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Increased asymmetric dimethylarginine levels in severe transient tachypnea of the newborn

Journal of Perinatology volume 36, pages 459–462 (2016)Cite this article

Subjects

Abstract

Objective:

Nitric oxide (NO) is synthesized by NO synthase (NOS), and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. We aimed to investigate l-arginine and ADMA levels in transient tachypnea of the newborn (TTN) and their relationship with systolic pulmonary artery pressure (PAP) and disease severity.

Study design:

Infants born at ⩾35 weeks gestational age with clinical signs and chest X-ray findings consistent with TTN were enrolled; controls were recruited at the same time. l-arginine and ADMA levels were measured at 12 to 24 h (first samples) and at 48 to 72 h (second samples). Systolic PAP was evaluated on the second day. Patients were divided according to the duration of tachypnea and designated as group A (duration ⩽72 h) and group B (duration >72 h).

Results:

In the first samples, the ADMA levels were significantly higher in patients with TTN compared with controls (P<0.001). In the second samples, the ADMA levels were significantly higher in group B compared with that in group A (P=0.019). In group A patients, the second ADMA levels were significantly lower compared with that in the first samples (P<0.001), whereas the second ADMA levels remained unchanged compared with the first samples in group B. Systolic PAP values were significantly higher in group B compared with that in group A patients (P=0.033).

Conclusion:

Increased ADMA concentration may reduce NO synthesis, leading to increased PAP and thus longer duration of tachypnea.

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References

  1. Miller LK, Calenoff L, Boehm JJ, Riedy MJ . Respiratory distress in the newborn. JAMA 1980; 243 (11): 1176–1179.

    Article  CAS  Google Scholar 

  2. Gowen CW Jr, Lawson EE, Gingras J, Boucher RC, Gatzy JT, Knowles MR . Electrical potential difference and ion transport across nasal epithelium of term neonates: correlation with mode of delivery, transient tachypnea of the newborn, and respiratory rate. J Pediatr 1988; 113 (1, Part 1): 121–127.

    Article  Google Scholar 

  3. Guglani L, Lakshminrusimha S, Ryan RM . Transient tachypnea of the newborn. Pediatr Rev 2008; 29 (11): e59–e65.

    Article  Google Scholar 

  4. Ramachandrappa A, Jain L . Elective cesarean section: its impact on neonatal respiratory outcome. Clin Perinatol 2008; 35 (2): 373–393.

    Article  Google Scholar 

  5. Crowley MA . Neonatal respiratory disorders. In: Martin RJ, Fanaroff AA, Walsh MC (eds). Fanaroff and Martin’s Neonatal–Perinatal Medicine: Diseases of the Fetus and Infant, 10th edn. Elsevier Mosby: St Louis, MO, USA, 2015, pp 1127–1128.

    Google Scholar 

  6. Moncada S, Palmer RMJ, Higgs EA . Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43: 109–142.

    CAS  PubMed  Google Scholar 

  7. Barnes PJ, Belvisi MG . Nitric oxide and lung disease. Thorax 1993; 48 (10): 1034–1043.

    Article  CAS  Google Scholar 

  8. Cooke JP . Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000; 20 (9): 2032–2037.

    Article  CAS  Google Scholar 

  9. Millatt LJ, Whitley GS, Li D, Leiper JM, Siragy HM, Carey RM et al. Evidence of dysregulation of dimethylarginine dimethylaminohydrolase I in Chronic Hypoxia-Induced Pulmonary Hypertension. Circulation 2003; 108: 1493–1498.

    Article  CAS  Google Scholar 

  10. Sanli C, Oguz D, Olgunturk R, Tunaoglu FS, Kula S, Pasaoglu H et al. Elevated homocysteine and asymmetric dimethyl arginine levels in pulmonary hypertension associated with congenital heart disease. Pediatr Cardiol 2012; 33 (8): 1323–1331.

    Article  Google Scholar 

  11. Gorenflo M, Zheng C, Werle E, Fiehn W, Ulmer HE . Plasma levels of asymmetrical dimethyl-L-arginine in patients with congenital heart disease and pulmonary hypertension. J Cardiovasc Pharmacol 2001; 37: 489–492.

    Article  CAS  Google Scholar 

  12. Bordigato MA, Piva D, Di Gangi IM, Giordana G, Chiandetti L, Philippone M . Asymmetric dimethylarginine in ELBW newborns exposed to chorioamnionitis. Early Hum Dev 2010; 87: 143–145.

    Article  Google Scholar 

  13. Lopez-Alarcon M, Montalvo-Velarde I, Vital-Reyes VS, Hinojosa-Cruz JC, Leanos-Miranda A, Martinez-Basila A . Serial determinations of asymmetric dimethylarginine and homocysteine during pregnancy to predict pre-eclampsia: a longitudinal study. BJOG 2015; 122: 1586–1592.

    Article  CAS  Google Scholar 

  14. Sertkaya AC, Kafkasli A, Turkcuoglu I, Karabulut AB . Asymmetric dimethylarginine levels in hyperglycemic gestation. Endocrine 2011; 40: 237–242.

    Article  CAS  Google Scholar 

  15. Martin R . Pathophysiology and clinical manifestations of respiratory distress syndrome in the newborn. In: Garcia-Prats JA (ed). UpToDate, Waltham, MA, 2014 (last date accessed 7 November 2014).

  16. Chan KL, Currie PJ, Seward JB, Hagler DJ, Mair DD, Tajik AJ . Comparison of three Doppler ultrasound methods in the prediction of pulmonary artery pressure. J Am Coll Cardiol 1987; 9: 549–554.

    Article  CAS  Google Scholar 

  17. Lam CS, Borlaug BA, Kane GC, Enders FT, Rodeheffer RJ, Redfield MM . Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation 2009; 119 (20): 2663–2670.

    Article  Google Scholar 

  18. Teerlink T . ADMA metabolism and clearance. Vasc Med 2005; 10: 73–81.

    Article  Google Scholar 

  19. Zakrzewicz D, Eickelberg O . From arginine methylation to ADMA: a novel mechanism with therapeutic potential in chronic lung diseases. BMC Pulm Med 2009; 9: 5.

    Article  Google Scholar 

  20. Lücke T, Kanzelmeyer N, Kemper MJ, Tsikas D, Das AM . Developmental changes in the l-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age. Clin Chem Lab Med 2007; 45: 1525–1530.

    Article  Google Scholar 

  21. Kul M, Demirkaya E, Ipçioğlu OM, Karadeniz RS, Tunç T, Vurucu S et al. Perinatal risk factors affecting the maternal and fetal asymmetric dimethylarginine levels. Turk J Pediatr 2009; 51 (2): 141–145.

    PubMed  Google Scholar 

  22. Tsukahara H, Ohta N, Tokuriki S, Nishijima K, Kotsuji F, Kawakami H et al. Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood. Metabolism 2008; 57 (2): 215–220.

    Article  CAS  Google Scholar 

  23. Mittermayer F, Prusa AR, Pollak A, Wolzt M . Umbilical vein plasma concentrations of asymmetrical dimethylarginine are increased in male but not female neonates delivered preterm: a pilot study. Early Hum Dev 2006; 82 (7): 421–424.

    Article  CAS  Google Scholar 

  24. Vida G, Sulyok E, Ertl T, Martens-Lobenhoffer J, Bode-Böger SM . Birth by cesarean section is associated with elevated neonatal plasma levels of dimethylarginines. Pediatr Int 2012; 54 (4): 476–479.

    Article  CAS  Google Scholar 

  25. Richir MC, van Leeuwen PA, van den Berg A, Wessels R, Twisk JW, Rauwerda JA et al. Plasma ADMA concentrations at birth and mechanical ventilation in preterm infants: a prospective pilot study. Pediatr Pulmonol 2008; 43 (12): 1161–1166.

    Article  Google Scholar 

  26. Leiper JM, Vallance P . The synthesis and metabolism of asymmetric dimethylarginine (ADMA). Eur J Clin Pharmacol 2006; 62: 33–38.

    Article  Google Scholar 

  27. Trittmann JK, Peterson E, Rogers LK, Chen B, Backes CH, Klebanoff MA et al. Plasma asymmetric dimethylarginine levels are increased in neonates with bronchopulmonary dysplasia-associated pulmonary hypertension. J Pediatr 2015; 166 (2): 230–233.

    Article  CAS  Google Scholar 

  28. Richir MC, Siroen MP, van Elburg RM, Fetter WP, Quik F, Nijveldt RJ et al. Low plasma concentrations of arginine and asymmetric dimethylarginine in premature infants with necrotizing enterocolitis. Br J Nutr 2007; 97 (5): 906–911.

    Article  CAS  Google Scholar 

  29. Moonen RM, Huizing MJ, Cavallaro G, Gonzalez-Luis G, Bas-Suarez P, Bakker JA et al. Plasma levels of dimethylarginines in preterm very low birth weight neonates: its relation with perinatal factors and short term outcome. Int J Mol Sci 2014; 16: 19–39.

    Article  Google Scholar 

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Acknowledgements

This study was oral presented in the 2013 European Academy of Pediatrics Educational Congress and Master Course, September 19–22, Lyon, France.

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Authors and Affiliations

  1. Department of Neonatology, Neonatal Intensive Care Unit, Etlik Zubeyde Hanim Women’s Health Training and Research Hospital, Ankara, Turkey

    D U Isik, A Y Bas, N Demirel, S Kavurt & O Aydemir

  2. Department of Pediatric Cardiology, Türkiye Yüksek İhtisas Education and Research Hospital, Ankara, Turkey

    A V Kavurt

  3. Department of Pediatric Cardiology, Ankara Children's Hematology Oncology Research and Training Hospital, Ankara, Turkey

    I Cetin

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  1. D U Isik
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Correspondence to D U Isik.

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Isik, D., Bas, A., Demirel, N. et al. Increased asymmetric dimethylarginine levels in severe transient tachypnea of the newborn. J Perinatol 36, 459–462 (2016). https://doi.org/10.1038/jp.2016.9

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