WESTERN SURGICAL ASSOCIATION ARTICLE

Association Between Trimester and

Outcomes after Cholecystectomy During
Pregnancy
Vincent Cheng, MD, Kazuhide Matsushima, MD, FACS, Matthew Ashbrook, MD, Koji Matsuo, MD, PhD,
Morgan Schellenberg, MD, FACS, Kenji Inaba, MD, FACS, Kulmeet Sandhu, MD, FACS

BACKGROUND: Conventional philosophy promotes the second trimester as the ideal time during pregnancy
for cholecystectomy. However, literature supporting this belief is sparse. The purpose of this
study is to examine the association of trimester and clinical outcomes after cholecystectomy
during pregnancy.
STUDY DESIGN: The National Inpatient Sample was queried for pregnant women who underwent cholecys-
tectomy between October 2015 and December 2017. Patients were categorized by trimester.
Multivariable logistic and continuous outcome regression models were used to evaluate the
association of trimester and outcomes, including maternal and fetal complications, length
of stay, and hospital charges. The primary outcome was any complicationda composite of
specific clinical complications, each of which were designated as secondary outcomes.
RESULTS: A total of 819 pregnant women satisfied our inclusion criteria. Of these, 217 (26.5%) were in
the first trimester, 381 (47.5%) were in the second trimester, and 221 (27.0%) were in the
third trimester. Median age was 27 years (interquartile range: 23e31 years). Compared with
the second trimester, cholecystectomy during the first trimester was not associated with higher
rates of complications (adjusted odds ratio [AOR] 0.88, 95% confidence interval [CI]:
0.47e1.63, p ¼ 0.68). However, cholecystectomy during the third trimester was associated
with a higher rate of preterm delivery (AOR 7.20, 95% CI 3.09e16.77, p < 0.001) and
overall maternal and fetal complications (AOR 2.78, 95% CI 1.71e4.53, p < 0.001).
Compared with the second trimester, the third trimester was associated with 21.3% higher
total hospital charges (p ¼ 0.003).
CONCLUSIONS: Our results suggest that cholecystectomy can be performed in the first trimester without
significantly increased risk of maternal and fetal complications, compared to the second
trimester. In contrast, cholecystectomy during pregnancy should not be delayed until the
third trimester. (J Am Coll Surg 2021;-:1e8.
2021 by the American College of Surgeons.
Published by Elsevier Inc. All rights reserved.)

Cholecystectomy is one of the most frequently performed
nonobstetric operations in pregnant women.1,2 The rec-
ommended timing of cholecystectomy during pregnancy
has a wavering history (eFig. 1). In 1992, the National
Institutes of Health (NIH) recommended the second
trimester as the optimal timing of cholecystectomy.3
While laparoscopic cholecystectomy was recommended
as the treatment of choice in the general population, the
NIH stated, “The use of laparoscopic cholecystectomy
in patients in the first trimester of pregnancy is

Disclosure Information: Nothing to disclose.

From the Divisions of Acute Care Surgery (Cheng, Matsushima, Ashbrook,
Disclosures outside the scope of this work: Dr Matsuo receives honorar-
Schellenberg, Inaba) and Upper GI and General Surgery (Sandhu), Depart-
ium payments from Chugai Pharmaceutical Co to reimburse textbook
ment of Surgery, and the Department of Obstetrics and Gynecology (Mat-
editorial expenses from Springer, and receives honorarium payments
suo), University of Southern California, Los Angeles, CA.
from VBL Therapeutics to reimburse investigator meeting attendance ex-
penses. Other authors have nothing to disclose. Correspondence address: Kazuhide Matsushima, MD, FACS, Division of
Acute Care Surgery, Department of Surgery, University of Southern Cali-
Presented virtually at the Western Surgical Association 128th Scientific Ses-
fornia, 2051 Marengo St, Inpatient Tower, C5L100, Los Angeles, CA
sion, November 2020.
90033. email: kazuhide.matsushima@med.usc.edu
Received December 26, 2020; Revised March 15, 2021; Accepted March
16, 2021.

