PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates
PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates
There is increasing evidence linking a fetal and early neonatal systemic inflammatory
 response syndrome to the subsequent development of bronchopulmonary dysplasia (BPD) and white
 matter injury (WMI) in very preterm infants. Babies with evidence of adrenal insufficiency
 early in life may not be able to control the inflammatory response and are thereby more
 likely to develop BPD than babies who do not show such evidence of inflammation. We designed
 a randomized controlled trial to test the hypothesis whether very preterm babies at high-risk
 of BPD, treated with low doses of HC during the first 10 days of life, are more likely to
 survive without BPD at 36 weeks of post-menstrual age (PMA), compared to babies treated with
 placebo.
Individual patients and study procedures. Entry criteria: gestational age between 24 weeks
 and 27 weeks + 6 days, babies born to mother with either clinical chorioamnionitis, preterm
 and prelabor rupture of the membranes (PPROM), or preterm labor, written informed consent
 obtained before inclusion and randomization. Exclusion criteria: babies born with birth
 weight below the 3th percentile, PPROM before 22 weeks, major fetal anomaly or congenital
 malformation, mother refusal or inability to provide consent. Stratification: stratum A:
 24-25 weeks and stratum B: 26-27 weeks. Centrally controlled randomization takes place
 between 12 and 48 hours of age and patients assigned to the HC group are treated with 0,5
 mg/kg HC intravenously twice a day for seven days and once a day for the next three days.
 Ibuprofen is only given to babies with persistent ductus arteriosis (PDA)
 echocardiographically confirmed at 24 hours of age or older.

 Outcome variables. The primary outcome is a dichotomous variable: survival without BPD at 36
 weeks PMA. A consistent physiologic definition of BPD will be used by all participating
 centres (Walsh MC, Pediatrics 2004;114:1305-11). Secondary outcome variables include features
 of WMI on MRI performed at 40 weeks PMA and neurodevelopmental outcome at 2-year of corrected
 age. Other outcome variables include death before discharge, BPD at 28 days and 36 weeks,
 duration of mechanical ventilation and O2 supplementation, need for vasopressors, use of
 open-labeled postnatal steroids (HC or dexamethasone), confirmed or suspected early and late
 onset sepsis, PDA, gastrointestinal perforation, NEC, ROP, IVH, biological markers of the
 neonatal inflammatory response syndrome.
Inclusion Criteria:

 -  Gestational age between 24 weeks and 27 weeks + 6 days

 -  Babies born to mother with either clinical chorioamnionitis, preterm and prelabor
 rupture of the membranes (PPROM), or preterm labor

 -  Written informed consent obtained before inclusion and randomization.

 Exclusion Criteria:

 -  Babies born to mothers with birth weight below the 3th percentile

 -  PPROM before 22 weeks

 -  Major fetal anomaly or congenital malformation

 -  Mother refusal or inability to provide consent.