Impact of antenatal corticosteroids on subcortical volumes in preterm infants at term-equivalent age: A retrospective observational study

Objective: Antenatal corticosteroids (ACS) is a well-established treatment for women at risk of preterm birth that improves neonatal outcomes. However, several concerns have been raised regarding the potential long-term adverse effects of ACS on the offspring's developing brain. Here we investigated the association between ACS and subcortical segmental volumes in preterm infants at term-equivalent age. Study design: This retrospective observational study was conducted using the clinical data of preterm singleton infants born between 22(0/7) and 33(6/7) gestational weeks at Nagoya University Hospital in 2014-2020. Subcortical volumes of the bilateral thalami, caudate nuclei, putamens, pallidums, hippocampi, amygdalae, and nuclei accumbens were evaluated using an automated segmentation tool, Infant FreeSurfer, and compared between neonates exposed to a single course of ACS (n = 46) and those who were not (n = 13) by multiple linear regression analysis (covariates: postmenstrual age at magnetic resonance imaging, infant sex, and gestational age at birth). We compared each subcortical volume stratified by gestational age at birth (<28 vs. >= 28 gestational weeks). Results: Multivariate analyses revealed significantly smaller volumes in the bilateral amygdalae (left, p < 0.03; right, p < 0.03) and caudate nuclei (left, p < 0.03; right, p = 0.04) in neonates with ACS. Significantly smaller volumes in these regions were observed only in neonates born at 28 weeks of gestation or later. Conclusions: ACS was associated with smaller volumes of the bilateral amygdalae and caudate nuclei at term- equivalent age. This association was observed exclusively in infants born at 28 weeks of gestation or later.