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Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared
M Mendoza1, P Garcia-Manau1, S Arévalo1
1Maternal Fetal Medicine Unit, Department of Obstetrics, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Insights
First-trimester screening for pre-eclampsia (PE) using pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) shows similar predictive ability for early-onset and preterm PE regardless of measurement timing. This supports a flexible two-step approach for risk assessment.
Area of Science:
- Obstetrics and Gynecology
- Maternal-Fetal Medicine
- Biomarker Research
Background:
- Pre-eclampsia (PE) poses significant risks to maternal and fetal health.
- Accurate prediction of early-onset and preterm PE is crucial for timely intervention.
- First-trimester screening involves assessing maternal serum biomarkers like PAPP-A and PlGF.
Purpose of the Study:
- To compare the predictive performance of first-trimester combined screening for early-onset and preterm PE.
- To evaluate the impact of measuring PAPP-A and PlGF before versus after 11 weeks' gestation on PE prediction.
- To assess the utility of different risk calculation algorithms (Gaussian and FMF) in relation to biomarker measurement timing.
Main Methods:
- Secondary analysis of a prospective cohort study involving 2641 singleton pregnancies.
- Serum PAPP-A and PlGF levels were assessed and categorized based on measurement timing (before vs. at/after 11 weeks' gestation).
- Prediction models (Gaussian and FMF) were used to calculate risk scores for early-onset and preterm PE, with performance evaluated using ROC curves and AUCs.
Main Results:
- No significant differences in the prediction of early-onset or preterm PE were observed between measuring PAPP-A and PlGF before or after 11 weeks' gestation using the Gaussian model.
- The FMF model also showed no significant differences in AUCs, except for a slightly higher AUC for early-onset PE prediction when PAPP-A was measured at or after 11 weeks.
- Overall detection rates for early-onset and preterm PE were comparable across different measurement timings.
Conclusions:
- First-trimester screening for PE demonstrates similar predictive accuracy for early-onset and preterm PE irrespective of whether PAPP-A and PlGF are measured before or after 11 weeks' gestation.
- This finding supports the flexibility of a two-step PE risk assessment strategy, allowing for immediate risk calculation during the first-trimester scan.
- The study highlights that the timing of biomarker assessment within the first trimester does not substantially compromise the ability to predict early-onset and preterm PE.
Objectives:
To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation.
Methods:
This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks.
Results:
Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks.
Conclusions:
The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
