Gallstones in Pregnancy - UpToDate

4/22/2019 Gallstones in pregnancy - UpToDate
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Gallstones in pregnancy
Author: David C Brooks, MD
Section Editors: Stanley W Ashley, MD, Vincenzo Berghella, MD
Deputy Editors: Wenliang Chen, MD, PhD, Vanessa A Barss, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2019. | This topic last updated: Apr 15, 2019.
INTRODUCTION
Gallstones are more common during pregnancy due to decreased gallbladder motility and increased
cholesterol saturation of bile. Gallstone disease during pregnancy has been associated with
increased risk of preterm birth, maternal morbidity and readmission, as well as neonatal morbidity [1].
In pregnant women with biliary colic, supportive care will lead to resolution of symptoms in most
cases, but the symptoms frequently recur later in pregnancy. Some pregnant women will require an
invasive procedure because of repeated attacks of biliary colic or because of complicated gallstone
disease: acute cholecystitis, choledocholithiasis, cholangitis, or gallstone pancreatitis. After acute
appendicitis, acute cholecystitis is the second most common nonobstetrical indication for surgery in
pregnant women (table 1).
Issues related primarily to gallstones in pregnant women will be reviewed here. Detailed discussions
on biliary disease in the nonpregnant population, which may also apply to pregnant women, are
available separately.
● (See "Gallstones: Epidemiology, risk factors and prevention".)

● (See "Approach to the management of gallstones".)
● (See "Overview of gallstone disease in adults".)
● (See "Acute calculous cholecystitis: Clinical features and diagnosis".)
● (See "Treatment of acute calculous cholecystitis".)
● (See "Acalculous cholecystitis: Clinical manifestations, diagnosis, and management".)
● (See "Functional gallbladder disorder in adults".)
● (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management".)
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PATHOPHYSIOLOGY
Increased levels of reproductive hormones during pregnancy induce a variety of physiologic changes
in the biliary system, which promote gallstone formation [2-4]:
● Estrogen increases cholesterol secretion and progesterone reduces bile acid secretion, which
ultimately causes bile to become supersaturated with cholesterol. A relative overproduction of
hydrophobic bile acids, such as chenodeoxycholate, reduces the ability of bile to solubilize
cholesterol.
● Progesterone slows gallbladder emptying, which further promotes the formation of stones by
causing bile stasis.
These changes normalize one to two months following delivery.
Symptoms related to gallstones develop when the gallbladder contracts in response to hormonal or
neural stimulation, usually due to a fatty meal. Contraction forces stones (or possibly sludge or
microlithiasis) against the gallbladder outlet or cystic duct opening, leading to increased intra-
gallbladder pressure and pain. The stones often fall back from the cystic duct as the gallbladder
relaxes, with amelioration of symptoms.
PERSONAL RISK FACTORS
The major independent risk factor for gallstones is prepregnancy obesity [5,6]. Although the
prevalence of gallstones has been reported to be higher in multiparous versus nulliparous women [7-
9], increasing age and obesity as well as genetic background may account for the persistence and
further growth of the stones that develop during pregnancy [10].
In a prospective study, dietary fat and protein intake during pregnancy did not appear to affect
women's risk of forming biliary sludge and stones during pregnancy or up to four to six weeks
postpartum [11]. Likewise, efforts to decrease the likelihood of stones and sludge developing during
pregnancy by increasing metabolic expenditure have proven unsuccessful [12].
INCIDENCE AND COURSE
The reported incidence of gallstone-related disease in pregnant women is low (0.05 to 0.33 percent)
[13-15], with reported values depending on patient selection, frequency of assessment, and
diagnostic definitions and techniques [16,17]. In one of the largest studies, a prospective serial
ultrasound study of over 3200 pregnant women without gallstones at their first ultrasound
examination, new sludge/new stones/progression of baseline sludge was noted in 7.1 percent of
women on at least one ultrasound by the second trimester, in 7.9 percent of women by the third
trimester, and in 10.2 percent of women by four to six weeks postpartum [6]. However, among women
with sludge or stones, only 1.2 percent developed any symptoms attributable to the gallbladder during
pregnancy.
In the postpartum period, bile composition and gallbladder function return to normal. Gallbladder
sludge resolved in 40 to 61 percent of cases, in two studies [10,18]. Sludge is more likely to resolve
than stones (39 versus 9 percent) [18]. Approximately 30 percent of stones smaller than 10 mm
disappeared due, at least in part, to unsaturation of bile [7,10]. By one year postpartum, most women
with sludge during pregnancy had a normal ultrasound examination, but abnormal ultrasound findings
remained in approximately 80 percent of patients with stones [10,19].
Serious complications of gallstones, such as acute cholecystitis, choledocholithiasis, gangrenous

gallbladder, or pancreatitis, developed in <10 percent of symptomatic patients [7,20].
CLINICAL FEATURES
Categorization of presentations — The presentation of gallstone disease during pregnancy is

similar to that in the nonpregnant state. It is helpful to categorize presentation into the following
clinical groups:
● No symptoms, but gallstones on ultrasound examination (incidental gallstones)

● Typical biliary symptoms and gallstones on ultrasound examination
● Atypical symptoms and gallstones on ultrasound examination
● Typical biliary symptoms, but no gallstones on ultrasound examination
Asymptomatic patients — Almost all pregnant women undergo one or more obstetrical ultrasound
examinations, which may include the right upper quadrant (RUQ). Thus, an incidental finding of
gallstones is not uncommon.
Symptomatic patients — In most patients, the first symptoms experienced from gallstones are
recurrent pain attacks (biliary colic). Patients with biliary colic complain of epigastric or RUQ pain. The
onset of pain is typically between one and three hours postprandially. A history of fatty food ingestion
before the initial onset of pain is common. The discomfort progresses in less than one hour to a
steady plateau that ranges from moderate to excruciating and remains constant for more than one
hour, then slowly subsides over several hours.
Less frequently, the initial symptoms are those of one of the complications of gallstones, most
commonly acute cholecystitis. The presentation of acute cholecystitis is similar to that in nonpregnant
women: RUQ or epigastric pain that is steady and severe, prolonged (more than four to six hours),
and possibly radiating to the right shoulder or back. Associated symptoms include fever, anorexia,
nausea, and vomiting. Abdominal examination usually demonstrates voluntary and involuntary
guarding and, frequently, a positive Murphy's sign. The constitutional symptoms and prolonged
duration of pain help to distinguish acute cholecystitis from biliary colic. (See "Acute calculous
cholecystitis: Clinical features and diagnosis", section on 'Clinical manifestations'.)
Some patients present with a variety of atypical symptoms, and gallstones are observed on
ultrasound examination, but they do not have typical biliary colic. These patients should be evaluated
for alternative diagnoses. (See "Overview of gallstone disease in adults", section on 'Atypical
symptoms'.)
Laboratory findings — Laboratory studies should be normal in patients with uncomplicated

gallstone disease, both during asymptomatic periods and during attacks of pain. Abnormal blood tests
such as leukocytosis, elevated liver, or pancreas tests suggest the development of a complication of
gallstone disease, such as cholecystitis, cholangitis, or pancreatitis. Laboratory results need to be
interpreted with respect to the normal range for pregnant women, which is sometimes different from
the nonpregnant state. (See 'Laboratory evaluation' below.)
DIFFERENTIAL DIAGNOSIS OF PREGNANT WOMEN WITH RUQ OR

EPIGASTRIC PAIN
In pregnant women with right upper quadrant (RUQ) or epigastric pain, both pregnancy-related and
nonpregnancy-related clinical diagnoses must be considered, even if gallstones are observed on
ultrasound examination, since they may be an incidental finding.
Pregnancy-related conditions — Pregnancy-related conditions that may be associated with RUQ or

epigastric pain include severe preeclampsia and HELLP syndrome (ie, Hemolysis, Elevated Liver
enzymes, Low Platelet count), acute fatty liver, abruptio placentae, uterine rupture, and intra-amniotic
infection. These conditions can usually be differentiated from gallstone disease by the clinical setting
in which they occur and by obtaining the appropriate diagnostic studies. (See "Approach to acute
abdominal pain in pregnant and postpartum women".)
● Preeclampsia/HELLP – Hypertension is the requisite criterion for preeclampsia (table 2) and is

common in HELLP syndrome (table 3). Thrombocytopenia is a requisite criterion for HELLP
syndrome and is common in preeclampsia. Both disorders occur after 20 weeks of gestation.
Gallbladder disease is not associated with either hypertension or thrombocytopenia and can
occur anytime in pregnancy. Women with severe preeclampsia or HELLP syndrome can have
elevated liver enzymes (typically at least twice normal), which can also occur with complicated
gallstone disease. (See "Preeclampsia: Clinical features and diagnosis" and "HELLP syndrome".)
● Acute fatty liver – Acute fatty liver occurs in the second half of pregnancy, usually in the third
trimester. The most frequent initial symptoms are nausea or vomiting (approximately 75 percent
of patients), abdominal pain (particularly epigastric, 50 percent), anorexia, and jaundice. Serum
aminotransferase elevations are usually higher in fatty liver than in gallbladder disease, ranging
from modest increases to up to 1000 IU/L. About one-half of patients have signs of preeclampsia
at presentation or at some time during the course of illness. Hypoglycemia is a feature of severe
acute fatty liver but is not present in preeclampsia, HELLP syndrome, or gallbladder disease.
Severe acute fatty liver is also characterized by renal failure and disseminated intravascular
coagulation, which are not features of gallbladder disease. (See "Acute fatty liver of pregnancy".)
● Abruption – An acute abruption (ie, decidual hemorrhage leading to the premature separation of
the placenta prior to delivery) classically presents with vaginal bleeding, uterine contractions, and
abdominal/uterine pain that is typically not limited to the RUQ or epigastrium. In severe cases,
the fetal heart rate pattern is abnormal, and disseminated intravascular coagulation occurs.
These features distinguish abruption from gallbladder disease. (See "Placental abruption:
Pathophysiology, clinical features, diagnosis, and consequences".)
● Uterine rupture – Most uterine ruptures occur in laboring women with a prior cesarean delivery
or prior transmyometrial surgery. Signs and symptoms of uterine rupture can include an abnormal
fetal heart rate tracing or fetal death, uterine tenderness, peritoneal irritation, vaginal bleeding,
and shock. Uterine rupture prior to the onset of labor is rare and usually due to sharp or blunt
abdominal trauma. This clinical setting is quite different from that in biliary disease. (See "Uterine
rupture: After previous cesarean delivery".)
● Intra-amniotic infection – Signs and symptoms of intra-amniotic infection include fever,

abdominal pain, uterine tenderness, leukocytosis, maternal and fetal tachycardia, and uterine
contractions. Intra-amniotic infection is common after premature rupture of the fetal membranes.
Women with acute cholecystitis have some of these signs and symptoms, but the location of pain
is different (RUQ/epigastrium versus uterine) and the fetal membranes are typically intact. (See
"Intra-amniotic infection (clinical chorioamnionitis or triple I)".)
Nonpregnancy-related conditions — Nonpregnancy-related conditions include non-gallstone-

related biliary disease, gastroesophageal reflux, peptic ulcer disease, hepatitis, and right-sided
pneumonia. Of note, the location of the appendix migrates cephalad with the enlarging uterus as
shown in the figure; thus, appendicitis may be more likely to present with RUQ pain in pregnancy
(figure 1). The differential diagnosis of RUQ or epigastric pain unrelated to pregnancy is reviewed
separately. (See "Causes of abdominal pain in adults" and "Approach to acute abdominal pain in
pregnant and postpartum women", section on 'Upper abdominal pain'.)
DIAGNOSIS
Criteria for diagnosis of gallstone-related diseases in pregnancy are the same as in nonpregnant
women.
● Biliary colic (see "Overview of gallstone disease in adults", section on 'Evaluation for
uncomplicated gallstone disease')
● Acute cholecystitis (see "Acute calculous cholecystitis: Clinical features and diagnosis", section
on 'Diagnostic approach')
● Choledocholithiasis (see "Choledocholithiasis: Clinical manifestations, diagnosis, and

management", section on 'Diagnosis')
● Acute cholangitis (see "Acute cholangitis: Clinical manifestations, diagnosis, and management",
section on 'Diagnostic approach')
● Biliary pancreatitis (see "Clinical manifestations and diagnosis of acute pancreatitis", section on
'Diagnosis')
DIAGNOSTIC TESTING IN PREGNANCY
Laboratory evaluation — Laboratory studies should be normal in patients with uncomplicated biliary
colic, both during asymptomatic periods and during attacks of symptoms. However, laboratory studies
can be helpful for diagnosis of complicated gallbladder disease and for excluding conditions in
differential diagnosis. Although the choice and order of testing varies depending upon the clinical
presentation and suspicion of a particular diagnosis, the following are a reasonable baseline
evaluation:
● Aspartate aminotransferase/alanine aminotransferase (AST/ALT), total bilirubin, alkaline

phosphatase (to evaluate for complicated gallbladder disease, HELLP [Hemolysis, Elevated
Liver enzymes, Low Platelet count], severe preeclampsia)
● Serum amylase and lipase (to evaluate for pancreatitis)
● Complete blood count (to evaluate for infection, HELLP syndrome, severe preeclampsia)
● Urine protein (to evaluate for preeclampsia)
Bilirubin and transaminases are not affected by normal pregnancy, while amylase and lipase levels
have been reported to remain in the normal range or increase slightly (table 4) [21-24]. Elevation in
the serum total bilirubin is not common in uncomplicated cholecystitis, since biliary obstruction is
limited to the gallbladder. However, mild elevations in serum aminotransferases and amylase, along
with hyperbilirubinemia and jaundice, may occur as a result of the passage of small stones, sludge, or
pus [25]. (See "Acute calculous cholecystitis: Clinical features and diagnosis", section on 'Laboratory
findings'.)
Significant elevations of the transaminases and alkaline phosphatase or direct bilirubin should raise
the possibility of a common bile duct stone, cholangitis, or Mirizzi syndrome (a gallstone impacted in
the distal cystic duct causing extrinsic compression of the common bile duct). It should be noted that
transaminases are elevated to at least twice normal in HELLP syndrome and can be elevated in
severe preeclampsia, and the normal alkaline phosphatase level may be markedly elevated in
pregnancy (table 4). (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management"
and "Acute cholangitis: Clinical manifestations, diagnosis, and management" and "Mirizzi syndrome".)
The normal range for the white blood cell count is higher in pregnancy (normal range 9000 to 15,000
cells/microL), which reduces the diagnostic usefulness of this test for infection. However, a left shift
and/or bandemia suggests infection. The platelet count may be slightly lower in normal pregnancy but
generally remains within the normal range. A low platelet count suggests one of several causes of
pregnancy-related thrombocytopenia (eg, HELLP, severe preeclampsia). (See "Thrombocytopenia in
pregnancy".)
Proteinuria is a frequent finding in preeclampsia but is no longer considered necessary for the
diagnosis if features of severe disease are present (table 2).
Imaging
Ultrasonography — Ultrasonography is a reliable and safe method for identifying gallstones in

