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Grant Abstract

Grant Number: 5R21HL093532-02
PI Name: KRUMMEL, DEBRA ANN
Project Title: DHA, INFLAMMATION, AND INSULIN SENSITIVITY IN OBESE PREGNANT WOMEN

Abstract: Obesity prevalence is increasing worldwide and with the difficulty to treat this condition, the need for early intervention is urgent. Obesity in pregnancy is rapidly becoming a major obstetric complication since it increases the risk of gestational diabetes and pre-eclampsia, and predisposes the mother for later metabolic and cardiovascular disease. A common problem for the baby is fetal overgrowth, which is associated with traumatic birth injuries and the development of the metabolic syndrome in childhood or later in life. The obese, pregnant woman has increased serum levels of pro-inflammatory cytokines and low circulating levels of adiponectin leading to decreased insulin sensitivity, which has been suggested to link obesity in pregnancy to metabolic and cardiovascular disease later in life. Fetal growth is determined by placental nutrient supply and our preliminary data show that placental nutrient transport is increased in obesity. Up-regulation of placental nutrient transporters in obesity may be caused by the abnormal maternal metabolic profile, since high insulin and pro-inflammatory cytokines and low adiponectin have been shown to stimulate placental nutrient transport. Approximately one third of all women enter pregnancy being obese and despite the serious adverse consequences for the health of the woman and her child, no specific treatment is currently available. The aim of our study is to supplement the diet of obese pregnant women with docosahexaenoic acid (DHA), a safe, low cost, readily available dietary component that we have shown is extremely low in the diet of our mid-western urban population (10% of recommended levels for pregnancy). This omega-3 fatty acid has been shown to have a significant impact on improving insulin sensitivity and circulating levels of pro-inflammatory cytokines and adiponectin in non-pregnant obese women. DHA has been studied extensively as a dietary supplement in pregnancy as a potential mechanism to improve cognitive function in children. However the effect of DHA maternal metabolic status and placental function has not been previously reported. We hypothesize that DHA supplementation will improve maternal insulin sensitivity, reduce pro-inflammatory cytokines, increase circulating adiponectin, down-regulate placental nutrient transport and reduce fetal growth. Our approach for this pilot study will be to recruit 90 obese (BMI 30-45), pregnant women in mid gestation and randomize these subjects into placebo or DHA treatment (800 mg/day) groups. Subjects will be studied again in late gestation after 12 weeks of supplementation. In Aim 1 we will determine the effect of DHA supplementation on maternal inflammatory status and insulin sensitivity. In Aim 2 we will establish the impact of DHA supplementation in obese pregnant women on placental nutrient transport and fetal growth. We propose that improved maternal metabolic status and reduced nutrient delivery to the fetus will result in a significant improvement in the long term health of women and their children. PUBLIC HEALTH RELEVANCE: Obesity in pregnancy is a major concern for women's health since no specific treatment is currently available for this common condition and obesity in pregnancy increases the risk for pregnancy complications and predisposes both the woman and her child to develop diabetes and cardiovascular disease later in life. This project will study the effect of a safe dietary supplement, the long chain polyunsaturated fatty acid DHA, on the obese woman's metabolic status during pregnancy, the transport of nutrients to the fetus by the placenta and the size of the baby at birth. The proposed research is relevant to public health because we expect that it may lead to the development of a novel treatment, which could prevent a number of perinatal complications as well as metabolic disease later in life in women and their children.

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