P0918 EFFECTS OF ANTENATAL GLUCOCORTICOID TREATMENT ON GUT ENZYME MATURATION PRIOR TO PRETERM BIRTH

Abstract

Introduction: Glucocorticoid therapy is used prior to preterm birth in part to improve fetal gut maturation and reduce the incidence of gut disorders like necrotising enterocolitis (NEC). The optimal treatment regimen remains debated and limited information is available about the responsiveness of the gut to glucocor-ticoids during the prenatal period. Methods: First, the effects of fetal glucocorticoid infusion were studied in lamb fetuses given saline or physiological doses of cortisol (1–3 mg/kg/day, i.v., n=10) for five days preceding caesarean delivery at 78–89% gestation. Second, the effects of reduced endogenous glucocorticoid secretion were studied in lambs subjected to fetal adrenalectomy from 82–100% gestation (n=9). Finally, the effects of short term pharmacological glucocorticoid treatment were studied in both sheep and baboons (non-human primates) after treatment of the pregnant mother for 2 d with bethamethasone (0.3–0.8 mg/kg, i.m.) at 90% gestation in sheep (n=8) and at 75% gestation in baboons (n=5). After treatment, the small intestine was removed for measurements of the tissue-specific activity (U/g) of brush border enzymes (sucrase, maltase, lactase and the peptidases ApA, ApN and DPP IV) as markers of intestinal differentiation. Results: In control lamb fetuses, proximal intestinal ApN activities and protein contents increased during the last 20% of gestation (+50%, P<0.05), while lactase and DPP IV activities declined (−30%). During late gestation, fetal baboons had higher disaccharidase and lower peptidase activities than lambs, probably reflecting ontogenetic differences in intestinal maturation between the primate and ovine species. Five days of fetal cortisol infusion significantly stimulated, and adrenalectomy inhibited, the normal developmental change in proximal lactase, ApN and DPP IV activities in fetal lambs (P<0.05). In contrast, 2 d of pharmacological bethamethasone treatment had no effect on any brush border enzyme, neither in fetal lambs, nor in fetal baboons, relative to control fetuses. Conclusion: Endogeneous glucocorticoid secretion stimulates intestinal enzyme maturation in prenatal lambs. This effect is not mimicked however, by short-term treatment of pregnant mothers with pharmacological doses of synthetic glucocorticoid, neither in fetal lambs nor in the primate (baboon) model of fetal development. Hence, short term maternal glucocorticoid treatment is unlikely to exert rapid maturational effects on the fetal intestine prior to preterm labour.