Intrauterine infection during pregnancy

Dolgushina V.F., Kurnosenko I.V., Astashkina M.V.

South Ural Medical University, Ministry of Health of Russia, Chelyabinsk, Russia
Recently, there have been more and more reports on the role of intrauterine infection (IUI) in pregnant women in the occurrence of a wide spectrum of obstetric and perinatal complications. To date, there is no generally accepted terminology for this complication. IUI should be considered as a spectrum of infectious and inflammatory processes in various placental structures. The diagnosis of IUI during pregnancy presents significant difficulties. IUI can be verified only on the basis of placental morphological examination. In this connection, this diagnosis is made mainly retrospectively after the related complications have occurred. At the present stage, the search for non-invasive markers of subclinical IUI is being continued. Much attention is paid to the peculiarities of the course of pregnancy, ultrasound signs, and the study of immune factors. The treatment of IUI is no less difficult than its diagnosis. Recent publications on the pathogenesis, diagnosis, and treatment of IUI during pregnancy are reviewed.
Conclusion. Despite the clinical significance of the problem of IUI during pregnancy, there is still no algorithm that allows for a comprehensive approach to diagnostic and therapeutic measures. The timely diagnosis and reasonable use of antimicrobial drugs can become a promising area in the package of therapeutic measures for the prevention of pregnancy complications and adverse perinatal outcomes in the presence of IUI.

