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Meta-Analysis
. 2019 Oct 30;2019(10):CD004659.
doi: 10.1002/14651858.CD004659.pub3.

Antiplatelet agents for preventing pre-eclampsia and its complications

Lelia Duley  1 , Shireen Meher  2 , Kylie E Hunter  3 , Anna Lene Seidler  3 , Lisa M Askie  3
Affiliations
Meta-Analysis

Antiplatelet agents for preventing pre-eclampsia and its complications

Lelia Duley et al. Cochrane Database Syst Rev. .

Abstract

Background: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia.

Objectives: To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia.

Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review.

Selection criteria: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet.

Data collection and analysis: Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.

Main results: Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups.

Authors' conclusions: Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.

PubMed Disclaimer

Conflict of interest statement

Lelia Duley LD was a member of the steering committee for Barbados 1998 and a co‐author of the report, and a member of the PARIS Collaborative Group. She was awarded an NIHR grant for applied research for a programme of work on care at very preterm birth

Lisa Askie received a postdoctoral fellowship (Australian NHMRC 2003‐2006) to conduct the PARIS Collaboration.

Kylie Hunter: none known.

Shireen Meher: none known.

Anna Lene Seidler: none known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' graph for the nine large trials: review authors' judgements about each risk of bias item presented as percentages across all studies.
4
4
Risk of bias, summary: review authors' judgements about each risk of bias item for each included study.
5
5
'Risk of bias' summary for the nine large trials: review authors' judgements about each risk of bias item for each study
6
6
Funnel plot of comparison: 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), outcome: 1.1 Pre‐eclampsia (IPD vs AD).
7
7
Pre‐specified subgroup analysis using PARIS IPD
8
8
Condensed version of Figure 4 (2 subgroups only) using PARIS IPD
9
9
Funnel plot of comparison: 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (subgrouped by maternal risk), outcome: 1.4 Fetal and neonatal deaths.
10
10
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.12 Fetal, neonatal, infant and childhood deaths (subgroups by time of death).
11
11
Funnel plot of comparison: 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), outcome: 1.3 Preterm birth (IPD vs AD).
12
12
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.15 Preterm birth (< 34 weeks).
13
13
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.16 Preterm birth (< 32 weeks).
14
14
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.17 Preterm birth (< 28 weeks).
15
15
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.18 Preterm birth (mutually exclusive subgroups) ‐ IPD only.
16
16
Funnel plot of comparison: 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), outcome: 1.4 Small‐for‐gestational age (IPD vs AD).
17
17
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.19 Small‐for‐gestational age (subgrouped by severity) ‐ AD only, trial definition.
18
18
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.20 Any baby SGA < 3rd centile or as reported ‐ IPD only.
19
19
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.8 Gestational hypertension using best available definition ‐ IPD only.
20
20
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.9 Gestational hypertension using trialists own definition ‐ IPD only.
21
21
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.10 Gestational hypertension PARIS definition ‐ IPD only.
22
22
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.27 Postpartum haemorrhage > 500 mL.
23
23
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.22 Pregnancy with SAO (including maternal death, baby death, PE, SGA, preterm) ‐ IPD only.
24
24
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.26 Placental abruption.
25
25
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.21 Birthweight < 2500 g.
26
26
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.28 Any baby required assisted ventilation.
27
27
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.24 Non spontaneous labour (induced labour or pre‐labour caesarean) ‐ IPD only.
28
28
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.11 Gestation at onset proteinuria by best definition ‐ IPD only.
29
29
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.14 Gestation at birth (mean, weeks).
30
30
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.25 Antepartum haemorrhage ‐ IPD only.
31
31
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.40 Caesarean section.
32
32
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.1 Severe maternal morbidity (eclampsia, renal failure, liver failure, HELLP syndrome, stroke ‐ IPD only).
33
33
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.29 Intraventricular haemorrhage.
34
34
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.30 Other neonatal bleed.
35
35
Funnel plot of comparison: 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), outcome: 5.35 Admission to a special care baby unit.
1.1
1.1. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 1 Pre‐eclampsia (IPD vs AD).
1.2
1.2. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 2 Fetal death, neonatal death, or death before hospital discharge (IPD vs AD).
1.3
1.3. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 3 Preterm birth (IPD vs AD).
1.4
1.4. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 4 Small‐for‐gestational age (IPD vs AD).
1.5
1.5. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 5 Pre‐eclampsia (IPD/AD combined).
1.6
1.6. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 6 Fetal death, neonatal death, or death before hospital discharge (IPD/AD combined).
1.7
1.7. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 7 Preterm birth (IPD/AD combined).
1.8
1.8. Analysis
Comparison 1 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by maternal risk), Outcome 8 Small‐for‐gestational age (IPD/AD combined).
2.1
2.1. Analysis
Comparison 2 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by gestation at entry), Outcome 1 Pre‐eclampsia.
2.2
2.2. Analysis
Comparison 2 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by gestation at entry), Outcome 2 Fetal death, neonatal death, or death before hospital discharge.
2.3
2.3. Analysis
Comparison 2 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by gestation at entry), Outcome 3 Preterm birth.
2.4
2.4. Analysis
Comparison 2 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (primary outcomes, subgroups by gestation at entry), Outcome 4 Small‐for‐gestational age.
3.1
3.1. Analysis
Comparison 3 Antiplatelet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by use of placebo), Outcome 1 Pre‐eclampsia.
3.2
3.2. Analysis
Comparison 3 Antiplatelet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by use of placebo), Outcome 2 Fetal death, neonatal death, or death before hospital discharge.
3.3
3.3. Analysis
Comparison 3 Antiplatelet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by use of placebo), Outcome 3 Preterm birth.
3.4
3.4. Analysis
Comparison 3 Antiplatelet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by use of placebo), Outcome 4 Small‐for‐gestational age.
4.1
4.1. Analysis
Comparison 4 Antiplatet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by dose), Outcome 1 Pre‐eclampsia.
4.2
4.2. Analysis
Comparison 4 Antiplatet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by dose), Outcome 2 Fetal death, neonatal death, or death before hospital discharge.
4.3
4.3. Analysis
Comparison 4 Antiplatet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by dose), Outcome 3 Preterm birth.
4.4
4.4. Analysis
Comparison 4 Antiplatet agents versus placebo/no treatment for primary prevention (primary outcomes, subgroups by dose), Outcome 4 Small‐for‐gestational age.
5.1
5.1. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 1 Severe maternal morbidity (eclampsia, renal failure, liver failure, HELLP syndrome, stroke ‐ IPD only).
5.2
5.2. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 2 HELLP syndrome.
5.3
5.3. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 3 Disseminated intravascular coagulation ‐ IPD only.
5.4
5.4. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 4 Stroke ‐ IPD only.
5.5
5.5. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 5 Renal failure ‐ IPD only.
5.6
5.6. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 6 Liver failure ‐ IPD only.
5.7
5.7. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 7 Pulmonary oedema ‐ IPD only.
5.8
5.8. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 8 Gestational hypertension using best available definition ‐ IPD only.
5.9
5.9. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 9 Gestational hypertension using trialists own definition ‐ IPD only.
5.10
5.10. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 10 Gestational hypertension PARIS definition ‐ IPD only.
5.11
5.11. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 11 Gestation at onset proteinuria by best definition ‐ IPD only.
5.12
5.12. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 12 Fetal, neonatal, infant and childhood deaths (subgroups by time of death).
5.13
5.13. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 13 Baby deaths after discharge from hospital ‐ AD only.
5.14
5.14. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 14 Gestation at birth (mean, weeks).
5.15
5.15. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 15 Preterm birth (< 34 weeks).
5.16
5.16. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 16 Preterm birth (< 32 weeks).
5.17
5.17. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 17 Preterm birth (< 28 weeks).
5.18
5.18. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 18 Preterm birth (mutually exclusive subgroups) ‐ IPD only.
5.19
5.19. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 19 Small‐for‐gestational age (subgrouped by severity) ‐ AD only, trial definition.
5.20
5.20. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 20 Any baby SGA < 3rd centile or as reported ‐ IPD only.
5.21
5.21. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 21 Birthweight < 2500 g.
5.22
5.22. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 22 Pregnancy with SAO (including maternal death, baby death, PE, SGA, preterm) ‐ IPD only.
5.23
5.23. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 23 Hospital admission for the woman during pregnancy ‐ AD only.
5.24
5.24. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 24 Non spontaneous labour (induced labour or pre‐labour caesarean) ‐ IPD only.
5.25
5.25. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 25 Antepartum haemorrhage ‐ IPD only.
5.26
5.26. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 26 Placental abruption.
5.27
5.27. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 27 Postpartum haemorrhage > 500 mL.
5.28
5.28. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 28 Any baby required assisted ventilation.
5.29
5.29. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 29 Intraventricular haemorrhage.
5.30
5.30. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 30 Other neonatal bleed.
5.31
5.31. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 31 Developmental problems at 18 months ‐ AD only.
5.32
5.32. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 32 Behaviour problems at 18 months ‐ AD only.
5.33
5.33. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 33 Malformations at 18 months ‐ AD only.
5.34
5.34. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 34 Growth at 18 months ‐ AD only.
5.35
5.35. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 35 Admission to a special care baby unit.
5.36
5.36. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 36 Child admitted to hospital ‐ AD only.
5.37
5.37. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 37 Non‐routine GP consultation for child ‐ AD only.
5.38
5.38. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 38 Eclampsia.
5.39
5.39. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 39 Maternal death ‐ IPD only.
5.40
5.40. Analysis
Comparison 5 Antiplatelet agents versus placebo/no antiplatelet for primary prevention (secondary outcomes), Outcome 40 Caesarean section.
6.1
6.1. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 1 Severe pre‐eclampsia.
6.2
6.2. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 2 Pre‐eclampsia.
6.3
6.3. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 3 Eclampsia.
6.4
6.4. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 4 Severe hypertension using trialists own definition ‐ IPD only.
6.5
6.5. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 5 Severe hypertension PARIS definition ‐ IPD only.
6.6
6.6. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 6 Severe hypertension using best available def ‐ IPD only.
6.7
6.7. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 7 Gestation at onset proteinuria by best definition ‐ IPD only.
6.8
6.8. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 8 Fetal death, neonatal death, or death before hospital discharge ‐ AD only.
6.9
6.9. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 9 Fetal and neonatal deaths ‐ IPD only.
6.10
6.10. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 10 Preterm birth (< 37 weeks).
6.11
6.11. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 11 Small‐for‐gestational age.
6.12
6.12. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 12 Caesarean section.
6.13
6.13. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 13 Non spontaneous labour IPD only.
6.14
6.14. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 14 Antepartum haemorrhage ‐ IPD only.
6.15
6.15. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 15 Placental abruption ‐ IPD only.
6.16
6.16. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 16 Postpartum haemorrhage > 500 mL ‐ IPD only.
6.17
6.17. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 17 HELLP Syndrome ‐ IPD only.
6.18
6.18. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 18 Severe maternal morbidity ‐ IPD only.
6.19
6.19. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 19 Pregnancy with SAO (including maternal death, baby death, PE, SGA, preterm) ‐ IPD only.
6.20
6.20. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 20 Gestation at birth ‐ IPD only.
6.21
6.21. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 21 Birthweight < 2500 g.
6.22
6.22. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 22 Admission to a special care baby unit ‐ IPD only.
6.23
6.23. Analysis
Comparison 6 Antiplatelet agents versus placebo/no antiplatelet for secondary prevention, Outcome 23 Any baby required assisted ventilation ‐ IPD only.
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Update of