pregnant women. Gallstones and sludge are easily visualized on ultrasound, with sensitivity and
specificity approaching 100 percent [14,26,27]. Experienced ultrasonographers can often make an
accurate diagnosis of acute or chronic cholecystitis (sensitivity 85 to 95 percent, specificity 95
percent) [27]. A diagnosis of acute cholecystitis is suggested by additional findings of gallbladder
distention, gallbladder wall thickening, pericholecystic fluid, and the ultrasonographic Murphy's sign.
(See "Acute calculous cholecystitis: Clinical features and diagnosis", section on 'Ultrasonography'.)
Transabdominal ultrasonography is relatively insensitive for the detection of common bile duct stones,
whereas endoscopic ultrasound is highly accurate for the detection of common bile duct stones and
may be useful prior to considering endoscopic retrograde cholangiopancreatography (ERCP). (See
'Endoscopy' below.)
Magnetic resonance imaging — Magnetic resonance cholangiopancreatography (MRCP) is not

typically used in the evaluation of biliary colic or acute cholecystitis but may be useful in some
complicated cases, such as women with choledocholithiases or pancreatitis if ultrasound is
nondiagnostic. Noncontrast magnetic resonance imaging is an accepted, alternative imaging modality
for pregnant women when other nonionizing forms of diagnostic imaging are inadequate, and when
the examination provides important information that would otherwise require exposure to ionizing
radiation [28,29]. There are no known harmful fetal effects of noncontrast magnetic resonance during
pregnancy; however, the use of magnetic resonance during the first trimester is not recommended
since information is limited regarding fetal safety during the period of organogenesis. The
administration of gadolinium during pregnancy is controversial, and we avoid gadolinium whenever
possible but realize that, at times, it may be needed [29,30]. (See "Magnetic resonance
cholangiopancreatography" and "Diagnostic imaging in pregnant and nursing women".)
HIDA scan — Cholescintigraphy using 99mTc-hepatic iminodiacetic acid (generically referred to

as a HIDA scan) is not a first-line imaging test in patients with suspected gallstone-related disease
and is rarely needed for decision making. The fetal dose is <5 mGy (milligray) [31]; there is no
evidence of an increased risk of fetal anomalies, intellectual disability, growth restriction, or pregnancy
loss at this dose. (See "Acute calculous cholecystitis: Clinical features and diagnosis", section on
'Cholescintigraphy (hepatic iminodiacetic acid [HIDA] scan)' and "Diagnostic imaging in pregnant and
nursing women", section on 'Fetal effects from ionizing radiation'.)
Other imaging modalities — Other imaging modalities, such as computed tomography and plain
radiographs, are generally avoided in pregnancy for the evaluation of the gallbladder because they
are inferior to ultrasound and magnetic resonance imaging and they expose the fetus to ionizing
radiation [29]. (See "Diagnostic imaging in pregnant and nursing women" and "Overview of gallstone
disease in adults", section on 'Evaluation for uncomplicated gallstone disease' and "Acute calculous
cholecystitis: Clinical features and diagnosis", section on 'Diagnostic imaging'.)
Endoscopy — Endoscopy of the biliary system, typically ERCP, can be performed safely in pregnant
women when clinically indicated [32-35]. (See 'Choledocholithiasis/cholangitis' below.)
MANAGEMENT
Most of the literature discussing the surgical management of gallstones in pregnancy is from case
series and retrospective reviews, many of which were performed prior to the era of laparoscopic
cholecystectomy. Recommendations for management are largely extrapolated from evidence for
treatment in the nonpregnant population, but taking into consideration the specific issues of
pregnancy, and the available evidence where it exists.
Supportive care — Supportive care includes pain control, intravenous fluid therapy, and nutritional
support, as needed, and antibiotic therapy depending upon the clinical presentation.
Pain control — Pain control can usually be achieved with intravenous opioids. Although
nonsteroidal anti-inflammatory drugs (NSAIDs) can produce effective analgesia, these drugs are
generally avoided in pregnancy, especially after 32 weeks of gestation, because of potential adverse
fetal effects when used for more than 48 hours (eg, premature closure of the ductus arteriosus,
oligohydramnios). Acetaminophen can be used to manage mild pain.
Antibiotic therapy — Initial management for patients with symptomatic gallstone disease may
include empiric antibiotic therapy. Antibiotic therapy is required only for patients with acute
cholecystitis or cholangitis. In a patient with biliary pancreatitis, antibiotics are not required unless
there is reliable evidence of infection. (See "Management of acute pancreatitis", section on
'Antibiotics'.)
Although acute cholecystitis is primarily an inflammatory process, secondary infection of the

gallbladder can occur as a result of cystic duct obstruction and bile stasis. The most frequent isolates
from the gallbladder or common bile duct are Escherichia coli, Enterococcus, Klebsiella, and
Enterobacter. (See "Treatment of acute calculous cholecystitis", section on 'Antibiotics' and "Acute
cholangitis: Clinical manifestations, diagnosis, and management", section on 'Management'.)
Monotherapy with a beta-lactam/beta-lactamase inhibitor, such as one of the following, is appropriate

in pregnancy:
● Ampicillin-sulbactam 3 g intravenously every six hours
● Piperacillin-tazobactam 3.375 g intravenously every six hours
● Ticarcillin-clavulanate 3.1 g intravenously every four hours
An acceptable alternative is a third-generation cephalosporin, such as ceftriaxone 1 g intravenously

every 24 hours, plus metronidazole 500 mg intravenously every eight hours. In patients with a
significant penicillin allergy, clindamycin is given instead.
Cephalosporins, clindamycin, and aztreonam have a good safety profile in pregnant women.
Aminoglycosides are relatively safe but carry a risk of fetal (and maternal) ototoxicity and
nephrotoxicity, so drug levels should be monitored. Additional information about perioperative

antibiotic use in pregnant women is available elsewhere. Fluoroquinolones and carbapenems are
generally avoided in pregnant women because of potential fetal toxicity.
Biliary colic — The initial management of biliary colic is supportive, which is usually successful.
Some patients with biliary colic may be initially observed in an outpatient setting; however, most
pregnant women with right upper abdominal pain are generally observed in, or admitted to, labor and
delivery for pain control and fluid therapy, and to rule out the conditions listed above in differential
diagnosis.
During an acute attack of biliary colic, patients should be instructed to avoid eating, which may
exacerbate the pain by releasing cholecystokinin. When the pain has resolved, patients are
encouraged to eat a well-balanced diet. Whether or not a particular diet may reduce the formation
and future risk of biliary colic is unknown.
Additional imaging and repeat laboratory studies are indicated if symptoms do not resolve with
supportive care, to assess for complicated gallstone disease. (See 'Complicated gallstone disease'
below.)
If recurrent bouts of biliary colic occur, we feel that primary surgical management during pregnancy is
reasonable because recurrence is common with conservative therapy and surgical therapy appears
to be safe for mother and fetus [36] (see 'Supportive care' above and 'Cholecystectomy during
pregnancy' below). For these women, cholecystectomy is ideally performed in the second or early
third trimester [14,37-43]. (See 'Cholecystectomy during pregnancy' below.)
The decision to offer cholecystectomy for biliary colic during pregnancy is based upon the clinical
scenario, gestational age, and other factors.
● For pregnant patients with a first episode of biliary colic, we suggest initial supportive care. If
symptoms of biliary colic (pain, nausea/vomiting) cannot be controlled with dietary manipulation,
surgery should be offered.
● For patients with recurrent bouts of bothersome pain, or who are unable to gain weight at an
acceptable rate due to the symptoms, cholecystectomy is reasonable. (See "Gestational weight
gain", section on 'Recommendations for gestational weight gain'.)
● If biliary colic occurs near term, we avoid cholecystectomy and reevaluate the patient after
delivery. We generally wait six weeks following delivery to allow the mother to recover from the
delivery, bond with the infant, and regain her strength.
Although ursodeoxycholic acid has been administered in the management of intrahepatic cholestasis
of pregnancy and has a good fetal safety history, its efficacy for the treatment of gallbladder stones
during pregnancy has not been evaluated. We do not use it. In nonpregnant patients, medical therapy
is not preferred to surgical therapy and takes weeks before episodes of biliary pain decrease. (See
"Approach to the management of gallstones", section on 'Uncomplicated gallstone disease' and
"Overview of nonsurgical management of gallbladder stones".)
We suggest reimaging women who had uncomplicated biliary colic during pregnancy with abdominal
ultrasound four to six weeks postpartum. Further management depends on findings on follow-up
imaging studies:
● If sludge/stones persist, we suggest performing cholecystectomy within three months after

delivery to prevent recurrent attacks of biliary colic and more severe complications. In such
patients, postpartum restoration of gallbladder motility may exacerbate passage of sludge or
stones from the gallbladder.
● If sludge/stones disappear postpartum, we believe it is reasonable to take a watchful waiting

approach but maintain a low threshold for reimaging and surgical intervention should any
suggestion of symptoms recur. Dietary and lifestyle measures that may reduce the risk of new
gallstone formation are reviewed separately. (See "Gallstones: Epidemiology, risk factors and
prevention", section on 'Prevention of gallstones'.)
The postpartum cholecystectomy rate in women with biliary colic during pregnancy varies widely from
0.8 to 56 percent, depending on studies [6,18,44].
Complicated gallstone disease — As with nonpregnant women, pregnant women with complicated
gallstone disease, such as acute calculous cholecystitis, choledocholithiasis, cholangitis, or biliary
pancreatitis, require initial supportive care with hospitalization, pain control, intravenous fluid therapy
and nutritional support, and possibly antibiotics. Most will require prompt intervention with endoscopic
retrograde cholangiopancreatography (ERCP) and/or surgery to eliminate the gallstones. (See
'Supportive care' above.)
No randomized trials of the surgical treatment of biliary disease in pregnant women have been
performed. Recommendations for treatment are based primarily upon indirect evidence from the
nonpregnant population, which supports early intervention. These are discussed in detail in separate
topic reviews:
● (See "Treatment of acute calculous cholecystitis".)
● (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management", section on

'Management'.)
● (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on

'Management'.)
● (See "Management of acute pancreatitis", section on 'Gallstone pancreatitis'.)
In addition, observational data in pregnant women support an early intervention approach, which
appears to be equally safe and also more effective than expectant management/supportive medical
therapy in the pregnant population:
● A retrospective analysis of hospital discharges from 1999 to 2006 from the Healthcare Cost and
Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) identified 36,929 pregnant women
hospitalized with biliary tract disease (eg, gallstones, cholecystitis, cholangitis, biliary
pancreatitis, other biliary diseases) [39]. Of these, 9714 underwent cholecystectomy; most (89
percent) were performed laparoscopically. Surgical treatment was associated with lower
complication rates than nonoperative management (maternal complication rate 4.3 versus 16.5
percent; fetal complication rate 5.8 versus 16.5 percent). However, the choice of surgery versus
nonoperative management and laparoscopic versus open surgery in this retrospective study
likely reflects patient-specific factors, such as the type and severity of gallstone-related disease;
thus, the results cannot be used alone to guide decision making.
● Surgical intervention is not associated with a high risk of premature labor and/or delivery
(prevalence 0 to 10 percent); the risk is similar to that in the general obstetrical population
[14,41,42,45]. However, medical management has been associated with an increased risk of
cesarean delivery. In one small retrospective review of 112 pregnant patients who presented with
complications of gallstone disease (eg, acute cholecystitis, choledocholithiasis, pancreatitis), the
cesarean delivery rate was significantly higher in those treated conservatively (n = 68) compared
with those undergoing surgery, ERCP, or both (34 versus 8 percent) [36]. This may have been
due to an increased frequency of labor induction in conservatively treated patients.
● A Markov model that attempted to determine the best treatment option for biliary disease (biliary
colic, acute cholecystitis, gallstone pancreatitis) during pregnancy concluded that laparoscopic
cholecystectomy was preferable to conservative treatment of women presenting in the first or
second trimester [40]. This conclusion was based on the very low risk of fetal mortality
associated with laparoscopic surgery during pregnancy and the high rate of disease relapse (55
percent) and need for urgent surgery (19.5 percent) in patients treated nonoperatively. However,
the applicability of this analysis to clinical decision making is limited for several reasons; the
studies included women with a variety of biliary diseases, and it assumed the risk of perinatal
morbidity (including prematurity risk) was the same for patients treated surgically and
nonsurgically.
Acute cholecystitis — Definitive, prompt surgical therapy is required for any patient with
cholecystitis and signs of sepsis, suspected gangrene or perforation, as well as disease progression
while on antibiotic therapy. (See "Treatment of acute calculous cholecystitis", section on 'Indications
for emergency cholecystectomy'.)
In the absence of such indications for urgent or emergency surgery, the optimal treatment for acute
cholecystitis depends on the gestational age:
● For women in their first and second trimesters, good surgical candidates (American Society of
Anesthesiologists [ASA] I or II) should undergo cholecystectomy during their initial hospitalization
[14]. Although symptoms of cholecystitis may abate within 7 to 10 days of initiating nonoperative
treatment, there is a high risk of recurrence or serious complications.
● For women in the third trimester, nonoperative medical management with antibiotics and fluid
therapy should be tried first, whenever possible, to allow delay of cholecystectomy until the
postpartum period. Cholecystectomy in the third trimester can be technically difficult and has
been associated with increased for preterm delivery [46].
• If she responds to nonoperative treatment, we generally wait six weeks following delivery to
allow the mother to recover from the delivery, bond with the infant, and regain her strength.
• If she continues to have symptoms or shows signs of developing complications in spite of

nonoperative treatment, cholecystectomy is performed in good surgical candidates with an
approach (open or laparoscopic) suitable for the gestational age. (See 'Surgical approach'
below.)
• For women deemed at high risk for surgery, alternatives to cholecystectomy include
percutaneous or open gallbladder decompression. (See "Treatment of acute calculous
cholecystitis", section on 'High-risk patients' and "Open cholecystectomy", section on 'Open
cholecystostomy tube placement'.)
These recommendations are based on the following lines of evidence:
● In a review of six retrospective reports that included a total of 310 pregnant patients with acute
cholecystitis or biliary colic who were initially conservatively treated (study dates: 1994 to 2004)
[15,37,42,47-49], the readmission rate was 38 to 70 percent, and each relapse of disease was
more severe than the previous one [14]. Conservative treatment failed in 27 percent of patients,
who then required surgery. The need for surgery was not associated with any greater risk for
fetal or maternal morbidity or mortality. The risk of recurrence has been estimated as 55 percent
with disease in the first or second trimester, and 40 percent with disease in the third trimester
[40], but most recurrences were not associated with serious complications. In a later review of
the National Inpatient Sample, pregnant women who underwent cholecystectomy had
significantly lower maternal complication rates (4.3 versus 16.5 percent) and fetal complication
rates (5.8 versus 16.5 percent) compared with pregnant women hospitalized with biliary tract
disease who did not undergo surgery [39]. However, as noted above, these differences may in
part be due to differences in disease severity.
● In an administrative database study, compared with women who underwent cholecystectomy

postpartum, those who underwent cholecystectomy during the third trimester had higher rates of
preterm delivery (odds ratio 2.05), hospitalization (85 versus 63 percent), readmission (odds ratio
2.05), and open cholecystectomy (13 versus 2 percent), as well as a longer hospital stay (+0.83
days) [46]. The third trimester was defined as the period within 90 days before date of childbirth
and absence of preterm delivery ICD-9 codes; the mean and range of gestational ages at
cholecystectomy were not described.
Choledocholithiasis/cholangitis — Patients who develop symptomatic choledocholithiasis or

