Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence

Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence

Introduction Pierre Robin Sequence, PRS, incidence is about one hundred births per year in France. The main neonatal clinical manifestations are secondary to airway obstruction and food difficulties related to swallowing disorders. Despite recent progress, the pathogenesis of PRS is not fully understood.

The hypothesis is that brainstem dysfunction, BSD, plays a central role in the pathogenesis of PRS.

The purpose of the study is to achieve a complete evaluation of BSD to specify its role in the pathogenesis of PRS.

The primary objective is to compare central apnea index (CAI) of infants with PRS with those of infants with isolated airway obstruction (AWO) and those of healthy infants in order to clarify the direct role of BSD.

Material and Methods This prospective interventional study will be carried out in Lyon at the Hôpital Femme-Mère-Enfant and in Paris at the Hôpital Necker-Enfants Malades for 2 years. 3 groups of patients will be studied: PRS, 50 patients, AWO, 50 patients and healthy, 30 patients, included before 2 months of life. Infants will be followed for a maximum of 10 months. The evaluations will be carried out for 48 hours between birth and 2 months of life and then for 24 hours between 6 and 10 months of life for PRS and AWO group. Concerning the healthy group, the evaluation will be carried out during 48h during a single hospitalization before 2 months. Polysomnography, holter-ECG, 24h gas exchange, impedance-pH monitoring and mental region EEG will be performed. The central apnea index (mean number per hour), obstructive apnea index, non-nutritive swallowing index (NNS), gastroesophageal reflux and NNS-respiration coordination will be assessed for each stage of sleep and compared between the three groups of patients.

Inclusion Criteria for the group 1

- infants with PRS

Inclusion Criteria for the group 2 - infant with isolated airway obstruction

Inclusion Criteria for the group 3

- healthy infant : siblings of sudden unexpected death of the infant or with any known pathology

Inclusion Criteria for the 3 groups

• During one hospitalization or program for one hospitalization
• Parental consent
• Social safety affiliation

Exclusion Criteria:

• Birth before 37 SA
• Neonatal complication
• Group 2 only: AWO with neurological disease including brainstem dysfunction
• Group 3 only : AWO, ENT disease or syndromic disease, neurological disease including brainstem dysfunction, Intra uterine growth retardation