[Gender-dependent differences in glutathione (GSH) metabolism in very preterm infants]. / Différences liées au sexe dans le métabolisme du glutathion (GSH) du grand prématuré

BACKGROUND: Gender differences in mortality and morbidity are often reported in very preterm infants. In studies aiming to understand the underlying mechanisms, better protection against oxidative stress in baby girls has been suggested. OBJECTIVES: Shortly after birth, we compared glutathione (GSH) metabolism in female and male preterm infants and its relationship with prenatal and postnatal parameters. METHODS: We took the opportunity of a prospective randomised controlled trial evaluating the safety-efficacy balance of inhaled nitric oxide (Hamon and al., 2005) [12] to assess, in vivo, the antioxidant defences within the first 48 h of life in 240 premature infants less than 32 weeks gestational age (GA). We measured total plasmatic GSH level (nmol/L), intraerythrocyte glutathione peroxidase (GPX, µmol/min/g haemoglobin) and intraerythrocyte glutathione reductase (GR, µmol/min/g haemoglobin) from venous blood samples withdrawn through central lines. RESULTS: Expressed as mean ± standard error of the mean: soon after birth (at 24h median), plasmatic GSH was not different between females (n=123) and males (n=117): 0.932 ± 0.016 vs 0.956 ± 0.012 nmol/L. However, at the same time, GPX, the enzyme involved in GSH synthesis, was at a significantly higher level in baby girls (p<0.001): 11.63 ± 0.25 vs 10.21 ± 0.24 µmol/min/g haemoglobin, as was GR, the enzyme responsible for GSH regeneration (p=0.02): 12.18 ± 0.23 vs 11.22 ± 0.21 µmol/min/g haemoglobin. We observed no significant correlation between GSH levels, GPX, or GR activities with prenatal steroids, GA, birth weight, severity of respiratory disease, and oxygen requirements for the entire population or between the two genders. CONCLUSION: Whereas the level of glutathione, a key molecule in the defence against oxidative stress in humans, appears to be identical in preterm females and males soon after birth, the enzymes involved in its synthesis (GPX) and regeneration (GR) are higher in females. SPECULATION: Study of the sequential progression of GSH, GPX, and GR with regard to prolonged oxidative stress exposure in preterm females and males is needed to better evaluate their potential clinical relevance.

The safety and efficacy of nitric oxide therapy in premature infants.

OBJECTIVES: To assess the safety-efficacy balance of low-dose inhaled nitric oxide (iNO) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects. STUDY DESIGN: Eight hundred and sixty infants <32 weeks were randomized at birth to receive 5 ppm iNO or placebo when they presented with hypoxemic respiratory failure (HRF) defined by a requirement for mechanical ventilation, fraction of inspired oxygen (FIO 2 ) >40%, and arterio-alveolar ratio in oxygen (aAO 2 ) <0.22. The primary end point was intact survival at 28 days of age. RESULTS: Sixty-one of 415 infants presented with HRF and were compared with 84 of 445 controls who presented with HRF. There was no difference in the primary end point (61.4% in infants [23% with HRF who were treated with iNO] vs 61.1% in controls [21.4% in controls with HRF]; P = .943). For the infants with HRF who were treated with iNO, there was no significant difference from controls for intraventricular hemorrhage (IVH) (6% vs 7%), necrotizing enterocolitis (8% vs 6 %), or patent ductus arteriosus (PDA) (34% vs 37%). Compared with nonhypoxemic infants, the risk of bronchopulmonary displasia (BPD) increased significantly in HRF controls (OR = 3.264 [CI 1.461-7.292]) but not in infants with HRF who were treated with iNO (OR = 1.626 [CI 0.633-4.178]). CONCLUSIONS: iNO appears to be safe in premature infants but did not lead to a significant improvement in intact survival on day 28.