cholangitis require initial supportive care with hospitalization, intravenous fluid therapy and nutritional
support, pain control, antibiotics, and prompt intervention, typically initial ERCP with sphincterotomy
followed by cholecystectomy. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and
management", section on 'Management' and 'Antibiotic therapy' above.)
There have been no randomized trials in pregnant patients comparing ERCP followed by interval
cholecystectomy with common bile duct exploration at the time of laparoscopic cholecystectomy.
ERCP with sphincterotomy can be performed expeditiously by experienced gastroenterologists, and
multiple studies have demonstrated low rates of maternal or fetal morbidity [33,34,49-55]. Although
good outcomes have been described with intraoperative common bile duct exploration, few cases
have been reported for pregnant patients. ERCP generally uses fluoroscopy for imaging, which can
be accomplished safely during pregnancy with fetal shielding. Exposure to ionizing radiation during
ERCP can also be minimized or eliminated by using specific techniques [52], which are discussed in
detail elsewhere. (See "Endoscopic ultrasound in patients with suspected choledocholithiasis" and
"Endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy".)
If the stone cannot be cleared by ERCP, then cholecystectomy should be performed with
intraoperative cholangiography or ultrasound followed by laparoscopic or open common bile duct
exploration, if indicated [56-58]. As with ERCP, the fetus should be shielded during intraoperative
cholangiography [59].
If ERCP is not available, not successful, or if the patient is deemed high risk, percutaneous or open
biliary tract decompression may be appropriate for the patient with cholangitis. (See "Treatment of
acute calculous cholecystitis", section on 'High-risk patients' and "Open cholecystectomy", section on
'Open cholecystostomy tube placement'.)
Gallstone pancreatitis — Gallstone disease is the most common cause of acute pancreatitis
during pregnancy, accounting for at least 65 percent of cases [17]. Acute gallstone pancreatitis is
caused by a stone passing through the ampulla of Vater and is associated with maternal mortality if
not recognized and treated appropriately [53,60-62]. (See "Management of acute pancreatitis",
section on 'Gallstone pancreatitis'.)
Management consists of initial supportive care with hospitalization, pain control, intravenous fluid
therapy, and nutritional support. (See 'Supportive care' above and "Management of acute
pancreatitis", section on 'Antibiotics' and 'Antibiotic therapy' above.)
Many patients will improve rapidly with supportive care. A systematic review identified 12 studies that
included a total of 113 patients with confirmed gallstone-induced acute pancreatitis (study dates: 1972
to 2004) [42,63-73]. Maternal mortality was no different for conservative compared with surgical
management, but fetal mortality trended higher with conservative management (six cases) compared
with surgery (two cases) in patients who did not improve quickly [14]. Thus, women who do not
respond promptly to supportive medical care, and those with concomitant cholangitis, should undergo
prompt intervention with ERCP and sphincterotomy, biliary stent placement, or cholecystectomy.
Cholecystectomy is also indicated for patients with mild disease that resolves, usually during the
same hospitalization, to prevent recurrence and reduce costs [74]. (See
'Choledocholithiasis/cholangitis' above and 'Cholecystectomy during pregnancy' below.)
CHOLECYSTECTOMY DURING PREGNANCY
Cholecystectomy can be performed safely and effectively during pregnancy with appropriate attention
to the altered anatomy and physiology of pregnancy but may be more difficult in the pregnant patient,
particularly in the late third trimester [75-77]. An experienced surgeon and anesthesiologist, and early
involvement of the patient's obstetrician, are important for providing optimal outcomes for mother and
child. In a review of the Nationwide Inpatient Sample (NIS) database, surgical treatment by high-
volume surgeons (≥75th percentile) was associated with fewer maternal complications and fetal
complications than treatment by low-volume surgeons (maternal complications 0.9 versus 14.3
percent; fetal complications 3.9 versus 9.5 percent) [39].
Pregnancy alone does not appear to increase postoperative morbidity for cholecystectomy in
pregnant women compared with nonpregnant women [78,79]. In a review of data from the American
College of Surgeons database from 2005 to 2009, composite 30-day major morbidity was similar after
cholecystectomy between pregnant and nonpregnant women at 1.8 percent [78]. In a review of the
Nationwide Inpatient Sample that compared cholecystectomy in 9714 pregnant with 53,598
nonpregnant female controls from 1996 to 2006, pregnant women had higher rates of unadjusted
surgical complications (10.7 versus 9.6 percent) [39]. In this study, pregnant women were more likely
than nonpregnant women to undergo an open procedure; have multiple biliary diagnoses; be white;
have Medicaid insurance; or be treated at hospitals that were rural, teaching, in the South, and that
treated more high-risk obstetric volume. Pregnant women also were more likely to be treated by low-
volume surgeons. After adjustment for patient and provider characteristics, pregnancy was not a
significant predictor for having a surgical complication, but was an independent predictor for longer
adjusted length of stay.
Anesthesia and preoperative preparation — Women with uncomplicated gallbladder disease who
are already receiving antibiotic therapy should be administered prophylactic antibiotics prior to
cholecystectomy. Women with complicated gallbladder disease should already be receiving
antibiotics, and should be re-dosed prior to surgery. Appropriate antibiotic choices are discussed
above (table 5). (See 'Antibiotic therapy' above.)
Other anesthetic and preoperative considerations in the pregnant patient, including positioning,
monitoring, thromboprophylaxis, and pharmacologic management of preterm labor, are discussed in
detail elsewhere. Prophylactic tocolytic agents are not necessary [59]. (See "Management of the
pregnant patient undergoing nonobstetric surgery" and "Inhibition of acute preterm labor".)
Surgical approach — Either an open or laparoscopic approach to cholecystectomy may be chosen;

however, laparoscopic cholecystectomy is the recognized standard for removal of the gallbladder and
is also the preferred technique in pregnant women [59]. A laparoscopic approach, in general, offers
earlier recovery, reduced postoperative pain with a reduction in opioid usage, smaller incisions, and
fewer wound complications such as hernia or surgical site infections [80,81]. The surgical approach
needs to consider uterine size, maternal body habitus, past surgical history, surgeon experience, and
the availability of appropriate staff and equipment. A laparoscopic approach may provide better
surgical exposure than the open approach during pregnancy and reduces the need to manipulate the
uterus away from the operative field. However, if the laparoscopic procedure cannot be safely and/or
effectively completed, the approach should be converted to an open cholecystectomy to avoid injury
to surrounding structures. This reflects good judgment and should not be viewed as a failure or
complication of the laparoscopic approach. Indications for choosing an open surgical approach or
conversion to an open procedure are discussed in detail elsewhere. (See "Open cholecystectomy",
section on 'Indications for open surgery' and "Complications of laparoscopic surgery", section on
'Conversion to an open procedure' and "Laparoscopic surgery in pregnancy".)
Reviews of older studies comparing open with laparoscopic cholecystectomy found no significant
differences for maternal or fetal outcomes, dispelling the earlier notion that laparoscopic surgery was
unsafe for pregnant women [62,82]. Laparoscopy was not associated with any increased risk for fetal
mortality, low birth weight, preterm delivery, or low Apgar scores [83-89]. A 2008 systematic review
identified 20 studies (each including at least five patients undergoing laparoscopic cholecystectomy)
during pregnancy [14]. Among 195 patients, there were no maternal deaths, and the three fetal
deaths were not attributable to laparoscopic cholecystectomy. Four retrospective studies directly
comparing open with laparoscopic cholecystectomy during pregnancy also did not identify any
significant differences for maternal and fetal outcomes between the approaches [69,81,86,90]. The
rate of conversion from open to laparoscopic cholecystectomy was 10 to 26 percent in these studies.
A 2009 study of the National Inpatient Sample identified 9714 pregnant women who underwent
cholecystectomy [39]. The overall rates of maternal or fetal complications were 4.3 and 5.8 percent,
respectively. Compared with pregnant women who underwent open cholecystectomy (n = 1069),
pregnant women who underwent laparoscopic cholecystostomy (n = 8645) had significantly fewer
surgical (10.1 versus 18.9 percent), maternal (3.8 versus 9.1 percent), and fetal complications (5
versus 11.3 percent). However, as noted above, the overall complication rates were high in this study,
and demographics between the groups differed.
Laparoscopic cholecystectomy can be offered to women in any trimester requiring cholecystectomy,

although it is technically more challenging near term [59,86,87,91-97]. In small reviews of patients
undergoing laparoscopic cholecystectomy in the third trimester, the number of cases with preterm
contractions were 0 of 15, 2 of 5, and 5 of 6 [93,95,97]. The indications for tocolytics to manage
preterm contractions are discussed elsewhere. (See "Inhibition of acute preterm labor".)
Surgical techniques
Laparoscopic cholecystectomy — A few modifications to standard techniques for laparoscopic

cholecystectomy are needed when the patient is pregnant. The patient should be placed slightly
head-up and tilted to her left, allowing the uterus to fall away from the cava. For laparoscopic
cholecystectomy, we prefer to use the open (Hasson) technique to gain initial access to the abdomen.
An alternative during the later stages of pregnancy is subcostal access [59]. Other aspects of
laparoscopy in pregnancy are reviewed separately. (See "Abdominal access techniques used in
laparoscopic surgery", section on 'Peritoneal access' and "Laparoscopic surgery in pregnancy".)
The cannulas are generally placed in the usual locations, although as the uterus enlarges in the third
trimester (figure 2), it can be advantageous to move the epigastric port into the left upper quadrant to
provide greater perspective (figure 3). This modification should be determined after the
pneumoperitoneum has been established. The gallbladder and the liver are retracted in the usual
fashion, and the dissection is begun around the cystic duct-infundibular junction. Typically, an
avascular area can be identified on the lateral aspect of this junction.
The remainder of the technique of laparoscopic cholecystectomy, including intraoperative evaluation

and laparoscopic management of common bile duct stones, is similar to surgery in nonpregnant
patients, as is discussed in detail elsewhere and shown in the figures (figure 4 and figure 5). (See
"Laparoscopic cholecystectomy", section on 'Evaluation for choledocholithiasis' and "Surgical
common bile duct exploration".)
Open cholecystectomy — The surgical technique of open cholecystectomy is modified only

slightly during pregnancy. Patients are placed slightly head-up and tilted toward the left, allowing the
uterus to fall away from the inferior vena cava. A subcostal incision is preferred, as it allows an easier
approach to the gallbladder when the uterus is very large. The procedure is otherwise performed in
standard fashion, as discussed in detail elsewhere. (See "Open cholecystectomy".)
Intraoperative cholangiography should be considered if the biliary anatomy is unclear and/or if there is
a substantial possibility of common duct stones. Radiation exposure to the fetus is not significant if
shielded by a lead apron (figure 6) [59]. If available, intraoperative ultrasound of the bile duct can be
performed as an alternative to cholangiography and has equivalent diagnostic accuracy for common
duct stones in experienced hands. (See "Open cholecystectomy", section on 'Intraoperative
cholangiography' and "Choledocholithiasis: Clinical manifestations, diagnosis, and management",
section on 'Intraoperative ultrasonography'.)
POSTOPERATIVE CARE
General considerations for the postoperative care of the pregnant patients are reviewed separately.
Fetal heart rate and uterine activity should be assessed in the recovery room, as appropriate for
gestational age. (See "Laparoscopic surgery in pregnancy", section on 'Postoperative care' and
"Management of the pregnant patient undergoing nonobstetric surgery", section on 'Postoperative
obstetric management'.)
Following cholecystectomy, the patient can usually resume drinking clear liquids once the effects of
anesthesia have worn off and then advance as tolerated to a low-fat diet. Patients who have had
laparoscopic surgery can usually be discharged home on the day of surgery or the following day
unless there are extenuating circumstances, such as uterine contractions, vaginal bleeding, pain, or
unremitting nausea. A two- to four-day stay is usually necessary after open surgery.
Opioids and antiemetics can be used, as needed, to control postoperative pain and nausea.
Analgesic requirements should be met in consultation with the obstetrician. Short-term use of
acetaminophen or narcotics is safe in pregnancy, although prolonged use of these medications (>2
weeks) postoperatively should be avoided. Nonsteroidal anti-inflammatory drugs (NSAIDs) should be
avoided, especially after 32 weeks of gestation, because they may cause premature closure of the
fetal ductus arteriosus. Epidural analgesia is an option for postoperative pain control after an open
procedure and carries less risk of opioid-induced hypoventilation when compared with intravenous
opioids.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Gallbladder surgery" and "Society
guideline links: Gallstones".)
SUMMARY AND RECOMMENDATIONS
● Gallstones are common during pregnancy due to decreased gallbladder motility and increased
cholesterol saturation of bile. The major independent risk factor for gallstones is prepregnancy
obesity. (See 'Pathophysiology' above and 'Personal risk factors' above.)
● The clinical presentation of gallstone disease during pregnancy is not significantly different than
in the nongestational state. Among pregnant women who develop gallstones or have sludge,
fewer than 2 percent develop symptoms. In most patients, recurrent right upper quadrant (RUQ)
pain (biliary colic) is the first symptom related to gallstones. Less frequently, initial manifestations
may be related to complications of gallstones (acute cholecystitis, cholangitis, gallstone
pancreatitis). (See 'Clinical features' above.)
● Criteria for diagnosis of gallstone-related diseases in pregnancy are the same as in nonpregnant
women. Ultrasonography is a reliable and safe method for identifying stones in the gallbladder.
Common bile duct stones are poorly identified with transabdominal ultrasound. Other imaging
that may be useful and is considered safe in pregnancy includes magnetic resonance imaging,
cholescintigraphy, and cholangiography (endoscopic, laparoscopic). (See 'Imaging' above.)
● Laboratory studies can be helpful for diagnosing complicated gallbladder disease and excluding
conditions in differential diagnosis. Routine laboratory studies are generally normal in patients
with uncomplicated biliary colic. Significant elevations of the transaminases and alkaline
phosphatase or direct bilirubin should raise the possibility of a common bile duct stone,
cholangitis, or Mirizzi syndrome, keeping in mind that the normal ranges for some laboratory
values are altered in pregnancy (table 4). (See 'Laboratory evaluation' above.)
● In pregnant women with RUQ or epigastric pain, pregnancy-related conditions must be

considered, even if gallstones are observed on ultrasound examination, since they may be an
incidental finding. These conditions can usually be differentiated from gallstone disease using the
clinical setting in which they occur. (See 'Differential diagnosis of pregnant women with RUQ or
epigastric pain' above.)
● The initial management of pregnant patients with gallstone disease is supportive and includes
pain control, intravenous fluid therapy, and, for selected patients, antibiotic therapy (acute
cholecystitis, evidence of biliary infection). Additional imaging and repeat laboratory studies are
indicated to assess for potential complications if symptoms worsen. (See 'Supportive care'
above.)
● Cholecystectomy can be performed safely and effectively during any trimester of pregnancy.
Pregnancy alone does not appear to increase postoperative morbidity for cholecystectomy.
However, cholecystectomy can be technically challenging near term. (See 'Cholecystectomy
during pregnancy' above.)
• For pregnant patients with a first episode of biliary colic, we suggest initial supportive care
(Grade 2C). For recurrent biliary colic during pregnancy, we suggest cholecystectomy
(Grade 2C). (See 'Biliary colic' above.)
• For pregnant patients who develop acute cholecystitis during the first two trimesters, we
suggest cholecystectomy during their initial hospitalization rather than conservative therapy
alone or interval cholecystectomy (Grade 2B). Prompt surgical intervention decreases
relapse rates and hospital readmissions.
• If biliary colic or acute cholecystitis occurs during the third trimester, we make every effort to
avoid surgery. Cholecystectomy during the trimester is not only technically difficult but also
has been associated with worse outcomes (eg, increased premature delivery). Once the
woman has delivered her baby, we wait six weeks to perform cholecystectomy to allow her
to recover from the delivery, bond with the infant, and regain her strength.
• Urgent or emergent intervention (cholecystectomy, biliary tract or gallbladder drainage) is

