The n e w e ng l a n d j o u r na l
Case Records of the Massachusetts General Hospital
From the Departments of Surgery
(N.N.S., P.J.F.), Radiology (A.K.), Obstet­
rics and Gynecology (R.L.), and Pathol­
ogy (M.K.-W.), Massachusetts General
Hospital, and the Departments of Sur­
gery (N.N.S., P.J.F.), Radiology (A.K.),
Obstetrics and Gynecology (R.L.), and
Pathology (M.K.-W.), Harvard Medical
School — both in Boston.
N Engl J Med 2019;381:656-64.
DOI: 10.1056/NEJMcpc1900596
Copyright © 2019 Massachusetts Medical Society.
656
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of m e dic i n e
Founded by Richard C. Cabot
Eric S. Rosenberg, M.D., Editor
Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D.,
Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors
Kathy M. Tran, M.D., Case Records Editorial Fellow
Emily K. McDonald, Sally H. Ebeling, Production Editors
Case 25-2019: A 41-Year-Old Pregnant
Woman with Abdominal Pain
Noelle N. Saillant, M.D., Aoife Kilcoyne, M.D., Peter J. Fagenholz, M.D.,
Raymond Lui, M.D., and Melissa Krystel‑Whittemore, M.D.​​
Pr e sen tat ion of C a se
Dr. Madhukar S. Patel (Surgery): A 41-year-old pregnant woman was seen in the emer-
gency department of this hospital at 36 weeks 3 days of gestation because of ab-
dominal pain.
Six and a half months before this evaluation, when the patient was at her initial
routine prenatal visit, transvaginal ultrasonography revealed a normal intrauterine
gestational sac and embryo. The date of the last menstrual period was unknown,
and ultrasonographic measurements were used to determine the estimated due
date. Thereafter, prenatal follow-up was uneventful.
Fifteen hours before the current evaluation, abdominal pain developed suddenly
after the patient had eaten breakfast. The pain was in the right lower quadrant and
was described as sharp and constant. She rated the pain at 8 on a scale of 0 to 10,
with 10 indicating the most severe pain; she noted that the pain was more severe
than it had been during her two previous vaginal deliveries, which had occurred
without epidural anesthesia. She had no fever, chills, diarrhea, dysuria, hematuria,
vaginal bleeding, or contractions, and fetal movement was normal. The patient
took oral docusate, which did not relieve the pain, and then took acetaminophen,
after which the pain decreased slightly. She called her obstetrician, who recom-
mended that she present to the clinic for evaluation.
In the obstetrics clinic, transabdominal and transvaginal ultrasonography were
performed. The fetus was in cephalic presentation, with a biophysical profile score
of 8/8 (indicating normal fetal well-being) and a fetal heart rate of 134 beats per
minute. The placenta was positioned anteriorly, the cervical length was 21 mm,
and the umbilical artery appeared normal on Doppler examination. The patient
was referred to the emergency department of a local hospital for further evaluation
and arrived approximately 7 hours after the onset of symptoms.
In the emergency department of the other hospital, the patient reported that
the abdominal pain persisted and that nausea had developed. Her surgical history
consisted of breast augmentation surgery and extraction of wisdom teeth in the
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 Case Records of the Massachuset ts Gener al Hospital

