Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis

Valeska Candrawinata; Ricarhdo Hanafi; Bernard Agung Baskoro; Andry Irawan; Christofani Ekapatria; Natalia Maria Christina; Heru Sutanto Koerniawan; Freda Halim

doi:10.12688/f1000research.129906.2

Home Browse Antibiotic versus surgery in the treatment of acute appendicitis in...

ALL Metrics

Views

Downloads

Get PDF

Get XML

Export

▬

✚

Systematic Review

Revised

Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis

[version 2; peer review: 2 approved, 1 approved with reservations]

Valeska Candrawinata ¹, Ricarhdo Hanafi¹, Bernard Agung Baskoro², [...] Andry Irawan³, Christofani Ekapatria⁴, Natalia Maria Christina⁵, Heru Sutanto Koerniawan⁵, Freda Halim⁶

Valeska Candrawinata ¹, Ricarhdo Hanafi¹, [...] Bernard Agung Baskoro², Andry Irawan³, Christofani Ekapatria⁴, Natalia Maria Christina⁵, Heru Sutanto Koerniawan⁵, Freda Halim⁶

PUBLISHED 06 Sep 2023

Author details Author details

¹ Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, 15811, Indonesia
² Division of Oncology, Department of Surgery, Faculty of Medicine, Pelita Harapan University, Siloam General Hospital, Tangerang, Banten, 15811, Indonesia
³ Division of Digestive Surgery, Department of Surgery, Faculty of Medicine, Pelita Harapan University, Siloam General Hospital, Tangerang, Banten, 15811, Indonesia
⁴ Division of Reproductive Endocrinology and Fertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Pelita Harapan University, Siloam General Hospital, Tangerang, Banten, 15811, Indonesia
⁵ Department of Surgery, Faculty of Medicine, Pelita Harapan University, Siloam General Hospital, Tangerang, Banten, 15811, Indonesia
⁶ Department of Surgery, Pelita Harapan University, Tangerang, Banten, 15811, Indonesia

Valeska Candrawinata
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Ricarhdo Hanafi
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Bernard Agung Baskoro
Roles: Supervision, Validation, Writing – Review & Editing

Andry Irawan
Roles: Supervision, Validation, Writing – Review & Editing

Christofani Ekapatria
Roles: Supervision, Validation, Writing – Review & Editing

Natalia Maria Christina
Roles: Supervision, Validation, Writing – Review & Editing

Heru Sutanto Koerniawan
Roles: Supervision, Validation, Writing – Review & Editing

Freda Halim
Roles: Supervision, Validation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Introduction: Acute appendicitis is the most common surgical emergency in pregnant women. There has been a wide variance in clinical practice worldwide, with some favoring an antibiotic-only approach while others prefer surgery as the first-line management. Therefore, we designed the current analysis to synthesize the available evidence on the efficacy and safety of antibiotics versus surgery management.
Methods: We searched PubMed, Scopus, EuropePMC, and Cochrane Central from March 4, 1904 until November 25, 2022, to look for studies comparing antibiotics and surgery in pregnant patients with acute appendicitis. We only included studies that provided a comparison between the two treatments. Measured outcomes included preterm delivery, fetal loss, maternal death, and complications, defined as those arising from the pathological processes or treatment, including, but not limited to, sepsis or septic shock, pneumonia, venous thromboembolism (VTE), and surgical site infection. The results were compared using an odds ratio and 95% confidence interval. We also performed a sensitivity analysis by excluding studies with a serious risk of bias.
Results: We included five non-randomized studies for the analysis. We found that patients in the antibiotic group had a lower risk of preterm labor (OR 0.63 [95% CI 0.43–0.92]; p 0.02) but a higher risk of complications (OR 1.79 [95% CI 1.19–2.69]; p 0.005). We did not find any difference in the other outcomes.
Conclusion: The increased risk of complications should caution clinicians about using antibiotics as the first-line management. More studies are required to identify patients who would benefit the most before antibiotics could be adopted as a treatment for acute appendicitis in pregnant patients.

Keywords

Antibiotic, Surgery, Acute Appendicitis, Pregnant

Corresponding author: Valeska Candrawinata

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2023 Candrawinata V et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Candrawinata V, Hanafi R, Baskoro BA et al. Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis [version 2; peer review: 2 approved, 1 approved with reservations]. F1000Research 2023, 12:188 (https://doi.org/10.12688/f1000research.129906.2) First published: 16 Feb 2023, 12:188 (https://doi.org/10.12688/f1000research.129906.1) Latest published: 06 Sep 2023, 12:188 (https://doi.org/10.12688/f1000research.129906.2)

Revised Amendments from Version 1

We revised the abstract and keywords to provide better understanding to the readers. We added two updated and more comprehensive journals as references.

