Acute Appendicitis in Pregnancy

10/9/2019 Acute appendicitis in pregnancy - UpToDate
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Acute appendicitis in pregnancy

Authors: Andrei Rebarber, MD, Brian P Jacob, MD
Section Editors: Charles J Lockwood, MD, MHCM, Deborah Levine, MD, Martin Weiser, MD
Deputy Editor: Kristen Eckler, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2019. | This topic last updated: Jun 13, 2019.
INTRODUCTION
Acute appendicitis is the most common general surgical problem encountered during pregnancy
[1]. The diagnosis is particularly challenging during pregnancy because of the relatively high
prevalence of abdominal/gastrointestinal discomfort, anatomic changes related to the enlarged
uterus, and the physiologic leukocytosis of pregnancy. Appendiceal rupture occurs more frequently
in pregnant women, especially in the third trimester, possibly because these challenges and
reluctance to operate on pregnant women delay diagnosis and treatment [2,3].
INCIDENCE
Acute appendicitis is suspected in 1/600 to 1/1000 pregnancies and confirmed in 1/800 to 1/1500
pregnancies [4-7]. In a case control study of 53,000 women undergoing appendectomy, pregnant
women were less likely to have appendicitis than age-matched, nonpregnant women [8]. The
incidence of appendicitis was slightly higher in the second trimester than in the first and third
trimesters or postpartum. In addition, cohort study of over 350,000 pregnancies reported that the
rate of acute appendicitis was 35 percent lower during the antepartum period than the time outside
of pregnancy. This study reported the lowest rates of appendicitis during the third trimester [9]. For
women aged 15 to 34 years, there was no increased risk in postpartum appendicitis compared
with the time outside of pregnancy. In contrast, an 84 percent increased risk of postpartum
appendicitis was reported for women older than 35 years.
CLINICAL FEATURES
Patient presentation — In the "classic" presentation, the patient describes the onset of
abdominal pain as the first symptom. The pain is periumbilical initially and then migrates to the
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right lower quadrant as the inflammatory process progresses [10-12]. Anorexia, nausea and
vomiting, if present, follow the onset of pain. Fever up to 101.0ºF (38.3ºC) and leukocytosis
develop later.
However, many patients have a nonclassical presentation, with symptoms such as heartburn,
bowel irregularity, flatulence, malaise, or diarrhea. If the appendix is retrocecal, patients often
complain of a dull ache in the right lower quadrant rather than localized tenderness. Rectal or
vaginal examination in such patients is more likely to elicit pain than abdominal examination. A
pelvic appendix can cause tenderness below McBurney's point (described below); these patients
often complain of urinary frequency and dysuria or rectal symptoms, such as tenesmus and
diarrhea. The spectrum of clinical and laboratory findings associated with acute appendicitis is
described in detail separately [13]. (See "Acute appendicitis in adults: Clinical manifestations and
differential diagnosis".)
Pregnant women are less likely to have a classic presentation of appendicitis than nonpregnant
women, especially in late pregnancy. The most common symptom of appendicitis (ie, right lower
quadrant pain) occurs close to McBurney's point in the majority of pregnant women, regardless of
the stage of pregnancy [5,14,15]; however, the location of the appendix migrates a few
centimeters cephalad with the enlarging uterus, so in the third trimester, pain may localize to the
mid or even the upper right side of the abdomen [16-18].
McBurney's point tenderness is described as maximal tenderness at 1.5 to 2 inches from the
anterior superior iliac spine (ASIS) on a straight line from the ASIS to the umbilicus [19]. This
tenderness may be less prominent during pregnancy because the gravid uterus lifts and stretches
the anterior abdominal wall away from the inflamed appendix [20-22]. Since direct contact
between the area of inflammation and parietal peritoneum is impeded, there is less rebound
tenderness or guarding. The gravid uterus may also inhibit contact between the omentum and the
inflamed appendix.
The largest review describing the frequency of the clinical signs and symptoms of appendicitis in
pregnancy included 720 cases reported in the literature [23]. The strength of this review is its size,
which is 10-fold larger than other series; however, it has several limitations, including
nonconsecutive selection of cases and case ascertainment prior to widespread use of current
diagnostic imaging procedures. The following summary illustrates the cumulative frequency of
signs and symptoms of appendicitis reported in this review. It does not account for differences in
frequency according to gestational age and consists of a case mix of 75 percent acute
inflammation only and 25 percent perforation.
● Symptoms:
• Abdominal pain: 96 percent
- Right lower quadrant: 75 percent

- Right upper quadrant: 20 percent
• Nausea: 85 percent
• Vomiting: 70 percent
• Anorexia: 65 percent
• Dysuria: 8 percent
● Signs:
• Right lower quadrant tenderness: 85 percent

