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

Pregnancy Related Clinical Trial

— GHISPE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05142410
• Other study ID #: NIMAO/2021-1/SB01
• Status: Completed
• Start date: March 1, 2019
• Est. completion date: December 1, 2023

Study information

• Verified date: January 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 1, 2023
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia
• Pregnancy Related

Intervention

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).

Locations

Country	Name	City	State
France	Nîmes University Hospital	Nîmes	Gard

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Intensity of methylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of methylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of methylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of methylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of methylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of methylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of methylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of methylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of acetylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of phosphorylation in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of ubiquitination in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H2A in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H2A in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H2B in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H2B in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H3 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H3 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H4 in pregnant women with normal pregnancies	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Intensity of citrullination in histone H4 in pregnant women developing pre-eclampsia	Mass spectrometry, quantitative	At pregnancy term (max 41 weeks gestation)
Secondary	Presence of methylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of methylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of methylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of methylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of acetylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	Presence of acetylation in histone H2A in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	34 to 41 of pregnancy
Secondary	Presence of acetylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of acetylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	Presence of acetylation in histone H3 in pregnant women developing pre-eclampsia after 34 weeks of pregnancy	YES/NO	After 34 weeks of pregnancy
Secondary	Presence of acetylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of phosphorylation in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of phosphorylation in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of phosphorylation in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of phosphorylation in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of ubiquitination in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of ubiquitination in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of ubiquitination in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of ubiquitination in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of citrullination in histone H2A in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of citrullination in histone H2B in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of citrullination in histone H3 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	Presence of citrullination in histone H4 in pregnant women developing pre-eclampsia before 34 weeks of pregnancy	YES/NO	Before 34 weeks of pregnancy
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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