distant past. She was gravida 4, 2-0-1-2. Her first Table 1. Laboratory Data.*
and third pregnancies had been uncomplicated
and had resulted in vaginal deliveries at full term; Reference Range, On Presentation,
Variable Other Hospital Other Hospital
the second pregnancy had ended in a spontane-
ous abortion. She was immune to varicella and Hemoglobin (g/dl) 11.0–16.0 12.5
rubella; tests performed during this pregnancy Hematocrit (%) 34.0–45.0 37.5
for syphilis, hepatitis B virus surface antigen, Platelet count (per mm3) 150,000–400,000 160,000
gonorrhea, chlamydia, human immunodeficiency White-cell count (per mm3) 4500–11,000 14,300
virus, and group B streptococcus had been nega-
Differential count (%)
tive. The patient was taking prenatal vitamins
and was allergic to iodine-containing contrast Neutrophils 85.9
material, which had caused anaphylaxis. She lived Lymphocytes 7.2
with her husband and two children in a subur- Monocytes 6.5
ban neighborhood in New England. She did not Eosinophils 0.1
drink alcohol, smoke tobacco, or use illicit drugs. Basophils 0.1
Her father had died of liver disease associated
Immature granulocytes 0.2
with alcohol use disorder; her mother had had
Sodium (mmol/liter) 137–146 136
cervical cancer and hypertension and had died
of a ruptured cerebral aneurysm. Potassium (mmol/liter) 3.5–5.3 3.5
On examination, the temperature was 36.7°C, Chloride (mmol/liter) 98–107 99
the pulse 71 beats per minute, the blood pressure Carbon dioxide (mmol/liter) 23–32 20
113/67 mm Hg, the respiratory rate 16 breaths Anion gap (mmol/liter) 5–15 18
per minute, and the oxygen saturation 100% Urea nitrogen (mg/dl) 5–25 7
while the patient was breathing ambient air. The
Creatinine (mg/dl) 0.5–1.1 0.6
abdomen was gravid and soft, with hyperactive
bowel sounds; on palpation, there was severe Fasting glucose (mg/dl) <100 111
tenderness in the right lower quadrant that ex- Aspartate aminotransferase (U/liter) 15–41 17
tended inferiorly to the inguinal region, with Alanine aminotransferase (U/liter) 14–54 13
voluntary guarding and without rebound tender- Alkaline phosphatase (U/liter) 35–104 116
ness. Rovsing’s sign (pain in the right lower Total bilirubin (mg/dl) <1.2 0.4
quadrant with palpation of the left lower quad-
Total protein (g/dl) 6.4–8.3 6.9
rant) was present. A limited pelvic examination
Albumin (g/dl) 4.0–5.0 3.5
revealed that the cervix was closed, and the re-
mainder of the examination was normal. Urinaly- Lipase (U/liter) 13–60 25
sis showed cloudy, yellow urine, with a specific * To convert the values for urea nitrogen to millimoles per liter, multiply by 0.357.
gravity of 1.002, moderate ketones, and few bac- To convert the values for creatinine to micromoles per liter, multiply by 88.4. To
teria. The blood type was O, Rh-positive; other convert the values for glucose to millimoles per liter, multiply by 0.05551. To con­
vert the values for bilirubin to micromoles per liter, multiply by 17.1.
laboratory test results are shown in Table 1.
Acetaminophen and ondansetron were admin-
istered orally and normal saline intravenously.
An imaging study was obtained; after the results at 36 weeks 3 days of gestation with abdominal
were available, ampicillin–sulbactam and clinda­ pain. The differential diagnosis and evaluation
mycin were administered intravenously, and the of abdominal pain during pregnancy can be com-
patient was transferred by ambulance to the plicated because maternal adaptations lead to an
emergency department of this hospital for further insidious presentation of intraabdominal disor-
treatment. ders. For example, in pregnant patients, the typi-
Management decisions were made. cal findings associated with peritoneal irritation,
such as rebound and guarding, may be delayed
by uterine growth and increased abdominal
Differ en t i a l Di agnosis
muscular laxity that is mediated by progesterone
Dr. Noelle N. Saillant: I am aware of the diagnosis and relaxin. Furthermore, some laboratory find-
in this case. This 41-year-old woman presented ings that would usually be suggestive of an ab-