ª 2021 by the American College of Surgeons. Published by Elsevier Inc. https://doi.org/10.1016/j.jamcollsurg.2021.03.034

All rights reserved. 1 ISSN 1072-7515/21
2 Cheng et al Trimester and Cholecystectomy Outcomes
Abbreviations and Acronyms
AOR ¼ adjusted odds ratio
CCI ¼ Charlson Comorbidity Index
ICD- ¼ International Classification of Disease-Clinical
CM Modification
NIS ¼ Nationwide Inpatient Sample
RC ¼ regression coefficient
SAGES ¼ Society of American Gastrointestinal and
Endoscopic Surgeons
controversial because of the unknown effects of carbon
dioxide pneumoperitoneum on the developing fetus.” In
addition, the NIH stated, “patients in the third trimester
of pregnancy should not usually undergo laparoscopic
cholecystectomy, because of risk of damage to the uterus
during the procedure.” Although women in their second
trimester “may be candidates for laparoscopic cholecystec-
tomy,” the NIH warned that these women should only be
operated on “providing the operating surgeon is experi-
enced in treating patients with complex laparoscopic cho-
lecystectomy problems.” Six years later, the Society of
American Gastrointestinal and Endoscopic Surgeons
(SAGES) published similar guidelines stating, “When
possible, operative intervention should be deferred until
the second trimester, when fetal risk is lowest.”4 At that
time, cholecystectomy was considered the less preferable
management option for gallbladder disease during preg-
nancy.5-7
In 2008, SAGES revised its guidelines and published,
“Laparoscopy can be performed safely during any
trimester of pregnancy with minimal morbidity to the
fetus and mother.”8 Furthermore, “Laparoscopic chole-
cystectomy is the treatment of choice in the pregnant pa-
tient with symptomatic gallbladder disease, regardless of
trimester.” SAGES 2017 guidelines continue with the
same recommendations. Accounting for new data and
literature, it grades the former recommendation, deeming
laparoscopy safe for all trimesters as “strong,” and laparo-
scopic cholecystectomy for treatment of symptomatic
gallbladder disease regardless of trimester as “weak.”9
Despite this description of the evidence, rates of cholecys-
tectomy have increased since SAGES updated its
recommendations.1,10,11
No consensus exists regarding the optimal timing of
cholecystectomy during pregnancy. For example, the
World Society of Emergency Surgery suggests the second
trimester and early third trimester as the ideal time for
laparoscopic cholecystectomy.12 Contrary to these societal
guidelines, Fong and colleagues13 published a large retro-
spective statewide database study of women in California
J Am Coll Surg
showing higher rates of maternal complications associated
with third trimester cholecystectomy compared with post-
partum cholecystectomy.13 Existing data describing the
optimal timing of cholecystectomy during pregnancy are
not only sparse, but also conflicting. Therefore, the aim
of this study is to compare the outcomes of cholecystec-
tomy during pregnancy by trimester.
METHODS
Data source and patient eligibility
This is a retrospective cohort study using the National
Inpatient Sample (NIS) database between October 2015
and December 2017. This time frame was chosen because
October 2015 is when the NIS dataset first began using
the International Classification of Diseases, Tenth
Revision, Clinical Modification (ICD-10-CM), which is
the first version to include pregnancy trimester codes.
Data from December 2017 is the most recent available
data. The study was approved by the Institutional Review
Board at the University of Southern California. The NIS
database is deidentified and approximates a 20% stratified
sample of all US inpatient hospital discharges.14 The data-
base was queried for all pregnant women with biliary dis-
ease during the study period using diagnostic codes from
the ICD-10-CM. Table 1 summarizes the list of ICD-10-
CM codes used for patient selection. The NIS database
also contains an “elective” variable differentiating between
elective and nonelective admissions. ICD-10 Procedure
Coding System (ICD-10-PCS) codes were used to filter
for patients who underwent laparoscopic or open
cholecystectomy.
Baseline demographic and outcomes variables
Baseline patient and hospital characteristics were
abstracted from the NIS database. These included age,
race, payer, income, and discharge year. Using coding
algorithms validated for defining comorbidities in ICD-
10-CM administrative data, the Charlson Comorbidity
Index (CCI) was identified for each patient.15 Clinical
outcomes variables included bile duct injury, maternal
