A variable)
Open Neural Tube Defects:
↑ AFP (other markers usually within normal range)
Risk Assessment
The Quad Screen does not diagnose; it provides an adjusted risk estimate (e.g., 1 in 250) for each condition. Results are interpreted as:
- Screen Negative: Risk below a defined threshold (e.g., <1 in 270 for Down syndrome)
- Screen Positive: Risk above the threshold, prompting consideration of further testing
Results should be interpreted in the context of the entire clinical picture, including ultrasound findings and patient history.
Clinical Significance
The Quad Screen is a vital component of prenatal risk stratification, with significant implications for patient management:
- Down Syndrome (Trisomy 21):
- Quad Screen identifies pregnancies at increased risk, enabling timely genetic counselling and consideration of confirmatory diagnostic tests (e.g., amniocentesis, cell-free fetal DNA analysis).
- Trisomy 18 (Edwards Syndrome):
- Early detection allows for informed decision-making regarding pregnancy management and perinatal care.
- Neural Tube Defects:
- Elevated AFP prompts targeted ultrasound evaluation for structural anomalies and, if indicated, further diagnostic procedures.
- Other Conditions:
- Abnormal patterns may indicate other rare chromosomal or structural abnormalities, placental dysfunction, or adverse pregnancy outcomes (e.g., intrauterine growth restriction).
Limitations and Risks
False Positives and Negatives
Despite its utility, the Quad Screen is a screening—not diagnostic—test. As such, it is prone to:
- False Positives: Elevated risk estimate in an unaffected pregnancy, potentially leading to unnecessary anxiety or invasive testing.
- False Negatives: Normal results in an affected pregnancy, failing to identify some cases of chromosomal or structural abnormalities.
The overall detection rate for Down syndrome is approximately 75-80%, with a false-positive rate of about 5%.
Factors Affecting Accuracy
Several variables can influence test accuracy:
- Incorrect estimation of gestational age
- Maternal weight, diabetes, or ethnicity
- Multiple gestation (twins, triplets)
- Laboratory error or sample mishandling
These factors must be considered when interpreting results and communicating risk to patients.
Ethical Considerations
Prenatal screening raises important ethical issues, including:
- Ensuring informed consent and patient autonomy
- Balancing the benefits of early risk identification with the risk of anxiety or unnecessary interventions
- Addressing potential discrimination or stigmatization related to abnormal findings
Healthcare providers must offer sensitive, non-directive counselling and respect patient choices.
Follow-Up Actions
Further Diagnostic Testing
A screen-positive result indicates increased risk but is not diagnostic. Confirmatory testing options include:
- High-resolution ultrasound: To assess fetal anatomy for structural abnormalities
- Amniocentesis: Invasive procedure to obtain fetal cells for karyotyping and genetic analysis
- Cell-free fetal DNA testing (Non-Invasive Prenatal Testing, NIPT): Highly sensitive, non-invasive screening for aneuploidies
The choice of follow-up depends on risk level, gestational age, and patient preferences.
Counselling and Patient Management
Following abnormal results, comprehensive genetic counselling is essential. This includes:
- Explaining the significance of the findings and residual risks
- Discussing the nature, risks, and benefits of further diagnostic options
- Supporting patients in making informed decisions regarding pregnancy management and potential interventions
Ongoing multidisciplinary support may be necessary, involving obstetricians, geneticists, and specialist midwives.
Documentation and Communication
Clear documentation of results, discussions, and decisions is vital for continuity of care. Effective communication with the patient and the broader healthcare team ensures coordinated management and optimal outcomes.
Nursing Care of Patients Undergoing Quad Screen Procedure
Nursing care is critical in ensuring the safety, comfort, and well-being of patients undergoing this procedure, as well as in providing education and emotional support throughout the process.
Pre-Procedure Nursing Care
Patient Education and Informed Consent
One of the primary responsibilities of the nurse is to educate the patient about the quad screen procedure. The nurse should explain the purpose of the test, what conditions are being screened for, and the limitations of the test (such as the fact that it is a screening test, not a diagnostic one). Patients should understand that abnormal results do not necessarily mean their baby has a condition, but rather that further testing may be needed. The nurse must ensure that the patient provides informed consent before the procedure is performed.
- Discuss the rationale for the quad screen and what information it provides.
- Describe the substances being measured and their relevance to fetal health.
- Explain the timing of the test (usually between 15 and 22 weeks of gestation).
- Address common concerns and misconceptions about the procedure, including anxiety about results.
- Encourage questions and provide clear, culturally sensitive answers.
Assessment of Patient Readiness
The nurse should assess the patient’s readiness for the procedure by reviewing their medical history, noting any previous complications with blood draws, and identifying any factors that may affect the accuracy of the test (such as incorrect gestational age, multiple pregnancies, or maternal weight). Ensuring that the patient is physically and emotionally prepared contributes to a smooth procedure.
- Verify gestational age to ensure appropriate timing of the test.
- Review any history of bleeding disorders or phobias related to needles.
- Assess for allergies to materials used in the procedure (such as latex).
- Evaluate the patient’s emotional state and provide reassurance as needed.
Preparation for the Blood Draw
The nurse should prepare the patient by explaining the steps involved in the blood draw, including the location (usually the antecubital fossa), and the use of tourniquets and antiseptics. The nurse must also ensure that all necessary equipment is available, including appropriate tubes for collecting the blood samples.