Comment in

References

References to studies included in this review

Algeria 2011 {published data only}
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ASPRE 2017 {published data only}
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Australia 1988 {published data only}
    1. Trudinger BJ, Cook CM, Connelly AJ, Giles WB, Thompson RS. Aspirin improves fetal weight in placental insufficiency. Proceedings of 8th Annual Meeting of the Society of Perinatal Obstetricians; 1988 February 3‐6; Las Vegas, Nevada, USA. 1988:10.
    1. Trudinger BJ, Cook CM, Thompson RS, Giles WB, Connelly AJ. Low‐dose aspirin improves fetal weight in umbilical placental insufficiency. Lancet 1988;2:214‐5. - PubMed
    1. Trudinger BJ, Cook CM, Thompson RS, Giles WB, Connelly AJ. Low‐dose aspirin therapy improves fetal weight in umbilical placental insufficiency. American Journal of Obstetrics and Gynecology 1988;159:681‐5. - PubMed
Australia 1993 {published and unpublished data}
    1. Michael CA, Seville P, Wadeisha P, Walters BN. Randomised double blind placebo controlled trial of aspirin in the prevention of pre‐eclampsia. Proceedings of 7th World Congress of Hypertension in Pregnancy; 1990 October; Perugia, Italy. 1990:73.
    1. Michael CA, Walters BN. Low‐dose aspirin in the prevention of pre‐eclampsia: current evaluation. In: Teoh ES, Ratnam SS, Macnaughton MC editor(s). Maternal Physiology and Pathology. The Current Status of Gynaecology and Obstetrics Series. Carnforth: Parthenon Publishing Group Limited, 1992:183‐9.
Australia 1995 {published data only}
    1. Newnham JP, Godfrey M, Walters BJ, Philips J, Evans SF. Low dose aspirin for the treatment of fetal growth restriction: a randomised controlled trial. Australian and New Zealand Journal of Obstetrics and Gynaecology 1995;35:370‐4. - PubMed
Australia 1995a {published data only}
    1. Kincaid Smith P, North RA, Fairley KF, Kloss M, Ihle BU. Prevention of pre‐eclampsia in high risk women with renal disease: a prospective randomized trial of heparin and dipyridamole. Nephrology 1995;1:297‐300.
    1. North RA, Fairley KF, Kloss M, Ihle B, Kincaid‐Smith P. Prevention of pre‐eclampsia in women with renal disease. Proceedings of 7th World Congress of Hypertension in Pregnancy; 1990 October; Perugia, Italy. 1990:75.
    1. North RA, Fairley KF, Kloss M, Ihle B, Kincaid‐Smith P. Prevention of preeclampsia in women with renal disease [abstract]. 26th Annual Meeting of the Australasian Society of Nephrology; 1990 March 14‐16; Brisbane, Australia. 1990:9.
    1. North RA, Fairley KF, Kloss M, Ihle B, Oats J, Kincaid‐Smith P. Prevention of pre‐eclampsia in women with renal disease. Proceedings of 6th International Congress of the International Society for the study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:193.
Australia 1996 {published and unpublished data}
    1. Ferrier C, North R, Kincaid‐Smith P. Low dose aspirin delays the onset of pre‐eclampsia in pregnancies with abnormal uteroplacental circulation. Proceedings of the 10th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1996 August 4‐8; Seattle, Washington, USA. 1996:151.
    1. Kincaid‐Smith P. [personal communication] Trial to evaluate the role of aspirin (60mg) in the prevention of idiopathic intrauterine growth retardation and pregnancy induced hypertension in primigravid women with abnormal uterine artery waveforms on Doppler examination at 22‐24 weeks gestation. Letter to: Cochrane Pregnancy and Childbirth Group, Oxford UK 30 October 1991.
Australia 1996a {published data only}
    1. Morris JM, Fay RA, Ellwood DA, Cook C, Devonald KJ. A randomized controlled trial of aspirin in patients with abnormal uterine artery blood flow. Obstetrics & Gynecology 1996;87:74‐8. - PubMed
Australia 1997 {published data only}
    1. Gallery ED, Hawkins M, Ross M, Gyory AZ, Leslie G. Low‐dose aspirin in high risk pregnancy. Proceedings of 9th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1994 March 15‐18; Sydney, Australia. 1994:71.
    1. Gallery ED, Ross MR, Hawkins M, Leslie GI, Gyory AZ. Low‐dose aspirin in high‐risk pregnancy. Hypertension in Pregnancy 1997;16:229‐38.
    1. Leslie GI, Gallery ED, Arnold JD, Ross MR, Gyory AZ. Neonatal outcome in a randomized controlled trial of low‐dose aspirin in high‐risk pregnancies. Journal of Paediatrics and Child Health 1995;31:549‐52. - PubMed
Austria 1992 {published data only}
    1. Schrocksnadel H, Sitte B, Alge A, Stechel‐Berger G, Schwegel P, Pastner E, et al. Low‐dose aspirin in primigravidae with positive roll‐over test. Gynecologic and Obstetric Investigation 1992;34:146‐50. - PubMed
    1. Schrocksnadel H, Sitte B, Alge A, Steckel‐Berger G, Daxenbichler G, Dapunt O. Low‐dose aspirin in prevention and therapy of hypertension in pregnancy [Low‐dose Aspirin in prophylaxe und therapie des schwangerschaftshochdrucks]. Gynakologisch Geburtshilfliche Rundschau 1992;32:90‐1. - PubMed
Barbados 1998 {published data only}
    1. Cruickshank J, Rotchell Y. The Barbados low‐dose aspirin study in pregnancy (BLASP). 8th World Congress on Hypertension in Pregnancy; 1992 November 8‐12; Buenos Aires, Argentina. 1992:49.
    1. Elder MG, Swiet M, Sullivan M. A randomised trial of low dose aspirin for primiparae in pregnancy (golding)/barbados low dose aspirin study in pregnancy (blasp) (rotchell et al.) [Letter; comment]. British Journal of Obstetrics and Gynaecology 1999;106(2):180. - PubMed
    1. Griffiths J, Rotchell YE, Cruickshank JK, Philips‐Gay M, Stewart A, Farrell B, et al. The Barbados Low‐dose Aspirin Study in Pregnancy (BLASP): a population‐based trial in a developing country with excess pre‐eclampsia and perinatal mortality [abstract]. West Indian Medical Journal 1996;45(2 Suppl):26‐7.
    1. Rotchell YE, Cruickshank JK, Griffiths J, Phillips G, Stuart A, Ayers S, et al. Results of the Barbados low dose aspirin study in pregnancy (BLASP): a population‐based trial in a developing country with excess pre‐eclampsia (PE) and perinatal mortality. 27th British Congress of Obstetrics & Gynaecology; 1995 July 4‐7; Dublin, Ireland. 1995:31.
    1. Rotchell YE, Cruickshank JK, Phillips Gay M, Griffiths J, Stuart A, Farrell B, et al. Barbados low dose aspirin study in pregnancy (BLASP): a randomized controlled trial for the prevention of pre‐eclampsia and its complications. British Journal of Obstetrics and Gynaecology 1998;105:286‐92. - PubMed
Brazil 1992a {published data only}
    1. Essinger S. The use of low dose acetylsalicylic acid in prevention of pregnancy‐induced hypertension [Uso do acido acetilsalicilico em baixa dosagem na prevencao da doenca hipertensiva especifica da gestacao (DHEG)]. Revista do Colegio Brasileiro de Cirurgioes 1992;19(2):58‐62.
Brazil 1996 {published data only}
    1. Anonymous. ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnancies. British Journal of Obstetrics and Gynaecology 1996;103:39‐47. - PubMed
    1. Atallah AN. ECPPA: randomized trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women [abstract]. Journal of Clinical Epidemiology 1997;50 Suppl 1:3S.
    1. Atallah AN, Taborda WC. ECPPA: the Brazilian low‐dose aspirin study in high risk pregnant women. Hypertension in Pregnancy 1997; Vol. 16, issue 1:139.
Brazil 2006 {published data only}
    1. Souza EV, Torloni MR, Atallah AN, Dos Santos GM, Kulay L Jr, Sass N. Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial. Brazilian Journal of Medical and Biological Research 2014;47(5):419‐25. - PMC - PubMed
    1. Souza EV. Aspirin and calcium to prevent preeclampsia in chronic hypertensive women with abnormal uterine artery Doppler ultrasound [abstract] [Acido acetilalicilico associado ao calcio na prevencao da pre‐eclampsia em gestantes hipertensas cronicas selecionadas pela dopplervelocimetria das arterias uterinas]. Revista Brasileira de Ginecologia y Obstetricia 2006;28(2):136.
    1. Souza EV, Sass N, Atallah AN, Kular L Jr. Aspirin and calcium to prevent pre eclampsia in chronic hypertension women with abnormal uterine artery doppler ultrasound [abstract]. Hypertension in Pregnancy 2006;25(Suppl 1):152.
Canada 2017 {published data only}
    1. Bujold E, NCT02280031. Effect of low dose aspirin on birthweight in twins: the GAP trial. clinicaltrials.gov/ct2/show/NCT02280031 (31 October 2014).
    1. Carpentier C, Bujold E, Camire B, Tapp S, Boutin A, Demers S. P08.03: Low‐dose aspirin for prevention of fetal growth restriction and pre‐eclampsia in twins: the GAP pilot randomised trial. Ultrasound in Obstetrics and Gynecology 2017;50(Suppl 1):178.
China 1996 {published data only}
    1. Wang Z, Li W. A prospective randomized placebo‐controlled trial of low dose aspirin for prevention of intra uterine growth retardation. Chinese Medical Journal 1996;109:238‐42. - PubMed
    1. Wang Z, Li W. Prevention of growth retardation by low dose aspirin. Chung‐Hua Fu Chan Ko Tsa Chih [Chinese Journal of Obstetrics and Gynecology] 1993;28:492‐5. - PubMed
China 1996a {published data only}
    1. Wu J, Yang WW, Shen WH, He Y. Small dosage aspirin in the prevention of hypertension of pregnancy. Acta Academiae Medicinae Suzhou 1996;16:551‐3.
China 1999 {published and unpublished data}
    1. Rogers MS, Fung HY, Hung CY. Calcium and low‐dose aspirin prophylaxis in women at high risk of pregnancy‐induced hypertension. Hypertension in Pregnancy 1999;18:165‐72. - PubMed
    1. Rogers MS, Hung C, Arumanayagam M. Platelet angiotensin II receptor status during pregnancy in Chinese women at high risk of developing pregnancy‐induced hypertension. Gynecologic and Obstetric Investigation 1996;42:88‐94. - PubMed
CLASP 1994 {published data only}
    1. Bar J, Hod M, Pardo J, Fisch B, Rabinerson D, Kaplan B, et al. Effect on fetal circulation of low‐dose aspirin for prevention and treatment of pre‐eclampsia and intrauterine growth restriction: Doppler flow study. Ultrasound in Obstetrics & Gynaecology 1997;9:262‐5. - PubMed
    1. Bar J, Padoa A, Hod M, Sullivan MH, Kaplan B, Kidron D. Decreased pathological placental findings in aspirin‐treated pregnant women at risk of hypertensive complications. Hypertension in Pregnancy 1997;16:435‐44.
    1. Bower SJ, Harrington KF, Schuchter K, McGirr C, Campbell S. Prediction of pre‐eclampsia by abnormal uterine Doppler ultrasound and modification by aspirin. British Journal of Obstetrics and Gynaecology 1996;103:625‐9. - PubMed
