Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial.
BACKGROUND
The efficacy and safety of repeat doses of prenatal corticosteroids remains uncertain. Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm.


METHODS
In this hospital-based study, 982 women who remained at risk of preterm birth at less than 32 weeks' gestation, 7 or more days after receiving a first course of prenatal corticosteroids, were randomly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone (as Celestone Chronodose), or saline placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks' gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome, use and duration of oxygen and mechanical ventilation, and weight, length, and head circumference at birth and hospital discharge. Statistical analyses were on an intention to treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN48656428.


RESULTS
Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome (33%vs 41%; relative risk 0.82, 95% CI 0.71-0.95, p=0.01) and fewer had severe lung disease (12%vs 20%; relative risk 0.60, 95% CI 0.46-0.79, p=0.0003) than those in the placebo group. In keeping with these benefits, babies exposed to repeat corticosteroids needed less oxygen therapy (p=0.03), and shorter duration of mechanical ventilation (p=0.01). Mean weight, length, and head circumference at birth and hospital discharge did not differ between treatment groups. Z-scores for weight (p=0.04) and head circumference (p=0.03) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups (p=0.29 for weight, p=0.48 for head circumference).


CONCLUSIONS
Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course.
Crowther
Caroline A
CA
Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, South Australia 5006, Australia. caroline.crowther@adelaide.edu.au
Haslam
Ross R
RR
Hiller
Janet E
JE
Doyle
Lex W
LW
Robinson
Jeffrey S
JS
D001623:Betamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D001724:Birth Weight; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000517:prevention & control*; D011295:Prenatal Care; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology / Q000517:prevention & control*
D005938:Glucocorticoids; D003907:Dexamethasone; D001623:Betamethasone