Low-dose aspirin and preterm birth: a randomized controlled trial.
OBJECTIVE
To evaluate the association between low-dose aspirin initiated before conception and the risk of preterm birth.


METHODS
This was a secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial. Women with a history of pregnancy loss (original stratum: one loss less than 20 weeks of gestation during the previous year; expanded stratum: one or two losses with no restrictions on timing or gestational age of the losses) were randomized to either daily low-dose aspirin (81 mg, n=615) and folic acid or folic acid alone (placebo; n=613). Preterm birth was compared between groups using intent-to-treat analysis.


RESULTS
Preterm birth rates were 4.1% (22/535 low-dose aspirin) and 5.7% (31/543 placebo) (relative risk [RR] 0.72, 95% confidence interval [CI] 0.42-1.23); spontaneous preterm birth rates were 1.1% (6/535 low-dose aspirin) and 2.2% (12/543 placebo) (RR 0.51, 95% CI 0.19-1.34); medically indicated preterm birth rates were 2.6% (14/535 low-dose aspirin) and 2.9% (16/543 placebo) (RR 0.89, 95% CI 0.44-1.80). After restriction to confirmed pregnancies using inverse probability weighting, preterm birth rates were 5.7% and 9.0% (RR 0.63, 95% CI 0.37-1.09) and spontaneous preterm birth rates were 1.4% and 3.2% (RR 0.44, 95% CI 0.17-1.18). In confirmed pregnancies in the original stratum, preterm birth occurred in 3.8% and 9.7% of the low-dose aspirin and placebo groups, respectively (RR 0.39, 95% CI 0.16-0.94).


CONCLUSIONS
Preconception low-dose aspirin was not significantly associated with the overall rate of preterm birth. Although the study was underpowered for this secondary analysis, numeric trends in favor of benefit, particularly in the women with a recent, single early pregnancy loss, warrant further investigation.


BACKGROUND
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00467363.
Departments of Obstetrics and Gynecology, University of Utah Health Sciences Center and Intermountain Health Care, Salt Lake City, Utah, and University of Colorado, Aurora, Colorado; the Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Maryland; the Department of Statistics, University of Haifa, Mt. Carmel, Haifa, Israel; the Department of Social and Preventive Medicine, University at Buffalo, Buffalo, New York; the Department of Family, Community and Rural Health, Commonwealth Medical College, Scranton, Pennsylvania.
Robert M
RM
Silver
Katherine
K
Ahrens
Luchin F
LF
Wong
Neil J
NJ
Perkins
Noya
N
Galai
Laurie L
LL
Lesher
David
D
Faraggi
Jean
J
Wactawski-Wende
Janet M
JM
Townsend
Anne M
AM
Lynch
Sunni L
SL
Mumford
Lindsey
L
Sjaarda
Enrique F
EF
Schisterman
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D057194:Intention to Treat Analysis; D016742:Preconception Care; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D014803:Vitamin B Complex / Q000627:therapeutic use; D055815:Young Adult
D016861:Cyclooxygenase Inhibitors; D014803:Vitamin B Complex; D005492:Folic Acid; D001241:Aspirin