See the authors' detailed response to the review by Rıfat Peksöz

Introduction

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.

Methods

Database and literature search

We searched PubMed, Scopus, EuropePMC, and Cochrane Central from the March 4, 1904 until November 25, 2022, using the following keywords: [“acute appendicitis” or “appendicitis” and “pregnancy” and “conservative” or “antibiotic” or “antibiotics”]. We also reviewed the bibliographies of relevant studies to identify any other studies. We only included English-language literature. The initial search and screening were done by two independent authors. Any discrepancies were resolved by discussion with a third author.

Study selection/design

The inclusion criteria were: 1) types of patients: pregnant patients with uncomplicated and complicated acute appendicitis; 2) types of intervention: conservative management with antibiotics alone; 3) types of comparison: open or laparoscopic appendectomy; 4) analyzed outcomes: preterm delivery, fetal loss, maternal death, and complications; and 5) types of studies: prospective and retrospective studies. We defined complications as those arising from the pathological processes or treatment, including, but not limited to, sepsis or septic shock, pneumonia, venous thromboembolism (VTE), and surgical site infection. Studies that did not provide the aforementioned variables as outcomes were excluded. We excluded review articles, editorials, case reports, and case series. This analysis was started in July 31, 2022 and finished in November 9, 2022.

Data extraction

After the studies were selected, two authors independently extracted the data on study authors, publication year, study design, patients’ characteristics, treatment characteristics, and outcomes using a standardized form. Patients were then dichotomized according to the treatment they received.

Statistical analysis

We inputted patients’ data in a 2-by-2 contingency table according to the analyzed outcomes. We compared each outcome between conservative and surgical groups using odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using the I² statistic and Cochrane Q-statistic test. An I² value higher than 40% or a P value higher than 0.10 indicated a significant presence of heterogeneity. However, a random-effect model was used regardless of heterogeneity because we expected the studies to have significant differences in the choice of antibiotics. We also planned a subgroup analysis according to whether the studies’ participants had uncomplicated or complicated appendicitis. As performing a randomized controlled trial on a pregnant population is ethically difficult, we expected most studies to be non-randomized. Therefore, we also planned a sensitivity analysis by excluding studies with a serious risk of bias.

We assessed the risk of bias using the Cochrane risk-of-bias tool (The Cochrane Collaboration) for randomized studies and the Risk of Bias in Non-randomized Studies - of Intervention tool (ROBINS-I) for non-randomized studies. We used a funnel plot analysis to assess publication bias. We graded the strength of evidence for each outcome using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We used the Review Manager version 5.4 (The Cochrane Collaboration) (https://training.cochrane.org/online-learning/core-software/revman/revman-5-download) program for all statistical analysis. We conducted this study according to the 2015 PRISMA guidelines for a systematic review. This review has been registered at The International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022371119.

Results

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

Figure 1. PRISMA flow diagram.

Study characteristics

The characteristics of the included studies are presented in Table 1. All of the studies were non-randomized and mostly retrospective. Patients were mostly 25 to 35 years old and in their second trimester. Liu et al. included only uncomplicated appendicitis case⁶ while Abbasi et al., Nakashima et al., and Vasileiou et al. included both complicated and uncomplicated appendicitis case.⁷^,¹³ However, Yang et al. did not report the severity of appendicitis in their samples.¹⁴ Four studies reported their antibiotic use.⁶^,⁷^,¹²^,¹⁴ Third-generation cephalosporin was the main choice. Five studies reported surgery type, and all used either open or laparoscopic appendectomy.⁶^,⁷^,¹²^,¹⁴

Table 1. Characteristics of included studies.

