Cellular immune responses in amniotic fluid of women with a sonographic short cervix

Jose Galaz 1 , 2 , 3 , Roberto Romero 1 , 4 , 5 , 6 , 7 , 8 , Yi Xu 1 , 2 , Derek Miller 1 , 2 , Dustyn Levenson 1 , 2 , Robert Para 1 , 2 , Aneesha Varrey 1 , 2 , Richard Hsu 9 , Anna Tong 9 , Sonia S. Hassan 2 , 10 , 12 , Chaur-Dong Hsu 1 , 2 , 10 ,  and Nardhy Gomez-Lopez 1 , 2 , 11
  • 1 Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, USA
  • 2 Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, USA
  • 3 Department of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
  • 4 Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, USA
  • 5 Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, USA
  • 6 Center for Molecular Medicine and Genetics, Wayne State University, Detroit, USA
  • 7 Detroit Medical Center, Detroit, USA
  • 8 Department of Obstetrics and Gynecology, Florida International University, Miami, USA
  • 9 Wayne State University School of Medicine, Detroit, USA
  • 10 Department of Physiology, Wayne State University School of Medicine, Detroit, USA
  • 11 Department of Immunology, Microbiology, and Biochemistry, Wayne State University School of Medicine, Detroit, USA
  • 12 Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, USA
Jose Galaz
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
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, Roberto Romero
  • Corresponding author
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
  • Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
  • Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA
  • Detroit Medical Center, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA
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, Yi Xu
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
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, Derek Miller
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
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, Dustyn Levenson
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
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, Robert Para
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
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, Aneesha Varrey
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
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, Richard Hsu, Anna Tong, Sonia S. Hassan
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
  • Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA
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, Chaur-Dong Hsu
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
  • Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
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and Nardhy Gomez-Lopez
  • Corresponding author
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA
  • Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
  • Department of Immunology, Microbiology, and Biochemistry, Wayne State University School of Medicine, Detroit, MI, USA
  • Email
  • Search for other articles:
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Abstract

Objectives

A sonographic short cervix is one of the strongest predictors of preterm delivery. However, the cellular immune composition of amniotic fluid in women with a short cervix has not yet been described. Herein, we determined cellular and soluble immune responses in amniotic fluid from pregnant women with a mid-trimester asymptomatic short cervix.

Methods

Amniotic fluid samples (n=77) were collected from asymptomatic women with a cervical length between 15 and 25 mm (n=36, short cervix) or ≤15 mm (n=41, severely short cervix) diagnosed by ultrasound. Flow cytometry and multiplex measurement of cytokines/chemokines were performed.

Results

(1) The cellular immune composition of amniotic fluid did not differ between women with a severely short cervix (≤15 mm) and those with a short cervix 15–25 mm; (2) amniotic fluid concentrations of multiple cytokines/chemokines were higher in women with a severely short cervix (≤15 mm) than in those with a short cervix 15–25 mm; (3) the cellular immune composition of amniotic fluid did not differ between women with a severely short cervix (≤15 mm) who ultimately underwent preterm delivery and those who delivered at term; and (4) amniotic fluid concentrations of IL-2, but not other immune mediators, were increased in women with a severely short cervix (≤15 mm) who ultimately delivered preterm compared to those who delivered at term.

Conclusions

Women with a severely short cervix (≤15 mm) have increased concentrations of pro-inflammatory mediators in the amniotic cavity; yet, these do not translate to changes in the cellular immune response.

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    Romero, R, Espinoza, J, Chaiworapongsa, T, Kalache, K. Infection and prematurity and the role of preventive strategies. Semin Neonatol 2002;7:259–74. https://doi.org/10.1053/siny.2002.0121.

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    Goncalves, LF, Chaiworapongsa, T, Romero, R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev 2002;8:3–13. https://doi.org/10.1002/mrdd.10008.

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    Romero, R, Espinoza, J, Goncalves, LF, Kusanovic, JP, Friel, LA, Nien, JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med 2006;11:317–26. https://doi.org/10.1016/j.siny.2006.05.001.

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    Romero, R, Espinoza, J, Goncalves, LF, Kusanovic, JP, Friel, L, Hassan, S. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007;25:21–39. https://doi.org/10.1055/s-2006-956773.

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    Romero, R, Gomez-Lopez, N, Winters, AD, 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;47:915–31. https://doi.org/10.1515/jpm-2019-0297.

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    Oh, KJ, Romero, R, Park, JY, Lee, J, Conde-Agudelo, A, Hong, JS, et al. Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency. Am J Obstet Gynecol 2019;221:140. e1–18. https://doi.org/10.1016/j.ajog.2019.03.017.

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    Oh, KJ, Romero, R, Park, JY, Hong, JS, Yoon, BH. 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 2019;47:516–27. https://doi.org/10.1515/jpm-2019-0003.

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    Yoon, BH, Romero, R, Park, JY, Oh, KJ, Lee, J, Conde-Agudelo, A, et al. 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;221:142 e1–e22. https://doi.org/10.1016/j.ajog.2019.03.018.

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    Oh, KJ, Romero, R, Park, JY, Kang, J, Hong, JS, Yoon, BH. A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes. J Perinat Med 2019;47:288–303. https://doi.org/10.1515/jpm-2018-0351.

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