Skip to main content

Advertisement

SpringerLink
Log in

Maternal Ureaplasma exposure during pregnancy and the risk of preterm birth and BPD: a meta-analysis

  • Review
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Perinatal Ureaplasma infection is associated with a variety of adverse outcomes and neonatal diseases. This meta-analysis is to evaluate current evidence evaluating the association between Ureaplasma and adverse pregnancy outcomes and bronchopulmonary dysplasia (BPD) in preterm infants.

Methods

We searched for published articles on Ureaplasma, preterm and BPD in PubMed, the Cochrane Library, and Embase databases posted before August 28, 2021. In addition, the references of these articles were screened. A random/fixed-effect model was used to synthesize predefined outcomes.

Results

A total of 19 cohort studies involving 11,990 pregnancy women met our inclusion criteria. Pregnancy Ureaplasma positive increased the risk of preterm birth [odds ratios (OR) 2.76, 95% confidence intervals (CI) 1.63–4.68], BPD (OR 2.39 95% CI 1.73–3.30), chorioamnionitis (OR 2.71, 95% CI 2.02–3.64) and premature rupture of membranes (PROM, OR 2.19, 95% CI 1.34–3.58).

Conclusions

Pregnancy Ureaplasma positive may increase the risk of developing preterm birth, chorioamnionitis, PROM and BPD in the preterm infant. The evidence base is, however, of low quality and well-designed studies are needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Waites KB, Katz B, Schelonka RL (2005) Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev 18(4):757–789. https://doi.org/10.1128/CMR.18.4.757-789.2005

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sprong KE, Mabenge M, Wright CA, Govender S (2020) Ureaplasma species and preterm birth: current perspectives. Crit Rev Microbiol 46(2):169–181. https://doi.org/10.1080/1040841X.2020.1736986

    Article  CAS  PubMed  Google Scholar 

  3. Chu A, de St MA, Sim MS, Kallapur SG (2020) Neonatal Mycoplasma and Ureaplasma infections. Pediatr Ann 49(7):e305–e312. https://doi.org/10.3928/19382359-20200625-01

    Article  PubMed  Google Scholar 

  4. Kasper DC, Mechtler TP, Bohm J, Petricevic L, Gleiss A, Spergser J, Witt A, Herkner KR, Berger A (2011) In utero exposure to Ureaplasma spp. is associated with increased rate of bronchopulmonary dysplasia and intraventricular hemorrhage in preterm infants. J Perinat Med 39(3):331–336. https://doi.org/10.1515/jpm.2011.022

    Article  PubMed  Google Scholar 

  5. Olomu IN, Hecht JL, Onderdonk AO, Allred EN, Leviton A, Extremely Low Gestational Age Newborn Study I (2009) Perinatal correlates of Ureaplasma urealyticum in placenta parenchyma of singleton pregnancies that end before 28 weeks of gestation. Pediatrics 123(5):1329–1336. https://doi.org/10.1542/peds.2008-1113

    Article  Google Scholar 

  6. Witt A, Berger A, Gruber CJ, Petricevic L, Apfalter P, Worda C, Husslein P (2005) Increased intrauterine frequency of Ureaplasma urealyticum in women with preterm labor and preterm premature rupture of the membranes and subsequent cesarean delivery. Am J Obstet Gynecol 193(5):1663–1669. https://doi.org/10.1016/j.ajog.2005.03.067

    Article  PubMed  Google Scholar 

  7. DiGiulio DB (2012) Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med 17(1):2–11. https://doi.org/10.1016/j.siny.2011.10.001

    Article  PubMed  Google Scholar 

  8. Levin G, Rottenstreich A, Tsur A, Shai D, Cahan T, Yoeli R, Meyer R (2020) Determinants of adverse neonatal outcome in vaginal deliveries complicated by suspected intraamniotic infection. Arch Gynecol Obstet 302(6):1345–1352. https://doi.org/10.1007/s00404-020-05717-w

    Article  PubMed  Google Scholar 

  9. Shane AL, Sanchez PJ, Stoll BJ (2017) Neonatal sepsis. Lancet 390(10104):1770–1780. https://doi.org/10.1016/S0140-6736(17)31002-4

    Article  PubMed  Google Scholar 

  10. Viscardi RM, Terrin ML, Magder LS, Davis NL, Dulkerian SJ, Waites KB, Ambalavanan N, Kaufman DA, Donohue P, Tuttle DJ, Weitkamp JH, Hassan HE, Eddington ND (2020) Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants. Arch Dis Child Fetal Neonatal Ed 105(6):615–622. https://doi.org/10.1136/archdischild-2019-318122