death, preterm delivery, preterm labor, abortion, prema-
ture rupture of membranes, amniotic infection, and other
maternal and fetal outcomes (Table 1). An “Any Compli-
cation” outcome variable was created and defined as a
composite of all these clinical complications. Given the
anticipated infrequency of each specific clinical outcome,
“Any Complication” was designated as the primary
outcome, and the specific clinical outcomes were desig-
nated as secondary outcomes. Other secondary outcomes
variables included hospital length of stay and total
Vol. -, No. -, - 2021
Table 1. Diagnosis and Procedure Codes
Diagnosis or procedure
Acute cholecystitis
Biliary colic
Choledocholithiasis
Gallstone pancreatitis
Other diseases associated with cholelithiasis (eg chronic
cholecystitis)
Laparoscopic cholecystectomy
Open cholecystectomy
First trimester of pregnancy
Second trimester of pregnancy
Third trimester of pregnancy
Bile duct injury
Preterm delivery/preterm labor/abortion
Premature rupture of membrane
Amniotic infection
Other maternal complication (eg, placenta abruption,
antepartum hemorrhage, eclampsia, HELLP syndrome)
and other fetal complications (eg decreased movement,
abnormal heart rate or rhythm, abnormality and
damage, abnormal acid-base balance)
HELLP, hemolysis, elevated liver enzymes, low platelet count.
hospital charges. The latter outcome was adjusted for
inflation using the consumer price index measured by
the US Bureau of Labor Statistics.16
Statistical analysis
Using ICD-10-CM codes, study patients were divided
into 3 groups based on trimester (Table 1). Patient base-
line characteristics were compared across these 3 groups
using univariate analysis (Table 2). As required by the
Healthcare Cost and Utilization Project (HCUP) Data
Use Agreement, summary data based on 10 observa-
tions were suppressed. A chi-square test was used to
compare the 3 trimester groups to examine associations
between treatment strategy (ie trimester when procedure
was done) and dichotomous outcome variables. The
Kruskal-Wallis test was used to examine associations be-
tween treatment strategy and continuous outcome vari-
ables. Multivariable logistic regression analysis was used
to examine the associations between trimester and dichot-
omous outcome variables while adjusting for potential
confounding factors including age, comorbidities, race,
payer, and income quartile following the recommended
methodologic standards for studies using the NIS
database.17 Multivariable linear regression analysis was
Cheng et al Trimester and Cholecystectomy Outcomes 3
ICD-10, Clinical Modification and Procedure Coding System code
K80.0, K80.12, K80.13, K80.42, K80.43, K80.46, K80.47, K80.62,
K80.63, K80.66, K80.67
K80.20, K80.80, K80.81, K80.80
K80.11, K80.13, K80.19, K80.21, K80.3, K80.4, K80.5, K80.6,
K80.7, K80.81
K85.1
K80.10, K80.18, K80.20
0FT44ZZ, 0FB44ZZ
0FT40ZZ, 0FB40ZZ
Z3A.01, Z3A.08, Z3A.09, Z3A.10, Z3A.11, Z3A.12, Z3A.13,
Z34.01, Z34.81, Z34.91
Z3A.14, Z3A1.5, Z3A.16, Z3A.17, Z3A.18, Z3A.19, Z3A.20,
Z3A.21, Z3A.22, Z3A.23, Z3A.24, Z3A.25, Z3A.26, Z3A.27,
Z34.02, Z34.82, Z34.92
Z3A.28, Z3A.29, Z3A.3, Z3A.4, Z34.03, Z34.83, Z34.93
S36.13
O36.4, P95, O02.1, O03, O60.1, O60.0, O60.2
O42
O41.1
O45.9, O46.9, O20.9, O15, O14.2, O36.81, O36.83, O35.9, O68
used for continuous outcome variables and adjusted for
the same potential confounders. Hospital type and region
were excluded from multivariable analyses because they
had high percentages of missing values. To satisfy statisti-
cal assumptions necessary for linear regression, base 10
logarithmic transformations were required for hospital
length of stay and total charges. The results from base
10 logarithmic transformations were then back-
transformed to the original scale by exponentiating the
coefficient, subtracting 1, and multiplying by 100 in order
to interpret them as percent increases or decreases when
comparing the 3 trimesters. Data were analyzed using
SPSS version 20.0 (IBM Corporation). Statistical
significance was defined as p < 0.05.
RESULTS
Included for analysis were a total of 819 pregnant women
with biliary disease, who underwent cholecystectomy dur-
ing the study period (Fig. 1). Of these patients, 217
(26.5%) were in their first trimester, 381 (46.5%) were
in their second trimester, and 221 (27.0%) were in their
third trimester. Table 2 compares patient and hospital
characteristics among these 3 groups. The median age of
all patients was 27 years (interquartile range [IQR]:
4 Cheng et al Trimester and Cholecystectomy Outcomes J Am Coll Surg

Table 2. Baseline Characteristics of Pregnant Women Undergoing Cholecystectomy in the Healthcare Cost and Utilization
Project: National Inpatient Sample 2015Q4e2017
All patients First trimester Second trimester Third trimester
Characteristic (n ¼ 819) (n ¼ 217) (n ¼ 381) (n ¼ 221) p Value
Age, y, median (IQR)* 27 (23e31) 27 (22e32) 27 (23e31) 27 (23e30) 0.82
CCI  2, n (%)y 12 (1.5) z z z
0.65
z z z
Diabetes 11 (1.3) 0.24
Obese 146 (17.8) 49 (22.6) 60 (15.7) 37 (16.7) 0.10
Payer, n (%)y 0.002
z z z
Medicare 13 (1.6)
Medicaid 455 (55.7) 119 (54.8) 206 (54.4) 130 (58.8)
Private 296 (36.2) 69 (31.8) 150 (39.6) 77 (34.8)
z z
Self-pay 30 (3.7) 18 (8.3)
z z z z
No charge
z z z
Other 21 (2.6)
Income, n (%)*,y 0.47
1st Quartile 292 (36.0) 88 (41.1) 131 (34.6) 73 (33.5)
2nd Quartile 245 (30.2) 67 (31.3) 112 (29.6) 66 (30.3)
3rd Quartile 181 (22.3) 39 (18.2) 90 (23.7) 52 (23.9)
4th Quartile 93 (11.5) 20 (9.3) 46 (12.1) 27 (12.4)
Race, n (%)y 0.030
White 360 (46.1) 84 (40.2) 179 (49.2) 97 (46.6)
Black 104 (13.3) 34 (16.3) 49 (13.5) 21 (10.1)
Hispanic 267 (34.2) 86 (40.7) 110 (41.2) 72 (34.6)
z z z
Asian/Pacific Islander 12 (1.5)
z
Other 38 (4.9) 20 (5.5) 15 (7.2)
Hospital type, n (%)y 0.004
z z
Rural 26 (5.9) 10 (7.8)
Urban nonteaching 117 (26.6) 44 (39.6) 46 (22.9) 27 (21.1)
Urban teaching 297 (67.5) 60 (54.1) 146 (72.6) 91 (71.1)
Region, n (%)y 0.47
z
Northeast 54 (12.3) 27 (13.4) 20 (15.6)
Midwest 84 (19.1) 21 (18.9) 38 (18.9) 25 (19.5)
South 180 (40.9) 49 (44.1) 82 (40.8) 49 (38.3)
West 122 (27.7) 34 (30.6) 54 (26.9) 34 (26.6)
*Continuous variable expressed as median values (interquartile range [IQR]); significance determined with 1-way Kruskal-Wallis test.
y
Categorical variables expressed as percent of patients; significance determined with chi-square test.
z
Suppressed per the Healthcare Cost and Utilization Project requirement.
CCI, Charlson Comorbidity Index.

