Keywords appendectomy in pregnancy - appendicitis in pregnancy - cesarean section - surgical intervention pregnancy - imaging diagnostics appendicitis
Schlüsselwörter Appendektomie in der Schwangerschaft - Appendizitis in der Schwangerschaft - Sectio caesarea - operativer Eingriff in der Schwangerschaft - diagnostische Bildgebung und Appendizitis
Introduction
One in 500 pregnant women requires a surgical intervention that is not primarily pregnancy related [1 ]. Elective surgeries ought to be postponed until after delivery [2 ]. Nonobstetric surgeries that need to be performed due to urgency include abdominal, dental, skin-related or bone-related surgeries [2 ]. An appendectomy is among the most frequent intraabdominal surgical procedures performed during pregnancy [3 ]. In most cases appendectomy during pregnancy is performed in women who exhibit clinical signs of appendicitis. Histopathologically, appendicitis is classified into 4 stages as depicted in [Table 1 ]
[4 ]. In 0.1% of all pregnancies appendicitis is suspected [5 ]. Acute appendicitis with peritonitis is associated with higher rates of morbidity and mortality for the mother and her offspring [6 ].
Table 1
Histopathological stages of appendicitis. Overview of classification of appendicitis and associated histopathological changes.
Classification
Histopathological changes
Acute appendicitis
Erosive appendicitis
Inflammation limited to the mucosa or submucosa. It is usually not accompanied by macroscopic changes.
Ulcerative phlegmonous appendicitis
Phlegmonous appendicitis is characterized by neutrophilic infiltration and often circumferential involvement of the muscularis propria. The mucosa is usually inflamed, ulcerated and often accompanied by edema, serositis and microabscesses.
Gangrenous appendicitis
Necrotic changes occur due to transmural inflammation of the wall layers. As the inflammation progresses, the organ can perforate.
Chronic appendicitis
Chronic appendicitis is characterized by fibrosis and inflammatory infiltrates such as lymphocytes, histiocytes and plasma cells. In addition, periappendicitous adhesions and lipomatous transformations can be detected.
Due to changes in anatomy related to the growing uterus, physiological leukocytosis and nonspecific or altered symptoms throughout gestation, diagnosing acute appendicitis in pregnant women is challenging. Mentioned factors could cause a delay in diagnosis and treatment [3 ]
[7 ]. Through the visualization of the vermiform appendix, ultrasound technology can aid in the more precise classification of suspected non-obstetrical illnesses affecting the abdomen [8 ]. Unfortunately, it frequently lacks conclusiveness and is heavily dependent on the operator [1 ]
[9 ]. Magnetic resonance imaging (MRI) is advised as the preferred imaging
modality after an inconclusive ultrasound in order to visualize and evaluate the appearance of the appendix in pregnant women [10 ]
[11 ].
In some cases chronic or even acute appendicitis do not present clinically but are suspected when looking at the vermiform appendix during elective cesarean delivery. However, visual diagnosis and histopathological analysis might not match.
We conducted a retrospective data analysis from January 2013 to January 2023 on the performance of appendectomy during pregnancy beyond 24 0/7 weeks of gestation. The primary aim of this study was to assess surgical access and pregnancy outcome. Secondary outcomes were clinical symptoms and diagnostics as well as histopathological analysis ([Fig. 1 ]).
Fig. 1
Flowchart describing the study population.
Methods and Material
Study design
This is a single-center retrospective data analysis conducted at a tertiary perinatal center in the metropolitan region of Berlin, Germany. Selection of study population is shown in [Fig. 1 ]. The study was approved by the local Ethics Committee (Eth-23/23, June 2nd, 2023) (Clinical Trial Registration: drks.de, DRKS number: DRKS00032003). Due to the retrospective nature of the study, written patient consent was not necessary. This study was performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The analysis period was January 2013 to January 2023. A digital search of the hospital record archive for obstetrical cases encoding for German operation and procedure code numbers 5–470 (appendectomy), 5–470.0 (open appendectomy), 5–470.1 (laparoscopic appendectomy), 5–470.10
(laparoscopic appendectomy via ligature), 5–470.11 (laparoscopic appendectomy via stapler), 5–470.1x (other laparoscopic appendectomy), 5–470.2 (changing from laparoscopic appendectomy to open appendectomy), 5–470.x (other appendectomy) was conducted.
