InSPIRe

Scientific justification:

Maternal-fetal or early neonatal bacterial infections (MFIs) are one of the main preventable causes of neonatal mortality and morbidity. Current indications for antibiotic therapy are probabilistic, leading to limitations in efficacy and an impact in terms of antibiotic resistance. The future holds the prospect of personalized, tailored antibiotic therapy, based on the search for and rapid identification, during delivery, of bacteria associated with the risk of MFI. However, the performance of current screening tests is inadequate, being limited to the detection of group B streptococcus. Other germs are implicated in premature rupture of membranes. The study is part of the development of a diagnostic kit (also called InSPIRe) that will be able to detect potentially pathogenic metagenomic signatures in a vaginal swab (VS): prediction of the result of conventional culture and antibiotic susceptibility testing, virulence factors, microbiota profiles, as well as the host’s immunological response.

Main objective:

• Validate the InSPIRe multiplex molecular test for group B Streptococcus in a biological collection of vaginal swabs from pregnant women.

Secondary objectives:

• Validate the InSPIRe multiplex molecular test for the detection of other pathogens and associated virulence and antibiotic resistance markers;
• Identify clinical (gestational age, signs of chorioamniotitis, oligohydramnios), biological (hyperleukocytosis, CRP elevation) and microbiological (presence of pathogens, dysbiosis) predictive factors associated with maternal-fetal infections in this population;
• Identify bacterial signatures associated with MFI risk through metagenomic analysis;
• Identify local maternal biomarkers associated with MFI risk (IL6 levels and other biomarkers currently under investigation);
• Identify bacterial signatures and biomarkers associated with the risk of clinical or histological chorioamniotitis;
• Set up a serum library to provide a particularly important bio-bank of sera for validating the presence of antibodies to the various pathogens under investigation;

Design of the study :

Prospective study without intervention. PV samples were collected at inclusion and at delivery and frozen. Metagenomic and immunological analyses using the InSPIRe kit were carried out at a later stage.

Four cohorts are followed according to their inclusion:

Group A: prenatal consultation between 33 and 38 SA+ 6J, benefiting from a vaginal swab for streptococcus B screening.

Group B: rupture of membranes at term before labor (RMTAT) from 37 SA.

Group C: threatened preterm birth (CPB) or preterm birth between 22 and 36 + 6 days’ gestation.

Group D: premature rupture of membranes (RPM) between 22 and 36 SA + 6 days.

Newborns will not be specifically examined, but the results of examinations and diagnoses carried out as part of routine care will be analyzed as an evaluation criterion for examinations carried out on the mother.

Benefits for participants and society

• Development of a rapid diagnostic kit to better predict the risk of MFI;
• Improved obstetrical management, including timely and appropriate antibiotic indications;
• Limit antibiotic resistance and the effects on microbiota of probabilistic antibiotic use.

End of inclusions June 30^th, 2023

Three centers participated in the inclusions: Louis Mourier, Port Royal (Cochin) and Bichat.

Inclusion targets were met for 3 of the 4 groups:

• Group A (routine screening) ended 04/03/2020 (N=1102/1000)
• Group C (MAP) ended 02/19/2021 (n=506/500).
• Group B (pre-labour rupture of membranes at term) completed 08/31/2022 (n=498/500)
• Group D (premature rupture of membranes), ended June 30, 2023 (n=463/500)