    1. CLASP (Collaborative Low‐dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low‐dose aspirin for the prevention and treatment of pre‐eclampsia among 9364 pregnant women. Lancet 1994;343:619‐29. - PubMed
    1. CLASP Collaborative Group. Low dose aspirin in pregnancy and early childhood development: follow up of the collaborative low dose aspirin study in pregnancy. British Journal of Obstetrics and Gynaecology 1994;102:861‐8. - PubMed
Colorado 1993 {published data only}
    1. Porreco RP, Hickok DE, Williams MA, Krenning C. Low‐dose aspirin and hypertension in pregnancy. Lancet 1993;341:312. - PubMed
Egypt 2005 {published data only}
    1. Ebrashy A, Ibrahim M, Marzook A, Yousef D. Usefulness of aspirin therapy in high‐risk pregnant women with abnormal uterine artery doppler ultrasound at 14‐16 weeks pregnancy: randomized controlled clinical trial. Croatian Medical Journal 2005;46(5):826‐31. - PubMed
EPREDA 1991 {published data only}
    1. Beaufils M, Uzan S, Breart G, Bazin B, Paris J. Prevention of preeclampsia with low‐dose aspirin: results of the epreda trial. XIth International Congress of Nephrology; 1990 July 15‐20; Tokyo, Japan. 1990:319A.
    1. Sureau C. Prevention of perinatal consequences of pre‐eclampsia with low‐dose aspirin: results of the EPREDA trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 1991;41:71‐3. - PubMed
    1. Uzan M, Beaufils M, Breart G, Bazin B, Capitant C, Paris J, et al. Prevention of pre‐eclampsia with low‐dose aspirin: results of the EPREDA trial. Journal of Perinatal Medicine 1990;18 Suppl:116.
    1. Uzan S, Beaufils M, Breart G, Bazin B, Capitant C, Paris J. Prevention of fetal growth retardation with low‐dose aspirin: findings of the EPREDA trial. Lancet 1991;337:1427‐31. - PubMed
    1. Uzan S, Beaufils M, Breart G, Bazin B, Capitant C, Paris J. Prevention of pre‐eclampsia with low‐dose aspirin: results of the EPREDA trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 1992;44:12.
ERASME 2003 {published data only}
    1. ERASME collaborative group. Failure of systematic low dose aspirin to prevent preeclampsia in primigravidae. Hypertension in Pregnancy 2000;19(Suppl 1):34.
    1. Subtil D, Goeusse P, Puech F, Lequien P, Biausque S, Breart G, et al. Aspirin (100mg) used for prevention of pre‐eclampsia in nulliparous women: the Essai Regional Aspirine Mere‐Enfant study (Part 1). BJOG: an international journal of obstetrics and gynaecology 2003;110:475‐84. - PubMed
    1. Subtil D, Quandalle F, Houfflin‐Debarge V, Malek Y, Truffert P, Breart G, et al. Low dose aspirin to prevent preeclampsia: what do we learn from a new "negative" trial? [abstract]. European Journal Obstetrics & Gynecology and Reproductive Biology 2002;104:179.
Finland 1993 {published data only}
    1. Viinikka L, Hartikainen‐Sorri AL, Lumme R, Hiilesmaa V, Ylikorkala O. Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin‐thromboxane balance in mother and newborn. British Journal of Obstetrics and Gynaecology 1993;100:809‐15. - PubMed
    1. Viinikka L, Hartikainen‐Sorri AL, Lumme R, Hiilesmaa V, Ylikorkala O. The effect of 50mg of ASA daily on pregnancy outcome and maternal and newborn prostacyclin and thromboxane. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30‐May 3; The Hague, Netherlands. 1991:93.
Finland 1997 {published data only}
    1. Zimmermann P, Eirio V, Koskinen J, Niemi K, Nyman R, Kujansuu E, et al. Effect of low dose aspirin treatment on vascular resistance in the uterine, uteroplacental, renal and umbilical arteries ‐ a prospective longitudinal study on a high risk population with persistent notch in the uterine arteries. European Journal of Ultrasound 1997;5:17‐30.
Finland 1997a {published data only}
    1. Tulppala M, Marttunen M, Soderstrom‐Anttila V, Ailus K, Palosuo T, Ylikorkala O. Low dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2. Human Reproduction 1997;12(1):191. - PubMed
    1. Tulppala M, Marttunen M, Soderstrom‐Anttila V, Foudila T, Ailus K, Palosuo T, et al. Low‐dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2. Human Reproduction 1997;12(7):1567‐72. - PubMed
Finland 2002 {published data only}
    1. Vainio M, Kujansuu E, Iso‐Mustajarvi M, Maenpaa J. Low dose acetylsalicylic acid in prevention of pregnancy‐induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches. BJOG: an international journal of obstetrics and gynaecology 2002;109:161‐7. - PubMed
    1. Vainio M, Kujansuu E, Riutta A, Maenpaa J. Effect of ASA on the risk of gestational hypertension and prostanoid synthesis in pregnant women screened by Doppler ultrasound. XXXIV Congress of Nordic Federation of Societies of Obstetrics and Gynecology; 2004 June 12‐15; Helsinki, Finland. 2004:21.
    1. Vainio M, Riutta A, Koivisto AM, Maenpaa J. 9 alpha,11 beta‐prostaglandin f2 in pregnancies at high risk for hypertensive disorders of pregnancy, and the effect of acetylsalicylic acid. Prostaglandins Leukotrienes & Essential Fatty Acids 2003;69(1):79‐83. - PubMed
    1. Vainio M, Riutta A, Koivisto AM, Maenpaa J. Prostacyclin, thromboxane a2 and the effect of low‐dose asa in pregnancies at high risk of hypertensive disorders. Acta Obstetricia et Gynecologica Scandinavica 2004;83:1119‐23. - PubMed
Finland 2013 {published data only}
    1. Kajantie E, Taipale P, Murtoniemi K, Pesonen A‐K, Raikkonen K, Laivuori H, et al. The effect of low‐dose aspirin on placental growth factor concentration in a high‐risk predo cohort. Reproductive Sciences 2018;25(1 Suppl):100A. - PubMed
    1. Taipale P, ISRCTN14030412. Prediction and prevention of preeclampsia, intrauterine growth restriction, prenatal stress and fetal programming of child's psychological development (ongoing trial). isrctn.com/ISRCTN14030412 (first received 28 February 2007).
    1. Villa P, Kajantie E, Raikkonen K, Pesonen AK, Hamalainen E, Vainio M, et al. Aspirin in the prevention of pre‐eclampsia in high‐risk women: a randomised placebo‐controlled PREDO Trial and a meta‐analysis of randomised trials. BJOG: an International Journal of Obstetrics and Gynaecology 2013;120(1):64‐74. - PubMed
    1. Villa P, Taipale P, Raikkonen K, Hamalainen E, Pesonen A, Kajantie, E, et al. PREDO trial ‐ acetylsalicylic acid in preventing pre‐eclampsia in high‐risk women. Pregnancy Hypertension 2010;1 Suppl 1:S20.
France 1985 {published data only}
    1. Beaufils M, Uzan S, Donsimoni R, Colau JC. A controlled trial of prophylactic treatment of preeclampsia: preliminary results. Archives des Maladies du Coeur 1984;77:1226‐8. - PubMed
    1. Beaufils M, Uzan S, Donsimoni R, Colau JC. Prevention of pre‐eclampsia by early antiplatelet therapy. Lancet 1985;1:840‐2. - PubMed
France 1990 {published data only}
    1. Azar R, Turpin D. Effect of antiplatelet therapy in women at high risk for pregnancy‐induced hypertension. Proceedings of 7th World Congress of Hypertension in Pregnancy; 1990 October; Perugia, Italy. 1990:257.
Germany 1995 {published data only}
    1. Nieder J, Claus P, Augustin W. Prevention of pre‐eclampsia and fetal growth retardation by trapidil. Zentralblatt fur Gynakologie 1995;117:23‐8. - PubMed
Germany 2000 {published data only}
    1. Erdmann M, Paulus WE, Flock F, Herget I, Terinde R, Grab D. Utero and fetoplacental hemodynamic measurements with low dose aspirin [Utero‐und fetoplazentae haemodynamische Messiungen unter low‐dose aspirin]. Zeitschrift fur Gerburtshilfe und Neonatologie 1999;203(1):18‐23. - PubMed
    1. Grab D, Erdmann M, Paulus W, Oberhoffer R, Lang D. Effects of low dose aspirin on uterine and fetal blood flow during pregnancy: a randomized placebo controlled double blind trial. Acta Obstetricia et Gynecologica Scandinavica 1997;76:38. - PubMed
    1. Grab D, Paulus WE, Erdmann M, Terinde R, Oberhoffer R, Lang D, et al. Effects of low‐dose aspirin on uterine and fetal blood flow during pregnancy: results of a randomized, placebo‐controlled, double‐blind trial. Ultrasound in Obstetrics & Gynecology 2000;15:19‐27. - PubMed
India 1991 {published data only}
    1. Grover V, Sachdeva S, Kumari S. Evaluation of dipyridamole and aspirin in prevention and management of intrauterine growth retardation. Journal of Perinatal Medicine 1991;19(2):104.
India 1993 {published data only}
    1. Rai U, Chakravorty M, Juneja Y. Role of low dose aspirin in PIH. Journal of Obstetrics and Gynaecology of India 1993:883‐6.
India 1994 {published data only}
    1. Roy UK, Pan S. A study of low dose aspirin in prevention of pregnancy induced hypertension. Journal of the Indian Medical Association 1994;92:188‐91. - PubMed
India 1999 {published data only}
    1. Shenoy S, Chandrika D, Pisharody R. RCT of low dose aspirin to prevent the progression of pregnancy induced hypertension grade A to B. Journal of Clinical Epidemiology 1999;52 Suppl 1:28S.
India 2017 {published data only}
    1. Sharma N, Srinivasan KJ, Nadhamuni K, Srinivasan S. Role of aspirin in high pulsatility index of uterine artery: a consort study. Journal of Obstetrics and Gynecology of India 2017 [Epub ahead of print]. - PMC - PubMed
Iran 1992 {published data only}
    1. Omrani GH, Karimi MM, Zareh F. Prevention of pregnancy‐induced hypertension by low dose aspirin. Iranian Journal of Medical Sciences 1992;17(3‐4):131‐6.
Iran 2006 {published data only}
    1. Vaseie M. The effect of low‐dose acetylsalicylic acid (ASA) on control of hypertensive in pregnancy [abstract]. Hypertension in Pregnancy 2006;25(Suppl 1):148.
Iran 2010 {published data only}
    1. Kalahroudi MA. The effect of aspirin in prevention of pre eclampsia and its complication in women with abnormal uterine artery doppler ultrasound. https://en.irct.ir/trial/2718 (first received 24 April 2010).
Iran 2012 {published data only}
    1. Jamal A, IRCT138812123485N1. The effect of metformine on the uteroplacental circulation in comparison with aspirin in pregnant women with poly cystic ovary syndrome. http://en.irct.ir/trial/3595 (first received 6 April 2010).
    1. Jamal A, IRCT201011295272N1. The effect of metformine on the uteroplacental circulation in comparison with Aspirin in pregnant women with poly cystic ovary syndrome. http://en.irct.ir/trial/5621 (first received 29 December 2012).
