Neurodevelopmental impacts of betamethasone in the late preterm period: a randomized controlled trial in mice

Antenatal (AN) betamethasone (BM) exposure has been shown to disrupt offspring behavior and neuroanatomy in several animal models; however, impacts of administration in the late preterm period (LPP) are unknown. This study aims to determine if exposure to BM in the LPP 1) induces behavioral changes and 2) alters cerebral structural anatomy. This blinded placebo controlled randomized trial was conducted in a murine model of CD-1 mice. Pups were exposed to BM on postnatal day (PND) 5, at which time mouse brain development is equivalent to that of humans at 34-36 weeks’ gestation. In order to discern the impact of transplacental passage of BM, a group of gravid mice was exposed to BM on gestation day (GD) 18. Four and six CD-1 gravid mice were included in the PN and AN groups, respectively. Gravid mice in the AN group and pups in the PN group were randomly assigned to receive BM or placebo (p) in a 1:1 ratio. ANBM mice and PNBM pups received 0.1 mg and 0.03 mg of BM subcutaneously (SC) on GD 18 and PND 5, respectively. ANp and PNp mice received a saline solution SC. Pups from both groups (n=112) were subjected to behavioral tests on PND 21-50. On PND 61, a structural magnetic resonance imaging of the brain was performed on sedated mice(n=80). Within the AN and PN groups, outcomes of behavioral tests and brain region volumes were compared between the BM and p subgroups using Kruskal-Wallis or Student t tests in R Studio, with a statistical significance threshold of p< 0.05. No differences were identified between the BM and p subgroups for the Open Field, Novel Object recognition, and Social Interaction tests. Within the AN group, a small but statistically significant difference in the frontal cortex volume was identified (ANBM mean volume (mv) 10.3 mm3, ANp mv 9.62 p =0.03). No other differences in total brain volume or in the volume of brain regions were identified. In a murine model of the LPP, BM exposure did not alter behavior or cerebral structural anatomy. While these findings are reassuring, human studies will be necessary to confirm the safety of BM in the LPP.View Large Image Figure ViewerDownload Hi-res image Download (PPT)