Authors & year	Study design	Cohort Size (n)	Age (yrs)	Trimester	Complicated	Antibiotics	Surgery	Outcome
Abbasi et al., 2014¹	Retrospective cohort	413/6701	<25: 42.5%; 25–25: 48.5%; >35: 9.0%	Not specified	7271 (20.3%)	Not specified	Open and laparoscopic	SIRS, sepsis, or severe sepsis; septic shock; peritonitis; VTE
Liu et al., 2021⁶	Retrospective cohort	34/20	29.0 ± 4.1 / 30.5 ± 4.8	1^st trimester: 8 (23.5%) / 8 (40%); 2^nd trimester: 20 (58.8%) / 9 (45%); 3^rd trimester 6 (17.6%) / 3 (15%)	All uncomplicated	Ceftriaxone, ertapenem/meropenem, ceftriaxone + metronidazole	Open and laparoscopic	Preterm delivery; mode of delivery; fetal loss; birth weight; APGAR scores; postpartum complications; maternal death; LOS; recurrence.
Nakashima et al., 2021⁷	Retrospective cohort	113/56	29.7 ± 5.6 / 30.1 ± 4.2	1^st trimester: 26 (23%) / 12 (21%); 2^nd trimester: 54 (48%) / 33 (59%); 3^rd trimester 31 (27%) / 9 (16%); unknown: 2 (2%) / 2 (4%)	7 (6%) / 23 (41%)^*	2^nd, 3^rd, 4^th generation cephalosporin	Open and laparoscopic	Fetal loss; maternal death; SSI; VTE; pneumonia; LOS
Vasileiou et al., 2020¹³	Prospective cohort	6/35	29 ± 7	Not specified	9 (25%)	3^rd generation cephalosporin, fluoroquinolene, clindamycin, aminoglicoside, sulfonamide, piperacillin/tazobactam, amoxicillin clavulanate, metronidazole	Not specified	Complication; LOS
Yang et al., 2021¹⁴	Retrospective cohort	2996/7275	<20: 15%; 20–24: 21.8%; 25–29: 21.1%; 30–34: 17.6%; 35–49: 24.4%	Not specified	Not specified	Not specified	Open and laparoscopic	Fetal loss; mode of delivery; preterm delivery

* Mean.

† Median.

We used the ROBINS-I tool to assess the risk of bias, and the results are presented in Table 2. We judged the study by Nakashima et al. to have a serious risk of bias because there was a significantly higher rate of complicated appendicitis in the surgery group. We assessed the remaining study to be of moderate risk of bias because confounding had been sufficiently controlled. However, the possibility of unmeasured confounding variables inherent in the design of non-randomized studies gave a moderate risk of confounding bias. We judged bias from the outcome measurement to be low because although no blinding was used, the outcomes were fairly objective. We did not perform analysis for publication bias because funnel plot analysis or other statistical methods did not have enough power to detect bias in a small number of studies.

Table 2. Risk of bias assessment The Risk of Bias in Non-Randomized Studies – of Interventions (ROBINS-I) tool.

Authors	Confounding	Selection	Intervention classification	Deviation from intervention	Missing data	Measurement of outcome	Selection of reported results	Overall
Abbasi et al., 2014¹	Moderate	Low	Low	Low	Low	Low	Low	Moderate
Liu et al., 2021⁶	Moderate	Low	Low	Low	Low	Low	Low	Moderate
Nakashima et al., 2021⁷	Serious	Low	Low	Low	Low	Low	Low	Serious
Vasileiou et al., 2020¹³	Moderate	Low	Low	Low	Low	Low	Low	Moderate
Yang et al., 2021¹⁴	Moderate	Low	Low	Low	Low	Low	Low	Moderate

Preterm delivery

Two studies with a total of 10,325 patients assessed the occurrence of preterm labor. Overall, patients in the antibiotic group had a significantly lower risk of preterm delivery (OR 0.63 [95% CI 0.43–0.92]; p 0.02) (Figure 2).

Figure 2. Forest plot showing preterm delivery between antibiotic and surgery group.

Fetal loss

Three studies with a total of 10,494 patients assessed the occurrence of fetal loss. Overall, there were no significant differences in fetal loss between the two groups (OR 1.02 [95% CI 0.84–1.24]; p 0.81) (Figure 3).

Figure 3. Forest plot showing fetal loss between antibiotic and surgery group.

Maternal death

From the two studies with a total of 223 patients, there was no report of maternal death either in the antibiotic or the surgery group. Therefore, a meta-analysis could not be performed.

Complications

Four studies with a total of 7,378 patients assessed complications. Abbasi et al. included sepsis, septic shock, peritonitis, and VTE as complications. Liu et al. reported one grid iron complication in the surgery group. Nakashima et al. included surgical site infection, VTE, and pneumonia as complications. Lastly, Vasileiou et al. used Clavien-Dindo complications. Overall, there was a lower risk of complications in the antibiotic group, but it was not statistically significant (OR 0.72 [95% CI 0.16–3.32]; p 0.68) (Figure 4). However, only Abbasi et al. reported peritonitis, and they found that patients in the antibiotic group significantly had a higher rate of peritonitis (28.8% vs. 19.8%; p < 0.001).

Figure 4. Forest plot showing complications between antibiotic and surgery group.

