Preconception low-dose aspirin and pregnancy outcomes: Results from the EAGeR randomised trial

Enrique F. Schisterman, Robert M. Silver, Laurie L. Lesher, David Faraggi, Jean Wactawski-Wende, Janet M. Townsend, Anne M. Lynch, Neil J. Perkins, Sunni L. Mumford, Noya Galai

Research output: Contribution to journalArticle

Abstract

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. Findings: 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. Interpretation: 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. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalThe Lancet
Volume384
Issue number9937
DOIs
StatePublished - 2014
Externally publishedYes

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Pregnancy Outcome
Aspirin
Placebos
Pregnancy
National Institute of Child Health and Human Development (U.S.)
Folic Acid
Uterine Hemorrhage
National Institutes of Health (U.S.)
Menstrual Cycle
Gestational Age
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Schisterman, E. F., Silver, R. M., Lesher, L. L., Faraggi, D., Wactawski-Wende, J., Townsend, J. M., ... Galai, N. (2014). Preconception low-dose aspirin and pregnancy outcomes: Results from the EAGeR randomised trial. The Lancet, 384(9937), 29-36. https://doi.org/10.1016/S0140-6736(14)60157-4

Preconception low-dose aspirin and pregnancy outcomes : Results from the EAGeR randomised trial. / Schisterman, Enrique F.; Silver, Robert M.; Lesher, Laurie L.; Faraggi, David; Wactawski-Wende, Jean; Townsend, Janet M.; Lynch, Anne M.; Perkins, Neil J.; Mumford, Sunni L.; Galai, Noya.

In: The Lancet, Vol. 384, No. 9937, 2014, p. 29-36.

Research output: Contribution to journalArticle

Schisterman, EF, Silver, RM, Lesher, LL, Faraggi, D, Wactawski-Wende, J, Townsend, JM, Lynch, AM, Perkins, NJ, Mumford, SL & Galai, N 2014, 'Preconception low-dose aspirin and pregnancy outcomes: Results from the EAGeR randomised trial', The Lancet, vol. 384, no. 9937, pp. 29-36. https://doi.org/10.1016/S0140-6736(14)60157-4
Schisterman EF, Silver RM, Lesher LL, Faraggi D, Wactawski-Wende J, Townsend JM et al. Preconception low-dose aspirin and pregnancy outcomes: Results from the EAGeR randomised trial. The Lancet. 2014;384(9937):29-36. https://doi.org/10.1016/S0140-6736(14)60157-4
Schisterman, Enrique F. ; Silver, Robert M. ; Lesher, Laurie L. ; Faraggi, David ; Wactawski-Wende, Jean ; Townsend, Janet M. ; Lynch, Anne M. ; Perkins, Neil J. ; Mumford, Sunni L. ; Galai, Noya. / Preconception low-dose aspirin and pregnancy outcomes : Results from the EAGeR randomised trial. In: The Lancet. 2014 ; Vol. 384, No. 9937. pp. 29-36.
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abstract = "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. Findings: 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. Interpretation: 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. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).",
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TY - JOUR

T1 - Preconception low-dose aspirin and pregnancy outcomes

T2 - Results from the EAGeR randomised trial

AU - Schisterman, Enrique F.

AU - Silver, Robert M.

AU - Lesher, Laurie L.

AU - Faraggi, David

AU - Wactawski-Wende, Jean

AU - Townsend, Janet M.

AU - Lynch, Anne M.

AU - Perkins, Neil J.

AU - Mumford, Sunni L.

AU - Galai, Noya

PY - 2014

Y1 - 2014

N2 - 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. Findings: 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. Interpretation: 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. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).

AB - 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. Findings: 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. Interpretation: 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. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).

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