title: Expanded findings from a randomized controlled trial of preconception low-dose aspirin and pregnancy loss.
abstract: OBJECTIVE
  What is the association between daily preconception-initiated low-dose aspirin (LDA) treatment and very early pregnancy losses or euploid (chromosomally normal) losses among women with one to two prior losses?
  
  
  CONCLUSIONS
  Daily LDA initiated preconception was not associated with the rate or type of pregnancy loss among women with a history of one to two prior pregnancy losses.
  
  
  BACKGROUND
  LDA is often used to treat recurrent pregnancy loss with reductions in pregnancy loss generally only observed among women with antiphospholipid antibodies, and null associations observed among women without antiphospholipid antibodies. We previously evaluated the association between LDA and pregnancy loss overall among women with one to two prior losses in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial and found no association, though did not distinguish between potential effects at different stages of pregnancy loss, including implantation failure, or between euploid and aneuploid losses.
  
  
  METHODS
  The EAGeR trial was a multi-site prospective block-randomized double-blind placebo-controlled trial. In total, 1228 women were randomized to daily LDA (81 mg/day) plus folic acid (400 mcg/day), or placebo plus folic acid. Participants were assigned study drug for less than or equal to six menstrual cycles or if they conceived, throughout pregnancy with study drug discontinued at 36 weeks gestation. This analysis includes additional outcome information obtained from chart abstractions after the completion of the trial, as well as testing of stored urine for measurement of hCG and detection of very early pregnancy losses, and karyotyping of the products of conception for assessment of aneuploidy of the losses.
  
  
  METHODS
  Women aged 18-40 with a history of one to two prior losses and actively trying to conceive were randomized (n = 615 LDA and n = 613 placebo) at four clinical centers in the USA (2007-2011). Log-binomial regression was used to estimate risk ratios under the intent-to-treat approach.
  
  
  RESULTS
  Daily LDA initiated preconception was not associated with clinically recognized pregnancy losses or implantation failures among women with proved fecundity and a history of one to two prior losses. Specifically, 1088 (88.6%) women completed the trial with 797 having an hCG detected pregnancy (64.9%). Overall there were 133 clinical losses (12.7% LDA versus 11.8% placebo, P = 0.71) and 55 implantation failures (5.2% LDA versus 4.9% placebo, P = 0.89). No differences were found in rate of euploid losses (RR 1.11, 95% confidence interval: 0.99, 1.26).
  
  
  CONCLUSIONS
  Generalizability of these findings is limited to women with a history of one to two prior losses, and may further be limited to women of white race with higher socioeconomic status as given the rigors of the study protocol participants tended to be white and have higher incomes and more education. We were also missing karyotype information on approximately one-third of the clinically recognized pregnancy losses, which may limit our power to detect effects on euploid losses, though detailed sensitivity analysis showed similar results.
  
  
  CONCLUSIONS
  Our data do not support the general use of LDA to decrease pregnancy loss and further demonstrate no increased risk of loss for women on LDA treatment.
  
  
  BACKGROUND
  This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426). The authors have no conflicts of interest.
  
  
  BACKGROUND
  The trial was registered at ClinicalTrials.gov #NCT00467363.
  27 April 2007.
  15 June 2007.
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd. 7B03, Rockville, MD 20852, USA mumfords@mail.nih.gov.
authors.forename: Sunni L
authors.initials: SL
authors.lastname: Mumford
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Room 2B200 SOM, 50 North Medical Drive, Salt Lake City, UT 84132, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Silver
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd. 7B03, Rockville, MD 20852, USA.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Sjaarda
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Department of Family, Community and Rural Health, Commonwealth Medical College, 525 East Pine Street, Scranton, PA 18509, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Townsend
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado, 12700 East 19th Avenue, Aurora, CO 80045, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Lynch
authors.affiliation: Department of Statistics, University of Haifa, Mt Carmel, Haifa 31905, Israel.
authors.forename: Noya
authors.initials: N
authors.lastname: Galai
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Room 2B200 SOM, 50 North Medical Drive, Salt Lake City, UT 84132, USA.
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Lesher
authors.affiliation: Department of Statistics, University of Haifa, Mt Carmel, Haifa 31905, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Faraggi
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd. 7B03, Rockville, MD 20852, USA.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Perkins
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd. 7B03, Rockville, MD 20852, USA.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Schliep
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd. 7B03, Rockville, MD 20852, USA.
authors.forename: Shvetha M
authors.initials: SM
authors.lastname: Zarek
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd. 7B03, Rockville, MD 20852, USA.
authors.forename: Enrique F
authors.initials: EF
authors.lastname: Schisterman
mesh_terms: D000022:Abortion, Spontaneous / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D011247:Pregnancy; D011256:Pregnancy Outcome; D012044:Regression Analysis
chemical_list: D001241:Aspirin
keywords: conception; fertility; live birth; low-dose aspirin; pregnancy loss