Evaluation of Patients With Hypertensive Disorders of Pregnancy: An Ambispective Observational Study (PREP)

The overall objective of this study is to evaluate the prognostic role of ultrasound and laboratory parameters, specifically their potential ability to predict severe forms of preeclampsia and adverse maternal-fetal outcomes.

In particular, the aim of the present research is to obtain data on the prognostic value of ultrasonographic and biochemical parameters in patients with hypertensive disorders of pregnancy.

Study Overview

• Status: Not yet recruiting
• Conditions: Preeclampsia; Hypertensive Disorder of Pregnancy; Preeclampsia (PE)
• Intervention / Treatment: Diagnostic test: Doppler evaluation

Detailed Description

This is an ambispective, observational cohort study conducted at a national tertiary obstetric center. This study investigates maternal hemodynamic, Doppler, ultrasound, and biochemical parameters as potential predictors of disease progression in women with gestational hypertension or preeclampsia. The study integrates non-invasive cardiovascular monitoring, placental biomarkers, ophthalmic and uterine artery Doppler velocimetry, carotid flow time index (CFTI), optic nerve sheath diameter (ONSD), and lung ultrasound.

The primary objective is to evaluate the prognostic performance of these parameters in predicting severe forms of preeclampsia and adverse maternal or perinatal outcomes. Secondary objectives include assessing the utility of lung ultrasound and carotid Doppler in characterizing maternal fluid status and supporting clinical decision-making regarding fluid management.

At enrollment and near delivery, participants undergo the following assessments:

1. Non-invasive Maternal Hemodynamics (USCOM-1A) Parameters include heart rate, stroke volume, cardiac output, total vascular resistance, inotropy index, pulse pressure, and peripheral vascular measurements. Values will be converted to Z-scores using gestational age-adjusted reference curves where applicable.
2. Placental Biomarkers Maternal blood samples are collected to determine the sFlt-1/PlGF ratio as an indicator of angiogenic imbalance.
3. Uterine Artery Doppler Uterine artery systolic peak velocities and pulsatility index are measured bilaterally using standardized transabdominal technique.
4. Ophthalmic Artery Doppler and ONSD Bilateral ophthalmic artery velocimetry is performed in a supine position to assess intracranial vascular impedance. Optic nerve sheath diameter is measured 3 mm behind the globe using a linear probe.
5. Carotid Doppler (CFTI) Carotid flow time index is measured at baseline and after a passive leg raise (PLR) maneuver. A PLR-induced ΔCFTI of 10-15% is explored as a surrogate of fluid responsiveness.
6. Lung Ultrasound (POCUS) Eight thoracic zones are evaluated using a curvilinear probe. The presence and distribution of B-lines are recorded to identify early interstitial pulmonary edema.

Clinical, obstetric, laboratory, and therapeutic data are collected longitudinally until delivery. Maternal and neonatal outcomes include timing of delivery, mode of delivery, birthweight, neonatal morbidity, and the interval between diagnosis and delivery.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Elvira Di Pasquo, Medical Doctor; Phone Number: 003906301555589; Email: elvira.dipasquo@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

preeclamptic women > 22 weeks

Description

Inclusion Criteria:

• Pregnancies complicated by preeclampsia or gestational hypertension ≥22 weeks
• Age ≥18 years
• Signed informed consent

Exclusion Criteria:

• intrauterine fetal demise
• Major fetal anomalies or chromosomal abnormalities
• Maternal cardiac disease or ongoing cardiologic therapy
• Chronic kidney disease
• Twin or multiple pregnancies
• Pregestational diabetes

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

preeclamptic women > 22 weeks; All eligible patients meeting inclusion criteria during the study period will be enrolled, as no sample-size calculation is feasible due to the absence of prior literature. Inclusion Criteria Pregnancies complicated by preeclampsia or gestational hypertension ≥22 weeks Age ≥18 years Signed informed consent Exclusion Criteria Intrauterine fetal demise Major fetal anomalies or chromosomal abnormalities Maternal cardiac disease or ongoing cardiologic therapy Chronic kidney disease Twin or multiple pregnancies Pregestational diabetes Study Procedures At enrollment and near delivery, all patients will undergo: Non-invasive hemodynamic assessment (USCOM-1A): HR, SV, CO, TVR, inotropy index, PKR, systolic and diastolic blood pressure. Maternal blood testing for sFlt-1/PlGF ratio. Uterine artery Doppler: systolic peak and pulsatility index. Ophthalmic artery Doppler and ONSD measurement: performed bilaterally in supine position; PSV peaks and PSV ratio calculated. Carotid Doppler (CFTI): meas

Diagnostic test: Doppler evaluation; Non-invasive hemodynamic assessment (USCOM-1A): HR, SV, CO, TVR, inotropy index, PKR, systolic and diastolic blood pressure. Maternal blood testing for sFlt-1/PlGF ratio. Uterine artery Doppler: systolic peak and pulsatility index. Ophthalmic artery Doppler and ONSD measurement: performed bilaterally in supine position; PSV peaks and PSV ratio calculated. Carotid Doppler (CFTI): measured at baseline and after PLR; ΔCFTI of 10-15% considered indicative of fluid responsiveness. Lung ultrasound POCUS: evaluation of 8 thoracic zones using a curvilinear probe; ≥3 B-lines bilaterally considered positive for interstitial edema.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prediction of preeclampsia with severe features	Correlation between: hemodynamic assessment using USCOM serum levels of the biochemical markers sFlt-1/PlGF Doppler velocimetry of the uterine arteries Doppler velocimetry of the ophthalmic artery ultrasound assessment of the optic nerve sheath diameter ultrasound evaluation of carotid artery blood flow using CFTI presence of B-lines on lung ultrasound and the incidence of preeclampsia with severe features.	at enrollment

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: preeclampsia; ophtalmic nerve; ophtalmic artery
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Infections; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Toxemia
• Other Study ID Numbers: 8162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No