Without exception, cholesterol gallstone is more common among women than men in every population studied. This consistent and conspicuous gender difference starts during puberty, continues throughout the childbearing years, but fades alter menopause. Biliary sludge, a newly described ultrasonographic diagnosis, is a mixture of cholesterol monohydrate crystals and other precipitates within the gallbladder, and it is regarded as a precursor form of gallstones. Sludge is frequently found in pregnant women, although the risk factors for the development of gallbladder sludge and stones during pregnancy have not been clearly defined. The investigators propose a prospective investigation of gallstones and biliary sludge that develop during pregnancy to accomplish several specific aims. First, they will determine the incidence rate of biliary sludge and gallstones during pregnancy and compare this rate to a nonpregnant control sample. Second, they will look for factors predictive of the development of biliary sludge gallstones during pregnancy, including obesity, age, hyperinsulinemia, hyperlipidemia and serum estradiol and progesterone levels. Lastly, they will examine predictors of persistent gallstones and biliary sludge disease in the postpartum period by following women until one year after delivery.
They aim to include as many as 7,280 women in this study. They will be recruited from the prenatal and genealogy clinics of Madigan Army Hospital. Development of gallstones and biliary sludge will be defined by ultrasonographic examination of the gallbladder contents performed at pre-specified intervals during gestation and postpartum, and at an equivalent time in the non-pregnant control group. A variety of analytic methods will be used to achieve these specific aims of this study. Gallstone and biliary sludge are common in women and represent major causes of morbidity. The investigators state that this study will add new and important insight into the risk factors leading to these outcomes and affecting their natural history. They further note that this information, in turn, may lead to effective strategies for treatment and prevention of these conditions.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Serrano, Jose
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Mathew, Lisa K; Ko, Cynthia (2015) Dietary fat and protein intake are not associated with incident biliary sludge and stones during pregnancy. JPEN J Parenter Enteral Nutr 39:124-8
Ko, Cynthia W; Napolitano, Peter G; Lee, Sum P et al. (2014) Physical activity, maternal metabolic measures, and the incidence of gallbladder sludge or stones during pregnancy: a randomized trial. Am J Perinatol 31:39-48
Wong, Alan C; Ko, Cynthia W (2013) Carbohydrate intake as a risk factor for biliary sludge and stones during pregnancy. J Clin Gastroenterol 47:700-5
Ko, Cynthia W; Beresford, Shirley A A; Schulte, Scott J et al. (2008) Insulin resistance and incident gallbladder disease in pregnancy. Clin Gastroenterol Hepatol 6:76-81
Elliott, Dawn; Patience, Troy; Boyd, Emily et al. (2006) Fetal growth curves for an ethnically diverse military population: the American Institute of Ultrasound in Medicine-accredited platform experience. Mil Med 171:508-11
Ko, Cynthia W; Schulte, Scott J; Lee, Sum P (2005) Biliary sludge is formed by modification of hepatic bile by the gallbladder mucosa. Clin Gastroenterol Hepatol 3:672-8
Ko, Cynthia W; Beresford, Shirley A A; Schulte, Scott J et al. (2005) Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy. Hepatology 41:359-65
Haigh, W G; Lee, S P (2001) Identification of oxysterols in human bile and pigment gallstones. Gastroenterology 121:118-23
Ko, C W; Beresford, S A; Alderman, B et al. (2000) Apolipoprotein E genotype and the risk of gallbladder disease in pregnancy. Hepatology 31:18-23
Ko, C W; Sekijima, J H; Lee, S P (1999) Biliary sludge. Ann Intern Med 130:301-11

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