    1. Jamal A, Milani F, Al‐Yasin A. Evaluation of the effect of metformin and aspirin on utero placental circulation of pregnant women with PCOS. Iranian Journal of Reproductive Medicine 2012;10(3):265‐70. - PMC - PubMed
    1. Jamal A, Milani F, Shabani P, Aleyasin A. The effect of metformin on the uteroplacental circulation in comparison with aspirin in pregnant women with polycystic ovary syndrome. Ultrasound in Obstetrics and Gynecology 2010;36(Suppl 1):1.
Iran 2014a {published data only}
    1. Khazardoost S, IRCT201203018954N1. Aspirin for prevention of adverse pregnancy outcome in women with elevated alfa‐feto protein in second trimester screening,a randomised clinical trial. http://en.irct.ir/trial/9411 (first received 5 June 2012).
    1. Khazardoost S, Mousavi S, Borna S, Hantoushzadeh S, Alavi A, Khezerlou N. Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha‐fetoprotein. Journal of Maternal‐Fetal and Neonatal Medicine 2014; Vol. 27, issue 6:561‐5. - PubMed
    1. Mousavi S. Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha‐fetoprotein. Journal of Perinatal Medicine 2015;43(Suppl 1):Abstract no: P‐0743. - PubMed
Israel 1989 {published data only}
    1. Schiff E, Peleg E, Goldenberg M, Rosenthal T, Ruppin E, Tamarkin M, et al. The use of aspirin to prevent pregnancy‐induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. New England Journal of Medicine 1989;321:351‐6. - PubMed
Israel 1990 {published data only}
    1. Schiff E, Barkai G, Ben‐Baruch G, Mashiach S. Low‐dose aspirin does not influence the clinical course of women with mild pregnancy‐induced hypertension. Obstetrics & Gynecology 1990;76:742‐4. - PubMed
Israel 1994 {published data only}
    1. Caspi E, Raziel A, Sherman D, Arieli S, Bukovski I, Weintraub Z. Prevention of pregnancy induced hypertension in twins by early administration of low‐dose aspirin: a preliminary report. American Journal of Reproductive Immunology 1994;31:19‐24. - PubMed
Italy 1989 {published data only}
    1. Ballerini S, Valcamonico A, Greorini G, Frusca T, Benigni A, Orisio S, et al. Low dose aspirin (ASA) given to prevent preeclampsia only partially inhibits platelet cyclooxygenase activity. Proceedings of 6th World Congress of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:234.
    1. Benigni A, Gregorini G, Frusca T, Chiabrando C, Ballerini S, Valcamonico A, et al. Effect of low‐dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy‐induced hypertension. New England Journal of Medicine 1989;321:357‐62. - PubMed
    1. Frusca T, Gregorini G, Ballerini S, Marchesi D, Bruni M. Low dose aspirin in preventing preeclampsia and IUGR. Proceedings of 6th World Congress of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:232.
Italy 1993 {published data only}
    1. Italian Study of Aspirin in Pregnancy. Low‐dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy‐induced hypertension. Lancet 1993;341:396‐400. - PubMed
    1. Parazzini DF. Low‐dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy‐induced hypertension. Geburtshilfe und Frauenheilkunde 1993;53:822.
    1. Parazzini F. Multicenter randomized Italian study of low‐dose aspirin for the prevention of pre‐eclampsia and intrauterine growth retardation. Journal of Nephrology 1991;4:127‐9.
    1. Parazzini F, Benedetto C, Frusca T, Guaschino S, Romero M. The Italian study on low‐dose aspirin for the prevention of pre‐eclampsia and intrauterine growth retardation. Proceedings of 7th World Congress of Hypertension in Pregnancy; 1990 October; Perugia, Italy. 1990:32.
    1. Parazzini F, Bortolus R, Chatenoud L, Restelli S, Benedetto C. Follow‐up of children in the Italian Study of Aspirin in Pregnancy. Lancet 1994;343:1235. - PubMed
Italy 1999 {published data only}
    1. Volpicelli T, D'Anto V, Faticato A, Galante L, Civitillo RM, Rappa C, et al. [Trial prospettico sull'uso profilattico dell'aspirina in donne gravide ad alto rischio di preeclampsia]. Gestosi '99. 1999:159‐60.
Italy 2004 {published data only}
    1. Chiaffarino F, Parazzini F, Paladini D, Acaia B, Ossola W, Marozio L, et al. A small randomised trial of low‐dose aspirin in women at high risk of pre‐eclampsia. European Journal of Obstetrics & Gynecology and Reproductive Biology 2004;112:142‐4. - PubMed
Jamaica 1998 {unpublished data only}
    1. Elder MG, Swiet M, Sullivan M. A randomised trial of low dose aspirin for primiparae in pregnancy (golding)/barbados low dose aspirin study in pregnancy (blasp) (rotchell et al.) [Letter; comment]. British Journal of Obstetrics & Gynaecology 1999;106(2):180. - PubMed
    1. Forrester TE, Jones D, McCaw‐Binns A, Palmer‐Levy M, Wilks R, Bernard GW, et al. Low‐dose aspirin in pregnancy ‐ are there any benefits? [abstract]. West Indian Medical Journal 1996;45(2 Suppl):26.
    1. Golding J. A randomised trial of low dose aspirin for primiparae in pregnancy. British Journal of Obstetrics and Gynaecology 1998;105:293‐9. - PubMed
    1. Kahwa EK, Sargeant LA, McCaw‐Binns A, McFarlane‐Anderson N, Smikle M, Forrester T, et al. Anticardiolipin antibodies in jamaican primiparae. Journal of Obstetrics and Gynaecology 2006;26(2):122‐6. - PubMed
    1. McCaw‐Binns A, Ashley D, Hawkins N, MacGillivray I, Golding J. International variation in the incidence of hypertension in pregnancy among primiparae: the jamaican experience. 10th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1996 August 4‐8; Seattle, Washington, USA. 1996:168.
Japan 1999 {published data only}
    1. Seki H, Kuromaki K, Takeda S, Kinoshita K, Satoh K. Trial of prophylactic administration of TXA2 synthetase inhibitor, ozagrel hydrochloride, for preeclampsia. Hypertension in Pregnancy 1999;18:157‐64. - PubMed
Korea 1997 {published data only}
    1. Kim HS, Kim KS, Kim TY, Cho JS, Park YW, Song CH. Clinical efficacy of doppler ultrasound for low dose aspirin therapy in high risk pregnancy. Korean Journal of Obstetrics and Gynecology 1997;40(1):71‐7.
Netherlands 1986 {published data only}
    1. Dekker GA. Low dose aspirin prevents pregnancy‐induced hypertensive disease in angiotensin‐sensitive primigravidae. Prediction and Prevention of Pregnancy‐Induced Hypertensive Disorders: a Clinical and Pathophysiologic Study. [MD thesis]. Rotterdam, The Netherlands: University Medical School, 1989:91‐102.
    1. Wallenburg HC, Dekker GA, Makovitz JW, Rotmans P. Low‐dose aspirin prevents pregnancy‐induced hypertension and pre‐eclampsia in angiotensin‐sensitive primigravidae. Lancet 1986;1:1‐3. - PubMed
Netherlands 1989 {published data only}
    1. Dekker GA. Prediction and prevention of pregnancy‐induced hypertensive disorders: a clinical and pathophysiologic study [MD thesis]. Rotterdam, The Netherlands: University Medical School, 1989.
Netherlands 1991a {published data only}
    1. Wallenburg HC, Dekker GA, Makowitz JW. Reversal of elevated vascular angiotensin II responsiveness in pregnancy by low‐dose aspirin. Proceedings of 34th Annual Meeting of the Society for Gynecologic Investigation; 1987 March 18‐21; Georgia, USA. 1987:22.
    1. Wallenburg HCS, Dekker GA, Makovitz JW, Rotmans N. Effect of low‐dose aspirin on vascular refractoriness in angiotensin‐sensitive primigravid women. American Journal of Obstetrics and Gynecology 1991;164:1169‐73. - PubMed
Netherlands 2009 {published data only}
    1. Lambers MJ, Groeneveld E, Hoozemans DA, Schats R, Homburg R, Lambalk CB, et al. Lower incidence of hypertensive complications during pregnancy in patients treated with low‐dose aspirin during in vitro fertilization and early pregnancy. Human Reproduction 2009;24(10):2447‐50. - PubMed
    1. Lambers MJ, Hoozemans DA, Schats R, Homburg R, Lambalk Cornelis B, Hompes PG. Low‐dose aspirin in non‐tubal IVF patients with previous failed conception: a prospective randomized double‐blind placebo‐controlled trial. Fertility and Sterility 2009;92(3):923‐9. - PubMed
Pergar 1987 {unpublished data only}
    1. Uzan S, Beaufils M, Bazin B, Danays T. Idiopathic recurrent fetal growth retardation and aspirin‐dipyridamole therapy [letter]. American Journal of Obstetrics and Gynecology 1989;160:763‐4. - PubMed
Romania 2018 {published data only}
    1. Stanescu AD, Banica R, Sima RM, Ples L. Low dose aspirin for preventing fetal growth restriction: a randomised trial. Journal of Perinatal Medicine 2015;43(Suppl 1):Abstract no: O‐0040. - PubMed
    1. Stanescu AD, Banica R, Sima RM, Ples L. Low dose aspirin for preventing fetal growth restriction: a randomised trial. Journal of Perinatal Medicine 2018 [epub ahead of print]. - PubMed
Russia 1993 {published and unpublished data}
    1. Rogov V, Tareeva I, Sidorova S, Androsova S. Prevention of pregnancy complications with acetylsalicylic acid (ASA) and dipyridamol (DP) in women with chronic glomerulonephritis (CGN) and essential hypertension (EH). Proceedings of 9th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1994 March 15‐18; Sydney, Australia. 1994:280.
    1. Rogov VA, Tareeva I, Sidorova S, Androsova SO, Katamadze KT, Nikiforova OV. Prevention of pregnancy complications in glomerulonephritis and hypertension with acetylsalicylic acid and curantyl. Terapevticheskii Arkhiv 1993;65:65‐8. - PubMed
S Africa 1988 {published and unpublished data}
    1. Railton A, Davey A. Aspirin and dipyridamole in the prevention of pre‐eclampsia: effect on plasma prostanoids 6 keto PG1a and TXB2 and clinical outcome of pregnancy. Proceedings of the 6th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:60.
    1. Railton A, Davey DA. Aspirin and dipyridamole in the prevention of pre‐eclampsia: effect on plasma 6 keto PGF1alpha and TxB2 and clinical outcome of pregnancy. Proceedings of 1st European Congress on Prostaglandins in Reproduction; 1988 July 6‐9; Vienna, Austria. 1988:48.
Spain 1997 {published data only}
    1. Hermida RC, Ayala DE, Iglesias M, Mojon A, Silva I, Ucieda R, et al. Time‐dependant effects of low dose aspirin administration on blood pressure in pregnant women. Hypertension 1997;30:589‐95. - PubMed
Spain 1999 {published data only}
    1. Hermida R, Ayala D, Mojon A, Fernandez J, Alonso I, Silva I, et al. Time dependant effects of low dose aspirin administration on blood pressure in high risk pregnancy. Hypertension in Pregnancy 2000;19(Suppl 1):81.
    1. Hermida RC, Ayala DE, Fernandez JR, Mojon A, Alonso I, Silva I, et al. Administration time‐dependent effects of aspirin in women at differing risk for preeclampsia. Hypertension 1999;33(4):1079. - PubMed
