Understanding Post-translational Modifications to Circulating Histones Via Mass Spectrometry in Pregnant Women Developing Pre-eclampsia: A Retrospective Study (GHISPE)

A Retrospective Study Using Mass Spectrometry to Characterize Post-translational Modifications to Circulating Histones in Pregnant Women Developing Pre-eclampsia

This is a descriptive pilot study on a ready-constituted biobank (outside the Jardé Law). It is an ancillary study to the "GrossPath" cohort (RCB ID number: 2014-A01120-47).

Pregnancy generates an increased risk of thrombosis, and placenta-mediated diseases constitute a risk factor for cardiovascular pathologies responsible for significant maternal-fetal morbidity and mortality. Understanding and exploring the cellular and molecular mechanisms of dysfunctions of the vascular-placental interface could provide arguments to understand the systemic vascular risk, characterize it and finally detect it on the basis of new markers, thus opening the way for targeted preventive management to reinforce the general principles of precision medicine.

Netosis is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Netosis occurs in pregnancy and is increased in vascular-placental complications. It can be studied by measuring circulating histones, particularly the citrullinated histone H3. Levels of this modified histone H3, as well as those of two other modifications, have recently been shown to increase during pregnancy. These levels have also been shown to be even greater in pregnancy complications.

The aim of this study is to complete this mapping in order to obtain a precise signature for all post-translational histone modifications in normal pregnancies and pregnancies complicated by pre-eclampsia from the "GrossPath" cohort in order to propose new circulating biomarkers for placental vascular pathologies.

The post-translational histone modification profiles (mapping) of pregnant women with normal pregnancies will be compared with those developing pre-eclampsia.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Pre-Eclampsia
• Intervention / Treatment: Diagnostic test: Analysis of post-translational histone modifications via mass spectrometry

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• France
  • Gard
    • Nîmes, Gard, France, 30900
      • Nîmes University Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study is based on frozen plasma samples from pregnant women, taken at the time of them giving birth from among the 50 women who constituted the GrossPath cohort. Fourteen of these women had had normal pregnancies and fourteen had developed pre-eclampsia. Cases are matched on maternal age, clinical event (delivery) and gestational age will be included from the GrossPath cohort.

Description

Inclusion Criteria:

• Not applicable as this study is on samples from a biobank. The inclusion criteria for the "GrossPath" cohort were:
• pregnant women followed at Nîmes University hospital for normal pregnancy or pregnancy with placental vascular pathology (pre-eclampsia and/or intra-uterine growth retardation).
• The patient must have given her free and informed consent and signed the consent form.
• The patient must be a member or beneficiary of a health insurance plan
• Only women are included
• Patients are at least 18 years old

Exclusion Criteria:

