Investigation of possible effect of maternal CDP-choline treatment on newborn rat lung maturation

Bronchopulmonary Dysplasia (BPD) is one of the most common complications in preterm birth. Currently, BPD in newborns can be prevented by antenatal betamethasone injection to pregnant women having the risk of preterm birth. However, maternal steroids are inadequate in some cases and alternative treatments are required. CDP-choline, an endogenous compound formed during phospholipid synthesis, was shown to enhance phospholipid levels and alveolarization in newborn rats subjected to hyperoxic lung injury. However, the effect of CDP-choline on hyperoxic lung injury in newborns when applied to pregnant rats during prenatal period has not yet been investigated. Additionally, the potential effect of CDP-choline has not been compared with that of a steroid and the effect of CDP-choline and steroid combination has not been evaluated. In the light of this information, we aimed to investigate CDP-choline's effect by maternal administration on lung maturation in newborns with hyperoxic lung injury for the first time in the literature. Pregnant Spraque-Dawley rats were grouped to receive betamethasone and/or CDP-choline injections. Pups born to these dams were than subjected to hyperoxic lung injury to investigate the effect of maternally-administered betamethasone and/or CDP-choline on lung phospholipid levels, apoptotic cell death and alveolarization. We found in our study that prenatal administration of CDP-choline enhanced the levels of total phospholipids and phosphatidylcholine, improved alveolarization, and it reduced apoptotic cell death in newborns subjected to hyperoxic lung injury.In addition, lung phospholipid levels were greater and apoptotic cell death was potently reduced in newborns whose dams received the combination of betamethasone and CDP-choline, compared to the administration of these agents alone. These findings show that the combination of betamethasone and CDP-choline provides greater benefit in reducing newborn hyperoxic lung injury and suggest the clinical utility of this combination in newborns with BPD. Key Words: Bronchopulmonary Dysplasia, betamethasone, CDP-choline, phospholipid, newborn rat