Prenatal screening is a standard part of modern pregnancy care, offering a window into the health of both you and your baby. These tests, which often involve a blood draw and an ultrasound, can screen for chromosomal conditions like Down syndrome (trisomy 21), trisomy 18, and trisomy 13, as well as neural tube defects. While they are incredibly useful tools, it is critical to remember that they are screening tests, not diagnostic tests. They indicate risk, not certainty. A result that is flagged as "high risk" can be deeply unsettling, but it does not automatically mean something is wrong. Conversely, a "low risk" result is not a guarantee of perfect health.
Understanding when a screening result might warrant a closer look—and what that second look entails—can empower you to make informed decisions with your healthcare provider. False positives, technical issues, and the inherent limitations of screening mean that certain results should prompt further conversation and, often, diagnostic testing. Here are five symptoms or signals from your prenatal screening that could mean your results require a second review.
1. A High-Risk Result on a Cell-Free DNA (cfDNA) Test
A noninvasive prenatal screening (NIPS or NIPT) via cell-free DNA is highly accurate for detecting common trisomies, but it is not perfect. A positive or "high-risk" result for trisomy 21, 18, or 13 is the single most common reason a doctor recommends follow-up. It is vital to understand that while the detection rate is high (over 99% for Down syndrome in some studies), the positive predictive value (PPV)—the chance that a positive result truly means the baby has the condition—varies greatly depending on the condition and the mother's age and baseline risk.
For example, a positive result for a rare condition like trisomy 13 or 18 has a lower PPV than a positive result for Down syndrome. Furthermore, false positives can occur for several reasons, including a vanishing twin, a maternal chromosome abnormality (often benign), or laboratory error. A high-risk result on cfDNA should always be confirmed with a diagnostic test, such as chorionic villus sampling (CVS) or amniocentesis, before making any irreversible decisions. Do not let a screening result stand alone as the final word.
2. Discordant Results Between Multiple Screening Modalities
Many women undergo sequential screening, which might include a first-trimester combined screen and a second-trimester quad screen, or cfDNA alongside an anatomy scan ultrasound. If these results tell different stories, this is a major red flag. For instance, a first-trimester screen might indicate low risk, but a later anatomy ultrasound reveals concerning structural findings, such as a thickened nuchal fold or a heart defect.
Similarly, if a cfDNA test is negative for trisomy 18 but an ultrasound shows features strongly suggestive of trisomy 18 (like overlapping fingers, a strawberry-shaped head, or a congenital heart defect), the ultrasound findings should not be ignored. The screening blood test may have missed a rare pathogenic variant or a mosaic form of the condition. When screening methods paint a discordant picture, a detailed anatomy scan by a maternal-fetal medicine specialist and genetic counseling are the essential next steps.
3. A Nuchal Translucency (NT) Measurement of 3.5 mm or Greater
The nuchal translucency measurement taken during the first-trimester ultrasound (usually around 11 to 14 weeks) is a powerful piece of data. While a measurement between 2.5 and 3.5 mm is considered borderline, an NT that is 3.5 mm or greater is considered significantly increased. This is not a diagnosis of any specific condition, but it is a strong signal that further evaluation is needed.
An elevated NT can be associated not only with chromosomal abnormalities (like Down syndrome, Turner syndrome, or Noonan syndrome) but also with structural heart defects, genetic syndromes not detected by standard screening, and even metabolic disorders. In many cases of isolated increased NT, the baby is ultimately healthy. However, it is a clear indicator that you should be offered a detailed fetal echocardiogram and genetic testing, including a chromosomal microarray analysis if you choose amniocentesis or CVS. Do not dismiss a high NT as "just a soft marker."
4. Absent or Low Nasal Bone
During the same first-trimester ultrasound, the sonographer will look for the presence of the fetal nasal bone. An absent or significantly hypoplastic (underdeveloped) nasal bone is a well-known soft marker for aneuploidy, particularly trisomy 21. It is not a definitive sign of a problem—many babies with a missing nasal bone are born perfectly healthy. However, it does increase the odds that a chromosomal abnormality is present.
This is especially relevant if it is seen in combination with other markers, like an increased NT or a tricuspid regurgitation on Doppler ultrasound. If your screening report notes the nasal bone is absent but your cfDNA came back low-risk, you should still discuss this with your provider. In this scenario, it may be appropriate to have a detailed anatomy scan later in the pregnancy to rule out other associated findings, particularly cardiac issues.
5. Unusual or Abnormal Placental Findings
Prenatal screening is not just about the baby; it also involves evaluating the placenta. On ultrasound, an abnormal-looking placenta—for example, a thickened, cystic, or "prematurely aged" placenta—can sometimes correlate with an increased risk of aneuploidy or other pregnancy complications, including preeclampsia.
Additionally, a condition called confined placental mosaicism is a known source of false positives on cfDNA screening. In this rare scenario, the placenta has an abnormal chromosome pattern, but the baby is genetically normal. Conversely, a normal placenta can mask a true fetal abnormality. If your screening reports an unexpected finding in placental appearance, or if your cfDNA result is high-risk for something like trisomy 16 (which is often placental in origin), a diagnostic test (amniocentesis, which evaluates fetal cells in the amniotic fluid) is the only way to confirm the baby's actual genetic makeup.
A final, grounded thought: Prenatal screening is a process of risk stratification, not crystal-ball gazing. The vast majority of women who get a "flagged" result will go on to have a healthy baby. Your best action is to find a genetic counselor or a maternal-fetal medicine specialist who can walk you through the specific numbers, your personal history, and your options. Never make a decision based solely on a screening report.
