Background
Benefits of antenatal corticosteroids
Concerns about antenatal corticosteroids
Dose-related effects of antenatal corticosteroids
Dose reduction of antenatal corticosteroids
Aims of the trial
Methods/design
Study design
Setting
Inclusion criteria
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Age ≥ 18 years
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Singleton pregnancy
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First betamethasone injection already performed
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Gestational age < 32 weeks at first betamethasone injection
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Informed consent form has been obtained by the investigating obstetrician or mid-wife
Exclusion criteria
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They had already received a full course of betamethasone.
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The first injection has been given by the intravascular route
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In case of preterm labor:
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○ Cervical dilatation at or greater than 4 cm, or
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○ Ultrasonographic cervical length at or greater than 20 mm
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Any chromosomal aberrations and/or major fetal malformations
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Poor understanding of the French language
Study interventions
Study procedures (Fig. 1)
Recruitment
Allocation of treatment and blinding
Unblinding procedures
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the DRCD in a situation other than an emergency during the work day and during working hours, addressed to the DRCD’s project referent.
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the poison centre of Fernand Widal Hospital, in the case of an emergency (see emergency situations requiring unblinding), on weekends, bank holidays, when the DRCD is closed and when unblinding cannot be carried out at the DRCD
Women follow-up
Neonatal follow-up
Long-term children follow-up
Outcome measures
Primary outcome measure
Secondary outcome measures
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Respiratory distress syndrome defined within the first 72 h as the use of continuous positive airway pressure and/or supplemental oxygen during at least 24 h, or the use of mechanical ventilation.
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Transient tachypnea of the newborn defined as a need for continuous positive airway pressure and/or supplemental oxygen, resolving within 24 h.
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Outcomes related to the severity of RDS:
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○ Highest appropriate fractional inspired oxygen (FiO2),
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○ Maximum appropriate Mean Airway Pressure (MAP),
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○ Use and duration of mechanical ventilation,
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○ Use and duration of oxygen therapy,
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○ Need for oxygen therapy after 36 weeks post conception.
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Outcomes related to betamethasone impact on other prematurity-induced complications:
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○ Neonatal death before discharge*,
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○ Admission to neonatal intensive care unit,
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○ Use of inotropic support including dopamine, epinephrine, dobutamine, and norepinephrine,
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○ Pneumothorax,
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○ Patent ductus arteriosus requiring either medical or surgical treatment,
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○ Bronchopulmonary dysplasia at 36 weeks of PMA (need for continuous positive airway pressure or supplemental oxygen, or mechanical ventilation),
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○ NEC and grade according to Bell classification [49],*
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○ IVH and grade according to the Papile classification [50],*
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○ Cystic periventricular leukomalacia,
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○ Use of postnatal steroids (either inhaled or systemic),
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○ Retinopathy of prematurity requiring anti-VEGF treatment or laser*,
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○ Length of hospital stay before the first discharge home,
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○ Survival without severe RDS, IVH grade 3 and 4, NEC grade ≥ 2, or retinopathy of prematurity treated by anti-VEGF or laser.
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Outcomes related to potential adverse events of betamethasone
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○ Birth weight at birth,
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○ Head circumference at birth,
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○ Body length at birth,
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○ Suspected or confirmed early onset sepsis treated using antibiotics during 7 days,
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○ Hypoglycaemia requiring oral or IV glucose administration or glucagon within 7 days.
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Data collection and management
Confidentiality and data handling
Statistical analysis
Sample size
Analysis population
Interim analysis
Final analyses
Subgroup analyses
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Gestational age at birth (born before 28 weeks, between 28 and 32 weeks, and after 32 weeks)
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Gender of the newborn
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The primary analysis, using the confidence interval for the difference between full-dose and half-dose.
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The following secondary analysis: death, IVH grade 3 and 4, NEC grade ≥ 2, or retinopathy of prematurity treated by anti-VEGF or laser, survival without severe RDS, IVH grade 3 and 4, NEC grade ≥ 2, or retinopathy of prematurity treated by anti-VEGF or laser, using 2-sided tests, as stated above.