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

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.

• Authors: Jose Galaz, Roberto Romero, Marcia Arenas-Hernandez, Bogdan Panaitescu, Robert Para, Nardhy Gomez-Lopez
• Journal: Journal of perinatal medicine (J Perinat Med) Vol. 49 Issue 7 Pg. 897-906 (Sep 27 2021) ISSN: 1619-3997 [Electronic] Germany
• PMID: 33878254 (Publication Type: Journal Article)
• Copyright: © 2021 Walter de Gruyter GmbH, Berlin/Boston.

Chemical References

• Alarmins
• Anti-Inflammatory Agents
• HMGB1 Protein
• Betamethasone

Topics

• Alarmins
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Betamethasone (therapeutic use)
• Chorioamnionitis (chemically induced, physiopathology)
• Female
• HMGB1 Protein
• Injections, Subcutaneous
• Kaplan-Meier Estimate
• Mice
• Mice, Inbred C57BL
• Pregnancy
• Premature Birth (etiology, prevention & control)
• Treatment Outcome