Relationship between Ureaplasma urealyticum Colonization and Bronchopulmonary Dysplasia in Very Low Birth Weight Premature Infants: A Prospective Cohort Study

Document Type : Original Article


1 Pediatric Health Research Center of Tabriz, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Pathology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Pediatric, Tabriz Branch, Islamic Azad University, Tabriz, Iran


Background: Bronchopulmonary dysplasia (BPD) is the second prevalent lung disease and one of the care challenges of premature newborns. Different risk factors play an important role in the development of this disease. Therefore, the aim of the present study was to investigate the relationship between colonization with Ureaplasma urealyticum and BPD.
Methods: This prospective cohort study was conducted in 2017 in the neonatal intensive care unit of Alzahra Hospital in Tabriz, Iran. The samples included newborns weighing less than 1500 g with the gestational age of less than 32 weeks who required intubation within 72 h after birth. Following recording the initial information, the secretions within the trachea were aspirated and Ureaplasma urealyticum was detected in reference laboratory by polymerase chain reaction. Afterwards, we completed a follow-up of 28 days after birth for BPD.
Results: Our findings demonstrated that out of 82 infants, 21 cases (26.3%) were excluded from the study due to discharge from hospital or death before the age of 28 days. Among the rest (61 newborns), three cases (4.3%) were shown to have secretions infected with Ureaplasma and 33 cases (54.1%) suffered from BPD. All the three newborns infected with Ureaplasma had BPD. However, no significant relationship was observed between Ureaplasma infection and BPD (P=0.24).
According to the analysis of data, the most important factors contributing to BPD among the patients were the gestational age and birth weight. In other words, for one week increase in the age of pregnancy and for each 100 g increase in birth weight, the likelihood of BPD is reduced by 55% and 1%, respectively. In the present study, no relationship was found between Ureaplasma infection and BPD, which might be due to the low prevalence of this infection. Nonetheless, prematurity and low birth weight could be regarded as the two considerable risk factors for BPD.
Conclusion: In order to perfectly determine the role of bacterial colonization within the trachea in BPD, collecting and analyzing various samples for the existence of other bacteria are recommended.


