Placental Transfer and Fetal Effects of Maternal Sodium ß-Hydroxybutyrate Infusion in the Baboon

Abstract

ABSTRACT: We examined the effects of maternal sodium ß-hydroxybutyrate (NaBOHB) on the primate fetus to investigate the impact of ketosis not associated with acidosis on fetal metabolism. After a loading dose (600 mg/ kg), NaBOHB was infused for 70 min (300 mg/kg hr) into the maternal femoral vein of eight pregnant baboons, and placental transfer and fetal and maternal metabolic changes were observed during an acute experimental protocol. Maternal arterial levels rose from 0.70 ± 0.21 to 5.42 ± 0.93 mM (p<0.001), and fetal arterial levels from 0.34 ± 0.09 to 2.76 ± 0.64 mM (p<0.01). A maternalfetal gradient of approximately 2:1 was observed in both baseline and steady-state infusion conditions and is similar to the human maternal-fetal ketone gradient. This is in contrast to the sheep where significantly higher gradients have been described. The elevated lactate, from 1.90 ± 0.34 to 2.88 ± 0.54 mM (p<0.05) and somewhat decreased pO₂ values in the fetus from 54.8 ± 8.9 to 45.0 ± 3.8 mm Hg (p>0.05<0.1), without change in oxygen consumption (2.00 ± 0.28 versus 1.73 ± 0.15 mM/min) are features common to conditions of increased levels of fetal energy substrate. NaBOHB does not appear to contribute to oxidative energy metabolism of the whole fetus but may contribute to lipid stores. The significance of higher levels of BOHB in the primate fetus compared to the sheep fetus remains to be elucidated.