- Confirm the patient’s identity using two identifiers.
- Prepare the venipuncture site with proper antiseptic technique.
- Ensure all materials are sterile and ready for use.
- Provide a comfortable environment and privacy for the patient.
During the Procedure
Venipuncture Technique
The nurse performing the venipuncture must use aseptic technique to minimize the risk of infection. The nurse should also be skilled at selecting an appropriate vein and minimizing discomfort for the patient. Good communication during the procedure can help alleviate anxiety.
- Apply the tourniquet and identify a suitable vein.
- Use a sterile needle and appropriate blood collection tubes.
- Monitor the patient for signs of discomfort, anxiety, or adverse reactions.
- Engage the patient in conversation or offer relaxation techniques if needed.
Monitoring and Immediate Care
During the procedure, the nurse should closely monitor the patient for any signs of distress, such as dizziness, fainting, or allergic reactions. It is important to be prepared to manage vasovagal responses, which can occur in some patients during blood draws.
- Observe for pallor, sweating, or complaints of nausea.
- Be prepared to stop the procedure and provide support if the patient becomes unwell.
- Provide reassurance and maintain communication throughout the process.
Post-Procedure Nursing Care
Site Care and Monitoring
After the blood draw, the nurse should ensure proper care of the venipuncture site to prevent complications such as bleeding or infection. The nurse should apply pressure to the site, cover it with a sterile dressing, and monitor for any adverse effects.
- Apply gentle pressure to the site until bleeding stops.
- Cover with a sterile adhesive bandage.
- Educate the patient on signs of infection or hematoma and when to seek help.
- Document the procedure and any reactions or complications.
Emotional Support and Counseling
Many patients experience anxiety regarding the results of the quad screen. The nurse should provide emotional support, answer questions about the next steps if results are abnormal, and offer information on available resources, such as genetic counseling.
- Discuss the timeline for receiving results and what they mean.
- Provide information on follow-up procedures if needed (e.g., amniocentesis).
- Encourage patients to reach out with any concerns.
- Refer to support groups or counseling services as appropriate.
Patient Education After the Procedure
Post-procedure education is essential for helping patients understand what to expect. The nurse should review possible side effects from the blood draw, signs and symptoms to watch for, and the importance of following up with their healthcare provider for results.
- Advise on mild bruising or soreness at the venipuncture site.
- Explain the importance of rest and hydration after the procedure.
- Review the process for obtaining test results and scheduling follow-up visits.
Special Considerations in Nursing Care
Cultural Sensitivity and Communication
Ireland is a multicultural society, and nurses must be sensitive to the cultural beliefs and practices of their patients. Some patients may have religious or cultural concerns about prenatal testing. Nurses should approach these conversations with respect and provide information tailored to the patient’s values and needs.
- Use interpreters when language barriers exist.
- Respect patient autonomy and cultural beliefs regarding pregnancy and testing.
- Offer information in a nonjudgmental and supportive manner.
Care for High-Risk Patients
Patients with high-risk pregnancies, multiple gestations, or underlying medical conditions may require additional support. Nurses should collaborate with obstetricians and other healthcare professionals to coordinate care and ensure that these patients receive appropriate monitoring and follow-up.
- Identify patients at higher risk for abnormal results or complications.
- Ensure timely communication with the multidisciplinary team.
- Provide individualized care plans and frequent check-ins.
Documentation and Legal Considerations
Accurate documentation is essential. The nurse must record all aspects of the procedure, patient education, informed consent, and any adverse reactions. Proper documentation protects both the patient and the healthcare provider and ensures continuity of care.
- Document patient education and informed consent.
- Record details of the blood draw and any complications.
- Note follow-up instructions and referrals provided.
REFERENCES
- American Pregnancy Association. Quad Screen Test (https://americanpregnancy.org/prenatal-testing/quad-screen-742). Accessed 6/12/2023.
- Centers for Disease Control and Prevention. Diagnosis of Birth Defects (https://www.cdc.gov/ncbddd/birthdefects/diagnosis.html). Accessed 6/12/2023.
- FASTER Trial Research Consortium; Dugoff L, Hobbins JC, Malone FD, Vidaver J, Sullivan L, Canick JA, et al. Quad screen as a predictor of adverse pregnancy outcome (https://pubmed.ncbi.nlm.nih.gov/16055573/). Obstet Gynecol. 2005 Aug;106(2):260-7. Accessed 6/12/2023.
- March of Dimes. Prenatal Tests (https://www.marchofdimes.org/pregnancy/prenatal-tests.aspx). Accessed 6/12/2023.
- Prenatal Information Research Consortium. ACOG/SMFM Issue New Guidelines for Prenatal Genetic Screening (https://prenatalinformation.org/2020/08/25/acog-smfm-issue-new-guidelines). Accessed 6/12/2023.
- The American College of Obstetricians and Gynecologists. Prenatal Genetic Screening Tests (https://www.acog.org/patient-resources/faqs/pregnancy/prenatal-genetic-screening-tests). Accessed 6/12/2023.
Stories are the threads that bind us; through them, we understand each other, grow, and heal.
JOHN NOORD
Connect with “Nurses Lab Editorial Team”
I hope you found this information helpful. Do you have any questions or comments? Kindly write in comments section. Subscribe the Blog with your email so you can stay updated on upcoming events and the latest articles.
