Abstract
Background: Amino acids are increasingly recognized as bioactive molecules in numerous physiological and pathophysiological pathways. The non-essential amino acid glutamate is vasoactive in the rat ductus arteriosus (DA) and a decrease in its levels within the 1st days of life has been associated with the presence of patent DA (PDA) in extremely preterm infants. However, these findings have not been confirmed in other studies.Objective: To investigate the possible association between amino acid concentrations in the 1st day of life and the presence of PDA in a cohort of 121 newborns with gestational age (GA) below 30 weeks and birth weight (BW) below 1,500 g.Methods: Plasma samples were collected 6–12 h after birth and amino acid concentrations were determined by tandem mass spectrometry. Besides PDA, we analyzed the potential association of amino acid concentrations with infant sex, small for GA (SGA, defined as BW < third percentile), antenatal corticosteroids, chorioamnionitis, and preeclampsia. Group differences were analyzed by ANOVA adjusted for GA and BW. A Bonferroni significance threshold of P < 0.0024 was used to correct for multiple testing.Results: PDA was found in 48 of the 121 infants examined. We observed higher mean levels of glutamate in infants with PDA (147.0 μmol/L, SD 84.0) as compared with those without (106.7 μmol/L, SD 49.1, P = 0.0006). None of the other amino acid concentrations in the PDA group reached the level of statistical significance that was pre-set to correct for multiple comparisons. Glutamate levels were not significantly affected by infant sex, being SGA, or by exposure to antenatal corticosteroids, clinical chorioamnionitis, or preeclampsia.Conclusion: Our study not only does not confirm the previous findings of low glutamate levels in preterm infants with PDA, but we have even found elevated glutamate concentrations associated with PDA. Nevertheless, despite the high statistical significance, the difference in glutamate levels may lack clinical significance or may be an epiphenomenon associated with the particular clinical condition of infants with PDA.
Highlights
Failed or delayed closure of the ductus arteriosus (DA) after birth leads to patent DA (PDA), a common condition among very preterm infants [1,2,3,4,5,6]
They reported that plasma glutamate concentration was significantly lower in extremely preterm infants with PDA compared to those without the condition [7]
They showed that the mRNA of the glutamate ionotropic receptor α-amino-3-hydroxy-5-methyl4-isoxazolepropionate (AMPA) type subunit one was highly expressed in rat DA compared to the aorta, and was co-localized with autonomic nerve terminals in the human and rat DA
Summary
Failed or delayed closure of the ductus arteriosus (DA) after birth leads to patent DA (PDA), a common condition among very preterm infants [1,2,3,4,5,6]. Fujita et al proposed a role for the nonessential amino acid glutamate in the postnatal closure of the DA [7] They reported that plasma glutamate concentration was significantly lower in extremely preterm infants (gestational age
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