e19da5a3472afe1eaad226b7fac8fcff pmc_9406877.pdf 6675222526af535f1e0ba98f95567f48aebdd315 pmc_9406877.pdf 92565c16cdf87acd447f698e5c24ec8fbbbd01a4f24fdb3cb8c19cfb972277b0 pmc_9406877.pdf Title: Reduction in Preterm Preeclampsia after Contingent First-Trimester Screening and Aspirin Prophylaxis in a Routine Care Setting Subject: Objectives: Several multivariate algorithms for preeclampsia (PE) screening in the first trimester have been developed over the past few years. These models include maternal factors, mean arterial pressure (MAP), uterine artery Doppler (UtA-PI), and biochemical markers (pregnancy-associated plasma protein-A (PAPP-A) or placental growth factor (PlGF)). Treatment with low-dose aspirin (LDA) has shown a reduction in the incidence of preterm PE in women with a high-risk assessment in the first trimester. An important barrier to the implementation of first-trimester screening is the cost of performing tests for biochemical markers in the whole population. Theoretical contingent strategies suggest that two-stage screening models could also achieve high detection rates for preterm PE with lower costs. However, no data derived from routine care settings are currently available. This study was conducted to validate and assess the performance of a first-trimester contingent screening process using PlGF for PE, with prophylactic LDA, for decreasing the incidence of preterm PE. Methods: This was a two-phase study. In phase one, a contingent screening model for PE was developed using a multivariate validated model and a historical cohort participating in a non-interventional PE screening study (n = 525). First-stage risk assessment included maternal factors, MAP, UtA-PI, and PAPP-A. Several cut-off levels were tested to determine the best screening performance, and three groups were then defined (high-, medium-, and low-risk groups). PlGF was determined in the medium-risk group to calculate the final risk. Phase two included a validation cohort of 847 singleton pregnancies prospectively undergoing first-trimester PE screening using this approach. Women at high risk of PE received prophylactic treatment with 150 mg of LDA. The clinical impact of the model was evaluated by comparing the incidence of early-onset (<34 weeks) and preterm (<37 weeks) PE between groups. Results: Cut-off levels for the contingent screening model were chosen in the first and second stages of screening to achieve a performance with sensitivities of 100% and 80% for early-onset and preterm PE detection, respectively, with a 15% false positive rate. In the development phase, 21.5% (n = 113) of the women had a medium risk of PE and required second-stage screening. In the prospective validation phase, 15.3% (n = 130) of the women required second-stage screening for PlGF, yielding an overall screen-positive rate of 14.9% (n = 126). The incidence of preterm PE was reduced by 68.4% (1.9% vs. 0.6%, p = 0.031) after one year of screening implementation. Conclusions: Implementation of contingent screening for PE using PlGF in a routine care setting led to a significant reduction (68.4%) in preterm PE, suggesting that contingent screening can achieve similar results to protocols using PlGF in the whole population. This could have financial benefits, with a similar reduction in the rate of preterm PE. Keywords: preeclampsia screening; first trimester; placental growth factor; low-dose aspirin; obstetric outcome; clinical practice Author: Cristina Trilla, Josefina Mora, Nuria Ginjaume, Madalina Nicoleta Nan, Obdulia Alejos, Carla Domínguez, Carmen Vega, Yessenia Godínez, Monica Cruz-Lemini, Juan Parra and Elisa Llurba Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jul 28 11:25:16 2022 CEST ModDate: Thu Jul 28 11:30:11 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1064785 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 VZMQBZ+VnURWPalladioL Type 1 Custom yes yes no 15 0 XHWQXU+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 MRFHTP+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 JXODMD+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 BXZUUH+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 RWBCRL+CMSY10 Type 1 Builtin yes yes no 71 0 HMLFCN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 81 0 HMLFCO+PalatinoLinotype CID TrueType Identity-H yes yes yes 84 0 HMLFCP+PalatinoLinotype TrueType WinAnsi yes yes no 90 0 HMLFDB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 93 0 JLZORU+EURM10 Type 1 Builtin yes yes no 100 0 HMLFCN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 107 0 HMLFCO+PalatinoLinotype CID TrueType Identity-H yes yes yes 110 