Early Vascular Adjustments to Prevent Preeclampsia

Completed

• Conditions: HELLP Syndrome; Small for Gestational Age at Delivery; Preeclampsia
• Interventions: Drug: tailored pharmaceutical treatment

• Registration Number: NCT04216706
• Lead Sponsor: Maastricht University Medical Center

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.

Study Timeline

• Study Start: 2014-11-01
• Status Verified: 2019-12
• Study First Submitted: 2019-12-19
• Study First Submitted QC: 2019-12-30
• Primary Completion: 2020-01-01
• Study First Posted: 2020-01-03
• Study Completion: 2020-03-01
• Last Update Submitted: 2020-03-10
• Last Update Posted: 2020-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 314

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tailored treatment advise in suboptimal adaptation	tailored pharmaceutical treatment	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.

Primary Outcome Measures

Name	Time	Method
Number of women that develop preeclampsia	during pregnancy, or up to 6 weeks after delivery	Preeclampsia is defined as new-onset hypertension along with de novo proteinuria or other maternal organ dysfunction (i.e. renal insufficiency, liver involvement, neurological complications or hematological complications) after 20 weeks of gestation in previously normotensive women, or superimposed on chronic hypertension.

Secondary Outcome Measures

Name	Time	Method
Number of women that develop HELLP syndrome	during pregnancy, or up to 6 weeks after delivery	HELLP-syndrome is defined as hemolysis (LDH \> 600 U/L), elevated liver enzymes (AST -aspartate aminotransferase- and ALT -alanine aminotransferase- \> 70 U/L) and low platelets (platelet count \< 100.109/L)
Number of women that develop eclampsia	during pregnancy, or up to 6 weeks after delivery	Seizures in women with preeclampsia
Number of women that have placental abruption during pregnancy	During pregnancy or at delivery
Neonatal mortality	after delivery up to hospital discharge, which is assessed 6 weeks after due date of the mother	Number of neonatal demise related to prematurity or as a consequence of maternal disease related to preeclampsia
Pregnancy outcome of women included	at delivery	Gestational age at delivery
Stillbirth	during pregnancy until delivery	Number of stillbirths in included women
Neonatal birth weight	measured at delivery	birth weight of neonates
Neonatal birth weight centile	birth weight and other parameters measured at delivery	Neonatal birth weight centile (adjusted for sex of neonate, gestational age at delivery and maternal parity)

Trial Locations

Locations (1)

Maastricht UMC; 🇳🇱 Maastricht, Netherlands