Home Medicine Betamethasone as a potential treatment for preterm birth associated with sterile intra-amniotic inflammation: a murine study
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Betamethasone as a potential treatment for preterm birth associated with sterile intra-amniotic inflammation: a murine study

  • Jose Galaz , Roberto Romero EMAIL logo , Marcia Arenas-Hernandez , Bogdan Panaitescu , Robert Para and Nardhy Gomez-Lopez EMAIL logo
Published/Copyright: April 20, 2021
Journal of Perinatal Medicine
From the journal Journal of Perinatal Medicine Volume 49 Issue 7

Abstract

Objectives

Preterm birth remains the leading cause of perinatal morbidity and mortality worldwide. Preterm birth is preceded by spontaneous preterm labor, which is commonly associated with sterile intra-amniotic inflammation; yet, no approved treatment exists for this clinical condition. Corticosteroids are the standard of care to improve neonatal outcomes in women at risk of preterm birth. Herein, we first validated our model of alarmin-induced preterm birth. Next, we investigated whether treatment with betamethasone could prevent preterm birth resulting from sterile intra-amniotic inflammation in mice.

Methods

Under ultrasound guidance, the first cohort of dams received an intra-amniotic injection of the alarmin high-mobility group box-1 (HMGB1, n=10) or phosphate-buffered saline (PBS, n=9) as controls. A second cohort of dams received HMGB1 intra-amniotically and were subcutaneously treated with betamethasone (n=15) or vehicle (n=15). Dams were observed until delivery, and perinatal outcomes were observed.

Results

Intra-amniotic HMGB1 reduced gestational length (p=0.04), inducing preterm birth in 40% (4/10) of cases, of which 100% (4/4) were categorized as late preterm births. Importantly, treatment with betamethasone extended the gestational length (p=0.02), thereby reducing the rate of preterm birth by 26.6% (from 33.3% [5/15] to 6.7% [1/15]). Treatment with betamethasone did not worsen the rate of neonatal mortality induced by HMGB1 or alter weight gain in the first three weeks of life.

Conclusions

Treatment with betamethasone prevents preterm birth induced by the alarmin HMGB1. This study supports the potential utility of betamethasone for treating women with sterile intra-amniotic inflammation.

Keywords: alarmins; antenatal corticosteroids; high-mobility group box-1 (HMGB1); pregnancy; prematurity; preterm labor
Corresponding authors: Nardhy Gomez-Lopez, MSc, PhD, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, 275 E. Hancock, Detroit, MI 48201, USA, Phone: +1 (313) 577 8904, E-mail: ; and Roberto Romero, MD, D. Med. Sci., 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, Wayne State University, Hutzel Women’s Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA, Phone: +1 (313) 993 2700, Fax: +1 (313) 993 2694, E-mail:

Funding source: National Institutes of Health

Award Identifier / Grant number: HHSN275201300006C

Funding source: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Funding source: Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health

  1. Research funding: This research was supported, in part, by the Perinatology Research Branch (PRB), 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 (NICHD/NIH/DHHS), and, in part, with federal funds from the NICHD/NIH/DHHS under Contract No. HHSN275201300006C. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors have no conflicts of interest to declare.

  4. Informed consent: Not applicable.

  5. Ethical approval: All procedures were approved by the Institutional Animal Care and Use Committee (IACUC) (Protocol No. A-07-03-15 and 18-03-0584).

