Clinical Review & Education

JAMA Network Insights

Management of Gallstone Disease During Pregnancy

Steven J. Schwulst, MD; Moeun Son, MD, MSCI

Symptomatic gallstone disease during pregnancy is common. Acute effective radiation dose from endoscopic retrograde cholangiopan-
cholecystitis is the second most common nonobstetric creatography ranges between 2 and 12 mGy—doses far less than
indication for surgery during pregnancy, occurring in about 1 per 1600 those concerning for deterministic radiation outcomes to the fetus.4
pregnancies. During pregnancy, elevated estrogen increases choles- Pregnant women with symptomatic gallstone disease should be
terol secretion and progesterone reduces bile acid secretion and de- admitted for observation, and surgical consultation should be ob-
lays gallbladder emptying, leading to the supersaturation of bile with tained. Conservative management can initially be attempted for un-
cholesterol and predisposition to gallstone formation. In a prospec- complicated gallstone disease (ie, biliary colic) with bowel rest, in-
tive ultrasonography study of 3200 pregnant patients, new gall- travenous hydration, and pain control. Nonsteroidal anti-
stones were identified in nearly 8% of women by the third trimester, inflammatory drugs are generally avoided during pregnancy because
and 1.2% of them developed symptomatic gallstone disease.1 There- of potential adverse fetal outcomes, and therefore opioids are of-
fore, most clinicians will encounter pregnant patients with sympto- ten used. In cases of biliary colic that fail to respond to conservative
maticcholelithiasis,acutecholecystitis,andgallstonepancreatitiswithin management, cholecystectomy should be offered. The risk for re-
their practice. Unfortunately, the current literature is limited to current symptoms and subsequent hospital admission is high, rang-
retrospective case series and reports, and this has led to varying ing between 38% and 72%, depending on the study. Additionally,
management strategies. In what is to our knowledge the largest popu- relapses are often more severe than prior episodes, and progres-
lation-based data linkage study, including more than 1 million preg- sion to complicated gallstone disease, such as acute cholecystitis,
nancies, 87.3% of women with gallstone disease were managed con- choledocholithiasis, and gallstone pancreatitis, is reportedly as high
servatively, without surgery.2 This is despite evidence suggesting that as 27%.5 Therefore, most studies recommend consideration of cho-
surgicaltreatmenthaslowercomplicationratesthanconservativeman- lecystectomy for recurrent symptomatic biliary colic. In a system-
agement for gallstone disease in pregnancy.3 Given the limitations of atic review6 of 600 laparoscopic cholecystectomies, complicated
the current available data, the purpose of this article is to provide best gallstone disease was reported to lead to preterm labor in about 20%
care practices for the management of gallstone disease during of cases and fetal loss in 10% to 60% of cases. In a cross-sectional
pregnancy. analysis of discharge data from 40 000 pregnant women hospital-
Most pregnant women with gallstones are asymptomatic, mean- ized with gallstone disease, those who underwent cholecystec-
ing gallstones are incidentally found on abdominal imaging. Pa- tomy had significantly lower maternal complication rates (4.3% vs
tients who are asymptomatic require no further evaluation or inter- 16.5%) and fetal complication rates (5.8% vs 16.5%) compared with
vention. Symptomatic gallstone disease presents similarly in those who did not.3 Despite a recent retrospective review suggest-
pregnant and nonpregnant women, typically with biliary colic— ing higher preterm delivery in the third trimester, the preponder-
postprandial epigastric or right upper quadrant pain. ance of evidence shows that pregnant patients with complicated gall-
Pregnancy-associated conditions should first be excluded, be- stone disease should undergo cholecystectomy regardless of
cause they remain the most common source of abdominal pain dur- trimester.
ing pregnancy. The evaluation of nonobstetric causes should then A laparoscopic surgical approach is recommended, with con-
include laboratory tests, such as a complete blood cell count, trans- version to open cholecystectomy reserved for challenging surgical
aminase levels, a total bilirubin level, a serum amylase level, and a cases. A study of 664 pregnant women who underwent cholecys-
lipase level. Regardless of pregnancy status, ultrasonography is the tectomies showed the laparoscopic approach was associated with
first-choice imaging modality for suspected biliary symptoms. Ul- a shorter operative time, a shorter length of hospital stay, and fewer
trasonography is the most useful and sensitive test for detecting postoperative complications. Furthermore, most contemporary stud-
sludge and gallstones, even those as small as 2 mm. It has nearly ies show laparoscopy has lower rates of adverse maternal and fetal
100% sensitivity for detecting gallstones and 95% sensitivity and outcomes when compared with laparotomy for gallstone disease.
specificity for detecting signs of acute cholecystitis. Ultrasonogra- The Society of American Gastrointestinal and Endoscopic Sur-
phy is less sensitive in diagnosing choledocholithiasis. If choledo- geons endorses laparoscopic cholecystectomy as the treatment of
cholithiasis is suspected on the basis of a biliary dilatation on ultra- choice in the pregnant patient with gallstone disease, regardless of
sonography, abnormal liver test results, or pancreatitis, further trimester.7 The decision to proceed with surgical intervention is made
diagnostic modalities should be used. While there are no published after shared decision-making with the patient but should be rec-
guidelines for the use of magnetic resonance cholangiopancreatog- ommended for complicated gallstone disease, regardless of trimes-
raphy during pregnancy, given the safety of magnetic resonance ter. If surgery is planned when the fetus is considered viable, an ob-
imaging in pregnancy, magnetic resonance cholangiopancreatog- stetric care professional should be involved and corticosteroids
raphy is also likely safe. Endoscopic retrograde cholangiopancrea- administered for fetal benefit, for the unlikely but possible need for
tography followed by sphincterotomy and stone extraction for symp- preterm delivery. In addition, fetal heart rate monitoring may assist
tomatic choledocholithiasis is also likely safe, since the median in maternal positioning, cardiorespiratory management, or the

jamasurgery.com (Reprinted) JAMA Surgery Published online September 30, 2020 E1

© 2020 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a UNSW Library User on 10/01/2020