Keywords

intrauterine infection
pregnancy
inflammatory process
antibacterial therapy

References

  1. Elovitz M.A., Gajer P., Riis V., Brown A.G., Humphrys M.S., Holm J.B., Ravel J. Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery. Nat. Commun. 2019; 2110(1): 1305. https://dx.doi.org/10.1038/s41467-019-09285-9.
  2. Ходжаева З.С., Припутневич Т.В., Муравьева В.В., Гусейнова Г.Э., Горина К.А., Мишина Н.Д. Оценка состава и стабильности микробиоты влагалища у беременных в процессе динамического наблюдения. Акушерство и гинекология. 2019; 7: 30-8. [Khodzhaeva Z.S., Priputnevich T.V., Murav'eva V.V., Gusejnova G.Je., Gorina K.A., Mishina N.D. Assessment of the composition and stability of the vaginal microbiota in pregnant women during dynamic observation. Obstetrics and gynecology. 2019; 7: 30-8. (in Russian)].
  3. Копылов А.В., Рыжков В.В. Судебно-медицинские аспекты перинатальных потерь от внутриутробных инфекций. Судебно-медицинская экспертиза. 2016; 59(6): 18-21. [Kopylov A.V., Ryzhkov V.V. Forensic aspects of perinatal losses from intrauter-ine infections. Forensic Medical Examination. 2016; 59(6): 18-21. (in Russian)]. https://dx.doi.org/10.17116/sudmed201659618-21.
  4. Хамадьянов У.Р., Русакова Л.А., Хамадьянова А.У., Тихонова Т.Ф., Хамадьянова С.У., Галимов А.И., Иваха В.И. Внутриутробное инфицирование плода: современный взгляд на проблему. Российский вестник акушера-гинеколога. 2013; 13(5): 16-9. [Hamad'janov U.R., Rusakova L.A., Hamad'janova A.U. et al. Intrauterine infection of the fetus: a modern view of the problem. Russian Bulletin of the obstetrician-gynecologist. 2013; 13(5): 16-9. (in Russian)].
  5. Бондаренко К.Р., Бондаренко В.М. Бактериальные липосахариды в пато-генезе гинекологических заболеваний и акушерских осложнений. Журнал микробиологии, эпидемиологии и иммунобиологии. 2014; 4: 80-6. [Bondarenko K.R., Bondarenko V.M. Bacterial liposaccharides in the pathogen-esis of gynecological diseases and obstetric. Journal of Microbiology, Epide-miology and Immunobiology. 2014; 4: 80-6. (in Russian)].
  6. Синякова А.А., Шипицына Е.В., Будиловская О.В., Болотских В.М., Савичева А.М. Клинико-анамнестические и микробиологические предикторы невынашивания беременности. Журнал акушерства и женских болезней. 2019; 68(2): 59-70. [Sinjakova A.A., Shipicyna E.V., Budilovskaja O.V., Bolotskih V.M., Savicheva A.M. Clinical, anamnestic, microbiological predictors nevynosimo-tion of pregnancy. Journal of obstetrics and women's diseases. 2019; 68(2): 59-70. (in Russian)].
  7. Prince A.L., Chu D.M., Seferovic M.D., Antony K.M., Ma J., Aagaard K.M. The perinatal microbiome and pregnancy: moving beyond the vaginal microbi-ome. Cold Spring Harb. Perspect. Med. 2015; 5(6): a023051. https://dx.doi.org/10.1101/cshperspect.a023051.
  8. Роговская С.И., Бебнева Т.Н. Бактериальный вагиноз при беременности. Второй этап терапии. Акушерство и гинекология: новости, мнения, обу-чения. 2014; 4(6): 100-4. [Rogovskaja S.I., Bebneva T.N. Bacterial vaginosis during pregnancy. The second stage of therapy. Obstetrics and gynecology: News. Opinions. Trainings. 2014; 4 (6): 100-4. (in Russian)].
  9. Shimaoka M., Yo Y., Doh K., Kotani Y., Suzuki A., Tsuji I. et al. Association between preterm delivery and bacterial vaginosis with or without treatment. Sci. Rep. 2019; 9(1): 509. https://dx.doi.org/10.1038/s41598-018-36964-2.
  10. Долгушина В.Ф., Долгушин И.И., Курносенко И.В., Лебедева Ю.В. Клинико-иммунологические критерии внутриматочной инфекции. Акушерство и гинекология. 2017; 1: 40-5. [Dolgushina V.F., Dolgushin I.I., Kurnosenko I.V., Lebedeva Ju.V. Clinical and immunological cri-teria for intrauterine infection. Obstetrics and gynecology. 2017; 1: 40-5. (in Russian)]. https://dx.doi.org/10.18565/aig.2017.1.40-45.
  11. Romero R., Gomez-Lopez N., Winters A.D., Jung E., Shaman M., Bieda J. et al. Evidence that intra-amniotic infections are often the result of an ascending invasion – a molecular microbiological study, J. Perinat. Med. 2019; 47(9): 915-31. https://dx.doi.org/10.1515/jpm-2019-0297.
  12. Conti N., Torricelli M., Voltolini C., Vannuccini S., Clifton V.L., Bloise E., Petraglia F. Term histologic chorioamnionitis: a heterogeneous condition. Eur. J. Obstet. Gynecol. Reprod. Biol. 2015; 188: 34-8. https://dx.doi.org/10.1016/j.ejogrb.2015.02.034.
  13. Walsh S.W., Chumble A.A., Washington S.L., Archer K.J., Sahingur S.E., Strauss J.F. Increased expression of toll-like receptors 2 and 9 is associated with reduced DNA methylation in spontaneous preterm labor. J. Reprod. Immunol. 2017; 121: 35-41. https://dx.doi.org/10.1016/j.jri.2017.05.003.
  14. Etyang A.K., Omuse G., Mukaindo A.M., Temmerman M. Maternal inflammatory markers for chorioamnionitis in preterm prelabour rupture of membranes: a systematic review and meta-analysis of diagnostic test accuracy studies. Syst. Rev. 2020; 9(1): 141. https://dx.doi.org/10.1186/s13643-020-01389-4.
  15. Тютюнник В.Л., Кан Н.Е., Ломова Н.А., Карапетян Т.Э., Коган Е.А., Щеголев А.И. Роль врожденного иммунитета у беременных с вульвовагинальными инфекциями в развитии внутриутробной инфекции у новорожденного. Бюллетень экспериментальной биологии и медицины. 2014; 158(7): 82-4. [Tutjunnik V.L., Kan N.E., Lomova N.A. et al. The role of innate immunity in pregnant women with vulvovaginal infections in the development of intrauterine infection in the new-born. Bulletin of Experimental Biology and Medicine. 2014; 158(7): 82-4. (in Russian)].
  16. Peng C.C., Chang J.H., Lin H.Y., Cheng P.J., Su B.H. Intrauterine inflammation, infection, or both (Triple I): A new concept for chorioamnionitis. Pediatr. Neonatol. 2018; 59(3): 231-7. https://dx.doi.org/10.1016/j.pedneo.2017.09.001.
  17. Yoon B.H., Romero R., Park J.Y., Oh K.J., Lee J., Conde-Agudelo A., Hong J.S. Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. Am. J. Obstet. Gynecol. 2019; 221(2): 142.e1-22. https://dx.doi.org/10.1016/j.ajog.2019.03.017.
  18. Menon R. Human fetal membranes at term: Dead tissue or signalers of parturi-tion? Placenta. 2016; 44: 1-5. https://dx.doi.org/10.1016/j.placenta.2016.05.013.
  19. Romero R., Kim Y.M., Pacora P., Kim C.J., Benshalom-Tirosh N., Jaiman S. et al. The frequency and type of placental histologic lesions in term pregnancies with normal outcome. J. Perinat. Med. 2018; 46(6): 613-30. https://dx.doi.org/10.1515/jpm-2018-0055.
  20. Pelzer E., Gomez-Arango L.F., Barrett H.L., Nitert M.D. Review: Maternal health and the placental microbiome. Placenta. 2017; 54: 30-7. https://dx.doi.org/10.1016/j.placenta.2016.12.003.
  21. Romero R., Miranda J., Chaiworapongsa T. Chaemsaithong P., Gotsch F., Dong Z. et al. Sterile intra-amniotic inflammation in asymptomatic patients with a so-nographic short cervix: prevalence and clinical significance. J. Matern. Fetal Neonatal Med. 2015; 28(11): 1343-59. https://dx.doi.org/10.3109/14767058.2014.954243.
  22. Kusanovic J.P., Romero R., Martinovic C., Silva K., Erez O., Maymon E. et al. Transabdominal collection of amni-otic fluid "sludge" and identification of Candida albicans intra-amniotic infection. J. Matern. Fetal Neonatal Med. 2018; 31(10): 1279-84. https://dx.doi.org/10.1080/14767058.2017.1315095.
  23. Шварц Т.А. Биопленки как микробное сообщество. Вестник Курганского государственного университета. 2015; 1: 41-4. [Shvarts T.A. Biofilms as a microbi-al community. Bulletin of Kurgan State University. 2015; 1: 41-4. (in Russian)].
  24. Aagaard K., Ma J., Antony K.M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Sci. Transl. Med. 2014; 6(237): 237ra65. https://dx.doi.org/10.1126 / scitranslmed.3008599.
  25. Theis K.R., Romero R., Winters A.D., Greenberg J.M., Gomez-Lopez N., Alhousseini A. et al. Does the human placenta delivered at term have a microbiota? Results of cultivation, quantitative real-time PCR, 16S rRNA gene sequencing, and meta-genomics. Am. J. Obstet. Gynecol. 2019; 220(3): 267.e1-267. https://dx.doi.org/10.1016/j.ajog.2018.10.018.
  26. Oh K.J., Kim S.M., Hong J.S., Maymon E., Erez O., Panaitescu B. et al. Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflamma-tion. Am. J. Obstet. Gynecol. 2017; 216(6): 604.e1-604. https://dx.doi.org/10.1016/j.ajog.2017.02.035.
  27. Ведощенко Т.В., Клычева О.И., Лазарева Г.А., Хурасева А.Б. Влияние восходящего бактериального инфицирования на невынашивание беременности. Курский научно-практический вестник «Человек и его здоровье». 2014; 1: 32-41. [Vedoschenko T.V., Klycheva O.I., Lazareva G.A., Huraseva A.B. Influence of ascending bacterial infection on miscarriage. Kursk scientific and practical Bulletin "Man and his health". 2014; 1: 32-41. (in Russian)].
  28. Walther-António M.R., Jeraldo P., Berg Miller M.E., Yeoman C.J., Nelson K.E., Wilson B.A. et al. Pregnancy's stronghold on the vaginal microbiome. PLoS One. 2014; 9(6): e98514. https://dx.doi.org/10.1371/journal.pone.0098514.
  29. Пустотина О.А., Остроменский В.В. Инфекционный фактор в генезе невынашивания беременности. Эффективная фармакотерапия. 2019; 15(13): 26-33. [Pustotina O.A., Ostromenskij V.V. Infectious factor in the Genesis of miscarriage. Effective pharmacotherapy. 2019; 15(13): 26-33. (in Russian)]. https://dx.doi.org/10.33978/2307-3586-2019-15-13-26-33.
  30. Радзинский В.Е., Петров Ю.А., Полина М.Л. Хронический эндометрит: современные аспекты. Кубанский научный медицинский вестник. 2017; 5: 69-74. [Radzinskij V.E., Petrov Yu.A., Polina M.L. Chronic endometritis: modern aspects. Kuban Scientific Medical Bulletin. 2017; 5: 69-74. (in Russian)]. https://dx.doi.org/10.25207/1608-6228-2017-24-5-69-74.