• Not applicable as this is a study on samples from a biobank. The non-inclusion criteria of the "GrossPath" cohort were :
• twin pregnancies.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Plasma from women with normal pregnancies; Plasma collected from women with normal pregnancies will be analyzed by mass spectrometry	Diagnostic test: Analysis of post-translational histone modifications via mass spectrometry; During the "GrossHist" study (NCT04205383), only 3 post-translational histone modifications available in ELISA at the time were quantified thanks to a collaboration with the VOLITION™ company [Bouvier and Fortier et al. 2021]. The development of a new mass spectrometry approach based on nucleosome enrichment of plasma, developed by collaborators at VOLITION™, has made it possible to consider the description of all post-translational histone modifications (about 40 post-translational modifications involving histones H2A, H2B, H3 and H4).
Plasma from women with placenta-mediated complications; Plasma collected from women who developed preeclampsia during pregnancy will be analyzed by mass spectrometry	Diagnostic test: Analysis of post-translational histone modifications via mass spectrometry; During the "GrossHist" study (NCT04205383), only 3 post-translational histone modifications available in ELISA at the time were quantified thanks to a collaboration with the VOLITION™ company [Bouvier and Fortier et al. 2021]. The development of a new mass spectrometry approach based on nucleosome enrichment of plasma, developed by collaborators at VOLITION™, has made it possible to consider the description of all post-translational histone modifications (about 40 post-translational modifications involving histones H2A, H2B, H3 and H4).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of methylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of methylation in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of methylation in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of methylation in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of methylation in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of methylation in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of methylation in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of methylation in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of methylation in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of acetylation in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of acetylation in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of acetylation in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of acetylation in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of acetylation in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of acetylation in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of acetylation in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of acetylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of acetylation in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of phosphorylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of phosphorylation in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H2A in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H2B in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H3 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H4 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of ubiquitination in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of ubiquitination in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H2A in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of citrullination in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of citrullination in histone H2A and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H2B in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of citrullination in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of citrullination in histone H2B and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H3 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of citrullination in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of citrullination in histone H3 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H4 in pregnant women with normal pregnancies	Mass spectrometry will be used to detect the presence or not of citrullination in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)
Presence of citrullination in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry will be used to detect the presence or not of citrullination in histone H4 and recorded as YES/NO.	At pregnancy term (max 41 weeks gestation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity of methylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of methylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of methylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of methylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of methylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of methylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of methylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of methylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of acetylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of phosphorylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of ubiquitination in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Intensity of citrullination in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Presence of methylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of methylation in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of methylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of methylation in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of methylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of methylation in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of methylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of methylation in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of acetylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of acetylation in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 of pregnancy
Presence of acetylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of acetylation in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of acetylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of acetylation in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	After 34 weeks of pregnancy
Presence of acetylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of acetylation in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of phosphorylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of phosphorylation in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of phosphorylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of phosphorylation in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of phosphorylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of phosphorylation in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of phosphorylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of phosphorylation in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of ubiquitination in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of ubiquitination in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of ubiquitination in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of ubiquitination in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of ubiquitination in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of ubiquitination in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of ubiquitination in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of ubiquitination in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of citrullination in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of citrullination in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of citrullination in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of citrullination in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of citrullination in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of citrullination in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Presence of citrullination in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Presence of citrullination in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 weeks of pregnancy
Intensity of methylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of methylation in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of methylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of methylation in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of methylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of methylation in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of methylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of methylation in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of acetylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of acetylation in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of acetylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of acetylation in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of acetylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of acetylation in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of acetylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of acetylation in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of phosphorylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of phosphorylation in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of phosphorylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of phosphorylation in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of phosphorylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of phosphorylation in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of phosphorylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of phosphorylation in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of ubiquitination in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of ubiquitination in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of ubiquitination in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of ubiquitination in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 of pregnancy
Intensity of ubiquitination in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of ubiquitination in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of ubiquitination in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of ubiquitination in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of citrullination in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of citrullination in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of citrullination in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of citrullination in histone H2B in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of citrullination in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of citrullination in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Intensity of citrullination in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of citrullination in histone H4 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy
Modifications in histones H2A, H2B, H3 and H4 in women developing pre-eclampsia early on compared with modifications in histones H2A, H2B, H3 and H4 in women with normal pregnancies.	The presence of methylation, acetylation, phosphorylation, ubiquitination and citrullination in each histone in women developing pre-eclampsia early on will be recorded as YES/NO.	Before 34 weeks of pregnancy
Modifications in histones H2A, H2B, H3 and H4 in women developing pre-eclampsia later on compared with modifications in histones H2A, H2B, H3 and H4 in women with normal pregnancies.	The presence of methylation, acetylation, phosphorylation, ubiquitination and citrullination in each histone in women developing pre-eclampsia later on will be recorded as YES/NO.	34 to 41 weeks of pregnancy
Intensity of modifications in histones H2A, H2B, H3 and H4 in women developing pre-eclampsia early on compared with modifications in histones H2A, H2B, H3 and H4 in women with normal pregnancies.	Mass spectrometry, quantitative	Before 34 weeks of pregnancy
Intensity of modifications in histones H2A, H2B, H3 and H4 in women developing pre-eclampsia later on compared with modifications in histones H2A, H2B, H3 and H4 in women with normal pregnancies.	Mass spectrometry, quantitative	34 to 41 weeks of pregnancy

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Sylvie BOUVIER, Dr., Nîmes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Mass spectrometry; Pre-eclampsia; Neutrophils; Histones; Extracellular traps
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Eclampsia; Pre-Eclampsia
• Other Study ID Numbers: NIMAO/2021-1/SB01

Plan for Individual participant data (IPD)

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

IPD Plan Description

All data collection and management will be carried out by the BESPIM (Biostatistique, Epidémiologie clinique, Santé Publique & Innovation en Méthodologie).

The conditions of transfer of all or part of the research database are decided by the principal investigator and the research sponsor and are the subject of a written contract.

Drug and device information, study documents

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