Sensitivity analysis

We excluded the study by Nakashima et al. in our sensitivity analysis. Regarding fetal loss, the result did not differ from our primary analysis. However, regarding the outcome, we found that patients in the antibiotic group significantly had a higher rate of complications (OR 1.79 [95% CI 1.19–2.69]; p 0.005) (Figure 5).

Figure 5. Forest plot showing the sensitivity analysis for fetal loss (A) and complications (B) between antibiotic and surgery group.

Certainty of evidence

The certainty of the evidence was very low to low (Table 3). Evidence regarding fetal loss and complication had a serious risk of bias and inconsistency, so we judged them to be of very low quality. Evidence regarding fetal loss did not have serious concerns, but we assessed them to be of low quality due to the observational design of studies. Table 3 gives a summary of the assessment.

Table 3. Certainty of evidence.

Outcome	No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other consideration	OR (95% CI)	Overall
Preterm delivery	3	Observational	Serious^*	Not serious	Not serious	Serious^†	Plausible residual confounding, would suggest spurious effect	1.02 (0.84 – 1.24)	Very low
Fetal loss	2	Observational	Not serious	Not serious	Not serious	Not serious	None	0.63 (0.43 – 0.92)	Low
Complication	4	Observational	Serious^*	Serious^‡	Not serious	Serious^†	Plausible residual confounding, would suggest spurious effect	0.72 (0.16 – 3.32)	Very low

* One study rated as having a serious risk of bias. Downgraded by one point.

† 95% CI overlaps no effect. Downgraded by one point.

‡ I² > 40%. Downgraded by one point.

Discussion

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^,¹⁶ During pregnancy, there is evidence of increased neutrophil activation, but its activity and phagocytosis function are limited.¹⁷ 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^,¹⁸ 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.¹⁹^–²¹ 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%.²² 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.²³^,²⁴ 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. Compared with open appendectomy, laparoscopic appendectomy was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that laparoscopic appendectomy shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with open appendectomy in pregnant women with suspected appendicitis.²⁵ Furthermore, resources needed to carry out laparoscopic procedures in developing countries are still limited - hence open appendectomy remains a viable and equal option.²⁴

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.²⁶ 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.²⁷

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.

Conclusion

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.

Data availability

Underlying data

All data underlying the results are available as part of the article and no additional source data are required.

Extended data

Zenodo: Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis, https://doi.org/10.5281/zenodo.7538790.²⁸

This project contains the following extended data:

- Database and Literature Search
- Fig 1. PRISMA flow diagram.
- Fig 2. Forest plot showing preterm delivery between antibiotic and surgery group.
- Fig 3. Forest plot showing fetal loss between antibiotic and surgery group.
- Fig 4. Forest plot showing complications between antibiotic and surgery group.
- Fig 5. Forest plot showing the sensitivity analysis for fetal loss (A) and complications (B) between antibiotic and surgery group.
- Table 1. Characteristics of Included Studies.
- Table 2. Risk of bias assessment The Risk of Bias in Non-Randomized Studies – of Interventions (ROBINS-I) tool.
- Table 3. Certainty of evidence.

Reporting guidelines

Zenodo: PRISMA checklist for ‘Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis’, https://doi.org/10.5281/zenodo.7538790.²⁸

