Introduction

Appendicitis is the most common general surgery problem during pregnancy. Its diagnosis represents a challenge, as its classic clinical presentation is not always present, its common symptoms are nonspecific and often associated with normal pregnancy, and the gravid state may mask the clinical picture. Also, obstetric causes may obscure the diagnosis, and physical examination of the pregnant patient may be difficult as a result of the gravid uterus and its effect on displacing the appendix within the abdomen. Furthermore, biochemical and laboratory indicators used to support the diagnosis of appendicitis may be unreliable during pregnancy.[1] General principles of pathophysiology, diagnosis, workup, and management for appendicitis during pregnancy follow the same pattern as in non-pregnant patients and are revised and discussed in the present review.

Etiology

The cause of appendicitis is the obstruction of its lumen. Fecal stasis and fecaliths most commonly cause this phenomenon; however, lymphoid hyperplasia, neoplasms, fruit and vegetable material, ingested barium, and parasites are other possible agents responsible for the obstruction.[2]

Epidemiology

Acute appendicitis is diagnosed in 1 in 800 to 1 in 1500 pregnancies[3], with a higher incidence during the second trimester.[4]

Maternal morbidity and mortality following appendectomy are low and comparable to non-pregnant women.[5] The risk of fetal loss during uncomplicated appendectomies is 2%, however, in the presence of generalized peritonitis, and peritoneal abscess, the fetal loss may increase to 6%.[6] In the presence of free perforation, the risk of fetal loss may rise to 36%.[7]

The incidence of preterm labor due to appendectomy is 4%, and 11% in complicated cases. The association between negative appendectomy to preterm labor and fetal loss is 10% and 4%, respectively.[6]

Pathophysiology

The obstruction of the appendix results in increased intraluminal pressure and distention due to ongoing mucus secretion as well as gas production by bacteria that lie within the appendix; this results in progressive impairment of the venous drainage, causing first mucosal ischemia, followed by full-thickness ischemia, and ultimately perforation of the appendiceal wall. Stasis distal to the obstruction allows bacterial overgrowth within the appendix, resulting in the release of a larger bacterial inoculum to the peritoneal cavity in cases of perforated appendicitis.[2]

Intraluminal bacteria within the appendix are similar to those found in the colon; therefore, antibiotic therapy should include coverage for both gram-negative and gram-positive bacteria as well as anaerobes.[8]

Distention of the appendix is responsible for the initial visceral and vague abdominal pain often described by the affected patient. The pain typically does not localize to the right lower quadrant until the tip becomes inflamed and irritates the adjacent parietal peritoneum or perforation occurs, resulting in localized peritonitis.

History and Physical

In the classic scenario of appendicitis, the patient first describes periumbilical pain that migrates to the right lower quadrant. Following the onset of pain, anorexia, nausea, vomiting, fever may develop. Non-classic symptoms include malaise, heartburn, flatulence, constipation, and diarrhea.[9][2][10][11][12][13]

The abdominal examination usually reveals tenderness, rebound tenderness, and involuntary guarding on palpation of the right lower quadrant. The location of the tenderness is classically over the McBurney point, which is located one-third the distance between the anterior superior iliac spine (ASIS) and the umbilicus. Diffuse peritonitis or abdominal wall rigidity is strongly suggestive of appendiceal perforation.[9][2]

When the appendix is in the retrocecal region, pain is usually described as dull rather than localized, and it will be elicited more likely by rectal or vaginal examination than by abdominal examination. Accordingly, a pelvic appendix may cause tenderness below the McBurney point, urinary frequency, dysuria, tenesmus, and diarrhea.[9][2][10][11][12][13]

Several signs have been described to help in the diagnosis of appendicitis. Some of them are the Rovsing sign (presence of right lower quadrant pain on palpation of the left lower quadrant), the obturator sign (right lower quadrant pain on internal rotation of the hip), and the psoas sign (pain with extension of the ipsilateral hip).[9]

Gravid women are less likely to have a classic presentation of appendicitis than age-matched nonpregnant women, especially in the late stages of pregnancy; however, the majority of pregnant women will still present abdominal pain, close to the McBurney point. As the location of the appendix may migrate cephalad with the enlarging uterus, pain may be described in the right flank or even in the right upper quadrant as pregnancy advances.[14][15][16][17][18][13]

Abdominal tenderness may be less prominent during pregnancy because the gravid uterus lifts the anterior abdominal wall away from the inflamed appendix. In the pregnant patient, the uterus may also inhibit contact between the omentum and the inflamed appendix.[19][20][21]

Evaluation

Laboratory Workup

As opposed to most of the non-pregnant patients with appendicitis who have a preoperative leukocytosis (greater than 10000 cells/microL) and a neutrophilic predominance, leukocytosis as high as 16900 cell/microL may be a normal finding in pregnant women, and during labor the count may rise as high as 29000 cells/microL, with a slight neutrophilic predominance.[22][23][24][25][26][27] Therefore the presence of leukocytosis is an unreliable indicator in the workup of appendicitis. 

