Pregnancy and gallbladder disease

Gallbladder disease is a highly prevalent disease in western countries as the consequence of several genetic, biochemical, and environmental factors. The most important factor involved in gallstone formation is an increased biliary secretion of cholesterol from the liver, producing cholesterol-supersaturated bile. Subsequently, biliary cholesterol precipitates as cholesterol monohydrate mi- crocrystals, which grow and agglomerate, with the formation of macroscopic stones in the gallbladder.

The prevalence of gallbladder disease differs in several populations. For example, in the United States, 10%– 15% of the adult population has gallstones. In other populations, such as those of Latin-American countries, the prevalence of gallstones is higher, up to 50% in adult women. This sex dominance implies some risk in pregnancy. In fact, gallbladder disease is the second most common indication for nonobstetric surgical intervention in pregnancy, with 31% attacks of biliary colic in women with gallstones.

The most common causes of gallbladder disease in pregnancy are gallstones and biliary sludge. Pregnancy is associated with an increased frequency of gallstones. Studies in the United States have demonstrated gallstones in 5%–12% of pregnant women. The risk of gallstones is also thought to increase with the number of pregnancies. The incidence of gallbladder disease in pregnancy is approximately 0.05%– 0.3%, and asymptomatic gallstones occur in 3.5%–10% of all pregnancies.

In a study by the University of Southern California, ultrasonography initially revealed biliary sludge in 15% and gallstones in 6% of the pregnant women examined. New sludge or stones were found in 30% and 2% of the women, respectively, at the end of their pregnancies. Postpartum sonography revealed the disappearance of the sludge in 61% of those women who had previously demonstrated sludge, and the disappearance of stones in 28% of those who had had stones. Therefore, the study concluded that some patients who have symptomatic cholelithiasis during pregnancy may not have it after delivery. Unfortunately, about 50% of women presenting with symptoms will have a recurrence of symptoms before delivery. However, recent data derived from a German population do not support this hypothesis.

Gallstones during pregnancy, especially when complicated by pancreatitis, has traditionally been managed conservatively, with cholecystectomy performed selectively during the postpartum period. However, untreated gallstone pancreatitis has an associated maternal mortality rate as high as 37%. The rate of fetal wastage is 38% for fetuses over 20 weeks or 500 g.

Risk factors

Many risk factors have been associated with gallbladder disease. Probably some of the most important are obesity (and its consequence, the metabolic syndrome), diet, and some new hormones. However, in pregnancy, other risk factors have been described, including body mass index, prenatal weight gain, prenatal physical activity, dietary fat, iron supplementation, age, parity, a history of gallbladder disease, and serum cholesterol. After multiple regression analyses the most important predictors of cholelithiasis in pregnancy were a history of gallbladder disease, body mass index, and prenatal physical activity. When other variables were evaluated, such as fasting, postprandial gallbladder volume, and the gallbladder ejection fraction, only the gallbladder ejection fraction and the number of previous pregnancies were significant factors related to new gallstones and biliary sludge formation in the pregnant group. Recent information from a well-designed prospective study indicates that prepregnancy obesity and serum leptin are strong risk factors for pregnancy associated gallbladder disease.


Transient changes in the biliary system during pregnancy increase the risk of gallbladder disease. These changes include gallbladder stasis and the secretion of bile with increased amounts of cholesterol and

decreased amounts of chenodeoxycholic acid. An increase in the lithogenic index of bile is observed in both the hepatic and gallbladder bile, in concert with an increase in cholesterol secretion.

The size of the total bile acid pool also increases by about 50% during pregnancy, although the relative percentages of the various bile acids change. The percentage of cholic acid increases in association with an increase in synthesis, whereas the percentages of chenodeoxycholic acid and deoxycholic acid decrease. These changes in the composition of gallbladder bile revert rapidly after delivery, even in patients with gallstones. Other changes in bile composition and gallbladder function support gallstone formation during pregnancy, such as the decreased number of enterohepatic cycles.

Sex steroids cause changes in the biliary lipid composition, and gallbladder hypomotility leads to an increase in cholesterol gallstone formation. In vitro models suggest that progesterone inhibits the contractility of the gastrointestinal smooth muscle. In animals pretreated with progesterone, the reduction in the contractile responsiveness to agonists was similar to that seen in pregnant animals. Other findings include an enhanced clearance of lowdensity lipoprotein cholesterol (increased source of the cholesterol secreted in the bile) and the inhibition of acyl coenzyme A: cholesterol acyltransferase.

Fasting and residual gallbladder volumes are larger in pregnant women who are in the second and third trimesters than in the normal population. Incomplete postprandial gallbladder emptying has also been reported in pregnant women. Another mechanism involved in the production of gallstones in the general population is related to apolipoprotein E,31 but apoE4 appears to have little or no association with the development of biliary sludge and/or gallstones in pregnancy.


The symptoms of gallbladder disease in pregnancy mimic those in the nonpregnant state. They include the classic colicky or stabbing pain in the right upper quadrant and/or epigastric area, which can radiate to the right flank, scapula, and shoulder. Other symptoms of gallbladder disease include anorexia, nausea, vomiting, dyspepsia, low-grade fever, tachycardia, and often, fatty-food intolerance. Differential diagnoses may include viral hepatitis (alcoholic hepatitis is rare in pregnancy), pyelonephritis, duodenal ulcer, acute pancreatitis, pulmonary embolism, acute myocardial infarction, sepsis, and specific pregnancy-related disorders such as preeclampsia, the HELLP (hemolysis, elevated liver function, low platelets) syndrome, and fatty liver disease of pregnancy. Pregnant women who present with acute epigastric pain during pregnancy make diagnosis difficult when they initially present for care, secondary to the displacement of abdominal organs during pregnancy.

The imaging method of choice in diagnosing gallstones, both in pregnancy and in the nonpregnant state, is ultrasound. Ultrasound is about 95% effective in diagnosing gallbladder disease and avoids radiation exposure altogether.


Initial management includes the discontinuation of oral intake, intravenous fluid replacement, analgesia, and the administration of antibiotics when signs of infection are present.

Gallbladder disease is an important issue for the gastroenterologist and hepatologist, particularly its prevention and treatment. These topics require ongoing research. An experienced team consisting of a gastroenterologist, obstetrician, and surgeon should be involved in the management of women with this undesirable effect of pregnancy.

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