Clinical trial NCT04952870: Perinatal Covid-19 Infection, NO Pathway, and Minipuberty
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Newborn, Infant, Disease
Neurodevelopmental Disorders
Keywords: Perinatal COVID
newborn
minipuberty
HPG axis
nitric oxide
neurodevelopmental outcome
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2021-07-07
Enrollment: 180
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newborn infants at risk for neurodevelopmental disorders

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: The follicle stimulating hormone (FSH) plasma concentrations measured at the postnatal age of 3 months
timeFrame: at the postnatal age of 3 months
Secondary outcomes:
measure: The change in reproductive hormones
timeFrame: From the day at inclusion (D0), to Day 2 (48 hours after inclusion), Month 1 and the postnatal age of 3 months
measure: The change in metabolic hormones
timeFrame: From the day at inclusion (D0), to Day 2 (48 hours after inclusion), Month 1 and the postnatal age of 3 months
measure: Rate of negative hearing and olfactive tests
timeFrame: At the postnatal age of 3 months;
measure: Ages and Stages Questionnaire (ASQ-3 ) score
timeFrame: At the corrected age of 9 and 18 months
measure: Ages and Stages Questionnaire (ASQ-2E) score
timeFrame: At the corrected age of 9 and 18 months
measure: Bayley-III score
timeFrame: at the corrected age of 9 months of age
measure: The time of mutual gaze interactions (versus non-interactive periods) measured by eye-tracking glasses (mother and children)
timeFrame: At the corrected age of 9 months
measure: The specific changes in Nos1-associated genes
timeFrame: 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.
measure: The specific changes in miRNAs in blood sampled
timeFrame: 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.
Other outcomes:
Locations:
city: Lille
country: France
facility: Hop Jeanne de Flandre Chu Lille
city: Athens
country: Greece
facility: Uri-National and Kapodistrian University of Athens
Study officials:
affiliation: University Hospital, Lille
name: Laurent STORME, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: