The prevalence of acute appendicitis in pregnancy is quite high, making it one of the most common surgical emergencies in the pregnant population. Its prevalence ranges from 1 in 700 to 1500 live births. ^{1 – 3} Although not as common as other non-surgical emergencies, acute appendicitis has dire consequences both for the mother and her fetus. Acute appendicitis correlates with placental abruption, preterm labor, fetal loss, and even maternal death.

Acute appendicitis in pregnancy could be treated with surgery, either open or laparoscopic appendectomy, or with antibiotics alone. The 2020 update of the World Society of Emergency Surgery (WSES) Jerusalem guidelines gave a low-strength recommendation against treating acute appendicitis non-operatively during pregnancy and recommended using laparoscopic appendectomy. ⁴ One of the reasons for this recommendation was the lack of high-level evidence, where they only considered three studies, of which two were case reports. As a result, clinical practices regarding the treatment of acute appendicitis in pregnancy worldwide continued to vary from one region to another. In Korea, 25% of pregnancy affected by acute appendicitis was treated conservatively, ⁵ compared to 63% in China, ⁶ 67% in Japan, ⁷ and 45% in the United States of America. ⁸ This wide variance and high usage of conservative strategy could mean that not all clinicians adopted the existing guideline.

Some considerations for treating acute appendicitis conservatively were the lack of surgical resources, patient’s preference, and uncomplicated type of appendicitis. There has also been controversy regarding the type of appendectomy, with one systematic review reporting a higher proportion of fetal loss in patients treated with laparoscopic appendectomy. ⁹ Moreover, two meta-analyses have reported that antibiotics treatment alone for uncomplicated appendicitis in the general population had a lower rate of complications, with an acceptable, albeit lower, rate of success. ^{10 , 11} Therefore, seeing the lack of strong evidence and variance in clinical practice, we planned the current review to identify the efficacy and safety of conservative treatment in the treatment of acute appendicitis in pregnancy.

Our initial search resulted in 3,275 records. After duplicate removal, 2,165 titles and abstracts were screened. This initial screening resulted in 92 studies being sought for retrieval. All studies were retrieved, and we assessed their full texts for eligibility. We excluded 87 studies because they did not provide a comparison between antibiotics and surgery and did not provide data on the outcomes we planned to analyze. Finally, five studies were included for final analysis ( Figure 1). ^{6 , 7 , 12 – 14}

Our analysis showed that conservative management of acute appendicitis in pregnant patients resulted in a lower risk of preterm labor (OR 0.63 [95% CI 0.43–0.92]; p 0.02). The rate of complications in our primary analysis was also comparable between the two groups. However, after excluding the study by Nakashima et al. in our sensitivity analysis, we found that antibiotic treatment resulted in a significantly higher risk of complications (OR 1.79 [95% CI 1.19–2.69]; p 0.005). The result of this analysis mainly came from the study by Abbasi et al., which had the highest number of participants. Abbasi et al. was also the only one that reported the occurrence of sepsis and peritonitis. ¹² Several newer studies have suggested that conservative management is a safe option in treating acute appendicitis in the pregnant population. ^{6 , 7 , 13} Interestingly, none of those studies found any occurrence of sepsis and peritonitis. We suspected those studies did not have adequate statistical power to detect those complications. Immunological changes during pregnancy are one of the possible reasons for an increase in infectious complication, such as peritonitis and sepsis. Immune response in patients with acute appendicitis includes increased neutrophil and C-reactive Protein (CRP). ¹⁵ During pregnancy, there is evidence of increased neutrophil activation, but its activity and phagocytosis function are limited. ¹⁶ In conclusion, decreased activities of activated neutrophils in pregnancy may explain higher rates of infectious complications, such as sepsis, in the pregnant population.

Another concern is the difference in the number of patients with complicated appendicitis. Abbasi et al. in their study, had 20.3% of the study population diagnosed with complicated appendicitis, ¹² Vasileiou et al. had 25%, ¹³ while Liu et al. only included patients with uncomplicated appendicitis. ⁶ Liu et al. in their study, expectedly did not report a higher complication rate in the antibiotic group. ⁶ However, Vasileiou et al., comparable with the study by Abbasi et al. in terms of patients with complicated appendicitis also reported a lower rate of complication. ¹³ This made it difficult to arrive at a definite conclusion on whether patients with complicated appendicitis could benefit from conservative management.

