Elevated plasma corticotrophin release factor levels and in utero meconium passage

Intrauterine meconium (MEC) passage and aspiration may result in significant newborn morbidity, though there is little understanding of the physiologic mechanisms for MEC passage. We hypothesized that stress induces fetal MEC passage via corticotrophin releasing factor (CRF), a known mediator of colonic motility in adult rats. Pregnant rats at e22 were subjected to acute hypoxia or normoxia for 35 min, after which rats were anesthetized and fetuses operatively delivered. Amniotic fluid bilirubin and intestinal alkaline phosphatase were measured as markers for MEC passage, and fetal and maternal plasma CRF and corticosterone levels determined. Hypoxic stress induced defecation in all dams and provoked visible MEC passage in all fetuses. Amniotic fluid bilirubin content was significantly higher in hypoxic fetuses versus controls (1.064 +/- 0.101 versus 0.103 +/- 0.003 O.D. at 410 nm) and intestinal alkaline phosphatase was consistently elevated in MEC stained amniotic fluid. Hypoxia significantly increased plasma CRF (maternal, 82 +/- 5 to 196 +/- 14 pg/mL; fetal, 284 +/- 15 to 1523 +/- 185 pg/mL) and corticosterone (maternal, 417 +/- 50 to 1150 +/- 50 ng/mL; fetal, 96 +/- 5 to 182 +/- 10 ng/mL) compared with controls. In view of the known action of CRF in adult colonic motility, these results suggest that hypoxic stress-mediated MEC passage in term fetal rats is mediated by a CRF dependent pathway.