33dad8c4f019531f4493bc5b348a7e39 274122.pdf 325f7c5e9c1df0d383959b8dc28c3a5398c048b8 274122.pdf fe23bab93c820797aca113fbb00a87cd4e2f17e3da6a925081e6782d9b42f549 274122.pdf Title: Impact of Angiogenic and Cardiovascular Biomarkers for Prediction of Placental Dysfunction in the First Trimester of Pregnancy Subject: Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small for gestational age infants or preterm birth. The aim of this study was to assess the screening performance of PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), uric acid, and high-sensitivity cardiac troponin T (hs-TnT) in the prediction of adverse obstetric outcomes related to placental insufficiency. This retrospective case–control study was based on a cohort of 1390 pregnant women, among which 210 presented pre-eclampsia, small for gestational age infants, or preterm birth. Two hundred and eight women with healthy pregnancies were selected as controls. Serum samples were collected between weeks 9 and 13 of gestation, and maternal serum concentrations of PlGF, sFlt-1, NT-proBNP, uric acid, and hs-TnT were measured. Multivariate regression analysis was used to generate predictive models combining maternal factors with the above-mentioned biomarkers. Women with placental dysfunction had lower median concentrations of PlGF (25.77 vs. 32.00 pg/mL; p < 0.001), sFlt-1 (1212.0 vs. 1363.5 pg/mL; p = 0.001), and NT-proBNP (51.22 vs. 68.71 ng/L; p < 0.001) and higher levels of uric acid (193.66 mol/L vs. 177.40 mol/L; p = 0.001). There was no significant difference between groups regarding the sFlt-1/PlGF ratio. Hs-TnT was not detected in 70% of the maternal serums analyzed. Altered biomarker concentrations increased the risk of the analyzed complications both in univariate and multivariate analyses. The addition of PlGF, sFlt-1, and NT-proBNP to maternal variables improved the prediction of pre-eclampsia, small for gestational age infants, and preterm birth (area under the curve: 0.710, 0.697, 0.727, and 0.697 vs. 0.668, respectively). Reclassification improvement was greater in maternal factors plus the PlGF model and maternal factors plus the NT-p roBNP model (net reclassification index, NRI: 42.2% and 53.5%, respectively). PlGF, sFlt-1, NT-proBNP, and uric acid measurements in the first trimester of pregnancy, combined with maternal factors, can improve the prediction of adverse perinatal outcomes related to placental dysfunction. In addition to PlGF, uric acid and NT-proBNP are two promising predictive biomarkers for placental dysfunction in the first trimester of pregnancy. Keywords: angiogenic factors; placental growth factor (PlGF); soluble fms-like tyrosine kinase-1 (sFlt-1); N-terminal pro-brain natriuretic peptide (NT-proBNP); high-sensitivity cardiac troponin T (hs-TnT); uric acid; preeclampsia; small for gestational age; preterm birth Author: Madalina Nicoleta Nan, Álvaro García-Osuna, Josefina Mora, Cristina Trilla, Assumpta Antonijuan, Vanesa Orantes, Mónica Cruz-Lemini, Francisco Blanco-Vaca and Elisa Llurba Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Apr 29 10:20:15 2023 CEST ModDate: Sat Apr 29 10:25:20 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1073635 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UZLFPZ+VnURWPalladioL Type 1 Custom yes yes no 10 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 15 0 AZMEUD+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 XLSWDK+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 YGRZVH+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 OPETZR+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 FFDGWE+CMSY10 Type 1 Builtin yes yes no 75 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 82 0 EUQOAW+EURM7 Type 1 Builtin yes yes no 92 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 96 0 FHBIAZ+EURB7 Type 1 Builtin yes yes no 100 0 PDXFNG+PazoMath-Bold Type 1 Builtin yes yes no 104 0 HJNBHP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 118 0 HJNBIA+PalatinoLinotype CID TrueType Identity-H yes yes yes 121 0 HJNBIB+PalatinoLinotype TrueType WinAnsi yes yes no 127 0 HJNBID+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 130 0 HJNCIO+PalatinoLinotype TrueType MacRoman yes yes no 133 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-16 02:28:45 CEST RepresentationInformation: 274122.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-05-15 10:28:13 CEST Size: 1073635 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 276 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Sample Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Info: Title: Impact of Angiogenic and Cardiovascular Biomarkers for Prediction of Placental Dysfunction in the First Trimester of Pregnancy Author: Madalina Nicoleta Nan, Álvaro García-Osuna, Josefina Mora, Cristina Trilla, Assumpta Antonijuan, Vanesa Orantes, Mónica Cruz-Lemini, Francisco Blanco-Vaca and Elisa Llurba Subject: Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small for gestational age infants or preterm birth. The aim of this study was to assess the screening performance of PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), uric acid, and high-sensitivity cardiac troponin T (hs-TnT) in the prediction of adverse obstetric outcomes related to placental insufficiency. This retrospective case control study was based on a cohort of 1390 pregnant women, among which 210 presented pre-eclampsia, small for gestational age infants, or preterm birth. Two hundred and eight women with healthy pregnancies were selected as controls. Serum samples were collected between weeks 9 and 13 of gestation, and maternal serum concentrations of PlGF, sFlt-1, NT-proBNP, uric acid, and hs-TnT were measured. Multivariate regression analysis was used to generate predictive models combining maternal factors with the above-mentioned biomarkers. Women with placental dysfunction had lower median concentrations of PlGF (25.77 vs. 32.00 pg/mL; p < 0.001), sFlt-1 (1212.0 vs. 1363.5 pg/mL; p = 0.001), and NT-proBNP (51.22 vs. 68.71 ng/L; p < 0.001) and higher levels of uric acid (193.66 mol/L vs. 177.40 mol/L; p = 0.001). There was no significant difference between groups regarding the sFlt-1/PlGF ratio. Hs-TnT was not detected in 70% of the maternal serums analyzed. Altered biomarker concentrations increased the risk of the analyzed complications both in univariate and multivariate analyses. The addition of PlGF, sFlt-1, and NT-proBNP to maternal variables improved the prediction of pre-eclampsia, small for gestational age infants, and preterm birth (area under the curve: 0.710, 0.697, 0.727, and 0.697 vs. 0.668, respectively). Reclassification improvement was greater in maternal factors plus the PlGF model and maternal factors plus the NT-p roBNP model (net reclassification index, NRI: 42.2% and 53.5%, respectively). PlGF, sFlt-1, NT-proBNP, and uric acid measurements in the first trimester of pregnancy, combined with maternal factors, can improve the prediction of adverse perinatal outcomes related to placental dysfunction. In addition to PlGF, uric acid and NT-proBNP are two promising predictive biomarkers for placental dysfunction in the first trimester of pregnancy. Keywords: angiogenic factors; placental growth factor (PlGF); soluble fms-like tyrosine kinase-1 (sFlt-1); N-terminal pro-brain natriuretic peptide (NT-proBNP); high-sensitivity cardiac troponin T (hs-TnT); uric acid; preeclampsia; small for gestational age; preterm birth Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Apr 29 10:20:15 CEST 2023 ModDate: Sat Apr 29 10:25:20 CEST 2023 ID: 0x517af6cd91aa6c77956e30060966757f, 0x517af6cd91aa6c77956e30060966757f Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: OPETZR+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: OPETZR+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: MPUDFL+PazoMath FontSubset: true FirstChar: 68 LastChar: 68 FontDescriptor: FontName: MPUDFL+PazoMath Flags: Symbolic FontBBox: -40, -283, 878, 946 FontFile: true Font: BaseFont: 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