PMID- 30797761
OWN - NLM
STAT- Publisher
LR  - 20190414
IS  - 1097-6868 (Electronic)
IS  - 0002-9378 (Linking)
DP  - 2019 Feb 21
TI  - Aspirin delays the development of preeclampsia.
LID - S0002-9378(19)30386-2 [pii]
LID - 10.1016/j.ajog.2019.02.034 [doi]
AB  - BACKGROUND: In the Combined Multimarker Screening and Randomized Patient
      Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial, risks of
      preterm preeclampsia were obtained from the competing risk model. Consenting
      women with risks of greater than 1 in 100 were randomized to treatment with
      aspirin or placebo. The trial showed strong evidence of an effect (odds ratio,
      0.38, 95% confidence interval, 0.20-0.74) on the incidence of preterm
      preeclampsia, which was the primary outcome of Aspirin for Evidence-Based
      Preeclampsia Prevention. There was a small and insignificant effect on the
      incidence of term preeclampsia, which was a secondary outcomes (odds ratio, 0.95,
      95% confidence interval, 0.64-1.39). These differential effects on term and
      preterm preeclampsia could reflect a mechanism in which the action of aspirin is 
      to delay the delivery with preeclampsia, thereby converting what would be,
      without treatment, preterm preeclampsia to term preeclampsia. OBJECTIVE: The
      objective of the study was to examine the hypothesis that the effect of aspirin
      is to delay the time of delivery in women who have preeclampsia. STUDY DESIGN:
      This was an unplanned exploratory analysis of data from the Aspirin for
      Evidence-Based Preeclampsia Prevention trial. The delay hypothesis predicts that 
      in groups for which preterm preeclampsia, without aspirin, were infrequent
      relative to term preeclampsia, a reduction in term preeclampsia would be expected
      because few cases of preterm preeclampsia would be converted to term
      preeclampsia. In contrast, in groups for which preterm preeclampsia were frequent
      relative to term preeclampsia, the conversion of preterm preeclampsia to term
      preeclampsia by aspirin would reduce or even reverse any effect on the incidence 
      term preeclampsia. This is examined using the Aspirin for Evidence-Based
      Preeclampsia Prevention trial data by analysis of the effect of aspirin on the
      incidence of term preeclampsia stratified according to the risk of preterm
      preeclampsia at randomization. Given that women were included in Aspirin for
      Evidence-Based Preeclampsia Prevention with risks of preterm preeclampsia >1 in
      100, a risk cutoff if 1 in 50 was used to define higher risk and lower risk
      strata. A statistical model in which the effect of aspirin is to delay the
      gestational age at delivery was fitted to the Aspirin for Evidence-Based
      Preeclampsia Prevention trial data and the consistency of the predictions from
      this model with the observed incidence was demonstrated. RESULTS: In the
      lower-risk group (<1 in 50), there was a reduction in the incidence of term
      preeclampsia (odds ratio, 0.62, 95% confidence interval, 0.29-1.30). In contrast,
      in the higher risk group (>/=1 in 50) there was a small increase in the incidence
      of term- preeclampsia (odds ratio 1.11, 95% confidence interval, 0.71- .75).
      Although these effects fail to achieve significance, they are consistent with the
      delay hypothesis. Within the framework of the aspirin-related delay hypothesis,
      the effect of aspirin was to delay the gestational age at delivery with
      preeclampsia by an estimated 4.4 weeks (95% confidence interval, 1.4-7.1 weeks)
      for those that in the placebo group would be delivered at 24 weeks and the effect
      decreased by an estimated 0.23 weeks (95% confidence interval, 0.021-0.40 weeks) 
      for each week of gestation so that at 40(+0) weeks, the estimated delay was by
      0.8 weeks (95% confidence interval, -0.03 to 1.7 weeks). CONCLUSION: The Aspirin 
      for Evidence-Based Preeclampsia Prevention trial data are consistent with the
      hypothesis that aspirin delays the gestational age at delivery with preeclampsia.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Wright, David
AU  - Wright D
AD  - Institute of Health Research, University of Exeter, Exeter, United Kingdom.
FAU - Nicolaides, Kypros H
AU  - Nicolaides KH
AD  - Harris Birthright Research Centre for Fetal Medicine, King's College, London,
      United Kingdom. Electronic address: kypros@fetalmedicine.com.
LA  - eng
PT  - Journal Article
DEP - 20190221
PL  - United States
TA  - Am J Obstet Gynecol
JT  - American journal of obstetrics and gynecology
JID - 0370476
OTO - NOTNLM
OT  - Aspirin for Evidence-Based Preeclampsia Prevention trial
OT  - aspirin
OT  - competing risks model
OT  - first-trimester screening
OT  - preeclampsia
OT  - pregnancy
OT  - preterm delivery
OT  - pyramid of pregnancy care
OT  - term delivery
EDAT- 2019/02/25 06:00
MHDA- 2019/02/25 06:00
CRDT- 2019/02/25 06:00
PHST- 2018/11/19 00:00 [received]
PHST- 2019/02/14 00:00 [revised]
PHST- 2019/02/15 00:00 [accepted]
PHST- 2019/02/25 06:00 [pubmed]
PHST- 2019/02/25 06:00 [medline]
PHST- 2019/02/25 06:00 [entrez]
AID - S0002-9378(19)30386-2 [pii]
AID - 10.1016/j.ajog.2019.02.034 [doi]
PST - aheadofprint
SO  - Am J Obstet Gynecol. 2019 Feb 21. pii: S0002-9378(19)30386-2. doi:
      10.1016/j.ajog.2019.02.034.