Effect of oestradiol and progesterone replacement on bronchopulmonary dysplasia in extremely preterm infants.
OBJECTIVE
To study whether postnatal replacement of oestradiol and progesterone may help to prevent bronchopulmonary dysplasia (BPD).


METHODS
This randomised placebo-controlled double-blind study enrolled 83 infants of <29 weeks gestational age and 1000 g birth weight requiring mechanical ventilation within 12 h after birth. Oestradiol (2.5 mg/kg/day) and progesterone (22.5 mg/kg/day) were given by continuous intravenous infusion of a standard lipid emulsion (15 ml/kg/day) in the replacement group (ESTRA-PRO). The placebo group received the same lipid emulsion without oestradiol or progesterone. A replacement period of at least 2 weeks but not >4 weeks was strived for and defined as "according to protocol". The primary outcome variable was the incidence of BPD or death.


RESULTS
The median birth weight was 670 g (min-max 400-990 g) and the gestational age 25 weeks (23.1-28.1 weeks). The incidence of BPD or death was 48% in the placebo group and 44% in the ESTRA-PRO group (p = 0.38, one-sided testing, intention to treat analysis). In infants treated according to protocol, 32% (9 of 28) in the placebo group and 14% (3 of 21) in the ESTRA-PRO group developed BPD (p = 0.08).


CONCLUSIONS
Replacement of oestradiol and progesterone was not effective for prevention of BPD or death in extremely preterm born infants. Better-powered trials are needed to evaluate this new approach.
Trotter
A
A
Section of Neonatology and Pediatric Critical Care Medicine, Children's Hospital, University of Ulm, Ulm, Germany. andreas.trotter@web.de
Maier
L
L
Kron
M
M
Pohlandt
F
F
D001724:Birth Weight; D001997:Bronchopulmonary Dysplasia / Q000097:blood / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008297:Male; D011374:Progesterone / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
D011374:Progesterone; D004958:Estradiol