Lethal Neonatal Respiratory Failure by Perinatal Transmission of Ureaplasma Parvum after Maternal PPROM

Abstract

A primiparous pregnant woman was admitted due to preterm premature rupture of membranes (PPROM) at 27+0 week of gestational age (WGA). Conventional vaginal microbiological analysis had no pathological finding. Management decisions based on national guidelines included antenatal corticoids, tocolytics and antibiotics. Unstoppable efforts of preterm labor in 28+0 WGA and supposed amniotic infection syndrome necessitated emergency cesarean section. The preterm infant underwent NICU therapy, developed an early-onset neonatal sepsis and therapy-refractory pulmonary insufficiency with consecutive right heart failure, resulting in death on the 36^th day of life. Microbiota analyses by 16Sr DNA sequencing was performed from maternal vaginal swabs and from neonatal pharyngeal swabs. Maternal antibiotic treatment resulted in depletion of physiological vaginal colonization with Lactobacillus crispatus. Ureaplasma parvum became the dominant vaginal microorganism at delivery and was detected in high relative abundance in the neonatal specimen. Progressive radiological air-space changes and interstitial pathologies associated with Ureaplasma infection (bronchopulmonary dysplasia type III) were seen early at the 3^rd and distinctly from 14^th day of life. This clearly demonstrates the need of vaginal colonization diagnostics in PPROM patients and awareness of the consecutive risks in the preterm. Vaginal microbiome analysis may allow individualized and targeted maternal and fetal diagnostic, prophylactic and therapeutic strategies to identify, protect and treat the high-risk neonates after PPROM.

Zusammenfassung

Die Aufnahme erfolgte in der 27+0 Schwangerschaftswoche (SSW) aufgrund eines frühen vorzeitigen Blasensprunges (PPROM). Die konventionelle vaginale mikrobiologische Diagnostik verblieb unauffällig. Das Management umfasste leitliniengerecht die Applikation antenataler Steroide, Tokolytika und Antibiotika. Unaufhaltsame Frühgeburtsbestrebungen in der 28+0 SSW unter Verdacht eines Amnioninfektionssyndroms erforderten eine Notsectio. Das Frühgeborene erhielt eine sofortige NICU-Versorgung, entwickelte eine early-onset neonatale Sepsis und eine therapierefraktäre Lungen- mit konsekutiver Rechtsherzinsuffizienz, die zum Tod am 36. Lebenstag führte. Es wurden Mikrobiomanalysen mittels 16Sr DNA-Sequenzierung aus mütterlichen Vaginalabstrichen und aus neonatalen Rachenabstrichen durchgeführt. Die Antibiotikatherapie depletierte die physiologische vaginalen Kolonisation mit Lactobacillus crispatus. Ureaplasma parvum wurde als die dominierende vaginale mikrobielle Spezies und in den neonatalen Proben mit hoher relativer Abundanz nachgewiesen. Radiologisch wurden progressive Lungenveränderungen im Zusammenhang mit Ureaplasmen (bronchopulmonale Dysplasie Typ III) nachgewiesen. Dies zeigt deutlich die Notwendigkeit einer exakten vaginalen Kolonisationsdiagnostik bei PPROM-Patientinnen mit Relevanz für konsekutive Risiken bei Frühgeborenen. Die vaginale Mikrobiomanalyse kann dabei individualisierte mütterliche und neonatale diagnostische, prophylaktische und therapeutische Strategien zur Identifizierung, zum Schutz und zur Behandlung der Hochrisiko-Neugeborenen nach PPROM verbessern.

Key words

PPROM - EONS - Ureaplasma parvum - bronchopulmonary dysplasia - microbiome analysis