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 The n e w e ng l a n d j o u r na l
dominal emergency, such as leukocytosis with a
neutrophil shift and a low blood bicarbonate
level indicative of metabolic acidosis, would be
considered normal in pregnant patients. Finally,
early sepsis and hypovolemia may be difficult to
detect in pregnant patients, because such signs
are obscured by the increase in maternal cardiac
output (from 4 liters to 6 liters) and robust plasma
volume expansion (from 1500 ml to 2000 ml)
during gestation. These adaptive changes lead to
the late manifestation of tachycardia or hypoten-
sion.1 Therefore, it is not surprising that this
patient had a normal heart rate and was hemo-
dynamically stable.
In a study involving pregnant patients who
presented with abdominal pain, the percentage
of women who had nonspecific abdominal pain
was nearly equal to the percentage who had an
operative condition (38% and 41%, respectively).2
Differentiating between an intraabdominal emer-
gency and a more benign condition requires fo-
cus on the intraabdominal pathological features
combined with consideration of a broad list of
possible causes related and unrelated to obstet-
rics and gynecology.
Intraabdominal Disorders
Appendicitis and biliary complications are the
most common indications for operative inter-
vention during pregnancy and therefore would
be highest on the differential diagnosis. The fre-
quency of appendicitis is the same among preg-
nant patients as in the general adult population
(1 per 500 to 1000 persons). The risk of biliary
complications is higher among pregnant patients
than in the general population because of the
decreased gallbladder ejection fraction and in-
creased stone formation during pregnancy.
This patient’s examination revealed pain in
the right lower quadrant, which is found in 85%
of pregnant patients with appendicitis, and did
not reveal any hernias as a source of obstruction
and abdominal pain.3 In addition, she had had
no sick contacts or known exposures to raw or
undercooked foods that would suggest infec-
tions that mimic appendicitis, such as Yersinia
enterocolitica infection. She had no history of in-
flammatory bowel disease or diverticular disease
and had not undergone many surgeries, so
bowel obstruction is unlikely. Furthermore, she
had no signs of preeclampsia, and thus hepatic
capsular swelling would be an unlikely cause of
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of m e dic i n e
her abdominal pain.4 The laboratory test results
were not suggestive of hepatitis or pancreatitis,
and the elevated alkaline phosphatase level was
probably due to placental production. Urinalysis
and ultrasonography would have shown any evi-
dence of ureteral compression from the growing
uterus or of urinary tract infection or pyelonephri-
tis.5 Other, rare complications to consider in-
clude intussusception, volvulus, internal hernia,
peptic ulcer disease, and visceral artery aneu-
rysm. Finally, consideration of intimate partner
violence should prompt a confidential, safe dis-
cussion with the patient, if appropriate.
Given this patient’s history, laboratory test
results, and findings on physical examination,
appendicitis is the most likely diagnosis in this
case. To establish the diagnosis, I would per-
form abdominal ultrasonography, and if the study
is inconclusive, I would perform magnetic reso-
nance imaging (MRI).
Dr . Noel l e N. S a il l a n t ’s
Di agnosis
Appendicitis during pregnancy.
Discussion of Im aging S t udie s
Dr. Aoife Kilcoyne: Non–contrast-enhanced MRI of
the abdomen and pelvis (Fig. 1) revealed a dilated,
thickened distal appendix, which contained hy-
perintense material on T2-weighted imaging. The
appendix measured up to 11 mm in diameter.
There was trace periappendiceal fluid but no
abscess. There was no evidence of perforation.
The imaging findings were consistent with acute
appendicitis.
Imaging Approach
What is the preferred imaging approach in a
pregnant patient in whom appendicitis is sus-
pected? Graded-compression ultrasonography has
long been considered the preferred initial imag-
ing method for the evaluation of pregnant pa-
tients with suspected appendicitis.6 It is safe,
inexpensive, and easily available and does not
use ionizing radiation. Test performance, how-
ever, is challenging, with high rates of nonvisual-
ization of the appendix.7-9 Also, ultrasonography
is operator dependent and affected by variables
such as maternal body-mass index and gesta-
tional age.10
 Case Records of the Massachuset ts Gener al Hospital

Figure 1. MRI of the Abdomen and Pelvis. A

An axial, T2­weighted, single­shot fast spin echo (SSFSE)
image (Panel A) shows a thickened distal appendix
(arrow) posterior to the gravid uterus. A coronal, T2­
weighted, SSFSE image (Panel B) shows a normal right
ovary (arrow), a normal proximal appendix (arrowhead),
and a gravid uterus. Another coronal, T2­weighted,
SSFSE image (Panel C) shows a thickened distal ap­
pendix (arrow) measuring up to 11 mm in diameter.

