Is There Need a Specific Scoring System for Acute Appendicitis During Pregnancy?

Acute appendicitis is the most common non-gynecological emergency during pregnancy. The diagnosis of appendicitis during pregnancy is challenging due to both physiological and laboratory changes. As such, the surgeon needs additional guidance, other than imaging methods, before deciding a surgical intervention. Various scoring methods have been defined and evaluated for the diagnosis of acute appendicitis for a long time. There is no definition of a score for the gestation period, and the comparison of the currently applied scoring methods during the gestation period is not available in the literature. The purpose of our study is to evaluate the efficacy of the most popular scoring systems applied in the diagnosis of acute appendicitis in pregnancy and the tips for introduction to a scoring method for the pregnancy period. Methods This single-center retrospective study consists of 79 pregnant patients who were admitted to the emergency department with abdominal pain between May 2014, May 2019 and were diagnosed with acute appendicitis and underwent an appendectomy together with 79 non-pregnant control group who underwent appendectomy for the last 1.5 years. Both laboratory and examination findings required for the scoring methods of the patients were obtained and calculated separately for each patient. Negative appendectomy rates were evaluated according to pathology results. Categorical variables were compared by the Chi-Square test. Categorical variables were presented as a count and percentage. A p-value <0.05 was considered significant. Receiver operator characteristic (ROC) curve analysis was used to identify the best cut-off value and assess the performance of the test score for appendicitis.

pregnant women. While PPV of this scoring method is 94.40%, NPV is 44%, its sensitivity and specificity are 78.46% and 78.57%, respectively.

Conclusions
Although the RIPASA score is considerable effective in pregnancy in the diagnosis of acute appendicitis among all scoring systems, a specific scoring system is necessitated for the gestation period.

Background
Acute appendicitis is the most common cause of non-obstetric emergency surgery in pregnant women. Appendicitis known to occur once in every 1,500 pregnant women (1). Besides, negative appendectomy rates in females of reproductive age reported at values reaching 26% (2). The differential diagnosis of acute abdominal pain during pregnancy is more complicated than a regular physiological patient in many aspects. In addition to symptoms such as nausea, vomiting, and abdominal pain that occurs during pregnancy, physiologically increasing white blood cell (WBC) count and limited radiological methods make the diagnosis of acute appendicitis complicated during pregnancy (3)(4)(5). It is unfortunately not possible to reset the negative appendectomy rate despite all the tests, whether pregnant or not (6)(7)(8)(9)(10). High suspicion in diagnosis is important, the delay that will occur causes both maternal (< 1-4%) and fetal (1.5-35%) mortality due to appendix perforation (11).
In the diagnosis of appendicitis, the main object is permanent to reduce negative appendicitis rates, avoid perforation, and to protect the patient from unnecessary surgical intervention, moreover for this purpose, various scoring methods described in addition to imaging methods, clinical findings and laboratory correlation (12)(13)(14)(15)(16)(17)(18)(19)(20). This study aims to evaluate the extent to which of these scoring methods can support us in the diagnosis of appendicitis in pregnancy.

Methods
This study consists of 79 pregnant patients who were admitted to Sakarya University Faculty of Medicine with abdominal pain between May 2014 and May 2019 and were diagnosed with acute appendicitis and underwent appendectomy and 79 non-pregnant control group who underwent appendectomy for the last 1.5 years. In the control group; patients under the age of 20 and older than 45 and those with chronic co-morbid diseases (i.e. hypertension, Diabetes Mellitus, chronic renal failure or chronic pulmonary disease) were excluded. All pregnant patients were examined by the obstetrician both before and after surgery. The laboratory and examination findings required for the scoring methods of the patients were obtained separately for each patient, including formulas were written for each scoring method in the Excel file, furthermore, the results of each score calculated by entering the data. The patients' pain related data were evaluated using the VAS score. Negative appendectomy rates were evaluated according to pathology results. The ethics committee approval of our study was provided by the ethics committee of our university.

Statistical Analysis
Descriptive analyses were performed to provide information on general characteristics of the study population. Kolmogorov-Smirnov test was used to evaluate whether the distributions of numerical variables were normal. Accordingly, either independent sample t test or Mann Whitney U test were used to compare the numeric variables between pregnant and non-pregnant. The numeric variables were presented as mean ± standard deviation or median [interquartile range]. Categorical variables were compared by Chi-Square test. Categorical variables were presented as a count and percentage.
A p-value < 0.05 was considered significant. Receiver operator characteristic (ROC) curve analysis was used to identify the best cut-off value and assess the performance of test score for appendicitis.
Analyses were performed using SPSS statistical software (IBM SPSS Statistics, Version 22.0. Armonk, NY: IBM Corp.)

