Impact of Antenatal Corticosteroids on Respiratory and Neurodevelopmental Outcomes in the FGR Rabbit Model

Background/Objectives: Antenatal corticosteroids (ACSs) are widely used to improve outcomes in preterm infants, but their effects in the context of fetal growth restriction (FGR) remain incompletely understood. This study investigated the impact of ACSs on pulmonary and neurodevelopmental outcomes using a rabbit mod (K.Z.el) of FGR. Methods: FGR was induced at a gestational age (GA) of 25 days (term 31.5 days) by partial uteroplacental vessel ligation (UPVL) in one uterine horn, with the contralateral horn serving as a control. Dams received intramuscular betamethasone (0.1 mg/kg) or saline 24 and 12 h before expected delivery. At GA 30 days, offspring were delivered by caesarean section and allocated to four groups for pulmonary function testing or neurobehavioral assessment on postnatal day 1, followed by histological analyses of the brain, lungs, and placenta. Results: ACSs improved respiratory mechanics, particularly static and dynamic compliance, in FGR offspring. PND 1 survival showed a concerning pattern, with numerically lower model-estimated survival in both ACS-exposed groups, although the only statistically significant adjusted comparison was between Control/NoACS and FGR/ACS offspring. Neurobehavioral testing showed lower neurosensory performance after ACS exposure within both control and FGR offspring. Lung morphometry and apoptosis were not significantly altered, while neuronal density and astrogliosis showed isolated regional differences. Placental histology showed a higher junctional zone proportion in untreated FGR placentas than in untreated controls. Conclusions: ACSs improved short-term respiratory mechanics without detectable alveolar structural benefit. The observed PND 1 survival pattern and lower neurobehavioral performance warrant cautious interpretation, and these animal findings should not be directly extrapolated to clinical ACS decision-making in FGR pregnancies.