Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perinatal/Neonatal Case Presentation
  • Published:

Perinatal/Neonatal Case Presentation

Initial experience using Sivelestat to manage preterm labor with a bulging fetal membrane in pregnant women

Abstract

Intrauterine infection and inflammation are recognized as major contributors to the onset of preterm labor. We describe two cases of severe preterm labor with bulging membrane that were treated by intravenous injection of Sivelestat, a neutrophil elastase inhibitor. Ritodrine hydrochloride and magnesium sulfate were intravenously administered for tocolysis, and ampicillin was provided as an antibiotic. Urinary trypsin inhibitor (UTI) was administered transvaginally. Sivelestat was infused intravenously at 4.8 mg kg−1 day−1 through the maternal vein. No side effects were observed. Levels of interleukin (IL)-6 and IL-8 in amniotic fluid decreased, and gestations were prolonged without complications for >1 week. Two healthy infants were delivered. Our experience suggests that multidrug therapy with Sivelestat offers a new therapeutic strategy for preterm labor, but further investigations of the indications, administration period and dosage are required.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Romero R, Mazor M . Infection and preterm labor. Clin Obstet Gynecol 1998; 31: 553–584.

    Article  Google Scholar 

  2. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH . Fetal medicine foundation second trimester screening group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med 2007; 357: 462–469.

    Article  CAS  Google Scholar 

  3. Haga Y, Ogawa M . Neutrophil elastase inhibitor(ONO-5046.Na) decreases production of proinflammatory cytokines by lipopolysaccharide-stimulated human monocytes. Res Commun Mol Pathol Pharmacol 1997; 98: 243–248.

    CAS  PubMed  Google Scholar 

  4. Iams JD, Creasy RK . Preterm labor and delivery In: Creasym RK, Resnik R, Iams JD (eds). Maternal-Fetal Medicine Principles and Practice, 5th edn. Saunders: Pennsylvania, 2004, pp 623–662.

    Google Scholar 

  5. Chauleur C, Rochigneux S, Seffert P, Chene G, Billiemaz K, Collet F . Neonatal outcomes and four-year follow-up after spontaneous or iatrogenic preterm prelabor rupture of membranes before 24 weeks. Acta Obstet Gynecol Scand 2009; 88: 801–806.

    Article  Google Scholar 

  6. King J, Flenady V . Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev 2002; (4): CD000246.

  7. Hutzal CE, Boyle EM, Kenyon SL, Nash JV, Winsor S, Taylor DJ et al. Use of antibiotics for the treatment of preterm parturition and prevention of neonatal morbidity: a metaanalysis. Am J Obstet Gynecol 2008; 199: 620.e1–620.e8.

    Article  Google Scholar 

  8. Matsuda Y, Kouno S, Nakano H . The significance of interleukin-6 concentrations in cervicovaginal fluid: its relation to umbilical cord plasma and the influence of antibiotic treatment. J Perinat Med 2000; 28: 129–132.

    Article  CAS  Google Scholar 

  9. Kanayama N, el Maradny E, Yamamoto N, Tokunaga N, Maehara K, Terao T . Urinary trypsin inhibitor: a new drug to treat preterm labor: a comparative study with ritodrine. Eur J Obstet Gynecol Reprod Biol 1996; 67: 133–138.

    Article  CAS  Google Scholar 

  10. Matsuda Y, Yunohara N . Effects of urinary trypsin inhibitor in patients at risk for premature labor with a bulging fetal membrane. Fetal Diagn Ther 2002; 17: 69–74.

    Article  Google Scholar 

  11. Helmig BR, Romero R, Espinoza J, Chaiworapongsa T, Bujold E, Gomez R et al. Neutrophil elastase and secretory leukocyte protease inhibitor in prelabor rupture of membranes, parturition and intra-amniotic infection. J Matern Fetal Neonatal Med 2002; 12: 237–246.

    Article  CAS  Google Scholar 

  12. Tromp G, Kuivaniemi H, Romero R, Chaiworapongsa T, Kim YM, Kim MR et al. Genome-wide expression profiling of fetal membranes reveals a deficient expression of proteinase inhibitor 3 in premature rupture of membranes. Am J Obstet Gynecol 2004; 191: 1331–1338.

    Article  CAS  Google Scholar 

  13. Chowdhury MA, Kuivaniemi H, Romero R, Edwin S, Chaiworapongsa T, Tromp G . Identification of novel functional sequence variants in the gene for peptidase inhibitor 3. BMC Med Genet 2006; 23 7: 49.

    Article  Google Scholar 

  14. Tamakuma S, Ogawa M, Aikawa N, Kubota T, Hirasawa H, Ishizaka A et al. Relationship between neutrophil elastase and acute lung injury in humans. Pulm Pharmacol Ther 2004; 17: 271–279.

    Article  CAS  Google Scholar 

  15. Masaoka N, Watanabe M, Nakajima Y . The effects of sivelestat sodium hydrate on uterine contraction and the concentration of maternal and fetal blood cytokines in a sheep model of intra-amniotic infection induced by lipopolysaccharide. J Matern Fetal Neonatal Med 2011; 24: 1013–1018.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Y Nakajima.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakajima, Y., Masaoka, N. Initial experience using Sivelestat to manage preterm labor with a bulging fetal membrane in pregnant women. J Perinatol 32, 466–468 (2012). https://doi.org/10.1038/jp.2011.132

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2011.132

Keywords

Search

Quick links