First Trimester Screening Patterns: Trisomy 21, 18, and 13
First trimester screening is performed at 11-13 weeks and combines a nuchal translucency (NT) ultrasound measurement with two maternal serum markers: PAPP-A and free β-hCG. This combination detects roughly 85% of Down syndrome cases with a 5% false-positive rate. The key exam skill is recognizing that all three common autosomal trisomies increase NT and decrease PAPP-A — so the discriminating marker is the free β-hCG, which is HIGH only in Trisomy 21.
Components and Timing
First trimester screening occurs at 11-13 weeks and has three moving parts: (1) nuchal translucency (NT) measured by ultrasound, (2) maternal serum PAPP-A, and (3) maternal serum free β-hCG. Detection rate is about 85% for Down syndrome at a 5% false-positive rate. Remember this is a screening test, not diagnostic — any positive result should be followed by an offer of confirmatory diagnostic testing (CVS or amniocentesis).
Down Syndrome (Trisomy 21)
The pattern is increased NT, decreased PAPP-A, and increased free β-hCG. The key differentiator is that hCG is HIGH — this is what sets Trisomy 21 apart from the other trisomies, which suppress hCG. A useful anchor from second trimester serum screening reinforces the same theme: in Down syndrome, hCG (and inhibin) are UP while AFP and estriol are down.
Trisomy 18 (Edwards)
The pattern is increased NT, decreased PAPP-A, and decreased free β-hCG. The key differentiator is that everything is LOW — both serum markers are suppressed. This uniformly depressed serum profile, with only NT elevated, distinguishes Edwards syndrome from Down syndrome, where hCG rises.
Trisomy 13 (Patau)
The pattern is increased NT, decreased PAPP-A, and decreased free β-hCG. Trisomy 13 classically resembles Trisomy 18 — both show a uniformly depressed serum profile with only NT elevated. Because the hCG is LOW, Patau does not show the high-hCG signature that defines Down syndrome.
Cell-Free DNA (NIPT) in Context
Cell-free DNA (cfDNA/NIPT) analyzes fragments of placental DNA in maternal blood and offers the highest sensitivity and specificity for trisomies 21, 18, and 13, plus detection of sex chromosome abnormalities and fetal sex, with no procedural risk. It remains a screening test — a positive result requires confirmatory amnio or CVS. It can yield false positives (especially in low-risk populations), may fail in obesity or early gestation, and does not detect structural abnormalities, which still require anatomy ultrasound.
High-yield
- First trimester screening = NT + PAPP-A + free β-hCG at 11-13 weeks.
- All three common trisomies (21, 18, 13) show INCREASED NT and DECREASED PAPP-A.
- Free β-hCG is the great differentiator: HIGH in Down (T21), LOW in both Edwards (T18) and Patau (T13).
- Down syndrome detection ~85% with 5% false-positive rate.
- Second trimester mnemonic: AFP and estriol are down in Down; hCG and inhibin are up.
- cfDNA/NIPT has the highest sensitivity/specificity for trisomies 21, 18, 13 and no procedural risk.
- Every positive screen must be offered diagnostic testing (CVS or amniocentesis) before pregnancy decisions.
Pitfalls
- Assuming a low PAPP-A points to a specific trisomy — it is decreased in all three, so it does not distinguish them.
- Forgetting that hCG goes UP (not down) in Down syndrome; the low-AFP intuition tempts students to expect low hCG.
- Treating cfDNA/NIPT as diagnostic — it is still screening and needs confirmatory amnio/CVS.
- Expecting cfDNA to catch structural anomalies; it does not — anatomy ultrasound is still required.
- Thinking Trisomy 13 has a high or 'variable' hCG — it is LOW, resembling Trisomy 18, and only Trisomy 21 shows high hCG.
Clinical pearls
- If free β-hCG is HIGH with increased NT and low PAPP-A, think Down syndrome.
- If everything is LOW except NT, think Trisomy 18 (Edwards) or Trisomy 13 (Patau).
- NIPT can determine fetal sex and detect sex chromosome abnormalities, but never replaces diagnostic testing.
- A positive screen changes probability, not diagnosis — always offer CVS or amniocentesis next.
Frequently asked
What are the three components of first trimester screening and when is it done?
Nuchal translucency ultrasound plus maternal serum PAPP-A and free β-hCG, performed at 11-13 weeks.
How do you distinguish Trisomy 21 from Trisomy 18 on first trimester screening?
Both show increased NT and decreased PAPP-A. The difference is free β-hCG: HIGH in Trisomy 21 (Down), LOW in Trisomy 18 (Edwards).
What is the free β-hCG pattern in Trisomy 13?
Decreased (LOW). Patau classically resembles Trisomy 18 — increased NT, decreased PAPP-A, and low free β-hCG — so it lacks the high-hCG signature of Down syndrome.
What is the detection rate for Down syndrome with first trimester screening?
About 85%, with a 5% false-positive rate.
How is cell-free DNA (NIPT) different from standard first trimester screening?
NIPT analyzes placental DNA fragments in maternal blood, offering the highest sensitivity and specificity for trisomies 21, 18, and 13 with no procedural risk, but it is still screening and does not detect structural abnormalities.
If a screening test is positive, what is the next step?
Offer diagnostic testing — CVS or amniocentesis — to confirm before making any decisions about the pregnancy.
Why is a low PAPP-A not useful for telling the trisomies apart?
PAPP-A is decreased in Trisomy 21, 18, and 13 alike, so it flags risk but cannot specify which trisomy.
What are the limitations of cfDNA/NIPT?
It can produce false positives (especially in low-risk populations), may fail in obesity or early gestation, remains a screening test, and does not screen for structural anomalies, which require anatomy ultrasound.
Turn this into reasoning you can use on exam day — practice First Trimester Screening Patterns on branching cases where your decisions shape the patient.