0 HMLFCP+PalatinoLinotype TrueType WinAnsi yes yes no 116 0 HMLFDB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 119 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 127 0 HMLFCN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 137 0 HMLFCP+PalatinoLinotype TrueType WinAnsi yes yes no 140 0 HMLFDB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 143 0 HMLFCN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 153 0 HMLFCP+PalatinoLinotype TrueType WinAnsi yes yes no 156 0 HMLFDB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 159 0 AWDAAW+VnURWPalladioL-Italic Type 1 Custom yes yes no 172 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-27 02:37:31 CEST RepresentationInformation: pmc_9406877.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-09-23 02:17:58 CEST Size: 1064785 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 280 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Study Design: Model Development Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Study Design: Validation Cohort Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Sample Collection and Laboratory Procedures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Data Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Info: Title: Reduction in Preterm Preeclampsia after Contingent First-Trimester Screening and Aspirin Prophylaxis in a Routine Care Setting Author: Cristina Trilla, Josefina Mora, Nuria Ginjaume, Madalina Nicoleta Nan, Obdulia Alejos, Carla Domínguez, Carmen Vega, Yessenia Godínez, Monica Cruz-Lemini, Juan Parra and Elisa Llurba Subject: Objectives: Several multivariate algorithms for preeclampsia (PE) screening in the first trimester have been developed over the past few years. These models include maternal factors, mean arterial pressure (MAP), uterine artery Doppler (UtA-PI), and biochemical markers (pregnancy-associated plasma protein-A (PAPP-A) or placental growth factor (PlGF)). Treatment with low-dose aspirin (LDA) has shown a reduction in the incidence of preterm PE in women with a high-risk assessment in the first trimester. An important barrier to the implementation of first-trimester screening is the cost of performing tests for biochemical markers in the whole population. Theoretical contingent strategies suggest that two-stage screening models could also achieve high detection rates for preterm PE with lower costs. However, no data derived from routine care settings are currently available. This study was conducted to validate and assess the performance of a first-trimester contingent screening process using PlGF for PE, with prophylactic LDA, for decreasing the incidence of preterm PE. Methods: This was a two-phase study. In phase one, a contingent screening model for PE was developed using a multivariate validated model and a historical cohort participating in a non-interventional PE screening study (n = 525). First-stage risk assessment included maternal factors, MAP, UtA-PI, and PAPP-A. Several cut-off levels were tested to determine the best screening performance, and three groups were then defined (high-, medium-, and low-risk groups). PlGF was determined in the medium-risk group to calculate the final risk. Phase two included a validation cohort of 847 singleton pregnancies prospectively undergoing first-trimester PE screening using this approach. Women at high risk of PE received prophylactic treatment with 150 mg of LDA. The clinical impact of the model was evaluated by comparing the incidence of early-onset (<34 weeks) and preterm (<37 weeks) PE between groups. Results: Cut-off levels for the contingent screening model were chosen in the first and second stages of screening to achieve a performance with sensitivities of 100% and 80% for early-onset and preterm PE detection, respectively, with a 15% false positive rate. In the development phase, 21.5% (n = 113) of the women had a medium risk of PE and required second-stage screening. In the prospective validation phase, 15.3% (n = 130) of the women required second-stage screening for PlGF, yielding an overall screen-positive rate of 14.9% (n = 126). The incidence of preterm PE was reduced by 68.4% (1.9% vs. 0.6%, p = 0.031) after one year of screening implementation. Conclusions: Implementation of contingent screening for PE using PlGF in a routine care setting led to a significant reduction (68.4%) in preterm PE, suggesting that contingent screening can achieve similar results to protocols using PlGF in the whole population. This could have financial benefits, with a similar reduction in the rate of preterm PE. 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