Results
The median age in pregnant and non-pregnant groups is 28 [6] and 26 [10]. ) patients were not appendicitis, and these consequences were similar in the non-pregnant group, and 66 (83.5%), 13 (16.5%) respectively. When the severity of pain between the groups evaluated, the moderate pain prominent in the non-pregnant group, 54 (68.4%), the high degree of pain was prominent in the pregnant group 57 (72.2%), and statistically significant < 0.001.
While there is a difference in the spread of pain from umbilicus in favor of the pregnant group, both groups show similar findings in terms of nausea, vomiting, and anorexia. Pregnant patients applied to the hospital in less than 24 hours from the onset of symptoms. Besides, in the examination of this patient group, the guarding and rebound were statistically significantly higher than the other group.
When the scoring systems are adapted to pregnant and non-pregnant groups; The Tzanakis Score is the strongest among the scoring systems used in non-pregnant women. The positive predictive value (PPV = 90.60) of the Tzanakis Score is 90.6% while the negative predictive value (NPV = 46.7) is 46.7%. The sensitivity of the Tzanakis score was 87.8% and the specificity was 53.8%. As assessment continues with area under curve (AUC), appendicitis predictive power, the Tzanakis score was followed by the AIR score and Alvarado score in the non-pregnant group. (Table 3)

Discussion
The diagnosis of appendicitis generally performed in the light of clinical and laboratory findings, including the help of imaging methods. However, with the presence of numerous gynecological pathologies in female patients, the diagnosis of acute appendicitis becomes challenging, and the diagnosis becomes even more complicated when pregnancy added to the condition (21). In our pregnant patient group, besides the findings inherent in pregnancy, such as nausea and vomiting, there were laboratory findings similar to acute appendicitis and pregnancy.
Radiological examinations have high diagnostic value in the diagnosis of acute appendicitis (22). The teratogenic effect and high cost of computed tomography (CT) in imaging are its major disadvantages (23,24). Having positive abdominal ultrasonography (USG) findings in pregnant women with suspected appendicitis does not require additional testing to confirm the condition. Besides, cases where appendicitis cannot be diagnosed in USG, magnetic resonance imaging (MRI) is the recommended imaging method that provides a high diagnostic rate and accuracy in pregnant patients (25)(26)(27). When using new scoring systems that combine clinical and imaging features, 95% of patients considered uncomplicated appendicitis correctly identified (28).
Delay in diagnosis and treatment of the disease has been shown to result in more complicated appendicitis and increased preterm labor, perinatal morbidity, mortality, and fetal loss rates (6-10).
The use of scoring systems helps to support imaging methods (29,30). The goal of applying clinical scoring systems (CSS) in acute appendicitis is assist early diagnosis of the disease and prevent morbidity, including cost increases due to delay and the Alvarado score is the one of the most common used clinical scoring system in this respect (22). Although the Alvarado score meant for pregnant patients, its use extensively validated in the non-pregnant population (31).
CSS mainly aims to predict the diagnosis of appendicitis by enumerating signs, symptoms, and laboratory results. In this context, parameters in some CSS are not available in others. An example of this is the presence of USG in the Tzanakis score, gender in the Lintula and Fenyo-Lindberg scores, moreover negative urinary symptoms in the Ripasa and Ohmann scores can be counted among them.
In our study, we adopted nine different scoring systems which are used commonly in worldwide in the diagnosis of appendicitis in pregnant and non-pregnant appendicitis groups.
Both the presence of nausea, vomiting, and physiological leukocytosis during pregnancy and changing the position of the appendix with the gestational week, make the diagnosis of appendicitis challenging in this period (21). Precisely at this point, negative appendectomy rates are around 35% in pregnant patients (32). Currently, no suitable and valid scoring system in the literature evaluates appendicitis during pregnancy. Therefore, we evaluated the accuracy of the previously defined scoring systems for the pregnancy period. Considering the AUC in non-pregnant women for this CSS, the most valuable scoring systems were Tzanakis, AIR, and Alvarado scores, respectively. Lintula and Fenyo-Lindberg scoring systems have the lowest AUC value among the nine scoring systems.
Considering those who have high scores in the non-pregnant group, it is thought that the advantage of USG reflected in the Tzanakis scoring system in patients who are not pregnant. In pregnant women, the AUC value of the Ripasa score is determined to be high, followed by the AIR and Tzanakis scores.
CSS, heavily based on signs and detailed laboratory findings, were observed to be more predictive in the pregnant group. Although we determined the RIPASA score as the strongest score in pregnancy, its sensitivity and specificity are below 80%. As it turns out, there is a requirement for a CSS to be applied during pregnancy. Under the supervision of our data, we plan to conduct a CSS study for the gestation period.

Conclusions
Among defined CSSs, the RIPASA score in pregnancy was found to be the most precious, and this data may additionally benefit the imaging methods in pregnant patients in the clinic. Besides, a scoring system that can be defined for acute appendicitis during pregnancy will be beneficial for the surgical necessity of both mother and fetus.

Availability of data and materials
There is no additional data available to share with the readers.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Sakarya Univercity Ethics Committee has approved this research project.

Consent for publication
All patients or their caregivers signed a consent form giving permission to use their anonymous data for research. Figure 1 ROC curves for diagnostic performance of appendicitis scoring systems for non-pregnant women.

Figure 2
ROC curves for diagnostic performance of appendicitis scoring systems in pregnant women.