Brainstem and Prematurity

Not Applicable

Completed

• Conditions: Very Premature Infants
• Interventions: Other: 5-HT measurement; Other: cerebral MRI; Other: Video recording; Other: EEG; Other: growth curves; Other: ASQ questionnaire

• Registration Number: NCT02669056
• Lead Sponsor: Assistance Publique Hopitaux De Marseille

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2015-12-17
• Study First Submitted: 2016-01-27
• Study First Submitted QC: 2016-01-27
• Study First Posted: 2016-01-29
• Primary Completion: 2019-01-01
• Status Verified: 2023-05
• Study Completion: 2023-05-12
• Last Update Submitted: 2023-05-12
• Last Update Posted: 2023-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
preterm babies	growth curves	preterm babies (less than 28 weeks)
preterm babies	EEG	preterm babies (less than 28 weeks)
preterm babies	cerebral MRI	preterm babies (less than 28 weeks)
preterm babies	ASQ questionnaire	preterm babies (less than 28 weeks)
preterm babies	5-HT measurement	preterm babies (less than 28 weeks)
preterm babies	Video recording	preterm babies (less than 28 weeks)
term babies	5-HT measurement	term babies with blood test prescription

Primary Outcome Measures

Name	Time	Method
5-HT levels	term age (37 weeks)	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Assistance Publique Hôpitaux de Marseille; 🇫🇷 Marseille, France