Single Antenatal Exposure to Ciclesonide Reduces Long-Term Cardiac Structural and Functional Alterations Compared to Currently Approved Synthetic Corticosteroids.

Synthetic corticosteroids (sCS), Dexamethasone (Dex) or Betamethasone (Beta) are administered to mothers at risk of preterm birth to promote fetal organ maturation and reduce neonatal morbidity. Repeated prenatal or postnatal sCS exposure is associated with long term negative cardiovascular and neurologic outcomes. We previously demonstrated that repeated postnatal exposure to Ciclesonide (Cic) promotes lung maturation and minimizes birthweight or white matter reductions observed with repeated Dex administration. The long-term cardiac effects of a single antenatal sCS exposure are poorly understood. This study demonstrates that a single prenatal exposure to sCS reduces birth weight in a graded manner, with Dex>Beta > Cic. In aged animals Dex exposure led to an increase in body weight, Beta showed a trend towards a decrease, while Cic was indistinguishable from controls. Structural, histological, and electrophysiological cardiac abnormalities consistent with bradycardia and QTc prolongation were exclusively observed in aged Dex-exposed animals. Adult cardiac ion channel expression was decreased with Dex>Beta > Cic, indicating that the antenatal environment plays a pivotal role in short-term and long-term cardiac reprogramming. A single antenatal exposure to Cic minimizes adverse cardiometabolic effects compared to Dex or Beta suggesting that Cic may be a safer alternative for preterm birth compared to the current sCS clinical regimen.