    1. Hermida RC, Ayala DE, Fernandez JR, Mojon A, Alonso I, Silva I, et al. Administration time‐dependent effects of aspirin in women at differing risk for preeclampsia. Hypertension 1999;34(4 Pt 2):1016‐23. - PubMed
Spain 2003 {published data only}
    1. Ayala DE, Ucieda R, Hermida RC. Chronotherapy with low‐dose aspirin for prevention of complications in pregnancy. Chronobiology International 2013;30(1‐2):260‐79. - PubMed
    1. Hermida RC, Ayala DE, Fernandez JR, Mojon A, Alonso I, Ucieda R, et al. Administration‐time dependent effects of aspirin in women at high risk for preeclampsia. [abstract]. Hypertension in Pregnancy 2000;19(Suppl 1):35. - PubMed
    1. Hermida RC, Ayala DE, Iglesias M. Administration time‐dependant influence of aspirin on blood pressure in pregnant women. Hypertension 2003;41:651‐6. - PubMed
    1. Hermida RC, Ayala DE, Iglesias M. Administration‐time dependent effects of low‐dose aspirin on blood pressure in women at high risk for preeclampsia [abstract]. Hypertension in Pregnancy 2002;21(Suppl 1):47.
    1. Hermida RC, Ayala DE, Iglesias M. Administration‐time dependent effects of low‐dose aspirin on the incidence of complications in women at high risk for preeclampsia [abstract]. Hypertension in Pregnancy 2002;21(Suppl 1):20.
Spain 2017 {published data only}
    1. EudraCT Number: 2012‐000622‐22. Aspirin for the enhancement of trophoblastic invasion in women with abnormal uterine artery Doppler at 11‐14 weeks of gestation. https://www.clinicaltrialsregister.eu/ctr‐search/search?query=eudract_nu... (first received 10 May 2012).
    1. Scazzocchio E, Oros D, Diaz D, Ramirez JC, Ricart M, Meler E, et al. Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery doppler at 11 ‐ 14 weeks: a randomized controlled study (asap). Ultrasound in Obstetrics & Gynecology 2017;49:435‐41. - PubMed
Tanzania 1995 {published data only}
    1. Ramaiya C, Mgaya H. Low dose aspirin in prevention of pregnancy‐induced hypertension in primigravidae at the Muhimbili Medical Centre, Dar Es Salaam. Acta Obstetricia et Gynecologica Scandinavica 1997;76(167):1. - PubMed
    1. Ramaiya C, Mgaya HN. Low dose aspirin in prevention of pregnancy‐induced hypertension in primigravidae at the Muhimbili Medical Centre, Dar es Salaam. East African Medical Journal 1995;72:690‐3. - PubMed
    1. Ramaiya CP. Low dosage of aspirin in prevention of pregnancy induced hypertension (PIH) in primigravidae at Muhimbili Medical Centre, Dar es Salaam [MD thesis]. Ethiopia: University of Dar es Salaam, 1992.
UK+others 2003 {published data only}
    1. Yu CK, Papageorghiou AT, Parra M, Palma Dias R, Nicolaides KH. Randomized controlled trial using low‐dose aspirin in the prevention of pre‐eclampsia in women with abnormal uterine Doppler at 23 weeks gestation. Ultrasound in Obstetrics & Gynecology 2003;22:233‐9. - PubMed
UK 1990 {published data only}
    1. McParland PJ, Pearce JM. Low dose aspirin prevents proteinuric hypertension in women with abnormal uteroplacental waveforms. Proceedings of Silver Jubilee Congress of Obstetrics and Gynaecology; 1989 July 4‐7; London, UK. 1989:8.
    1. McParland, Pearce JM, Chamberlain GVP. Doppler ultrasound and aspirin in recognition and prevention of pregnancy‐induced hypertension. Lancet 1990;335:1552‐5. - PubMed
UK 1992 {published data only}
    1. Louden KA, Broughton PF, Heptinsall S, Mitchell JR, Symonds EM. Maternal low‐dose aspirin spares the neonate. Proceedings of Silver Jubilee Congress of Obstetrics and Gynaecology; 1989 July 4‐7; London, UK. 1989:9.
    1. Louden KA, Broughton PF, Symonds EM, Tuohy P, O'Callaghan C, Heptinstall S, et al. A randomized placebo‐controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non‐pregnant women, in normal pregnancy and in gestational hypertension. International Journal of Gynecology & Obstetrics 1993;40:186. - PubMed
    1. Louden KA, Broughton Pipkin F, Heptinstall S, Mitchell JR, Symonds EM. Studies of the effect of low‐dose aspirin on thromboxane production and platelet reactivity in normal pregnancy, pregnancy‐induced hypertension and neonates. Proceedings of 1st European Congress on Prostaglandins in Reproduction; 1988 July 6‐9; Vienna, Austria. 1988:30.
    1. Louden KA, Broughton Pipkin F, Symonds EM, Tuohy P, O'Callaghan C, Heptinstall S, et al. A randomized placebo‐controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non‐pregnant women, in normal pregnancy, and in gestational hypertension. British Journal of Obstetrics and Gynaecology 1992;99:371‐6. - PubMed
    1. Louden KA, Broughton‐Pipkin F, Heptinstall S, Fox SC, Tuohy P, O'Callaghan C, et al. Neonatal platelet reactivity and serum thromboxane B2 production in whole blood: the effect of maternal low dose aspirin. British Journal of Obstetrics and Gynaecology 1994;101:203‐8. - PubMed
UK 1992b {published data only}
    1. Quenby S, Farquharson R, Ramsden G. The obstetric outcome of patients with positive anticardiolipin antibodies: aspirin vs no treatment. Proceedings of 26th British Congress of Obstetrics and Gynaecology; 1992 July 7‐10; Manchester, UK. 1992:443.
UK 1995 {published data only}
    1. Davies NJ. A study of low dose aspirin for the prevention of hypertensive disorders of pregnancy in primiparous women. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30‐May 3; The Hague, Netherlands. 1991:183.
    1. Davies NJ, Farquharson RG, Walkinshaw SA. Low‐dose aspirin and nulliparae. Lancet 1991;338:324. - PubMed
    1. Davies NJ, Gazvani MR, Farquharson RG, Walkinshaw SA. Low‐dose aspirin in the prevention of hypertensive disorders of pregnancy in relatively low‐risk nulliparous women. Hypertension in Pregnancy 1995;14:49‐55.
USA 1993 {published and unpublished data}
    1. Copper R, Hauth J, Cutter G, DuBard M, Goldenberg R. Prerandomization compliance testing may predict pregnancy outcome in a randomized clinical trial. American Journal of Obstetrics and Gynecology 1993;168:414.
    1. Goldenberg RL, Hauth JC, Copper RL, DuBard MB, Cutter GR. The effect of low dose aspirin on fetal growth in low risk primiparas. American Journal of Obstetrics and Gynecology 1993;168:383. - PubMed
    1. Goldenberg RL, Hauth JC, DuBard MB, Copper RL, Cutter GR. Fetal growth in women using low‐dose aspirin for the prevention of preeclampsia: effect of maternal size. Journal of Maternal Fetal Medicine 1995;4:218‐24.
    1. Hauth J, Goldenberg R, Parker C, DuBard M, Copper R, Cutter G. Maternal serum thromboxane B2 reduction vs pregnancy outcome in a low‐dose aspirin trial. American Journal of Obstetrics and Gynecology 1993;168:316. - PubMed
    1. Hauth J, Goldenberg R, Philips J, Copper R, DuBard M, Cutter G. Low‐dose aspirin therapy to prevent preeclampsia: safety considerations. American Journal of Obstetrics and Gynecology 1993;168:389. - PubMed
USA 1993a {published data only}
    1. Abramovici A, Jauk V, Wetta L, Edwards R, Biggio J, Tita A. Analysis of low‐dose aspirin by smoking status for select perinatal outcomes. American Journal of Obstetrics and Gynecology 2013;208(1 Suppl 1):S261.
    1. Andrikopoulou M, Purisch SE, Handal‐Orefice R, Gyamfi‐Bannerman C. Beyond preeclampsia: low dose aspirin reduces spontaneous preterm birth. American Journal of Obstetrics and Gynecology 2018;218(1):S10. - PubMed
    1. Caritis S, Sibai B, Thorn E, McLaughlin S, NICHD‐MFM Network. Pregnancy effects of non‐proteinuric gestational hypertension (GH). American Journal of Obstetrics and Gynecology 1995;172:376.
    1. Connealy B, Carreno C, Kase B, Hart L, Blackwell S, Sibai B. A history of prior preeclampsia is a major risk factor for preterm birth. American Journal of Obstetrics and Gynecology 2013;208(1 Suppl 1):S264. - PubMed
    1. Sessa TG, Moretti ML, Khoury A, Pulliam DA, Arheart KL, Sibai BM. Cardiac function in fetuses and newborns exposed to low‐dose aspirin during pregnancy. American Journal of Obstetrics and Gynecology 1994;171:892‐900. - PubMed
USA 1994 {published data only}
    1. August P, Helseth G, Edersheim TG, Hutson JM, Druzin M. Sustained release, low‐dose aspirin ameliorates but does not prevent preeclampsia (PE) in a high risk population. Proceedings of 9th International Congress, International Society for the Study of Hypertension in Pregnancy; 1994 March 15‐18; Sydney, Australia. 1994:72.
USA 1997 {published data only}
    1. Cowchock S, Reece EA. Do low‐risk pregnant women with antiphospholipid antibodies need to be treated? Organizing group of the antiphospholipid antibody treatment trial. American Journal of Obstetrics and Gynecology 1997;176(5):1099‐100. - PubMed
USA 1998 {published and unpublished data}
    1. Abramovici A, Jauk V, Wetta L, Cantu J, Edwards R, Biggio J, et al. Low‐dose aspirin, smoking status, and the risk of spontaneous preterm birth. American Journal of Perinatology 2015;32(5):445‐50. - PubMed
    1. Abramovici A, Jauk V, Wetta L, Edwards R, Biggio J, Tita A. Low‐dose aspirin is associated with a reduction in spontaneous preterm birth among non‐smokers. American Journal of Obstetrics and Gynecology 2013;208(1 Suppl 1):S260‐S261.
    1. Adkins K, Allshouse AA, Metz TD, Heyborne KD. Impact of aspirin on fetal growth in diabetic pregnancies according to white classification. American Journal of Obstetrics and Gynecology 2017;217(4):465. - PMC - PubMed
    1. Adkins K, Metz T, Heyborne K, Allshouse A. Impact of low‐dose aspirin on fetal growth in diabetic pregnancies: the importance of white classification. American Journal of Obstetrics and Gynecology 2017;216(1 Suppl 1):S292. - PMC - PubMed
    1. Allshouse AA, Jessel RH, Heyborne KD. The impact of low‐dose aspirin on preterm birth: secondary analysis of a randomized controlled trial. Journal of Perinatology 2016;36(6):427‐31. - PubMed
Venezuela 2000 {published data only}
    1. Rivas‐Echeverria CA, Echeverria Y, Molina L, Novoa D. Synergic use of aspirin, fish oil and vitamins C and E for the prevention of preeclampsia. Hypertension in Pregnancy 2000;19:30.
Zimbabwe 1998 {published data only}
    1. Byaruhanga RN, Chipato T, Rusakaniko S. A randomized controlled trial of low‐dose aspirin in women at risk from pre‐eclampsia. International Journal of Gynecology & Obstetrics 1998;60:129‐35. - PubMed