Microscopic hematuria and pyuria may occur when the inflamed appendix is close to the bladder or ureter, but these findings are not specific and generally reported in less than 20 percent of patients.[28]

Mild elevations in serum bilirubin (total bilirubin over 1.0 mg/dL) have been described as a marker for appendiceal perforation (70% sensitivity and 86% specificity). However, clinicians should not use this finding alone as a diagnostic tool.[29]

An elevated c-reactive protein level occurs in appendicitis, but it is a nonspecific sign of inflammation. (citation needed)

Imaging

Due to the risks of negative appendectomies, routine imaging is recommended in all pregnant patients with suspected appendicitis, to obtain accuracy in diagnosis. The initial study of choice is ultrasound with graded compression of the right lower quadrant starting at the point of maximal tenderness and scanning between the border of the pelvis, iliac artery, and psoas muscle. Ultrasound has the advantage of being pregnancy-safe and easily available.[30] Ultrasound is also helpful for providing information on fetal well-being and obstetric causes of abdominal pain. The criteria for US diagnosis are the same as in the nonpregnant patient; the inflamed appendix appears enlarged (greater than 6 mm), immobile, and noncompressible.[30][31] However, ultrasound is a user-dependent tool, and the presence of the gravid uterus during pregnancy will reduce ultrasound sensitivity (78%) and specificity (83%).[30]

If ultrasound findings are inconclusive, magnetic resonance imaging (MRI) without gadolinium contrast remains a safe alternative for confirmation or exclusion of appendicitis during pregnancy, as it provides good soft-tissue resolution and lacks ionizing radiation, with excellent sensitivity and specificity that remains intact in the pregnant patient. Routine use of MRI in pregnant patients reduces the negative appendectomy rate by almost 50% and does not increase the rate of perforation. For these reasons, when available, the liberal use of MRI in pregnant patients suspected to have acute appendicitis is recommended. When MRI is not available or is available only on a limited basis, the decision about any delay in appendectomy to obtain an MRI study requires all available clinical and imaging information available, as the potential consequences associated with both negative appendectomy and appendiceal perforation are severe.[30] MRI has been shown to perform relatively well in a few limited retrospective studies ranging from 97 to 100% sensitive.[32][33]

Although debatable, the use of CT scanning might be permissible when ultrasound is inconclusive and MRI not available. The use of CT scanning reduces the rate of negative appendectomy significantly compared to clinical assessment alone or combined with ultrasound imaging, and some authors conclude that it should be used if ultrasound findings are equivocal. Arguably, the amount of radiation during a limited CT scan is below the threshold required to cause fetal malformations, and most cases of appendicitis in pregnancy occur in later stages of pregnancy when organogenesis is already complete. If it is decided to use CT during pregnancy for inconclusive cases, care should be taken to perform a study as limited as possible with no intravenous administration of contrast material.[30][34][28][35][33][32]

Differential Diagnosis

The differential diagnosis of suspected acute appendicitis during pregnancy includes disorders typically considered in non-pregnant individuals. Therefore the clinician should consider cecal diverticulitis, Meckel diverticulitis, acute ileitis, inflammatory bowel disease (Crohn and ulcerative colitis), renal colic, and urinary tract infections. Gynecological conditions in the differential diagnosis include tubo-ovarian abscess, pelvic inflammatory disease, ruptured ovarian cyst, ovarian, and fallopian tube torsion. 

Also, and more importantly, pregnancy-related causes of lower abdominal pain, fever, leukocytosis, nausea/vomiting, and changes in bowel function need to be considered, such as placental abruption, uterine rupture, preeclampsia, HELLP (hemolysis, elevated liver function tests, low platelets) syndrome. During early pregnancy, ectopic pregnancy requires exclusion. Also, consider round ligament syndrome as a possibility. This condition is a common cause of mild right lower quadrant pain in early pregnancy.

Prognosis

According to observational series, the long-term prognosis for women who undergo appendectomy during pregnancy is generally good. Preexisting morbidities, and not the surgery itself, are the greater risk factors for postoperative adverse obstetric events.[42][43]

Complications

Untreated appendicitis can develop into severe complications with high morbidity, appendiceal perforation and will manifest as one of two outcomes: free perforation, or contained or "walled-off" perforation. Open perforations cause the dissemination of pus and fecal material into the peritoneal cavity, which will likely result in a very ill-looking and septic patient with an increased risk of preterm labor and delivery and fetal loss. Contained perforations can cause peritoneal abscess or phlegmon that forms around a burst appendix and require extended antibiotic treatment and likely drainage. 

