Understanding your NIPT result

During pregnancy, small fragments of placental DNA circulate in the pregnant person's bloodstream alongside her own DNA. NIPT sequences these fragments and looks for over- or under-representation of specific chromosomes. Because the DNA is placental rather than directly fetal, NIPT measures the placenta — which almost always matches the fetus but occasionally doesn't (a phenomenon called confined placental mosaicism).

NIPT can be drawn from about 10 weeks of pregnancy onward. It is typically offered to screen for:

• Trisomy 21 (Down syndrome)
• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)
• Sex chromosome aneuploidies — XYY, XXX, XXY (Klinefelter), monosomy X (Turner)
• Fetal sex
• Optionally, specific microdeletion syndromes (e.g., 22q11.2 / DiGeorge)

A screening test tells you how likely it is that something is present. It gives a probability.

A diagnostic test confirms or rules out the condition. CVS (chorionic villus sampling) at 10–13 weeks or amniocentesis at 15+ weeks are the diagnostic tests in pregnancy. Both carry a small procedure-related miscarriage risk (modern estimates: roughly 0.1–0.2% above background).

NIPT is a screen. No matter how it's marketed, "99% accurate" never means "99% diagnostic." It means high sensitivity for the conditions tested — the screen rarely misses a true positive. What you also need to know is its positive predictive value: if the screen says "high risk," what's the chance it's actually correct?

A "low risk" or "negative" NIPT result is highly reassuring for the conditions screened. The false-negative rate for trisomy 21, the most-studied indication, is roughly 0.1–0.3% — meaning a low-risk result misses an affected pregnancy roughly 1–3 times per 1,000. False-negative rates for trisomies 18 and 13 are similar in modern labs.

A low-risk NIPT does not tell you anything about the many other genetic conditions that can affect a pregnancy. It does not replace the anatomy scan. It does not detect single-gene disorders, neural tube defects, or most structural anomalies.

A "high risk" NIPT result is a probability statement, not a diagnosis. The chance that a high-risk result reflects a truly affected pregnancy — the positive predictive value (PPV) — depends on three things:

• The condition tested
• The age of the pregnant person (which affects the background rate)
• The lab's specific performance

Rough PPV estimates from the published literature:

• Trisomy 21: PPV roughly 80–90% depending on age (much higher in pregnant people over 35; somewhat lower in those under 25)
• Trisomy 18: PPV roughly 60–80%
• Trisomy 13: PPV roughly 40–60%
• Sex chromosome aneuploidies (XXY, XYY, XXX, monosomy X): PPV often only 30–50%
• Microdeletions (22q11.2 and others): PPV can be as low as 5–20%

What this means: a "high risk" for a microdeletion is much more likely to be wrong than right. A "high risk" for trisomy 21 in a 38-year-old is much more likely to be right than wrong. The same headline word — "positive" or "high risk" — carries very different real-world meaning depending on what it flagged.

A high-risk NIPT should be followed by diagnostic testing (CVS or amniocentesis) before any irreversible decision. Genetic counseling is the appropriate next step in nearly every case.

Beyond a true fetal aneuploidy, several things can produce an unexpected NIPT result:

• Confined placental mosaicism — the placenta has the change but the fetus doesn't. This is the most common reason for a "false-positive."
• Vanishing twin — DNA from a co-twin lost early in pregnancy can confuse the result.
• Maternal mosaicism or maternal chromosomal differences — the change is in the pregnant person, not the fetus.
• Maternal cancer — rare but documented; certain occult cancers can shed DNA that confuses the screen.
• Low fetal fraction — too little fetal DNA in the sample. The test should be redrawn; results from low-fraction samples are unreliable.