Clinical trial NCT03780712: Immune Dysfunction in Newborn Sepsis
Official title: Neonatal Immune Dysfunction Associated to the Risk of Newborn Sepsis in Benin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis Newborn
Malaria
Immune Responses
Lead sponsor: BioMérieux
Sponsor class: INDUSTRY
Collaborators: name: Institut de Recherche pour le Developpement
name: Centre National de la Recherche Scientifique, France
name: IRCB (Institut de la Recherche Clinique du Bénin)
First posted: 2018-12-19
Enrollment: 585
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The targeted population is newborns with a high risk to develop sepsis recruited at delivery compared to a control infant population with a low infection risk.

Brief summary: The aim of the project is to study neonatal immune dysfunction associated to the risk of newborn sepsis in a malaria endemic area in Benin.

Detailed description: The fetal immunological responses maturate gradually during the last 3 months of pregnancy. To respond to pathogens, newborns depend essentially on their innate immune system. Premature babies have a significant impairment of innate and immune regulatory functions, thus promoting neonatal sepsis. In addition, chronic infections during pregnancy, including those of parasitic origin, fetal immunity. In utero exposure to P. falciparum antigens impacts particularly the newborn immune development and is a risk factor predisposing to malaria and also to other infections during the first year of life.

The major objectives are to assess:

* The relevance of a host biomarker driven diagnostic of sepsis in newborns,
* The relevance of immune markers as indicators of sepsis incidence, secondary infections occurrence, and mortality
* The role of novel diagnostic techniques (FilmArray panels) as part of the microbiological diagnostic,
* The immunological profile of the infants in the 3 first months of life.

The targeted population is newborns with a high risk to develop sepsis recruited at delivery compared to a control infant population with a low infection risk.

Eligibility criteria: Inclusion Criteria for the sepsis risk group (400 infants):

* Child born from mothers having one of the following criteria before delivery will be included in this study:

  * Spontaneous preterm delivery (\<37 weeks of gestation time)
  * Foul smelling / with meconium / colored / bloody amniotic liquid
  * Rupture of membranes \> 18 hours
  * Maternal fever at delivery
  * Vaginal infection
* Child born at the maternity of CNHU (Centre National Hospitalier et Universitaire, Cotonou, Benin) or CHUMEL (Centre Hospitalier et Universitaire de la Mère et de l'Enfant Lagune, Cotonou, Benin) or HZAC (Hopital de zone d' Abomey-Calavi, Benin).
* Mother located near Abomey-Calavi. This criterion has been included to limit the follow-up expenses and spare the travel to the project staff in charge of the 3 month follow-up.

Inclusion Criteria for the control group (170 infants):

- Child born from mothers enrolled in the RECIPAL study (Pregnancy-associated malaria and Intrauterine growth restriction in Benin)

Exclusion Criteria for both groups:

* HIV + status or unknown HIV status of the mother (as the mother and child will be part of the national program to take care of mother and child HIV+ at delivery)
* Parents do not consent to be included in the study.

Primary outcomes:
measure: Evaluate Procalcitonin (PCT) for early onset neonatal sepsis diagnostic
timeFrame: At birth
Secondary outcomes:
measure: Evaluate Procalcitonin (PCT) for late onset neonatal sepsis diagnostic
timeFrame: At one week after birth
measure: To draw Procalcitonin (PCT) expression profile during 12 weeks after birth
timeFrame: Twelve weeks follow-up after birth
measure: Evaluate 2 host biomarkers mRNA expression (CD74 and CX3CR1) to prognostic neonatal sepsis
timeFrame: Twelve weeks follow-up after birth
measure: FilmArray panels for early diagnosis of neonatal sepsis
timeFrame: Twelve weeks follow-up after birth
Other outcomes:
Locations:
Study officials:
References:
citation: Fievet N, Ezinmegnon S, Agbota G, Sossou D, Ladekpo R, Gbedande K, Briand V, Cottrell G, Vachot L, Yugueros Marcos J, Pachot A, Textoris J, Blein S, Lausten-Thomsen U, Massougbodji A, Bagnan L, Tchiakpe N, d'Almeida M, Alao J, Dossou-Dagba I, Tissieres P; SEPSIS study group collaborators; SEPSIS study group. SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region. BMJ Open. 2020 Jul 23;10(7):e036905. doi: 10.1136/bmjopen-2020-036905.