Perinatal Covid-19 Infection, NO Pathway, and Minipuberty

Neurodevelopmental Disorders Clinical Trial

— miniNO-COVID  

Official title:

Exploratory Multicenter Observational Study to Assess the Outcome of Infants With Perinatal SARS-COV-2 Infection and Its Link With the NO Pathway: the Minipuberty Hypothesis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04952870
• Other study ID #: 2020_38
• Secondary ID: 2020-A02122-37gr
• Status: Recruiting
• Start date: November 3, 2022
• Est. completion date: November 2026

Study information

• Verified date: February 2023
• Source: University Hospital, Lille
• Contact: Laurent STORME, MD,PhD
• Phone: 0320445962
• Email: laurent.storme[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Some evidence exists that SARS-COV-2 may infect pituitary axis, and therefore may alter hypothalamic function. Whether perinatal COVID-19 is associated with alterations in the maturation of the Hypothalamic-Pituitary-Gonadal (HPG) axis, and specifically with its transient activation occurring during infancy, namely minipuberty, is a major concern. Among the various pathogenic features related to COVID-19, altered minipuberty could be a key factor underlying many multimorbidities later in life, suggesting that they could involve a common causative mechanism that occurs within this short and critical period of time following birth. Altered minipuberty together with NO deficiency seem to be key factors underlying many of these multimorbidities, suggesting that they involve a common causative mechanism that occurs within this short and critical period of time following birth

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: November 2026
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 3 Months

Eligibility

Inclusion Criteria:

• Group 1 : Newborn infants (24 to 41 weeks gestational age) or young infants (< 3 months) admitted at the maternity ward or at the Department of Neonatology at Jeanne de Flandre Hospital, CHU of Lille with perinatal COVID-19 infection defined by:

• Antenatal COVID-19 infection: pregnant women with positive PCR test at any time of the pregnancy;

• Post-natal COVID-19 infection: newborn or young infants (< 3 months) with positive PCR test in pharynx or stools as part of their treatment.

• Group 2 : Newborn infants (24 to 41 weeks gestational age) or young infants (< 3 months) admitted at the maternity ward or at the Department of Neonatology at Jeanne de Flandre Hospital, CHU of Lille for severe cardiorespiratory diseases requiring inhaled NO treatment.

• Group 3 : The control group without perinatal COVID-19 infection and no inhaled NO treatment will be matched to the two other groups on age at birth (± 2 weeks of gestation), on postnatal age (± 3 weeks), on respiratory failure (yes/no).

• No inclusion in another ante- or post-natal trial;

• Written consents from both parents.

• Social security affiliation

Exclusion Criteria:

• Preterm birth less than 24 weeks gestational age.

• Severe brain lesions: bilateral and extensive periventricular leukomalacia, intracranial hemorrhage grade 3 or 4;

• One or both of the parents is unable to read or understand French language, or refuse to participate

Related Conditions & MeSH terms

• Neurodevelopmental Disorders
• Newborn, Infant, Disease

Intervention

Other:
• Inhaled NO
Newborn or young infants (< 3 months) receiving inhaled NO as part of their treatment for severe respiratory failure
• routine care
Patients treated for respiratory failure

Locations

Country	Name	City	State
France	Hop Jeanne de Flandre Chu Lille	Lille
Greece	Uri-National and Kapodistrian University of Athens	Athens

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	European Commission

Countries where clinical trial is conducted

France,  Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The follicle stimulating hormone (FSH) plasma concentrations measured at the postnatal age of 3 months		at the postnatal age of 3 months
Secondary	The change in reproductive hormones		From the day at inclusion (D0), to Day 2 (48 hours after inclusion), Month 1 and the postnatal age of 3 months
Secondary	The change in metabolic hormones		From the day at inclusion (D0), to Day 2 (48 hours after inclusion), Month 1 and the postnatal age of 3 months
Secondary	Rate of negative hearing and olfactive tests		At the postnatal age of 3 months;
Secondary	Ages and Stages Questionnaire (ASQ-3 ) score	The ASQ-3 is a questionnaire aimed to pinpoint developmental progress in children between 1 month to 5.5 years in age. It is parent-centric and is administered through paper and pencil. It takes 10 to 15 minutes to complete. Change in score will be calculated by comparing ASQ-3 scores of FNI and non-FNI participants by measuring across five developmental areas: communication, gross motor, fine motor, problem solving, and personal-social.	At the corrected age of 9 and 18 months
Secondary	Ages and Stages Questionnaire (ASQ-2E) score		At the corrected age of 9 and 18 months
Secondary	Bayley-III score	The Bayley Scale of Infant and Toddler Development, Third Edition (Bayley III) measures physical, motor, sensory, and cognitive development in babies and young children. The scale encompasses five developmental domains - cognitive, language, motor, social-emotional and adaptive behaviour. The structure of the Bayley-III Scales allows clinicians to administer each of the five scales (cognitive, language-receptive and expressive, motor-fine and gross, social-emotional, and adaptive behaviour) independent of others. Higher scores in each scale indicates more advanced development. Performance is summarised via scaled scores for each subtest, and composite scores for each scale, together with percentile ranks, developmental age equivalents, and growth scores. Discrepancy information is used to determine whether there are significant differences between a child's abilities in the domains measured, and how prevalent these differences are in the norming sample. A total score is not provided.	at the corrected age of 9 months of age
Secondary	The time of mutual gaze interactions (versus non-interactive periods) measured by eye-tracking glasses (mother and children)		At the corrected age of 9 months
Secondary	The specific changes in Nos1-associated genes		From the day at inclusion (D0), Day 2, 1 month and 3 months of age and in buccal cells collected at the postnatal age of 3 months of age.
Secondary	The specific changes in miRNAs in blood sampled		From the day at inclusion (D0), Day 2, 1 month and 3 months of age and in buccal cells collected at the postnatal age of 3 months of age.