    Article  PubMed  Google Scholar 

  11. Motomura K, Romero R, Xu Y, Theis KR, Galaz J, Winters AD, Slutsky R, Garcia-Flores V, Zou C, Levenson D, Para R, Ahmad MM, Miller D, Hsu CD, Gomez-Lopez N (2020) Intra-amniotic infection with Ureaplasma parvum causes preterm birth and neonatal mortality that are prevented by treatment with clarithromycin. MBio. https://doi.org/10.1128/mBio.00797-20

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kusanovic JP, Vargas P, Ferrer F, Diaz F, Cordova V, Martinovic C, Valdes R, Rosas A, Luna D, Silva P, Silva K, Nilo ME, Silva MJ, Espejo E, Zambrano MA, Garcia J, Parra-Lara LG, Escobar MF (2020) Comparison of two identification and susceptibility test kits for Ureaplasma spp and Mycoplasma hominis in amniotic fluid of patients at high risk for intra-amniotic infection. J Matern Fetal Neonatal Med 33(20):3409–3417. https://doi.org/10.1080/14767058.2019.1572742

    Article  CAS  PubMed  Google Scholar 

  13. Bartkeviciene D, Opolskiene G, Bartkeviciute A, Arlauskiene A, Lauzikiene D, Zakareviciene J, Ramasauskaite D (2020) The impact of Ureaplasma infections on pregnancy complications. Libyan J Med 15(1):1812821. https://doi.org/10.1080/19932820.2020.1812821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kayem G, Doloy A, Schmitz T, Chitrit Y, Bouhanna P, Carbonne B, Jouannic JM, Mandelbrot L, Benachi A, Azria E et al (2018) Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: a randomized trial. PLoS ONE 13(11):e0206290. https://doi.org/10.1371/journal.pone.0206290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. https://doi.org/10.1136/bmj.b2700

    Article  PubMed  PubMed Central  Google Scholar 

  16. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. https://doi.org/10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  17. Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163(7):1723–1729. https://doi.org/10.1164/ajrccm.163.7.2011060

    Article  CAS  PubMed  Google Scholar 

  18. Van Mechelen K, Meeus M, Matheeussen V, Donders G, Jacquemyn Y, Mahieu L (2021) Association between maternal cervicovaginal swab positivity for Ureaplasma spp. or other microorganisms and neonatal respiratory outcome and mortality. J Perinatology 41(6):9. https://doi.org/10.1038/s41372-020-00808-7

    Article  Google Scholar 

  19. Takakura S, Kodama Y, Yamashita R, Kino E, Kawano N, Tomimori K, Maki Y, Doi K, Kaneko M, Sameshima H (2020) Characteristics and influence of Mycoplasma/Ureaplasma cultures in amniotic fluid on perinatal outcomes. J Obstet Gynaecol Res 46(3):389–395. https://doi.org/10.1111/jog.14183

    Article  PubMed  Google Scholar 

  20. Miyoshi Y, Suga S, Sugimi S, Kurata N, Yamashita H, Yasuhi I (2020) Vaginal Ureaplasma urealyticum or Mycoplasma hominis and preterm delivery in women with threatened preterm labor. J Matern-Fetal Neonatal Med. https://doi.org/10.1080/14767058.2020.1733517

    Article  PubMed  Google Scholar 

  21. Rittenschober-Böhm J, Waldhoer T, Schulz SM, Pimpel B, Goeral K, Kasper DC, Witt A, Berger A (2019) Vaginal Ureaplasma parvum serovars and spontaneous preterm birth. Am J Obstet Gynecol 220(6):594.e591-594.e599. https://doi.org/10.1016/j.ajog.2019.01.237

    Article  Google Scholar 

  22. Kim SH, Chun J, Ko KH, Sung TJ (2019) Effect of antenatal azithromycin for Ureaplasma spp. on neonatal outcome at ≤30 weeks’ gestational age. Pediatrics Int 61(1):58–62. https://doi.org/10.1111/ped.13738

    Article  CAS  Google Scholar 

  23. Chun J, Chun SH, Han YS, Sung TJ (2019) Different degrees of maternal Ureaplasma colonization and its correlation with bronchopulmonary dysplasia in <32 weeks’ preterm infants. Pediatr Neonatol 60(4):441–446. https://doi.org/10.1016/j.pedneo.2018.11.004

