The quad screen is a non-invasive prenatal blood test offered to pregnant individuals during the second trimester. This laboratory analysis assesses the likelihood that a developing fetus may have certain chromosomal anomalies or structural defects. The quad screen functions solely as a screening tool, which calculates risk based on statistical probabilities, rather than providing a definitive medical diagnosis. A screen-positive result suggests that a pregnancy has a higher-than-average chance for a condition, indicating that further evaluation may be warranted.
The Four Components and Timing
The quad screen is optimally performed between the 15th and 20th weeks of gestation, with testing between 16 and 18 weeks yielding the most accurate results. This test is named for the four specific substances, or analytes, it measures in the mother’s blood sample. These four markers include Alpha-fetoprotein (AFP), a protein produced by the fetal liver and yolk sac, and Human Chorionic Gonadotropin (hCG), a hormone generated by the placenta. The two remaining substances are Unconjugated Estriol (uE3), an estrogen made by the fetus and the placenta, and Inhibin A, a protein hormone produced by the placenta and ovaries. The laboratory compares the measured levels of these four markers to median values established for a given gestational age. This comparison, along with maternal factors such as age, weight, and ethnicity, generates a personalized risk assessment.
Conditions Assessed
Variations in the measured levels of the four markers correlate with an altered risk for three primary groups of fetal conditions. One condition screened for is Down syndrome (Trisomy 21), which results from an extra copy of chromosome 21. Pregnancies affected by Down syndrome often show lower-than-normal levels of AFP and uE3, combined with elevated levels of hCG and Inhibin A. The quad screen also assesses the risk for Trisomy 18 (Edwards syndrome), a severe chromosomal anomaly involving an extra copy of chromosome 18. In these cases, the levels of all four markers—AFP, uE3, hCG, and Inhibin A—tend to be significantly lower than expected.
The test also screens for an increased risk of Neural Tube Defects (NTDs), which are birth defects of the brain, spine, or spinal cord, such as spina bifida and anencephaly. Elevated levels of AFP are often the primary indicator for open NTDs, where fetal tissue is exposed to the amniotic fluid, allowing AFP to leak into the mother’s bloodstream.
The specific combination and degree of abnormality in the four markers inform the individualized risk for each condition. For example, an elevated AFP level alone might suggest an NTD, but when combined with the other marker levels, it contributes to the risk calculation for a chromosomal condition.
Interpreting the Risk Calculation
The quad screen provides a probability, not a definitive diagnosis. The result is typically presented as a risk ratio, such as “1 in 300” or “1 in 1,000,” indicating the statistical chance of the fetus being affected by a specific condition. A “high-risk” or “screen-positive” result means the calculated probability exceeds a pre-determined cutoff, such as 1 in 270 for Down syndrome. Most individuals who receive this result go on to have healthy babies.
The quad screen has a detection rate for Down syndrome of approximately 81 to 83 percent. It has a false-positive rate—a high-risk result when the fetus is actually unaffected—of about 5 percent. This relatively high false-positive rate emphasizes why the test is considered a statistical indicator rather than a diagnostic tool. One common reason for a screen-positive result is an inaccurate calculation of the pregnancy’s gestational age, as expected marker levels change rapidly week to week. If the gestational age is miscalculated, the laboratory’s reference range will be incorrect, leading to a skewed risk ratio.
Next Steps After a High-Risk Result
A high-risk result prompts a discussion with a healthcare provider about the available next steps. Often, the first step is a targeted ultrasound to confirm the gestational age and look for structural findings associated with the conditions. If a screen-positive result persists, Non-Invasive Prenatal Testing (NIPT) is a highly accurate, non-invasive option that analyzes cell-free fetal DNA circulating in the mother’s blood. NIPT offers a higher detection rate and a lower false-positive rate for chromosomal conditions, helping to reduce the need for more invasive procedures.
For those who desire a definitive diagnosis, two invasive procedures are available: amniocentesis and chorionic villus sampling (CVS). Amniocentesis, typically performed after 15 weeks, involves collecting a small sample of the amniotic fluid surrounding the fetus. CVS, performed earlier, samples placental tissue. Both diagnostic tests analyze fetal chromosomes directly to provide a conclusive answer for the conditions screened by the quad screen. Consultation with a genetic counselor is routinely offered to ensure a complete understanding of the risks, benefits, and emotional implications of each option.