Baseline variables
Baseline characteristics were obtained and recorded anonymously in a data base. Baseline characteristics included maternal age, gestational age, past obstetric history, existence of symptoms of appendicitis (maternal fever, lower right abdominal pain, upper abdominal pain), elevated inflammation parameters including white blood cell count > 10.5/nl and C-reactive protein > 5 mg/l according to hospital laboratory standards, sonographic reference of appendicitis, performance of computer tomography, performance of magnetic resonance imaging, preoperative application of antibiotics and application of antenatal corticosteroid therapy.
Obstetrical management as well as maternal and fetal outcome
Outcome of interest were spontaneous vaginal delivery, operative vaginal delivery, cesarean delivery, 5 minutes APGAR, umbilical cord arterial pH and maternal or fetal admission to Intensive Care Unit (ICU) or Neonatal Intensive Care Unit (NICU).
Surgical outcome
The surgical technique as well as intra- and postoperative complications were recorded.
Histopathological analysis
Appendices underwent routine clinical examination consisting of storage at 4 °C prior to fixation, fixation in 4% buffered formalin, measurement, trimmed weight, sectioning, and examination of the cut surface. Sections underwent routine processing, embedding, sectioning at 2 µm and staining with hematoxylin and eosin strain. Histologic examination was performed by authorized pathologists.
Statistical analysis
Descriptive statistical analysis was performed, calculating means and standard deviation for continuous variables and actual values or percentages for categorical variables. Analyses were conducted in SPSS Version 24.
Results
The clinic recorded 31057 deliveries between January 2013 and January 2023, of which 20 deliveries (0.06%) were complicated by appendectomy during pregnancy with gestational age beyond 24 0/7 weeks of pregnancy.
Baseline variables
Baseline variables are shown in [Table 2 ]. Mean patient age at the time of surgery was 32.1 years (± 6.25 years).
Table 2
Baseline variables and obstetrical outcome.
Appendectomy in pregnancy > 24 0/7 weeks of gestation
n = 20
Results are shown in absolute numbers and percentages respectively mean and standard deviation when applicable.
d = days; ICU = intensive care unit; min = minute; n = number; NICU = neonatal intensive care unit; Perc. = percentile
Maternal characteristics
Nullipara (n)
12 (60.0%)
Smoker (n)
1 (5.0%)
BMI (kg/m2 )
25.8 (± 7.4)
In-hospital stay (d)
7.4 (± 3.4)
Gestational week at time of appendectomy
37 (± 3.8)
Gestational week at time of birth
38 (± 3.3)
Mode of delivery
Vaginal
1 (5.0%)
Vaginal operative
0
Cesarean delivery
19 (95.0%)
Neonatal outcome
Weight (Perc.)
50.7 (± 27.2)
APGAR < 7 5 min (n)
1 (5.0%)
Arterial pH umbilical cord < 7.15 (n)
0
Preterm delivery
6 (30.0%)
Admission NICU
5 (25.0%)
Maternal outcome
Admission ICU
0
Clinical symptoms and diagnostic methods
13/20 patients (65.0%) presented with clinical symptoms. Mentioned symptoms are shown in [Table 3 ]. In 10/20 cases (50.0%) a conciliar presentation to the surgical attending had occurred prior to surgery. Performance of imaging diagnostics is shown in [Table 3 ]. An ultrasound of the vermiform appendix was performed in 6/20 patients (30.0%). In two cases the sonography was positive and substantiated suspicion of appendicitis which was confirmed in histopathologic work-up. In 66.7% of the cases the performed ultrasound was inconclusive.
Table 3
Overview of clinical and paraclinical symptoms of appendicitis in pregnant women.
Appendectomy in pregnancy > 24 0/7 weeks of gestation
n = 20
Results are presented in absolute numbers and percentages respectively mean and standard deviation when applicable.
h = hour; n = number
Symptoms
Fever
5 (25.0%)
Right abdominal pain
11 (55.0%)
Upper abdominal pain
4 (20.0%)
Defensive tension
6 (30.0%)
Nausea
5 (25.0%)
Vomiting
5 (25.0%)
Diarrhea
1 (5.0%)
Time interval of symptom onset to surgery in h
51.0 (± 39.3)
Laboratory findings
Leukocytes > 15
11 (55.0%)
C-reactive protein > 5
12 (60.0%)
Imaging
Performance of ultrasound
6 (30.0%)
Performance of computer tomography
0
Performance of magnetic resonance imaging
1 (5.0%)
One patient underwent an MRI due to an unclear clinical presentation that included diffuse abdominal pain, elevated paraclinical inflammation parameters and incohesive ultrasound. The MRI revealed a tubular structure with a retrocecal wall that was up to 8 mm in diameter and basal surrounding adipose tissue, which corresponded to the picture of phlegmonous appendicitis ([Fig. 2 ]).