indicated for patients with gallstone disease and signs of sepsis, gangrene or perforation, or
for patients who develop intractable pain or fever while being observed.
● For pregnant patients who require cholecystectomy, we suggest a laparoscopic approach rather
than open surgery, when feasible and available (Grade 2B). If a laparoscopic procedure cannot
be safely and/or effectively completed, an open cholecystectomy should be performed. (See
'Surgical approach' above.)
● In the postpartum period, gallbladder sludge resolves in many patients and is more likely to
resolve than stones. We suggest reimaging women who had uncomplicated biliary colic during
pregnancy with abdominal ultrasound four to six weeks postpartum. Further management
depends on findings on follow-up imaging studies. If sludge/stones persist, we suggest
performing cholecystectomy to prevent recurrent attacks of biliary colic and more severe
complications. If sludge/stones disappear postpartum, we believe it is reasonable to take a
watchful waiting approach but maintain a low threshold for reimaging and surgical intervention
should any suggestion of symptoms recur. (See 'Incidence and course' above and 'Biliary colic'
above.)
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REFERENCES
1. Ibiebele I, Schnitzler M, Nippita T, Ford JB. Outcomes of Gallstone Disease during Pregnancy: a
Population-based Data Linkage Study. Paediatr Perinat Epidemiol 2017; 31:522.
2. Everson GT. Pregnancy and gallstones. Hepatology 1993; 17:159.
3. Everson GT. Gastrointestinal motility in pregnancy. Gastroenterol Clin North Am 1992; 21:751.
4. Kern F Jr, Everson GT, DeMark B, et al. Biliary lipids, bile acids, and gallbladder function in the
human female. Effects of pregnancy and the ovulatory cycle. J Clin Invest 1981; 68:1229.
5. Igbinosa O, Poddar S, Pitchumoni C. Pregnancy associated pancreatitis revisited. Clin Res

Hepatol Gastroenterol 2013; 37:177.
6. Ko CW, Beresford SA, Schulte SJ, et al. Incidence, natural history, and risk factors for biliary
sludge and stones during pregnancy. Hepatology 2005; 41:359.
7. Valdivieso V, Covarrubias C, Siegel F, Cruz F. Pregnancy and cholelithiasis: pathogenesis and

natural course of gallstones diagnosed in early puerperium. Hepatology 1993; 17:1.
8. Barbara L, Sama C, Morselli Labate AM, et al. A population study on the prevalence of
gallstone disease: the Sirmione Study. Hepatology 1987; 7:913.
9. Liu B, Beral V, Balkwill A, Million Women Study Collaborators. Childbearing, breastfeeding,

other reproductive factors and the subsequent risk of hospitalization for gallbladder disease. Int
J Epidemiol 2009; 38:312.
10. Maringhini A, Ciambra M, Baccelliere P, et al. Biliary sludge and gallstones in pregnancy:
incidence, risk factors, and natural history. Ann Intern Med 1993; 119:116.
11. Mathew LK, Ko C. Dietary fat and protein intake are not associated with incident biliary sludge
and stones during pregnancy. JPEN J Parenter Enteral Nutr 2015; 39:124.
12. Ko CW, Napolitano PG, Lee SP, et al. Physical activity, maternal metabolic measures, and the
incidence of gallbladder sludge or stones during pregnancy: a randomized trial. Am J Perinatol
2014; 31:39.
13. Ellington SR, Flowers L, Legardy-Williams JK, et al. Recent trends in hepatic diseases during
pregnancy in the United States, 2002-2010. Am J Obstet Gynecol 2015; 212:524.e1.
14. Date RS, Kaushal M, Ramesh A. A review of the management of gallstone disease and its
complications in pregnancy. Am J Surg 2008; 196:599.
15. Elamin Ali M, Yahia Al-Shehri M, Abu-Eshy S, et al. Is surgical intervention in acute cholecystitis
in pregnancy justified? J Obstet Gynaecol 1997; 17:435.
16. Mendez-Sanchez N, Chavez-Tapia NC, Uribe M. Pregnancy and gallbladder disease. Ann
Hepatol 2006; 5:227.
17. Ducarme G, Maire F, Chatel P, et al. Acute pancreatitis during pregnancy: a review. J Perinatol
2014; 34:87.
18. Galyani Moghaddam T, Fakheri H, Abdi R, et al. The incidence and outcome of pregnancy-
related biliary sludge/stones and potential risk factors. Arch Iran Med 2013; 16:12.
19. Maringhini A, Marcenò MP, Lanzarone F, et al. Sludge and stones in gallbladder after
pregnancy. Prevalence and risk factors. J Hepatol 1987; 5:218.
20. Ramin KD, Ramsey PS. Disease of the gallbladder and pancreas in pregnancy. Obstet Gynecol
Clin North Am 2001; 28:571.
21. Larsson A, Palm M, Hansson LO, Axelsson O. Reference values for clinical chemistry tests
during normal pregnancy. BJOG 2008; 115:874.
22. Kaiser R, Berk JE, Fridhandler L. Serum amylase changes during pregnancy. Am J Obstet
Gynecol 1975; 122:283.
23. Strickland DM, Hauth JC, Widish J, et al. Amylase and isoamylase activities in serum of
pregnant women. Obstet Gynecol 1984; 63:389.
24. Karsenti D, Bacq Y, Bréchot JF, et al. Serum amylase and lipase activities in normal pregnancy:
a prospective case-control study. Am J Gastroenterol 2001; 96:697.
25. Kurzweil SM, Shapiro MJ, Andrus CH, et al. Hyperbilirubinemia without common bile duct
abnormalities and hyperamylasemia without pancreatitis in patients with gallbladder disease.
Arch Surg 1994; 129:829.
26. Boregowda G, Shehata HA. Gastrointestinal and liver disease in pregnancy. Best Pract Res
Clin Obstet Gynaecol 2013; 27:835.
27. Gilo NB, Amini D, Landy HJ. Appendicitis and cholecystitis in pregnancy. Clin Obstet Gynecol
2009; 52:586.
28. Oto A, Ernst R, Ghulmiyyah L, et al. The role of MR cholangiopancreatography in the evaluation
of pregnant patients with acute pancreaticobiliary disease. Br J Radiol 2009; 82:279.
29. Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and
magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol 2008;
112:333.
30. Kanal E, Barkovich AJ, Bell C, et al. ACR guidance document for safe MR practices: 2007. AJR
Am J Roentgenol 2007; 188:1447.
31. Adelstein SJ. Administered radionuclides in pregnancy. Teratology 1999; 59:236.
32. Baillie J, Cairns SR, Putman WS, Cotton PB. Endoscopic management of choledocholithiasis
during pregnancy. Surg Gynecol Obstet 1990; 171:1.
33. Jamidar PA, Beck GJ, Hoffman BJ, et al. Endoscopic retrograde cholangiopancreatography in
pregnancy. Am J Gastroenterol 1995; 90:1263.
34. Tham TC, Vandervoort J, Wong RC, et al. Safety of ERCP during pregnancy. Am J
Gastroenterol 2003; 98:308.
35. European Association for the Study of the Liver. EASL Clinical Practice Guidelines:
management of cholestatic liver diseases. J Hepatol 2009; 51:237.
36. Othman MO, Stone E, Hashimi M, Parasher G. Conservative management of cholelithiasis and
its complications in pregnancy is associated with recurrent symptoms and more emergency
department visits. Gastrointest Endosc 2012; 76:564.
37. Glasgow RE, Visser BC, Harris HW, et al. Changing management of gallstone disease during
pregnancy. Surg Endosc 1998; 12:241.
38. Davis A, Katz VL, Cox R. Gallbladder disease in pregnancy. J Reprod Med 1995; 40:759.
39. Kuy S, Roman SA, Desai R, Sosa JA. Outcomes following cholecystectomy in pregnant and
nonpregnant women. Surgery 2009; 146:358.
40. Jelin EB, Smink DS, Vernon AH, Brooks DC. Management of biliary tract disease during
pregnancy: a decision analysis. Surg Endosc 2008; 22:54.
41. Dhupar R, Smaldone GM, Hamad GG. Is there a benefit to delaying cholecystectomy for
symptomatic gallbladder disease during pregnancy? Surg Endosc 2010; 24:108.
42. Lu EJ, Curet MJ, El-Sayed YY, Kirkwood KS. Medical versus surgical management of biliary
tract disease in pregnancy. Am J Surg 2004; 188:755.
43. Chiappetta Porras LT, Nápoli ED, Canullán CM, et al. Minimally invasive management of acute
biliary tract disease during pregnancy. HPB Surg 2009; 2009:829020.
44. Hedström J, Nilsson J, Andersson R, Andersson B. Changing management of gallstone-related

disease in pregnancy - a retrospective cohort analysis. Scand J Gastroenterol 2017; 52:1016.
45. Tang SJ, Mayo MJ, Rodriguez-Frias E, et al. Safety and utility of ERCP during pregnancy.
Gastrointest Endosc 2009; 69:453.
46. Fong ZV, Pitt HA, Strasberg SM, et al. Cholecystectomy During the Third Trimester of
Pregnancy: Proceed or Delay? J Am Coll Surg 2019; 228:494.
47. Swisher SG, Schmit PJ, Hunt KK, et al. Biliary disease during pregnancy. Am J Surg 1994;
168:576.
48. Daradkeh S, Sumrein I, Daoud F, et al. Management of gallbladder stones during pregnancy:
conservative treatment or laparoscopic cholecystectomy? Hepatogastroenterology 1999;
46:3074.
49. Sungler P, Heinerman PM, Steiner H, et al. Laparoscopic cholecystectomy and interventional
endoscopy for gallstone complications during pregnancy. Surg Endosc 2000; 14:267.
50. Gupta R, Tandan M, Lakhtakia S, et al. Safety of therapeutic ERCP in pregnancy - an Indian
experience. Indian J Gastroenterol 2005; 24:161.
51. Kahaleh M, Hartwell GD, Arseneau KO, et al. Safety and efficacy of ERCP in pregnancy.
52. Simmons DC, Tarnasky PR, Rivera-Alsina ME, et al. Endoscopic retrograde
cholangiopancreatography (ERCP) in pregnancy without the use of radiation. Am J Obstet
Gynecol 2004; 190:1467.
53. Howden JK, Baillie J. Preoperative versus postoperative endoscopic retrograde

cholangiopancreatography in mild to moderate pancreatitis: a prospective randomized trial.
54. Barthel JS, Chowdhury T, Miedema BW. Endoscopic sphincterotomy for the treatment of
gallstone pancreatitis during pregnancy. Surg Endosc 1998; 12:394.
55. Farca A, Aguilar ME, Rodriguez G, et al. Biliary stents as temporary treatment for
choledocholithiasis in pregnant patients. Gastrointest Endosc 1997; 46:99.
56. Kim YW, Zagorski SM, Chung MH. Laparoscopic common bile duct exploration in pregnancy
with acute gallstone pancreatitis. JSLS 2006; 10:78.
57. Liberman MA, Phillips EH, Carroll B, et al. Management of choledocholithiasis during
pregnancy: a new protocol in the laparoscopic era. J Laparoendosc Surg 1995; 5:399.
58. DePaula AL, Hashiba K, Bafutto M. Laparoscopic management of choledocholithiasis. Surg

Endosc 1994; 8:1399.
59. Guidelines for Laparoscopic Surgery During Pregnancy. Los Angeles, CA: Society of American
Gastrointestinal Endoscopic Surgeons. http://www.sages.org/publications/guidelines/guidelines-
for-diagnosis-treatment-and-use-of-laparoscopy-for-surgical-problems-during-pregnancy/ (Acce
ssed on July 03, 2014).
60. Working Party of the British Society of Gastroenterology, Association of Surgeons of Great
Britain and Ireland, Pancreatic Society of Great Britain and Ireland, Association of Upper GI
Surgeons of Great Britain and Ireland. UK guidelines for the management of acute pancreatitis.
Gut 2005; 54 Suppl 3:iii1.
61. Pitchumoni CS, Yegneswaran B. Acute pancreatitis in pregnancy. World J Gastroenterol 2009;
15:5641.
62. Ghumman E, Barry M, Grace PA. Management of gallstones in pregnancy. Br J Surg 1997;
84:1646.
63. Ramin KD, Ramin SM, Richey SD, Cunningham FG. Acute pancreatitis in pregnancy. Am J
Obstet Gynecol 1995; 173:187.
64. Chen CP, Wang KG, Su TH, Yang YC. Acute pancreatitis in pregnancy. Acta Obstet Gynecol
Scand 1995; 74:607.
65. Wilkinson EJ. Acute pancreatitis in pregnancy: a review of 98 cases and a report of 8 new
cases. Obstet Gynecol Surv 1973; 28:281.
66. Robertson KW, Stewart IS, Imrie CW. Severe acute pancreatitis and pregnancy. Pancreatology
2006; 6:309.
67. Swisher SG, Hunt KK, Schmit PJ, et al. Management of pancreatitis complicating pregnancy.
Am Surg 1994; 60:759.
68. Legro RS, Laifer SA. First-trimester pancreatitis. Maternal and neonatal outcome. J Reprod Med
1995; 40:689.
69. Cosenza CA, Saffari B, Jabbour N, et al. Surgical management of biliary gallstone disease
during pregnancy. Am J Surg 1999; 178:545.
70. Block P, Kelly TR. Management of gallstone pancreatitis during pregnancy and the postpartum
period. Surg Gynecol Obstet 1989; 168:426.
71. McKay AJ, O'Neill J, Imrie CW. Pancreatitis, pregnancy and gallstones. Br J Obstet Gynaecol
1980; 87:47.
72. Jouppila P, Mokka R, Larmi TK. Acute pancreatitis in pregnancy. Surg Gynecol Obstet 1974;
139:879.
73. Corlett RC Jr, Mishell DR Jr. Pancreatitis in pregnancy. Am J Obstet Gynecol 1972; 113:281.
74. Juo YY, Khrucharoen U, Sanaiha Y, et al. Cumulative Financial Burden of Readmissions for
Biliary Pancreatitis in Pregnant Women. Obstet Gynecol 2018; 132:415.
75. Steinbrook RA, Brooks DC, Datta S. Laparoscopic cholecystectomy during pregnancy. Review
of anesthetic management, surgical considerations. Surg Endosc 1996; 10:511.
76. Veerappan A, Gawron AJ, Soper NJ, Keswani RN. Delaying cholecystectomy for complicated
gallstone disease in pregnancy is associated with recurrent postpartum symptoms. J
Gastrointest Surg 2013; 17:1953.
77. Athwal R, Bhogal RH, Hodson J, Ramcharan S. Surgery for gallstone disease during pregnancy
does not increase fetal or maternal mortality: a meta-analysis. Hepatobiliary Surg Nutr 2016;
5:53.
78. Silvestri MT, Pettker CM, Brousseau EC, et al. Morbidity of appendectomy and cholecystectomy
in pregnant and nonpregnant women. Obstet Gynecol 2011; 118:1261.
79. McKellar DP, Anderson CT, Boynton CJ, Peoples JB. Cholecystectomy during pregnancy
without fetal loss. Surg Gynecol Obstet 1992; 174:465.
80. Corneille MG, Gallup TM, Bening T, et al. The use of laparoscopic surgery in pregnancy:
evaluation of safety and efficacy. Am J Surg 2010; 200:363.
81. Curet MJ. Special problems in laparoscopic surgery. Previous abdominal surgery, obesity, and
pregnancy. Surg Clin North Am 2000; 80:1093.
82. Nezhat FR, Tazuke S, Nezhat CH, et al. Laparoscopy during pregnancy: a literature review.
JSLS 1997; 1:17.
83. Reedy MB, Källén B, Kuehl TJ. Laparoscopy during pregnancy: a study of five fetal outcome
parameters with use of the Swedish Health Registry. Am J Obstet Gynecol 1997; 177:673.
84. Lanzafame RJ. Laparoscopic cholecystectomy during pregnancy. Surgery 1995; 118:627.
85. Lachman E, Schienfeld A, Voss E, et al. Pregnancy and laparoscopic surgery. J Am Assoc
Gynecol Laparosc 1999; 6:347.
86. Affleck DG, Handrahan DL, Egger MJ, Price RR. The laparoscopic management of appendicitis
and cholelithiasis during pregnancy. Am J Surg 1999; 178:523.
87. Rollins MD, Chan KJ, Price RR. Laparoscopy for appendicitis and cholelithiasis during
pregnancy: a new standard of care. Surg Endosc 2004; 18:237.
88. Conron RW Jr, Abbruzzi K, Cochrane SO, et al. Laparoscopic procedures in pregnancy. Am
Surg 1999; 65:259.
89. Graham G, Baxi L, Tharakan T. Laparoscopic cholecystectomy during pregnancy: a case series
and review of the literature. Obstet Gynecol Surv 1998; 53:566.
90. Barone JE, Bears S, Chen S, et al. Outcome study of cholecystectomy during pregnancy. Am J
Surg 1999; 177:232.
91. Pucci RO, Seed RW. Case report of laparoscopic cholecystectomy in the third trimester of
pregnancy. Am J Obstet Gynecol 1991; 165:401.
92. Sen G, Nagabhushan JS, Joypaul V. Laparoscopic cholecystectomy in third trimester of