• Rebound tenderness: 80 percent
• Abdominal guarding: 50 percent
• Rectal tenderness: 45 percent
• Right upper quadrant tenderness: 20 percent
• Temperature >37.80 Celsius (1000 F): 20 percent
Laboratory — Approximately 80 percent of nonpregnant patients with appendicitis have a

preoperative leukocytosis (white cells >10,000 cells/microL) and a left shift in the differential [23-
26]. However, mild leukocytosis can be a normal finding in pregnant women: the total leukocyte
count may be as high as 16,900 cell/microL in the third trimester (table 1), rising as high as 29,000
cells/microL during labor, and a slight left shift may occur [27,28] (see "Maternal adaptations to
pregnancy: Hematologic changes", section on 'White blood cells'). In a retrospective review of
66,993 consecutive deliveries including 67 women with a probable diagnosis of acute appendicitis,
the mean leukocyte counts in women with proven appendicitis and in those with histologically
normal appendices were 16,400 cells/microL and 14,000 cells/microL, respectively [5].
Microscopic hematuria and pyuria may occur when the inflamed appendix is close to the bladder
or ureter, but these findings are generally reported in less than 20 percent of patients [20,23,29-
32].
Mild elevations in serum bilirubin (total bilirubin >1.0 mg/dL) have been described as a marker for
appendiceal perforation (sensitivity 70 percent and specificity 86 percent [33]).
An elevated c-reactive protein level occurs in appendicitis, but is a nonspecific sign of

inflammation.
DIAGNOSIS
Acute appendicitis is a histological diagnosis. The clinical diagnosis should be strongly suspected
in pregnant women with classic findings: abdominal pain that migrates to the right lower quadrant,
right lower quadrant tenderness, nausea/vomiting, fever, and leukocytosis with left shift. (See
'Clinical features' above.)

With a nonclassical presentation, which often happens in pregnancy, imaging is indicated [1,4,32].
The primary goal of imaging is to reduce delays in surgical intervention due to diagnostic
uncertainty. A secondary goal is to reduce, but not eliminate, the negative appendectomy rate. In
these cases, ultrasound may reveal the probable cause of the patient’s symptoms (eg, ovarian
cyst or torsion, degeneration or torsion of a fibroid, nephrolithiasis, cholecystitis).
The diagnosis of acute appendicitis in a laboring patient requires a high index of suspicion, is
especially difficult, and may not be possible. Labor can be associated with pain that may be
lateralized, fever if chorioamnionitis is present, leukocytosis, and vomiting. Persistence or
progression of these symptoms after delivery should prompt physical examination and imaging
studies to evaluate for appendicitis.
Imaging
Ultrasonography — The initial modality of choice for diagnostic imaging of the appendix in
pregnancy is graded compression ultrasonography [34]. The clinical diagnosis of suspected
appendicitis is supported by identification of a noncompressible blind-ended tubular structure in
the right lower quadrant with a maximal diameter greater than 6 mm (image 1A-B) [35,36]. The
diagnosis should not be excluded if the appendix is not visualized.
Test performance appears to be lower in pregnant women than nonpregnant individuals because
the gravid uterus can alter the location of the appendix, can interfere with visualizing the appendix
and performing graded compression, particularly in the third trimester, and can lead to
inconclusive ultrasound findings [37-39]. Several studies reported nonvisualization of the appendix
in a large percentage of pregnant women with suspected appendicitis [40-44]. However, in one
review of studies of the value of ultrasound in diagnosing appendicitis in pregnancy, sensitivity
ranged from 67 to 100 percent and specificity ranged from 83 to 96 percent, compared with the
general population in whom sensitivity and specificity were 86 and 96 percent, respectively [45].
We believe that the wide variation in the reported diagnostic performance of graded compression
ultrasonography for appendicitis during pregnancy is due to multiple factors such as gestational
age, maternal body mass index (BMI), and importantly, the training and experience of the
sonologist or radiologist. (See "Diagnostic imaging in pregnant and nursing women" and "Acute
appendicitis in adults: Clinical manifestations and differential diagnosis".)
Magnetic resonance imaging — For pregnant women whose ultrasound examination is

inconclusive for appendicitis, magnetic resonance imaging (MRI) is the preferred next test as it
avoids the ionizing radiation of computed tomography (CT) and appears to be cost-effective
(image 2) [34,46,47]. When MRI is performed in pregnant women, gadolinium is not routinely
administered because of both demonstrated and theoretical fetal safety concerns, although use
may be considered if essential to maternal evaluation. At least one study has reported an
increased risk of a broad set of rheumatologic, inflammatory, or infiltrative skin conditions and for