 Clinical Review & Education JAMA Network Insights

Figure. Management of Gallstone Disease During Pregnancy

Review symptoms and history Obtain laboratory studies, including

and perform physical examination Obtain abdominal or right upper complete blood cell count
(assess for presence of Murphy sign, quadrant ultrasonography with differential, liver function
rebound, or guarding) tests, serum amylase, and lipase

Rule out pregnancy-associated

complications, such as preeclampsia,
HELLP syndrome, acute fatty liver
of pregnancy, and cholestasis
of pregnancy

Consider MRCP or ERCP if there Cholelithiasis Complicated gallstone disease

is a concern for choledocholithiasis (presence of gallstones (acute cholecystitis, cholangitis,
(gallstones in the bile duct) within gallbladder) pancreatitis, or ileus)

Laparoscopic cholecystectomy
Asymptomatic Symptomatic with conversion to open procedure
if necessary

No further evaluation Trial of conservative management Failure to improve, progression

with nothing by mouth, IVF, to complicated disease,
and opioid analgesia or recurrent symptoms

ECRP indicates endoscopic retrograde cholangiopancreatography; HELLP, hemolysis, elevated liver enzymes, and a low platelet level; IVF, intravenous fluid; MRCP,
magnetic resonance cholangiopancreatography.

decision to deliver a fetus. If the fetus is previable, it is generally suf- determinant of adverse maternal and fetal outcomes. Patients who
ficient to obtain a fetal heart rate by Doppler auscultation before and present with or progress to complicated gallstone disease are at an
after the procedure. No currently used anesthetic agent has been elevated risk for adverse maternal and fetal outcomes and should
shown to have teratogenic outcomes when used at standard con- undergo laparoscopic cholecystectomy, regardless of trimester
centrations at any gestational age. (Figure). When balancing the potential risks of surgical interven-
In summary, in pregnant women with symptomatic gallstone dis- tion vs expectant management, cholecystectomy is also favored for
ease, progression to complicated gallstone disease is the greatest patients with recurrent uncomplicated gallstone disease.

ARTICLE INFORMATION REFERENCES during pregnancy and lactation. Obstet Gynecol.

Author Affiliations: Division of Trauma and Critical 1. Ko CW, Beresford SA, Schulte SJ, Matsumoto AM, 2017;130(4):e210-e216. doi:10.1097/AOG.
Care, Department of Surgery, Northwestern Lee SP. Incidence, natural history, and risk factors 0000000000002355
University Feinberg School of Medicine, Chicago, for biliary sludge and stones during pregnancy. 5. Jorge AM, Keswani RN, Veerappan A, Soper NJ,
Illinois (Schwulst); Section of Maternal-Fetal Hepatology. 2005;41(2):359-365. doi:10.1002/hep. Gawron AJ. Non-operative management of
Medicine, Department of Obstetrics, Gynecology, 20534 symptomatic cholelithiasis in pregnancy is
and Reproductive Sciences, Yale School of 2. Ibiebele I, Schnitzler M, Nippita T, Ford JB. associated with frequent hospitalizations.
Medicine, New Haven, Connecticut (Son). Outcomes of gallstone disease during pregnancy: J Gastrointest Surg. 2015;19(4):598-603. doi:10.
Corresponding Author: Steven J. Schwulst, MD, a population-based data linkage study. Paediatr 1007/s11605-015-2757-8
Division of Trauma and Critical Care, Department of Perinat Epidemiol. 2017;31(6):522-530. doi:10.1111/ 6. Nasioudis D, Tsilimigras D, Economopoulos KP.
Surgery, Northwestern University Feinberg School ppe.12406 Laparoscopic cholecystectomy during pregnancy:
of Medicine, 676 N St Clair St, Ste 650, Chicago, IL 3. Kuy S, Roman SA, Desai R, Sosa JA. Outcomes a systematic review of 590 patients. Int J Surg.
60611 (s-schwulst@northwestern.edu). following cholecystectomy in pregnant and 2016;27:165-175. doi:10.1016/j.ijsu.2016.01.070
Published Online: September 30, 2020. nonpregnant women. Surgery. 2009;146(2):358- 7. Pearl JP, Price RR, Tonkin AE, Richardson WS,
doi:10.1001/jamasurg.2020.3683 366. doi:10.1016/j.surg.2009.03.033 Stefanidis D. SAGES guidelines for the use of
Conflict of Interest Disclosures: None reported. 4. Committee on Obstetric Practice. Committee laparoscopy during pregnancy. Surg Endosc. 2017;31
opinion No. 723: guidelines for diagnostic imaging (10):3767-3782. doi:10.1007/s00464-017-5637-3

E2 JAMA Surgery Published online September 30, 2020 (Reprinted) jamasurgery.com

© 2020 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a UNSW Library User on 10/01/2020