Are we prescribing multiple courses of antenatal corticosteroids? A survey of practice in the UK



Brocklehurst et al. (Vol 106, September 1999)1 ought to be congratulated for their short communication on this contentious issue and their proposed randomised trial looking at the effects of antenatal steroids on neonatal mortality and children's neurodevelopment.

Prematurity is the major cause of neonatal death and antenatal corticosteroid administration is one of the main, sometimes the only positive intervention that the obstetrician is able to offer to improve the outcome of a premature infant. In 1972 Liggins and Howie2 described the beneficial effects of corticosteroid administration to accelerate lung maturity in premature infants. Since then corticosteroids have been used to reduce morbidity and mortality in preterm neonates with great success.

The pharmacological effects of corticosteroid treatment seem to disappear in seven days and this has prompted clinicians to use multiple doses in a bid to further its beneficial role in pulmonary maturity in the absence of clear cut proof of its efficacy. The potential risks of multiple doses of steroids are possible suppression of fetal hypothalamic adrenal axis, growth retardation or neurodevelopmental delay. Newborn infants whose mothers had received multiple corticosteroids for lung maturity, exhibited an appropriate response to external stresses such as infection, allaying the fear about fetal hypothalamic adrenal axis suppression3. Animal studies have shown retardation in brain development with the use of antenatal steroids, however the animals used were small, the dosage used was higher and for prolonged duration with a shorter period of gestation4. A recent post hoc nonrandomised analysis of 710 neonates enrolled in the North American Thyrotrophin-Releasing Hormone Trial4, showed that more than two courses of antenatal steroids was associated with a small decrease in fetal growth, did not improve survival and there was no change in the head circumference.

Corticosteroids are powerful regulators of differentiation and maturation in the central nervous system. They regulate maturation of oligodendrocytes and hence myelination and can alter brain development. Most studies agree that the effects of steroids correspond to their dose. Till the results of the proposed randomised trials are available obstetricians need to temper their enthusiasm for repeated administration of antenatal corticosteroids.