Neonatal CNS infection and inflammation caused by Ureaplasma species: rare or relevant?

Abstract

Colonization with Ureaplasma species has been associated with adverse pregnancy outcome, and perinatal transmission has been implicated in the development of bronchopulmonary dysplasia in preterm neonates. Little is known about Ureaplasma-mediated infection and inflammation of the CNS in neonates. Controversy remains concerning its incidence and implication in the pathogenesis of neonatal brain injury. In vivo and in vitro data are limited. Despite improving care options for extremely immature preterm infants, relevant complications remain. Systematic knowledge of ureaplasmal infection may be of great benefit. This review aims to summarize pathogenic mechanisms, clinical data and diagnostic pitfalls. Studies in preterm and term neonates are critically discussed with regard to their limitations. Clinical questions concerning therapy or prophylaxis are posed. We conclude that ureaplasmas may be true pathogens, especially in preterm neonates, and may cause CNS inflammation in a complex interplay of host susceptibility, serovar pathogenicity and gestational age-dependent CNS vulnerability.

Keywords:

• cerebral morbidities
• neonatal meningitis
• preterm infants
• ureaplasma parvum
• ureaplasma urealyticum

Acknowledgements

We thank C Siauw for critical reading of the manuscript.

Financial & competing interests disclosure

CP Speer has a consultancy agreement with Chiesi Farmaceutici S. P. A. (Italy). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Neonatal CNS infection caused by Ureaplasma spp. might be more prevalent and more relevant than previously suspected, especially in very immature preterm infants.

• Sustained cerebrospinal fluid (CSF) inflammation and internal hydrocephalus of unknown origin may be highly suggestive of ureaplasma meningitis, especially in very immature preterm infants. Significantly diminished CSF glucose levels and highly elevated CSF protein levels may be particularly striking.

• Early diagnosis and appropriate treatment may be essential to control inflammation and prevent adverse sequelae. Infection may escape detection if not explicitly considered.

• Treatment of invasive ureaplasma infections in neonatal patients is challenging, standardized regimens are missing.

• Ureaplasma-induced neonatal brain injury may occur due to direct invasion of the immature CNS or may be caused by sustained systemic inflammation and adverse systemic cytokine effects.

• In vivo and in vitro data provide evidence of a relevant pro-inflammatory capacity of ureaplasmas.

• A complex interplay of host immune factors and isolate-specific virulence factors may determine clinical course and outcome.

• Consistent isolate classification might help to identify serovars more pathogenic than others and designate virulence factors.

Notes