Despite a higher risk of complications, we found that conservative management reduced the risk of preterm labor. Therefore, the potential benefits of conservative management should not be crossed out just yet. Two meta-analyses on non-pregnant patients also concluded that conservative management is a viable option. ^{10 , 11} Aside from the studies included in the analysis, there were two studies that also supported the use of antibiotic for acute appendicitis in the pregnant population. However, we excluded those two studies because they did not provide a comparison with a control group. ^{5 , 17} Rather than focusing solely on comparing the efficacy and safety between conservative and surgical approaches, more attention should be given to tailoring a strategy for each patient. Several studies have identified predictors for the failure of conservative management in non-pregnant patients, such as high serum C-reactive protein, presence of appendicolith, diabetes, longer duration of symptoms, higher temperature, higher Alvarado score, and larger appendiceal diameter. ^{18 – 20} However, those studies only studied patients with uncomplicated appendicitis.

Diagnosis of acute appendicitis in pregnancy also has its consideration. Negative appendectomy in the pregnant population ranges from 25 to 50%, higher than those in the general population, which only ranges from 15 to 35%. ²¹ To reduce unneeded surgery, radiographical imaging is usually ordered to supplement the diagnosis. As computed tomography (CT) scan is often contraindicated in pregnant patients, ultrasonography and magnetic resonance imaging (MRI) are the main radiographical modalities for diagnosing appendicitis. As ultrasonography has a low sensitivity and specificity, MRI is often warranted in patients with a negative ultrasonography finding. ^{22 , 23} However, MRI is not widely available, especially in low to middle-income settings. Therefore, in those settings, it can be expected that a significant number of pregnant patients with suspected appendicitis would receive a misdiagnosis. In a pregnant patient with a doubtful clinical presentation of acute appendicitis and a negative ultrasonography finding, a conservative approach might be appropriate as first-line management. However, a surgical approach should always be preferred for a patient with a set of specific and characteristic symptoms of acute appendicitis.

We listed comparison as surgical treatment, either open or laparoscopic based on insufficient evidence of suspected association between laparoscopic appendectomy and miscarriage. This association needs further research which results in no recommendation of one method superior of the other. Furthermore, resources needed to carry out laparoscopic procedures in developing countries are still limited - hence open appendectomy remains a viable and equal option. ²³

One limitation of the available studies on this subject is the lack of information on whether appendicitis recurred or not after conservative management. Vasileiou et al. reported that patients in the antibiotic and surgery group had a comparable emergency department (ED) return rate after 30 days. ¹³ However, they did not specify the reason for the ED visit. One meta-analysis by Sallinen et al. found that 8.5% of patients in the antibiotic group required an appendectomy within one month. ¹⁰ Future studies intending to study conservative management for acute appendicitis in pregnant patients should include recurrence as one of the outcomes.

Additionally, the use of tocolytic agents was not mentioned in any of the journals included in this review. Although there had been some evidence in the past regarding the function of tocolytic agents administration for pregnant women undergoing surgery, latest systematic review and recommendation do not recommend its use because it has not been shown to improve outcomes. ²⁴ Lastly, the studies did not provide information regarding complications in accordance with each trimester. There has been evidence in the past regarding lower risk of acute appendicitis in the third trimester of pregnancy, therefore, future studies should evaluate any complication in accordance with the patients’ trimester. ²⁵

Our analysis has several limitations. One limitation is the small number of studies and the non-randomized design. It is indeed difficult to perform a clinical trial on pregnant patients. Therefore, future cohorts should be carefully designed as they are the main modality to address this issue. Another limitation is the potential risk of confounding bias. We addressed this issue by performing a sensitivity analysis. However, unmeasured confounding inherent in the design of cohort studies remained a problem.

Patients in the antibiotic group had a significantly lower risk of preterm labor but a higher risk of complications. Seeing the result and the available evidence, we suggested that conservative management should not be given indiscriminately to pregnant patients until it is found which patients could benefit the most from such a strategy. Conservative management must also be given with close and routine monitoring to prevent life-threatening complications, such as sepsis and peritonitis. Nevertheless, the potential benefit should warrant future studies addressing the identified concerns, namely patient selection and recurrence.