Predict III – second-trimester prenatal screening (total hCG + AFP + uE3), 15–21+3 weeks of gestation
2 days Predict III – second-trimester prenatal screening is a maternal serum screening test performed between 15 – 21+3 weeks of gestation. The investigation is intended to estimate the individual pregnancy risk for certain chromosomal abnormalities assessed through serum screening and for open neural tube defects evaluated primarily via AFP / AFP MoM, in particular:
- trisomy 21 – Down syndrome;
- trisomy 18 – Edwards syndrome;
- neural tube defects (NTD) – including spina bifida.
For optimal accuracy in interpreting serum markers, the recommended sampling window is 16 – 18+6 weeks of gestation.
The test includes the determination of maternal biochemical markers hCG total, AFP, and uE3, as well as their expression in standardized MoM values — multiples of the median: hCG MoM, AFP MoM, and uE3 MoM.
Biochemical marker values are integrated into a risk calculation algorithm together with maternal data and gestational age. For correct interpretation, accurate ultrasound dating of the pregnancy is required, including BPD — biparietal diameter, as indicated in the second-trimester ultrasound report.
Predict III is a screening test, not a diagnostic one. A high-risk result does not confirm the presence of a fetal abnormality but indicates the need for obstetric/genetic counseling and, if necessary, further investigations: detailed morphological ultrasound, NIPT for aneuploidies, amniocentesis, or other investigations recommended by the obstetrician-gynecologist or maternal-fetal medicine specialist.
The test is particularly useful when first-trimester prenatal screening was not performed, was not available, or could not be fully interpreted.
Component | Description and role |
| AFP — alpha-fetoprotein | A protein predominantly produced by the fetus. Elevated levels may be associated with neural tube defects, fetal abdominal wall defects, gestational dating errors, multiple pregnancy, or other obstetric conditions. Interpretation requires ultrasound correlation. Reduced levels may contribute to the risk calculation for trisomy 21. |
AFP MoM | AFP value expressed as multiples of the median (MoM), adjusted for gestational age and relevant maternal factors. It is used in the algorithm, including for the assessment of neural tube defect risk. |
| hCG total — total human chorionic gonadotropin | A hormone produced by trophoblastic/placental tissue. In trisomy 21, hCG levels are frequently elevated; in trisomy 18 they may be reduced. |
hCG MoM | hCG value expressed as multiples of the median (MoM). It is used in the biochemical risk calculation for aneuploidies. |
| uE3 — unconjugated estriol / free estriol | An estrogen hormone produced by the feto-placental unit. Reduced levels may be associated with an increased risk of trisomy 21 and trisomy 18. |
uE3 MoM | uE3 value expressed as multiples of the median (MoM). It is used in the risk calculation algorithm. |
| BPD — biparietal diameter | Ultrasound parameter used for pregnancy dating in the second trimester and for validating the gestational age required for risk calculation. |
These changes do not establish a diagnosis. They contribute to probability estimation and must be interpreted in a clinical and ultrasound context.
The Predict III report presents values determined for maternal biochemical markers hCG total, AFP, and uE3, expressed in concentration units and as MoM — multiples of the median. The report includes the calculation of individual risk for the evaluated conditions, namely:
- age-related risk for trisomy 21;
- calculated risk for trisomy 21 based on serum markers;
- calculated risk for trisomy 18;
- LR — likelihood ratio for T18 risk;
- calculated risk for neural tube defects (NTD);
- AFP MoM assessment for neural tube defect risk;
- cut-off thresholds for T21 and T18;
- graphical representation of T21 risk in relation to maternal age;
- interpretation of the result as low, intermediate/borderline, or increased risk according to report thresholds.
Role of the test
Predict III is designed to identify pregnancies with an increased probability of trisomy 21, trisomy 18, and neural tube defects in the second trimester.
The result allows risk stratification and appropriate clinical management, including:
- routine obstetric care;
- obstetric/genetic counselling;
- detailed fetal morphological ultrasound;
- NIPT in cases of increased aneuploidy risk;
- amniocentesis or other diagnostic tests when indicated;
- specialist evaluation in fetal medicine.
