Clinical trial NCT04216706: Early Vascular Adjustments to Prevent Preeclampsia
Official title: Early Vascular Adjustments to Prevent Preeclampsia and Related Complications
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preeclampsia
Small for Gestational Age at Delivery
HELLP Syndrome
Keywords: cardiac output
total peripheral vascular resistance
hemodynamic parameters
adaptation to pregnancy
tailored treatment
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2020-01-03
Enrollment: 314
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women who had preeclampsia in their first pregnancy

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.

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

Primary outcomes:
measure: Number of women that develop preeclampsia
timeFrame: during pregnancy, or up to 6 weeks after delivery
Secondary outcomes:
measure: Number of women that develop HELLP syndrome
timeFrame: during pregnancy, or up to 6 weeks after delivery
measure: Number of women that develop eclampsia
timeFrame: during pregnancy, or up to 6 weeks after delivery
measure: Number of women that have placental abruption during pregnancy
timeFrame: During pregnancy or at delivery
measure: Stillbirth
timeFrame: during pregnancy until delivery
measure: Neonatal mortality
timeFrame: after delivery up to hospital discharge, which is assessed 6 weeks after due date of the mother
measure: Neonatal birth weight
timeFrame: measured at delivery
measure: Neonatal birth weight centile
timeFrame: birth weight and other parameters measured at delivery
measure: Pregnancy outcome of women included
timeFrame: at delivery
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
Study officials:
References:
citation: 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.