pregnancy. J Obstet Gynaecol 2002; 22:556.
93. Geisler JP, Rose SL, Mernitz CS, et al. Non-gynecologic laparoscopy in second and third
trimester pregnancy: obstetric implications. JSLS 1998; 2:235.
94. Eichenberg BJ, Vanderlinden J, Miguel C, et al. Laparoscopic cholecystectomy in the third
trimester of pregnancy. Am Surg 1996; 62:874.
95. Upadhyay A, Stanten S, Kazantsev G, et al. Laparoscopic management of a nonobstetric

emergency in the third trimester of pregnancy. Surg Endosc 2007; 21:1344.
96. Abuabara SF, Gross GW, Sirinek KR. Laparoscopic cholecystectomy during pregnancy is safe
for both mother and fetus. J Gastrointest Surg 1997; 1:48.
97. Halkic N, Tempia-Caliera AA, Ksontini R, et al. Laparoscopic management of appendicitis and
symptomatic cholelithiasis during pregnancy. Langenbecks Arch Surg 2006; 391:467.
Topic 15095 Version 28.0
GRAPHICS
Indications for nonobstetric surgery during pregnancy
Indication Incidence
Appendicitis 1:1500 pregnancies
Cholecystitis 1:1500 to 1:10,000 pregnancies
Bowel 1:1500 to 1:3500 pregnancies

obstruction
Adnexal 1:3000 to 1:4000 pregnancies

torsion
Breast or 1:3000 to 1:5000 pregnancies

cervical
disease
Trauma Variable (trauma complicates 4 to 8 percent of all pregnancies, but the incidence of severe life-
threatening trauma possibly requiring surgery is 0.3 to 0.4 percent)
Graphic 71938 Version 6.0
Criteria for the diagnosis of preeclampsia
Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on at least two occasions at
least four hours apart after 20 weeks of gestation in a previously normotensive patient AND the new onset
of one or more of the following*:
Proteinuria ≥0.3 g in a 24-hour urine specimen or protein/creatinine ratio ≥0.3 (mg/mg) (30 mg/mmol) in a
random urine specimen or dipstick ≥2+ if a quantitative measurement is unavailable
Platelet count <100,000/microL
Serum creatinine >1.1 mg/dL (97.2 micromol/L) or doubling of the creatinine concentration in the absence of
other renal disease
Liver transaminases at least twice the upper limit of the normal concentrations for the local laboratory
Pulmonary edema
Cerebral or visual symptoms (eg, new-onset and persistent headaches not accounted for by alternative diagnoses
and not responding to usual doses of analgesics ¶; blurred vision, flashing lights or sparks, scotomata)
In a woman with chronic/preexisting hypertension, criteria for superimposed preeclampsia are new onset of
proteinuria, significant end-organ dysfunction, or both after 20 weeks of gestation. For women with
chronic/preexisting hypertension who have proteinuria prior to or in early pregnancy, superimposed preeclampsia is
defined by worsening or resistant hypertension (especially acutely) in the last half of pregnancy or development of
signs/symptoms of the severe end of the disease spectrum.
* If systolic blood pressure is ≥160 mmHg or diastolic blood pressure is ≥110 mmHg, confirmation within minutes is
sufficient.
¶ Response to analgesia does not exclude the possibility of preeclampsia.
Adapted from: American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 202: Gestational
Hypertension and Preeclampsia. Obstet Gynecol 2019; 133:e1-e25.
Reported frequency of signs and symptoms of HELLP syndrome
Sign/symptom Frequency, percent
Proteinuria 86 to 100
Hypertension 82 to 88
Right upper quadrant/epigastric pain 40 to 90
Nausea, vomiting 29 to 84
Headache 33 to 61
Visual changes 10 to 20
Jaundice 5
Changes in appendiceal position during pregnancy
Reproduced with permission from: Harwood-Nuss A, Wolfson AB, et al. The Clinical
Practice of Emergency Medicine, 3rd ed, Lippincott Williams & Wilkins, Philadelphia
2001. Copyright © 2001 Lippincott Williams & Wilkins.
Normal reference ranges in pregnant women
Nonpregnant First Second Third

References
woman* trimester trimester trimester
Hematology
Erythropoietin ¶ 4 to 27 12 to 25 8 to 67 14 to 222 1-3

(units/L)
Ferritin ¶ (ng/mL) 10 to 150 Δ 6 to 130 2 to 230 0 to 116 1-8
Folate, red blood cell 150 to 450 137 to 589 94 to 828 109 to 663 6, 9, 10
(ng/mL)
Folate, serum (ng/mL) 5.4 to 18.0 2.6 to 15.0 0.8 to 24.0 1.4 to 20.7 1, 6, 9-13
Haptoglobin (mg/mL) 25 to 250 130 ± 43 115 ± 50 135 ± 65 93
Hemoglobin ¶ (g/dL) 12 to 15.8 Δ 11.6 to 13.9 9.7 to 14.8 9.5 to 15.0 2, 3, 6, 7, 13
Hematocrit ¶ (percent) 35.4 to 44.4 31.0 to 41.0 30.0 to 39.0 28.0 to 40.0 1, 2, 5, 6, 13-
15
Iron, total binding 251 to 406 278 to 403 Not reported 359 to 609 7
capacity ¶ (mcg/dL)
Iron, serum ¶ (mcg/dL) 41 to 141 72 to 143 44 to 178 30 to 193 2, 7
Mean corpuscular 27 to 32 30 to 32 30 to 33 29 to 32 5
hemoglobin (pg/cell)
Mean corpuscular 79 to 93 81 to 96 82 to 97 81 to 99 5, 6, 13, 14

volume (xm 3)
Platelet (x10 9/L) 165 to 415 174 to 391 155 to 409 146 to 429 5, 6, 14, 16, 17
Mean platelet volume 6.4 to 11.0 7.7 to 10.3 7.8 to 10.2 8.2 to 10.4 5
(mcm 3)
Red blood cell count 4.00 to 5.20 Δ 3.42 to 4.55 2.81 to 4.49 2.71 to 4.43 5, 6, 13, 14
(x10 6/mm 3)
Red cell distribution <14.5 12.5 to 14.1 13.4 to 13.6 12.7 to 15.3 5
width (percent)
White blood cell count 3.5 to 9.1 5.7 to 13.6 5.6 to 14.8 5.9 to 16.9 5, 6, 13, 14, 18
(x10 3/mm 3)
Neutrophils 1.4 to 4.6 3.6 to 10.1 3.8 to 12.3 3.9 to 13.1 5, 14, 16, 18
(x10 3/mm 3)
Lymphocytes 0.7 to 4.6 1.1 to 3.6 0.9 to 3.9 1.0 to 3.6 5, 14, 16, 18
(x10 3/mm 3)
Monocytes 0.1 to 0.7 0.1 to 1.1 0.1 to 1.1 0.1 to 1.4 5, 14, 18
(x10 3/mm 3)
Eosinophils 0 to 0.6 0 to 0.6 0 to 0.6 0 to 0.6 14, 18
(x10 3/mm 3)
Basophils (x10 3/mm 3) 0 to 0.2 0 to 0.1 0 to 0.1 0 to 0.1 14, 18
Transferrin (mg/dL) 200 to 400 254 to 344 220 to 441 288 to 530 4, 5
Transferrin, saturation 22 to 46 ¶ Not reported 10 to 44 5 to 37 3

without iron (percent)
Transferrin, saturation 22 to 46 ¶ Not reported 18 to 92 9 to 98 3

with iron (percent)
Coagulation
Antithrombin, functional 70 to 130 89 to 114 78 to 126 82 to 116 17, 19, 20

(percent)
D-dimer (mcg/mL) 0.22 to 0.74 0.05 to 0.95 0.32 to 1.29 0.13 to 1.7 17, 20-24, 87
Factor V (percent) 50 to 150 75 to 95 72 to 96 60 to 88 25
Factor VII (percent) 50 to 150 100 to 146 95 to 153 149 to 211 17
Factor VIII (percent) 50 to 150 90 to 210 97 to 312 143 to 353 17, 25
Factor IX (percent) 50 to 150 103 to 172 154 to 217 164 to 235 17
Factor XI (percent) 50 to 150 80 to 127 82 to 144 65 to 123 17
Factor XII (percent) 50 to 150 78 to 124 90 to 151 129 to 194 17
Fibrinogen (mg/dL) 211 to 496 244 to 510 291 to 538 301 to 696 5, 17, 20, 21,
23, 24, 87
Homocysteine (mmol/L) 4.4 to 10.8 3.34 to 11 2.0 to 26.9 3.2 to 21.4 6, 9, 10-12
International 0.9 to 1.04 ◊ 0.86 to 1.08 0.83 to 1.02 0.80 to 1.09 19, 24
Normalized Ratio
Partial thromboplastin 26.3 to 39.4 23.0 to 38.9 22.9 to 38.1 22.6 to 35.0 5, 17, 19, 24
time, activated
(seconds)
Plasminogen activator 17.3 ± 5.7 17.7 ± 1.9 Not reported 66.4 ± 4.9 87
inhibitor-1 (PAI-1)
antigen (pg/mL)
Plasminogen activator 9.3 ± 1.9 9.0 ± 0.8 Not reported 31.4 ± 3.0 87
inhibitor-1 (PAI-1)
activity (arbitrary units)
Prothrombin time 12.7 to 15.4 9.7 to 13.5 9.5 to 13.4 9.6 to 12.9 5, 17, 24
(seconds)
Protein C, functional 70 to 130 78 to 121 83 to 133 67 to 135 19, 25, 26

(percent)
Protein S, total 70 to 140 39 to 105 27 to 101 33 to 101 17, 25, 26

(percent)
Protein S, free (percent) 70 to 140 34 to 133 19 to 113 20 to 65 25, 26
Protein S, functional 65 to 140 57 to 95 42 to 68 16 to 42 25

activity (percent)
Tissue plasminogen 1.6 to 13 § 1.8 to 6.0 2.36 to 6.6 3.34 to 9.20 17, 19, 87
activator (ng/mL)
Tissue plasminogen 4 to 43 16 to 33 36 to 55 67 to 92 17
activator inhibitor-1
(ng/mL)
von Willebrand measurements
von Willebrand factor 75 to 125 62 to 318 90 to 247 84 to 422 20, 27, 28

antigen (percent)
ADAMTS-13, von 40 to 170 ¥ 40 to 160 22 to 135 38 to 105 20, 28

Willebrand cleaving
protease
Blood chemical constituents
Alanine transaminase 7 to 41 3 to 30 2 to 33 2 to 25 4, 5, 8, 29
(units/L)
Albumin (g/dL) 4.1 to 5.3 Δ 3.1 to 5.1 2.6 to 4.5 2.3 to 4.2 29-32
Alkaline phosphatase 33 to 96 17 to 88 25 to 126 38 to 229 4, 5, 8, 29, 30

(units/L)
Alpha-1 antitrypsin 100 to 200 225 to 323 273 to 391 327 to 487 5
(mg/dL)
Alpha-fetoprotein — — Approximately Approximately 95

(ng/mL) 130-400 130-590
Ammonia (microM) 31 ± 3.2 — — 27.3 ± 1.6 94
Amylase (units/L) 20 to 96 24 to 83 16 to 73 15 to 81 4, 5, 33, 34
Anion gap (mmol/L) 7 to 16 13 to 17 12 to 16 12 to 16 5
Aspartate transaminase 12 to 38 3 to 23 3 to 33 4 to 32 4, 5, 8, 29
(units/L)
Bicarbonate (mmol/L) 22 to 30 20 to 24 20 to 24 20 to 24 5
Bilirubin, total (mg/dL) 0.3 to 1.3 0.1 to 0.4 0.1 to 0.8 0.1 to 1.1 4, 29
Bilirubin, unconjugated 0.2 to 0.9 0.1 to 0.5 0.1 to 0.4 0.1 to 0.5 5, 29
(mg/dL)
Bilirubin, conjugated 0.1 to 0.4 0 to 0.1 0 to 0.1 0 to 0.1 29

(mg/dL)
Bile acids (micromol/L) 0.3 to 4.8 ‡ 0 to 4.9 0 to 9.1 0 to 11.3 29, 35
CA-125 antigen 7.2 to 27.0 2/2 to 268 12 to 25.1 16.8 to 43.8 88, 89, 90
(units/mL)
Calcium, ionized 4.5 to 5.3 4.5 to 5.1 4.4 to 5.0 4.4 to 5.3 5, 31, 36, 37
(mg/dL)
Calcium, total (mg/dL) 8.7 to 10.2 8.8 to 10.6 8.2 to 9.0 8.2 to 9.7 4, 5, 30, 32,
36-38
Ceruloplasmin (mg/dL) 25 to 63 30 to 49 40 to 53 43 to 78 5, 39
Chloride (mEq/L) 102 to 109 101 to 105 97 to 109 97 to 109 4, 5, 40
Creatinine (mg/dL) 0.5 to 0.9 Δ 0.4 to 0.7 0.4 to 0.8 0.4 to 0.9 4, 5, 46
Gamma-glutamyl 9 to 58 2 to 23 4 to 22 3 to 26 4, 5, 8, 29
transpeptidase (units/L)
Lactate dehydrogenase 115 to 221 78 to 433 80 to 447 82 to 524 4, 5, 32, 8