Fig. 2
T2 weighted MR image of the mid abdominal axial plane displaying the fetus in the middle of the image and the inflamed appendix (arrow).
Maternal and fetal outcome
The average week of pregnancy at the time of appendectomy was 37 weeks of gestation (± 3.8 weeks of gestation). The average week of pregnancy at the time of birth was 38 weeks of gestation (± 3.3 weeks of gestation).
Details of obstetrical management as well as maternal and fetal outcome can be found in [Table 2 ].
There were 6/20 cases (30.0%) of preterm delivery before 37 0/7 weeks of gestation. In four cases the premature delivery took place before 34 0/7 weeks of gestation. Of these women, only two received corticosteroids prior to delivery. Instead of the standard two injections, each patient received a single intramuscular injection of 12 mg of betamethasone. These two preterm deliveries occurred in 33 0/7 weeks of gestation and 30 4/7 weeks of gestation. Both patients required urgent therapy because they presented in a significantly reduced general condition with an acute abdomen. In both cases a cesarean delivery combined with open appendectomy was performed within two hours after application of the first dose of betamethasone. The other two preterm deliveries occurred in 33 4/7 weeks of gestation and 31 3/7 weeks of gestation. In both cases, patients were in a significantly reduced general condition and presented with an acute abdomen. Both patients required immediate
surgical care.
Only one patient delivered spontaneously in 41 6/7 weeks of gestation after appendectomy had been performed at 32 weeks of gestation. In 7/20 cases (35.0%) the appendectomy was performed due to an incidental visual finding of an altered vermiform appendix in an asymptomatic patient during a planned cesarean delivery. Out of the 13/20 cases (65.0%) where appendectomy occurred because the patient was symptomatic, 12/20 cases (60.0%) had a simultaneous cesarean delivery due to fear of fetal impairment.
During the observation period all 20 appendectomies were performed as open appendectomies. A perforated appendicitis was found in three cases (15.0%). There were neither intraoperative complications such as injuries or increased bleeding nor postoperative complications such as wound infections or events of thrombosis or embolisms. No repeat laparotomies were performed within 30 days after surgery.
Histopathological analysis
Histopathology examination was performed in all cases. The histopathological analysis of the 20 appendices revealed information as follows. [Table 4 ] gives an overview.
Table 4
Overview of histopathological findings.
Appendectomy in pregnancy > 24 0/7 weeks of gestation
n = 20
Results are shown in absolute numbers and percentages
n = number; WPF = without pathological findings
Histopathology examination
Acute appendicitis
11 (55.0%)
Chronic appendicitis
4 (20.0%)
Tumor
0
Other
1 (5.0%)
WPF
5 (25.0%)
Three appendectomy specimens showed catarrhal stage of appendicitis being described as catarrhal appendicitis with cicatricial obliteration and fatty degeneration in the apex.
In four cases pathological analysis showed appendicitis with ulcerated mucosa, streaked lympho-follicular architecture, transmural granulocytes and focal wall necrosis corresponding to an ulcero-phlegmonous appendicitis ([Fig. 3 ]
a, b ).
Fig. 3
a Histological specimen of appendix vermiformis, H.E. stain, 20× magnification: Purulent exudate in the lumen, ulceration of the mucous membrane, phlegmonous inflammatory infiltrates in all wall layers. b Histological specimen of appendix vermiformis, H.E. stain, 100× magnification: granulocytic inflammatory infiltrate.
In one case in addition to diagnosing phlegmonous appendicitis, serosal decidual tissue parts were noted compatible with endometriosis.
Gangrenous appendicitis was diagnosed in four cases showing appendix with a dense transmural infiltrate of neutrophilic granulocytes with a completely necrotic wall of the appendix.
Pathological work-up showed chronic inflammation in four cases described as chronic recurrent cicatricial appendicitis with luminal obliteration, adipose tissue degeneration and localized minimal fibrous serositis.
In five cases histopathological examinations showed no significant inflammation or other abnormalities.
Discussion
Principal findings
Pregnancy rarely necessitates the need for appendectomies, according to this retrospective analysis. Only open appendectomies were done on this small patient group. According to our research, if an open appendectomy is required during pregnancy, it can be safely done. From our data we were able to show low risk for adverse maternal as well as fetal outcome and intraoperative and postoperative surgical complications for pregnancies complicated by appendectomy. At the same time, cesarean deliveries increased in this small patient cohort. In our cohort all of the symptomatic patients had histopathological evidence of appendicitis.
