Aspirin in Pregnancy: Beyond Preeclampsia
Aspirin in Pregnancy: Beyond Preeclampsia
Emmanuel Bujold, MD, MSc, is an investigator on the following study:
Roberge S, Nicolaides K, Demers S, Villa P, Bujold E. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol. 2013 Jan 29. [Epub ahead of print]
Emmanuel Bujold, MD, MSc, is Associate Professor in the Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval, Québec, Canada. Dr. Bujold holds a Clinician Scientist Award from the Canadian Institutes of Health Research and the Jeanne et Jean-Louis Lévesque Perinatology Research Chair. His research is focused on the discovery of biomarkers of prematurity and other major obstetric syndromes and the consequences for the infant at birth.
The safety and generally positive effects of low-dose aspirin on reproductive outcomes have been demonstrated in several randomized clinical trials. Meta-analyses of these trials suggested that administration of low-dose aspirin at or before the 16th week of pregnancy is associated with a significant reduction in the risk for preeclampsia.
At Université Laval, Dr. Bujold and colleagues, together with investigators in London and Helsinki, performed a new meta-analysis of trials to determine whether early (≤ 16 weeks) or late (> 16 weeks) administration of low-dose aspirin would also effectively reduce the risk for perinatal death and other adverse perinatal outcomes. They identified 42 trials in which a total of 27,222 pregnant women were randomly assigned to prophylactic use of aspirin (50-150 mg/day) with or without dipyridamole (≤ 300 mg), or to placebo or no treatment. Inclusion criteria for the trials included nulliparity, multiple pregnancy, chronic hypertension, cardiovascular or endocrine disease, prior gestational hypertension or fetal growth restriction, or abnormal findings on uterine artery Doppler ultrasonography.
The analysis showed that when aspirin therapy was started at 16 weeks' gestation or earlier, it was associated with a significant reduction (59%) in the risk for perinatal death compared with control participants (P = .03), whereas the reduction associated with aspirin therapy started after 16 weeks (7%) was not significant. The difference in risk reduction between the 2 gestational age subgroups was also significant (P = .02). Significant reductions were also seen in preeclampsia (53%), severe preeclampsia (0.82%), fetal growth restriction (48%), and preterm birth (0.64%) when aspirin therapy started at 16 weeks' gestation or earlier (all P < .001 vs control participants). Aspirin administered at or earlier than 16 weeks was also associated with small but significant reductions in preeclampsia and preterm birth; this finding also differed significantly from the later-than-16-weeks group.
Aspirin given later than 16 weeks had no significant effect on fetal growth restriction. No differences in the effects of early aspirin prophylaxis were seen between the low (≤ 80 mg) or the higher (≥ 100 mg) daily dose, or between women who were selected or not selected for study according to abnormal findings on uterine artery Doppler ultrasonography.
On the basis of their meta-analysis and other evidence, Dr. Bujold and coauthors recommend that women determined to be at high risk for preeclampsia or other placenta-mediated adverse pregnancy outcomes should be offered low-dose aspirin daily, starting before 16 weeks of gestation. They found insufficient evidence from the analysis to draw conclusions about the effect of aspirin given after 16 weeks on the risk for severe preeclampsia but noted that benefits on other outcomes appeared modest.
Dr. Bujold spoke with Linda Brookes, MSc, for Medscape about the latest meta-analysis of clinical trials on aspirin in pregnant women, its implications for current recommendations for aspirin prophylaxis in pregnancy, and the outstanding questions remaining to be answered in ongoing and future studies.
An Expert Interview With Emmanuel Bujold, MD, MSc
The Study
Emmanuel Bujold, MD, MSc, is an investigator on the following study:
Roberge S, Nicolaides K, Demers S, Villa P, Bujold E. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol. 2013 Jan 29. [Epub ahead of print]
About the Interviewee
Emmanuel Bujold, MD, MSc, is Associate Professor in the Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval, Québec, Canada. Dr. Bujold holds a Clinician Scientist Award from the Canadian Institutes of Health Research and the Jeanne et Jean-Louis Lévesque Perinatology Research Chair. His research is focused on the discovery of biomarkers of prematurity and other major obstetric syndromes and the consequences for the infant at birth.
Background to the Study
The safety and generally positive effects of low-dose aspirin on reproductive outcomes have been demonstrated in several randomized clinical trials. Meta-analyses of these trials suggested that administration of low-dose aspirin at or before the 16th week of pregnancy is associated with a significant reduction in the risk for preeclampsia.
At Université Laval, Dr. Bujold and colleagues, together with investigators in London and Helsinki, performed a new meta-analysis of trials to determine whether early (≤ 16 weeks) or late (> 16 weeks) administration of low-dose aspirin would also effectively reduce the risk for perinatal death and other adverse perinatal outcomes. They identified 42 trials in which a total of 27,222 pregnant women were randomly assigned to prophylactic use of aspirin (50-150 mg/day) with or without dipyridamole (≤ 300 mg), or to placebo or no treatment. Inclusion criteria for the trials included nulliparity, multiple pregnancy, chronic hypertension, cardiovascular or endocrine disease, prior gestational hypertension or fetal growth restriction, or abnormal findings on uterine artery Doppler ultrasonography.
The analysis showed that when aspirin therapy was started at 16 weeks' gestation or earlier, it was associated with a significant reduction (59%) in the risk for perinatal death compared with control participants (P = .03), whereas the reduction associated with aspirin therapy started after 16 weeks (7%) was not significant. The difference in risk reduction between the 2 gestational age subgroups was also significant (P = .02). Significant reductions were also seen in preeclampsia (53%), severe preeclampsia (0.82%), fetal growth restriction (48%), and preterm birth (0.64%) when aspirin therapy started at 16 weeks' gestation or earlier (all P < .001 vs control participants). Aspirin administered at or earlier than 16 weeks was also associated with small but significant reductions in preeclampsia and preterm birth; this finding also differed significantly from the later-than-16-weeks group.
Aspirin given later than 16 weeks had no significant effect on fetal growth restriction. No differences in the effects of early aspirin prophylaxis were seen between the low (≤ 80 mg) or the higher (≥ 100 mg) daily dose, or between women who were selected or not selected for study according to abnormal findings on uterine artery Doppler ultrasonography.
On the basis of their meta-analysis and other evidence, Dr. Bujold and coauthors recommend that women determined to be at high risk for preeclampsia or other placenta-mediated adverse pregnancy outcomes should be offered low-dose aspirin daily, starting before 16 weeks of gestation. They found insufficient evidence from the analysis to draw conclusions about the effect of aspirin given after 16 weeks on the risk for severe preeclampsia but noted that benefits on other outcomes appeared modest.
Dr. Bujold spoke with Linda Brookes, MSc, for Medscape about the latest meta-analysis of clinical trials on aspirin in pregnant women, its implications for current recommendations for aspirin prophylaxis in pregnancy, and the outstanding questions remaining to be answered in ongoing and future studies.
