Infantile NO Replenishment as a New Therapeutic Possibility

Study Overview
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Brief Summary
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Case-control study of inhaled Nitric Oxide (iNO) treatment of full-term and preterm infants. The main objective of this study is to investigate the association between premature birth and its later comorbidities (neuroendocrine, metabolic, cognitive, etc) with iNO treatment and the maturation of the HPG axis during minipuberty.

Detailed Description
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In preterm infants, inhaled NO (iNO) is routinely used to treat respiratory failure and pulmonary hypertension, while preclinical studies have shown that it markedly increases NO concentrations in the brain. Animal and human studies have shown that NO deficiency may jeopardize the establishment of a mature and functional HPG axis whereas it is also associated with a series of comorbidities affecting the overall brain development (e.g. sensory, fertility and cognitive functions). Prematurity has been associated with a series of non-communicable diseases of major importance in public health, including neurodevelopmental impairments, metabolic abnormalities (e.g. obesity, type 2 diabetes mellitus, impaired glucose tolerance) and cardiovascular disease. This study aims to evaluate the associations between altered minipuberty in preterm infants and the later development of multi-comorbidities (mental and non-mental disorders), and identify the possible implication of the NO pathway as a causative mechanism. Specific objectives : Assess the efficiency of NO replenishment therapy (i.e. role of NO pathway) as a therapeutic against alterations of minipuberty resulting from preterm birth. Assess the efficiency of NO replenishment therapy (i.e. role of NO pathway) as a therapeutic against the multi-comorbidities (mental and non-mental disorders) related to altered minipuberty as a result of preterm birth.

Official Title
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Association Between Premature Birth and Its Comorbidities With NO and the HPG Activation at Minipuberty

Conditions
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Prematurity, Respiratory Distress Syndrome, Newborn

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm (GA<37 weeks) or full-term (≥37 weeks of gestation) infants Requiring respiratory support Admitted to Neonatal Care Unit Exclusion Criteria: Severe congenital anomalies Suspected major chromosomal anomalies Infants judged by the physician as nonviable

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 3 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Infants treated with iNO (from birth to 1-3 weeks of life) or sequential treatment with iNO and sildenafil (for 1 to 3 months). | |
| Controls<br>Infants matched to cases (gestational/postnatal age, gender, disease state) and no iNO treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gonadotrophin levels | Serial blood levels of gonadotrophins (FSH and LH) | up to 9 months of age | 
| Body fat and fat-free mass | Serial fat and fat-free mass measurements by air displacement plethysmography | up to 9 months of age | 
| HOMA-IR | Serial measurements of blood glucose/insulin (HOMA-IR) | up to 9 months | 
| Bayleys scale score | The Bayley Scales of Infant and Toddler Development will be used to assess neurodevelopment. Values <85 indicate developmental delay. | at 9 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Otoacoustic emissions | Serial otoacoustic emissions as a screening test for hearing ability | up to 9 months | 
| Fundoscopy | Ophthalmological follow-up for retina and visual assessment | up to 9 months | 
| gusto-facial reflex | Assessment of olfaction will be performed using a citrus, vanilla or neutral odor, delivered on a cotton swab. The facial expressions in reaction to the different smells (the gusto-facial reflex) will be monitored while at rest (baseline), and in response to stimuli. | at 3 and 9 months of age | 
| Leptin levels | Serial measurements of serum leptin levels | up to 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm birth, neurodevelopment, cardiometabolic, minipuberty