Nicolette A Hodyl1, Tara M Crawford2, Lorna McKerracher3, Andrew Lawrence4, Julia B Pitcher2, Michael J Stark5. 1. Robinson Research Institute, School of Medicine, University of Adelaide, South Australia, Australia; Department of Neonatal Medicine, Women's and Children's Hospital, Adelaide, South Australia, Australia. Electronic address: Nicolette.hodyl@adelaide.edu.au. 2. Robinson Research Institute, School of Medicine, University of Adelaide, South Australia, Australia. 3. Department of Neonatal Medicine, Women's and Children's Hospital, Adelaide, South Australia, Australia. 4. Microbiology and Infectious Diseases, SA Pathology, Adelaide, South Australia, Australia. 5. Robinson Research Institute, School of Medicine, University of Adelaide, South Australia, Australia; Department of Neonatal Medicine, Women's and Children's Hospital, Adelaide, South Australia, Australia.
Abstract
BACKGROUND: Neurotrophins are proteins critically involved in neural growth, survival and differentiation, and therefore important for fetal brain development. Reduced cord blood neurotrophins have been observed in very preterm infants (<32weeks gestation) who subsequently develop brain injury. Antenatal steroid exposure can alter neurotrophin concentrations, yet studies to date have not examined whether this occurs in the late preterm infant (33-36weeks gestation), despite increasing recognition of subtle neurodevelopmental deficits in this population. AIM: To assess the impact of antenatal steroids on cord blood neurotrophins in late preterm infants following antenatal steroid exposure. STUDY DESIGN: Retrospective analysis. SUBJECTS: Late preterm infants (33-36weeks; n=119) and term infants (37-41weeks; n=129) born at the Women's and Children's Hospital, Adelaide. OUTCOME MEASURES: Cord blood neurotrophin-3 (NT-3), NT-4, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) concentrations measured by ELISA. RESULTS: Cord blood NT-4 and NGF were increased at term compared to the late preterm period (p<0.001), while BDNF and NT-3 were not different. In the late preterm period, cord blood NT-3 was reduced when antenatal steroids were administered >24h prior to delivery (p<0.01). CONCLUSION: This study identified an association between reduced cord blood NT-3 and antenatal steroid exposure in the late preterm period. The reduced NT-3 may be a consequence of steroids inducing neuronal apoptosis, thereby reducing endogenous neuronal NT3 production, or be an action of steroids on other maternal or fetal NT-3 producing cells, which may then affect neuronal growth, differentiation and survival. Regardless of the specific mechanism, a reduction in NT-3 may have long term implications for child neurodevelopment, and emphasizes the ongoing vulnerability of the fetal brain across the full preterm period.
BACKGROUND: Neurotrophins are proteins critically involved in neural growth, survival and differentiation, and therefore important for fetal brain development. Reduced cord blood neurotrophins have been observed in very preterm infants (<32weeks gestation) who subsequently develop brain injury. Antenatal steroid exposure can alter neurotrophin concentrations, yet studies to date have not examined whether this occurs in the late preterm infant (33-36weeks gestation), despite increasing recognition of subtle neurodevelopmental deficits in this population. AIM: To assess the impact of antenatal steroids on cord blood neurotrophins in late preterm infants following antenatal steroid exposure. STUDY DESIGN: Retrospective analysis. SUBJECTS: Late preterm infants (33-36weeks; n=119) and term infants (37-41weeks; n=129) born at the Women's and Children's Hospital, Adelaide. OUTCOME MEASURES: Cord blood neurotrophin-3 (NT-3), NT-4, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) concentrations measured by ELISA. RESULTS: Cord blood NT-4 and NGF were increased at term compared to the late preterm period (p<0.001), while BDNF and NT-3 were not different. In the late preterm period, cord blood NT-3 was reduced when antenatal steroids were administered >24h prior to delivery (p<0.01). CONCLUSION: This study identified an association between reduced cord blood NT-3 and antenatal steroid exposure in the late preterm period. The reduced NT-3 may be a consequence of steroids inducing neuronal apoptosis, thereby reducing endogenous neuronal NT3 production, or be an action of steroids on other maternal or fetal NT-3 producing cells, which may then affect neuronal growth, differentiation and survival. Regardless of the specific mechanism, a reduction in NT-3 may have long term implications for child neurodevelopment, and emphasizes the ongoing vulnerability of the fetal brain across the full preterm period.