PhD student: Fanny Salmon

Title: Perinatal inflammation and neurodevelopment at 5 years, EPIPAGE 2 cohort

Supervisors: Gilles Kayem, Mathilde Letouzey

Doctoral school: ED 393 Epidemiology and Biomedical Information Sciences, Université Paris Cité

Promotion: 2022-2025

Funding:Bourse SF APHP

Thesis abstract:

My thesis focuses on the neurodevelopment at the age of 5 in children born prematurely who were exposed to inflammation during the perinatal period. Low gestational age is the primary risk factor for neurodevelopmental disorders in childhood. The cause of prematurity, meaning the reason for the premature birth, can be another risk factor for neurodevelopmental disorders. Inflammatory mechanisms, common in cases of spontaneous prematurity, could be harmful to the developing brain, particularly the cerebral white matter. Studies have examined the outcomes of children born in inflammatory contexts, but the results were contradictory. Furthermore, these studies had small sample sizes, were single-center, and did not distinguish between different causes of prematurity.

Our objective is to determine whether perinatal inflammation, in its various forms, is associated with neurodevelopmental disorders at the age of 5 in prematurely born children. The national population-based cohort EPIPAGE 2 allows us to study this association precisely, with a large sample that includes 93% of births between 22+0 and 34+6 weeks of gestational age in 25 regions of France in 2011. Perinatal data have very few missing values, and at 5 years of age, 66% of the children have undergone a comprehensive medical and neuropsychological assessment by specifically trained teams. Detailed information is available on fine motor skills and coordination (M-ABC scale), cognitive development (WPPSI IV test), executive function disorders (specific NEPSY II scales), as well as environmental interactions (SCQ score). These comprehensive and validated data, along with the substantial study population, will allow us to precisely address the objective of this doctoral work.

This thesis is divided into four axes, corresponding to the four levels of potentially detrimental inflammation for the developing brain:

  • Clinical chorioamnionitis: which indicates a strong inflammatory response but is difficult to diagnose clinically.
  • Histological chorioamnionitis: defined retrospectively by histological examination of the placenta. This information is not available at birth but constitutes a definite diagnosis of the presence of antenatal inflammation.
  • Births in the context of spontaneous labor and premature rupture of membranes before term. These birth contexts account for more than half of premature births and are associated with acute or chronic inflammatory mechanisms.
  • In the postnatal period, as early neonatal infection is a consequence of intrauterine inflammation.

The exposure of the fetal and neonatal brain to inflammation should be viewed as a continuum between the antenatal and postnatal periods, with potential consequences on neurodevelopment that are interesting to evaluate at each stage.


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