1. Carmichael SL, Kan P, Gould JB, Stevenson DK, Shaw GM, Lee HC. Maternal prepregnancy body mass index and risk of bronchopulmonary dysplasia. Pediatric. 2017; 82(1):8-13.
2. Inatomi T, Oue S, Ogihara T, Hira S, Hasegawa M, Yamaoka S, et al. Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants. Pediatric. 2012; 71(3):267-73.
3. Lundstrøm K, Shaw N, Thomson MA. Chronic lung disease-cracking the condition in the 21st century. Neonatology. 2000; 78(3):233-68.
4. Day CL, Ryan RM. Bronchopulmonary dysplasia: old becomes New Again! Pediatr Res. 2016; 81(1-2):210-3.
5. Zheng XD, Li D, Yang DH, Xiang X, Mei H, Pu JR, et al. Association of Ureaplasma urealyticum colonization with development of bronchopulmonary dysplasia: a systemic review and meta-analysis. J Huazhong Univ Sci Technolog Med Sci. 2014; 34(2):265-9.
6. Soleimani F, Sharifi N, Rasti Borujeni F, Amiri M, Khazaiyan S. Nourodevelopmental follow-up in high-risk infants. Tehran Univ Med J. 2015; 72(11):733-41.
7. Rennie JM. Rennie & roberton's textbook of neonatology e-book. New York: Elsevier Health Sciences; 2012.
8. Colaizy TT, Morris CD, Lapidus J, Sklar RS, Pillers DA. Detection of ureaplasma DNA in endotracheal samples is associated with bronchopulmonary dysplasia after adjustment for multiple risk factors. Pediatric. 2007; 61(5 Pt 1):578-83.
9. Manktelow B, Draper E, Annamalai S, Field D. Factors affecting the incidence of chronic lung 
disease of prematurity in 1987, 1992, and 1997. Arch Dis Child Fetal Neonatal Ed. 2001; 85(1):F33-5.
10. Ng G, da Silva O, Ohlsson A. Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2016; 12:CD003214.
11. Abbott MB, Vlasses CH. Nelson textbook of pediatrics. JAMA. 2011; 306(21):2387-8.
12. Davidson LM, Berkelhamer SK. bronchopulmonary dysplasia: chronic lung disease of infancy and long-term pulmonary outcomes. J Clin Med. 2017; 6(1):E4.
13. Jobe AH. The new bronchopulmonary dysplasia. Curr Opin Pediatr. 2011; 23(2):167-72.
14. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001; 163(7):1723-9.
15. Heggie AD, Bar-Shain D, Boxerbaum B, Fanaroff AA, O’riordan MA, Robertson JA. Identification and quantification of ureaplasmas colonizing the respiratory tract and assessment of their role in the development of chronic lung disease in preterm infants. Pediatr Infect Dis J. 2001; 20(9):854-9.
16. Northway Jr WH, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease: bronchopulmonary dysplasia. N Engl J Med. 1967; 276(7):357-68.
17. Ollikainen J, Korppi M, Heiskanen‐Kosma T, Heinonen K. Chronic lung disease of the newborn is not associated with Ureaplasma urealyticum. Pediatr Pulmonol. 2001; 32(4):303-7.
18. Najar Peerayeh S, Samimi R. Detection of ureaplasma urealyticum in clinical samples from infertile women by polymerase chain reaction. Iran J Pharmacol Ther. 2007; 6(1):23.
19. Viscardi RM. Ureaplasma species: role in diseases of prematurity. Clin Perinatol. 2010; 37(2):393-409.
20. Viscardi RM, Manimtim WM, Sun CC, Duffy L, Cassell GH. Lung pathology in premature infants with Ureaplasma urealyticum infection. Pediatr Dev Pathol. 2002; 5(2):141-50.
21. Viscardi RM, Hashmi N, Gross GW, Sun CC, Rodriguez A, Fairchild KD. Incidence of invasive ureaplasma in VLBW infants: relationship to severe intraventricular hemorrhage. J Perinatol. 2008; 28(11):759-65.
22. Waites K, Crouse D, Cassell GH. Therapeutic considerations for Ureaplasma urealyticum infections in neonates. Clin Infect Dis. 1993; 17(Suppl 1): S208-14.
23. Ollikainen J, Hiekkaniemi H, Korppi M, Sarkkinen H, Heinonen K. Ureaplasma urealyticum infection associated with acute respiratory insufficiency and death in premature infants. J Pediatr. 1993; 122(5 Pt 1):756-60.
24. Ollikainen J. Perinatal Ureaplasma urealyticum infection increases the need for hospital treatment during the first year of life in preterm infants. Pediatr Pulmonol. 2000; 30(5):402-5.
25. Crouse DT, Odrezin GT, Cutter GR, Reese JM, Hamrick WB, Waites KB, et al. Radiographic changes
associated with tracheal isolation of Ureaplasma urealyticum from neonates. Clin Infect Dis. 1993; 17(Suppl 1):S122-30.
26. Gancia P, Delogu A, Pomero G. Ureaplasma and bronchopulmonary dysplasia. Early Hum Dev. 2014; 90:S39-41.
27. Castro-Alcaraz S, Greenberg EM, Bateman DA, Regan JA. Patterns of colonization with Ureaplasma urealyticum during neonatal intensive care unit hospitalizations of very low birth weight infants and the development of chronic lung disease. Pediatrics. 2002; 110(4):e45.
28. Benstein BD, Crouse DT, Shanklin DR, Ourth DD. Ureaplasma in lung. 2. Association with broncho-pulmonary dysplasia in premature newborns. Exp Mol Pathol. 2003; 75(2):171-7.
29. Da Silva O, Gregson D, Hammerberg O. Role of Ureaplasma urealyticum and Chlamydia trachomatis in development of bronchopulmonary dysplasia in very low birth weight infants. Pediatr Infect Dis J. 1997; 16(4):364-9.
30. Hannaford K, Todd DA, Jeffery H, John E, Blyth K, Gilbert GL. Role of Ureaplasma urealyticum in lung disease of prematurity. Arch Dis Child Fetal Neonatal Ed. 1999; 81(3):F162-7.
31. Pacifico L, Panero A, Roggini M, Rossi N, Bucci G, Chiesa C. Ureaplasma urealyticum and pulmonary outcome in a neonatal intensive care population. Pediatr Infect Dis J. 1997; 16(6):579-86.
32. Couroucli XI, Welty SE, Ramsay PL, Wearden ME, Fuentes-Garcia FJ, Ni J, et al. Detection of microorganisms in the tracheal aspirates of preterm infants by polymerase chain reaction: association of adenovirus infection with bronchopulmonary dysplasia. Pediatr Res. 2000; 47(2):225-32.
33. Gien J, Kinsella JP. Pathogenesis and treatment of bronchopulmonary dysplasia. Curr Opin Pediatr. 2011; 23(3):305-13.
34. Payne NR, Steinberg SS, Ackerman P, Chrenka BA, Sane SM, Anderson KT, et al. New prospective studies of the association of Ureaplasma urealyticum colonization and chronic lung disease. Clin Infect Dis. 1993; 17(Suppl 1):S117-21.
35. Abele-Horn M, Genzel-Boroviczeny O, Uhlig T, Zimmermann A, Peters J, Scholz M. Ureaplasma urealyticum colonization and bronchopulmonary dysplasia: a comparative prospective multicentre study. Eur J Pediatr. 1998; 157(12):1004-11.
36. Maksić H, Heljić S, Skokić F, Šumanović-Glamuzina D, Milošević V, Zlatanović A, et al. Predictors and incidence of hospitalization due to respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI) in non-prophylaxed moderate-to-late preterm infants in Bosnia and Herzegovina. Bosnian J Basic Med Sci. 2018; 18(3):279-88.
37. Garland SM, Bowman ED. Role of Ureaplasma urealyticum and Chlamydia trachomatis in lung disease in low birth weight infants. Pathology. 1996; 28(3):266-9.