Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence

Not Applicable

Completed

• Conditions: Pierre Robin Sequence; Brainstem Dysfunction
• Interventions: Other: Recording of data

• Registration Number: NCT03423017
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-12
• Study First Submitted QC: 2018-01-30
• Study First Posted: 2018-02-06
• Study Start: 2018-05-24
• Primary Completion: 2023-03-23
• Study Completion: 2023-03-23
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-09
• Last Update Posted: 2024-01-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 113

Inclusion Criteria

Not provided

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy infants	Recording of data	Healthy infants : siblings of sudden unexpected death of the infant
Pierre Robin sequence	Recording of data	Infants with PRS : retrognathism, glossoptosis, cleft palate Group 1a : isolated PRS Group 1b : PRS with bone disease or collagen disease (Stickler) Group 1c : syndromic PRS or associated PRS without bone disease or collagen disease
Superior airway obstruction, AWO	Recording of data	Infants with AWO : laryngomalacia, tracheal stenosis, laryngeal stenosis, others etiology

Primary Outcome Measures

Name	Time	Method
Central apnea index (CAI) (mean number per hour)	2 months of life during one nocturne polysomnography	To compare central apnea index (CAI) (mean number per hour), according to the ASSM guidelines 2007, recording by one nocturne polysomnography, between 3 groups of infants by sleep step, between birth and 2 months of life, in order to clarify the direct role of BSD.; According to the ASSM guidelines 2007, the central apnea index is measured : mean number of central apnea per hour.

Secondary Outcome Measures

Name	Time	Method
Non-nutritive swallowing index (NNS) and apnea secondary to non-nutritive swallowing	up to 10 months of life	To compare non-nutritive swallowing index (NNS) and apnea secondary to non-nutritive swallowing between the 3 groups by sleep step between birth and 2 months of life and between PRS group and AWO group between 6 and 10 months of life to clarify the role of BSD in swallowing disorders and NNS-respiration coordination; non-nutritive swallowing index (NNS), mean number per hour, and apnea secondary to non-nutritive swallowing, mean number per hour, monitoring by the mental region EEG and the one nocturne polysomnography
Micro arousals index (mean number per hour)	up to 10 months of life	To compare micro arousals index (mean number per hour) between the 3 groups by sleep step between birth and 2 months of life and between PRS group and AWO group between 6 and 10 months of life to clarify the role of BSD in sleep microstructure; According to the ASSM guidelines 2007, micro arousals index (mean number per hour) are measured.
Obstructive apnea hypopnea index (OAHI)(mean number per hour)	2 months	To compare obstructive apnea hypopnea index (OAHI)(mean number per hour) according to the guidelines ASSM 2007, recording by one nocturne polysomnography, between 3 groups of infants by sleep step, between birth and 2 months of life According to the ASSM guidelines 2007, the obstructive apnea hypopnea index is measured: mean number of obstructive apnea and hypopnea per hour.
Positive and negative pressures, their temporal organizations evaluated using succimetry procedure between the 3 groups of patients at 0 and 2 months of life	up to 2 months of life	Compare the positive and negative pressures, their temporal organizations evaluated using succimetry procedure between the 3 groups of patients at 0 and 2 months of life.
Comparison of OAHI(mean number per hour) and CAI	between 6 and 10 months of life	To compare obstructive apnea hypopnea index (OAHI)(mean number per hour) and central apnea index (CAI) (mean number per hour), between PRS group and AWO group by sleep step between 6 and 10 months of life; According to the ASSM guidelines 2007, the obstructive apnea hypopnea index, mean number of obstructive apnea and hypopnea per hour, and the central apnea index are measured, mean number of central apnea per hour.

Trial Locations

Locations (2)

Hopital Femme Mère Enfant; 🇫🇷 Bron, France

APHP-Necker; 🇫🇷 Paris, France