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Impact of replacing or adding pregnancy-associated plasma protein-A at 11-13 weeks on screening for preterm
Y M I Wah1, D S Sahota1, P Chaemsaithong1
1Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China.
Insights
Pregnancy-associated plasma protein-A (PAPP-A) shows lower performance than placental growth factor (PlGF) in screening for preterm pre-eclampsia. Using PAPP-A instead of PlGF reduces detection rates for preterm pre-eclampsia.
Area of Science:
- Maternal-fetal medicine
- Biomarker research
- Obstetric screening
Background:
- Preterm pre-eclampsia (PE) is a significant cause of maternal and neonatal morbidity.
- First-trimester screening for preterm PE is crucial for timely intervention.
- Placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) are key biomarkers in PE screening.
Purpose of the Study:
- To compare the screening performance of PAPP-A versus PlGF for preterm PE at 11-13 weeks gestation.
- To evaluate the combined use of PAPP-A and PlGF in preterm PE screening.
- To assess the impact of substituting PAPP-A for PlGF in existing screening protocols.
Main Methods:
- Secondary analysis of a prospective screening study involving 6546 singleton pregnancies.
- Risk assessment for preterm PE using maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), PlGF, and PAPP-A.
- Comparison of screening performance via receiver-operating-characteristics (ROC) curves and detection rates at 10% false-positive rate (FPR).
Main Results:
- PlGF combined with other factors yielded an area under the ROC curve (AUC) of 0.854 and a detection rate of 59.46% at 10% FPR.
- Replacing PlGF with PAPP-A resulted in a lower AUC (0.813) and detection rate (51.35%).
- Using both PAPP-A and PlGF showed comparable AUC (0.855) and detection rates (59.46%) to PlGF alone, but PAPP-A did not identify additional cases missed by PlGF.
Conclusions:
- Screening for preterm PE using PAPP-A instead of PlGF leads to a reduced detection rate.
- PlGF demonstrates superior or equivalent performance compared to PAPP-A in first-trimester preterm PE screening.
- Current screening protocols relying on PlGF are more effective than those substituting PAPP-A.
Objective:
To assess whether pregnancy-associated plasma protein-A (PAPP-A) alters or provides equivalent screening performance as placental growth factor (PlGF) when screening for preterm pre-eclampsia (PE) at 11-13 weeks of gestation.
Methods:
This was a secondary analysis of a non-intervention screening study of 6546 singleton pregnancies that were screened prospectively for preterm PE in the first trimester between December 2016 and June 2018. Patient-specific risks for preterm PE were estimated by maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), PlGF and PAPP-A. A competing-risks model with biomarkers expressed as multiples of the median was used. All women and clinicians were blinded to the risk for preterm PE. The performance of screening for preterm PE using PlGF vs PAPP-A vs both PAPP-A and PlGF was assessed by comparing areas under the receiver-operating-characteristics (AUC) curves. McNemar's test was used to compare detection rate at a fixed false-positive rate (FPR) of 10%.
Results:
PlGF and PAPP-A were measured in 6546 women, of whom 37 developed preterm PE. The AUC and detection rate at 10% FPR using PlGF in combination with maternal history, MAP and UtA-PI were 0.854 and 59.46%, respectively. The respective values were 0.813 and 51.35% when replacing PlGF with PAPP-A and 0.855 and 59.46% when using both PAPP-A and PlGF. Statistically non-significant differences were noted in AUC when replacing PlGF with PAPP-A (ΔAUC, 0.04; P = 0.095) and when using both PAPP-A and PlGF (ΔAUC, 0.002; P = 0.423). However, on an individual case basis, screening using PlGF in conjunction with maternal history, MAP and UtA-PI identified three (8.1%) additional pregnancies that developed preterm PE and that were not identified when replacing PlGF with PAPP-A. Screening using PAPP-A in addition to maternal history and other biomarkers did not identify any additional pregnancies.
Conclusion:
On an individual case basis, adoption of a screening strategy that uses PAPP-A instead of PlGF results in reduced detection of preterm PE, consistent with previous literature. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