Second-trimester screening does not replace fetal morphological ultrasound. For neural tube defects and other structural anomalies, second-trimester ultrasound assessment remains essential.
Indications
The test is indicated for pregnant women between 15–21+3 weeks of gestation as part of second-trimester prenatal screening.
It may be recommended in the following situations:
- second-trimester screening for trisomy 21, trisomy 18, and neural tube defects;
- first-trimester screening not performed, incomplete, or performed outside the optimal window;
- late presentation to care after the optimal period for combined first-trimester screening;
- advanced maternal age, especially ≥35 years at expected delivery;
- previous pregnancy with fetal aneuploidy or neural tube defect;
- relevant personal or family history of congenital anomalies;
- ultrasound suspicion or need for correlation with biochemical data;
- patient request after counselling regarding the purpose and limitations of screening.
Special considerations in twin pregnancy
In twin pregnancies, interpretation of second-trimester serum screening is more complex than in singleton pregnancies.
Serum markers reflect contributions from both fetuses and the placenta(s), which may affect the performance of the algorithm. The calculated risk may have a higher false-positive rate or reduced sensitivity compared to singleton pregnancies.
In twin pregnancies, results must be interpreted by an obstetrician-gynaecologist or fetal medicine specialist in conjunction with ultrasound findings and the type of twin pregnancy.
Procedure
Patient identity, sampling date, gestational age, required maternal data, and the second-trimester ultrasound report including BPD are verified.
Blood is collected via standard venipuncture. The sample is analysed to determine hCG total, AFP, and uE3 concentrations. The values are then converted into MoM and integrated into the risk calculation algorithm.
The procedure takes only a few minutes and carries no significant risk for mother or fetus.
Interpretation of results
Results must be interpreted by an obstetrician-gynaecologist or fetal medicine specialist.
A low-risk result reduces the likelihood of the evaluated conditions but does not completely exclude chromosomal or structural abnormalities.
A high-risk result for trisomy 21 or trisomy 18 is not diagnostic. It indicates the need for counselling and discussion of further options, including NIPT or invasive diagnostic testing, according to clinical guidelines.
An increased risk for NTD or elevated AFP MoM requires correlation with gestational age, verification of pregnancy dating, and detailed ultrasound evaluation. Elevated AFP does not confirm a neural tube defect but indicates the need for further assessment.
Medical sources:
https://www.sciencedirect.com/science/article/pii/S1098360021038831
https://tjodistanbul.org/uploads/screening-for-fetal-chromosomal-abnormalities-number-226.pdf
https://pmc.ncbi.nlm.nih.gov/articles/PMC4812093/
https://www.isuog.org/static/4e2ed89e-fa8a-42c2-9c0929cd89cb58ff/ISUOG-Practice-Guidelines-routine-mid-trimester-fetal-ultrasound.pdf
https://labtestsonline.org.uk/tests/second-trimester-maternal-screening
https://link.springer.com/article/10.1186/s12884-026-08771-5
https://www.gfmer.ch/Endo/PGC_network/Second_trimester_maternal_serum_Paralloi.htm
Preparation:
No special preparation is required.
An interval of approximately 2–3 hours after the last meal is recommended before blood collection.
Blood is drawn from a vein via standard venipuncture.
The following data are mandatory for risk calculation:
- patient’s date of birth;
- blood sampling date;
- ultrasound examination date;
- gestational age at the time of ultrasound;
- patient’s weight;
- ethnicity;
- number of fetuses.
An ultrasound report from the second trimester is required, preferably performed on the same day or one day before blood collection, but not older than 2 weeks at the time of testing, and it must include BPD — biparietal diameter.
In the absence of mandatory data or the required ultrasound report, risk calculation may be incomplete, inaccurate, or impossible. The final result depends on the accuracy of the clinical and ultrasound information entered into the algorithm.
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