stillbirth or neonatal death for pregnancies exposed to MRI with gadolinium compared with no-MRI
pregnancies [48].
MRI has a high sensitivity and specificity for diagnosing appendicitis during pregnancy. A meta-
analysis of 12 studies that included 933 pregnant women who underwent MRI evaluation for
suspected acute appendicitis reported a sensitivity of 94 percent (95% CI 87-98 percent) and
specificity of 97 percent (95% CI 96-98 percent) [49]. The largest study of pregnant women
suspected of having acute appendicitis (over 700 women), which was not included in the above
meta-analysis, reported 61 women had surgically confirmed disease out of 66 women with
suggestive MRI findings (ie, appendiceal dilation, appendicolith, free fluid, and fat stranding) [50].
Based on this detection rate, the study reported the following pooled data for MRI assessment of
appendicitis in pregnant women:
● Positive predictive value 92.4 percent (95% CI 83.2-97.5)

● Negative predictive value 99.7 percent (95% CI 98.9-99.9)
● Sensitivity 96.8 percent (95% CI 89-99.6)
● Specificity 99.2 percent (95% CI 98.2-99.8)
● Accuracy 99.0 percent (95% CI 98.0-99.6)
Of the five women with false-positive MRI studies, pathologic evaluation identified one ovarian
torsion, one appendicolith with mild lymphoid hyperplasia, one fibrous obliteration of the
appendiceal lumen without changes of acute appendicitis, and two normal appendices.
Compared with ultrasound, additional benefits of MRI include potential identification of peri-
appendiceal findings when the appendix is not visualized and recognition of other causes of
abdominal pain. In the study of over 700 women above, of 207 women whose appendix was not
visible on MRI, three were surgically diagnosed with appendicitis; two women had positive
secondary MRI findings (ie, right lower quadrant fluid and pericecal stranding) for appendicitis and
one woman had a negative MRI [50]. Of 643 pregnant women whose MRI studies were negative
for appendicitis, 72 women had alternate MRI findings that could have accounted for their acute
pain.
In reviewing the MRI images, the T1 bright appendix sign can be a useful finding for excluding
appendicitis, in addition to the routinely used findings of enlarged appendix size, periappendiceal
fat stranding, and high signal intensity on diffusion-weighted images. The T1 bright appendix sign,
which is typically seen in normal pregnant women, is defined as a high intensity signal filling more
than half length of the appendix on T1-weighted imaging (image 3). In a retrospective study of 125
pregnant women with suspected appendicitis, the T1 bright appendix was identified in 51 percent
of women without appendicitis, but only in 4.5 percent of women with appendicitis [51]. The overall
sensitivity, specificity, positive predictive value, and negative predictive value were 44.9, 95.5,
97.6, and 30 percent, respectively. Thus, visualization of a bright appendix is helpful in excluding
appendicitis, but a negative finding is not diagnostic for the disease.

If there is a prolonged wait time for MRI evaluation, the risk of potential appendiceal rupture is
balanced against the potential benefits of the study, such as identifying a different cause of pain or
avoiding surgery. If MRI if not readily available, then CT scan can be performed if the diagnosis is
unclear. If either imaging modality is not available quickly or if the patient declines CT because of
the radiation exposure, surgery should not be delayed in pregnant women with findings suggestive
of appendicitis despite inconclusive ultrasound results.
Computed tomography — CT is generally widely available. The main findings of appendicitis

on CT are right lower quadrant inflammation, an enlarged nonfilling tubular structure, and/or an
appendicolith (image 4). The initial experience with helical CT for the diagnosis of appendicitis in
pregnancy appears promising, but data are limited to small case series [52]. Modifications to the
CT protocol can limit estimated fetal radiation exposure to less than 3 mGy, well below doses
known to potentially cause adverse fetal effects (30 mGy for risk of carcinogenesis, 50 mGy for
deterministic effects [53,54]), and do not limit diagnostic performance [52,55]. Standard abdominal
CT scanning with an oral contrast preparation and intravenous contrast or a specialized
appendiceal CT scanning protocol can also be used, but are associated with higher fetal radiation
exposure (20 to 40 mGy [54,56]). The relative advantages and disadvantages of the two protocols
and what constitutes a positive study are described separately. (See "Acute appendicitis in adults:
Clinical manifestations and differential diagnosis", section on 'Imaging exams'.)
We perform CT when clinical findings and ultrasound examination are inconclusive and MRI is not
available, given the proven diagnostic value of CT in nonpregnant individuals: overall sensitivity 94
percent (95% CI 91-95), specificity 95 percent (95% CI 93-96), positive likelihood ratio 13.3 (95%
CI 9.9-17.9), and negative likelihood ratio 0.09 (95% CI 0.07-0.12) [57].
Data from studies in pregnant women are more limited. A meta-analysis of three retrospective
studies in pregnant women reported the sensitivity and specificity of CT in cases of
normal/uncertain ultrasonography were: sensitivity 85.7 percent (95% CI 63.7-96) and specificity
97.4 percent (95% CI 86.2-99.9) [58]. These studies included 2 to 49 patients with appendicitis. In
one of the studies, the negative laparotomy rates among patients who underwent (1) clinical
examination alone, (2) clinical evaluation and ultrasound examination, and (3) clinical evaluation
and ultrasound examination followed by CT were 54 percent (7/13), 36 percent (20/55), and 8
percent (1/13), respectively [38]. The ultrasound studies were interpreted as either diagnostic of
appendicitis or as normal/inconclusive, thus the authors did not determine whether CT was useful
after a normal versus an inconclusive ultrasound study. (See "Diagnostic imaging in pregnant and
nursing women", section on 'Fetal risks from ionizing radiation' and "Acute appendicitis in adults:
Clinical manifestations and differential diagnosis", section on 'Imaging exams'.)
DIFFERENTIAL DIAGNOSIS