Comparison with other studies
During pregnancy, appendicitis occurs more often during the second than during the first and third trimester of pregnancy. It is therefore associated with increased fetal morbidity [2 ]. However, in this patient collective appendicitis occurred during the third trimester in all cases. Partially this can be explained by the study protocol which required patients to have reached 24 0/7 weeks of gestations to be included in this study.
Fetal death rate has been described as 1.8% in women with appendicitis during pregnancy [12 ]. Appendicitis complicated by peritonitis increases the fetal death rate of up to 10.9% [6 ]. In our study cohort no fetal death was noted.
If surgical intervention becomes necessary during pregnancy, appendectomy has been described to be related to surgery-induced labor [6 ]. The rate of surgery-induced labor is around 4.6% which is 1.3 times higher than in other non-obstetric related surgical interventions [6 ]. Only one case was recorded in which an appendectomy took place without parallel delivery, which is consistent with the data mentioned above.
Appendix perforation rate was low and comparable to other studies [13 ]. However, this has to be seen in contrast to the high rate of surgical removal of unaffected appendices. 7/20 patients (35.0%) did not show any symptoms of appendicitis. In all of these cases appendectomy was performed during cesarean delivery due to visual impression. In 5/20 cases (25.0%) histological analysis revealed no significant inflammation of the vermiform appendix. Negative appendectomy rate is higher in pregnant women than in non-pregnant women [14 ]. It has been described as 23–36% before [13 ]
[14 ]. It is associated with risk of fetal loss [14 ]. This is comparable to the data of this study. So far, there is no universally accepted guideline on whether or not to look for the vermiform appendix during cesarean delivery.
A Swedish registry study of 1991 indicated that in 64% of the cases of appendectomy during pregnancy an acute appendicitis was proven histopathologically [12 ]. This is comparable to the data of this study.
In one case histological work-up showed a phlegmonous appendicitis as well as serosal decidual tissue parts compatible with endometriosis. Deep infiltrating endometriosis is the most severe form and can affect the intestines in up to 25% of cases [15 ]. Only very rarely does endometriosis manifest itself in the vermiform appendix [16 ].
Clinical and research implications
Irrespective of gestational age, pain in the lower right quadrant of the abdomen is the most common sign of appendicitis in pregnant women which could also be shown in this study [5 ].
When assessing pregnant women experiencing pain in the lower right abdomen, we recommend using an accurate and safe imaging method in addition to clinical and laboratory testing [7 ].
The usage of imaging methods lowers the negative appendectomy rate in young women [17 ]. Sensitivity and specificity of ultrasound in diagnosing appendicitis is estimated to be 77% and 86% [18 ]. Sensitivity and specificity can be increased to 100% and 86% by additional usage of computer tomography [18 ]. However, risks of ionizing radiation associated with this imaging method limit the usability in pregnant women [7 ]
[19 ]. Risks associated with fetal exposure to ionizing radiation depend on the gestational age as well as the dose of radiation [20 ].
Fetuses are more susceptible to the dose-dependent teratogenic effects of ionizing radiation like malformations, mental retardation or growth restrictions [20 ]. No profound data exist on the risk of carcinogenesis after in utero exposure to ionizing radiation [19 ]. There seems to be a 1.5-fold increase in childhood leukemia dose-dependent after in utero radiation exposure [19 ]
[21 ].
Radiation exposure can be avoided by the usage of magnetic resonance imaging compared to computer tomography [22 ]
[23 ]. MRI performance can improve specificity and sensitivity of diagnosing appendicitis in pregnancy up to 100.0% and 98.3%, respectively, for patients with inconclusive ultrasound diagnostics [24 ].
To choose the optimal imaging technique, close collaboration with the supervising radiologist should be sought after [25 ].
In this patient collective in all cases open appendectomy was performed when a pathology of the vermiform appendix was suspected.
There are two ways of surgical access to perform appendectomy: conventional appendectomy via lower midline transverse abdominal incision and laparoscopic appendectomy [3 ]
[26 ]. In their systematic review Adamani et al. recommend laparoscopic approach until the 20th week of gestation or when the fundus uteri is below the level of the umbilicus [27 ]. In cases of suspected appendicitis in pregnant women beyond 20 weeks of gestation or in pregnant women with the fundus uteri being located above the level of the umbilicus surgical access should depend on the expertise and preference of the surgeon [27 ]. Due to the later pregnancy dates of the appendectomies performed on this patient group, the
technical challenges of performing laparoscopic surgery were considered significant by the performing surgeons. After ruling out all differential diagnosis at any stage of pregnancy, appendectomy should be performed when appendicitis is suspected [26 ]. If the appendix is not perforated, no simultaneous cesarean delivery is indicated [26 ]. There is currently a lack of clarity regarding the effects of laparoscopic surgery versus open appendectomy on preterm delivery and fetal loss [3 ]
[28 ]
[29 ]. An overview of recent systematic reviews on surgical access for appendectomy during pregnancy is provided in [Table 5 ].