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

References

1. Abbasi N, Patenaude V, Abenhaim HA: Evaluation of obstetrical and fetal outcomes in pregnancies complicated by acute appendicitis. Arch. Gynecol. Obstet. 2014; 290(4): 661–667. PubMed Abstract | Publisher Full Text
2. Andersen B, Nielsen TF: Appendicitis in pregnancy, Diagnosis, management and complications. Acta Obstet. Gynecol. Scand. 1999; 78(9): 758–762. Publisher Full Text
3. Mourad J, Elliott JP, Erickson L, et al.: Appendicitis in pregnancy: New information that contradicts long-held clinical beliefs. Am. J. Obstet. Gynecol. 2000; 182(5): 1027–1029. PubMed Abstract | Publisher Full Text
4. Di Saverio S, Podda M, De Simone B, et al.: Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J. Emerg. Surg. 2020; 15(1): 27. PubMed Abstract | Publisher Full Text | Free Full Text
5. Il JJ, Park HC, Kim MJ, et al.: Outcomes of Antibiotic Therapy for Uncomplicated Appendicitis in Pregnancy. Am. J. Med. 2017; 130(12): 1467–1469. PubMed Abstract | Publisher Full Text
6. Liu J, Ahmad M, Wu J, et al.: Antibiotic is a safe and feasible option for uncomplicated appendicitis in pregnancy - A retrospective cohort study. Asian J. Endosc. Surg. 2021; 14(2): 207–212. PubMed Abstract | Publisher Full Text
7. Nakashima M, Takeuchi M, Kawakami K: Clinical Outcomes of Acute Appendicitis During Pregnancy: Conservative Management and Appendectomy. World J. Surg. 2021; 45(6): 1717–1724. PubMed Abstract | Publisher Full Text
8. Ashbrook M, Cheng V, Sandhu K, et al.: Management of Complicated Appendicitis during Pregnancy in the US. JAMA Netw. Open. 2022; 5(4): E227555. PubMed Abstract | Publisher Full Text | Free Full Text
9. Chakraborty J, Kong JC, Su WK, et al.: Safety of laparoscopic appendicectomy during pregnancy: a systematic review and meta-analysis. ANZ J. Surg. 2019; 89(11): 1373–1378. PubMed Abstract | Publisher Full Text
10. Sallinen V, Akl EA, You JJ, et al.: Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br. J. Surg. 2016; 103(6): 656–667. PubMed Abstract | Publisher Full Text | Free Full Text
11. Poprom N, Numthavaj P, Wilasrusmee C, et al.: The efficacy of antibiotic treatment versus surgical treatment of uncomplicated acute appendicitis: Systematic review and network meta-analysis of randomized controlled trial. Am. J. Surg. 2019; 218(1): 192–200. PubMed Abstract | Publisher Full Text
12. Abbasi N, Patenaude V, Abenhaim HA: Management and outcomes of acute appendicitis in pregnancy - Population-based study of over 7000 cases. BJOG Int. J. Obstet. Gynaecol. 2014; 121(12): 1509–1514. PubMed Abstract | Publisher Full Text
13. Vasileiou G, Eid AI, Qian S, et al.: Appendicitis in Pregnancy: A post-hoc analysis of an EAST multicenter study. Surg. Infect. 2020; 21(3): 205–211. PubMed Abstract | Publisher Full Text
14. Yang J, Wen SW, Krewski D, et al.: Association of treatments for acute appendicitis with pregnancy outcomes in the United States from 2000 to 2016: Results from a multi-level analysis. PLoS One. 2021; 16(12 December): e0260991. PubMed Abstract | Publisher Full Text | Free Full Text
15. Peeters T, Martens S, D’Onofrio V, et al.: An observational study of innate immune responses in patients with acute appendicitis. Sci. Rep. 2020; 10(1): 17352. PubMed Abstract | Publisher Full Text | Free Full Text
16. Peksöz R, Dişçi E, Kaya A, et al.: Significance of laboratory parameters in diagnosing acute appendicitis during pregnancy. ANZ J. Surg. 2022; 92 (1-2): 121–127. PubMed Abstract | Publisher Full Text
17. Abu-Raya B, Michalski C, Sadarangani M, et al.: Maternal Immunological Adaptation During Normal Pregnancy. Front. Immunol. 2020; 11: 11. PubMed Abstract | Publisher Full Text | Free Full Text
18. Carstens AK, Fensby L, Penninga L: Nonoperative Treatment of Appendicitis during Pregnancy in a Remote Area. Am. J. Perinatol. Rep. 2018; 08(01): e37–e38. PubMed Abstract | Publisher Full Text | Free Full Text
19. Loftus TJ, Brakenridge SC, Croft CA, et al.: Successful nonoperative management of uncomplicated appendicitis: predictors and outcomes. J. Surg. Res. 2018; 222: 212–218.e2. PubMed Abstract | Publisher Full Text | Free Full Text
20. Shindoh J, Niwa H, Kawai K, et al.: Predictive factors for negative outcomes in initial non-operative management of suspected appendicitis. J. Gastrointest. Surg. 2010; 14(2): 309–314. PubMed Abstract | Publisher Full Text
21. Tsai MC, Lin HC, Lee CZ: Diabetes increases the risk of an appendectomy in patients with antibiotic treatment of noncomplicated appendicitis. Am. J. Surg. 2017; 214(1): 24–28. PubMed Abstract | Publisher Full Text
22. Kave M, Parooie F, Salarzaei M: Pregnancy and appendicitis: A systematic review and meta-analysis on the clinical use of MRI in diagnosis of appendicitis in pregnant women. World J. Emerg. Surg. 2019; 14(1): 37. PubMed Abstract | Publisher Full Text | Free Full Text
23. Baruch Y, Canetti M, Blecher Y, et al.: The diagnostic accuracy of ultrasound in the diagnosis of acute appendicitis in pregnancy. J. Matern. Neonatal Med. 2020; 33(23): 3929–3934. PubMed Abstract | Publisher Full Text
24. Konrad J, Grand D, Lourenco A: MRI: first-line imaging modality for pregnant patients with suspected appendicitis. Abdom. Imaging. 2015; 40(8): 3359–3364. PubMed Abstract | Publisher Full Text
25. Lee SH, Lee JY, Choi YY, et al.: Laparoscopic appendectomy versus open appendectomy for suspected appendicitis during pregnancy: a systematic review and updated meta-analysis. BMC Surg. 2019; 19(1): 41. PubMed Abstract | Publisher Full Text | Free Full Text
26. Ball E, Waters N, Cooper N, et al.: Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG). Facts, Views Vis. ObGyn. 2019; 11(1): 5–25. PubMed Abstract Reference Source
27. Zingone F, Sultan AA, Humes DJ, et al.: Risk of acute appendicitis in and around pregnancy a population-based cohort study from england. Ann. Surg. 2015; 261(2): 332–337. PubMed Abstract | Publisher Full Text
28. Candrawinata VS, Hanafi RV, Baskoro BA, et al.: Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis. [Dataset]. Zenodo. 2022. Publisher Full Text