The differential diagnosis of suspected acute appendicitis includes disorders typically considered
in nonpregnant individuals. (See "Acute appendicitis in adults: Clinical manifestations and
differential diagnosis", section on 'Differential diagnosis'.)
In addition, pregnancy-related causes of lower abdominal pain, fever, leukocytosis,

nausea/vomiting, and changes in bowel function, need to be considered:
● The possibility of ectopic pregnancy should be excluded in any woman with a positive
pregnancy test and right lower quadrant pain. (See "Ectopic pregnancy: Clinical
manifestations and diagnosis".)
● Indigestion, bowel irregularity, nausea/vomiting, and malaise are common symptoms of both
appendicitis and normal early pregnancy. In appendicitis, nausea and vomiting, if they occur,
follow the onset of pain, whereas nausea and vomiting of pregnancy are not associated with
pain. (See "Clinical manifestations and diagnosis of early pregnancy".)
● Round ligament syndrome is a common cause of mild right lower quadrant pain in early
pregnancy, but is not associated with other symptoms and is not progressive. (See "Clinical
manifestations and diagnosis of early pregnancy".)
● Pyelonephritis is more common in pregnant women than in nonpregnant women. If pregnant

women with right-sided pain, fever, leukocytosis, and pyuria are treated for pyelonephritis
without further investigation, the actual diagnosis of appendicitis may be delayed.
● In the second half of pregnancy, preeclampsia and HELLP (Hemolysis, Elevated Liver
function tests, Low Platelets) syndrome can be associated with nausea/vomiting and
abdominal pain, but in contrast to appendicitis, the pain is usually in the right upper quadrant
or epigastrium, hypertension is usually present, and fever and leukocytosis are atypical. (See
"Preeclampsia: Clinical features and diagnosis" and "HELLP syndrome (hemolysis, elevated
liver enzymes, and low platelets)".)
● Abruptio placenta and uterine rupture are associated with lower abdominal pain, which may
be midline or lateral. Unlike appendicitis, both diagnoses are often associated with vaginal
bleeding, fetal heart rate abnormalities, and uterine tenderness. (See "Placental abruption:
Pathophysiology, clinical features, diagnosis, and consequences" and "Uterine rupture: After
previous cesarean delivery".)
● In postpartum patients, ovarian vein thrombophlebitis (OVT) should be considered. These

patients usually present within one week after delivery and appear clinically ill; symptoms may
include fever and abdominal pain and tenderness localized to the right if the right ovarian vein
is affected. Nausea, ileus, and other gastrointestinal symptoms may occur but are usually
mild, which may be helpful in distinguishing right-sided OVT from appendicitis. (See "Septic
pelvic thrombophlebitis".)

MANAGEMENT AND SHORT-TERM OUTCOME
Appendectomy — The treatment of acute appendicitis is appendectomy, which is curative.