Schlüsselwörter

PPROM - EONS - Ureaplasma parvum - Bronchopulmonale Dysplasie - Mikrobiomanalyse

• References

• 1 Hanke K, Hartz A, Manz M. et al. Preterm prelabor rupture of membranes and outcome of very-low-birth-weight infants in the German Neonatal Network. PLoS One 2015; 10: e0122564
• 2 Goldenberg RL, Culhane JF, Iams JD. et al. Epidemiology and causes of preterm birth. Lancet 2008; 371: 75-84
• 3 Brown RG, Marchesi JR, Lee YS. et al. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Med 2018; 16: 9
• 4 Tchirikov M, Schlabritz-Loutsevitch N, Maher J. et al. Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome. J Perinat Med 2018; 46: 465-488
• 5 Shah BA, Padbury JF. Neonatal sepsis: an old problem with new insights. Virulence 2014; 5: 170-178
• 6 Bizzarro MJ, Raskind C, Baltimore RS. et al. Seventy-five years of neonatal sepsis at Yale: 1928–2003. Pediatrics 2005; 116: 595-602
• 7 Simonsen KA, Anderson-Berry AL, Delair SF. et al. Early-onset neonatal sepsis. Clin Microbiol Rev 2014; 27: 21-47
• 8 Viscardi RM, Hashmi N, Gross GW. et al. Incidence of invasive ureaplasma in VLBW infants: relationship to severe intraventricular hemorrhage. J Perinatol 2008; 28: 759-765
• 9 Sung TJ, Xiao L, Duffy L. et al. Frequency of ureaplasma serovars in respiratory secretions of preterm infants at risk for bronchopulmonary dysplasia. Pediatr Infect Dis J 2011; 30: 379-383
• 10 Vancutsem E, Faron G, Foulon W. et al. Genital tract colonization with Ureaplasma spp. and its association with abnormal vaginal flora. J Med Microbiol 2015; 64: 654-656
• 11 Kafetzis DA, Skevaki CL, Skouteri V. et al. Maternal genital colonization with Ureaplasma urealyticum promotes preterm delivery: association of the respiratory colonization of premature infants with chronic lung disease and increased mortality. Clin Infect Dis 2004; 39: 1113-1122
• 12 Silwedel C, Speer CP, Glaser K. Ureaplasma-associated prenatal, perinatal, and neonatal morbidities. Expert Rev Clin Immunol 2017; 13: 1073-1087
• 13 Viscardi RM. Ureaplasma species: role in neonatal morbidities and outcomes. Arch Dis Child Fetal Neonatal Ed 2014; 99: F87-F92
• 14 Schelonka RL, Katz B, Waites KB. et al. Critical appraisal of the role of Ureaplasma in the development of bronchopulmonary dysplasia with meta-analytic techniques. Pediatr Infect Dis J 2005; 24: 1033-1039
• 15 Honma Y, Yada Y, Takahashi N. et al. Certain type of chronic lung disease of newborns is associated with Ureaplasma urealyticum infection in utero. Pediatr Int 2007; 49: 479-484
• 16 Wang EE, Ohlsson A, Kellner JD. Association of Ureaplasma urealyticum colonization with chronic lung disease of prematurity: results of a meta-analysis. J Pediatr 1995; 127: 640-644
• 17 Viscardi RM, Kallapur SG. Role of Ureaplasma respiratory tract colonization in bronchopulmonary dysplasia pathogenesis: current concepts and update. Clin Perinatol 2015; 42: 719-738
• 18 Speer CP. Chorioamnionitis, postnatal factors and proinflammatory response in the pathogenetic sequence of bronchopulmonary dysplasia. Neonatology 2009; 95: 353-361
• 19 Kasper DC, Mechtler TP, Bohm J. et al. In utero exposure to Ureaplasma spp. is associated with increased rate of bronchopulmonary dysplasia and intraventricular hemorrhage in preterm infants. J Perinat Med 2011; 39: 331-336
• 20 Cultrera R, Seraceni S, Germani R. et al. Molecular evidence of Ureaplasma urealyticum and Ureaplasma parvum colonization in preterm infants during respiratory distress syndrome. BMC Infect Dis 2006; 6: 166
• 21 Donders GGG, Ruban K, Bellen G. et al. Mycoplasma/Ureaplasma infection in pregnancy: to screen or not to screen. J Perinat Med 2017; 45: 505-515
• 22 ISIDOG ISIDOG recommendations about the importance, need for testing, and treatment of mycoplasmata in pregnancy. 2016
• 23 Chu A, de St Maurice A, Sim MS. et al. Neonatal Mycoplasma and Ureaplasma infections. Pediatr Ann 2020; 49: e305-e312
• 24 Redline RW, Faye-Petersen O, Heller D. et al. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2003; 6: 435-448
• 25 Rath S, Heidrich B, Pieper DH. et al. Uncovering the trimethylamine-producing bacteria of the human gut microbiota. Microbiome 2017; 5: 54
• 26 Camarinha-Silva A, Jauregui R, Chaves-Moreno D. et al. Comparing the anterior nare bacterial community of two discrete human populations using Illumina amplicon sequencing. Environ Microbiol 2014; 16: 2939-2952
• 27 Sprong KE, Mabenge M, Wright CA. et al. Ureaplasma species and preterm birth: current perspectives. Crit Rev Microbiol 2020; 46: 169-181
• 28 Biernat-Sudolska M, Rojek-Zakrzewska D, Lauterbach R. Assessment of various diagnostic methods of ureaplasma respiratory tract infections in newborns. Acta Biochim Pol 2006; 53: 609-611
• 29 Pinna GS, Skevaki CL, Kafetzis DA. The significance of Ureaplasma urealyticum as a pathogenic agent in the paediatric population. Curr Opin Infect Dis 2006; 19: 283-289
• 30 Rittenschober-Bohm J, Waldhoer T, Schulz SM. et al. Vaginal Ureaplasma parvum serovars and spontaneous preterm birth. Am J Obstet Gynecol 2019; 220: 594 e591-594 e599
• 31 Jobe AJ. The new BPD: an arrest of lung development. Pediatr Res 1999; 46: 641-643
• 32 Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence. Arch Dis Child Fetal Neonatal Ed 2018; 103: F285-F291
• 33 Lowe J, Watkins WJ, Edwards MO. et al. Association between pulmonary ureaplasma colonization and bronchopulmonary dysplasia in preterm infants: updated systematic review and meta-analysis. Pediatr Infect Dis J 2014; 33: 697-702
• 34 Theilen U, Lyon AJ, Fitzgerald T. et al. Infection with Ureaplasma urealyticum: is there a specific clinical and radiological course in the preterm infant?. Arch Dis Child Fetal Neonatal Ed 2004; 89: F163-F167
• 35 Crouse DT, Odrezin GT, Cutter GR. et al. Radiographic changes associated with tracheal isolation of Ureaplasma urealyticum from neonates. Clin Infect Dis 1993; 17: S122-S130
• 36 Pacifico L, Panero A, Roggini M. et al. Ureaplasma urealyticum and pulmonary outcome in a neonatal intensive care population. Pediatr Infect Dis J 1997; 16: 579-586
• 37 Wagner BD, Sontag MK, Harris JK. et al. Airway microbial community turnover differs by BPD severity in ventilated preterm infants. PLoS One 2017; 12: e0170120
• 38 Castro-Alcaraz S, Greenberg EM, Bateman DA. et al. 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: e45
• 39 Viscardi RM, Terrin ML, Magder LS. et al. Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants. Arch Dis Child Fetal Neonatal Ed 2020; 105: 615-622
• 40 Sweeney EL, Dando SJ, Kallapur SG. et al. The human Ureaplasma species as causative agents of chorioamnionitis. Clin Microbiol Rev 2017; 30: 349-379