  31. Heerema-Mc Kenney A. Defense and infection of the human placenta. APMIS. 2018; 126(7): 570-88. https:/dx./doi.org/10.1111/apm.12847.
  32. Redline R.W. Classification of placental lesions. Am. J. Obstet. Gynecol. 2015; 213(4, Suppl.): S21-8. https://dx.doi.org/10.1016/j.ajog.2015.05.056.
  33. Курносенко И.В., Долгушина В.Ф., Пастернак А.Е. Воспалительный изменения в последе у женщин с преждевременными и своевременными родами. Современные проблемы науки и образования. 2016; 3: 172. [Kurnosenko I.V., Dolgushina V.F., Pasternak A.E. Inflammatory changes in the afterbirth in women with premature and timely delivery. Modern problems of science and education. 2016; 3: 172. (in Russian)].
  34. Palmsten K., Nelson K.K., Laurent L.C., Park S., Chambers C.D., Parast M.M. Subclinical and clinical chorioamnionitis, fetal vasculitis, and risk for preterm birth: A cohort study. Placenta. 2018; 67: 54-60. https://dx.doi.org/10.1016/j.placenta.2018.06.001.
  35. Di Renzo G.C., Cabero Roura L., Facchinetti F., Helmer H., Hubinont C., Jacobsson B. et al. Preterm labor and birth management: recommendations from the Euro-pean Association of Perinatal Medicine. J. Matern. Fetal Neonatal Med. 2017; 30(17): 2011-30. https://dx.doi.org/10.1080/14767058.2017.1323860.
  36. Maki Y. Antibiotics for preterm labor. In: Preterm labor and delivery. Springer; 2019: 131-9. https://dx.doi.org/10.1007/978-981-13-9875-9_13.
  37. NICE Guidance. Preterm labour and birth. 19 October 2016.
  38. Torricelli M., Voltolini C., Toti P., Vellucci F.L., Conti N., Cannoni. A. et al. His-tologic chorioamnionitis: different histologic features at different gestational ages. J. Matern. Fetal Neonatal Med. 2014; 27(9): 910-3. https://dx.doi.org/10.3109/14767058.2013.846313.
  39. Kim C.J., Romero R., Chaemsaithong P., Chaiyasit N., Yoon B.H., Kim Y.M. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical sig-nificance. Am. J. Obstet. Gynecol. 2015; 213(4, Suppl.): S29-52. https://dx.doi.org/10.1016/j.ajog.2015.08.040.
  40. Gomez-Lopez N., Romero R., Garcia-Flores V., Xu Y., Leng Y., Alhousseini A. et al. Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for microbial killing in the amniotic cavity. Am. J. Reprod. Immunol. 2017; 78(4): ID e12723. https://dx.doi.org/10.1111/aji.12723.
  41. Keelan J.A. Intrauterine inflammatory activation, functional progesterone with-drawal, and the timing of term and preterm birth. J. Reprod. Immunol. 2018; 125: 89-99. https://dx.doi.org/10.1016/j.jri.2017.12.004.
  42. Пустотина О.А. «Сладж» в околоплодных водах. Медицинский совет. 2018; 7: 64-73. [Pustotina O.A. "Sludge" in amniotic fluid. Medical Council. 2018; 7: 64-73. (in Russian)].
  43. Fuchs F., Boucoiran I., Picard A., Dube J., Wavrant S., Bujold E., Audibert F. Impact of amniotic fluid “sludge” on the risk of preterm delivery. J. Matern. Fetal Neonatal Med. 2015; 28(10): 1176-80. https://dx.doi.org/10.3109/14767058.2014.947575.
  44. Valent F., Gongolo F., Deroma L., Zanier L. Prescription of systemic antibiotics during pregnancy in primary care in Friuli. J. Matern. Fetal Neonatal Med. 2015; 28(2): 210-5. https://dx.doi.org/10.3109/14767058.2014.906572.
  45. Štefan M., Vojtěch J. Antibiotic therapy in pregnancy. Ceska Gynekol. 2018 Winter; 83(1): 70-80.
  46. Subramaniam A., Abramovici A., Andrews W.W., Tita A.T. Antimicrobials for preterm birth prevention: an overview. Infect. Dis. Obstet. Gynecol. 2012; 2012: 157159. https://dx.doi.org/10.1155/2012/157159.
  47. Le Doare K., Heath P.T. An overview of global GBS epidemiology. Vaccine. 2013; 31(Suppl. 4): D7-12. https://dx.doi.org/10.1016/j.vaccine.2013.01.009.
  48. Flenady V., Hawley G., Stock O.M., Kenyon S., Badawi N. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst. Rev. 2013; (12): CD000246. https://dx.doi.org/10.1002/14651858.CD000246.pub2
  49. Li D.K., Chen H., Ferber J., Odouli R. Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study. Lancet Diabetes Endo-crinol. 2017; 5(1): 18-25. https://dx.doi.org/10.1016/S2213-8587(16)30281-9.
  50. Milliken S., Allen R.M., Lamont R.F. The role of antimicrobial treatment during pregnancy on the neonatal gut microbiome and the development of atopy, asthma, allergy and obesity in childhood. Expert Opin. Drug Saf. 2019; 18(3): 173-85. https://dx.doi.org/10.1080/14740338.2019.1579795.
  51. Lee J., Romero R., Kim S.M., Chaemsaithong P., Yoon B.H. A new antibiotic reg-imen treats and prevents intra-amniotic infection/inflammation in patients with pre-term PROM. J. Matern. Fetal Neonatal Med. 2016; 29(17): 2727-37. https://dx.doi.org/10.3109/14767058.2015.1103729.
  52. Lamont R.F. Preterm labour prevention clinics. BJOG. 2014; 121(10): 1317-8. https://dx.doi.org/10.1111/1471-0528.12731.