Perioperative antibiotic treatment should provide Gram-negative and Gram-positive coverage (eg,
a second-generation cephalosporin) and coverage for anaerobes (eg, clindamycin or
metronidazole). Management with antibiotic therapy alone is not recommended because it is
associated with both short-term and long-term failure, with minimal data in pregnant patients
[59,60]. (See "Management of acute appendicitis in adults", section on 'Evidence for nonoperative
management'.)
Prompt diagnosis and surgical intervention are indicated, as delaying surgical intervention for
more than 24 hours after symptom onset increases the risk of perforation [2,40], which occurs in
14 to 43 percent of such patients. Maternal morbidity following appendectomy is comparable to
that in nonpregnant women and low [61], except in patients in whom the appendix has perforated.
Importantly, the risk of fetal loss is increased when the appendix perforates (fetal loss 36 versus
1.5 percent without perforation [62]) or when there is generalized peritonitis or a peritoneal
abscess (fetal loss 6 versus 2 percent; early delivery 11 versus 4 percent [63]).
Given the difficulties in the clinical diagnosis of appendicitis and the significant risk of fetal
mortality if the appendix perforates, a higher negative laparotomy rate (20 to 35 percent)
compared with nonpregnant women is generally considered acceptable. Aggressive use of
radiologic imaging, including ultrasound, magnetic resonance (MR), and computed tomography
(CT) scanning, has the potential to reduce the incidence of negative appendectomy. There is
some evidence that the higher rate of negative laparotomy in pregnant women is linked, at least in
part, to a reluctance to perform preoperative CT in these patients [38,64]. (See 'Imaging' above.)
A normal-appearing appendix at time of surgery should be removed because histological

examination may reveal acute inflammation, excision avoids the potential for future evaluation and
intervention for suspected appendicitis, and appendectomy is associated with a very low risk of
complications.
Cesarean delivery is rarely indicated at the time of appendectomy. For patients who remain
undelivered, the risk of dehiscence of the appendectomy incision during labor and vaginal delivery
should not be increased when the fascia has been appropriately reapproximated [6].
Perforated appendix — The management of appendiceal perforation depends on the nature of

the perforation: free versus walled-off.
Free perforation — A free perforation can cause intraperitoneal dissemination of pus and fecal
material. These patients are typically quite ill and may be septic; they are at increased risk of
preterm labor and delivery and fetal loss [62,63]. Urgent laparotomy is necessary for
appendectomy with irrigation and drainage of the peritoneal cavity.

Walled-off perforation — Nonpregnant patients who present with a long duration of symptoms
(more than five days) and have findings of a contained perforation can be treated initially with
antibiotics, intravenous fluids, bowel rest, and close monitoring. These patients will often have a
palpable mass on physical examination and imaging may reveal a phlegmon or abscess. Many of
these patients will respond to nonoperative management since the appendiceal process has
already been "walled-off." Moreover, immediate surgery in patients with a long duration of
symptoms and phlegmon formation is associated with increased morbidity due to dense
adhesions and inflammation. Under these circumstances, appendectomy often requires extensive
dissection and may lead to injury of adjacent structures. Complications such as a postoperative
abscess or enterocutaneous fistula may ensue, necessitating an ileocolectomy or cecostomy.
Because of these potential complications, a nonoperative approach is a reasonable option if the
patient is not ill-appearing. (See "Management of acute appendicitis in adults", section on
'Perforated appendicitis'.)
Although there is good evidence to support this approach to walled-off perforation in nonpregnant
individuals, there is only sparse evidence in pregnant women. In a single report including only two
patients, antibiotic therapy (ampicillin, gentamicin, and clindamycin), intravenous fluids, and bowel
rest were associated with improvement in symptoms over two to three days [59]. In one patient,
interval appendectomy was performed two months post-vaginal delivery. In the other patient,
appendectomy was performed at cesarean delivery because of breech presentation with preterm
labor; this patient had an appendiceal phlegmon that had been treated conservatively seven
weeks earlier, but with recurrence of acute appendiceal inflammation. In both cases, treatment
with antenatal glucocorticoids to induce fetal lung maturation and tocolytics was avoided due to
concerns of suppressing clinical manifestations of worsening infection and delaying delivery if
intraamniotic infection was also present. On the other hand, a letter to the editor described two
deaths related to appendicitis in pregnant women who appeared to recover after treatment with
antibiotics and were discharged from the hospital [65]. Until more information on nonoperative
management of ruptured, but contained, appendicitis during pregnancy is available, we suggest
that these patients be carefully monitored in the hospital for maternal sepsis and preterm labor.
While there is some support for interventional drainage of appendiceal abscesses in children,
there is no information regarding such management in pregnant patients.
SURGICAL APPROACH
Choice of approach — When the diagnosis is relatively certain, both open and laparoscopic
appendectomy are considered and are reasonable. No randomized trials have been performed to
suggest that one technique is better than another, and the choice of technique is based on the
patient's clinical status and preferences, gestational age, and the surgeon's experience level.

