Antihypertensive treatment escalation and maternal outcomes during expectant management of early-onset preeclampsia...

Early-onset preeclampsia with severe features is associated with substantial maternal morbidity. During expectant management, oral antihypertensive medications are frequently escalated and intravenous agents are administered for severe hypertension, yet the clinical significance of escalating antihypertensive treatment has not been well characterized.

To evaluate the association between antihypertensive treatment escalation during expectant management of early-onset preeclampsia with severe features and adverse maternal outcomes.

This retrospective cohort study included singleton pregnancies managed expectantly for preeclampsia with severe features between 23 weeks 0 days and 33 weeks 5 days at a single level IV referral center from January 2016 through December 2025. The primary exposure was the number of oral antihypertensive medication dose escalations during expectant management. Secondary analyses evaluated dose escalation rate, oral antihypertensive treatment intensity using hypertension daily dose, and intravenous antihypertensive medication pushes for urgent blood pressure control. The primary outcome was a composite maternal adverse outcome including placental abruption, intrauterine fetal death, acute kidney injury, pulmonary edema, myocardial infarction, hemolysis, elevated liver enzymes, and low platelet syndrome, disseminated intravascular coagulation, eclampsia, stroke, or maternal death. Multivariable Poisson and linear regression analyses were performed.

Among 396 patients undergoing expectant management, 157 (39.6%) had no oral antihypertensive dose escalations, whereas 100 (25.2%), 84 (21.2%), 33 (8.3%), and 22 (5.6%) had 1, 2, 3, and ≥4 escalations, respectively. The rate of the composite maternal adverse outcome increased across dose escalation categories (P=.01). Each additional dose escalation was associated with an absolute 4.2 percentage point increase in maternal risk (95% confidence interval, 2.0-6.5). Compared with no dose escalations, 3 and ≥4 dose escalations were associated with adjusted relative risks of 4.07 (95% confidence interval, 1.41-11.78) and 5.20 (95% confidence interval, 1.81-14.90), respectively. Daily dose escalation, compared to none, was associated with an adjusted relative risk of 7.92 (95% confidence interval, 2.90-21.63). Similar dose-dependent associations were observed with repeated intravenous antihypertensive medication pushes. Greater hypertension daily dose was associated with increased maternal risk but without a clear dose-response relationship. Neonatal outcomes did not differ across dose escalation categories.

Escalating antihypertensive treatment during expectant management of early-onset preeclampsia with severe features was associated with progressively higher maternal risk. Consistent findings across oral dose escalation, escalation rate, and intravenous antihypertensive medication use suggest that treatment trajectory may serve as a dynamic marker of disease progression and may complement maternal risk assessment and counseling during expectant management.