ETHANOL EFFECTS ON BONE FORMATION IN PREGNANCY

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DESCRIPTION (provided by applicant): It is well known that women are more susceptible to the adverse effects of alcohol than men. An estimated 5-20 percent of American women consume alcohol during pregnancy. Yet, almost no research has examined the effects of ethanol on pregnant and lactating women. We have developed a total enteral nutrition (TEN) -model that supports the additional nutritional demands of pregnancy. Using the TEN system we have made several important observations: First, with constant infusion of ethanol, blood and urine ethanol concentrations of male and non-pregnant female rats cycle between almost zero and over 500 mg/dl with a frequency of one pulse every 5-7 days. Second, the amplitude of these ethanol pulses is markedly reduced (80 percent) in pregnant female rats suggesting that ethanol metabolism is significantly increased in pregnancy. This would be protective since the rate of ethanol metabolism, at a given ethanol intake, determines the maternal blood ethanol concentrations and toxicity. Third, we have observed that undernutrition during pregnancy significantly elevates the amplitude of pulsatile ethanol concentrations to higher levels. This would be expected to increase maternal toxicity. Fourth, chronic ethanol infusion results in reduced bone formation and strength in non-pregnant animals. This effect is reversed by TNFa and IL-1f3 blockers. Fifth ethanol treatment during pregnancy results in significant reductions in trabecular and cortical bone mineral density at the end of gestation, over and above the effects of pregnancy itself Osteoporosis is an area of significant health care and concern. Normally there is no increased risk of osteoporosis with parity. However, we hypothesize that ethanol will inhibit bone formation during the period of high bone turnover in the latter part of pregnancy, increase bone loss during lactation and inhibit the anabolic phase of bone rebuilding which occurs post-partum in the absence of breast feeding or post-weaning in lactating mothers. This may result in permanent deficits in bone mineralization and strength. These effects may be exacerbated by undernutrition. The TEN system will used to determine the effects of ethanol/nutritional interactions on maternal bone in pregnancy and lactation and on skeletal rebuilding post-partum. The role of CYP2E1 and free radicals in the skeletal toxicity of ethanol during these periods will also be studied.