Comments on this article Comments (0)

Version 2

VERSION 2 PUBLISHED 16 Feb 2023

Author details Author details

Bernard Agung Baskoro
Roles: Supervision, Validation, Writing – Review & Editing

Andry Irawan
Roles: Supervision, Validation, Writing – Review & Editing

Christofani Ekapatria
Roles: Supervision, Validation, Writing – Review & Editing

Natalia Maria Christina
Roles: Supervision, Validation, Writing – Review & Editing

Heru Sutanto Koerniawan
Roles: Supervision, Validation, Writing – Review & Editing

Freda Halim
Roles: Supervision, Validation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (2)

version 2

Revised

Published: 06 Sep 2023, 12:188

https://doi.org/10.12688/f1000research.129906.2

version 1

Published: 16 Feb 2023, 12:188

https://doi.org/10.12688/f1000research.129906.1

© 2023 Candrawinata V et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download

Export To

metrics

	Views	Downloads
F1000Research	-	-
PubMed Central Data from PMC are received and updated monthly.	-	-

Citations

SEE MORE DETAILS

CITE

how to cite this article

Candrawinata V, Hanafi R, Baskoro BA et al. Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis [version 2; peer review: 2 approved, 1 approved with reservations]. F1000Research 2023, 12:188 (https://doi.org/10.12688/f1000research.129906.2)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

track

receive updates on this article

Track an article to receive email alerts on any updates to this article.

Open Peer Review

Current Reviewer Status: ?

Key to Reviewer Statuses VIEW HIDE

ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions

Version 2

VERSION 2

PUBLISHED 06 Sep 2023

Revised

Views

Reviewer Report 08 Jul 2024

Goran Augustin, University of Zagreb, Zagreb, Croatia

Approved with Reservations

https://doi.org/10.5256/f1000research.155547.r294632

A small number of studies were included. All were retrospective and non-randomized. Difficult to compare. it is unexpected that antibiotic treatment results in more complications. This bias is due to a population-based study of Abbas with more than 7000 people. this could lead to wrong conclusions. The same issue was with comparing open and laparoscopic appendectomy and outcome when the study by McGory (2007) was also nationwide database driven. Such large databases carry a big potential for errors. It was nicely uncovered in the article Augustin G, et al.,2020 [Ref-1].

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

I cannot comment. A qualified statistician is required.
Are the conclusions drawn adequately supported by the results presented in the review?

Yes
If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.)

Not applicable

References

1. Augustin G, Boric M, Barcot O, Puljak L: Discordant outcomes of laparoscopic versus open appendectomy for suspected appendicitis during pregnancy in published meta-analyses: an overview of systematic reviews.Surg Endosc. 2020; 34 (10): 4245-4256 PubMed Abstract | Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Abdominal surgery

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

Report a concern

Respond or Comment

Views

Reviewer Report 24 Jun 2024

kumar Hari Rajah, Taylors University School of Medicine and Health Science, Selangor, Malaysia

Approved

https://doi.org/10.5256/f1000research.155547.r294634

This systemic review and meta-analysis on antibiotic versus surgery in the management of acute appendicitis in pregnancy. I would suggest adding laparoscopic appendectomy and open appendectomy to the keywords. The PRISMA guide is done properly and the studies and type are clearly stated .The results section is clearly defined and the discussion and conclusions are consistent with the evidence provided. The references are adequate.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes
If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.)