23e31 years). A total of 12 (1.5%) patients had a
CCI  2. No significant difference in the proportion of
patients with CCI  2 was found across the 3 trimesters
in univariate analysis (p ¼ 0.65). Compared with the sec-
ond and third trimesters, the first trimester had a higher
proportion of lowest income earners (41.1%) and a lower
proportion of highest income earners (9.3%), though the
overall comparison of income distributions did not differ
significantly across the 3 trimesters (p ¼ 0.47). The distri-
bution of cholecystectomies performed at rural, urban
nonteaching, and urban teaching hospitals differed
significantly across the 3 trimesters (p ¼ 0.004); a
disproportionately high percentage of second and third
trimester cholecystectomies were performed at urban
teaching hospitals.
Figure 2 shows the distribution of the clinical diagnoses
leading to cholecystectomy. Acute cholecystitis was the
most common diagnosis associated with cholecystectomy,
representing 46.2% of all cases. Elective cholecystectomy
became more common in the second and third trimesters.
Although 7.8% of cholecystectomies in the first trimester
were performed in an elective setting, 21.8% and 33.2%
were considered elective in the second and third
trimesters, respectively. These percentages are not
Vol. -, No. -, - 2021 Cheng et al Trimester and Cholecystectomy Outcomes 5

Figure 1. Patient selection diagram.

directory displayed elsewhere in this manuscript; they
were based on the NIS characterization of each hospitali-
zation and cannot derived from Figure 2.
The median number of days that elapsed after admis-
sion until cholecystectomy was 1 day (IQR: 0e3 days)
in first trimester patients, 1 day (IQR: 0e2 days) in sec-
ond trimester patients, and 2 days (IQR: 0e3days) in
third trimester patients (p < 0.001). The median number
of postoperative days before hospital discharge was less in
second trimester patients (median 1 day, IQR: 1e2 days)
compared with those of first trimester patients (median 2
days, IQR: 1e3 days) and third trimester patients (me-
dian 2 days, IQR: 1e3 days, p ¼ 0.001). After adjusting
for inflation, the median total hospital charges of all
patients was $42,412 (IQR: $28,898e$62,489). The
median charges for first, second, and third trimester ad-
missions with cholecystectomy were $40,122 (IQR:
$30,791e$65,353), $37,578 (IQR: $25,026e$55,926),
and $47,515 (IQR: $30,995e$70,983, p ¼ 0.003),
respectively.
A total of 39 (4.8%) patients underwent open cholecys-
tectomy. None of these open procedures was accompa-
nied by an ICD-10-PCS code representing conversion
from laparoscopic to open surgery. Multivariable logistic
regression analysis showed that the third trimester was
associated with significantly higher rates of open
cholecystectomy compared with the second trimester
(adjusted odds ratio [AOR]: 13.21, 95% CI:
3.19e54.60, p < 0.001). No significant difference in
open cholecystectomy rates was found between the first

Figure 2. Frequency of diagnoses leading to cholecystectomy.

