Antenatal glucocorticoid therapy is administered to women in threatened preterm labour to prevent neonatal morbidity and mortality. Specifically, this reduces the risk of respiratory lung disease, intraventricular haemorrhage and death. Long-term follow up of preterm-born children indicates that neurodevelopmental impairment is reduced in those exposed to steroids compared to those unexposed. As 50% of preterm children will experience problems with motor function, language, reading and/or speech by school age, the neuro-protection conferred by this therapy appears to have profound benefits.
But how safe are these steroids? Evidence suggests that glucocorticoids can interact with proteins that are critical for normal brain development, such as the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3 and NT4). To assess the impact of antenatal steroid therapy on cortisol and neurotrophin levels, we have analysed cord blood from very preterm (≤32 weeks, n=145), late preterm (33-36 weeks, n=121) and term infants (37+ weeks, n=136). Protein expression was determined using ELISA. Results indicate that cortisol was differentially affected by antenatal steroid therapy, depending on the gestational age at the time of exposure. While cortisol increased with gestational age, steroid therapy in late preterm, but not very preterm infants, was associated with a reduction in cord blood cortisol concentrations. These gestation-specific changes in cortisol concentrations were associated with altered NT3, NT4 and BDNF levels.
These data suggest that the beneficial effects of antenatal steroids on neurodevelopment may not be uniform across gestation. In very preterm infants, improved neurodevelopmental outcome following steroid exposure is likely to be secondary to decreased respiratory morbidity. In late preterm infants, where the risk of adverse respiratory outcome is reduced, the steroid-induced reductions in neurotrophins may adversely affect neurodevelopment. These findings warrant further investigation.