Undernutrition Before Mating in Ewes Impairs the Development of Insulin Resistance During Pregnancy

OBJECTIVE: To assess the effects of periconceptional undernutrition on maternal adaptation of insulin-dependent metabolism during pregnancy. METHODS: Romney ewes were randomly assigned to receive normal nutrition (n=12) or undernutrition before (from 60 days before until mating, n=7), after (2 days before to 30 days after mating, n=6) or before and after mating (from 60 days before to 30 days after mating, n=10). Insulin sensitivity was measured by hyperinsulinaemic-euglycaemic clamp at 65 days of gestation (term=147 days). Lamb growth rate was measured in late gestation by chronically implanted growth catheters and weight at 133 days of gestation. RESULTS: Ewes undernourished before or both before and after mating failed to develop the insulin resistance of pregnancy seen in normally nourished ewes. Ewes undernourished after mating showed intermediate insulin sensitivity. This was not related to plasma concentrations of pregnancy-related hormones, but was related to insulin kinetics. There was an inverse relationship between insulin sensitivity and fetal growth, with ewes that were most insulin sensitive having smaller, more slowly growing lambs (highest compared with lowest tertile for insulin sensitivity: fetal weight 3.5 +/- 0.3 compared with 4.5 +/- 0.1 kg, P=.02; growth rate 2.0 +/- 0.2 compared with 2.6 +/- 0.2 mm.day-1, P=.05). CONCLUSION: Maternal undernutrition before conception impairs adaptation of insulin-related metabolism during pregnancy in ways that affect fetal growth. This suggests a key mechanism whereby prepregnancy nutritional status influences pregnancy outcome. (Obstet Gynecol 2009;114:869-76)