Influence of Intestinal Microbiota Implantation in Preterm Infants on Microbiota and Immune Orientation at 3 Years (PrimiBiota)

Influence of Intestinal Microbiota Implantation Parameters in the Neonatal Period in Premature Infants on Microbiota Profiles and Immune Orientation at 3 Years of Age

The main objective of this research is to study the links between changes in the intestinal microbiota (in terms of diversity) during the first 6 weeks of life for preterm infants and the presence / absence of a TH1 immune status at 36 months of age.

Study Overview

• Status: Active, not recruiting
• Conditions: Infant, Premature

Detailed Description

The secondary objectives are to study the links between changes of the intestinal microbiota premature infants in terms of:

• changing diversity of the microbiota in the first 6 weeks of life;
• changes in the bacterial community (UniFrac study) during the first 6 weeks of life;
• diversity of the microbiota up to 6 weeks;

-AND-

• diversity of the microbiota at 1, 2 & 3 years;
• bacterial communities (UniFrac study) at 1, 2 & 3 years;
• lymphocyte subpopulation profiles at 3 years;
• serum immunoglobulin A, G, M, E levels at 3 years;
• history of infectious episodes, allergic and inflammatory episodes during the first 3 years of life.

The links between certain variables known in the literature and neonatal microbiota will be confirmed / studied in our population:

• mode of delivery;
• length (and type) of antibiotic therapy in the neonatal period;
• duration of breastfeeding.

• Study Type: Observational
• Enrollment (Actual): 130

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • CHRU de Montpellier - Hôpital Arnaud de Villeneuve
  • Nîmes Cedex 09, France, 30029
    • CHRU de Nîmes - Hôpital Universitaire Carémeau
  • Saint Gely Du Fesc, France, 34980
    • Réseau GRANDIR EN LANGUEDOC-ROUSILLON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of premature babies born at < 33 months gestation.

Description

Inclusion Criteria:

• The parents of the patient (or legal guardian if any) have been informed about the implementation of the study, its objectives, its constraints, and patient rights
• The parents of the patient (or legal guardian if any) must have given their free and informed consent and signed the consent form
• The patient must be affiliated with or beneficiary of a health insurance plan
• Premature infants born at less than 33 weeks of gestation

Exclusion Criteria:

• The patient is participating in another interventional study (Excepted " Recherche du Portage de Clostridium butyricum et de Toxines de Clostridium chez les Prématurés Hospitalisés en Néonatologie afin de prédire la survenue d'Entérocolites Nécrosantes", RCB 2016-A00-529-42 ; " BetaDose Dose reduction of antenatal betamethasone given to prevent the neonatal complications associated with very preterm birth ", RCB 2016-001486-90.
• It is not possible to correctly inform the parent (or legal guardian, if applicable)
• A serious deformity or digestive malformation was diagnosed at birth
• During the hospital stay in the neonatology department, the patient had a digestive disease requiring surgery (except necrotizing enterocolitis)
• A transfer to another hospital is foreseen/predictable (eg, due to geographical distance)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
The study population; The study population corresponds to infants born at less than 33 weeks of gestation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The presence/absence of a Th1 type immune orientation	Immune orientation will be determined according to the following ratio determined by lymphocyte stimulation tests: INF-gamma/(INF-gamma+IL+4). The latter ratio varies between 0 and 0.5 with IL-4 > INF-gamma (TH2 orientation) and between 0.5 and 1 when INF-gamma > IL-4 (TH1 orientation).	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood lymphocyte subset determination	Subsets are determined according to the presence/absence of the following differentiation clusters: CD3, CD4, CD8, CD19, CD25, CD56, CD127, FOXP3.	36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Immunoglobulin A level		36 months
Serum Immunoglobulin G level		36 months
Serum Immunoglobulin M level		36 months
Serum Immunoglobulin E level		36 months
The number of days in good health and no medications		36 months
Richness of fecal microbiota (number of operational taxonomic units observed)		Day 0 (first meconium)
Richness of fecal microbiota (number of operational taxonomic units observed)		Week 1
Richness of fecal microbiota (number of operational taxonomic units observed)		Week 2
Richness of fecal microbiota (number of operational taxonomic units observed)		Week 3
Richness of fecal microbiota (number of operational taxonomic units observed)		Week 4
Richness of fecal microbiota (number of operational taxonomic units observed)		Week 5
Richness of fecal microbiota (number of operational taxonomic units observed)		Week 6
Richness of fecal microbiota (number of operational taxonomic units observed)		12 months
Richness of fecal microbiota (number of operational taxonomic units observed)		24 months
Richness of fecal microbiota (number of operational taxonomic units observed)		36 months
Diversity of fecal microbiota (Shannon's index)		Day 0 (first meconium)
Diversity of fecal microbiota (Shannon's index)		Week 1
Diversity of fecal microbiota (Shannon's index)		Week 2
Diversity of fecal microbiota (Shannon's index)		Week 3
Diversity of fecal microbiota (Shannon's index)		Week 4
Diversity of fecal microbiota (Shannon's index)		Week 5
Diversity of fecal microbiota (Shannon's index)		Week 6
Diversity of fecal microbiota (Shannon's index)		12 months
Diversity of fecal microbiota (Shannon's index)		24 months
Diversity of fecal microbiota (Shannon's index)		36 months
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Day 0 (first meconium)
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 1
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 2
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 3
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 4
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 5
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 6
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	12 months
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	24 months
Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	36 months
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Day 0 (first meconium)
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 1
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 2
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 3
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 4
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 5
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 6
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	12 months
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	24 months
Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	36 months
The relative abundance of primary fecal microbiota families		Day 0 (first meconium)
The relative abundance of primary fecal microbiota families		Week 1
The relative abundance of primary fecal microbiota families		Week 2
The relative abundance of primary fecal microbiota families		Week 3
The relative abundance of primary fecal microbiota families		Week 4
The relative abundance of primary fecal microbiota families		Week 5
The relative abundance of primary fecal microbiota families		Week 6
The relative abundance of primary fecal microbiota families		12 months
The relative abundance of primary fecal microbiota families		24 months
The relative abundance of primary fecal microbiota families		36 months
Fecal microbiota unifrac ordination score		Day 0 (first meconium)
Fecal microbiota unifrac ordination score		Week 1
Fecal microbiota unifrac ordination score		Week 2
Fecal microbiota unifrac ordination score		Week 3
Fecal microbiota unifrac ordination score		Week 4
Fecal microbiota unifrac ordination score		Week 5
Fecal microbiota unifrac ordination score		Week 6
Fecal microbiota unifrac ordination score		12 months
Fecal microbiota unifrac ordination score		24 months
Fecal microbiota unifrac ordination score		36 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Study Director: Anne Filleron, MD, PhD, Centre Hospitalier Universitaire de Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2017
• Primary Completion (Actual): November 28, 2022
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 13, 2016
• First Posted (Estimated): April 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: PHRC-I/2015/AF-01