Increased ADMA levels are associated with poor pulmonary outcome in preterm neonates

Abstract

Background: Nitric oxide (NO), synthesized from the amino acid L-arginine by the action of NO synthases (NOS), is a pulmonary vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. Preterm infants have higher plasma ADMA concentrations than term infants which could cause inhibition of NO synthesis and deterioration in pulmonary functions. We aimed to investigate the relationship between serum ADMA and L-arginine levels of preterm infants and respiratory distress syndrome (RDS), requirement of surfactant treatment, duration of mechanical ventilation, oxygen treatment, and development of bronchopulmonary dysplasia (BPD).Methods: A prospective cohort study was conducted including 80 preterm infants born with gestational age (GA) ≤ 32 weeks and birth weight (BW) ≤ 1500 g. Blood samples were obtained from all infants immediately after birth, and at postnatal 28th day of age. The relationship of first-day serum ADMA and L-arginine levels and surfactant requirement, duration of mechanical ventilation, oxygen treatment was investigated. Serum ADMA and L-arginine levels at 1st and 28th days were compared at patients with and without BPD. The role of serum ADMA levels at postnatal 28th day of age to predict the requirement of oxygen at postmenstrual 36 weeks of age was also investigated.Results: Eighty preterm infants (42 male, 38 female) were enrolled in the study. Mean BW and GA for the total cohort was 1144.81 ± 220.44 g and 28.3 ± 1.8 weeks, respectively. Sixty-one infants were diagnosed as RDS and 44 infants treated with surfactant. The first-day ADMA levels were significantly higher in infants with surfactant requirement (1.14 ± 0.23 versus 0.86 ± 0.37, p < 0.01). First-day L-arginine levels were lower in infants with surfactant requirement compared to infants without surfactant requirement (22.32 ± 2.33 versus 23.75 ± 2.42, p > 0.05) but not significantly. Serum ADMA and L-arginine concentrations at first day were not different among infants with and without BPD (p > 0.05). ADMA concentrations at 28th day was significantly higher in infants with BPD (1.00 ± 0.25 versus 0.81 ± 0.25, p < 0.05). The cutoff level of 0.875 μmol/L for ADMA at 28th day offered the best predictive value for oxygen requirement at postnatal 36 weeks of age with a sensitivity of 88% and a specificity of 54%.Conclusıon: Serum ADMA and L-arginine levels are related to pulmonary morbidities in newborn. The results of this study show that increased ADMA levels are associated with poor pulmonary outcomes in preterm infants.