(units/L)
Lipase (units/L) 3 to 43 21 to 76 26 to 100 41 to 112 33
Magnesium (mg/dL) 1.5 to 2.3 1.6 to 2.2 1.5 to 2.2 1.1 to 2.2 4, 5, 30-32, 36,
38
Osmolality (mOsm/kg 275 to 295 275 to 280 276 to 289 278 to 280 38, 41
H20)
Phosphate (mg/dL) 2.5 to 4.3 3.1 to 4.6 2.5 to 4.6 2.8 to 4.6 4, 5, 30, 31, 42
Potassium (mEq/L) 3.5 to 5.0 3.6 to 5.0 3.3 to 5.0 3.3 to 5.1 4, 5, 15, 31,
32, 38, 40
Prealbumin (mg/dL) 17 to 34 15 to 27 20 to 27 14 to 23 5
Protein, total (g/dL) 6.7 to 8.6 6.2 to 7.6 5.7 to 6.9 5.6 to 6.7 5, 31, 32
Sodium (mEq/L) 136 to 146 133 to 148 129 to 148 130 to 148 4, 5, 15, 31,
32, 38, 41
Urea nitrogen (mg/dL) 7 to 20 7 to 12 3 to 13 3 to 11 4, 5, 40
Uric acid (mg/dL) 2.5 to 5.6 Δ 2.0 to 4.2 2.4 to 4.9 3.1 to 6.3 4, 5, 41
Metabolic and endocrine tests
Aldosterone (ng/dL) 2 to 9 6 to 104 9 to 104 15 to 101 43, 44, 45
Angiotensin converting 9 to 67 1 to 38 1 to 36 1 to 39 39, 46

enzyme (units/L)
Alpha-fetoprotein 0 to 8.5 Not reported 50 to 425 50 to 590 84, 86

(ng/mL)
Cortisol (mcg/dL) 0 to 25 7 to 19 10 to 42 12 to 50 5, 45
Hemoglobin A 1C 4 to 6 4 to 6 4 to 6 4 to 7 36, 47, 48

(percent)
Parathyroid hormone 8 to 51 10 to 15 18 to 25 9 to 26 30
(pg/mL)
Parathyroid hormone- <1.3 † 0.7 to 0.9 1.8 to 2.2 2.5 to 2.8 30

related protein (pmol/L)
Renin, plasma activity 0.3 to 9.0 † Not reported 7.5 to 54.0 5.9 to 58.8 40, 44
(ng/mL/hour)
Thyroid-stimulating 0.34 to 4.25 0.60 to 3.40 0.37 to 3.60 0.38 to 4.04 4, 5, 49

hormone (milli-int.
units/mL)
[American Thyroid 0.1 to 2.5 0.2 to 3.0 0.3 to 3.0 85
Association
recommendation]**
Thyroxine-binding 1.3 to 3.0 1.8 to 3.2 2.8 to 4.0 2.6 to 4.2 5

globulin (mg/dL)
Thyroxine, free (ng/dL) 0.8 to 1.7 0.8 to 1.2 0.6 to 1.0 0.5 to 0.8 5, 49
Thyroxine, total 5.4 to 11.7 6.5 to 10.1 7.5 to 10.3 6.3 to 9.7 5, 32
(mcg/dL)
Triiodothyronine, free 2.4 to 4.2 4.1 to 4.4 4.0 to 4.2 Not reported 49
(pg/mL)
Triiodothyronine, total 77 to 135 97 to 149 117 to 169 123 to 162 5

(ng/dL)
Vitamins and minerals
Copper (mcg/dL) 70 to 140 112 to 199 165 to 221 130 to 240 50, 51, 5
Selenium (mcg/L) 63 to 160 116 to 146 75 to 145 71 to 133 5, 50
Vitamin A (retinol) 20 to 100 32 to 47 35 to 44 29 to 42 5

(mcg/dL)
Vitamin B12 (pg/mL) 279 to 966 118 to 438 130 to 656 99 to 526 6, 10
Vitamin C (ascorbic 0.4 to 1.0 Not reported Not reported 0.9 to 1.3 52
acid) (mg/dL)
Vitamin D, 1,25- 25 to 45 20 to 65 72 to 160 60 to 119 30, 36

dihydroxy (pg/mL)
Vitamin D, 24,25- 0.5 to 5.0 † 1.2 to 1.8 1.1 to 1.5 0.7 to 0.9 53
dihydroxy (ng/mL)
Vitamin D, 25-hydroxy 14 to 80 18 to 27 10 to 22 10 to 18 30, 53

(ng/mL)
Vitamin E (α- 5 to 18 7 to 13 10 to 16 13 to 23 5
tocopherol) (mcg/mL)
Zinc (mcg/dL) 75 to 120 57 to 88 51 to 80 50 to 77 5, 13, 50
Autoimmune and inflammatory mediators
C3 complement (mg/dL) 83 to 177 62 to 98 73 to 103 77 to 111 5
C4 complement (mg/dL) 16 to 47 18 to 36 18 to 34 22 to 32 5
C-reactive protein 0.2 to 3.0 Not reported 0.4 to 20.3 0.4 to 8.1 54
(mg/L)
Erythrocyte 0 to 20 Δ 4 to 57 7 to 47 13 to 70 55
sedimentation rate
(mm/hour)
Immunoglobulin A 70 to 350 95 to 243 99 to 237 112 to 250 5

(mg/dL)
Immunoglobulin G 700 to 1700 981 to 1267 813 to 1131 678 to 990 5

(mg/dL)
Immunoglobulin M 50 to 300 78 to 232 74 to 218 85 to 269 5

(mg/dL)
Sex hormones
Dehydroepiandrosterone 1.3 to 6.8 † 2.0 to 16.5 0.9 to 7.8 0.8 to 6.5 56

sulfate (mmol/L)
Estradiol (pg/mL) <20 to 443 Δ ,¶ ¶ 188 to 2497 1278 to 7192 614 to 3460 56, 57
Progesterone (ng/mL) <1 to 20 Δ 8 to 48 99 to 342 56, 57
Prolactin (ng/mL) 0 to 20 36 to 213 110 to 330 137 to 372 30, 47, 57, 58
Sex hormone binding 18 to 114 Δ 39 to 131 214 to 717 216 to 724 56, 59
globulin (nmol/L)
Testosterone (ng/dL) 6 to 86 Δ 25.7 to 211.4 34.3 to 242.9 62.9 to 308.6 56
17-hydroxyprogesterone 0.6 to 10.6 Δ ,† 5.2 to 28.5 5.2 to 28.5 15.5 to 84 56

(nmol/L)
Lipids
Cholesterol, total <200 141 to 210 176 to 299 219 to 349 5, 60-62
(mg/dL)
High-density lipoprotein 40 to 60 40 to 78 52 to 87 48 to 87 5, 60-63
cholesterol (mg/dL)
Low-density lipoprotein <100 60 to 153 77 to 184 101 to 224 5, 60-63
cholesterol (mg/dL)
Very-low-density 6 to 40 † 10 to 18 13 to 23 21 to 36 62
lipoprotein cholesterol
(mg/dL)
Triglycerides (mg/dL) <150 40 to 159 75 to 382 131 to 453 4, 5, 60-63
Apolipoprotein A-I 119 to 240 111 to 150 142 to 253 145 to 262 4, 47, 61
(mg/dL)
Apolipoprotein B 52 to 163 58 to 81 66 to 188 85 to 238 4, 47, 61

(mg/dL)
Cardiac function
Cardiac output 4.8 to 6.8 5.6 to 9.7 5.5 to 9.9 4.8 to 8.7 64, 65, 66, 67,
(L/minute) 68
Cardiac index 2.6 to 4.2 3.2 to 4.6 3.1 to 4.7 2.5 to 4.4 65, 68
(L/min/m 2)
Stroke volume (mL) 79 to 90 77.5 to 107.6 70.3 to 107.6 54 to 99 65, 68, 69
Stroke index (mL/m 2) 46 to 62 39 to 62 30 to 42 65
Systemic vascular 700 to 1600 747 to 1485 692 to 1201 1034 to 1201 65, 67, 70
resistance (dyns/cm 5)
Echocardiography
Intraventricular septal 0.7 to 0.9 0.63 to 0.83 0.65 to 0.85 0.66 to 0.9 68, 69, 70, 91,
dimension (cm) 92
Posterior ventricular 0.75 to 0.9 0.56 to 0.8 0.59 to 0.9 0.59 to 0.9 68, 69, 70, 91,
wall dimension (cm) 92
Left ventricular mass 116 to 143 108 to 167 115 to 150 128 to 162 68, 70, 91, 92
(g)
Left ventricular mass 40 to 78 53 to 79 58 to 82 60 to 88 68, 70, 91, 92
index
E/A ratio 1.4 to 1.75 1.6 1.4 1.3 68, 70
Left ventricular diastolic 4.3 to 4.8 4.3 to 4.6 4.4 to 4.9 5.1 69, 70
diameter (cm)
Left ventricular systolic 2.8 to 3.1 2.8 to 2.9 2.8 to 3.4 2.8 to 3.3 69, 70
diameter (cm)
Left vent, fractional 35 to 36 35 to 37 3.5 35 to 36 69, 70

shortening (percent)
Left vent ejection 60 to 73 61 to 75 61 to 63 60 to 73 69, 70

fraction (percent)
Diastolic function
Mitral E wave 0.77 ± 0.11 0.85 ± 0.13 0.84 ± 0.16 0.77 ± 0.15 91, 92
(m/second)
Mitral A wave 0.46 ± 0.1 0.5 ± 0.09 0.5 ± 0.1 0.55 ± 0.1 91, 92
(m/second)
Isovolumic relaxation 69 ± 10 50 ± 10 79 ± 18 72 ± 16 91, 92

time (m/second)
Cardiac function (blood tests)
Atrial natriuretic peptide Not reported Not reported 28.1 to 70.1 Not reported 73
(pg/mL)
B-type natriuretic <167 (age- and 18.4 13.5 to 29.5 15.5 to 46 71, 72, 73
peptide (pg/mL) gender-specific)
Creatine kinase 39 to 238 Δ 27 to 83 25 to 75 13 to 101 5, 74

(units/L)
Creatine kinase-MB <6 ΔΔ — — 1.8 to 2.4 74

(units/L)
N-terminal pro-brain 50 ± 26 60 ± 45 60 ± 40 43 ± 34 96
natriuretic peptide
(pg/mL)
Troponin I (ng/mL) 0 to 0.08 Not reported Not reported 0 to 0.064 75, 76

(intrapartum)
Blood gas
pH 7.38 to 7.42 7.36 to 7.52 7.40 to 7.52 7.41 to 7.53 31, 77

(arterial) (venous) (venous) (venous)
7.39 to 7.45
(arterial)
PO 2 (mmHg) 90 to 100 93 to 100 90 to 98 92 to 107 77, 78
PCO 2 (mmHg) 38 to 42 Not reported Not reported 25 to 33 77
Bicarbonate (HCO 3 –) 22 to 26 Not reported Not reported 16 to 22 77

(mEq/L)
Renal function tests
Effective renal plasma 492 to 696 Δ ,† 696 to 985 612 to 1170 595 to 945 79, 80
flow (mL/minute)
Glomerular filtration 106 to 132 Δ 131 to 166 135 to 170 117 to 182 79, 80, 81
rate (GFR) (mL/minute)
Filtration fraction 16.9 to 24.7 ◊ ◊ 14.7 to 21.6 14.3 to 21.9 17.1 to 25.1 79, 80, 81
(percent)
Osmolarity, urine 500 to 800 326 to 975 278 to 1066 238 to 1034 82
(mOsm/kg)
2-4h albumin excretion <30 5 to 15 4 to 18 3 to 22 82, 83

(mg/24 hours)
24-h calcium excretion <7.5 † 1.6 to 5.2 0.3 to 6.9 0.8 to 4.2 15
(mmol/24 hours)
24-h creatinine 91 to 130 69 to 140 55 to 136 50 to 166 15, 80

clearance (mL/minute)
24-h creatinine 8.8 to 14 † 10.6 to 11.6 10.3 to 11.5 10.2 to 11.4 82

excretion (mmol/24
hours)
24-h potassium 25 to 100 † 17 to 33 10 to 38 11 to 35 15

excretion (mmol/24
hours)
24-h protein excretion <150 19 to 141 47 to 186 46 to 185 83

(mg/24 hours)
24-h sodium excretion 100 to 260 † 53 to 215 34 to 213 37 to 149 15, 41

