Huizing Maurice J, Borges-Luján Moreyba, Cavallaro Giacomo, González-Luis Gema E, Raffaeli Genny, Bas-Suárez Pilar, Bakker Jaap A, Moonen Rob M, Villamor Eduardo
Department of Pediatrics, Maastricht University Medical Centre (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, Netherlands.
Department of Neonatology, Complejo Hospitalario Universitario Insular Materno-Infantil (CHUIMI) de Canarias, Las Palmas de Gran Canaria, Spain.
Front Pediatr. 2021 Feb 11;9:647018. doi: 10.3389/fped.2021.647018. eCollection 2021.
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. 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. 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 < 0.0024 was used to correct for multiple testing. 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, = 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. 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.
氨基酸在众多生理和病理生理途径中越来越被视为生物活性分子。非必需氨基酸谷氨酸在大鼠动脉导管(DA)中具有血管活性,在生命最初几天内其水平降低与极早产儿动脉导管未闭(PDA)的存在有关。然而,这些发现尚未在其他研究中得到证实。为了调查121名孕周(GA)低于30周且出生体重(BW)低于1500克的新生儿队列中,出生第一天的氨基酸浓度与PDA存在之间的可能关联。出生后6 - 12小时采集血浆样本,并通过串联质谱法测定氨基酸浓度。除了PDA,我们还分析了氨基酸浓度与婴儿性别、小于胎龄儿(SGA,定义为BW < 第三百分位数)、产前使用糖皮质激素、绒毛膜羊膜炎和子痫前期之间的潜在关联。通过对GA和BW进行校正的方差分析来分析组间差异。使用Bonferroni显著性阈值< 0.0024来校正多重检验。在121名接受检查的婴儿中,有48名发现患有PDA。我们观察到患有PDA的婴儿谷氨酸平均水平较高(147.0μmol/L,标准差84.0),而未患PDA的婴儿谷氨酸平均水平为(106.7μmol/L,标准差49.1,P = 0.0006)。PDA组中其他氨基酸浓度均未达到为校正多重比较而预先设定的统计学显著性水平。谷氨酸水平不受婴儿性别、是否为SGA或产前使用糖皮质激素、临床绒毛膜羊膜炎或子痫前期的显著影响。我们的研究不仅未证实先前关于患有PDA的早产儿谷氨酸水平低的发现,甚至还发现与PDA相关的谷氨酸浓度升高。然而,尽管具有高度统计学显著性,但谷氨酸水平的差异可能缺乏临床意义,或者可能是与患有PDA的婴儿特定临床状况相关的一种附带现象。