Immune Dysfunction in Newborn Sepsis (RECIPAL)

Neonatal Immune Dysfunction Associated to the Risk of Newborn Sepsis in Benin

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.

Study Overview

• Status: Completed
• Conditions: Malaria; Sepsis Newborn; Immune Responses
• Intervention / Treatment: Other: Non applicable

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.

• Study Type: Observational
• Enrollment (Actual): 585

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sepsis Risk Group; 419 infants born from mothers at risk to deliver babies with neonatal infections in Cotonou hospitals (Benin) 166 infants without sepsis born from mothers enrolled in a study to monitor pregnancy-associated malaria and Intrauterine growth restriction in Benin	Other: Non applicable; No intervention as it is an observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Procalcitonin (PCT) for early onset neonatal sepsis diagnostic	To measure in cord blood the association and performance of PCT and the early diagnosis of neonatal sepsis for infants at risk to develop infection	At birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Procalcitonin (PCT) for late onset neonatal sepsis diagnostic	To measure in peripheral blood the association and performance of PCT and the diagnosis of late onset neonatal sepsis for infants at risk to develop infection	At one week after birth
To draw Procalcitonin (PCT) expression profile during 12 weeks after birth	To measure PCT concentration during 12 weeks (sampling at birth, week 1, week 4, week 8 and week 12) and explore the relevance of host biomarker-driven antibiotherapy in a low-income country	Twelve weeks follow-up after birth
Evaluate 2 host biomarkers mRNA expression (CD74 and CX3CR1) to prognostic neonatal sepsis	To measure CD74 and CX3CR1 mRNA expression in order to evaluate their performance on the early prognostic of neonatal sepsis for infants at risk to develop infections (occurrence of secondary infections and mortality rate)	Twelve weeks follow-up after birth
FilmArray panels for early diagnosis of neonatal sepsis	To test commercial FilmArray panels in order to evaluate the role of novel diagnostic techniques as part of the diagnostic algorithm on the early diagnosis of neonatal sepsis over a period of 12 weeks for infants at risk to develop infection	Twelve weeks follow-up after birth

Collaborators and Investigators

• Sponsor: BioMérieux
• Collaborators: Institut de Recherche pour le Developpement; Centre National de la Recherche Scientifique, France; IRCB (Institut de la Recherche Clinique du Bénin)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 17, 2016
• Primary Completion (ACTUAL): March 12, 2018
• Study Completion (ACTUAL): March 12, 2018

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (ACTUAL): December 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Toxemia; Immune System Diseases; Neonatal Sepsis
• Other Study ID Numbers: RECIPAL

Drug and device information, study documents

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