Abstract
The role of infection in bronchopulmonary dysplasia (BPD) is unknown. We present an observational study of 55 premature infants born weighing less than 1.3 kg within two level III neonatal intensive care units. Endotracheal aspirates (ETA) and nasogastric aspirates (NGA) were studied with denaturing gradient gel electrophoresis (DGGE) profiling to elucidate the total bacterial community, and species-specific PCR was used to detect the presence of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. DGGE identified bacterial species in 59% of NGA and ETA samples combined. A diverse range of species were identified including several implicated in preterm labor. Species-specific PCR identified M. hominis in 25% of NGA and 11% of ETA samples. Among the 48 infants surviving up to 36 wk-postconceptual age, ordinal logistic regression showed the odds ratio for BPD or death where Ureaplasma was present/absent as 4.80 (95% CI 1.15–20.13). After adjusting for number of days ventilated, this was reduced to 2.04 (0.41–10.25). These data demonstrate how the combined use of DGGE and species-specific PCR identifies a high exposure in utero and around the time of birth to bacteria that might be causally related to preterm delivery and subsequent lung injury.
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Abbreviations
- BPD:
-
bronchopulmonary dysplasia
- CoNS:
-
coagulase-negative Staphylococci
- DGGE:
-
denaturing gradient gel electrophoresis
- ET:
-
endotracheal
- ETA:
-
endotracheal aspirate
- NG:
-
nasogastric
- NGA:
-
nasogastric aspirate
References
Speer CP 2006 Inflammation and bronchopulmonary dysplasia: a continuing story. Semin Fetal Neonatal Med 11: 354–362
Benstein BD, Crouse DT, Shanklin DR, Ourth DD 2003 Ureaplasma in lung. 2. Association with bronchopulmonary dysplasia in premature newborns. Exp Mol Pathol 75: 171–177
Cassell GH, Waites KB, Crouse DT, Rudd PT, Canupp KC, Stagno S, Cutter GR 1988 Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birth-weight infants. Lancet 2: 240–245
Castro-Alcaraz S, Greenberg EM, Bateman DA, Regan JA 2002 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 110: e45
Colaizy TT, Morris CD, Lapidus J, Sklar RS, Pillers DA 2007 Detection of Ureaplasma DNA in endotracheal samples is associated with bronchopulmonary dysplasia after adjustment for multiple risk factors. Pediatr Res 61: 578–583
Goldenberg RL, Andrews WW, Goepfert AR, Faye-Petersen O, Cliver SP, Carlo WA, Hauth JC 2008 The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol 198: 43.e1–43.e5
Kotecha S, Hodge R, Schaber JA, Miralles R, Silverman M, Grant WD 2004 Pulmonary Ureaplasma urealyticum is associated with the development of acute lung inflammation and chronic lung disease in preterm infants. Pediatr Res 55: 61–68
Oue S, Hiroi M, Ogawa S, Hira S, Hasegawa M, Yamaoka S, Yasui M, Tamai H, Ogihara T 2009 Association of gastric fluid microbes at birth with severe bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 94: F17–F22
Egawa T, Morioka I, Morisawa T, Yokoyama N, Nakao H, Ohashi M, Matsuo M 2007 Ureaplasma urealyticum and Mycoplasma hominis presence in umbilical cord is associated with pathogenesis of funisitis. Kobe J Med Sci 53: 241–249
Heggie AD, Bar-Shain D, Boxerbaum B, Fanaroff AA, O'Riordan MA, Robertson JA 2001 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 20: 854–859
Pandey A, Dhawan B, Gupta V, Chaudhry R, Deorari AK 2007 Clinical significance of airways colonization with Ureaplasma urealyticum in premature (<34 wk) neonates. Indian J Med Res 125: 679–684
Wang EE, Frayha H, Watts J, Hammerberg O, Chernesky MA, Mahony JB, Cassell GH 1988 Role of Ureaplasma urealyticum and other pathogens in the development of chronic lung disease of prematurity. Pediatr Infect Dis J 7: 547–551
Waites KB, Schelonka RL, Xiao L, Grigsby PL, Novy MJ 2009 Congenital and opportunistic infections: Ureaplasma species and Mycoplasma hominis. Semin Fetal Neonatal Med 14: 190–199
Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, Wrage LA, Poole K 2005 Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics 116: 1353–1360
Muyzer G, Dewaal EC, Uitterlinden AG 1993 Profiling of complex microbial-populations by denaturing gradient gel-electrophoresis analysis of polymerase chain reaction-amplified genes-coding for 16s ribosomal-RNA. Appl Environ Microbiol 59: 695–700
Muyzer G, Smalla K 1998 Application of denaturing gradient gel electrophoresis (DGGE) and temperature gradient gel electrophoresis (TGGE) in microbial ecology. Antonie Van Leeuwenhoek 73: 127–141
Waites KB, Katz B, Schelonka RL 2005 Mycoplasmas and Ureaplasmas as neonatal pathogens. Clin Microbiol Rev 18: 757–789
Couroucli XI, Welty SE, Ramsay PL, Wearden ME, Fuentes-Garcia FJ, Ni J, Jacobs TN, Towbin JA, Bowles NE 2000 Detection of microorganisms in the tracheal aspirates of preterm infants by polymerase chain reaction: association of adenovirus infection with bronchopulmonary dysplasia. Pediatr Res 47: 225–232
Fredricks DN, Fiedler TL, Marrazzo JM 2005 Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 353: 1899–1911
Pretorius C, Jagatt A, Lamont RF 2007 The relationship between periodontal disease, bacterial vaginosis, and preterm birth. J Perinat Med 35: 93–99
DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch F, Kim CJ, Erez O, Edwin S, Relman DA 2008 Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One 3: e3056
Han YW, Shen T, Chung P, Buhimschi IA, Buhimschi CS 2009 Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J Clin Microbiol 47: 38–47
Bjorkqvist M, Soderquist B, Tornqvist E, Sjoberg L, Fredlund H, Kuhn I, Colque-Navarro P, Schollin J 2002 Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn. APMIS 110: 332–339
Huang SY, Tang RB, Chen SJ, Chung RL 2003 Coagulase-negative staphylococcal bacteremia in critically ill children: risk factors and antimicrobial susceptibility. J Microbiol Immunol Infect 36: 51–55
Liljedahl M, Bodin L, Schollin J 2004 Coagulase-negative staphylococcal sepsis as a predictor of bronchopulmonary dysplasia. Acta Paediatr 93: 211–215
Chhibber A, Schroeder BG 2008 Single-molecule polymerase chain reaction reduces bias: application to DNA methylation analysis by bisulfite sequencing. Anal Biochem 377: 46–54
Ohse H, Gobel UB 1987 Analysis of rRNA operons in Ureaplasma urealyticum. Isr J Med Sci 23: 352–356
Acknowledgements
We thank the parents and babies for their participation in the study. Also, we thank the medical, nursing, laboratory, and support staff in the neonatal intensive care units of Portsmouth and Southampton for their assistance and encouragement throughout the course of the study.
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Support by the British Lung Foundation, Lung Disease in Children grant.
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Payne, M., Goss, K., Connett, G. et al. Molecular Microbiological Characterization of Preterm Neonates at Risk of Bronchopulmonary Dysplasia. Pediatr Res 67, 412–418 (2010). https://doi.org/10.1203/PDR.0b013e3181d026c3
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DOI: https://doi.org/10.1203/PDR.0b013e3181d026c3
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