Computed tomography (CT) is widely avail-

able and frequently used for the evaluation of
nonpregnant patients with suspected appendici-
tis. It provides excellent anatomical detail and has
a reported sensitivity of up to 93% and specific- B
ity of up to 96%.11,12 However, CT uses ionizing
radiation. The American College of Radiology
(ACR) recommends the use of radiation at a
level that is “as low as reasonably achievable” (a
safety principle referred to as ALARA) when
obtaining imaging studies in pregnant or poten-
tially pregnant patients, while indicating that the
medical benefit should outweigh the risk.
MRI, which was the imaging method used in
this case, is advantageous because it has multi-
planar capabilities, provides excellent soft-tissue
contrast, and does not use ionizing radiation.9,13
In pregnant patients, contrast material is not rou-
tinely administered during MRI.14 Some gadolin-
ium-based contrast agents can easily pass through
the placenta and enter the fetal circulation. The C
risk to the fetus remains unknown.14 Gadolinium
is used if it is deemed essential,14 but it is typi-
cally not necessary. For the diagnosis of acute
appendicitis in pregnant patients, MRI has a
reported sensitivity ranging from 94 to 97% and
specificity ranging from 97 to 99%.15,16
The ACR Committee on Appropriateness ex-
pert panel on gastrointestinal imaging recom-
mends the use of either MRI of the abdomen
and pelvis or ultrasonography for the evaluation
of pregnant patients with suspected appendici-
tis.17 A common approach would be initial ultra-
sonography, followed by non–contrast-enhanced
MRI if ultrasonography is inconclusive.

Discussion of M a nagemen t
General Surgery Perspective ble considerations. Expeditious treatment of ap-
Dr. Saillant: The management of appendicitis in pendicitis in pregnant patients is of paramount
pregnant patients is similar to its management importance. Once generalized peritonitis presents
in the nonpregnant population, with a few nota- as a symptom, the risk of fetal loss increases

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 The n e w e ng l a n d j o u r na l
from 2% to 6% and the risk of preterm labor
increases from 4% to 11%. Once perforation
(estimated to occur in a third of pregnant pa-
tients with appendicitis) ensues, the risk of fetal
loss increases to 24 to 36%.18 The decision to
perform urgent surgery must be balanced against
the risk of negative appendectomy (a situation in
which surgery is performed for the presumptive
diagnosis of appendicitis but intraoperative or
pathological findings do not show appendicitis),
which is associated with a risk of fetal loss of
4% and a risk of preterm labor of 11%.9,19
Current treatment recommendations of the
Society of American Gastrointestinal and Endo-
scopic Surgeons support the use of a laparoscopic
approach to appendectomy throughout all trimes-
ters of pregnancy when such an approach is tech-
nically feasible.20 This is in stark contrast to his-
torical recommendations, which supported the
use of laparoscopy only until 26 to 28 weeks of
gestation because of concerns about uterine in-
jury from trocar placement, technical difficulties,
and uterine malperfusion from insufflation.21
However, as experience has grown from the first
reports of successful laparoscopy during preg-
nancy,22 the safety of this approach throughout
all trimesters has been confirmed. Moreover,
laparoscopy has been associated with less uterine
manipulation, fewer wound complications, a
shorter hospital stay, and an earlier return to
work than the open technique. Also, the smaller
incisions have led to less postoperative pain and
narcotic use and therefore lower rates of fetal
exposure to narcotics.
Antibiotic agents that are considered safe to use
during pregnancy, such as a second-generation
cephalosporin and clindamycin or metronidazole,
are administered for broad coverage of bowel
flora. Recently, the use of medical therapy with
antibiotics alone for the treatment of appendici-
tis has gained some traction in the nonpregnant
population. Although most nonpregnant patients
with appendicitis have a response to nonopera-
tive treatment, 10% undergo a delayed rescue
appendectomy because of treatment failure. The
inability to predict which patients will have treat-
ment failure confers a risk that is unacceptable
in pregnant women,20,23-25 and therefore medical
therapy alone would not be recommended in this
patient.
In preparation for surgery, the prophylactic
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of m e dic i n e
administration of heparin or low-molecular-weight
heparin and the placement of sequential com-
pression devices on the patient’s legs would help
to counteract the risk of deep venous thrombosis
and pulmonary embolism, which is 5 times as
high in pregnant patients as in the general
population.1 The patient would be positioned with
the uterus displaced off the inferior vena cava,
which is an appropriate position for any pregnant
patient after the second trimester. Finally, preg-
nant patients in the third trimester are at an
increased risk for aspiration because of decreased
lower esophageal sphincter tone and displace-
ment of the stomach by the uterus. Precautions to
guard against this complication are warranted.
Dr. Virginia M. Pierce (Pathology): Dr. Fagenholz,
would you tell us how you treated this patient?
Dr. Peter J. Fagenholz: We discussed the possibil-
ity of medical therapy with the patient, but given
the lack of data regarding the medical manage-
ment of acute appendicitis during pregnancy, we
decided to proceed with appendectomy. On the
basis of the potential risks and benefits of laparo-
scopic surgery as compared with open appendec-
tomy during pregnancy, we chose a laparoscopic
approach. We placed the patient in a partial left
lateral decubitus position and administered anes-
thetic agents. After anesthesia was induced, fetal
monitoring was continued for 10 minutes before
the surgical procedure was begun. We entered the
abdomen and established pneumoperitoneum
through open trocar placement in the epigastrium,
cephalad to the uterine fundus. We insufflated
the abdomen to 12 mm Hg. Then, with direct
laparoscopic visualization, we were able to avoid
the uterus while placing two additional trocars
in the right upper quadrant (Fig. 2). We identi-
fied the appendix, which was inflamed. There
were no signs of perforation, and an appendec-
tomy was performed in standard fashion. The
total duration of the procedure was 28 minutes.
At the end of the surgery, we resumed fetal
monitoring for 10 minutes before the patient
emerged from anesthesia and was transferred to
the postanesthesia care unit.
Obstetrics Perspective
Dr. Raymond Lui: From an obstetrics perspective,
I agree with the surgical approach to this pa-
tient’s treatment. Preoperative evaluation is the
same in pregnant patients as in nonpregnant
 Case Records of the Massachuset ts Gener al Hospital

