Maternal Serum Screening Markers PAPP-A and AFP
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Direct answer
Maternal serum screening uses PAPP-A, free beta-hCG and AFP to estimate the risk of Down syndrome, Edwards syndrome and neural tube defects before any diagnostic test. PAPP-A is low and free beta-hCG is raised in Down syndrome, while AFP is raised in open neural tube defects and low in chromosomal aneuploidy. A screening result only estimates risk, so a karyotype from chorionic villus sampling or amniocentesis is needed to confirm.
What you must remember
- PAPP-A: Pregnancy-associated plasma protein A, made by the placenta, is low in Down and Edwards syndromes.
- Free beta-hCG: Raised in Down syndrome but low in Edwards syndrome, which is the key discriminating feature.
- Combined first-trimester test: Free beta-hCG and PAPP-A are read with nuchal translucency, done at 11 to 13 weeks plus 6 days.
- Quadruple test: AFP, hCG, unconjugated oestriol and inhibin A are measured at about 15 to 20 weeks.
- AFP in neural tube defects: Raised in open defects, because AFP leaks from the fetal lesion into amniotic fluid and maternal serum.
- Causes of raised AFP: Open neural tube defects, abdominal wall defects, twins, underestimated gestational age and fetal death.
- Causes of low AFP: Down and Edwards syndromes, and an overestimated gestational age.
- Confirmation: Level II ultrasound for structure, and karyotype from CVS or amniocentesis for chromosomes.
Reading the markers against the expected value
Each serum result is reported as a multiple of the median, or MoM, so it is read against the expected level for that gestational age. The table below shows the typical pattern in three common conditions.
| Condition | PAPP-A (first trimester) | Free beta-hCG (first trimester) | AFP (second trimester) |
|---|---|---|---|
| Down syndrome | Low | High | Low |
| Edwards syndrome | Low | Low | Low |
| Open neural tube defect | Normal | Normal | High |
| Gastroschisis | Normal | Normal | High |
A low PAPP-A with a high free beta-hCG points towards Down syndrome, while low values of both markers point more strongly to trisomy 18. AFP alone cannot separate Down from Edwards syndrome, so structural findings on ultrasound are needed.
Laboratories set their own MoM cut-offs, and a value far from 1.0 is flagged for review. Maternal age, weight and nuchal translucency are combined with the markers to give an individual risk estimate. A positive result leads to counselling and a confirmatory test, not to a diagnosis.
Where the exam tries to catch you
Most questions in this area test whether the student knows that a marker is nonspecific, and which test confirms it.
- Trap: Assuming raised AFP always means a neural tube defect Correct: Twins, wrong dating, fetal death and abdominal wall defects also raise AFP, so a level II scan and amniotic fluid acetylated cholinesterase help sort the cause.
- Trap: Reading low PAPP-A as specific to Down syndrome Correct: Low PAPP-A is also linked to pre-eclampsia and growth restriction, so it is a nonspecific marker.
- Trap: Treating a positive serum screen as a diagnosis Correct: Only karyotype from chorionic villus sampling or amniocentesis confirms aneuploidy.
Frequently asked questions
What is the first-trimester pattern of PAPP-A and free beta-hCG in Down syndrome?
In Down syndrome, first-trimester PAPP-A is low and free beta-hCG is raised. The combined test adds nuchal translucency and maternal age to produce an individual risk estimate. The result is a screening estimate, not a diagnosis.
Why is AFP raised in open neural tube defects?
Open neural tube defects expose fetal tissue to amniotic fluid, so AFP leaks from the fetal lesion into amniotic fluid and maternal serum. A raised maternal serum AFP therefore flags an open defect. Confirmation depends on a level II ultrasound and acetylated cholinesterase in amniotic fluid.
Is a raised maternal serum AFP always a neural tube defect?
No, raised maternal serum AFP can also reflect twin pregnancy, underestimated gestational age, fetal death and abdominal wall defects such as gastroschisis. The result is therefore a screening signal that needs ultrasound follow-up. Neural tube defect is only one of several causes.
Which test confirms a positive serum screen for aneuploidy?
Karyotyping of a chorionic villus sample or an amniotic fluid sample confirms the chromosomal diagnosis after a positive serum screen. Serum screening alone can never diagnose Down syndrome or Edwards syndrome. Counselling should precede any invasive test.
What is the second-trimester pattern in Edwards syndrome?
Edwards syndrome, or trisomy 18, shows low AFP, low hCG and low unconjugated oestriol on the quadruple test. This pattern is the basis for the low-marker groups that prompt invasive testing. A detailed ultrasound then looks for structural anomalies that support the diagnosis.