Infantile NO Replenishment as a New Therapeutic Possibility

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

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.

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 :

1. Assess the efficiency of NO replenishment therapy (i.e. role of NO pathway) as a therapeutic against alterations of minipuberty resulting from preterm birth.
2. 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.

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