Perinatal Covid-19 Infection, NO Pathway, and Minipuberty (miniNO-COVID)

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

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

Study Overview

• Status: Recruiting
• Conditions: Neurodevelopmental Disorders; Newborn, Infant, Disease
• Intervention / Treatment: Other: Inhaled NO; Other: routine care

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Laurent STORME, MD,PhD; Phone Number: +33 0320445962; Email: laurent.storme@chru-lille.fr

Study Locations

• France
  • Lille, France, 59037
    • Recruiting
    • Hop Jeanne de Flandre Chu Lille
    • Contact: Phone Number: 0320445962
• Greece
  • Athens, Greece
    • Not yet recruiting
    • Uri-National and Kapodistrian University of Athens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Newborn infants at risk for neurodevelopmental disorders

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 group; Perinatal COVID-19 infection group, including newborns born from COVID-19 infected mothers and newborns with postnatal COVID-19 infections;
NO group; Newborns admitted in NICU and receiving inhaled NO for respiratory failure	Other: Inhaled NO; Newborn or young infants (< 3 months) receiving inhaled NO as part of their treatment for severe respiratory failure
Control group; Newborns admitted in NICU for respiratory failure not receiving iNO and not infected with COVID-19;	Other: routine care; Patients treated for respiratory failure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The follicle stimulating hormone (FSH) plasma concentrations measured at the postnatal age of 3 months	at the postnatal age of 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Rate of negative hearing and olfactive tests		At the postnatal age of 3 months;
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
Ages and Stages Questionnaire (ASQ-2E) score		At the corrected age of 9 and 18 months
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
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
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.
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.

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: European Commission
• Investigators: Principal Investigator: Laurent Storme, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: July 5, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: newborn; nitric oxide; minipuberty; neurodevelopmental outcome; Perinatal COVID; HPG axis
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease; Neurodevelopmental Disorders
• Other Study ID Numbers: 2020_38; 2020-A02122-37 (Other Identifier: ID-RCB number, ANSM); grant agreement No 847941 (Other Grant/Funding Number: European Union's Horizon 2020)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No