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Updated: May 28, 2026
High Frequency Ultrasound for the Analysis of Fetal and Placental Development In Vivo
Published on: November 8, 2018
First trimester fetal ultrasound parameters associated with PAPP-A and fβ-hCG
Ioannis Papastefanou1, Athena Souka, Makarios Eleuftheriades
1Fetal Medicine Unit, 3rd Department of Obstetrics and Gynaecology, University of Athens, Attikon University Hospital, Athens, Greece.
Insights
Adjusting first-trimester screening markers, free beta-human chorionic gonadotropin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A), for ultrasound measurements like crown-rump-length (CRL) significantly improves accuracy. This adjustment refines the calculation of multiples of gestation (MoM) for better aneuploidy screening.
Area of Science:
- Prenatal diagnostics and screening
- Maternal-fetal medicine
- Biochemical and ultrasound markers in pregnancy
Background:
- First-trimester screening for chromosomal abnormalities relies on maternal serum markers and ultrasound biometry.
- Standardized algorithms, like the Fetal Medicine Foundation (FMF) method, calculate multiples of gestation (MoM) for these markers.
- Potential confounding factors in ultrasound measurements may affect the accuracy of MoM calculations.
Purpose of the Study:
- To investigate the associations between specific biochemical markers (fβ-hCG, PAPP-A) and ultrasound parameters (dCRL, dFHR, dNT) at 11-14 weeks.
- To calculate adjusted MoM values for fβ-hCG and PAPP-A by accounting for these associations.
- To evaluate the impact of these adjustments on the accuracy of first-trimester screening.
Main Methods:
- Retrospective analysis of 5,536 singleton euploid pregnancies undergoing first-trimester screening.
- Calculation of observed MoM for fβ-hCG and PAPP-A using the FMF algorithm.
- Calculation of adjusted MoM values incorporating associations with delta crown-rump-length (dCRL), delta fetal heart rate (dFHR), and delta nuchal translucency (dNT).
Main Results:
- Significant correlations were found: fβ-hCG positively correlated with dCRL and negatively with dNT; PAPP-A correlated positively with dNT and negatively with dCRL and dFHR.
- Adjusted MoM values for fβ-hCG and PAPP-A (0.98 and 0.99) differed significantly from observed MoM values (1.02 and 0.92) (p < 0.001).
- Crown-rump-length (CRL) measurements showed an increasing effect with gestation, particularly after 62 mm, potentially overestimating fetal size.
Conclusions:
- Adjusting MoM calculations for dCRL, dFHR, and dNT enhances the accuracy of fβ-hCG and PAPP-A measurements in first-trimester screening.
- The findings suggest that CRL measurement may overestimate fetal size towards the end of the 11-14 week screening window.
- Improved MoM calculation through adjustment can lead to more precise risk assessment for chromosomal abnormalities.
Objective:
To study the association of fβ-hCG and PAPP-A measured at 11-14 weeks of gestation with delta crown-rump-length (dCRL), delta fetal heart rate (dFHR) and delta nuchal translucency (dNT). To calculate adjusted MoM taking into consideration these associations.
Methods:
Retrospective cross-sectional study on 5,536 singleton euploid pregnancies participating in a first trimester screening program for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry. Adjusted MoM were calculated for fβ-hCG and PAPP-A and compared to the observed MoM (calculated by the Fetal Medicine Foundation screening algorithm).
Results:
fβ-hCG correlates positively with dCRL and negatively with dNT, whereas PAPP-A shows a positive correlation with dNT and a negative one with dCRL and dFHR. After adjustment for the ultrasound parameters, the median MoM values for fβ-hCG and PAPP-A changed from 1.02 and 0.92 observed MoM to 0.98 and 0.99 adjusted MoM respectively. The difference between the observed and adjusted MoM was statistically significant (p < 0.001). Delta CRL increases with gestation and this effect manifests mainly after CRL of 62 mm.
Conclusions:
Adjustment for dCRL, dFHR and dNT improves the calculation of MoM for fβ-hCG and PAPP-A. CRL measurement overestimates fetal size at the end of the screening period 11-14 weeks.
