ea7ea51d40970126e0eb525f43fc43d9 pmc_9148897.pdf e012a09bce42b6fbad3e440c243050fd15304314 pmc_9148897.pdf 47123177a389dcb10bda45d90196358419f5dd701d678a3f9c1dd786d419749b pmc_9148897.pdf Title: First-Trimester SARS-CoV-2 Infection: Clinical Presentation, Inflammatory Markers, and Obstetric Outcomes Subject: Objective: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. Methods: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8–14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. Results: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 109/L vs. 2.16 × 109/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90–1.82] vs. 1.08 [IQR 0.66–1.61] p = 0.014, vs. 1.08 [IQR 0.77–1.55] p = 0.019, respectively). Obstetric outcomes were not increased. Conclusions: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women. Author: Trilla C.; Mora J.; Crovetto F.; Crispi F.; Gratacos E.; Llurba E. Creator: Adobe InDesign 17.0 (Windows) Producer: Adobe PDF Library 16.0.3 CreationDate: Tue May 3 08:52:29 2022 CEST ModDate: Mon May 23 07:52:30 2022 CEST Custom Metadata: no Metadata Stream: yes Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 793.701 pts Page rot: 0 File size: 285208 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IQHQIX+MyriadPro-Bold Type 1C WinAnsi yes yes yes 281 0 FMNOSD+MyriadPro-Regular Type 1C Custom yes yes yes 282 0 FXKESD+MinionPro-Regular Type 1C Custom yes yes yes 296 0 PFACCJ+MyriadPro-BoldIt Type 1C WinAnsi yes yes yes 297 0 ZPBFMP+MyriadPro-It Type 1C WinAnsi yes yes yes 242 0 JRZNWV+MinionPro-It Type 1C WinAnsi yes yes yes 239 0 LCWUYR+SegoeUISymbol TrueType WinAnsi yes yes yes 232 0 FXKESD+MinionPro-Regular Type 1C WinAnsi yes yes yes 241 0 FXKESD+MinionPro-Regular Type 1C WinAnsi yes yes yes 235 0 CMLSCJ+SegoeUI TrueType WinAnsi yes yes no 247 0 YGNUYR+SegoeUI-Italic TrueType WinAnsi yes yes no 250 0 FXKESD+MinionPro-Regular Type 1C WinAnsi yes yes yes 248 0 FXKESD+MinionPro-Regular Type 1C WinAnsi yes yes yes 246 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-01 02:43:18 CEST RepresentationInformation: pmc_9148897.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-16 02:33:32 CEST Size: 285208 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 314 FreeObjects: 2 IncrementalUpdates: 2 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseThumbs Language: de-DE Outlines: Item: Title: startTableBody Item: Title: startTableBody Item: Title: startTableBody Item: Title: StartZeile Item: Title: Zwischenlinie Item: Title: startTableBody Item: Title: startTableBody Item: Title: startTableBody Info: Title: First-Trimester SARS-CoV-2 Infection: Clinical Presentation, Inflammatory Markers, and Obstetric Outcomes Author: Trilla C.; Mora J.; Crovetto F.; Crispi F.; Gratacos E.; Llurba E. Subject: Objective: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. Methods: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8 14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. Results: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 109/L vs. 2.16 × 109/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90 1.82] vs. 1.08 [IQR 0.66 1.61] p = 0.014, vs. 1.08 [IQR 0.77 1.55] p = 0.019, respectively). Obstetric outcomes were not increased. Conclusions: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women. Creator: Adobe InDesign 17.0 (Windows) Producer: Adobe PDF Library 16.0.3 CreationDate: Tue May 03 08:52:29 CEST 2022 ModDate: Mon May 23 08:22:30 CEST 2022 Trapped: False ID: 0x3ba7f9036dd2144aa08863c12eaf404b, 0x8cf3c4d7eb8170b9c951eeeb4dc22470 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ZPBFMP+MyriadPro-It FontSubset: true FirstChar: 82 LastChar: 116 FontDescriptor: FontName: ZPBFMP+MyriadPro-It Flags: Nonsymbolic, Italic FontBBox: -112, -250, 1090, 873 FontFile3: true Encoding: WinAnsiEncoding ToUnicode: true Font: BaseFont: FXKESD+MinionPro-Regular FontSubset: true FirstChar: 26 LastChar: 243 FontDescriptor: FontName: FXKESD+MinionPro-Regular Flags: Serif, Nonsymbolic FontBBox: -289, -360, 1684, 917 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: PFACCJ+MyriadPro-BoldIt FontSubset: true FirstChar: 58 LastChar: 118 FontDescriptor: FontName: PFACCJ+MyriadPro-BoldIt Flags: Nonsymbolic, Italic FontBBox: -96, -250, 1225, 889 FontFile3: true Encoding: WinAnsiEncoding ToUnicode: true Font: BaseFont: IQHQIX+MyriadPro-Bold FontSubset: true FirstChar: 32 LastChar: 121 FontDescriptor: FontName: IQHQIX+MyriadPro-Bold Flags: Nonsymbolic FontBBox: -92, -250, 1256, 897 FontFile3: true Encoding: WinAnsiEncoding ToUnicode: true Font: BaseFont: FMNOSD+MyriadPro-Regular FontSubset: true FirstChar: 30 LastChar: 243 FontDescriptor: FontName: FMNOSD+MyriadPro-Regular Flags: Nonsymbolic FontBBox: -46, -250, 1126, 881 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: JRZNWV+MinionPro-It FontSubset: true FirstChar: 82 LastChar: 116 FontDescriptor: FontName: JRZNWV+MinionPro-It Flags: Serif, Nonsymbolic, Italic FontBBox: -201, -360, 1684, 919 FontFile3: true Encoding: WinAnsiEncoding ToUnicode: true TrueType: Font: BaseFont: CMLSCJ+SegoeUI FontSubset: true FirstChar: 32 LastChar: 121 FontDescriptor: FontName: CMLSCJ+SegoeUI Flags: Nonsymbolic FontBBox: -573, -411, 1999, 1298 FontFile2: true Encoding: WinAnsiEncoding Font: BaseFont: LCWUYR+SegoeUISymbol FontSubset: true FirstChar: 174 LastChar: 174 FontDescriptor: FontName: LCWUYR+SegoeUISymbol Flags: Nonsymbolic FontBBox: -513, -789, 1961, 1499 FontFile2: true Encoding: WinAnsiEncoding ToUnicode: true Font: BaseFont: YGNUYR+SegoeUI-Italic FontSubset: true FirstChar: 32 LastChar: 110 FontDescriptor: FontName: YGNUYR+SegoeUI-Italic Flags: Nonsymbolic, Italic FontBBox: -458, -264, 1422, 1298 FontFile2: true Encoding: WinAnsiEncoding XMP: Adobe PDF Library 16.0.3 False 2022-05-03T08:52:29+02:00 2022-05-23T11:22:30+05:30 Trilla C.; Mora J.; Crovetto F.; Crispi F.; Gratacos E.; Llurba E. First-Trimester SARS-CoV-2 Infection: Clinical Presentation, Inflammatory Markers, and Obstetric Outcomes Objective: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. Methods: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8–14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. Results: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 10<sup>9</sup>/L vs. 2.16 × 10<sup>9</sup>/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90–1.82] vs. 1.08 [IQR 0.66–1.61] p = 0.014, vs. 1.08 [IQR 0.77–1.55] p = 0.019, respectively). Obstetric outcomes were not increased. Conclusions: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women. 2022-05-03T08:52:29+02:00 2022-05-23T11:22:30+05:30 2022-05-23T11:22:30+05:30 Adobe InDesign 17.0 (Windows) application/pdf Trilla C.; Mora J.; Crovetto F.; Crispi F.; Gratacos E.; Llurba E. First-Trimester SARS-CoV-2 Infection: Clinical Presentation, Inflammatory Markers, and Obstetric Outcomes Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.<br /> Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.<br /> Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Objective: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. Methods: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8–14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. Results: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 10<sup>9</sup>/L vs. 2.16 × 10<sup>9</sup>/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90–1.82] vs. 1.08 [IQR 0.66–1.61] p = 0.014, vs. 1.08 [IQR 0.77–1.55] p = 0.019, respectively). Obstetric outcomes were not increased. Conclusions: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women. Severe acute respiratory syndrome coronavirus 2 COVID-19 First trimester Preeclampsia Obstetric outcomes uuid:b26e9d5d-c6ca-4e4c-8514-50d757ff860a adobe:docid:indd:a1ace0ee-97e8-11da-8f16-a6a04fdc746b