Burchard, Julja

DeHoff, Peter

Fox, Angela C

Herrero, Tiffany

Hickok, Durlin E

Jay Boniface, J

Laurent, Louise C

Leonardo, Trevor

Olsen, Richelle

Ramos, Gladys A

Roeder, Hilary

Srinivasan, Srimeenakshi

To, Coung

Treacy, Ryan

English

Consortium, The PAPR Study

Boniface, J Jay

eScholarship - University of California

UC San DiegoUC San Diego Previously Published WorksTitle512: Discovery and verification of maternal serum miRNA biomarkers predictive of preeclampsiaPermalinkhttps://escholarship.org/uc/item/2jr25171AuthorsHerrero, TiffanySrinivasan, SrimeenakshiTreacy, Ryanet al.Publication Date2019DOI10.1016/j.ajog.2018.11.534 Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaPoster Session III ajog.org512 Discovery and verification of maternal serummiRNA biomarkers predictive of preeclampsiaTiffany Herrero1, Srimeenakshi Srinivasan2, Ryan Treacy3,Richelle Olsen4, Trevor Leonardo5, Peter DeHoff2, Coung To2,Angela C. Fox3, Gladys A. Ramos2, Hilary Roeder2, The PAPRStudy Consortium6, Durlin E. Hickok3, Julja Burchard3,J. Jay Boniface3, Louise C. Laurent21Stanford University, Stanford, CA, 2UC San Diego, La Jolla, CA, 3SeraPrognostics, Salt Lake City, UT, 4St Joseph Medical Center, Tacoma, WA,5University of Illinois at Chicago, Department of Medicine, Chicago, IL, 6ThePAPR Study Consortium, Salt Lake City, CAOBJECTIVE: Placental dysfunction, including preeclampsia and fetalgrowth restriction, is a leading contributor to maternal and fetalmorbidity and mortality. Development of effective prevention andtreatment strategies has been limited by lack of identification of at-risk pregnancies. We performed small RNA sequencing of maternalserum microRNAs (miRNAs) to discover and independently verifybiomarkers differentially expressed in patients who later developedpreeclampsia.STUDY DESIGN: Maternal serum was collected between 17-28 weeksgestation in two cohorts: The high-risk UCSD Placenta Study (19cases, 29 controls); and the Sera Prognostics PAPR Study (54 cases,110 controls). Samples were divided into Discovery (2/3) and Veri-fication sets (1/3). Cases and controls were matched for gestationalage (GA) at blood draw (Table 1). miRNAs were isolated andsequenced to yield miRNA counts. Individual miRNAs and pairwiseratios (reversals) were tested in blinded verification.RESULTS: Biomarker discovery and verification were performed onthe entire GA range and for 3 GA windows: 170/7 - 215/7 (Early);195/7 - 244/7 (Middle); and 222/7 - 280/7 (Late) weeks.In Discovery, best performing miRNAs and reversals were selectedfor each GA window. Performance was then confirmed in blindedVerification (Table 2). 7/50 Early GA reversals had significant AUCs(mean Discovery AUC 0.78, mean Verification AUC 0.79). 21/50Late GA reversals had significant AUCs (mean Discovery AUC 0.71,mean Verification AUC 0.68). Of biological importance, verifiedreversals contained a high proportion of miRNAs that were stronglyexpressed in placenta and/or encoded in the chr14q32 and chr19q13miRNA clusters. miR-155-5p, present in 21 verified reversals, hasbeen reported to mediate repression of eNOS by TNFa, which is aregulatory interaction associated with preeclampsia.CONCLUSION: We identified and verified differentially abundantmiRNAs in maternal serum at 17-28 weeks GA in pregnancies thatlater developed signs and symptoms of preeclampsia compared topregnancies with uncomplicated outcomes. Our findings suggestthat maternal serum miRNAs may be useful as biomarkers forprediction of placental dysfunction and warrant validation in largeindependent cohorts.S344 American Journal of Obstetrics & Gynecology Supplement to JANUARY513 Obstetric outcomes for women receiving newergeneration antiepileptic drugs: retrospective cohortstudy using claims databaseTiffany Herrero, Jason P. Bentley, Anna I. Girsen, Samantha Do,Sanaa Suharwardy, Danielle M. Panelli, Deirdre J. Lyell,Yasser El-Sayed, Maurice L. DruzinStanford University, Stanford, CAOBJECTIVE: Women with epilepsy are at increased risk for adversepregnancy outcomes. Since the 1990s, over 11 new antiepilepticdrugs (AEDs) have been introduced. We aimed to describe the use ofnewer AEDs in pregnancy and differences in rates of obstetricoutcomes.STUDY DESIGN: From the Truven Health MarketScan CommercialClaims and Encounters Database (years 2011-14), we identifiedwomen who had a delivery admission, outpatient pharmacy dis-penses for newer generation AEDs (Table) and an indication ofepilepsy based on diagnosis codes during the 12 months prior todelivery. Obstetric outcomes included preterm birth, cesarean de-livery, postpartum hemorrhage, placental abruption, hypertensivedisorders of pregnancy, preterm labor, and severe maternalmorbidity (SMM). We described the prevalence of the use of newerAEDs and rates of obstetric outcomes and absolute risk differencecompared to women without a diagnosis of epilepsy (Table).2019

512: Discovery and verification of maternal serum miRNA biomarkers predictive of preeclampsia

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512: Discovery and verification of maternal serum miRNA biomarkers predictive of preeclampsia

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