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: general surgery and gastroenterology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Respond or Comment

Views

Reviewer Report 26 Sep 2023

Rıfat Peksöz, Department of General Surgery, Faculty of Medicine, Ataturk University, Erzurum, Erzurum, Turkey

Approved

https://doi.org/10.5256/f1000research.155547.r204328

Necessary revisions have been made. ... Continue reading

CITE

Report a concern

Respond or Comment

Version 1

VERSION 1

PUBLISHED 16 Feb 2023

Views

Reviewer Report 01 Sep 2023

Rıfat Peksöz, Department of General Surgery, Faculty of Medicine, Ataturk University, Erzurum, Erzurum, Turkey

Approved with Reservations

https://doi.org/10.5256/f1000research.142624.r195177

The authors aimed to investigate the current review to identify the efficacy and safety of conservative treatment in the treatment of acute appendicitis in pregnancy in this study.

Acute appendicitis is the most frequently seen surgical emergency in pregnant women and the most frequently encountered cause of non-obstetric acute abdomen. Due to the physiological and anatomical changes that occur during pregnancy and the limited use of radiological methods, it is difficult to diagnose AA during pregnancy. These conditions increase the risk of morbidity and mortality. Studies on acute appendicitis in pregnant women will provide a better understanding of this issue. In this regard, this study is very important in terms of contributing to the literature. Howewer, some issues should be raised from my point of view. I hope my comments contribute to your article, good luck to the authors.

Plagiarism rate: didn’t evaluate because of this paper’s pre-review form published on the F1000 research page.

Comments to the author(s):

In the Abstract section, the complications which are seen more in the results section should be mentioned a little bit. This can be difficult to do, but when researchers read the articles, they read the abstract first. It is important to provide this information in order for the study to be more effective.
Keywords should be rewritten, comments; Add 'antibiotic therapy' instead of 'Antibiotic'. Add 'Pregnancy' instead of 'pregnant', and, add outcomes or complications words.
In your article, it was emphasized that the treatment of acute appendicitis in pregnant women is controversial, but in the introduction section, only the superiority of antibiotic therapy was emphasized, and the study highlighting surgery was not emphasized. I recommend that this study with good surgical results be emphasized in this section.
Discussion section: ‘’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, doi: 10.1111/ans.17443)}
I suggest adding an additional reference at the end of this sentence. Our work on this subject is up-to-date and has received many references in a short time (Peksöz et al., 2022¹).
Discussion section: "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"
Disadvantages of LA were mentioned in your article, but Laparascopic appendectomy has been routinely applied in pregnant women today. Although the subject of your study is antibiotic treatment or surgical treatment, this current information should be renewed and reviewed. An important study demonstrated the superiority of LA. ‘’Compared with OA, LA was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that LA shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with OA in pregnant women with suspected appendicitis’’ (Lee et al., 2019²).

Evaluation report: Congratulations to the authors for good work, this study well written. Introduction, materials and methods, results and discussion sections of the article have enough scientific knowledge. I think it is acceptable for indexing after minör revisions.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Partly
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes

References

1. Peksöz R, Dişçi E, Kaya A, Ağırman E, et al.: Significance of laboratory parameters in diagnosing acute appendicitis during pregnancy.ANZ J Surg. 2022; 92 (1-2): 121-127 PubMed Abstract | Publisher Full Text
2. Lee SH, Lee JY, Choi YY, Lee JG: Laparoscopic appendectomy versus open appendectomy for suspected appendicitis during pregnancy: a systematic review and updated meta-analysis.BMC Surg. 2019; 19 (1): 41 PubMed Abstract | Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: My areas of expertise are general surgery, especially acute appendicitis. Surgery interest: (General surgery, Gastrointestinal diseases): Emergencies in general surgery, ERCP, Endoscopy-colonoscopy, endoscopic interventions, colo-rectal diseases (colorectal cancers, diverticülitis), stomach diseaes (gastric cancer), gastrointestinal cancers, open or laparoscopic hernias (groin hernias, incisional, umbilical), anorectal diseases (pilonidal sinüs, hemorrhoid, anal fissure, perianal fistüla...), gallbladder surgery, spleen surgery, bariatric surgery (morbid obesity), nissen fundoplication.

CITE

Report a concern

Author Response 06 Oct 2023

Valeska Candrawinata, Faculty of Medicine, Pelita Harapan University, Tangerang, 15811, Indonesia

06 Oct 2023

Author Response
Dear Reviewer, we thank you for your kind review and insightful notes. We have revised the manuscript accordingly.
1. In the Abstract section, the complications which are seen more
... Continue reading
Dear Reviewer, we thank you for your kind review and insightful notes. We have revised the manuscript accordingly.