(mmol/24 hours)
* Unless otherwise specified, all normal reference values are from the seventeenth edition of Harrison's Principles of Internal
Medicine [84].
¶ Range includes references with and without iron supplementation.
Δ Normal reference range is specific range for females.
◊ Reference values are from Cerneca et al: Coagulation and fibrinolysis changes in normal pregnancy increased levels of
procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive
fibrinolysis [19].
§ References values are from Cerneca et al and Choi et al: Tissue plasminogen activator levels change with plasma fibrinogen
concentrations during pregnancy [17,19].
¥ Reference values are from Mannuci et al: Changes in health and disease of the metalloprotease that cleaves von Willebrand
factor [28].
‡ Reference values are from Bacq Y et al: Liver function tests in normal pregnancy: a prospective study of 102 pregnant
women and 102 matched controls [29].
† Reference values are from the fifteenth edition of Harrison's Principles of Internal Medicine [85].
** The American Thyroid Association recommends these TSH ranges if individual laboratories do not determine their own
trimester-specific reference ranges.
¶¶ Range is for premenopausal females and varies by menstrual cycle phase.
ΔΔ Reference values are from Leiserowitz GS et al: Creatine kinase and its MB isoenzyme in the third trimester and the
peripartum period [74].
◊◊ Reference values are from Dunlop W: Serial changes in renal haemodynamics during normal human pregnancy [79].
References:
1. Beguin Y, Lipscei G, Thourmsin H, et al: Blunted erythropoietin production and decreased erythropoiesis in early
pregnancy. Blood 78(1):89, 1991.
2. Bianco I, Mastropietro F, D'Aseri C, et al: Serum levels of erythropoietin and soluble transferrin receptor during
pregnancy in non-β-thalassemic and β-thalassemic women. Haematologica 85:902, 2000 [PMID: 10980626].
3. Milman N, Graudal N, Nielsen OJ: Serum erythropoietin during normal pregnancy: Relationship to hemoglobin and iron
status markers and impact of iron supplementation in a longitudinal, placebo-controlled study on 118 women. Int J
Hematol 66:159, 1997 [PMID: 9277046].
4. Larsson A, Palm M, Hansson L-O, et al: Reference values for clinical chemistry tests during normal pregnancy. BJOG
115:874, 2008 [PMID: 18485166].
5. Lockitch G: Handbook of Diagnostic Biochemistry and Hematology in Normal Pregnancy. Boca Raton, FL, CRC Press,
1993.
6. Milman N, Bergholt T, Byg KE, et al: Reference intervals for haematological variables during normal pregnancy and
postpartum in 434 healthy Danish women. Eur J Haematol 79:39, 2007 [PMID: 17598837].
7. Romslo I, Haram K, Sagen N, et al: Iron requirement in normal pregnancy as assessed by serum ferritin, serum
transferring saturation and erythrocyte protoporphyrin determinations. Br J Obstet Gynaecol 90:101, 1983 [PMID:
6824608].
8. Van Buul EJA, Steegers EAP, Jongsma HW, et al: Haematological and biochemical profile of uncomplicated pregnancy in
nulliparous women; a longitudinal study. Neth J Med 46:73, 1995.
9. Milman N, Byg KE, Hvas AM, et al: Erythrocyte folate, plasma folate and plasma homocysteine during normal
pregnancy and postpartum: A longitudinal study comprising 404 Danish women. Eur J Haematol 76:200, 2006 [PMID:
16412135].
10. Walker MC, Smith GN, Perkins SL, et al: Changes in homocysteine levels during normal pregnancy. Am J Obstet
Gynecol 180:660, 1999 [PMID: 10076144].
11. López-Quesada E, Vilaseca MA, Lailla JM: Plasma total homocysteine in uncomplicated pregnancy and in preeclampsia.
Eur J Obstet Gynecol Reprod Biol 108:45, 2003 [PMID: 19899161].
12. Özerol E, Özerol I, Gökdeniz R, et al: Effect of smoking on serum concentrations of total homocysteine, folate, vitamin
B12, and nitric oxide in pregnancy: A preliminary study. Fetal Diagn Ther 19:145, 2004.
13. Qvist I, Abdulla M, Jägerstad M, et al: Iron, zinc and folate status during pregnancy and two months after delivery.
Acta Obstet Gynecol Scand 65:15, 1986 [PMID: 3716775].
14. Balloch AJ, Cauchi MN: Reference ranges for haematology parameters in pregnancy derived from patient populations.
Clin Lab Haemat 15:7, 1993 [PMID: 8472501].
15. Singh HJ, Mohammad NH, Nila A: Serum calcium and parathormone during normal pregnancy in Malay women. J
Matern Fetal Med 8:95, 1999 [PMID: 10338062].
16. AzizKarim S, Khurshid M, Rizvi JH, et al: Platelets and leucocyte counts in pregnancy. J Pak Med Assoc 42:86, 1992.
17. Choi JW, Pai SH: Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy.
Ann Hematol 81:611, 2002 [PMID: 12454697].
18. Belo L, Santos-Silva A, Rocha S, et al: Fluctuations in C-reactive protein concentration and neutrophil activation during
normal human pregnancy. Eur J Obstet Gynecol Reprod Biol 123:46, 2005 [PMID: 16260340].
19. Cerneca F, Ricci G, Simeone R, et al: Coagulation and fibrinolysis changes in normal pregnancy increased levels of
procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a
reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 73:31, 1997 [PMID: 9175686].
20. Lattuada A, Rossi E, Calzarossa C, et al: Mild to moderate reduction of a von Willebrand factor cleaving protease
(ADAMTS-13) in pregnant women with HELLP microangiopathic syndrome. Haematologica 88(9):1029, 2003.
21. Francalanci I, Comeglio P, Liotta AA, et al: D-Dimer concentrations during normal pregnancy, as measured by ELISA.
Thromb Res 78:399, 1995 [PMID: 7660356].
22. Kline JA, Williams GW, Hernandez-Nino J: D-Dimer concentrations in normal pregnancy: New diagnostic thresholds are
needed. Clin Chem 51:825, 2005 [PMID: 15764641].
23. Morse M: Establishing a normal range for D-dimer levels through pregnancy to aid in the diagnosis of pulmonary
embolism and deep vein thrombosis. J Thromb Haemost 2:1202, 2004 [PMID: 15219216].
24. Liu XH, Jiang YM, Shi H, et al: Prospective, sequential, longitudinal study of coagulation changes during pregnancy in
Chinese women. Int J Gynaecol Obstet 105(3):240, 2009.
25. Lefkowitz JB, Clarke SH, Barbour LA: Comparison of protein S functional and antigenic assays in normal pregnancy. Am
J Obstet Gynecol 175:657, 1996 [PMID: 8828430].
26. Faught W, Garner P, Jones G, et al: Changes in protein C and protein S levels in normal pregnancy. Am J Obstet
Gynecol 172:147, 1995 [PMID: 7847526].
27. Wickström K, Edelstam G, Löwbeer CH, et al: Reference intervals for plasma levels of fibronectin, von Willebrand
factor, free protein S and antithrombin during third-trimester pregnancy. Scand J Clin Lab Invest 64:31, 2004 [PMID:
13035697].
28. Mannucci PM, Canciani MT, Forza I, et al: Changes in health and disease of the metalloprotease that cleaves von
Willebrand factor. Blood 98(9):2730, 2001.
29. Bacq Y, Zarka O, Bréchot JF, et al: Liver function tests in normal pregnancy: A prospective study of 102 pregnant
women and 102 matched controls. Hepatology 23:1030, 1996 [PMID: 8621129].
30. Ardawi MSM, Nasrat HAN, BA'Aqueel HS: Calcium-regulating hormones and parathyroid hormone-related peptide in
normal human pregnancy and postpartum: A longitudinal study. Eur J Endocrinol 137:402, 1997 [PMID: 9368509].
31. Handwerker SM, Altura BT, Altura BM: Serum ionized magnesium and other electrolytes in the antenatal period of
human pregnancy. J Am Coll Nutr 15:36, 1996 [PMID: 8632112].
32. Hytten FE, Lind T: Diagnostic Indices in Pregnancy. Summit, NJ, CIBA-GEIGY Corporation, 1975.
33. Karsenti D, Bacq Y, Bréchot JF, et al: Serum amylase and lipase activities in normal pregnancy: A prospective case-
control study. Am J Gastroenterol 96:697, 2001 [PMID: 11280536].
34. Strickland DM, Hauth JC, Widish J, et al: Amylase and isoamylase activities in serum of pregnant women. Obstet
Gynecol 63:389, 1984 [PMID: 6199704].
35. Carter J: Serum bile acids in normal pregnancy. BJOG 98:540, 1991 [PMID: 1873244].
36. Mimouni F, Tsang RC, Hertzbert VS, et al: Parathyroid hormone and calcitriol changes in normal and insulin-dependent
diabetic pregnancies. Obstet Gynecol 74:49, 1989 [PMID: 2733941].
37. Pitkin RM, Gebhardt MP: Serum calcium concentrations in human pregnancy. Am J Obstet Gynecol 127:775, 1977
[PMID: 848531].
38. Shakhmatova EI, Osipova NA, Natochin YV: Changes in osmolality and blood serum ion concentrations in pregnancy.
Hum Physiol 26:92, 2000.
39. Louro MO, Cocho JA, Tutor JC: Assessment of copper status in pregnancy by means of determining the specific oxidase
activity of ceruloplasmin. Clin Chim Acta 312:123, 2001 [PMID: 11580917].
40. Dux S, Yaron A, Carmel A, et al: Renin, aldosterone, and serum-converting enzyme activity during normal and
hypertensive pregnancy. Gynecol Obstet Invest 17:252, 1984 [PMID: 6329926].
41. Davison JB, Vallotton MB, Lindheimer MD: Plasma osmolality and urinary concentration and dilution during and after
pregnancy: Evidence that lateral recumbency inhibits maximal urinary concentrating ability. BJOG 88:472, 1981
[PMID: 7236550].
42. Kato T, Seki K, Matsui H, et al: Monomeric calcitonin in pregnant women and in cord blood. Obstet Gynecol 92:241,
1998 [PMID: 9699759].
43. Elsheikh A, Creatsas G, Mastorakos G, et al: The renin-aldosterone system during normal and hypertensive pregnancy.
Arch Gynecol Obstet 264:182, 2001 [PMID: 11205704].
44. Kim EH, Lim JH, Kim YH, et al: The relationship between aldosterone to renin ratio and RI value of the uterine artery in
the preeclamptic patient vs. normal pregnancy. Yonsei Med J 49(1):138, 2008.
45. Suri D, Moran J, Hibbard JU, et al: Assessment of adrenal reserve in pregnancy: Defining the normal response to the
adrenocorticotropin stimulation test. J Clin Endocrinol Metab 91:3866, 2006 [PMID: 16895954].
46. Parente JV, Franco JG, Greene LJ, et al: Angiotensin-converting enzyme: Serum levels during normal pregnancy. Am J
Obstet Gynecol 135:586, 1979 [PMID: 228554].
47. Montelongo A, Lasunción MA, Pallardo LF, et al: Longitudinal study of plasma lipoproteins and hormones during
pregnancy in normal and diabetic women. Diabetes 41:1651, 1992 [PMID: 1446807].
48. Radder JK, Van Roosmalen J: HbAIC in healthy, pregnant women. Neth J Med 63:256, 2005 [PMID: 16093576].
49. Price A, Obel O, Cresswell J, et al: Comparison of thyroid function in pregnant and non-pregnant Asian and western
Caucasian women. Clin Chim Acta 208:91, 2001.
50. Álvarez SI, Castañón SG, Ruata MLC, et al: Updating of normal levels of copper, zinc and selenium in serum of
pregnant women. J Trace Elem Med Biol 21(S1):49, 2007.
51. Ilhan N, Ilhan N, Simsek M: The changes of trace elements, malondialdehyde levels and superoxide dismutase
activities in pregnancy with or without preeclampsia. Clin Biochem 35:393, 2002 [PMID: 12270770].
52. Sharma SC, Sabra A, Molloy A, et al: Comparison of blood levels of histamine and total ascorbic acid in pre-eclampsia
with normal pregnancy. Hum Nutr Clin Nutr 38C:3, 1984.
53. Reiter EO, Braunstein GD, Vargas A, et al: Changes in 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D during
pregnancy. Am J Obstet Gynecol 135:227, 1979 [PMID: 474676].
54. Hwang HS, Kwon JY, Kim MA, et al: Maternal serum highly sensitive C-reactive protein in normal pregnancy and pre-
eclampsia. Int J Gynecol Obstet 98:105, 2007 [PMID: 17588579].
55. van den Broek NR, Letsky EA: Pregnancy and the erythrocyte sedimentation rate. Br J Obstet Gynaecol 108:1164,
2001.
56. O'Leary P, Boyne P, Flett P, et al: Longitudinal assessment of changes in reproductive hormones during normal
pregnancy. Clin Chem 35(5):667, 1991.
57. Carranza-Lira S, Hernández F, Sánchez M, et al: Prolactin secretion in molar and normal pregnancy. Int J Gynaecol
Obstet 60:137, 1998 [PMID: 9509951].
58. Larrea F, Méndez I, Parra A: Serum pattern of different molecular forms of prolactin during normal human pregnancy.
Hum Reprod 8:1617, 1993 [PMID: 8300816].
59. Acromite MT, Mantzoros CS, Leach RE, et al: Androgens in preeclampsia. Am J Obstet Gynecol 180:60, 1999 [PMID:
9914579].
60. Belo L, Caslake M, Gaffney D, et al: Changes in LDL size and HDL concentration in normal and preeclamptic
pregnancies. Atherosclerosis 162:425, 2002 [PMID: 11996963].
61. Desoye G, Schweditsch MO, Pfeiffer KP, et al: Correlation of hormones with lipid and lipoprotein levels during normal
pregnancy and postpartum. J Clin Endocrinol Metab 64:704, 1987 [PMID: 3546352].
62. Jimenez DM, Pocovi M, Ramon-Cajal J, et al: Longitudinal study of plasma lipids and lipoprotein cholesterol in normal
pregnancy and puerperium. Gynecol Obstet Invest 25:158, 1988 [PMID: 3391425].
63. Piechota W, Staszewski A: Reference ranges of lipids and apolipoproteins in pregnancy. Eur J Obstet Gynecol Reprod
Biol 45:27, 1992 [PMID: 1618359].
64. Rang S, van Montfrans GA, Wolf H. Serial hemodynamic measurement in normal pregnancy, preeclampsia, and
intrauterine growth restriction. Am J Obstet Gynecol. 198(5):519.e1-9, 2008 PMID: 18279824.
65. Moertl MG, Ulrich D, Pickel K, et al: Changes in haemodynamic and autonomous nervous system parameters measured
non-invasively throughout normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 144 Suppl 1:S179-83. 2009 PMID:
19285779.
66. Pandey Ak, Das A, Srinivas C, et al: Maternal myocardial performances in various stages of pregnancy and post-
partum. Research Jour of Cardiology 3(1):9-16, 2010.
67. Lees M. Central circulatory responses in normotensive and hypertensive pregnancy. Postgrad Med J. 55(643): 311–
314, 1979. PMCID: PMC2425449.
68. Poppas A, Shroff SG, Korcarz CE, et al: Serial assessment of the cardiovascular system in normal pregnancy: Role of
arterial compliance and pulsatile arterial load. Circulation 95:2407-2415, 1997.
69. Katz R, Karliner JS, Resnik R: Effects of a natural volume overload state (pregnancy) on left ventricular performance in
normal human subjects. Circulation 58: 434-441, 1978.
70. Mesa A, Jessurun C, Hernandez A, et al: Left ventricular diastolic function in normal human pregnancy. Circulation
99:511-517, 1999.
71. Resnik JL, Hong C, Resnik R, et al: Evaluation of B-type natriuetic peptide (BNP) levels in normal and preeclamptic
women. Am J Obstet Gynecol 193:450-458, 2005.
72. Hamid RR, Larsson A, Pernow J, et al: Assessment of left ventricular structure and function in preeclampsia by
echocardiography and cardiovascular biomarkers. J Hypertens 27L2257-2264, 2009.
73. Borghi CB, Esposti DD, Immordino V, et al: Relationship of systemic hemodynamics, left ventricular structure and
function, and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia. Am J Obstet
Gynecol 183:140, 2000 [PMID: 10920322].
74. Leiserowitz GS, Evans AT, Samuels SJ, et al: Creatine kinase and its MB isoenzyme in the third trimester and the
peripartum period. J Reprod Med 37:910, 1992 [PMID: 1460608].
75. Koscica KL, Bebbington M, Bernstein PS: Are maternal serum troponin I levels affected by vaginal or cesarean delivery?
Am J Perinatol 21(1):31, 2004.
76. Shivvers SA, Wians FH, Keffer JH, et al: Maternal cardiac troponin I levels during labor and delivery. Am J Obstet
Gynecol 180:122, 1999 [PMID: 9914590].
77. Fadel HE, Northrop G, Misenhimer HR, et al: Acid-base determinations in amniotic fluid and blood of normal late
pregnancy. Obstet Gynecol 53:99, 1979 [PMID: 32503].
78. Spiropoulos K, Prodromaki E, Tsapanos V: Effect of body position on PaO2 and PaCO2 during pregnancy. Gynecol
Obstet Invest 58:22, 2004 [PMID: 15028865].
79. Dunlop W: Serial changes in renal haemodynamics during normal human pregnancy. Br J Obstet Gynaecol 88:1, 1981
[PMID: 7459285].
80. Ezimokhai M, Davison JM, Philips PR, et al: Non-postural serial changes in renal function during the third trimester of
normal human pregnancy. Br J Obstet Gynaecol 88:465, 1981 [PMID: 7236549].
81. Moran P, Baylis PH, Lindheimer, et al: Glomerular ultrafiltration in normal and preeclamptic pregnancy. J Am Soc
Nephrol 14:648, 2003 [PMID: 12595500].
82. Risberg A, Larsson A, Olsson K, et al: Relationship between urinary albumin and albumin/creatinine ratio during normal
pregnancy and pre-eclampsia. Scand J Clin Lab Invest 64:17, 2004 [PMID: 15025425].
83. Higby K, Suiter CR, Phelps JY, et al: Normal values of urinary albumin and total protein excretion during pregnancy. Am
J Obstet Gynecol 171:984, 1994 [PMID: 7943114].
84. Kratz A, Pesce MA, Basner RC, Einstein AJ. Appendix: Laboratory values of clinical importance. In: Longo DL, Fauci AS,
Kasper DL, et al (Eds). Harrison's Principles of Internal Medicine, 18th ed, McGraw-Hill, New York 2012. Appendix 1, p
A-1.
85. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis
and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21:1081.
86. Leek AE, Ruoss CF, Kitau MJ, Chard T. Magernal plasma alphafetoprotein levels in the second half of normal pregnancy:
Relationship to fetal weight, and maternal age and parity. BJOG 1975; 82:669.
87. Hale SA, Sobel B, Benvenuto A, et al. Coagulation and fibrinolytic system protein profiles in women with normal
pregnancies and pregnancies complicated by hypertension. Pregnancy Hypertens 2012; 2:152.
88. Spitzer M, Kaushal N, Benjamin F. Maternal CA-125 levels in pregnancy and the puerperium. J Reprod Med 1998;
43:387.
89. Aslam N, Ong C, Woelfer B, et al. Serum CA-125 at 11-14 weeks of gestation in women with morphologically normal
ovaries. BJOG 2000; 107:689.
90. Jacobs IJ, Fay TN, Stabile I, et al. The distribution of CA 125 in the reproductive tract of pregnant and non-pregnant
women. Br J Obstet Gynaecol 1988; 95:1190.
91. Savu O, Jurcuţ R, Giuşcă S, et al. Morphological and functional adaptation of the maternal heart during pregnancy. Circ
Cardiovasc Imaging 2012; 5:289.
92. Vitarelli A, Capotosto L. Role of echocardiography in the assessment and management of adult congenital heart disease
in pregnancy. Int J Cardiovasc Imaging 2011; 27:843.
93. Haram K, Augensen K, Elsayed S. Serum protein pattern in normal pregnancy with special reference to acute-phase
reactants. BJOG 1983; 90:139.
94. Jozwik M, Jozwik M, Pierzycki K, et al. Maternal and fetal blood ammonia concentrations in normal term human
pregnancies. Biol Neonate 2005; 87:38.
95. Leek AE, Ruoss CF, Kitau MG, et al. Maternal plasma alphafetoprotein levels in the second half of normal pregnancy:
relationship to fetal weight and maternal age and parity. BJOG 1975; 82:669.
96. Burlingame J, Hyeong JA, Tang WHW. Changes in cardiovascular biomarkers throughout pregnancy and the remote
postpartum period. Am J Obstet Gynecol 2013; 208:S97.
Modified and reproduced with permission from: Abbassi-Ghanavati M, Greer LG. Reference Table of Normal Laboratory Values
in Uncomplicated Pregnancies. In: Cunningham FG, Leveno KJ, Bloom S, Hauth JC, Rouse DJ, Spong CY. Williams Obstetrics,
23rd Edition. New York: McGraw-Hill, 2010. Copyright © 2010 The McGraw-Hill Companies, Inc.
Antimicrobial prophylaxis for gastrointestinal surgery in adults
Nature of Common Recommended Usual adult Redose

