Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation

Abstract

Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n = 9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24 h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P < 0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E2. SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.