The relative benefits and concerns for the two different approaches were evaluated in a meta-
analysis of 20 studies (19 retrospective, 1 prospective) including over 6200 pregnant women who
underwent appendectomy (1926 laparoscopic and 4284 open procedures) [66]:
● Favoring laparoscopic approach – The laparoscopic approach was associated with lower
overall complication rates (odds ratio [OR] 0.48, 95% CI 0.29-0.80, 1835 patients) and shorter
hospital stays (mean difference -0.94 days, 95% CI -1.55 to -0.33, 2211 patients) compared
with open procedures.
● Favoring open approach – Women who underwent open surgery had a reduced risk of fetal
loss and increased gestational age at the time of term delivery compared with women who
underwent laparoscopic surgery (for laparoscopy, risk of fetal loss OR 1.82, 95% CI 1.30-
2.57, 4867 patients and mean difference in gestational age -0.46 weeks, 95% CI -0.87 to
0.04, 543 patients).
● Similar – Similar outcomes were reported for operative times, birth weight, incidence of
preterm birth (<37 weeks of gestation), and cesarean delivery rates.
However, this meta-analysis had important limitations. As the data were obtained from a large
international cohort, the range of patients, surgeons, and surgical settings limits the applicability to
any one patient group. Additionally, the meta-analysis included only one prospective study. Other
limitations included the small number of studies that had more than 50 patients in each study arm
(4 of 20) and the lack of information on gestational age in the three largest studies that accounted
for more than 50 percent of the study population. When the largest study, which did not include
information on gestational age, was removed from the analysis, there was no longer a statistical
difference in loss rate between the two surgical approaches.
Open appendectomy — When performing an open appendectomy in a pregnant woman, a

transverse incision is made at McBurney's point or, more commonly, over the point of maximal
tenderness [14,15]. When the diagnosis is less certain, we suggest a lower midline vertical
incision since it permits adequate exposure of the abdomen for diagnosis and treatment of
surgical conditions that mimic appendicitis. A vertical incision can also be used for a cesarean
delivery, if subsequently required for the usual obstetric indications. It is prudent to minimize
traction on the uterus and uterine manipulation, although an association between these
maneuvers and preterm birth is unproven.
Laparoscopic appendectomy — Case reports, case series and small cohort studies on the use
of laparoscopic appendectomy in pregnancy suggest that laparoscopy can be performed
successfully during all trimesters and with few complications [4,66-78]. The decision to proceed
with a laparoscopic approach should take into consideration the skill and experience of the
surgeon, as well as clinical factors such as the size of the gravid uterus. Suggestions for
modification of laparoscopic technique during pregnancy include slight left lateral positioning of the
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patient during the second half of pregnancy, avoiding the use of any cervical instruments, use of
open entry techniques or placement of trocars under direct visualization, and limiting
intraabdominal pressure to less than 12 mmHg [79]. The Society of American Gastrointestinal and
Endoscopic Surgeons (SAGES) guidelines recommend insufflation pressures of 10 to 15 mmHg
and that the port position should be adapted for fundal height [80]. (See "Laparoscopic surgery in
pregnancy".)
However, concern has been raised that laparoscopic appendectomy appears to be associated
with higher rates of preterm delivery and fetal loss [66,81-83]. In the largest meta-analysis to date,
including 20 studies and over 6200 pregnant women with appendicitis, laparoscopic surgery was
associated with an increased risk of fetal loss (OR 1.82, 95% CI 1.30-2.57, 4867 patients) [66].
Limitations of this study include that 19 of 20 studies were retrospective and that the gestational
age and timing relative to surgery at the time of loss were not identified.
In our practice, we find the use of laparoscopy safe, especially when patients are appropriately
monitored and no overt signs of preterm labor exist. Laparoscopy affords optimal visualization and
recovery when performed by experienced surgeons. We use slightly lower intraabdominal
pressures of 10 to 12 mmHg (which provides excellent visualization), an open entry technique,
and directly visualized trocar insertion.
Intraoperative management and monitoring — The intraoperative management of pregnant

women undergoing nonobstetric surgery and monitoring of the fetus are reviewed separately. (See
"Management of the pregnant patient undergoing nonobstetric surgery".)
LONG-TERM OUTCOME
The long-term prognosis for women who undergo appendectomy during pregnancy is generally
good, but data are limited to observational series. It appears that preexisting morbidities, and not
the surgery itself, are the greater risk factors for postoperative adverse obstetric events. In a
national cohort study of nearly 20,000 women who underwent either appendectomy or
cholecystectomy during pregnancy, risk factors most strongly associated with an adverse obstetric
outcome included cervical incompetence, preterm labor during the current pregnancy (but prior to
surgery), vaginitis or vulvovaginitis, and sepsis [84]. Other factors that had a more moderate
impact on risk included non-white race/ethnicity, Medicaid insurance, drug abuse or dependence,
multiple gestation, and open surgery (ie, laparotomy). In a prospective observational study of
pregnant patients who underwent appendectomy, none of the study respondents (29 patients,
56%) reported developmental delays in their children after a mean of 47 months of follow-up
(range 13 to 117 months) [85].
SUMMARY AND RECOMMENDATIONS