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Received: 2021-02-16
Accepted: 2021-03-31
Published Online: 2021-04-20
Published in Print: 2021-09-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Introduction to the cesarean section articles
  4. Highlight Section: Cesarean Section
  5. Three kinds of caesarean sections: the foetal/neonatal perspective
  6. The neonatal respiratory morbidity associated with early term caesarean section – an emerging pandemic
  7. Vaginal birth after cesarean (VBAC): fear it or dare it? An evaluation of potential risk factors
  8. Nationwide implementation of a decision aid on vaginal birth after cesarean: a before and after cohort study
  9. Induction of labor at 39 weeks and risk of cesarean delivery among obese women: a retrospective propensity score matched study
  10. Cervical ripening after cesarean section: a prospective dual center study comparing a mechanical osmotic dilator vs. prostaglandin E2
  11. An evidence-based cesarean section suggested for universal use
  12. Online survey on uterotomy closure techniques in caesarean section
  13. Analysis of cesarean section rates in two German hospitals applying the 10-Group Classification System
  14. Reviews
  15. Pregnancy in incarcerated women: need for national legislation to standardize care
  16. Imaging diagnosis and legal implications of brain injury in survivors following single intrauterine fetal demise from monochorionic twins – a review of the literature
  17. Mini Review
  18. Professionally responsible management of the ethical and social challenges of antenatal screening and diagnosis of β-thalassemia in a high-risk population
  19. Opinion Paper
  20. Teaching and training the total percutaneous fetoscopic myelomeningocele repair
  21. Corner of Academy
  22. Chronic hypertension in pregnancy: synthesis of influential guidelines
  23. Original Articles
  24. The effects of pre-pregnancy obesity and gestational weight gain on maternal lipid profiles, fatty acids and insulin resistance
  25. Determination of organic pollutants in meconium and its relationship with fetal growth. Case control study in Northwestern Spain
  26. Betamethasone as a potential treatment for preterm birth associated with sterile intra-amniotic inflammation: a murine study
  27. Diagnostic accuracy of modified Hadlock formula for fetal macrosomia in women with gestational diabetes and pregnancy weight gain above recommended
  28. Vasa previa: when antenatal diagnosis can change fetal prognosis
  29. Mode of delivery and adverse short- and long-term outcomes in vertex-presenting very preterm born infants: a European population-based prospective cohort study
  30. Short Communication
  31. Reference ranges for sphingosine-1-phosphate in neonates
https://doi.org/10.1515/jpm-2021-0049
Keywords for this article
alarmins; antenatal corticosteroids; high-mobility group box-1 (HMGB1); pregnancy; prematurity; preterm labor

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Introduction to the cesarean section articles
  4. Highlight Section: Cesarean Section
  5. Three kinds of caesarean sections: the foetal/neonatal perspective
  6. The neonatal respiratory morbidity associated with early term caesarean section – an emerging pandemic
  7. Vaginal birth after cesarean (VBAC): fear it or dare it? An evaluation of potential risk factors
  8. Nationwide implementation of a decision aid on vaginal birth after cesarean: a before and after cohort study
  9. Induction of labor at 39 weeks and risk of cesarean delivery among obese women: a retrospective propensity score matched study
  10. Cervical ripening after cesarean section: a prospective dual center study comparing a mechanical osmotic dilator vs. prostaglandin E2
  11. An evidence-based cesarean section suggested for universal use
  12. Online survey on uterotomy closure techniques in caesarean section
  13. Analysis of cesarean section rates in two German hospitals applying the 10-Group Classification System
  14. Reviews
  15. Pregnancy in incarcerated women: need for national legislation to standardize care
  16. Imaging diagnosis and legal implications of brain injury in survivors following single intrauterine fetal demise from monochorionic twins – a review of the literature
  17. Mini Review
  18. Professionally responsible management of the ethical and social challenges of antenatal screening and diagnosis of β-thalassemia in a high-risk population
  19. Opinion Paper
  20. Teaching and training the total percutaneous fetoscopic myelomeningocele repair
  21. Corner of Academy
  22. Chronic hypertension in pregnancy: synthesis of influential guidelines
  23. Original Articles
  24. The effects of pre-pregnancy obesity and gestational weight gain on maternal lipid profiles, fatty acids and insulin resistance
  25. Determination of organic pollutants in meconium and its relationship with fetal growth. Case control study in Northwestern Spain
  26. Betamethasone as a potential treatment for preterm birth associated with sterile intra-amniotic inflammation: a murine study
  27. Diagnostic accuracy of modified Hadlock formula for fetal macrosomia in women with gestational diabetes and pregnancy weight gain above recommended
  28. Vasa previa: when antenatal diagnosis can change fetal prognosis
  29. Mode of delivery and adverse short- and long-term outcomes in vertex-presenting very preterm born infants: a European population-based prospective cohort study
  30. Short Communication
  31. Reference ranges for sphingosine-1-phosphate in neonates
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