A B

Figure 2. Port Placement during Appendectomy in Pregnant and Nonpregnant Patients.

In nonpregnant patients (Panel A), laparoscopic appendectomy is typically performed with ports in the periumbili­
cal, left lower quadrant, and suprapubic regions. Initial port placement may be performed with the use of an open
technique or one of several closed techniques. In this patient, who was in the third trimester of pregnancy (Panel B),
the initial port was placed in the epigastrium with an open technique and was used as a camera port. Subsequent
ports were placed in the right upper quadrant with direct laparoscopic visualization and were used as working ports.

patients, but once the decision is made to pro-
ceed with surgery in a pregnant patient, a multi-
disciplinary team must be assembled that is
prepared to assess maternal and fetal well-being
and to optimize strategies to minimize the effect
of surgery on the fetus. Ideally, an anesthesi-
ologist who is knowledgeable about pregnancy-
related issues in anesthesia would be available.
A neonatal team needs to be available in case of
unplanned emergency delivery.26 A nursing team
should help with coordination of patient care
and fetal monitoring.
The fetal heart rate should be documented
before and after surgery. After 24 weeks of ges-
tation, the decision to perform intraoperative
monitoring of the fetal heart rate is made on a
case-by-case basis, since there are no clear data
indicating that fetal monitoring improves out-
comes. The American College of Obstetricians
and Gynecologists suggests that continuous intra-
operative fetal monitoring can be considered if it
is physically possible, depending on the location
and nature of the surgery. In this case, fetal
monitoring was performed at the beginning and
end of the procedure but not during the actual
surgery, since it would have interfered with the
surgical field.
If intraoperative fetal monitoring is performed,
an obstetrical care provider must be available to
interpret the tracing and an obstetrician must be
available to intervene if fetal well-being is at
risk. The nature of the planned surgery should
allow for safe interruption or alteration of the
surgery so that cesarean delivery can occur. In
this case, surgery was performed with the pa-
tient in the left lateral decubitus position to opti-
mize venous return. Maternal oxygenation was
maintained (oxygen saturation, >90%), as was
maternal blood pressure (>90/50 mm Hg). Efforts
were made to minimize uterine manipulation.

