Clinical trial NCT02738411: Influence of Intestinal Microbiota Implantation in Preterm Infants on Microbiota and Immune Orientation at 3 Years
Official title: Influence of Intestinal Microbiota Implantation Parameters in the Neonatal Period in Premature Infants on Microbiota Profiles and Immune Orientation at 3 Years of Age
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Infant, Premature
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2016-04-14
Enrollment: 130
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of premature babies born at \< 33 months gestation.

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: The presence/absence of a Th1 type immune orientation
timeFrame: 36 months
Secondary outcomes:
measure: Blood lymphocyte subset determination
timeFrame: 36 months
Other outcomes:
measure: Serum Immunoglobulin A level
timeFrame: 36 months
measure: Serum Immunoglobulin G level
timeFrame: 36 months
measure: Serum Immunoglobulin M level
timeFrame: 36 months
measure: Serum Immunoglobulin E level
timeFrame: 36 months
measure: The number of days in good health and no medications
timeFrame: 36 months
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: Day 0 (first meconium)
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: Week 1
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: Week 2
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: Week 3
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: Week 4
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: Week 5
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: Week 6
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: 12 months
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: 24 months
measure: Richness of fecal microbiota (number of operational taxonomic units observed)
timeFrame: 36 months
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: Day 0 (first meconium)
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: Week 1
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: Week 2
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: Week 3
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: Week 4
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: Week 5
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: Week 6
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: 12 months
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: 24 months
measure: Diversity of fecal microbiota (Shannon's index)
timeFrame: 36 months
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: Day 0 (first meconium)
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: Week 1
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: Week 2
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: Week 3
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: Week 4
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: Week 5
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: Week 6
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: 12 months
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: 24 months
measure: Functional richness of fecal microbiota (number of functional groups observed)
timeFrame: 36 months
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: Day 0 (first meconium)
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: Week 1
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: Week 2
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: Week 3
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: Week 4
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: Week 5
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: Week 6
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: 12 months
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: 24 months
measure: Functional diversity of fecal microbiota (Shannon's index)
timeFrame: 36 months
measure: The relative abundance of primary fecal microbiota families
timeFrame: Day 0 (first meconium)
measure: The relative abundance of primary fecal microbiota families
timeFrame: Week 1
measure: The relative abundance of primary fecal microbiota families
timeFrame: Week 2
measure: The relative abundance of primary fecal microbiota families
timeFrame: Week 3
measure: The relative abundance of primary fecal microbiota families
timeFrame: Week 4
measure: The relative abundance of primary fecal microbiota families
timeFrame: Week 5
measure: The relative abundance of primary fecal microbiota families
timeFrame: Week 6
measure: The relative abundance of primary fecal microbiota families
timeFrame: 12 months
measure: The relative abundance of primary fecal microbiota families
timeFrame: 24 months
measure: The relative abundance of primary fecal microbiota families
timeFrame: 36 months
measure: Fecal microbiota unifrac ordination score
timeFrame: Day 0 (first meconium)
measure: Fecal microbiota unifrac ordination score
timeFrame: Week 1
measure: Fecal microbiota unifrac ordination score
timeFrame: Week 2
measure: Fecal microbiota unifrac ordination score
timeFrame: Week 3
measure: Fecal microbiota unifrac ordination score
timeFrame: Week 4
measure: Fecal microbiota unifrac ordination score
timeFrame: Week 5
measure: Fecal microbiota unifrac ordination score
timeFrame: Week 6
measure: Fecal microbiota unifrac ordination score
timeFrame: 12 months
measure: Fecal microbiota unifrac ordination score
timeFrame: 24 months
measure: Fecal microbiota unifrac ordination score
timeFrame: 36 months
Locations:
city: Montpellier
country: France
facility: CHRU de Montpellier - Hôpital Arnaud de Villeneuve
city: Nîmes Cedex 09
country: France
facility: CHRU de Nîmes - Hôpital Universitaire Carémeau
city: Saint Gely Du Fesc
country: France
facility: Réseau GRANDIR EN LANGUEDOC-ROUSILLON
Study officials:
affiliation: Centre Hospitalier Universitaire de Nîmes
name: Anne Filleron, MD, PhD
role: STUDY_DIRECTOR
References: