How Accurate Is a Positive NIPT for Trisomy 18? Next Steps

Getting a “high-risk” or positive Non-Invasive Prenatal Test (NIPT) result for trisomy 18 (Edwards syndrome) can be frightening and overwhelming. It is important to know that this result is not caused by anything you did, and you do not have to navigate this alone. A positive NIPT means there is an increased chance your baby has the condition, but it is a screening test, not a diagnosis ^[1].

Because false-positive screens occur, medical guidelines strongly advise against making irreversible pregnancy decisions based solely on an NIPT result ^[1][2]. Diagnostic testing is the only way to know for certain before birth, though the choice to undergo these procedures is entirely up to you ^[1][3].

What you can do right now:

• Pause: Do not make any permanent decisions about your pregnancy based only on this screening result ^[1].
• Connect: Contact your obstetric clinician promptly to request a referral to a genetic counselor or a maternal-fetal medicine specialist (a doctor who specializes in high-risk pregnancies).
• Gather details: Ask your clinic for a copy of the full laboratory report, which includes details like your “fetal fraction” and the specific test used.

Screening vs. Diagnosis

The NIPT (also called cell-free DNA screening) analyzes fragments of DNA from the placenta that circulate in your blood. It is an excellent screening tool because it identifies who is at higher risk, but it cannot definitively diagnose a condition ^[1].

Sometimes, the genetic makeup of the placenta is different from the baby’s. This is called confined placental mosaicism ^[4]. When this happens, the NIPT can show a high risk for trisomy 18 even when the baby does not have the condition ^[5]. Diagnostic tests are offered to resolve this uncertainty.

How Accurate is the NIPT?

When looking at the NIPT’s performance for trisomy 18 in singleton pregnancies, the numbers are strong but not perfect:

• Sensitivity: The test correctly flags about 97.7% of pregnancies where trisomy 18 is actually present ^[2].
• Specificity: It correctly identifies unaffected pregnancies about 99.9% of the time, meaning the false-positive rate is roughly 0.1% ^[2].

Because trisomy 18 is a rare condition, even a 0.1% false-positive rate means that many “high-risk” screens turn out to be pregnancies without detected trisomy 18.

Positive Predictive Value (PPV)

To understand your actual chances, doctors look at the Positive Predictive Value (PPV). PPV answers the question: Out of everyone who gets a high-risk result, how many actually have a baby with the condition?

Your personal PPV is not just based on the test; it is heavily influenced by your underlying baseline risk (pretest probability), which factors in your age and ultrasound findings ^[6][7].

• If baseline risk is low (e.g., 0.1%): Statistical models suggest the PPV is roughly 49%. This means there is about a 51% chance the result is a false-positive screen ^[2].
• If baseline risk is higher (e.g., 1%): The PPV jumps to roughly 91% ^[2].
• In real-world studies: A large multicenter study found a PPV of about 35% across its general population, while studies focusing on older patients or higher-risk pregnancies saw PPVs around 67% or higher ^[8][9].

Your genetic counselor can calculate a personalized PPV for you based on the specific laboratory used, your age, and your medical history.

Next Steps: Ultrasound and Confirmatory Testing

Your specialist team will help you weigh your options. You may choose to pursue diagnostic testing, decline testing, or wait until the baby is born to arrange testing.

Targeted Ultrasound

A detailed ultrasound looks for physical signs or structural differences often seen with trisomy 18. While an ultrasound provides valuable context and can adjust your risk estimate, it cannot confirm or completely rule out the diagnosis on its own ^[10][11]. Ultrasound should complement, not unnecessarily delay, diagnostic testing.

Diagnostic Testing Options

If you want definitive answers before birth, you will be offered invasive diagnostic testing. There are two primary options depending on the timing of your pregnancy:

Chorionic Villus Sampling (CVS)

• Timing: Usually performed between 10 and 13 weeks of pregnancy ^[12].
• How it works: A doctor takes a tiny tissue sample from the placenta.
• Limitations: Because CVS samples the placenta (like the NIPT), it can be affected by confined placental mosaicism. In one large dataset, about 4% of high-risk trisomy 18 screens that went to CVS showed “mosaicism” (a mix of typical and atypical cells in the sample) ^[13]. A mosaic CVS result does not automatically mean the baby is affected, and it usually requires a follow-up amniocentesis to see if the fetus shares those cells ^[13].

Amniocentesis

• Timing: Typically performed from 15 weeks of pregnancy onward ^[12][14].
• How it works: A doctor takes a small sample of amniotic fluid, which contains cells shed directly by the baby.
• Advantage: Amniocentesis is considered highly definitive because it bypasses the placenta and looks directly at fetal cells, avoiding the confusion of confined placental mosaicism ^[15].

Procedure Risks and Safety

Both CVS and amniocentesis carry a small risk of procedure-attributable miscarriage. Large population analyses estimate this added risk at roughly 0.12% to 0.30% for amniocentesis, with similar or slightly different estimates for CVS depending on the study ^[16].

These are average numbers; your personal risk depends heavily on the specific clinic and the doctor’s experience. Ask your center for their specific complication rates. If you undergo a procedure, you will be monitored and should contact your clinic immediately if you experience heavy bleeding, fluid leakage, fever, or severe abdominal pain ^[17][18]. If you have an Rh-negative blood type, you will also receive guidance on anti-D (RhoGAM) injections.

Understanding the Results

Diagnostic testing can often provide rapid preliminary results within a few days, followed by a final comprehensive laboratory report (such as a full karyotype or microarray) a week or two later.

If trisomy 18 is confirmed, genetic counseling will focus on your values, your specific results, and your options ^[3]. While trisomy 18 is a severe condition, an NIPT or ultrasound cannot predict the exact severity or course for an individual baby. You will be supported in discussing pregnancy management options, including continuation of the pregnancy, palliative neonatal care, life-prolonging interventions, or pregnancy termination ^[19].