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 The n e w e ng l a n d j o u r na l of m e dic i n e

A B

C D

Figure 3. Appendectomy Specimen.

On hematoxylin and eosin staining, a whole­slide image of the serially sectioned appendix shows obliteration of the
lumen (Panel A, arrow). Necrotic epithelial glands of the mucosa (Panel B, arrows) and the underlying submucosa
show an acute inflammatory infiltrate (neutrophils), which traverses the muscular wall of the appendix (Panel C)
and extends into the periappendiceal soft tissue (adipose tissue) (Panel D).

After the operation, fetal monitoring and con- pink-red, ragged appearance and was remark-
traction assessment were performed. The patient able for an abundant amount of tan-yellow exu-
was kept in the left lateral decubitus position date involving the body and base. On serial
until she was fully awake. sectioning, the appendix had variegated mucosa
Acetaminophen and opioids are acceptable for that ranged from pink-red to dusky gray, and the
pain management. Nonsteroidal antiinflamma- luminal diameter ranged from pinpoint to 0.3 cm.
tory drugs are generally avoided after 32 weeks The average wall thickness was 0.2 cm. No per-
of gestation to prevent premature closure of the forations or fecaliths were identified.
fetal ductus arteriosus, reduced fetal renal perfu- On microscopic examination, the lumen of the
sion, reduced fetal urine production, and oligo- appendix was partially obliterated by necrosis of
hydramnios. the mucosa and transmural acute inflammation
(Fig. 3). The acute inflammatory infiltrate, which
consisted mostly of neutrophils, traversed the
Pathol o gic a l Discussion
mucosa, submucosa, and muscular wall and
Dr. Melissa Krystel-Whittemore: On gross examina- extended into the periappendiceal soft tissue.
tion, the appendix was 5.0 cm in length and These histologic findings are diagnostic of acute
0.8 cm in diameter. The serosa had a dusky suppurative appendicitis and periappendicitis.

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 Case Records of the Massachuset ts Gener al Hospital

In summary, when establishing the diagnosis have treated this patient if she had presented
of appendicitis in a pregnant patient, it is impor- later in the course of disease with a perforated
tant to consider the clinical differences between appendix and fluid collection suggestive of abscess?
pregnant and nonpregnant patients with appen- Dr. Fagenholz: There are four clinically relevant
dicitis. After the correct diagnosis has been types of appendicitis. If a patient presents with
made, early surgical intervention decreases both acute early appendicitis, surgery remains the
maternal and fetal morbidity and mortality. The standard of care, although recent studies have
histologic findings associated with acute appen- shown that treatment with antibiotics is often
dicitis do not differ between pregnant and non- successful. If a patient has appendicitis with a
pregnant patients. well-formed abscess, percutaneous drainage is
usually preferred. If a patient presents with ap-
pendicitis and phlegmon, I usually administer
Fol l ow-up
medical therapy with antibiotics. Finally, if a
Dr. Fagenholz: This patient was discharged home patient has appendicitis with free perforation
on the day of her procedure, after postoperative and peritonitis, with no organized or walled-off
fetal monitoring showed no abnormalities and perforation, surgery is the preferred approach.
she was able to eat and urinate without diffi- In each of these scenarios, I would treat preg-
culty. Postoperative analgesic agents consisted nant and nonpregnant patients similarly.
only of acetaminophen. She was seen for obstet-
rical follow-up on the 6th postoperative day, and A nat omic a l Di agnosis
she and the fetus were found to be in a normal
condition, with no signs of labor. She was seen Acute suppurative appendicitis and periappen-
for surgical follow-up on the 13th postoperative dicitis.
day, at which point her incisions were healing
This case was presented at Surgery Grand Rounds.
well and she had no problems. On the 22nd No potential conflict of interest relevant to this article was
postoperative day, she delivered a healthy baby reported.
boy without the use of anesthetics or analgesics Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
and with no complications. We thank Dr. Keith Lillemoe for review of the case and orga-
Dr. Keith Lillemoe (Surgery): How would you nization of the conference.

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