Correspondence: Dr P. Crowley, Academic Centre, Trinity College Dublin, Coombe Womens Hospital, Dublin 8, Ireland.
Numerous investigations have indicated that antenatal corticosteroid administration reduces neonatal morbidity in preterm infants. Despite this, antenatal corticosteroid usage continued to be low on both sides of the Atlantic up to the late 1980s and early 1990s. Antenatal corticosteroid therapy finally came of age in 1995 with the publication of the National Institutes of Health Consensus Statement on effects of corticosteroids for fetal maturation on perinatal outcomes. The randomised trials of antenatal corticosteroid therapy have been based on the use of dexamethasone or betamethasone. However, observational evidence indicates differences in outcome, which may relate to the preparations themselves or to the preservatives included.
While studying the effect of corticosteroids on the initiation of parturition in the ewe, Liggins1 observed that lambs exposed to prenatal corticosteroids appeared viable at an earlier gestational age than might have been expected. Subsequently, a randomised, placebo-controlled trial of betamethasone administration in women who were expected to give birth preterm, found a statistically significant reduction in the frequency of respiratory distress in babies born before 32 weeks' gestation and a five-fold reduction in neonatal mortality among preterm babies born after corticosteroids, compared with placebo administration. In the years since this initial study, numerous investigations have indicated that antenatal corticosteroid administration reduces neonatal morbidity in preterm infants.
Despite this, the recorded use of antenatal corticosteroids during the randomised controlled trials of surfactant therapy for neonatal respiratory distress syndrome (RDS) suggests that corticosteroid usage continued to be low on both sides of the Atlantic up until the late 1980s and early 1990s. Antenatal corticosteroid therapy finally came of age in 1995 with the publication of the National Institutes of Health Consensus Statement on Effects of Corticosteroids for Fetal Maturation on Perinatal Outcomes. This statement concludes ‘Antenatal corticosteroid therapy is indicated for women at risk of premature delivery with few exceptions and will result in a substantial decrease in neonatal morbidity and mortality, as well as substantial savings in health-care costs’2.
Setting Standards of Care for Antenatal Corticosteroid Prescribing
Audits of antenatal corticosteroid practice suggest that it should be possible to expose 80% of babies delivered before 35 weeks to a full or partial course of antenatal corticosteroids (while limiting the use of corticosteroids in pregnancies that eventually go to term)3. The development of more sensitive and specific methods of predicting preterm labour will contribute towards ensuring accurately targeted antenatal corticosteroid therapy.
Single Versus Repeat Courses of Antenatal Corticosteroids
In recent years the practice has arisen of repeating treatment with antenatal corticosteroids in women who remain undelivered more than one week after treatment. The scientific basis to support this practice is weak. Repeated courses of antenatal corticosteroids could result in either immediate or long-term adverse effects not seen with single courses of treatment (Table 1). Observational studies of repeated corticosteroid use give rise to concerns about fetal growth and adrenal suppression with conflicting outcomes with respect to pulmonary and extrapulmonary benefits (Fig. 1).
Table 1. Potential hazards of repeated course of antenatal steroids.
• Impaired glucose tolerance
• Adrenal suppression
• Impaired growth
• Impaired myelination
• Adrenal suppression
These concerns set the scene for a number of randomised controlled trials of single versus repeated courses of antenatal corticosteroids. The first of these multicentre trials reported in 20015. Composite neonatal morbidity occurred in 22.5% in the group receiving a weekly course vs 28.0% of the single course group (OR 0.80, CI 0.59–1.10). There was also a trend towards increased severe intraventricular haemorrhage (IVH) and chorioamnionitis with multiple courses. The results indicate little benefit and some potential adverse effects from repeated courses of corticosteroids.
Betamethasone Versus Dexamethasone
The randomised trials of antenatal corticosteroid therapy have been based on the use of dexamethasone or betamethasone. These corticosteroids are structurally almost identical yet, observational evidence indicates differences in outcome, which may relate to the preparations themselves or to the preservatives used in the commercially available preparations6. This area requires further research.
In summary, recent guidelines from the American College of Obstetricians and Gynecologists (ACOG) recommend that corticosteroids, either betamethasone or dexamethasone, should be administered prior to delivery at gestational ages between 24 and 34 weeks and that there is currently no evidence to support repeated doses.