xmp.id:32caacea-2733-3e45-a09f-6f3cdb3ec914 proof:pdf xmp.iid:2bfa3cdd-d452-bc4d-9bb9-599b9e044b42 xmp.did:31a9a67a-8f0c-114e-91d3-c2b07973b146 adobe:docid:indd:a1ace0ee-97e8-11da-8f16-a6a04fdc746b default converted from application/x-indesign to application/pdf Adobe InDesign 17.0 (Windows) / 2022-05-03T08:52:29+02:00 True https://www.karger.com/Article/FullText/523974#copyright application/pdf Trilla C.; Mora J.; Crovetto F.; Crispi F.; Gratacos E.; Llurba E. First-Trimester SARS-CoV-2 Infection: Clinical Presentation, Inflammatory Markers, and Obstetric Outcomes Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.<br /> Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.<br /> Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Objective: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. Methods: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8–14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. Results: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 10<sup>9</sup>/L vs. 2.16 × 10<sup>9</sup>/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90–1.82] vs. 1.08 [IQR 0.66–1.61] p = 0.014, vs. 1.08 [IQR 0.77–1.55] p = 0.019, respectively). Obstetric outcomes were not increased. Conclusions: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women. Severe acute respiratory syndrome coronavirus 2 COVID-19 First trimester Preeclampsia Obstetric outcomes Pages: Page: Sequence: 1 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 247, 387, 253, 373 ActionDest: 126 Annotation: Subtype: Link Rect: 228, 336, 233, 322 ActionDest: 126 Annotation: Subtype: Link Rect: 238, 336, 243, 322 ActionDest: 126 Annotation: Subtype: Link Rect: 252, 298, 257, 284 ActionDest: 126 Annotation: Subtype: Link Rect: 157, 247, 162, 233 ActionDest: 126 Annotation: Subtype: Link Rect: 201, 221, 207, 207 ActionDest: 126 Annotation: Subtype: Link Rect: 163, 132, 168, 118 ActionDest: 126 Annotation: Subtype: Link Rect: 215, 106, 220, 92 ActionDest: 126 Annotation: Subtype: Link Rect: 529, 718, 535, 704 ActionDest: 126 Annotation: Subtype: Link Rect: 541, 718, 546, 704 ActionDest: 126 Annotation: Subtype: Link Rect: 497, 680, 502, 666 ActionDest: 126 Annotation: Subtype: Link Rect: 495, 655, 500, 641 ActionDest: 126 Annotation: Subtype: Link Rect: 500, 655, 506, 641 ActionDest: 126 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 407, 317, 411, 305 ActionDest: 126 Annotation: Subtype: Link Rect: 411, 317, 416, 305 ActionDest: 126 Annotation: Subtype: Link Rect: 461, 275, 466, 263 ActionDest: 126 Annotation: Subtype: Link Rect: 466, 275, 471, 263 ActionDest: 126 Page: Sequence: 4 Page: Sequence: 5 Page: Sequence: 6 Page: Sequence: 7 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 167, 349, 173, 335 ActionDest: 126 Annotation: Subtype: Link Rect: 173, 349, 178, 335 ActionDest: 126 Annotation: Subtype: Link Rect: 149, 285, 155, 271 ActionDest: 126 Annotation: Subtype: Link Rect: 155, 285, 160, 271 ActionDest: 126 Annotation: Subtype: Link Rect: 256, 272, 261, 258 ActionDest: 126 Annotation: Subtype: Link Rect: 175, 247, 181, 233 ActionDest: 126 Annotation: Subtype: Link Rect: 181, 247, 186, 233 ActionDest: 126 Annotation: Subtype: Link Rect: 192, 106, 197, 92 ActionDest: 126 Annotation: Subtype: Link Rect: 197, 106, 202, 92 ActionDest: 126 Annotation: Subtype: Link Rect: 440, 667, 445, 653 ActionDest: 126 Annotation: Subtype: Link Rect: 445, 667, 451, 653 ActionDest: 126 Annotation: Subtype: Link Rect: 501, 642, 507, 628 ActionDest: 126 Annotation: Subtype: Link Rect: 507, 642, 512, 628 ActionDest: 126 Annotation: Subtype: Link Rect: 328, 604, 333, 590 ActionDest: 126 Annotation: Subtype: Link Rect: 333, 604, 338, 590 ActionDest: 126 Annotation: Subtype: Link Rect: 419, 553, 425, 539 ActionDest: 126 Annotation: Subtype: Link Rect: 425, 553, 430, 539 ActionDest: 126 Annotation: Subtype: Link Rect: 455, 374, 460, 360 ActionDest: 126 Annotation: Subtype: Link Rect: 307, 349, 313, 335 ActionDest: 126 Annotation: Subtype: Link Rect: 342, 336, 347, 322 ActionDest: 126 Annotation: Subtype: Link Rect: 347, 336, 353, 322 ActionDest: 126 Annotation: Subtype: Link Rect: 523, 310, 528, 296 ActionDest: 126 Annotation: Subtype: Link Rect: 528, 310, 533, 296 ActionDest: 126 Annotation: Subtype: Link Rect: 321, 183, 327, 169 ActionDest: 126 Annotation: Subtype: Link Rect: 327, 183, 332, 169 ActionDest: 126 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 82, 591, 87, 577 ActionDest: 126 Annotation: Subtype: Link Rect: 87, 591, 93, 577 ActionDest: 126 Annotation: Subtype: Link Rect: 207, 412, 212, 398 ActionDest: 126 Annotation: Subtype: Link Rect: 212, 412, 217, 398 ActionDest: 126 Annotation: Subtype: Link Rect: 223, 412, 228, 398 ActionDest: 126 Annotation: Subtype: Link Rect: 228, 412, 233, 398 ActionDest: 126 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 42, 585, 55, 574 ActionDest: 1 Annotation: Subtype: Link Rect: 171, 547, 204, 536 Annotation: Subtype: Link Rect: 55, 537, 122, 526 Annotation: Subtype: Link Rect: 42, 528, 55, 517 ActionDest: 1 Annotation: Subtype: Link Rect: 183, 499, 204, 488 Annotation: Subtype: Link Rect: 55, 490, 130, 479 Annotation: Subtype: Link Rect: 42, 471, 55, 460 ActionDest: 1 Annotation: Subtype: Link Rect: 107, 423, 156, 412 Annotation: Subtype: Link Rect: 42, 404, 55, 393 ActionDest: 1 Annotation: Subtype: Link Rect: 184, 385, 204, 374 Annotation: Subtype: Link Rect: 55, 376, 180, 365 Annotation: Subtype: Link Rect: 42, 357, 55, 346 ActionDest: 1 Annotation: Subtype: Link Rect: 110, 347, 155, 336 Annotation: Subtype: Link Rect: 42, 328, 55, 317 ActionDest: 1 Annotation: Subtype: Link Rect: 55, 300, 119, 289 Annotation: Subtype: Link Rect: 42, 290, 55, 279 ActionDest: 1 Annotation: Subtype: Link Rect: 67, 262, 112, 251 Annotation: Subtype: Link Rect: 42, 252, 55, 241 ActionDest: 1 Annotation: Subtype: Link Rect: 80, 186, 156, 175 Annotation: Subtype: Link Rect: 216, 585, 229, 574 ActionDest: 1 Annotation: Subtype: Link Rect: 335, 547, 378, 536 Annotation: Subtype: Link Rect: 229, 537, 240, 526 Annotation: Subtype: Link Rect: 216, 528, 229, 517 ActionDest: 1 Annotation: Subtype: Link Rect: 252, 509, 311, 498 Annotation: Subtype: Link Rect: 216, 499, 229, 488 ActionDest: 1 Annotation: Subtype: Link Rect: 259, 461, 290, 450 Annotation: Subtype: Link Rect: 216, 452, 229, 441 ActionDest: 33 Annotation: Subtype: Link Rect: 361, 433, 378, 422 Annotation: Subtype: Link Rect: 229, 423, 280, 412 Annotation: Subtype: Link Rect: 216, 414, 229, 403 ActionDest: 33 Annotation: Subtype: Link Rect: 324, 385, 378, 374 Annotation: Subtype: Link Rect: 229, 376, 247, 365 Annotation: Subtype: Link Rect: 216, 366, 229, 355 ActionDest: 58 Annotation: Subtype: Link Rect: 271, 338, 320, 327 Annotation: Subtype: Link Rect: 216, 319, 229, 308 ActionDest: 58 Annotation: Subtype: Link Rect: 254, 300, 335, 289 Annotation: Subtype: Link Rect: 216, 281, 229, 270 ActionDest: 58 Annotation: Subtype: Link Rect: 282, 252, 376, 241 Annotation: Subtype: Link Rect: 414, 556, 437, 545 Annotation: Subtype: Link Rect: 440, 528, 552, 517 Annotation: Subtype: Link Rect: 403, 518, 413, 507 Annotation: Subtype: Link Rect: 440, 471, 468, 460 Annotation: Subtype: Link Rect: 403, 423, 480, 412 Annotation: Subtype: Link Rect: 508, 385, 552, 374 Annotation: Subtype: Link Rect: 403, 376, 411, 365 Annotation: Subtype: Link Rect: 403, 338, 452, 327 Annotation: Subtype: Link Rect: 435, 281, 509, 270 Annotation: Subtype: Link Rect: 533, 233, 552, 222 Annotation: Subtype: Link Rect: 403, 224, 421, 213 Annotation: Subtype: Link Rect: 455, 186, 499, 175 Checksum: d9788272 Type: CRC32 Checksum: ea7ea51d40970126e0eb525f43fc43d9 Type: MD5 Checksum: e012a09bce42b6fbad3e440c243050fd15304314 Type: SHA-1 Checksum: 47123177a389dcb10bda45d90196358419f5dd701d678a3f9c1dd786d419749b Type: SHA-256