6 Cheng et al Trimester and Cholecystectomy Outcomes
and second trimesters (AOR: 1.75, 95% CI: 0.27e11.39,
p ¼ 0.56). Elective vs nonelective admission was not a
significant predictor of open cholecystectomy. Neither
maternal deaths nor bile duct injuries were observed in
the dataset.
Table 3 illustrates the crude outcome frequencies;
several secondary outcomes and specific complication
rates were observed in fewer than 10 patients within a
trimester. Multivariable logistic regression models also
indicated that the third trimester was significantly associ-
ated with a higher rate of any complication (AOR 2.78,
95% CI: 1.71e4.53, p < 0.001) compared with the sec-
ond trimester (Table 4). Overall complication rates did
not differ between the first and second trimesters (AOR
0.88, 95% CI: 0.47e1.63, p ¼ 0.68). Compared with
the second trimester, the third trimester was also
significantly associated with higher rates of preterm
delivery, preterm labor, or abortion compared to the
second trimester (AOR 7.20, 95% CI: 3.09e16.77,
p < 0.001). Rates of premature rupture of membranes
did not differ significantly across the 3 trimesters.
Similarly, no significant difference was observed in rates
of amniotic infection.
Compared with cholecystectomy performed in the
second trimester, both the first trimester (regression coeffi-
cient [RC] 0.076, 95% CI: 0.040e0.111, p < 0.001) and
third trimester (RC 0.119, 95% CI: 0.084e0.153,
p < 0.001) were significantly associated with longer hospi-
tal stays after adjusting for patient characteristics using
multivariable linear regression models (Table 5). After ac-
counting for the logarithmic transformation required to
normalize hospital days, these regression coefficients sug-
gest that first and third trimester cholecystectomies were
associated with 19.1% (95% CI: 9.6%e29.1%) and
31.5% (95% CI: 21.3%e42.2%) increases, respectively,
in hospital stay compared with the second trimester. How-
ever, only the third trimester was significantly associated
with greater hospital charges compared with the
second trimester (RC 0.084, 95% CI: 0.030e0.139,
p ¼ 0.003). After accounting for the logarithmic transfor-
mation required to normalize hospital charges, this regres-
sion coefficient suggests that the third trimester was
Table 3. Crude Outcome Counts and Percentages Analyzed in Multivariable Logistic Regression Models
All patients
Outcomes (n ¼ 819)
Any complication* 104 (12.7)
Preterm delivery/preterm labor/abortion* 38 (4.6)
Premature rupture of membrane* 56 (6.8)
Amniotic infection* 13 (1.6)
*Categorical variables expressed as percent of patients; Significance determined with chi-square test.
y
Suppressed per the Healthcare Cost and Utilization Project requirement.
J Am Coll Surg
associated with a 21.3% (95% CI: 7.2%e37.1%) increase
in total hospital charges compared to the second trimester.
DISCUSSION
The results of this study suggest that the frequencies of
maternal and fetal complications after cholecystectomy
during the first and second trimesters were not signifi-
cantly different. However, cholecystectomy during the
third trimester was significantly associated with increased
maternal and fetal complications and greater economic
burden (ie longer length of stay and greater hospital costs)
compared with the second trimester. These findings
suggest that the first and second trimesters of pregnancy
may represent the optimal timing of cholecystectomy
for the treatment of gallbladder disease in pregnancy.
Momentum in national guidelines8,9,18 has swung in
favor of laparoscopic cholecystectomy in any trimester
to treat symptomatic gallbladder disease. However, this
study shows that the second trimester is still the most
common time for cholecystectomy during pregnancy.
Of note, elective cholecystectomy was scheduled more
frequently with each successive trimester. This finding
likely reflects a combination of the natural pathophysi-
ology19-21 of symptomatic cholelithiasis to develop
throughout pregnancy as well as the tendency to avoid
or defer surgery until symptoms recur or worsen. In
fact, more than 36% of pregnant women with acute
cholecystitis were treated nonoperatively according to a
recent study despite its nonelective indication.11 It is
unclear whether pregnancy augments aversion to surgery,
despite literature showing that laparoscopic cholecystec-
tomy during pregnancy is safe and associated with
improved outcomes.1,11,22-24 Furthermore, this study
observed a disproportionately high percentage of second
and third trimester cholecystectomies performed at urban
teaching hospitals, which may reflect a referral pattern
from rural and urban nonteaching hospitals to urban
teaching or academic centers with higher acuity cases.
Another possibility is that this distribution simply reflects
the patient populations or practice patterns of the
surgeons at these hospitals.
First trimester Second trimester Third trimester
(n ¼ 217) (n ¼ 381) (n ¼ 221)
18 (8.3) 36 (9.4) 50 (22.6)
y y
29 (13.1)
14 (6.5) 25 (6.6) 17 (7.7)
y y y
Vol. -, No. -, - 2021 Cheng et al Trimester and Cholecystectomy Outcomes 7

Table 4. Multivariable Logistic Regression Analysis for Maternal and Fetal Outcomes*
First trimester Third trimester
Outcomes AOR 95% CI p Value AOR 95% CI p Value
Any complication 0.88 0.47e1.63 0.68 2.78 1.71e4.53 <0.001
Preterm delivery/preterm labor/abortion <0.01 <0.01e>999 >0.99 7.20 3.09e16.77 <0.001
Premature rupture of membrane 0.87 0.42e1.75 0.67 1.03 0.53e2.03 0.92
Amniotic infection 3.94 0.90e17.37 0.07 2.84 0.65e12.45 0.17
*Second trimester as control.
AOR, adjusted odds ratio.