Complications of the surgery itself can be extensive and include infections (postoperative peritoneal abscess), bleeding, and damage to adjacent structures.

Consultations

Any suspected case of appendicitis in pregnancy requires an ob-gyn consultation to rule out obstetric and gynecological causes of pain as well to establish the well being of the fetus before and after anesthesia.

Deterrence and Patient Education

The appendix is a thin pouch hanging down from the large intestine. When it gets infected and inflamed, it causes a condition called appendicitis. This condition can be very painful, and if left untreated, very serious, as the appendix can burst, causing a life-threatening infection. Fortunately, appendicitis, when caught on time, can be easily treatable.

Appendicitis usually first presents as severe abdominal pain. This pain can start near the belly button and then move to the lower right side. Other usual symptoms include loss of appetite, nausea, and vomiting, and elevated fever. However, a wide variety of symptoms can be present, including upset stomach, irregular bowel movements (constipation or diarrhea). During pregnancy, identification of the picture and its diagnosis might be challenging as many of these symptoms are present during a normal pregnancy. 

A clinician or clinician team will make the diagnosis of appendicitis through a thorough interview and physical examination. If necessary, they will order special tests such as an ultrasound or MRI to provide more precise information as to the source of the abdominal pain. It is crucial that during this time, a gynecologist should examine the pregnant patient.

When any of the symptoms listed above present, it is imperative to seek medical care. The risk for the appendix to burst rises after the first 24 hours of the onset of the symptoms; therefore, early identification and treatment is of great importance and will directly impact on the results of the patient's health and pregnancy. 

The treatment for appendicitis is surgery to remove the appendix that can be done in two ways: open surgery during which the appendix will be removed through a single incision that is large enough through which to pull the appendix or laparoscopic surgery in which thin instruments and a camera are introduced to the abdomen through a few small cuts to perform the surgery, and appendix removal occurs through one of the small openings. 

Treatment for a complicated or a "burst" appendix will probably be more complicated than it would be if it had not burst, as all the material spilled out of the appendix needs to be washed away. If an appendix did burst, but a few days have passed, it is likely that the body already formed a pocket around the appendix blocking the infection. In this case, treatment consists of antibiotic therapy and close monitoring and not having surgery right away. However, surgery will be eventually needed.

Treatment for simple appendicitis without surgery is not the standard of care, but it is conceivable to do so. However, the chances of appendicitis returning are high. Patients and their physicians should discuss alternatives, including risks for both the patient and the pregnancy itself. 

Enhancing Healthcare Team Outcomes

Acute appendicitis during pregnancy poses a diagnostic dilemma. These patients may exhibit non-specific signs and symptoms such as vomiting, nausea, and leukocytosis. The cause of acute abdominal pain may be due to a myriad of diagnoses, including gynecological, obstetrical, gastrointestinal, urological, metabolic, and vascular etiologies. While the physical exam may reveal that the patient has a surgical abdomen, the cause is difficult to know without proper imaging studies. The disorder is best managed by an interprofessional team to ensure prompt diagnosis and treatment.

The general surgeon should always be involved in the care of pregnant patients with suspected appendicitis. However, it is essential to consult with an obstetrician and gynecologist to rule out problems related to the pregnancy, and any other specialist according to clinical findings and suspicion.

The nurses are also a vital member of the interprofessional group, as they will monitor the patient's vital signs. The nurses should refrain from administering pain medications until the surgeon has examined the patient.

In the postoperative period, the pharmacist will ensure that the patient is on the right analgesics, antiemetics, and appropriate antibiotics, perform a medication record check for drug interactions and verify dosing on all drugs administered.

The radiologist also plays a vital role in determining the cause. 

The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines state that laparoscopic appendectomy is safe in pregnancy and is the standard of care in pregnant patients.[39] These are evidence-based guidelines that are reviewed by an interprofessional expert committee. The current guidelines have been developed after an exhaustive review of current medical literature from peer-reviewed journals to determine the appropriateness of radiological imaging and treatment procedures by the committee. In cases where evidence is not definitive or minimal, expert opinion from the specialist may be utilized to recommend the type of imaging or treatment. [Level 1] With the unique challenges of appendicitis in pregnancy, an interprofessional team approach is the best path for guiding successful outcomes for both mother and unborn child. [Level 5]