Abstract
Objective: To examine whether there are differences in the effect of aspirin on the incidence of preterm-PE in the ASPRE trial in subgroups defined according to maternal characteristics and medical and obstetrical history.
Study design: This was a secondary analysis of data from the ASPRE trial. In ASPRE women with singleton pregnancies had screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks’ gestation. Those with an estimated risk for preterm-PE of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/day) vs. placebo from 11 to 14 until 36 weeks’ gestation. Aspirin was associated with a significant reduction in the incidence of preterm-PE with delivery at <37 weeks’ gestation, which was the primary outcome (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm-PE in subgroups defined by maternal age (<30 and ≥30 years), body mass index (<25 and ≥25 kg/m2), racial origin (Afro-Caribbean, Caucasian and other), method of conception (natural and assisted), cigarette smoking (smoker and non-smoker), family history of PE (present and absent), obstetrical history (nulliparous, multiparous with previous PE and multiparous without previous PE), history of chronic hypertension (present and absent). Interaction tests were performed on the full data set of patients in the intention to treat population and on the data set of patients who took > 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons.
Results: There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm-PE occurred in 10.2% (5/49) in the aspirin group and in 8.2% (5/61) in the placebo group (adjusted odds ratio 1.29, 95% confidence interval, 0.33 to 5.12); the respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio 0.27, 95% confidence interval, 0.12 to 0.60). In all participants with adherence of >90% the adjusted odds ratio in the aspirin group was 0.24 (95% CI 0.09 to 0.65), in the subgroup with chronic hypertension it was 2.06 (95% CI 0.40 to 10.71) and in those without chronic hypertension it was 0.05 (95% CI 0.01 to 0.41). For the complete data set the test of interaction was not significant at the 5% level (p=0.055), but in those with adherence >90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (p=0.0019).
Conclusions: The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history.
Study design: This was a secondary analysis of data from the ASPRE trial. In ASPRE women with singleton pregnancies had screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks’ gestation. Those with an estimated risk for preterm-PE of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/day) vs. placebo from 11 to 14 until 36 weeks’ gestation. Aspirin was associated with a significant reduction in the incidence of preterm-PE with delivery at <37 weeks’ gestation, which was the primary outcome (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm-PE in subgroups defined by maternal age (<30 and ≥30 years), body mass index (<25 and ≥25 kg/m2), racial origin (Afro-Caribbean, Caucasian and other), method of conception (natural and assisted), cigarette smoking (smoker and non-smoker), family history of PE (present and absent), obstetrical history (nulliparous, multiparous with previous PE and multiparous without previous PE), history of chronic hypertension (present and absent). Interaction tests were performed on the full data set of patients in the intention to treat population and on the data set of patients who took > 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons.
Results: There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm-PE occurred in 10.2% (5/49) in the aspirin group and in 8.2% (5/61) in the placebo group (adjusted odds ratio 1.29, 95% confidence interval, 0.33 to 5.12); the respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio 0.27, 95% confidence interval, 0.12 to 0.60). In all participants with adherence of >90% the adjusted odds ratio in the aspirin group was 0.24 (95% CI 0.09 to 0.65), in the subgroup with chronic hypertension it was 2.06 (95% CI 0.40 to 10.71) and in those without chronic hypertension it was 0.05 (95% CI 0.01 to 0.41). For the complete data set the test of interaction was not significant at the 5% level (p=0.055), but in those with adherence >90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (p=0.0019).
Conclusions: The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history.
| Original language | English |
|---|---|
| Journal | American Journal of Obstetrics and Gynecology |
| Early online date | 4 Aug 2017 |
| DOIs | |
| Publication status | Published - 2017 |
Keywords
- First trimester screening
- Aspirin
- ASPRE trial
- Preeclampsia
- Chronic hypertension
- Uterine artery Doppler
- Mean arterial blood pressure
- Placental growth factor
- Pregnancy associated plasma protein-A