Brainstem and Prematurity

Brainstem Assesment in a Cohort of Very Preterm Babies (Less Than 28 Weeks)

Although significant advances in neonatal care have increased survival rates of preterm infants born before 28 weeks gestation, a concomitant decrease in neuro developmental disorders has not been achieved. Cerebral injuries, well documented during the previous years, in preterm babies are particularly deleterious since they occur in a developing brain. They affect both white and grey matter by complex mechanisms and the principal targets are the developing oligodendrocytes and neurons of the subplate. All these criteria define the encephalopathy of prematurity. Nevertheless, the consequences of prematurity at the level of the brainstem are not very well known and may explain neuro-developmental disorders with normal MRI.

The assessment of the motor repertoire is complementary to the neurological examination and may represent a diagnostic tool for cerebral palsy, mild motor deficits and delayed acquisition in children. The newborn have a rich motor repertoire. GMs play a key role in the development due to the feedback that they send to cortical neurons and reflect the maturational stage of the Central Nervous System (CNS). Lesions of the brainstem caused by prematurity may induce alterations of the motor repertoire.

Dysautonomic disorders, such as bradycardia, apneas, feeding problems, that occur frequently in very preterm babies reflect brainstem abnormalities. These symptoms are also described in other pathologies, in Rett syndrome and sudden infant death syndrome (SIDS). In these pathologies deficits of the 5-HT system have been described and associated with dysautonomia. It would then be interesting to evaluate 5-hydroxytryptamine (5-HT) levels in very preterm babies.

The serotonergic system develops very early during gestation and is one of the first neurotransmitter to appear in the developing brain. The main 5-HT nuclei are located within the brainstem. 5-HT plays an important role in the homeostasis and the modulation of the respiratory network. Moreover, previous studies have shown that 5-HT projections to the spinal cord are involved in posture and in the coordination. It is tempting to think that 5-HT deficits may have some repercussions on the development of the CNS, changing activity dependent processes, such as spontaneous activity recorded at the spinal level in rodents.

In this project, the 5-HT platelet levels in preterm infants born before 28 weeks will be compared with newborns. a correlation between the levels of 5-HT with MRI of the posterior fossa, GMs and dysautonomia different parameters such as heart rate variability, suction-swallowing and different breathing techniques will be established

Study Overview

• Status: Completed
• Conditions: Very Premature Infants
• Intervention / Treatment: Other: EEG; Other: 5-HT measurement; Other: cerebral MRI; Other: Video recording; Other: growth curves; Other: ASQ questionnaire

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine GIRE, MD; Email: catherine.gire@ap-hm.fr
• Study Contact Backup: Name: Blandine BELLOT, MD; Email: blandine.bellot@ap-hm.fr

Study Locations

• France
  • Marseille, France
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Birth less than 28 weeks
• known gestational age
• Birth in born
• Infant without genetic syndrom, evolutive neurologic disease, chronic disorder, malformative pathology
• Infant without intra-ventricular haemorrhage with dilatation or intraparenchymal haemorrhage
• Infants without mechanical ventilation

Exclusion Criteria:

• Infant with congenital cardiopathy, congenital brainstem disorder, Pierre Robin sequence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: preterm babies; preterm babies (less than 28 weeks)	Other: EEG; Other: 5-HT measurement; Other: cerebral MRI; Other: Video recording; Other: growth curves; Other: ASQ questionnaire
Other: term babies; term babies with blood test prescription	Other: 5-HT measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-HT levels	5-HT platelets levels will be measured in very preterm and in term infants and compared (5-HT platelets level reflect the central 5HT level.	term age (37 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Posterior fossa injury	MRI will be performed at term age to analyse preterm cerebral structure focusing on the posterior fossa	at term age (37 weeks)
General movements (GMs) assesment	GMs will be video taped at during the writing movements period and fidgety period and analyzed to detect abnormal GMs	3 times in the hospitalization period and at 3 month post-term age
R-R variability assesment	The autonomic nervous system activity level will be assessed by R-R variability analyze during polysomnographic recordings	at 36 weeks
Respiratory pattern assessment	Respiratory pattern assessment will be analyzed during polysomnographic recordings to detect apneas, sighs…	at 36 weeks
Ages and Stages Questionnaires (ASQ)	ASQ questionnaire as neurodevelopmental assessment will be send to parents	12 and 24 month post-term age
weight and statural growth assessment		until 24 month postterm age
statural growth assessment		until 24 month postterm age
Hospitalization duration		6 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Urielle Desalbres, APHM

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2015
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: January 27, 2016
• First Posted (Estimate): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2015-35; RCAPHM15_0265 (Other Identifier: APHM)