Received 30.11.2020

Accepted 29.01.2021

About the Authors

Valentina F. Dolgushina, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, South Ural Medical University, Ministry of Health of Russia.
Tel.: +7(351)721-46-32. E-mail: dolgushinavf@yandex.ru. ORCID: 0000-0002-3929-7708. 454092, Russia, Chelyabinsk, Vorovsky str., 64.
Ilona V. Kurnosenko, Dr. Med. Sci., Professor of the Department of Obstetrics and Gynecology, South Ural Medical University, Ministry of Health of Russia.
Tel.: +7(351)721-46-32. E-mail: kurnosenko.ilona@gmail.com. 454092, Russia, Chelyabinsk, Vorovsky str., 64.
Marina V. Astashkina, Assistant Professor, Department of Obstetrics and Gynecology, South Ural Medical University, Ministry of Health of Russia.
Tel.: +7(351)721-46-32. E-mail: astashkina-marina83@mail.ru. ORCID: 0000-0003-4756-4500. 454092, Russia, Chelyabinsk, Vorovsky str., 64.

For citation: Dolgushina V.F., Kurnosenko I.V., Astashkina M.V. Intrauterine infection during pregnancy.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 6: 41-46 (in Russian)
https://dx.doi.org/10.18565/aig.2021.6.41-46

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