Obstetrical History and Anti-HLA Antibodies Level (OBS-HLA)

Chronic histiocytic intervillositis (CHI) is associated with severe and recurrent obstetrical complications. A link between anti-HLA Antibodies (Ab) and CHI has recently been established. At the Etablissement Français du Sang (EFS), donors who have already given birth once and have high levels of anti-HLA are excluded from donating apheresis platelets and therapeutic plasma to prevent TRALI (Transfusion Related Acute Lung Injury). No studies have examined the obstetrical history of these donors. The question is: is there an association between anti-HLA levels and obstetrical complications?

Study Overview

• Status: Recruiting
• Conditions: Blood Donors; Anti-HLA Antibody
• Intervention / Treatment: Other: Obstetrical history; Other: Anti-HLA Antibody tests

Detailed Description

Chronic histiocytic intervillositis (CHI) is a rare condition with an incidence of around 5 in 10,000 pregnancies. It is defined by major infiltration of the intervillous cavity by CD68+ maternal histiocytes, associated with fibrin deposition on the villous surface.

CHI is associated with severe obstetrical complications and a very high recurrence rate, estimated at between 70% and 100%. These complications include early and late miscarriage, fetal death, severe growth retardation in surviving fetuses, and premature delivery. The survival rate reported in the literature varies between 30% and 50%.

Anti-HLA antibodies are present in 54% of pregnant women at the end of pregnancy, and their rate increases towards the end of pregnancy. The presence of HLA antibodies also increases with the number of pregnancies, and is found in up to 74% of cases after more than 2 deliveries.

The research question concerns the existence of a statistically significant association between the presence of high levels of anti-HLA antibodies and the occurrence of one or more obstetric complications.

• Study Type: Observational
• Enrollment (Estimated): 6000

Contacts and Locations

• Study Contact: Name: Xavier LAFARGE, Doctor; Phone Number: 05 56 90 83 93; Email: xavier.lafarge@efs.sante.fr
• Study Contact Backup: Name: Isabelle JOLLET; Phone Number: 05 49 61 57 27; Email: isabelle.jollet@efs.sante.fr

Study Locations

• France
  • Bordeaux, France, 33075
    • Recruiting
    • Etablissement Français du Sang Nouvelle Aquitaine
    • Contact: Isabelle JOLLET; Phone Number: 05 49 61 57 27; Email: isabelle.jollet@efs.sante.fr
    • Contact: Xavier LAFARGE; Phone Number: 05 56 90 83 93; Email: xavier.lafarge@efs.sante.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Blood donors who were screened for anti-HLA Ab between 2010 and 2020 as part of TRALI prevention at the EFS Poitiers site histocompatibility laboratory.

Description

Inclusion Criteria:

• Female blood donors who have been tested for anti-HLA antibodies in the context of TRALI prevention between 2010 and 2020 at EFS Nouvelle Aquitaine [The donors meet the conditions of the Order of December 17, 2019 establishing the selection criteria for blood donors and are over 18 years old, are not protected persons and understand French well]
• Women who have already given birth at least once (non-nulliparous women)
• Women who have not expressed their opposition at the time of donation to participating in a research project and to be contacted

Exclusion Criteria:

• None [Donors meet the conditions of the Order of December 17, 2019 establishing the selection criteria for blood donors and are over 18 years old, are not protected persons and understand French well]

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Blood donors tested for anti-HLA Antibody; Blood donors tested for anti-HLA Antibody between 2010 and 2020 as part of TRALI prevention program.	Other: Obstetrical history; Selection of donors by EFS retrospectively on the basis of inclusion criteria. Information note sent by e-mail, non-opposition as well as a questionnaire to be completed online to obtain data on obstetrical history.; Other: Anti-HLA Antibody tests; Analyze responses in relation to the results of the anti-HLA Antibody tests performed at the time of donation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the association between the occurrence of obstetrical complications and the level of anti-HLA Ab measured during the screening test performed by the EFS.	Obstetrical complications are defined as (binomial qualitative variable) : Preterm delivery < 37 WA; Fetal death in utero whatever the term; Early or late miscarriage; Early or late pre-eclampsia; Medical termination of pregnancy; Intrauterine growth retardation <3rd percentile	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type and precocity of obstetrical complication (multinomial qualitative variable)	Preterm deliveries < 37 WA and ≥ 34 WA; Premature deliveries < 34 WA; Fetal death in utero regardless of term; Late miscarriage < 22 WA and ≥ 14 WA; Early miscarriage < 14 WA; Late pre-eclampsia > 37 WA and ≥ 34 WA; Early pre-eclampsia < 34 WA; Medical termination of pregnancy; Intrauterine growth retardation <3rd percentile	2 months
Measure the association between the type and precocity of obstetrical complications according to the type of anti-HLA Ab (class I and/or class II), when these Ab are found during the screening test performed by the EFS	Preterm deliveries < 37 WA and ≥ 34 WA; Premature deliveries < 34 WA; Fetal death in utero regardless of term; Late miscarriage < 22 WA and ≥ 14 WA; Early miscarriage < 14 WA; Late pre-eclampsia > 37 WA and ≥ 34 WA; Early pre-eclampsia < 34 WA; Medical termination of pregnancy; Intrauterine growth retardation <3rd percentile	2 months
Verify the absence of response bias by comparing the HLA Ab levels of responding versus non-responding donors.	Anti-HLA antibody rate (median)	2 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Etablissement Français du Sang (Nouvelle Aquitaine)
• Investigators: Principal Investigator: Xavier LAFARGE, Doctor, Etablissement Français du Sang (Nouvelle Aquitaine); Study Director: Alexandra BENACHI, Professor, APHP, Antoine Béclère Hospital, CLAMART, France

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Estimated): June 13, 2024
• Study Completion (Estimated): June 13, 2024

Study Registration Dates

• First Submitted: August 25, 2023
• First Submitted That Met QC Criteria: August 25, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Obstetrical complications; Levels of anti-HLA antibody; Chronic histiocytic intervillositis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: APHP221333; 2021-A01199-32 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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