● Acute appendicitis is the most common general surgical problem encountered during
pregnancy. (See 'Introduction' above.)
● The clinical manifestations of appendicitis in pregnancy are similar to those in nonpregnant

individuals; however, the following points should be noted:
• Right lower quadrant pain is the most common symptom and occurs within a few
centimeters of McBurney's point in most pregnant women, regardless of the stage of
pregnancy. In late pregnancy, pain may be the right mid or upper quadrant. Rebound
tenderness and guarding are less prominent in pregnant women, especially in the third
trimester. (See 'Patient presentation' above.)
• Mild leukocytosis can be a normal finding in pregnant women: the total leukocyte count
may be as high as 16,900 cell/microL in the third trimester and 29,000 cells/microL during
labor, so leukocytosis may or may not be a sign of appendicitis. (See 'Laboratory' above.)
● The clinical diagnosis should be strongly suspected in pregnant women with classic findings:
abdominal pain that migrates to the right lower quadrant, right lower quadrant tenderness,
nausea/vomiting, fever, and leukocytosis with left shift. (See 'Diagnosis' above.)
With a nonclassical presentation, which often happens in late pregnancy, imaging is indicated.
The primary goal of imaging is to reduce delays in surgical intervention due to diagnostic
uncertainty. A secondary goal is to reduce, but not eliminate, the negative appendectomy rate.
● Imaging:
• We suggest graded compression ultrasonography in pregnant patients suspected of

having appendicitis. Appendicitis is diagnosed if a noncompressible blind ended tubular
structure is visualized in the right lower quadrant with a maximal diameter greater than 6
mm. (See 'Ultrasonography' above.)
• If clinical findings and ultrasound are inconclusive, or in centers where experience with
sonographic examination of the appendix is limited, we suggest noncontrast magnetic
resonance imaging (MRI), where available, because it avoids fetal exposure to ionizing
radiation and performs well in diagnosis of lower abdominal/pelvic disorders. (See
'Magnetic resonance imaging' above.)
• We suggest computed tomography (CT) when MRI is not available, given its proven
value in nonpregnant individuals. (See 'Computed tomography' above.)
● The decision to proceed to surgery should be based upon the clinical findings, diagnostic
imaging results, and clinical judgment. Delaying intervention for more than 24 hours increases
the risk of perforation. (See 'Management and short-term outcome' above.)

● When the diagnosis is relatively certain, we advise appendectomy by the method that the
surgeon is most skilled at performing, whether it be by minimally invasive or open surgery. If
being done by an open approach, we suggest using a transverse incision over the point of
maximal tenderness (Grade 2C). When the diagnosis is less certain and if laparoscopy is not
available, then we suggest using a lower midline vertical incision (Grade 2C). (See 'Surgical
approach' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge William Barth, Jr, MD, and Joel
Goldberg, MD, FACS, who contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 4804 Version 32.0

GRAPHICS
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

¶ Δ
Hemoglobin (g/dL) 12 to 15.8 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,
(x10 3/mm 3) 18
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
Δ
Δ
Progesterone (ng/mL) <1 to 20 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 34.3 to 242.9 62.9 to 308.6 56

211.4
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 70.3 to 107.6 54 to 99 65, 68, 69

107.6
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].
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Graphic 81137 Version 45.0

Sonogram of appendicitis in pregnancy
Sonogram of the right lower quadrant in a woman with appendicitis who is six
weeks pregnant. Note the markedly thick-walled appendix (calipers) measuring
16 mm.
Courtesy of Deborah Levine, MD.

Sonogram of appendicitis in pregnancy
Sonogram of the right lower quadrant in a woman with appendicitis at 21 weeks

of gestation. Note the fluid-filled appendix with appendicoliths (arrow).

Magnetic resonance image of appendicitis in pregnancy
T2-weighted magnetic resonance image of a woman with appendicitis at 9

weeks of gestation. The appendix was fluid-filled and measured 7 mm (arrow).
The gestational sac (gs) is seen lower in the pelvis.

MRI T1-weighted image of bright appendix in pregnancy
(A) Axial T2-weighted MRI of a 33-year-old pregnant woman (gestational age: 21

weeks) who presented with right lower quadrant pain. The appendix, located below the
right kidney (arrow), is superiorly displaced by the uterus.
(B) In the axial T1-weighted image, intraluminal high signal intensity in the appendix
(arrow), a typical positive T1 bright appendix sign, was noted. She was discharged after
symptom relief, and no residual pain was reported during a follow-up physical
examination after a few weeks.
MRI: magnetic resonance image.
Reprinted by permission from: Springer: European Radiology. Shin I, An C, Lim JS, et al. T1
bright appendix sign to exclude acute appendicitis in pregnant women. Eur Radiol 2017;
27:3310. Copyright © 2017. https://link.springer.com/journal/330.