References to studies excluded from this review

Argentina 1994 {published data only}
    1. Fraire JC, Lopez J. Cyclooxygenase and lipoxygenase inhibition in gestational hypertension. Journal of the American Society of Nephrology 1994;5(3):561.
Australia 1989 {unpublished data only}
    1. Robinson JS. [Personal communication] Can the genetic risk of pre‐eclampsia be reduced by low dose aspirin?. Letter to: Cochrane Pregnancy and Childbirth Group, Oxford, UK 25 March 1993.
Australia 1989a {published data only}
    1. Trudinger BJ, Cook CM, Giles WB, Connelly AJ, Thompson RS. Low‐dose aspirin and twin pregnancy. Lancet 1989;334(8673):1214. - PubMed
Brazil 1992 {published data only}
    1. Montenegro CA. The effect of aspirin therapy on the uterine circulation in preeclampsia. Proceedings of the 8th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1992 November 8‐12; Buenos Aires, Argentina. 1992:66.
Brazil 1995 {published data only}
    1. Camara Franca BE, Silva LG, Netto HC, Rezende Filho J, Mello LI, Montenegro CA. The role of acetylsalicylic acid in prostaglandins syntesis in mild preeclampsia. Jornal Brasileiro de Ginecologia 1995;105(6):249‐68.
Brazil 1996a {published and unpublished data}
    1. Sass N, Rocha NS, Callegari AH, Lima PC, Camano L. The low dose aspirin study in pregnancy with chronic hypertension (AASHAC). Proceedings of the 10th World Congress on Hypertension in Pregnancy; 1996 August 4‐8; Seattle, USA. 1996:152.
Canada 2015 {published data only}
    1. Bujold E, NCT01352234. Evaluation of dose‐response effect of acetylsalicylic acid on placental development, preterm birth, fetal growth and hypertension in pregnancy in women with previous history of preeclampsia. clinicaltrials.gov/ct2/show/NCT01352234 (first received 11 May 2011).
    1. Tapp S, Demers S, Giguere Y, Leclair G, Nicolaides K, Cote S, et al. Comparison of 80 versus 160 mg of aspirin in pregnant women with previous history of pre‐eclampsia: a randomised controlled trial. Ultrasound in Obstetrics & Gynecology 2015;46(Suppl 1):S4.
China 1991 {published data only}
    1. Cheng WW, Zhang ZJ. Low‐dose aspirin preventing pregnancy induced hypertension. Chung Hua Fu Chan Ko Tsa Chih 1991;26(6):342‐5. - PubMed
China 2016 {published data only}
    1. Liu FM, Zhao M, Wang M, Yang HL, Li L. Effect of regular oral intake of aspirin during pregnancy on pregnancy outcome of high‐risk pregnancy‐induced hypertension syndrome patients. European Review for Medical and Pharmacological Sciences 2016;20(23):5013‐6. - PubMed
China 2017 {published data only}
    1. Liu F, Yang H, Zou K, Chen Y, Li G. Effect of a small dose of aspirin on quantitative test of 24‐h urinary protein in patients with hypertension in pregnancy. Experimental and Therapeutic Medicine 2017;13(1):37‐40. - PMC - PubMed
Colombia 1996 {published data only}
    1. Hernandez F, Martinez MF, Camero A, Pinzon JA. Low dose aspirin as prophylactic therapy of pregnancy induced hypertension. Revista Colombiana de Obstetricia y Ginecologia 1996;47:197‐201.
East Germany 1986 {published data only}
    1. Peterseim H, Hofmann KD, Wagner F, Peterseim S, Meier P. Inhibition of prostaglandin synthetase by low‐dose acetylsalicylic acid ‐ effects on severity of pregnancy induced hypertension and fetal outcome. Proceedings of 10th European Congress of Perinatal Medicine; 1986 August 12‐16; Leipzig, Germany. 1986:290.
East Germany 1988 {published data only}
    1. Heinrich J. Prophylactic management of pregnancy induced hypertension (PIH). Proceedings of 11th European Congress of Perinatal Medicine; 1988; Rome, Italy. 1988:274.
Egypt 1991 {published data only}
    1. Toppozada M, Darwish EA, Osman YF, Abd‐Rabbo MS. Low dose acetyl salicylic acid in severe pre‐eclampsia. International Journal of Gynecology & Obstetrics 1991;35:311‐7. - PubMed
Egypt 1998 {published data only}
    1. Shalan H, Kurjak A, Lakkany N. The effect of low dose aspirin versus allylestrinol on uterine artery blood flow. Prenatal and Neonatal Medicine 1998;3 Suppl 1:141.
Egypt 2017 {published data only}
    1. Ali MK, Abbas AM, Yosef AH, Bahloul M. The effect of low‐dose aspirin on fetal weight of idiopathic asymmetrically intrauterine growth restricted fetuses with abnormal umbilical artery doppler indices: a randomized clinical trial. Journal of Maternal‐Fetal & Neonatal Medicine 2017 [Epub ahead of print]. - PubMed
    1. Ali MK, NCT03038607. Effect of low‐dose aspirin on fetal weight of idiopathic asymmetrically intrauterine growth restricted fetuses with abnormal umbilical doppler indices. clinicaltrials.gov/ct2/show/record/NCT03038607 (first received 31 January 2017). - PubMed
Equador 1998 {published data only}
    1. Armando CA, Martha CC, Galo EV. Prevention of the development of preeclampsia by means of the administration of low doses of aspirin. Quito 1998:80.
ERASME 2003a {published data only}
    1. Subtil D, Goeusse P, Houfflin‐Debarge V, Puech F, Lequien P, Breart G, et al. Aspirin (100mg) used for prevention of pre‐eclampsia in nulliparous women: the Essai Regional Aspirine Mere‐Enfant study (Part 2). BJOG: an international journal of obstetrics and gynaecology 2003;110:485‐91. - PubMed
Finland 1993a {published and unpublished data}
    1. Kaaja R, Julkunen H, Viinikka L, Ylikorkala O. Production of prostacyclin and thromboxane in lupus pregnancies: effect of small dose of aspirin. Obstetrics & Gynecology 1993;81:327‐31. - PubMed
Finland 2007 {published data only}
    1. Haapsamo M, Martikainen H, Tinkanen H, Heinonen S, Nuojua‐Huttunen S, Rasanen J. Low‐dose aspirin therapy and hypertensive pregnancy complications in unselected IVF and ICSI patients: a randomized, placebo‐controlled, double‐blind study. Human Reproduction 2010;25(12):2972‐7. - PubMed
    1. Haapsamo M, Rasanen J. Low‐dose aspirin reduces uteroplacental vascular impedance during the first half of pregnancy in IVF/ICSI patients: a randomized placebo‐controlled study. American Journal of Obstetrics and Gynecology 2007;197(6 Suppl 1):S31, Abstract no: 70. - PubMed
    1. Haapsamo M, Rasanen J, Gravett M, Nagalla S. Low‐dose aspirin influences early pregnancy placentation in IVF/ICSI patients: evidenced by a distinct maternal serum proteome profile. American Journal of Obstetrics and Gynecology 2007;197(6 Suppl 1):S83, Abstract no: 256.
France 2001 {published data only}
    1. Goffinet F. Aboulker D, Paris‐Llado J, Bucourt M, Uzan M, Papiernik E, et al. Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results: a multicenter randomised controlled trial. BJOG: an international journal of obstetrics and gynaecology 2001;108:510‐8. - PubMed
    1. Subtil D, Truffert P, Goeusse P, Dufour P, Uzan S, Breart G, et al. Value of systematic doppler +/‐ low dose aspirin to prevent vascular complications in primigravidae. Hypertension in Pregnancy 2000;19(Suppl 1):9.
Germany 1986 {published data only}
    1. Niedner W, Beller FK. The influence of ASA on pre‐eclampsia. Proceedings of the 5th International Congress of the Society for the Study of Hypertension in Pregnancy; 1986 July 7‐10; Nottingham, UK. 1986:101.
India 1986 {published data only}
    1. Bhattacharya N, Chaudhuri N, Ghosh S, Pradhan P, Ghosh CR. Effect of platelet aggregation inhibitor on fetal outcome in EPH gestosis with IUGR. Proceedings of the 5th Congress of the International Society for the Study of Hypertension in Pregnancy; 1986 July 7‐10; Nottingham, UK. 1986:82.
India 1997 {published data only}
    1. Tewari S, Kaushish R, Sharma S, Gulati N. Role of low dose aspirin in prevention of pregnancy induced hypertension. Journal of the Indian Medical Association 1997;95:43‐5, 47. - PubMed
India 1998 {published and unpublished data}
    1. Dasari R, Narang A, Vasishta K, Garewal G. Effect of maternal low dose aspirin on neonatal platelet function. Indian Pediatrics 1998;35:507‐11. - PubMed
India 2001 {published data only}
    1. Sehgal R, Sood M. Role of low dose aspirin for prevention of pregnancy induced hypertension. Journal of Obstetrics and Gynecology of India 2001;51(5):81‐4.
India 2002 {published data only}
    1. Desai P, Rao S. Role of low dose aspirin in mothers registering high serum HCG levels at mid trimester. Journal of Obstetrics and Gynecology of India 2002;52(5):30‐2.
India 2002a {published data only}
    1. Khanna A, Prabhakar S. Maternal and foetal outcome with low dose aspirin in pregnancy induced hypertension. Journal of Obstetrics and Gynecology of India 2002;52(3):62‐4.
India 2011 {published data only}
    1. Papalkar J, Rani D, Shrivastava. Comparison of lycopene and low dose aspirin with only low dose aspirin pre‐eclampsia. 54th All India Congress of Obstetrics and Gynaecology; 2011 January 5‐9; Hyderabad, Andhra Pradesh, India. 2011:310.
Iran 2002 {published data only}
    1. Taherian A, Taherian A, Shirvani A. Prevention of preeclampsia with low‐dose aspirin or calcium supplementation. Archives of Iranian Medicine 2002;5:151‐6.
Iran 2013 {published data only}
    1. Abdali K, IRCT138803211548N5. The effect of taking aspirin in two different diurnal times (morning and night) on mean of 24 hours blood pressure in women who are at preeclampsia risk. http://en.irct.ir/trial/5621 (first received 20 February 2010).
    1. Abdali K, Taghizadeh R, Amoei S, Tabatabai SH. Comparison between aspirin and placebo on the mean of 24 hour blood pressure in pregnant women at preeclampsia risk, a double blind randomized controlled clinical trial. International Journal of Community Based Nursing and Midwifery 2013;1:283‐9.
Iran 2014 {published data only}
    1. Mesdaghinia E, Talari H, Abedzadeh‐Kalahroudi M. Effect of aspirin for prevention of preeclampsia in women with abnormal ultrasonic findings in uterine artery. Journal of Kashan University of Medical Sciences 2011;15(2):98‐104.
    1. Talari H, Mesdaghinia E, Abedzadeh Kalahroudi M. Aspirin and preeclampsia prevention in patients with abnormal uterine artery blood flow. Iranian Red Crescent Medical Journal 2014;16(8):e17175. - PMC - PubMed
Iran 2016 {published data only}
    1. Hashemi M, Heshmat‐Ghahdarijani K, Bahrani S, Baktash F, Zarean E. Evaluation the effect of low‐dose aspirin on endothelial dysfunction in preeclamptic patients. Journal of Research in Medical Sciences 2016;21:128. - PMC - PubMed
    1. Heshmat K, IRCT2016040527135N2. Evaluation of the effect of low dose aspirin on endothelial dysfunction in preeclamptic patients. http://en.irct.ir/trial/22305 (first received 4 June 2016). - PMC - PubMed
Iran 2017 {published data only}
    1. Ebrahimi BM, IRCT2016022020035N2. Study of effect of vitamin E and low‐dose aspirin on uterine artery blood flow velocity in women with recurrent pregnancy loss due to impaired uterine perfusion: clinical trial. http://en.irct.ir/trial/17776 (first received 10 May 2016).
    1. Mesdaghinia E, Mohammad‐Ebrahimi B, Foroozanfard F, Banafshe HR. The effect of vitamin e and aspirin on the uterine artery blood flow in women with recurrent abortion: a single‐blind randomized controlled trial. International Journal of Reproductive Biomedicine (Yazd, Iran) 2017;15(10):635‐40. - PMC - PubMed
Ireland 1995 {published data only}
    1. Regan CL, McAdam BF, McParland P, Boylan PC, FitzGerald GA, Fitzgerald DJ. Reduced fetal exposure to aspirin using a novel controlled release preparation in normotensive and hypertensive pregnancies. British Journal of Obstetrics and Gynaecology 1998;105:732‐8. - PubMed
    1. Regan CL, McAdam BV, McParland P, Boylan P, FitzGerald GA, Fitzgerald DJ. Pharmacology of low dose aspirin in normotensive and hypertensive pregnancies. 27th British Congress of Obstetrics and Gynaecology; 1995 July 4‐7; Dublin, Ireland. 1995:301. - PubMed
Ireland 2014 {published data only}
    1. Breathnach F, ISRCTN13355246. Early aspirin to improve pregnancy outcome in diabetes. isrctn.com/ISRCTN13355246 (first received 12 February 2014).
    1. Subieh HA, McHugh A, Corcoran S, Backley S, Tully E, McDermott R, et al. Aspirin for optimising pregnancy outcome in pregestational diabetes: the value of objective testing of study participant compliance. Pilot for the IRELAND study (investigating the role of early low‐dose aspirin in pre‐existing diabetes). BJOG: an international journal of obstetrics and gynaecology 2017; Vol. 124:142‐3.
Israel 2006 {published data only}
    1. Dolitzky M, Inbal A, Segal Y, Weiss A, Brenner B, Carp H. A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages. Fertility and Sterility 2006;86(2):362‐6. - PubMed
Italy 1988 {published and unpublished data}
    1. Airoldi ML, Capetta P, Tasca A, Bertulessi C, Rossi E, Polvani F. Role of early prevention with heparin and dipyridamole in the prevention of pre‐eclampsia and placental insufficiency. Proceedings of the 6th International Congress of the International Society for the study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:233.
    1. Capetta P, Airoldi ML, Tasca A, Bertulessi C, Rossi E, Polvani F. Prevention of pre‐eclampsia and placental insufficiency. Lancet 1986;1:919. - PubMed
Italy 1990 {published data only}
    1. Iorio R, Horvath S, Marinoni E, Manzari G, Martinico E, Bresadola M. Use of a thromboxane receptor inhibitor in pregnancy‐induced hypertension. Proceedings of 7th World Congress of Hypertension in Pregnancy; 1990 October; Perugia, Italy. 1990:75.
Italy 1990a {published data only}
    1. Airoldi ML, Bertulessi C, Bosco P, Ossola MW, Barbieri M, Polvani F. Effectiveness of Heparin Calcium and Dipyridamole in preventing pregnancy hypertension. Proceedings of the 22nd International Congress on Pathophysiology of Pregnancy, June 21‐23, Budapest, Hungary. Department of Obstetrics and Gynecology Albert Szent‐Györgyi Medical University, 1990:17.
    1. Capetta P, Airoldi L, Iurlaro F, Rossi E, Polvani F. Prevention of pre‐eclampsia. New Trends in Gestational and Perinatal Hypertension 1990;1(3/4):265‐70.
