Pre-Eclampsia And Growth Restriction: a Longitudinal Study (PEARL)

Pré-Eclampsie et Retard de Croissance: Une étude Longitudinale Évaluative (PERLE)

Preeclampsia may have several causes leading to different characteristics of the pathology. Differentiation between the "type of preeclampsia" would help to treat patients more accurately. This project aims to identify early markers that are specific to each type of preeclampsia (early or late, with or without growth restriction). Through a case-control study, many data will be collected prospectively (serum markers, ultrasonographic markers, maternal factors) among nulliparous women with no sign of preeclampsia (as soon as the first trimester) and nulliparous women with preeclampsia (at diagnosis).

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Preeclampsia; Severe Preeclampsia; Fetal Growth Restriction

Detailed Description

Background: The current definition of preeclampsia is based on signs and symptoms without reference to the pathology. The majority of preeclampsia cases would come from placental dysfunction beginning early in pregnancy, even before the onset of clinical or biochemical events leading to the diagnosis. Defects in the development of the placenta (impaired transformation of the spiral arteries) would seem to lead to poor placental perfusion. Currently, the uterine artery Doppler is the marker used to predict placental perfusion in routine monitoring of the pregnant woman. However, other placental aspects, such as the ultrasonographic measurement of placental volume could also be useful for predicting preeclampsia. Also, several studies have shown that many blood markers (PAPP-A, PlGF, sFlt-1) detected as soon as the first trimester seem effective to predict the majority of early pre-eclampsia, those occurring before 34 weeks of gestation. However, the predictive value of these markers is not so strong regarding prediction of later preeclampsia, those occurring between 34-37 weeks and at term.

Other studies show that some maternal factors, including the value of arterial pressure, BMI, maternal age, could contribute to screening for pre-eclampsia. Recent studies have also been interested in the maternal ophthalmic artery Doppler to try to predict preeclampsia even before the development of clinical symptoms.

Our hypothesis is that each of these biomarkers may be specific to a certain type of pre-eclampsia (early or late; with or without intra uterine growth restriction). We believe that actual definition of preeclampsia includes heterogenous causes and that better understanding of this pathology would help practicians to offer a more individualised treatment to their patients.

Objective: Our main goal is to characterize from a biophysical, biochemical, ultrasonographic and placental perspective the pathology of preeclampsia.

Method: This case-control study will recruit:

1. nulliparous women at 1st trimester of pregnancy. They will provide blood sample and U/S examination at 4 different times during pregnancy.
2. nulliparous women at diagnosis of preeclampsia.

Data that will be collected are:

maternal age maternal BMI maternal ethnicity maternal mean arterial pressure (at recruitment/diagnosis and delivery) gestational age at recruitment/diagnosis and at delivery maternal serum PAPP-A, PlGF, endoglin, sFlt-1 (at recruitment and delivery) cord blood PlGf, endoglin, sFlt-1 fetal crown-rump length at 1st trimester (at recruitment) fetal growth (during pregnancy) Uterine arteries Doppler Cord arteries Doppler Maternal Ophthalmic arteries Doppler Placental volume newborn birthweight

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G2
    • CHU de Québec

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Nulliparous pregnant women

Description

Inclusion Criteria:

• Nulliparous women (no previous delivery ≥ 20 weeks)
• Expect to deliver in recruiting center
• Control group: recruited between 11 - 13 6/7 weeks of gestation
• Case group: recruited at time of diagnosis of preeclampsia > 20 weeks of gestation

Exclusion Criteria:

• multiple pregnancy
• pregnant women <18 years old at recruitment

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cases; Nulliparous women recruited at diagnosis of preeclampsia No intervention, only observation of biochemical and ultrasonographic markers at recruitment and at delivery N= 45
Control; Nulliparous women recruited at the beginning of pregnancy. No intervention, only observation of biochemical and ultrasonographic markers at recruitment (1st trimester), 3 other times during pregnancy (2nd and 3rd trimester) and at delivery N= 45

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
early onset preeclampsia	Preeclampsia will be defined according to the Canadian Guidelines for Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy guidelines, as de novo hypertension with diastolic blood pressure >90 mmHg on two occasions at least four hours apart, after 20 weeks of pregnancy, associated with proteinuria ≥300 mg/24 h or at least '2 +' protein on urine dipstick or an adverse conditions	diagnosed between 20 and 34 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal growth restriction	Fetal growth restriction will be defined as a birth weight below the 10th centile (or below the 3rd centile for severe FGR) of Canadian reference growth charts.	between 20 and 42 weeks of gestation

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Collaborators: Laval University; Chaire Jeanne-et-Jean-Louis Lévesque en périnatalogie

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: March 2, 2015
• First Submitted That Met QC Criteria: March 2, 2015
• First Posted (Estimate): March 5, 2015

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: biomarkers; preterm birth; ultrasound; pregnancy; placenta; preeclampsia; serum; fetal growth restriction; sFlt-1; PAPP-A; doppler; PlGF; intra-uterine growth restriction; endoglin
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Hypertension, Pregnancy-Induced; Growth Disorders; Premature Birth; Pre-Eclampsia; Fetal Growth Retardation
• Other Study ID Numbers: B14-07-2037 (Other Identifier: CER-CHU de Quebec)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO