Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial.
BACKGROUND
Preconception-initiated low-dose aspirin might positively affect pregnancy outcomes, but this possibility has not been adequately assessed. Our aim was to investigate whether low-dose aspirin improved livebirth rates in women with one to two previous pregnancy losses.


METHODS
In this multicentre, block-randomised, double-blind, placebo-controlled trial, women aged 18-40 years who were attempting to become pregnant were recruited from four medical centres in the USA. Participants were stratified by eligibility criteria--the original stratum was restricted to women with one loss at less than 20 weeks' gestation during the previous year, whereas the expanded stratum included women with one to two previous losses, with no restrictions on gestational age or time of loss. Women were block-randomised by centre and eligibility stratum in a 1:1 ratio. Preconception-initiated daily low-dose aspirin (81 mg per day) plus folic acid was compared with placebo plus folic acid for up to six menstrual cycles; for women who conceived, study treatment continued until 36 weeks' gestation. Participants, trial staff, and investigators were masked to the assigned treatment. The primary outcome was livebirth rate, which was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00467363.


RESULTS
Overall, 1228 women were recruited and randomly assigned between June 15, 2007, and July 15, 2011, 1078 of whom completed the trial and were included in the analysis (535 in the low-dose aspirin group and 543 in the placebo group). 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=0·0984; absolute difference in livebirth rate 5·09% [95% CI -0·84 to 11·02]). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=0·7812). In the original stratum, 151 (62%) of 242 women in the low-dose aspirin group had livebirths, compared with 133 (53%) of 250 in the placebo group (p=0·0446; absolute difference in livebirth rate 9·20% [0·51 to 17·89]). In the expanded stratum, 158 (54%) of 293 women in the low-dose aspirin group and 153 (52%) of 293 in the placebo group had livebirths (p=0·7406; absolute difference in livebirth rate 1·71% [-6·37 to 9·79]). Major adverse events were similar between treatment groups. Low-dose aspirin was associated with increased vaginal bleeding, but this adverse event was not associated with pregnancy loss.


CONCLUSIONS
Preconception-initiated low-dose aspirin was not significantly associated with livebirth or pregnancy loss in women with one to two previous losses. However, higher livebirth rates were seen in women with a single documented loss at less than 20 weeks' gestation during the previous year. Low-dose aspirin is not recommended for the prevention of pregnancy loss.


BACKGROUND
Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. Electronic address: schistee@mail.nih.gov.
Enrique F
EF
Schisterman
Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, School of Medicine, Salt Lake City, UT, USA.
Robert M
RM
Silver
Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, School of Medicine, Salt Lake City, UT, USA.
Laurie L
LL
Lesher
Department of Statistics, University of Haifa, Haifa, Israel.
David
D
Faraggi
Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY, USA.
Jean
J
Wactawski-Wende
Department of Family, Community and Rural Health, Commonwealth Medical College, Scranton, PA, USA.
Janet M
JM
Townsend
Department of Obstetrics and Gynecology, University of Colorado, Denver, CO, USA.
Anne M
AM
Lynch
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
Neil J
NJ
Perkins
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
Sunni L
SL
Mumford
Department of Statistics, University of Haifa, Haifa, Israel.
Noya
N
Galai
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D001724:Birth Weight; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005865:Gestational Age; D006801:Humans; D050498:Live Birth / Q000453:epidemiology*; D016742:Preconception Care / Q000379:methods*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology; D011256:Pregnancy Outcome / Q000453:epidemiology*; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005492:Folic Acid; D001241:Aspirin