Early Vascular Adjustments to Prevent Preeclampsia

NCT ID: NCT04216706

Last Updated: 2020-03-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 314 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-11-01
• Study Completion Date: 2020-03-01

Brief Summary

Women destined to develop gestational hypertensive complications often exhibit deviant hemodynamic adaptation patterns before overt clinical disease. Gestational hypertension and late onset preeclampsia are associated with an exaggerated rise in cardiac output on top of a higher prepregnant value, whereas a shallow rise in cardiac output and the lack of a peripheral resistance drop predisposes to the much less common early onset-preeclampsia along with impaired fetal growth. Early treatment of altered cardiac output and peripheral resistance adjustments might prevent development of gestational hypertensive complications. The investigators aim to evaluate early cardiovascular adjustments during pregnancy in a high-risk population, and to pharmaceutically adjust deviant cardiovascular adaptations with beta-blockade, centrally acting sympatholytic agents or vasodilating agents when appropriate to prevent adverse effects on neonatal birth weight.

Detailed Description

Healthy pregnancy is accompanied by major hemodynamic changes that benefit the uteroplacental circulation. A first-trimester drop in vascular resistance triggers several compensatory mechanisms, amongst an increase in blood volume and cardiac output, to maintain blood pressure. These adaptations continue and stand until delivery.

Women destined to develop gestational hypertensive complications often exhibit deviant hemodynamic adaptation patterns before overt clinical disease. On the one hand, gestational hypertension and late onset preeclampsia are associated with an exaggerated rise in cardiac output on top of a higher prepregnant value, whereas a shallow rise in cardiac output and the lack of a peripheral resistance drop predisposes to the much less common early onset-preeclampsia along with impaired fetal growth.

Antihypertensive therapy based on correction of the hemodynamic imbalance between cardiac output and peripheral resistance seems an effective strategy to improve blood pressure control in hypertensive pregnant women. Even more sophisticated, early treatment of altered cardiac output and peripheral resistance adjustments might prevent development of gestational hypertensive complications. One randomized controlled trial treated pregnant women with an augmented cardiac output with a selective beta-blocker, which resulted in a decreased prevalence of preeclampsia from 18% in the placebo group to 4% in the atenolol group (p = 0.04), at a cost of 440gram birth weight.

In line of this reasoning, the investigators aimed to evaluate early cardiovascular adjustments during pregnancy in a high-risk population (i.e. women with preeclampsia in their first pregnancy). In this health care traject, women with deviant adaptation to pregnancy were advised tailored medication, i.e. beta-blockade in women with an pronounced high cardiac output profile effectuated by a high heart rate, and a vasodilating agent in women with a high-resistance hemodynamic profile. Women with a mixed hemodynamic profile were advised a centrally acting sympatholytic agent. The investigators aimed to retrospectively compare outcome of women attending this health care project with women who received care as usual in their second pregnancy.

Conditions

Preeclampsia; Small for Gestational Age at Delivery; HELLP Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Tailored treatment advise in suboptimal adaptation

High-risk women admitted to a non-pregnant cardiovascular and cardiometabolic risk factor assessment are invited to participate in a follow-up program at four time-points during a subsequent pregnancy (i.e. at 12, 16, 20 and 30 weeks of gestational age). This program is additive to regular pregnancy check-ups, and all women are otherwise managed by their referring physicians. The aim of this program is to evaluate adaptation of maternal hemodynamic parameters in response to pregnancy, and to adjust deviant adaptation with tailored antihypertensive medication. Participation in this program is on voluntary basis, and not restricted to severity of complications in the first pregnancy.

tailored pharmaceutical treatment

Intervention Type: DRUG

Tailored medication is advised in women with inadequate hemodynamic adaptation to pregnancy. Type of medication depends on total peripheral vascular resistance and heart rate. In short, women with a low peripheral vascular resistance in parallel with a high heart rate are advised a betablocker (labetalol), while a vasodilating agent (calcium channel blocker, nifedipine) was advised in women with a high total peripheral vascular resistance in combination with a low heart rate. Women with suboptimal adaptation to pregnancy without an extreme pronounced vascular profile are advised a centrally acting sympatholytic agent (methyldopa).

Care as usual during pregnancy

High-risk women admitted to a non-pregnant cardiovascular and cardiometabolic risk factor assessment who do not participate in the additional follow-up program.

No interventions assigned to this group

Interventions

tailored pharmaceutical treatment

Tailored medication is advised in women with inadequate hemodynamic adaptation to pregnancy. Type of medication depends on total peripheral vascular resistance and heart rate. In short, women with a low peripheral vascular resistance in parallel with a high heart rate are advised a betablocker (labetalol), while a vasodilating agent (calcium channel blocker, nifedipine) was advised in women with a high total peripheral vascular resistance in combination with a low heart rate. Women with suboptimal adaptation to pregnancy without an extreme pronounced vascular profile are advised a centrally acting sympatholytic agent (methyldopa).

Intervention Type: DRUG

Other Intervention Names

Betablocker; Centrally acting sympatholytic agent; Calcium channel blocker

Eligibility Criteria

Inclusion Criteria

• first pregnancy complicated by preeclampsia
• admitted to an extensive non-pregnant cardiovascular and metabolic risk factor assessment

Exclusion Criteria

• women without an ongoing pregnancy after 24 weeks' gestational age

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Maastricht UMC

Maastricht, , Netherlands

Countries

Netherlands

References

Mulder EG, Ghossein-Doha C, Cauffman E, Lopes van Balen VA, Schiffer VMMM, Alers RJ, Oben J, Smits L, van Kuijk SMJ, Spaanderman MEA. Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy. Hypertension. 2021 Jun;77(6):2045-2053. doi: 10.1161/HYPERTENSIONAHA.120.16502. Epub 2021 Apr 5.

Reference Type: DERIVED

PMID: 33813842 (View on PubMed)

Other Identifiers

14-4-118

Identifier Type: -

Identifier Source: org_study_id