Italy 1991 {published data only}
    1. Airoldi ML, Bertulessi C, Bosco P, Capetta P, Ossola MW, Barbieri M, et al. Prevention of pregnancy hypertension and fetal damage in patients with LLAC and ANA. Clinical and Experimental Hypertension 1991;B10(1 & 2):180.
Italy 1994 {published data only}
    1. Valensise H, Romanini C. Uterine Doppler in the identification of patients at risk for hypertension and IUGR. Journal of Perinatal Medicine 1994;22 Suppl 1:69‐72. - PubMed
Italy 2002 {published and unpublished data}
    1. Frusca T, Lojacono A, Fratelli N, Platto C, Valcamonico A, Bianchi UA. Can low dose aspirin improve perinatal outcome in chronic hypertensive patients [abstract]. Hypertension in Pregnancy 2002;21(Suppl 1):44.
Italy 2005 {published data only}
    1. Mello G, Parretti E, Fatini C, Riviello C, Gensini F, Marchionni M, et al. Efficacy of LMWH in lowering the recurrence rate of preeclampsia and in restoring the physiological vascular changes in ACE DD genotype women [abstract]. Hypertension in Pregnancy 2004;23(Suppl 1):162.
    1. Mello G, Parretti E, Fatini C, Riviello C, Gensini F, Marchionni M, et al. Low‐molecular‐weight heparin lowers the recurrence rate of preeclampsia and restores the physiological vascular changes in angiotensin‐converting enzyme DD women. Hypertension 2005;45(1):86‐91. - PubMed
Italy 2006 {published data only}
    1. Chistolini A, Torelli F, Giancotti A, Pignoloni P, Muto B, Cosimo C, et al. Recurrent fetal loss: prospective evaluation of the efficacy of three different thromboprophylaxis regimens: aspirin versus low molecular weight heparin versus low molecular weight heparin plus aspirin [abstract]. Hematology Journal 2006;91(Suppl 1):146.
    1. Giancotti A, Torre RL, Spagnuolo A, D'Ambrosio V, Cerekja A, Piazze J, et al. Efficacy of three different antithrombotic regimens on pregnancy outcome in pregnant women affected by recurrent pregnancy loss. Journal of Maternal‐Fetal and Neonatal Medicine 2012;25(7):1191‐4. - PubMed
Italy 2009 {published data only}
    1. Lazzarin N, Vaquero E, Exacoustos C, Bertonotti E, Romanini ME, Arduini D. Low‐dose aspirin and omega‐3 fatty acids improve uterine artery blood flow velocity in women with recurrent miscarriage due to impaired uterine perfusion. Fertility and Sterility 2009;92(1):296‐300. - PubMed
Japan 1989 {published data only}
    1. Terao T, Kobayashi T, Imai N, Oda H, Karasawa T. Pathological state of the coagulatory and fibrinolytic system in preeclampsia and the the possibility of its treatment with AT III concentrate. Asia‐Oceania Journal of Obstetrics and Gynaecology 1989;15:25‐32. - PubMed
Libya 2000 {published data only}
    1. Elmahaishi. The uses of low dose aspirin (150mg/day) in primigravida reduces the severity and complications of pregnancy induced hypertension. XVI FIGO World Congress of Obstetrics and Gynaecology; 2000 Sept 3‐8; Washington DC, USA (Book 1). 2000:98.
New Zealand 1990 {published data only}
    1. Hutton JD, Wilkinson AM. Poor participation of nulliparous women in a low dose aspirin study to prevent preeclampsia. New Zealand Medical Journal 1990;103:511‐2. - PubMed
New Zealand 1998 {published data only}
    1. McCowan L, Harding J, Ford C, Barker S, Roberts A, Townend K. Prenatal treatment with low dose aspirin in small for gestational age fetuses with abnormal umbilical doppler: a randomised controlled trial. 2nd Annual Congress of the Perinatal Society of Australia and New Zealand; 1998 March 30‐April 4; Alice Springs, Australia. 1998:135.
    1. McCowan LM, Harding J, Roberts A, Barker S, Ford C, Stewart A. Administration of low dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double‐blind controlled trial. British Journal of Obstetrics and Gynaecology 1999;106:647‐51. - PubMed
New Zealand 2000 {published data only}
    1. Pattison N, Chamley L, Birdsall M, Zanderigo A, Liddell H, McDougall J. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. American Journal of Obstetrics and Gynecology 2000;183:1008‐12. - PubMed
Pakistan 1994 {published data only}
    1. Gilani A, Khan Z. Role of aspirin in management of pregnancy induced hypertension. A study in Pakistani population. Specialist 1994;10:323‐5.
Panama 2014 {published data only}
    1. Vigil‐De Gracia P, Dominguez L, Solis A. Management of chronic hypertension during pregnancy with furosemide, amlodipine or aspirin: a pilot clinical trial. Journal of Maternal‐Fetal and Neonatal Medicine 2014;27(13):1291‐4. - PubMed
Poland 1996 {published data only}
    1. Ciszek V, Kokot F, Wiecek A. Influence of acetylsalicylic acid on the hormonal profile of pregnant women with EPH gestosis [abstract]. Nephrology, Dialysis, Transplantation 1996;11:1419.
Poland 1999 {published and unpublished data}
    1. Kalinka J, Sieroszewski P, Hanke W, Laudanski T, Suzin J. Evaluation of the effectiveness of a low dose aspirin in the treatment of intrauterine growth retardation (IUGR). Ginekologia Polska 1999;70:126‐34. - PubMed
Russia 1997 {published data only}
    1. Zozulia OV, Rogov VA, Piatakova NV, Tareeva IE. Nitric oxide: its role in the development of pregnancy complications and in their prevention in women with hypertension and chronic glomerulonephritis. Terapevticheskii Arkhiv 1997;69(6):17‐20. - PubMed
Slovenia 1998 {published and unpublished data}
    1. Sajina‐Stritar B. The effect of acetylsalicylic acid and n‐3 fatty acids in prevention of complications of hypertension diseases in pregnancy. Zdravstveni Vestnik 1998;67:489‐93.
Spain + others 2000 {published and unpublished data}
    1. Cabero L, Bellart J, Bertini A, Althabe O, Bichou C, Bucheli R. Aspirin in early pregnancy to reduce the incidence and/or severity of pregnancy induced hypertension and intrauterine growth retardation in healthy pregnant women. Hypertension in Pregnancy 2000;19(1):98.
Sweden 2017 {published data only}
    1. Blomqvist L, Hellgren M, Strandell A. Acetylsalicylic acid for prevention of pregnancy loss: a randomized trial. Human Reproduction 2017;32:i11‐i12.
Thailand 1996 {published and unpublished data}
    1. Herabutya Y, Jetsawangsri T, Saropala N. The use of low‐dose aspirin to prevent preeclampsia. International Journal of Gynecology & Obstetrics 1996;54:177‐8. - PubMed
    1. Jetsawangsri T, Herabutya Y, Saropala N. The use of low‐dose aspirin to prevent pre‐eclampsia. Abstracts of 9th Congress of the Federation of the Asia and Oceania Perinatal Societies; 1996 November 10‐14; Singapore. 1996:129.
Trinidad 1998 {published data only}
    1. Bassaw B, Roopnarinesingh S, Roopnarinesingh A, Homer H. Prevention of hypertensive disorders of pregnancy. Journal of Obstetrics and Gynaecology 1998;18(2):123‐6. - PubMed
Tunisia 1989 {published data only}
    1. Hachicha J, Ammous A, Damak J, Hammami M, Ghorbel A, Rekik S, et al. Prevention of complications of hypertension in pregnancy with antiplatelets. Presse Medicale 1989;18:767‐9. - PubMed
    1. Hachicha J, Ammous A, Midassi H, Dammak J, Ghorbel A, Chaabouni MN, et al. Place of antiplatelet therapy (APT) in vasculo‐renal accidents's (VRA) preventive treatment during pregnancy. 6th International Congress, International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:185.
    1. Rekik S, Midassi H, Bayoudh H, Mezghani M, Abid R, Ghorbel A. Place of antiplatelet therapy (APT) in vasculorenal accidents (VRA) preventive treatment in pregnancy. World Congress of Gynecology and Obstetrics; 1988 October 23‐28; Brazil. 1988:185.
Tunisia 1990 {published data only}
    1. Hachicha J, Bellaj A, Ghorbel L, Abid R, Rekik S, Jarraya A. Aspirin or aspirin and dipyridamole to prevent vasculo‐renal accidents in pregnancy. Proceedings of 7th World Congress of Hypertension in Pregnancy; 1990 October; Perugia, Italy. 1990:256.
    1. Hachicha J, Ben Hmida M, Kharrat M, Jarraya F, Rekik S, Jarraya A. Aspirin or aspirin and dipyridamole to prevent pregnancy‐induced hypertension [abstract]. Nephrology, Dialysis, Transplantation 1994;9:926.
Turkey 1994 {published data only}
    1. Okten S, Polat G, Ayata D, Albayrak U. Low‐dose aspirin prophylaxis in high‐risk pregnancies [Riskli gebeliklerde proflaktik dusuk doz aspirin]. Jinekoloji Ve Obstetrik Dergisi 1994;8(4):150‐6.
UK 1992a {published and unpublished data}
    1. McParland P, Pearce JM. Effect of low dose aspirin on maternal and fetal flow velocity waveforms. American Journal of Obstetrics and Gynecology 1992;166:438.
UK 1993 {published data only}
    1. Williams HD, Howard R, O'Donnell N, Findley I. The effect of low dose aspirin on bleeding times. Anaesthesia 1993;48:331‐3. - PubMed
UK 1994 {published data only}
    1. Hamid R, Robson M, Pearce JM. Low dose aspirin in women with raised maternal serum alpha‐fetoprotein and abnormal Doppler waveform patterns from the uteroplacental bed. British Journal of Obstetrics and Gynaecology 1994;101:481‐4. - PubMed
    1. Hamid R, Robson M, Pearce JM. Low dose aspirin in women with raised maternal serum alpha‐fetoprotein and abnormal Doppler waveform patterns from the uteroplacental circulation. International Journal of Gynecology & Obstetrics 1995;48:348‐9. - PubMed
UK 2000 {published data only}
    1. Harrington K, Kurdi W, Aquilina J, England P, Campbell S. A prospective management study of slow‐release aspirin in the palliation of uteroplacental insufficiency predicted by uterine artery Doppler at 20 weeks. Ultrasound in Obstetrics & Gynecology 2000;15:13‐8. - PubMed
    1. Kurdi W, Fayyad A, Thakur V, Harrington K. Delayed normalisation of the uterine artery Doppler waveforms is not a benign phenomenon. European Journal of Obstetrics & Gynecology and Reproductive Biology 2004;117(1):20‐3. - PubMed
USA 1989 {published and unpublished data}
    1. Mirro R, Sibai BM, Leffler CW, Chesney CM. Low dose aspirin during pregnancy. Pediatric Research 1988;23:419A.
    1. Sibai BM, Mirro R, Chesney CM, Leffler C. Low‐dose aspirin in pregnancy. Obstetrics & Gynecology 1989;74:551‐7. - PubMed
USA 1990 {published data only}
    1. Roberts CS, Beeson JH. Low dose aspirin in the prevention of preeclampsia in nulliparas. Preliminary results of a prospective, placebo‐controlled, double blind study. Proceedings of 10th Annual Meeting of Society of Perinatal Obstetricians; 1990 January 23‐27; Houston, Texas, USA. 1990:89.
USA 1993b {published data only}
    1. Silver RK, MacGregor SN, Sholl JS, Hobart JM, Neerhof MG, Ragin A. Comparative trial of prednisone plus aspirin vs aspirin alone in the treatment of anticardiolipin antibody‐positive obstetric patients. American Journal of Obstetrics and Gynecology 1993;169:1411‐7. - PubMed
    1. Silver RK, Sholl JS, MacGregor SN, Hobart JH, Neerhof MG, Hickman AH. Prospective evaluation of single (low‐dose aspirin) vs combined (aspirin plus prednisone) therapy in the treatment of the antiphospholipid syndrome. Proceedings of 39th Annual Meeting of the Society for Gynecologic Investigation; 1992 March 18‐21; San Antonio, Texas, USA. 1992:125.
USA 1993c {published data only}
    1. O'Brien WF, Krammer J, O'Leary TD, Mastrogiannis DS. The effect of acetaminophen on prostacyclin production in pregnant women. American Journal of Obstetrics and Gynecology 1993;168:1164‐9. - PubMed
USA 1996 {published data only}
    1. Martin C, Varner MW, Branch DW, Rodgers G, Mitchell MD. Dose‐related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy. Prostaglandins 1996;51:321‐30. - PubMed
USA 2012 {published data only}
    1. Odibo A, NCT01547390. Early prediction and aspirin for prevention of preeclampsia. clinicaltrials.gov/ct2/show/record/NCT01547390 (first received 7 March 2012).
    1. Odibo AO, Goetzinger KR, Odibo L, Tuuli MG. Early Prediction and Aspirin for Prevention of Pre‐eclampsia study (EPAPP study): a randomized controlled trial. Ultrasound in Obstetrics & Gynecology 2015;46:414‐8. - PubMed
    1. Papatheodorou SI. Re: early prediction and aspirin for prevention of pre‐eclampsia (epapp) study: a randomized controlled trial. A. O. Odibo, K. R. Goetzinger, l. Odibo and M. G. Tuuli. Ultrasound Obstet Gynecol 2015; 46: 414‐8. Ultrasound in Obstetrics & Gynecology 2015;46(4):389. - PubMed
USA 2013 {published data only}
    1. Ahrens KA, Silver RM, Mumford SL, Sjaarda LA, Perkins NJ, Wactawski‐Wende J, et al. Complications and safety of preconception low‐dose aspirin among women with prior pregnancy losses. Obstetrics & Gynecology 2016;127(4):689‐98. - PMC - PubMed
    1. Connell MT, Sjaarda LA, Radin RG, Kuhr D, Mumford SL, Plowden TC, et al. The effects of aspirin in gestation and reproduction (eager) trial: a story of discovery. Seminars in Reproductive Medicine 2017;35(4):344‐52. - PMC - PubMed
    1. Gibbins KJ, Branch DW, Silver RM, Sjaarda LA, Mumford SL, Perkins NJ, et al. Recurrent pregnancy loss in women with and without antiphospholipid antibodies. American Journal of Obstetrics & Gynecology 2016;214(1 Suppl):S199.
    1. Lesher LL, Matyas RA, Sjaarda LA, Newman SL, Silver RM, Galai N, et al. Recruitment for longitudinal, randomised pregnancy trials initiated preconception: lessons from the Effects of Aspirin in Gestation and Reproduction trial. Paediatric and Perinatal Epidemiology 2015;29(2):162‐7. - PMC - PubMed
    1. Mone F, McAuliffe FM. Preconception low‐dose aspirin and pregnancy outcomes: results from the EAGeR randomized trial. Irish Medical Journal 2015;108(1):5. - PubMed
Vietnam 2017 {published data only}
    1. Cao NT, Vu QH, Truong QV, Vo VD, Tran ML. Effectiveness of low‐dose aspirin for the prevention of pre‐eclampsia. Journal of Obstetrics and Gynaecology Research 2017;43:69.
West Germany 1977 {published data only}
    1. Wolfrum R, Bordasch C, Holweg J, Schulz G. The therapy of chronic nutritional placenta disorders ‐ preliminary results of a double blind study. Archives of Gynecology 1977;224:114. - PubMed

