Preterm birth Pregnancy and Childbirth Preterm labour and delivery
Conditions
Interventions
Site-stratified individual randomization with permuted blocks of 12 will be used. The computer-generated randomization sequence will be prepared centrally at WHO by staff not involved in the trial. Al
Sponsors
World Health Organization
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 10/04/2025: The population of interest is women with singleton or multiple pregnancy at 34+0 weeks to 36+5 weeks and a high probability of late preterm birth (which extends up to 36 weeks 6 days). High probability of late preterm birth is defined as birth expected between 12 hours and 7 days Inclusion criteria (all to be met): 1. Gestational age from 34 weeks 0 days to 36 weeks 5 days 2. High probability of late preterm birth (up to 36+6 weeks) defined as birth expected between 12 hours and 7 days after randomization as a result of: 2.1. Membrane rupture without preterm labour (where preterm labour is defined as at least 6 regular uterine contractions/ hr and at least one of the following: cervical dilatation of =3 cm or effacement =75%). OR 2.2. Preterm labour with intact membranes, defined as at least 6 regular contractions/hr and at least one of the following: (i) cervix =3cm dilated or (ii) 75% effaced; OR 2.3. Planned delivery by induction of labour or caesarean section between 24 hours and 7 days, as deemed necessary by the provider. An induction must be scheduled to start by 36+5 weeks at the latest, whereas a caesarean delivery must be scheduled by 36+6 weeks at the latest 3. Singleton or multiple pregnancies, where the foetus/es (or at least one foetus in a multiple pregnancy) is/are confirmed alive by doppler or ultrasonography 4. Women with no clinical signs of severe infection (as per obstetric care physician’s assessment) 5. Women willing and able to provide consent (or if a minor, provides assent and guardian provides consent) Women recruited to the main trial will be invited to participate in the substudy on the pharmacokinetics and pharmacodynamics. Therefore, inclusion and exclusion criteria will be the same for the sub-study. However, women with severe anemia (Hb <7 mg/dL) or having received blood/blood product transfusion in <=7d before enrolment in the ACTION-III trial will be excluded. Previous participant inclusion criteria: The population of interest is women with singleton or multiple pregnancy at 34+0 weeks to 36+5 weeks and a high probability of late preterm birth (which extends up to 36 weeks 6 days). High probability of late preterm birth is defined as birth expected between 12 hours and 7 days Inclusion criteria (all to be met): 1. Gestational age from 34 weeks 0 days to 36 weeks 5 days 2. High probability of late preterm birth (up to 36+6 weeks) defined as birth expected between 12 hours and 7 days after randomization as a result of: 2.1. Membrane rupture without preterm labour (where preterm labour is defined as at least 6 regular uterine contractions/ hr and at least one of the following: cervical dilatation of =3 cm or effacement =75%). OR 2.2. Preterm labour with intact membranes, defined as at least 6 regular contractions/hr and at least one of the following: (i) cervix =3cm dilated or (ii) 75% effaced; OR 2.3. Planned delivery by induction of labour or caesarean section between 24 hours and 7 days, as deemed necessary by the provider. An induction must be scheduled to start by 36+5 weeks at the latest, whereas a caesarean delivery must be scheduled by 36+6 weeks at the latest 3. Singleton or multiple pregnancies, where the foetus/es (or at least one foetus in a multiple pregnancy) is/are confirmed alive by doppler or ultrasonography 4. Women with no clinical signs of severe infection (as per obstetric care physician’s assessment) 5. Women willing and
Exclusion criteria
Exclusion criteria: 1. Ruptured membranes with cervix dilated =3 cm or effaced =75%, or with more than 6 contractions per hour (or both) 2. Cervical dilation =8 cm with intact membranes 3. Clinical suspicion or evidence of clinical chorioamnionitis or severe infection, as per obstetric care physician assessment 4. Evidence of non-reassuring foetal status requiring immediate delivery 5. Major or lethal congenital foetal anomaly identified 6. No prior ultrasound-based estimate of gestational age available and immediate ultrasound examination is not possible 7. Any systemic corticosteroid use during the current pregnancy (outside of trial) 8. Unwilling or unable to provide consent or assent (including due to active labour) 9. Currently a participant in another clinical trial related to maternal and neonatal health, or previously participated in any ACTION trial 10. Any other clinical indication where the treating clinician considers corticosteroids to be contraindicated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stillbirth (post randomization) OR neonatal death within 72 hours of birth OR use of respiratory support within 72 hours of birth or until discharge from hospital, whichever is earlier. Use of respiratory support defined as any one of the following: (i) mechanical ventilation (ii) continuous use of CPAP for 12 hours or more with an FiO2 =0.4 at any time (iii) continuous use of supplementary oxygen for 24 hours or more with an FiO2 =0.4 at any time | — |
Secondary
| Measure | Time frame |
|---|---|
| Newborn: Efficacy outcomes: 1. Neonatal death, defined as the death of a live birth by 28 completed days of life 2. Early neonatal death, defined as the death of a live birth by 7 completed days of life 3. Need for resuscitation at birth, defined as the use of positive pressure ventilation for >1 min at birth 4. Severe respiratory distress (SRD) within 72 hours after birth or until discharge from hospital, whichever is earlier, defined as any of the following clinical signs for at least 12 h: respiratory rate =70/min, chest indrawing, grunting, or SpO2 <90% 5. Death or high settings for CPAP or mechanical ventilation: stillbirth OR neonatal death in 72h OR mechanical ventilation in 72 h OR need for very high CPAP settings (=8 cm water pressure and =0.7 FiO2) in 72 h 6. Cause-specific mortality, ascertained by two physicians with dissenting opinions settled by a third Safety outcomes: 1. Clinically suspected neonatal sepsis (=7 days), defined as new onset of at least two (or more) of the following signs at the same time between birth and 7 days: 1.1. Stopped feeding well 1.2. Severe chest in-drawing (or rise in respiratory support after 24 hours) 1.3. Fever (body temperature of 38 °C or greater) 1.4. Hypothermia (body temperature less than 35.5 °C) 1.5. Movement only when stimulated or no movement at all 1.6. Convulsions 2. Neonatal hypoglycaemia, defined as blood glucose by point of care glucometer or lab value < 45 mg% at 2, 6, 12, 24 or 36 h, or detected anytime < 36 h based on a test because of clinical suspicion requiring correction by IV fluids Health service utilization outcomes: 1. Admission to special newborn care unit, defined as any admission in the special newborn care unit during the first 3 days 2. Total days of hospital stay during birth hospitalization 3. Any parenteral antibiotic use, defined as parenteral antibiotics administered to the newborn before 7 days of life Maternal Safety outcomes: 1. Possible maternal bacterial infe | — |
Countries
Bangladesh, India, Kenya, Nigeria, Pakistan
Contacts
Public ContactAyesha De Costa
Outcome results
None listed