To date, few studies have incorporated pregnancy
trimester into their analyses to evaluate its impact on
clinical outcomes after cholecystectomy. Fong and
colleagues13 used a large California database to compare
clinical outcomes after cholecystectomy during the third
trimester vs those in the postpartum period. They found
significantly higher rates of maternal complications,
longer hospital stays, and increased readmission rates after
third trimester cholecystectomy compared to postpartum
cholecystectomy. For patients presenting with symptom-
atic cholelithiasis during the third trimester, the authors
recommended deferring cholecystectomy until the post-
partum period. It is important to reiterate that this study
neither refutes nor corroborates the study by Fong and
associates,13 as our study did not include patients who
underwent cholecystectomy in the postpartum period.
However, it is possible that the results shown here may
reconcile the results of studies by Fong and coworkers13
and Kuy and colleagues,1 which showed significantly
lower rates of maternal and fetal complications associated
with laparoscopic cholecystectomy compared to nonoper-
ative management of biliary disease during pregnancy.
Improved outcomes associated with first and second
trimester cholecystectomies may be driving the overall
trend in favor of surgery observed in pregnant patients
as a group.
This study has several limitations. First, the study may
be underpowered to assess individual maternal and fetal
complications. Although cholecystectomy is the second
most common nonobstetric surgery performed during
pregnancy after appendectomy,1,2 the percentage of
pregnant women undergoing cholecystectomy is low.
Even with the nationally representative data source used
in this study, only 819 cholecystectomies during preg-
nancy were included in this sample representing 10% of
national discharges over a 27-month period. The small
sample size and the low frequency of complications
(Table 3) contribute to higher variability and lower preci-
sion in multivariable analyses. Unfortunately, the sample
size could not be increased by extending the study period
to previous years because ICD-9-CM codes were used
before October 2015, and this system lacks codes assigned
to each trimester. Second, this NIS dataset does not cap-
ture longitudinal follow-up information for individual
cases. As a result, this study is unable to characterize
complications that may be found in readmissions after
cholecystectomy. This limitation is particularly restrictive
when considering fetal complications. Third, the database
does not include granular clinical details such as cholecys-
titis severity or number of episodes of biliary colicdqual-
ities that may influence surgical outcomes. This lack of
granularity also prevents parsing total hospital charges
to determine whether they are related to surgical
complications.
CONCLUSIONS
In conclusion, the results of this study favor the first and
second trimesters for cholecystectomy for treatment of
gallbladder disease in pregnant women. Though the
second trimester was the most common time for cholecys-
tectomy overall during the time period of this study, the
third trimester was the most frequently scheduled time for
elective cholecystectomy. Clinical outcomes may have

Table 5. Multivariable Linear Regression Analysis for Hospital Length of Stay and Total Charge*
First trimester Third trimester
Variable RC 95% CI p Value RC 95% CI p Value
Log10 (length of 0.076 (19.1) 0.040e0.111 (9.6e29.1) <0.001 0.119 (31.5) 0.084e0.153 (21.3e42.2) <0.001
hospital stay)y
Log10 (total hospital 0.046 (11.2) -0.012e0.104 (-2.7e27.1) 0.12 0.084 (21.3) 0.030e0.139 (7.2e37.1) 0.003
charge)y
*Second trimester as control.
y
Expressed as coefficient followed by back-transformations in parentheses.
RC, regression coefficient.
8 Cheng et al Trimester and Cholecystectomy Outcomes
improved if these operations had been performed during
an earlier trimester. Additional research is required to
develop a risk stratification that incorporates trimester
to help guide the treatment of biliary disease during
pregnancy.
Author Contributions
Study conception and design: Cheng, Matsushima,
Ashbrook, Matsuo, Schellenberg, Inaba, Sandhu
Acquisition of data: Cheng, Matsushima
Analysis and interpretation of data: Cheng, Matsushima,
Ashbrook, Matsuo, Schellenberg, Inaba, Sandhu
Drafting of manuscript: Cheng, Matsushima, Ashbrook
Critical revision: Matsuo, Schellenberg, Inaba, Sandhu
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Vol. -, No. -, - 2021 Cheng et al Trimester and Cholecystectomy Outcomes 8.e1

eFigure1. Evolution of societal recommendations regarding cholecystectomy during pregnancy. LC,

laparoscopic cholecystectomy; SAGES, Society of American Gastrointestinal and Endoscopic Surgeons;
WSES, World Society of Emergency Surgery.