CT appendicitis in pregnancy
The main findings of appendicitis on CT are right lower quadrant inflammation, an

enlarged nonfilling tubular structure, and/or an appendicolith.
CT: computed tomography.
Courtesy of Joel Goldberg, MD, FACS.

Contributor Disclosures
Andrei Rebarber, MD Nothing to disclose Brian P Jacob, MD Consultant/Advisory Boards: Medtronic.
Equity Ownership/Stock Options: International Hernia Collaboration. Charles J Lockwood, MD,
MHCM Nothing to disclose Deborah Levine, MD Nothing to disclose Martin Weiser,
MD Grant/Research/Clinical Trial Support: Clinical Genomics [Colorectal cancer (ctDNA)]. Kristen Eckler,
MD, FACOG Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
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10/9/2019 Acute appendicitis in pregnancy - UpToDate

Official reprint from UpToDate®

• Abdominal pain: 96 percent

- Right lower quadrant: 75 percent

- Right upper quadrant: 20 percent

• Right lower quadrant tenderness: 85 percent

Laboratory — Approximately 80 percent of nonpregnant patients with appendicitis have a

An elevated c-reactive protein level occurs in appendicitis, but is a nonspecific sign of

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Magnetic resonance imaging — For pregnant women whose ultrasound examination is

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● Positive predictive value 92.4 percent (95% CI 83.2-97.5)

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Computed tomography — CT is generally widely available. The main findings of appendicitis

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In addition, pregnancy-related causes of lower abdominal pain, fever, leukocytosis,

● Pyelonephritis is more common in pregnant women than in nonpregnant women. If pregnant

● In postpartum patients, ovarian vein thrombophlebitis (OVT) should be considered. These

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MANAGEMENT AND SHORT-TERM OUTCOME

Appendectomy — The treatment of acute appendicitis is appendectomy, which is curative.

A normal-appearing appendix at time of surgery should be removed because histological

Perforated appendix — The management of appendiceal perforation depends on the nature of

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Open appendectomy — When performing an open appendectomy in a pregnant woman, a

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Intraoperative management and monitoring — The intraoperative management of pregnant

SUMMARY AND RECOMMENDATIONS

● The clinical manifestations of appendicitis in pregnancy are similar to those in nonpregnant

• We suggest graded compression ultrasonography in pregnant patients suspected of

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3. Weingold AB. Appendicitis in pregnancy. Clin Obstet Gynecol 1983; 26:801.

4. Andersen B, Nielsen TF. Appendicitis in pregnancy: diagnosis, management and

7. Abbasi N, Patenaude V, Abenhaim HA. Management and outcomes of acute appendicitis in

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23. Mahmoodian S. Appendicitis complicating pregnancy. South Med J 1992; 85:19.

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31. Sugita K, Kobayashi S, Mutsuga N, et al. Microsurgery for acoustic neurinoma--lateral

33. Sand M, Bechara FG, Holland-Letz T, et al. Diagnostic value of hyperbilirubinemia as a

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56. Damilakis J, Perisinakis K, Voloudaki A, Gourtsoyiannis N. Estimation of fetal radiation dose

58. Basaran A, Basaran M. Diagnosis of acute appendicitis during pregnancy: a systematic

65. Vasireddy A, Atkinson S, Shennan A, Bewley S. Management of appendicitis. Surgical

74. Lemieux P, Rheaume P, Levesque I, et al. Laparoscopic appendectomy in pregnant patients:

80. Guidelines Committee of the Society of American Gastrointestinal and Endoscopic

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Topic 4804 Version 32.0

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Normal reference ranges in pregnant women

Nonpregnant First Second Third

Erythropoietin ¶ 4 to 27 12 to 25 8 to 67 14 to 222 1-3

Ferritin ¶ (ng/mL) 10 to 150 Δ 6 to 130 2 to 230 0 to 116 1-8

Haptoglobin (mg/mL) 25 to 250 130 ± 43 115 ± 50 135 ± 65 93

Iron, serum ¶ (mcg/dL) 41 to 141 72 to 143 44 to 178 30 to 193 2, 7

Mean corpuscular 79 to 93 81 to 96 82 to 97 81 to 99 5, 6, 13, 14

Transferrin, saturation 22 to 46 ¶ Not reported 18 to 92 9 to 98 3

Antithrombin, functional 70 to 130 89 to 114 78 to 126 82 to 116 17, 19, 20

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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