    Article  PubMed  Google Scholar 

  24. Koucký M, Malíčková K, Cindrová-Davies T, Smíšek J, Vráblíková H, Černý A, Šimják P, Slováčková M, Pařízek A, Zima T (2016) Prolonged progesterone administration is associated with less frequent cervicovaginal colonization by Ureaplasma urealyticum during pregnancy—results of a pilot study. J Reprod Immunol 116:35–41. https://doi.org/10.1016/j.jri.2016.04.285

    Article  CAS  PubMed  Google Scholar 

  25. Kim SM, Romero R, Lee J, Chaemsaithong P, Docheva N, Yoon BH (2016) Gastric fluid versus amniotic fluid analysis for the identification of intra-amniotic infection due to Ureaplasma species. J Matern-Fetal Neonatal Med 29(16):2579–2587. https://doi.org/10.3109/14767058.2015.1098614

    Article  CAS  PubMed  Google Scholar 

  26. Vouga M, Greub G, Prod’hom G, Durussel C, Roth-Kleiner M, Vasilevsky S, Baud D (2014) Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labour and neonatal complications. Clin Microbiol Infect 20(10):1074–1079. https://doi.org/10.1111/1469-0691.12686

    Article  CAS  PubMed  Google Scholar 

  27. Kasper DC, Mechtler TP, Reischer GH, Witt A, Langgartner M, Pollak A, Herkner KR, Berger A (2010) The bacterial load of Ureaplasma parvum in amniotic fluid is correlated with an increased intrauterine inflammatory response. Diagn Microbiol Infect Dis 67(2):117–121. https://doi.org/10.1016/j.diagmicrobio.2009.12.023

    Article  PubMed  Google Scholar 

  28. Kirchner L, Helmer H, Heinze G, Wald M, Brunbauer M, Weninger M, Zaknun D (2007) Amnionitis with Ureaplasma urealyticum or other microbes leads to increased morbidity and prolonged hospitalization in very low birth weight infants. Eur J Obstet Gynecol Reprod Biol 134(1):44–50. https://doi.org/10.1016/j.ejogrb.2006.09.013

    Article  PubMed  Google Scholar 

  29. Gerber S, Vial Y, Hohlfeld P, Witkin SS (2003) Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery. J Infect Dis 187(3):518–521. https://doi.org/10.1086/368205

    Article  PubMed  Google Scholar 

  30. Berger A, Witt A, Haiden N, Kretzer V, Heinze G, Kohlhauser C (2003) Microbial invasion of the amniotic cavity at birth is associated with adverse short-term outcome of preterm infants. J Perinat Med 31(2):115–121. https://doi.org/10.1515/JPM.2003.016

    Article  PubMed  Google Scholar 

  31. Aaltonen R, Jalava J, Laurikainen E, Kärkkäinen U, Alanen A (2002) Cervical Ureaplasma urealyticum colonization: comparison of PCR and culture for its detection and association with preterm birth. Scand J Infect Dis 34(1):35–40. https://doi.org/10.1080/00365540110077074

    Article  CAS  Google Scholar 

  32. Abele-Horn M, Scholz M, Wolff C, Kolben M (2000) High-density vaginal ureaplasma urealyticum colonization as a risk factor for chorioamnionitis and preterm delivery. Acta Obstet Gynecol Scand 79(11):973–978. https://doi.org/10.1034/j.1600-0412.2000.079011973.x

    Article  CAS  PubMed  Google Scholar 

  33. Bo Hyun Y, Romero R, Joong Shin P, Jae Won C, Young AhK, Ju Cheol K, Kyung Sun K (1998) Microbial invasion of the amniotic cavity with Ureaplasma urealyticum is associated with a robust host response in fetal, amniotic, and maternal compartments. Am J Obstet Gynecol 179(5):1254–1260. https://doi.org/10.1016/s0002-9378(98)70142-5

    Article  Google Scholar 

  34. Abele-Horn M, Peters J, Genzel-Boroviczény O, Wolff C, Zimmermann A, Gottschling W (1997) Vaginal Ureaplasma urealyticum colonization: influence on pregnancy outcome and neonatal morbidity. Infection 25(5):286–291. https://doi.org/10.1007/BF01720398

    Article  CAS  PubMed  Google Scholar 

  35. Viscardi RM, Kallapur SG (2015) Role of Ureaplasma respiratory tract colonization in bronchopulmonary dysplasia pathogenesis: current concepts and update. Clin Perinatol 42(4):719–738. https://doi.org/10.1016/j.clp.2015.08.003