References to studies awaiting assessment

Abdi 2019 {published data only}
    1. Abdi N, IRCT20181218042033N1. Evaluating the effect of aspirin on the occurrence of PLP, IUGR and preeclampsia in pregnant women with a history of preeclampsia in a previous pregnancies in Khalije fars hospital Bandar abbas,Iran in 2016‐2017. http://en.irct.ir/trial/36064 (first received 20 January 2019).
Agrawala 2019 {published data only}
    1. Agrawala S, Sjaarda LA, Omosigho UR, Perkins NJ, Silver RM, Mumford SL, et al. Effect of preconception low dose aspirin on pregnancy and live birth according to socioeconomic status: a secondary analysis of a randomized clinical trial. Plos One 2019; Vol. 14, issue 4:e0200533. - PMC - PubMed
Amro 2019 {published data only}
    1. Amro F, NCT03961360. Effectiveness of higher aspirin dosing for prevention of preeclampsia in high risk obese gravida: an open label, comparative effectiveness, randomized controlled trial (aspreo trial). https://clinicaltrials.gov/ct2/show/NCT03961360 (first received 23 May 2019).
Benavides 2016 {published data only}
    1. Benavides LG, NCT02838030. Efficacy of the combination of acetylsalicylic acid and l‐arginine to prevent preeclampsia in pregnant high risk. https://clinicaltrials.gov/ct2/show/NCT02838030. NCT02838030 (20 July 2016) 2016.
China 2012 {published data only}
    1. Zhao YM, Xiao LP, Hu H, Yang XN, Xu YQ, Guo LM. Low‐dose aspirin prescribed at bed time for the prevention of pre‐eclampsia in high‐risk pregnant women. Reproduction and Contraception 2012;32:355–9.
Cobaleda 2018 {published data only}
    1. Cobaleda M, NCT03741179. A phase iii, multicentric, randomized, open‐label, parallel‐group clinical trial to detect false positives from first‐trimester preeclampsia screening (stoppre) at the second‐trimester of pregnancy. https://clinicaltrials.gov/ct2/show/NCT03741179 (first received 14 November 2018).
Finneran 2019 {published data only}
    1. Finneran MM, Gonzalez‐Brown VM, Smith DD, Landon MB, Rood K. 48: effect of obesity on platelet inhibition in high‐risk pregnant women treated with low dose aspirin. American Journal of Obstetrics and Gynecology 2019;220(1):S38‐9. - PubMed
Finneran 2019a {published data only}
    1. Finneran MM, Gonzalez‐Brown VM, Smith DD, Landon MB, Rood KM. Obesity and laboratory aspirin resistance in high risk pregnant women treated with low dose aspirin. American Journal of Obstetrics and Gynecology 2019;220(4):385.e1‐385.e6.. - PubMed
India 1993a {unpublished data only}
    1. Regi A. [Personal communication] Randomised controlled trial of low dose aspirin in high risk pregnancy. Letter to: Cochrane Pregnancy and Childbirth Group, Oxford, Uk 1993.
Iran 2017a {published data only}
    1. Movahed F, IRCT201505103025N5. The effect of aspirin administration for prevention of preeclampsia in pregnant women with abnormal findings in uterine artery doppler sonograph. http://en.irct.ir/trial/2988 (first received 8 June 2015).
    1. Movahed F, Lalooha F, Dabbaghi Ghale T, Rezaee Majd Z, Moinodin R, Yazdi Z. The effect of aspirin in the prevention of preeclampsia in women with abnormal uterine artery doppler ultrasonography findings. Journal of Zanjan University of Medical Sciences and Health Services 2017;25(108):11‐9.
Lin 2018 {published data only}
    1. Lin L, Zhu Y, Li B, Yang H. Low‐dose aspirin in the prevention of pre‐eclampsia in China (APPEC study): protocol for a multicentre randomized controlled trial. Trials 2018;19(1):608. - PMC - PubMed
Matthews 2019 {published data only}
    1. Matthews KC, NCT04070573. A randomized controlled trial comparing low doses of aspirin in the prevention of preeclampsia (asapp). https://clinicaltrials.gov/ct2/show/NCT04070573 (first received 27 August 2019).
Meher 2019 {published data only}
    1. Meher R, CTRI/2019/05/019232. Low dose aspirin in prevention of preeclampsia. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=33792 (first received 20 May 2019).
Mirzamoradi 2018 {published data only}
    1. Mirzamoradi M, IRCT20120918010876N6. Comparison of two various aspirin dosage (80mg and 120mg daily) on prevention of pre‐eclampsia in high risk pregnant women. http://en.irct.ir/trial/35557 (first received 16 December 2018).
Mone 2018 {published data only}
    1. Mone F, Mulcahy C, McParland P, Breathnach F, Downey P, McCormack D, et al. Trial of feasibility and acceptability of routine low‐dose aspirin versus early screening test indicated aspirin for pre‐eclampsia prevention (test study): a multicentre randomised controlled trial. Bmj Open 2018;8(7):e022056. - PMC - PubMed
Mone 2019 {published data only}
    1. Mone F, Mulcahy C, McParland P, Downey P, Culliton M, Maguire OC, et al. Evaluation of the effect of low‐dose aspirin on biochemical and biophysical biomarkers for placental disease in low‐risk pregnancy: secondary analysis of a multicenter rct. American Journal of Perinatology 2019 [ahead of print]. - PubMed
Mulcahy 2019 {published data only}
    1. Mulcahy C, Mone F, McParland P, Breathnach F, Cody F, Morrison JJ, et al. The impact of aspirin on ultrasound markers of uteroplacental flow in low‐risk pregnancy: secondary analysis of a multicenter rct. American Journal of Perinatology 2019; Vol. 36, issue 8:855‐63. - PubMed
NCT03574909 2018 {published data only}
    1. NCT03574909. Investigating the role of early low‐dose aspirin in diabetes: a phase iii multicentre double‐blinded placebo‐controlled randomised trial of low‐dose aspirin initiated in the first trimester of diabetes pregnancy. https://clinicaltrials.gov/ct2/show/NCT03574909 (first received 2 July 2018). - PMC - PubMed
NCT03674606 2018 {published data only}
    1. NCT03674606. An open‐label randomized‐controlled trial of early screening test for pre‐eclampsia and growth restriction. https://clinicaltrials.gov/ct2/show/NCT03674606 (first received 17 September 2018). - PubMed
Netherlands/UK 1994 {published data only}
    1. Kraavenbrink A, Gans R, Geijn H, Dekker G. Insulin resistance, vasoactive mediators and preeclampsia. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S26. - PubMed
    1. Kraayenbrink AA, Robson M, Dekker GA, Pearce JM, Geijn HP. Prevention of preeclampsia and fetal growth retardation; allylestrenol vs aspirin, a two centered study. Proceedings of 9th International Congress, International Society for the Study of Hypertension in Pregnancy; 1994 March 15‐18; Sydney, Australia. 1994:125.
Netherlands 1991 {published data only}
    1. Noort WA, Rotmans N, Keirse MJ, Wallenburg HC. Effect of low‐dose aspirin with and without dipyridamole on prostanoid biosynthesis in pregnancy. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30‐May 3; The Hague, Netherlands. 1991:182.
    1. Wallenburg HC, Rotmans N, Noort WA, Keirse MJ. Effect of low‐dose aspirin with and without dipyridamole on prevention of recurrent idiopathic fetal growth retardation. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30‐May 3; The Hague, Netherlands 1991:92.
O'Brien 2019 {published data only}
    1. O'Brien J, NCT03893630. Role of aspirin in maternal endothelial dysfunction and uterine artery blood flow in women at risk for preeclampsia. https://clinicaltrials.gov/ct2/show/NCT03893630 (first received 28 March 2019).
Poon 2018 {published data only}
    1. Poon L. Prevention of preeclampsia. International Journal of Gynecology and Obstetrics 2018; Vol. 143:87.
Poon 2019 {published data only}
    1. Poon L, NCT03941886. Implementation of first‐trimester screening and prevention of preeclampsia: a stepped wedge cluster‐randomized trial in asia. https://clinicaltrials.gov/ct2/show/NCT03941886 (first received 8 May 2019). - PMC - PubMed
Qi 2019 {published data only}
    1. Qi H, NCT04051567. Low‐dose aspirin for prevention of adverse pregnancy outcomes in twin pregnancies‐‐a multicenter, prospective, open, randomized, controlled clinical trial. https://clinicaltrials.gov/ct2/show/NCT04051567 (first received 9 August 2019).
Rood 2018 {published data only}
    1. Rood K, NCT03735433. The effect of 81mg vs 162mg asa for preeclampsia prevention in obese women at high risk for developing preeclampsia. https://clinicaltrials.gov/ct2/show/NCT03735433 (first received 8 November 2018).
Sallam 2018 {published data only}
    1. Sallam HF, NCT03725891. Comparison of two doses (81 mg versus 162 mg) of aspirin for the prevention of preeclampsia in healthy, nulliparous obese and overweight pregnant women: a randomized controlled trial. https://clinicaltrials.gov/ct2/show/NCT03725891 (first received 31 October 2018).
Sallam 2018a {published data only}
    1. Sallam HF, NCT03726177. Comparison of two doses (81 mg versus 162mg) of aspirin for the prevention of preeclampsia in high‐risk pregnant women: a randomized controlled trial. https://clinicaltrials.gov/ct2/show/NCT03726177 (first received 31 October 2018).
Slovenia 1992 {published data only}
    1. Sajina‐Stritar B, Novak‐Antolic Z. Antiaggregational therapy in preventing EPH gestosis and its complications. Journal of Perinatal Medicine 1992;20(Suppl 1):73.
    1. Sajina‐Stritar B, Novak‐Antolic Z. Antiaggregational therapy in preventing EPH gestosis and its complications. Proceedings of 26th British Congress of Obstetrics and Gynaecology; 1992 July 7‐10; Manchester, UK. 1992:454.
Slovenia 1994 {published data only}
    1. Sajina‐Stritar B. Prevention of gestational hypertension and its complications with ASA and N‐3 fatty acids (comparative study). Proceedings of 14th European Congress of Perinatal Medicine; 1994 June 5‐8; Helsinki, Finland. 1994:182.
South Africa 1986 {published data only}
    1. Richards A, Moodley J, Norman R. The use of low dose aspirin in pregnancy induced hypertension. 23rd South African Congress of Obstetrics and Gynaecology; 1986 September 23‐26; South Africa. 1986:16.
Sutton 2018 {published data only}
    1. Sutton EF, Hauspurg A, Caritis SN, Powers RW, Catov JM. Maternal outcomes associated with lower range stage 1 hypertension. Obstetrics and Gynecology 2018;132(4):843‐849. - PMC - PubMed
Switzerland 2000 {published data only}
    1. Ferrier C, Koeferl U, Duerig P, Schneider H. Effects of LMW‐heparin and low‐dose aspirin on renal uric acid handling in high‐risk pregnancies. Hypertension in Pregnancy 2000;19(Suppl 1):O68.
    1. Ferrier C, Koferl U, Durig P, Schneider H. LMW heparin and low dose aspirin for prevention of preeclampsia: preliminary data of a randomised prospective study [abstract]. Hypertension in Pregnancy 2000;19(1):82.
Uganda 1992 {published data only}
    1. Lule J. [Personal communication] Trial of aspirin and methyldopa for moderate hypertension in pregnancy. Letter to: Cochrane Pregnancy and Childbirth Group, Oxford, UK 3 June 1993.
USA 1988a {published data only}
    1. O'Grady JP Wilson B. [Personal communication] Effects of low‐dose aspirin in improving fetal outcome in high risk pregnancies for intrauterine fetal growth retardation and/or preterm delivery. Letter to: Cochrane Pregnancy and Childbirth Group, Oxford, UK 19 March 1991.
USA 1990a {published data only}
    1. Carlson NJ. [Personal communication] Trial to evaluate the effectiveness of low dose aspirin versus placebo in the prevention of pregnancy induced hypertension in multiparous patients pregnant with multiple gestations. Letter to: Cochrane Pregnancy and Childbirth Group, Oxford, UK 6 September 1991.
Wright 2018 {published data only}
    1. Wright D, Rolnik DL, Syngelaki A, Paco Matallana C, Machuca M, Alvarado M, et al. Aspirin for evidence‐based preeclampsia prevention trial: effect of aspirin on length of stay in the neonatal intensive care unit. American Journal of Obstetrics and Gynecology 2018; Vol. 218, issue 6:612.e1‐6. - PubMed
Wright 2019 {published data only}
    1. Wright D, Nicolaides KH. Aspirin delays the development of preeclampsia. American Journal of Obstetrics and Gynecology 2019;220(6):580.e1‐580.e6. - PubMed
Zhang 2018 {published data only}
    1. Zhang J, ChiCTR1800015301. Aspirin for preventing placenta‐mediated pregnancy complications: A community‐based multicenter randomized controlled study. http://www.chictr.org.cn/showproj.aspx?proj=24982 (first received 22 March 2018).

References to ongoing studies

ASPIRIN trial 2017 {published data only}
    1. Goudar SS, CTRI/2016/05/006970. Aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) ‐ ASPIRIN. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=14886 (first received 31 May 2016).
    1. Hoffman M, NCT02409680. Aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN). clinicaltrials.gov/ct2/show/NCT02409680 (first received 16 December 2016).
    1. Hoffman MK, Goudar SS, Kodkany BS, Goco N, Koso‐Thomas M, Miodovnik M, et al. A description of the methods of the aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) study. BMC Pregnancy and Childbirth 2017;17(1):135. - PMC - PubMed
    1. Reyes OA, NCT01890005. Low dose aspirin between 13 and 16 weeks of pregnancy for the prevention of preeclampsia. double blind, randomized, controlled trial. clinicaltrials.gov/ct2/show/record/NCT01890005 (first received 1 July 2013).
China 2016a {published data only}
    1. Yang H, NCT02797249. Low dose aspirin in the prevention of preeclampsia in Chinese pregnant women. clinicaltrials.gov/ct2/show/record/NCT02797249 (first received 13 June 2016).
Egypt 2015 {published data only}
    1. Hassan A, PACTR201503001054393. Comparison between the roles of low dose aspirin and folic acid in preventing preeclampsia among high risk women screened by uterine artery Doppler at 22‐24 weeks of gestation: a randomised controlled trial. http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=... (first received 4 March 2015).
France 2012 {published data only}
    1. Perrotin F, NCT01729468. Prevention of pre‐eclampsia and sga by low‐dose aspirin in nulliparous women with abnormal first‐trimester uterine artery dopplers. clinicaltrials.gov/ct2/show/NCT01729468 (first received 20 November 2012).
Ghana 2016 {published data only}
    1. Browne JL, NCT02007837. Prospects for the prevention of pregnancy‐induced hypertension and preeclampsia (4p) ‐ a randomised, placebo‐controlled, double‐blind clinical trial. clinicaltrials.gov/ct2/show/NCT02007837 (first received 25 November 2016).
India 2018 {published data only}
    1. Kumar N, CTRI/2018/01/011155. Pilot interventional study by different low doses of aspirin versus placebo for prevention of preeclampsia ‐ a double blind randomized control trial. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=15679 (first received 5 January 2018).
Iran 2013 {published data only}
    1. Atarod Z, IRCT2013072914198N1. Using of low dose aspirin in the prevention of preeclampsia in pregnant women with abnormal uterin Doppler at 11‐14 weeks gestation. http://en.irct.ir/trial/13849 (first received 14 September 2013).
Iran 2015 {published data only}
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