Table 5
Overview of recent systematic reviews on the topic of surgical access for appendectomy during pregnancy.
Characteristics
Systematic review
Chakraborty 2019 [28 ]
Lee 2019 [3 ]
Frountzas 2019 [29 ]
CI = confidence interval; LA = laparoscopic appendectomy; NM = not mentioned; OA = open appendectomy; OR = odds ratio; p = p-value
Study aim
Safety of laparoscopic surgery in pregnancy
Safety of laparoscopic appendectomy versus open appendectomy for suspected appendicitis during pregnancy
Compare the surgical and obstetrical outcomes between laparoscopic and open appendectomy during pregnancy
Databases that were searched
Medline and Embase
PubMed, Embase and Cochrane Library
Medline, SCOPUS, Clinicaltrials.gov, CENTRAL and Google Scholar
Search time range
2000–2017
NM
1996–2016
Number of studies included
16 retrospective non-randomized studies, 1 prospective observational study
19 comparative retrospective reviews of patients’ medical records, 3 comparative prospective cohort studies
20 retrospective non-randomized studies, 1 prospective observational study
Number of women included
LA group: 1886 patients
OA group: 4261 patients
LA: 905 patients
OA: 3789 patients
LA: 1963 patients
OA: 4313 patients
Gestational week at appendectomy
LA 37.1–39.3 weeks
OA 36.7–39 weeks
NM
NM
Fetal loss
LA: pooled OR: 1.84 (95% CI: 1.31–2.58, p < 0.001)
LA: OR 1.16 (95% CI: 0.68–1.99; p = 0.581)
LA: OR: 2.11 (95% CI: 1.44–3.09, p = 0.0001)
Preterm delivery
LA: pooled OR: 0.39 (95% CI 0.27–0.55, p < 0.001)
LA: OR 0.76 (95% CI: 0.51–1.15)
LA: OR: 0.72 (95% CI 0.40–1.29, p = 0.27)
Wound infection
Wound infection (OR 0.40, 95% CI: 0.21–0.76)
Wound infection (OR 0.47, 95% CI 0.15–1.48, p = 0.20)
The sole use of antibiotics in treating appendicitis has not been analyzed methodically in pregnant women so far [1 ]. In this study in five cases antibiotic treatment was initiated before surgery. However, no patient received antibiotic therapy exclusively. Surgery was performed in all cases. Further studies are needed to evaluate conservative treatment for appendicitis in pregnancy.
Strengths
The findings of this study can be used to design prospective studies in the field of imaging diagnostics as well as treatment of pregnant women with suspected appendicitis or tumors of the vermiform appendix.
In addition, the study might suggest that all surgeries unrelated to pregnancy be registered in a registry in order to monitor the frequency, results, and complications among perinatal facilities.
Limitations
The study’s primary constraint is the small number of cases, which, however, can be classified as large for a single perinatal center. For this reason, further statistical analyses had to be omitted. Şahin et al. analyzed 11513 deliveries during 2015–2020 complicated by appendectomy during pregnancy. In their cohort they found 12 cases [30 ]. This number of cases is comparable to our data. An acute appendicitis rate of 6.3 and 9.9 per 10000 person-years, respectively, was determined for the antepartum and postpartum periods by Zingone et al. also supporting our case number [31 ].
In this small patient collective only open appendectomies were performed followed by cesarean deliveries in almost all cases. In contrast to the procedures presented in this case series, this study is intended to serve as a suggestion to reconsider laparoscopic appendectomy even in more advanced weeks of pregnancy and to optimize surgical skills accordingly. A careful assessment of the necessity of a simultaneous cesarean delivery should be made. Due to the retrospective character of the study findings of this study are limited.
Conclusion
This retrospective study showed that appendectomies rarely need to be performed during pregnancy. In the event of appendicitis being suspected during pregnancy, we advise pursuing additional diagnostic tests, such as ultrasound and MRI if needed, in addition to a serological work-up and consulting with general surgery and neonatology. In this small patient collective only open appendectomies were performed. Our data indicate that it is safe to perform an open appendectomy during pregnancy if necessary. In this small patient group, there was an increase in simultaneous cesarean deliveries.