    Article  PubMed  PubMed Central  Google Scholar 

  36. Romero R, Dey SK, Fisher SJ (2014) Preterm labor: one syndrome, many causes. Science 345(6198):760–765. https://doi.org/10.1126/science.1251816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yoon BH, Chang JW, Romero R (1998) Isolation of Ureaplasma urealyticum from the amniotic cavity and adverse outcome in preterm labor. Obstet Gynecol 92(1):77–82. https://doi.org/10.1016/s0029-7844(98)00122-7

    Article  CAS  PubMed  Google Scholar 

  38. Vornhagen J, Quach P, Boldenow E, Merillat S, Whidbey C, Ngo LY, Adams Waldorf KM, Rajagopal L (2016) Bacterial hyaluronidase promotes ascending GBS infection and preterm birth. MBio. https://doi.org/10.1128/mBio.00781-16

    Article  PubMed  PubMed Central  Google Scholar 

  39. Romero R, Miranda J, Kusanovic JP, Chaiworapongsa T, Chaemsaithong P, Martinez A, Gotsch F, Dong Z, Ahmed AI, Shaman M, Lannaman K, Yoon BH, Hassan SS, Kim CJ, Korzeniewski SJ, Yeo L, Kim YM (2015) Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques. J Perinat Med 43(1):19–36. https://doi.org/10.1515/jpm-2014-0249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Doster RS, Sutton JA, Rogers LM, Aronoff DM, Gaddy JA (2018) Streptococcus agalactiae induces placental macrophages to release extracellular traps loaded with tissue remodeling enzymes via an oxidative burst-dependent mechanism. MBio. https://doi.org/10.1128/mBio.02084-18

    Article  PubMed  PubMed Central  Google Scholar 

  41. Oh KJ, Lee KA, Sohn YK, Park CW, Hong JS, Romero R, Yoon BH (2010) Intraamniotic infection with genital mycoplasmas exhibits a more intense inflammatory response than intraamniotic infection with other microorganisms in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 203(3):211 e211-218. https://doi.org/10.1016/j.ajog.2010.03.035

    Article  Google Scholar 

  42. Dehaene I, Scheire E, Steen J, De Coen K, Decruyenaere J, Smets K, Roelens K (2020) Obstetrical characteristics and neonatal outcome according to aetiology of preterm birth: a cohort study. Arch Gynecol Obstet 302(4):861–871. https://doi.org/10.1007/s00404-020-05673-5

    Article  CAS  PubMed  Google Scholar 

  43. Schelonka RL, Waites KB (2007) Ureaplasma infection and neonatal lung disease. Semin Perinatol 31(1):2–9. https://doi.org/10.1053/j.semperi.2007.01.001

    Article  PubMed  Google Scholar 

  44. Oh KJ, Romero R, Park JY, Hong JS, Yoon BH (2019) The earlier the gestational age, the greater the intensity of the intra-amniotic inflammatory response in women with preterm premature rupture of membranes and amniotic fluid infection by Ureaplasma species. J Perinat Med 47(5):516–527. https://doi.org/10.1515/jpm-2019-0003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Glaser K, Gradzka-Luczewska A, Szymankiewicz-Breborowicz M, Kawczynska-Leda N, Henrich B, Waaga-Gasser AM, Speer CP (2019) Perinatal Ureaplasma exposure is associated with increased risk of late onset sepsis and imbalanced inflammation in preterm infants and may add to lung injury. Front Cell Infect Microbiol 9:68. https://doi.org/10.3389/fcimb.2019.00068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81873845).

Author information

Authors and Affiliations

  1. NICU, The Children’s Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, China

    Yan-ping Xu, Ye-qing Huang & Li-ping Shi

  2. Yiwu Branch of Children’s Hospital, Zhejiang University School of Medicine, Yiwu, China

    Jian-miao Hu

Authors
  1. Yan-ping Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian-miao Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ye-qing Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li-ping Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y-pX drafted the protocol and manuscript; acquired, analyzed, and interpreted the data; and provided final approval for publication. J-mH helped analyze and interpret the data, revised the manuscript for important intellectual content, provided final approval for publication, and agreed to be accountable for all aspects of the work. Y-qH helped analyze and interpret the data, and provided final approval for publication. L-pS constructed the search, contributed to the conception and design of the work, revised the manuscript for important intellectual content, and provided final approval for publication.

Corresponding author

Correspondence to Yan-ping Xu.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, Yp., Hu, Jm., Huang, Yq. et al. Maternal Ureaplasma exposure during pregnancy and the risk of preterm birth and BPD: a meta-analysis. Arch Gynecol Obstet 306, 1863–1872 (2022). https://doi.org/10.1007/s00404-022-06491-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-022-06491-7

Keywords

Search

Navigation