The Effect of Low Doses of Prednisone on the Prolongation of Pregnancy in Threatened Preterm Birth

The Effect of Low Doses of Intermediate Acting Corticosteroids on the Prolongation of Pregnancy in Threatened Preterm Birth

The goal of this clinical trial is to test the effect of a low dose of prednisone in the prevention of preterm labour in singleton pregnancies. The main question it aims to answer is whether prednisone prolongs singleton pregnancy in threatened preterm birth and reduces mortality and morbidity of newborns without harmful consequences for the mother and the foetus. Participants will be:

• administered low dose of prednisone in a period of a total of 3 weeks on top of standard therapy
• drown blood for standard laboratory tests
• cervical swab and urine for urine culture will be taken, and
• asked to sign Informed Consent The researcher will compare a low dose of prednisone to standard therapy.

Study Overview

• Status: Completed
• Conditions: Preterm Birth
• Intervention / Treatment: Drug: Prednisone 5Mg

Detailed Description

Prematurity is the leading cause of infant mortality and is associated with an increased risk of respiratory, neurological and metabolic disorders in survivors. Approximately 15 million babies are born preterm annually worldwide. Despite the rapid development of pharmacotherapy, there was no significant decline in premature birth (PTB) rates. So far, the most useful intervention for improving neonatal outcomes in premature children has been the antenatal administration of long-acting corticosteroids (CSs). Although the underlying causes of PTB are numerous, it is well established that infection and inflammation represent a highly significant risk factor for spontaneous PTB, characterized by the significant production of inflammatory mediators that lead to the weakening of the foetal membranes, cervical stroma and contraction of the myometrium. There is increasing evidence of the presence of sterile inflammation (intra-amniotic inflammation without the presence of microorganisms) in PTB with both intact membranes and preterm premature rupture of membranes (PPROM). CS and non-steroidal anti-inflammatory drugs (NSAID) are used today to treat most inflammatory diseases. NSAIDs are used as tocolytics. Indomethacin, one of the most commonly used NSAID tocolytics, has been associated with oligohydramnios and premature closure of the foetal ductus arteriosus when used for prolonged periods. As far back as 1972, Liggins and Howie proved that antenatal administration of CS reduces the incidence and severity of respiratory distress syndrome (RDS) and mortality of premature infants. Meta-analyses have confirmed a lower rate of intraventricular haemorrhage and necrotic enterocolitis in premature infants whose mothers received RDS prophylaxis. Therefore, their application proved to be the most useful intervention for improving neonatal outcomes in threatening PTB. Today, CS is a part of standard therapy for treating systemic autoimmune diseases and acts as a suppressor of immune response. Long acting CSs cross the placental barrier and are used to treat the foetus (foetal lupus, congenital adrenal hyperplasia, prevention of respiratory distress syndrome), and intermediate acting drugs are used to treat maternal diseases as they have a low affinity for passing through the placenta. The effect of low doses of intermediate acting corticosteroids on the prolongation of pregnancy in threatened preterm birth has not yet been studied. Given that PTB is a syndrome characterized by a strong inflammatory response, we present the hypothesis that low doses of an intermediate acting CS for 3 weeks after tocolysis and RDS prophylaxis help prolong singleton pregnancy in women with threatening PTB, without harmful consequences for mother and child.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Mostar, Bosnia and Herzegovina, 88000
    • University Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- primiparity, singleton pregnancy between 24+0 and 34+0 weeks, and signs of threatened PTB at admission. Threatened PTB was defined as regular uterine contractions (>4 in 20 minutes or >8 in 60 minutes), with or without bleeding, along with cervical dilation greater than 2 cm or cervical length less than 20 mm, confirmed by transvaginal ultrasound or clinical progression.

Exclusion Criteria:

- contraindications to tocolysis or systemic corticosteroid (CS) therapy, such as intrauterine fetal death, lethal fetal anomaly, abnormal CTG recording, severe preeclampsia or eclampsia, hemodynamically significant bleeding, infection, uncontrolled diabetes, ongoing CS therapy for underlying conditions, severe liver impairment, or preterm prelabour rupture of membranes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard therapy group; Two-day tocolysis and RDS prophylaxis, plus neuroprotection with magnesium sulphate.	Drug: Prednisone 5Mg; Prednisone administered for three weeks. If pregnant women weighs less than 90 kg , she will receive prednisone on altering days instead of every morning for pregnant women weighing more than 90 kg.
Experimental: Low dose of prednisone group; Low-dose prednisone was used for a total of three weeks from the initiation of RDS prophylaxis, following two-day tocolysis and magnesium sulphate for neuroprotection.	Drug: Prednisone 5Mg; Prednisone administered for three weeks. If pregnant women weighs less than 90 kg , she will receive prednisone on altering days instead of every morning for pregnant women weighing more than 90 kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days by which singleton pregnancies with threatened preterm birth are prolonged	Prolongation of singleton pregnancy in threatened preterm birth	10 weeks (from 24th till 34th week of pregnancy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of mortality and morbidity	Change mortality and morbidity of newborns without harmful consequences for the mother and the foetus.	10 weeks (from 24th till 34th week of pregnancy)

Collaborators and Investigators

• Sponsor: University of Mostar

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Actual): November 25, 2024
• Study Completion (Actual): December 2, 2024

Study Registration Dates

• First Submitted: October 21, 2023
• First Submitted That Met QC Criteria: October 21, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 15, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Premature birth, sterile inflammation, prednisone
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 1236/23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No