operation pathogens antimicrobials dose* interval ¶
Gastroduodenal surgery
Procedures Enteric gram-negative Cefazolin Δ <120 kg: 2 g IV Four hours

involving entry into bacilli, gram-positive ≥120 kg: 3 g IV
lumen of cocci
gastrointestinal
tract
Procedures not Enteric gram-negative High risk ◊ only: <120 kg: 2 g IV Four hours
involving entry into bacilli, gram-positive cefazolin Δ ≥120 kg: 3 g IV
lumen of cocci
gastrointestinal
tract (selective
vagotomy,
antireflux)
Biliary tract surgery (including pancreatic procedures)
Open procedure or Enteric gram-negative Cefazolin Δ ¥ <120 kg: 2 g IV Four hours

laparoscopic bacilli, enterococci, ≥120 kg: 3 g IV
procedure (high clostridia
risk) § OR cefotetan 2 g IV Six hours
OR cefoxitin 2 g IV Two hours
OR ampicillin- 3 g IV Two hours

sulbactam
Laparoscopic N/A None None None

procedure (low
risk)
Appendectomy ‡
Enteric gram-negative Cefoxitin Δ 2 g IV Two hours

bacilli, anaerobes,
OR cefotetan Δ 2 g IV Six hours
enterococci
OR cefazolin Δ <120 kg: 2 g IV Four hours
≥120 kg: 3 g IV
PLUS metronidazole 500 mg IV N/A
Small intestine surgery
Nonobstructed Enteric gram-negative Cefazolin Δ <120 kg: 2 g IV Four hours

bacilli, gram-positive ≥120 kg: 3 g IV
cocci
Obstructed Enteric gram-negative Cefoxitin Δ 2 g IV Two hours

bacilli, anaerobes,
enterococci
≥120 kg: 3 g IV
PLUS metronidazole 500 mg IV N/A
Hernia repair
Aerobic gram-positive Cefazolin Δ <120 kg: 2 g IV Four hours

organisms ≥120 kg: 3 g IV
Colorectal surgery †
Enteric gram-negative Parenteral:
bacilli, anaerobes, Cefoxitin Δ 2 g IV Two hours
enterococci

≥120 kg: 3 g IV
PLUS 500 mg IV N/A

metronidazole
OR ampicillin- 3 g IV (based on Two hours

sulbactam Δ,** combination)
Oral (used in conjunction with mechanical bowel preparation):
Neomycin PLUS ¶¶ ¶¶
erythromycin base
or metronidazole
IV: intravenous.
* Parenteral prophylactic antimicrobials can be given as a single IV dose begun within 60 minutes before the procedure. If
vancomycin or a fluoroquinolone is used, the infusion should be started within 60 to 120 minutes before the initial incision to
have adequate tissue levels at the time of incision and to minimize the possibility of an infusion reaction close to the time of
induction of anesthesia.
¶ For prolonged procedures (>3 hours) or those with major blood loss or in patients with extensive burns, additional
intraoperative doses should be given at intervals one to two times the half-life of the drug.
Δ For patients allergic to penicillins and cephalosporins, clindamycin (900 mg) or vancomycin (15 mg/kg IV; not to exceed 2
g) with either gentamicin (5 mg/kg IV), ciprofloxacin (400 mg IV), levofloxacin (500 mg IV), or aztreonam (2 g IV) is a
reasonable alternative. Metronidazole (500 mg IV) plus an aminoglycoside or fluoroquinolone are also acceptable alternative
regimens, although metronidazole plus aztreonam should not be used, since this regimen does not have aerobic gram-positive
activity.
◊ Morbid obesity, gastrointestinal (GI) obstruction, decreased gastric acidity or GI motility, gastric bleeding, malignancy or
perforation, or immunosuppression.
§ Factors that indicate high risk may include age >70 years, pregnancy, acute cholecystitis, nonfunctioning gall bladder,
obstructive jaundice, common bile duct stones, immunosuppression.
¥ Cefotetan, cefoxitin, and ampicillin-sulbactam are reasonable alternatives.
‡ For a ruptured viscus, therapy is often continued for approximately five days.
† Use of ertapenem or other carbapenems not recommended due to concerns of resistance.
** Due to increasing resistance of Escherichia coli to fluoroquinolones and ampicillin-sulbactam, local sensitivity profiles
should be reviewed prior to use.
¶¶ In addition to mechanical bowel preparation, the following oral antibiotic regimen is administered: neomycin (1 g) plus
erythromycin base (1 g) OR neomycin (1 g) plus metronidazole (1 g). The oral regimen should be given as three doses over
approximately 10 hours the afternoon and evening before the operation. Issues related to mechanical bowel preparation are
discussed further separately; refer to the UpToDate topic on overview of colon resection.
Data from:
1. Antimicrobial prophylaxis for surgery. Med Lett Drugs Ther 2016; 58:63.
2. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg
Infec (Larchmt) 2013; 14:73.
Expected height of the uterine fundus by month of

pregnancy
Reproduced with permission from: Bickley LS, Szilagyi P. Bates' Guide to Physical
Examination and History Taking, 8th ed, Lippincott Williams & Wilkins, Philadelphia
2003. Copyright © 2003 Lippincott Williams & Wilkins.
Laparoscopic cholecystectomy in pregnant women
Entry into the peritoneal cavity can be gained through the left upper quadrant or
via a supraumbilical port (shown in red in the figure).
For left upper quadrant access, a Veress needle is inserted. Gastric
decompression with an orogastric tube prior to needle insertion minimizes
the risk of gastric perforation. The needle should be angled approximately 15
degrees caudad to minimize the risk of splenic injury.
Placement of a supraumbilical port 6 cm above the fundus with a Hasson
technique is another entry method that reduces the risk of organ perforation.
Additional ports required for performing laparoscopic cholecystectomy include
two 5 mm ports in the right upper quadrant and an 11 mm port in the
epigastrium (shown in black in the figure).
Laparoscopic cholecystectomy
(A) Port placement.

(B) Initial retraction of gallbladder.
(C) Critical view of safety.
(D) Clipping and division of cystic artery and duct.
(E) Dissection of gallbladder from liver bed.
(F) Extraction of gallbladder.
Critical view of safety in laparoscopic cholecystectomy
The critical view of safety is a "window" crossed by two structures: the cystic duct
and artery. This is achieved by exposing the base of the liver bed and dissecting
Calot's triangle free of all tissue except for the cystic duct and artery. The two
structures emanating from the gallbladder (cystic duct and cystic artery) and the
interface with the liver at the base of the gallbladder fossa should be definitively
identified. The critical view of safety should be achieved prior to clipping or dividing
any tubular structures in a laparoscopic cholecystectomy. Difficulty with
identification of the critical view should lead the surgeon to consider performing
cholangiography or converting the laparoscopic cholecystectomy into an open
procedure.
Shielding fetus from irradiation during surgery
During cholangiography, the fetus should be shielded by placing a lead apron on

the lower abdomen of the patient. Because the biliary tree is in the upper
abdomen, shielding the fetus in this way does not usually compromise the field
of view necessary for proper imaging.
Contributor Disclosures
David C Brooks, MD Nothing to disclose Stanley W Ashley, MD Nothing to disclose Vincenzo Berghella,
MD Nothing to disclose Wenliang Chen, MD, PhD Nothing to disclose Vanessa A Barss, MD, FACOG Nothing
to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

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● (See "Gallstones: Epidemiology, risk factors and prevention".)

These changes normalize one to two months following delivery.

PERSONAL RISK FACTORS

INCIDENCE AND COURSE

Serious complications of gallstones, such as acute cholecystitis, choledocholithiasis, gangrenous

Categorization of presentations — The presentation of gallstone disease during pregnancy is

● No symptoms, but gallstones on ultrasound examination (incidental gallstones)

Laboratory findings — Laboratory studies should be normal in patients with uncomplicated

DIFFERENTIAL DIAGNOSIS OF PREGNANT WOMEN WITH RUQ OR

Pregnancy-related conditions — Pregnancy-related conditions that may be associated with RUQ or

● Preeclampsia/HELLP – Hypertension is the requisite criterion for preeclampsia (table 2) and is

● Intra-amniotic infection – Signs and symptoms of intra-amniotic infection include fever,

Nonpregnancy-related conditions — Nonpregnancy-related conditions include non-gallstone-

● Choledocholithiasis (see "Choledocholithiasis: Clinical manifestations, diagnosis, and

DIAGNOSTIC TESTING IN PREGNANCY

● Aspartate aminotransferase/alanine aminotransferase (AST/ALT), total bilirubin, alkaline

● Serum amylase and lipase (to evaluate for pancreatitis)

● Urine protein (to evaluate for preeclampsia)

Ultrasonography — Ultrasonography is a reliable and safe method for identifying gallstones in

Magnetic resonance imaging — Magnetic resonance cholangiopancreatography (MRCP) is not

HIDA scan — Cholescintigraphy using 99mTc-hepatic iminodiacetic acid (generically referred to

Although acute cholecystitis is primarily an inflammatory process, secondary infection of the

Monotherapy with a beta-lactam/beta-lactamase inhibitor, such as one of the following, is appropriate

● Ampicillin-sulbactam 3 g intravenously every six hours

● Piperacillin-tazobactam 3.375 g intravenously every six hours

● Ticarcillin-clavulanate 3.1 g intravenously every four hours

An acceptable alternative is a third-generation cephalosporin, such as ceftriaxone 1 g intravenously

nephrotoxicity, so drug levels should be monitored. Additional information about perioperative

● If sludge/stones persist, we suggest performing cholecystectomy within three months after

● If sludge/stones disappear postpartum, we believe it is reasonable to take a watchful waiting

● (See "Treatment of acute calculous cholecystitis".)

● (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management", section on

● (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on

● (See "Management of acute pancreatitis", section on 'Gallstone pancreatitis'.)

• If she continues to have symptoms or shows signs of developing complications in spite of

These recommendations are based on the following lines of evidence:

● In an administrative database study, compared with women who underwent cholecystectomy

Choledocholithiasis/cholangitis — Patients who develop symptomatic choledocholithiasis or

CHOLECYSTECTOMY DURING PREGNANCY

Surgical approach — Either an open or laparoscopic approach to cholecystectomy may be chosen;

Laparoscopic cholecystectomy can be offered to women in any trimester requiring cholecystectomy,

Laparoscopic cholecystectomy — A few modifications to standard techniques for laparoscopic

The remainder of the technique of laparoscopic cholecystectomy, including intraoperative evaluation

Open cholecystectomy — The surgical technique of open cholecystectomy is modified only

SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

● In pregnant women with RUQ or epigastric pain, pregnancy-related conditions must be

• Urgent or emergent intervention (cholecystectomy, biliary tract or gallbladder drainage) is

Use of UpToDate is subject to the Subscription and License Agreement.

2. Everson GT. Pregnancy and gallstones. Hepatology 1993; 17:159.

5. Igbinosa O, Poddar S, Pitchumoni C. Pregnancy associated pancreatitis revisited. Clin Res

7. Valdivieso V, Covarrubias C, Siegel F, Cruz F. Pregnancy and cholelithiasis: pathogenesis and

9. Liu B, Beral V, Balkwill A, Million Women Study Collaborators. Childbearing, breastfeeding,

31. Adelstein SJ. Administered radionuclides in pregnancy. Teratology 1999; 59:236.

44. Hedström J, Nilsson J, Andersson R, Andersson B. Changing management of gallstone-related

53. Howden JK, Baillie J. Preoperative versus postoperative endoscopic retrograde

58. DePaula AL, Hashiba K, Bafutto M. Laparoscopic management of choledocholithiasis. Surg

92. Sen G, Nagabhushan JS, Joypaul V. Laparoscopic cholecystectomy in third trimester of

95. Upadhyay A, Stanten S, Kazantsev G, et al. Laparoscopic management of a nonobstetric

Topic 15095 Version 28.0

Indications for nonobstetric surgery during pregnancy

Appendicitis 1:1500 pregnancies