Early Vascular Adjustments to Prevent Preeclampsia

Preeclampsia Clinical Trial

Official title:

Early Vascular Adjustments to Prevent Preeclampsia and Related Complications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04216706
• Other study ID #: 14-4-118
• Status: Completed
• Start date: November 1, 2014
• Est. completion date: March 1, 2020

Study information

• Verified date: December 2019
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: March 1, 2020
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HELLP Syndrome
• Pre-Eclampsia
• Preeclampsia
• Small for Gestational Age at Delivery

Intervention

Drug:
• 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).

Locations

Country	Name	City	State
Netherlands	Maastricht UMC	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of women that develop preeclampsia	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.	during pregnancy, or up to 6 weeks after delivery
Secondary	Number of women that develop HELLP syndrome	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)	during pregnancy, or up to 6 weeks after delivery
Secondary	Number of women that develop eclampsia	Seizures in women with preeclampsia	during pregnancy, or up to 6 weeks after delivery
Secondary	Number of women that have placental abruption during pregnancy		During pregnancy or at delivery
Secondary	Stillbirth	Number of stillbirths in included women	during pregnancy until delivery
Secondary	Neonatal mortality	Number of neonatal demise related to prematurity or as a consequence of maternal disease related to preeclampsia	after delivery up to hospital discharge, which is assessed 6 weeks after due date of the mother
Secondary	Neonatal birth weight	birth weight of neonates	measured at delivery
Secondary	Neonatal birth weight centile	Neonatal birth weight centile (adjusted for sex of neonate, gestational age at delivery and maternal parity)	birth weight and other parameters measured at delivery
Secondary	Pregnancy outcome of women included	Gestational age at delivery	at delivery