HELLP Syndrome, Preeclampsia, Small for Gestational Age at Delivery
Conditions
Keywords
cardiac output, total peripheral vascular resistance, hemodynamic parameters, adaptation to pregnancy, tailored treatment
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.
Interventions
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).
Sponsors
Study design
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Stillbirth | during pregnancy until delivery | Number of stillbirths in included women |
| 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) |
| 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) |
| Pregnancy outcome of women included | at delivery | Gestational age 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 |
Countries
Netherlands