Quadruple Marker Test: Second Trimester Genetic Screening | Mayflower Clinic
Second Trimester Scans & Testing

Quadruple Marker Test: Demystifying Second Trimester Genetic Screening

By Dr. Kunda Shahane | Fetal Medicine Specialist, Nagpur

The first trimester of pregnancy operates on a very strict timeline. For many mothers, especially those living in rural areas outside of Nagpur who may not have immediate access to specialized care, the narrow 11-to-14-week window for the NT scan and Double Marker test can easily slip by unnoticed. If you find yourself at 16 weeks pregnant and realize you missed your first-trimester screening, a wave of panic often sets in. "Did I miss my chance to make sure my baby is genetically healthy?"

As a Fetal Medicine Specialist at Mayflower Clinic, I frequently see mothers who are anxious about having "missed the boat." My immediate response is to reassure them: You have not missed your chance. Medical science provides a powerful safety net for the second trimester known as the Quadruple Marker Test (often simply called the Quad Screen).

Furthermore, even if you did have your first-trimester screening, your obstetrician might still recommend the Quad marker, or at least a specific portion of it. Let us break down exactly what this maternal blood test is, what the four markers stand for, and why it plays a crucial role in modern prenatal care.

What is the Quadruple Marker Test?

Like the Double Marker test, the Quadruple Marker is a simple, non-invasive maternal blood draw. It poses zero risk of miscarriage to your developing baby. It is typically performed between 15 weeks and 20 weeks + 6 days of pregnancy, making it the primary biochemical screening tool for the second trimester.

While the Double Marker looks at two substances in your blood, the Quad screen, as the name implies, evaluates the levels of four specific substances produced by the fetus and the placenta. By analyzing these four markers together—along with maternal factors like age, weight, and exact gestational age—we can calculate the statistical probability of your baby having certain chromosomal conditions or neural tube defects.

Decoding the Four Markers

When you receive your laboratory report, it will list the following four biochemical markers. Here is what they are and why we measure them:

1. AFP (Alpha-fetoprotein)

This is arguably the most important marker in the second trimester. AFP is a protein produced by the baby’s liver. It is perfectly normal for some AFP to cross the placenta into the mother's bloodstream. However, abnormally high levels of AFP can indicate that the baby has an opening in their tissue, most commonly a Neural Tube Defect (NTD) like Spina Bifida or Anencephaly. The Quad screen is the only blood test that screens for these structural spinal defects (unlike NIPT or the Double Marker, which only screen for chromosomal/genetic conditions).

2. hCG (Human Chorionic Gonadotropin)

This is the hormone produced by the placenta. While it peaks in the first trimester, it should steadily decline in the second trimester. Abnormally high levels of hCG in the second trimester, when combined with other specific marker levels, can be an indicator of an increased risk for Down Syndrome (Trisomy 21).

3. uE3 (Unconjugated Estriol)

This is a form of estrogen produced by both the placenta and the baby's liver. As the pregnancy progresses, estriol levels should normally rise. Abnormally low levels of estriol can be a flag for chromosomal abnormalities like Down Syndrome or Edwards Syndrome (Trisomy 18).

4. Inhibin-A

This is a protein produced by the placenta. Like hCG, abnormally high levels of Inhibin-A are statistically associated with a higher risk of Down Syndrome.

The Down Syndrome Profile:

To flag a high risk for Down Syndrome, the Quad screen typically looks for a specific pattern: Low AFP, Low Estriol, High hCG, and High Inhibin-A. It is the combination of these four markers that gives the test its predictive power.

Who Should Get the Quadruple Marker Test?

At our Nagpur clinic, we tailor screening recommendations to each individual patient. You will likely be advised to take the Quad screen if:

  • You Missed the First Trimester Window: If you did not get the NT scan or Double Marker test before 14 weeks, the Quad screen is your primary option for chromosomal screening.
  • You Had a "Borderline" First Trimester Result: Sometimes, the first-trimester screening comes back in a gray area—not high risk enough to warrant an immediate amniocentesis, but not low risk enough to completely ignore. The Quad screen can provide additional data.
  • You Need AFP Screening: Even if you had an NIPT or Double Marker test in the first trimester (which ruled out Down Syndrome), those tests do not check for Spina Bifida. Therefore, your doctor may recommend taking just the AFP portion of the Quad test between 15-20 weeks to ensure the baby's spine is closed safely.
  • Advanced Maternal Age: Mothers over the age of 35 have a naturally higher baseline risk for chromosomal conditions.

Factors That Can Skew Your Results

It is incredibly important to provide accurate clinical information to the laboratory before drawing your blood. The software that calculates your risk ratio relies heavily on these variables. Incorrect data can lead to false alarms.

  • Exact Gestational Age: Marker levels change by the week. If you think you are 16 weeks pregnant, but you are actually 18 weeks, the computer will interpret the hormone levels incorrectly. This is why having an early dating ultrasound is so crucial.
  • Maternal Weight: Blood volume increases with maternal weight, which dilutes the concentration of the markers.
  • Diabetic Status: Insulin-dependent diabetes can alter AFP levels.
  • Multiple Gestations: If you are carrying twins, you have two babies and two placentas producing hormones, which naturally drives all the marker levels up.

How to Read Your Quad Screen Report

Just like the Double Marker, the Quad screen is a screening test, not a diagnostic test. It cannot give you a "Yes" or "No" answer. It provides a statistical risk ratio.

If your report says "Screen Negative" or "Low Risk" (e.g., 1:2500), it means the statistical probability of your baby having a condition is very low. You can breathe easily, and routine prenatal care will continue.

If your report says "Screen Positive" or "High Risk" (e.g., 1:150), please do not panic. This is the most critical piece of advice I give my patients. A high-risk result simply means your specific hormone pattern crossed a predetermined threshold. It does not mean your baby definitely has Down Syndrome or Spina Bifida. In fact, due to a false-positive rate of around 5%, many women with high-risk screens go on to deliver perfectly healthy babies.

Next Steps After a High-Risk Result

If your Quad screen comes back positive, the team at Mayflower Clinic will guide you through the definitive next steps:

  1. Detailed TIFFA Scan: If the risk is for Spina Bifida (high AFP), we will perform a meticulous Level 2 Anomaly scan to look for physical openings in the baby's spine. Often, high AFP is simply due to slightly incorrect pregnancy dating!
  2. Amniocentesis: If the risk is for a chromosomal condition like Down Syndrome, we will discuss Amniocentesis. This is a diagnostic test where a tiny sample of amniotic fluid is taken to examine the baby's actual chromosomes, providing a 100% definitive answer.

Compassionate Care in Central India

Waiting for genetic test results is an anxious time for any family. At Mayflower Clinic in Nagpur, we prioritize rapid laboratory turnarounds and immediate, face-to-face counseling. We explain your risk ratios in clear language (Marathi, Hindi, or English), ensuring you understand the science behind the numbers and are empowered to make the best decisions for your pregnancy.

Are you in your second trimester and need to schedule your Quadruple Marker Test or review your recent results? Contact Mayflower Clinic in Dhantoli, Nagpur today for expert guidance with Dr. Kunda Shahane.