Maternal blood-pressure trends throughout pregnancy and development of pre-eclampsia in women receiving first-trimester aspirin prophylaxis

Objectives: To study women who initiated aspirin in the first trimester for high risk of pre-eclampsia, and compare blood-pressure trends throughout pregnancy between those with normal outcome and those who subsequently developed pre-eclampsia. Methods: Women were enrolled into a prospective observational study at 9–14 weeks' gestation. This was a secondary analysis of those who started daily doses of 81 mg of aspirin before 16 weeks for increased risk of pre-eclampsia based on maternal history and bilateral uterine artery notching. Enrollment characteristics and blood-pressure measurements throughout gestation were compared between women who did and those who did not develop pre-eclampsia. Results: Of the 237 women who initiated first-trimester aspirin prophylaxis, 29 (12.2%) developed pre-eclampsia. A total of 2881 serial blood-pressure measurements obtained between 4 and 41 weeks' gestation (747 in the first trimester, 1008 in the second and 1126 in the third) showed that women with pre-eclampsia started pregnancy with higher blood pressure and maintained this trend despite taking aspirin (mean arterial blood pressure in women with pre-eclampsia = (0.13 × gestational age (weeks)) + 93.63, vs (0.11 × gestational age (weeks)) + 82.61 in those without; P < 0.005). First-trimester diastolic and second-trimester systolic blood pressure were independent risk factors for pre-eclampsia (β = 1.087 and 1.050, respectively; r ²  = 0.24, P < 0.0001). When average first-trimester diastolic blood pressure was >74 mmHg, the odds ratio for pre-eclampsia was 6.5 (95% CI, 2.8–15.1; P < 0.001) and that for pre-eclampsia before 34 weeks was 14.6 (95% CI, 1.72–123.5; P = 0.004). If, in addition, average second-trimester systolic blood pressure was >125 mmHg, the odds ratio for pre-eclampsia was 9.4 (95% CI, 4.1–22.4; P < 0.001) and that for early-onset disease was 34.6 (95% CI, 4.1–296.4; P = 0.004). Conclusion: In women treated with prophylactic aspirin from the first trimester, those who develop pre-eclampsia have significantly and sustained higher blood pressure from the onset of pregnancy compared with those who do not develop pre-eclampsia. This raises the possibility that mildly elevated blood pressure predisposes women to abnormal placentation, which then acts synergistically with elevated blood pressure to predispose such women to pre-eclampsia to a degree that is incompletely mitigated by aspirin.