In the Abstract section, the complications which are seen more in the results section should be mentioned a little bit. This can be difficult to do, but when researchers read the articles, they read the abstract first. It is important to provide this information in order for the study to be more effective.

Response: We have revised the abstract accordingly and added more information about the complications in the abstract.

Keywords should be rewritten, comments; Add 'antibiotic therapy' instead of 'Antibiotic'. Add 'Pregnancy' instead of 'pregnant', and, add outcomes or complications words.

Response: We have revised the keywords accordingly.

In your article, it was emphasized that the treatment of acute appendicitis in pregnant women is controversial, but in the introduction section, only the superiority of antibiotic therapy was emphasized, and the study highlighting surgery was not emphasized. I recommend that this study with good surgical results be emphasized in this section.

Response: We have revised this section accordingly and added them.

Discussion section: ‘’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, doi: 10.1111/ans.17443)}
I suggest adding an additional reference at the end of this sentence. Our work on this subject is up-to-date and has received many references in a short time (Peksöz et al., 2022¹).

Response: We have added the reference.

Discussion section: "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"

Response: We have revised the article accordingly.

Disadvantages of LA were mentioned in your article, but Laparascopic appendectomy has been routinely applied in pregnant women today. Although the subject of your study is antibiotic treatment or surgical treatment, this current information should be renewed and reviewed. An important study demonstrated the superiority of LA. ‘’Compared with OA, LA was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that LA shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with OA in pregnant women with suspected appendicitis’’ (Lee et al., 2019²).

Response: We have revised the article accordingly.
Dear Reviewer, we thank you for your kind review and insightful notes. We have revised the manuscript accordingly.

In the Abstract section, the complications which are seen more in the results section should be mentioned a little bit. This can be difficult to do, but when researchers read the articles, they read the abstract first. It is important to provide this information in order for the study to be more effective.

Response: We have revised the abstract accordingly and added more information about the complications in the abstract.

Keywords should be rewritten, comments; Add 'antibiotic therapy' instead of 'Antibiotic'. Add 'Pregnancy' instead of 'pregnant', and, add outcomes or complications words.

Response: We have revised the keywords accordingly.

In your article, it was emphasized that the treatment of acute appendicitis in pregnant women is controversial, but in the introduction section, only the superiority of antibiotic therapy was emphasized, and the study highlighting surgery was not emphasized. I recommend that this study with good surgical results be emphasized in this section.

Response: We have revised this section accordingly and added them.

Discussion section: ‘’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, doi: 10.1111/ans.17443)}
I suggest adding an additional reference at the end of this sentence. Our work on this subject is up-to-date and has received many references in a short time (Peksöz et al., 2022¹).

Response: We have added the reference.

Discussion section: "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"

Response: We have revised the article accordingly.

Disadvantages of LA were mentioned in your article, but Laparascopic appendectomy has been routinely applied in pregnant women today. Although the subject of your study is antibiotic treatment or surgical treatment, this current information should be renewed and reviewed. An important study demonstrated the superiority of LA. ‘’Compared with OA, LA was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that LA shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with OA in pregnant women with suspected appendicitis’’ (Lee et al., 2019²).

Response: We have revised the article accordingly.
Competing Interests: None Close
Report a concern
Respond or Comment

COMMENTS ON THIS REPORT

Author Response 06 Oct 2023

Valeska Candrawinata, Faculty of Medicine, Pelita Harapan University, Tangerang, 15811, Indonesia

06 Oct 2023

Author Response
Dear Reviewer, we thank you for your kind review and insightful notes. We have revised the manuscript accordingly.
1. In the Abstract section, the complications which are seen more
... Continue reading
Dear Reviewer, we thank you for your kind review and insightful notes. We have revised the manuscript accordingly.

In the Abstract section, the complications which are seen more in the results section should be mentioned a little bit. This can be difficult to do, but when researchers read the articles, they read the abstract first. It is important to provide this information in order for the study to be more effective.

Response: We have revised the abstract accordingly and added more information about the complications in the abstract.

Keywords should be rewritten, comments; Add 'antibiotic therapy' instead of 'Antibiotic'. Add 'Pregnancy' instead of 'pregnant', and, add outcomes or complications words.

Response: We have revised the keywords accordingly.

In your article, it was emphasized that the treatment of acute appendicitis in pregnant women is controversial, but in the introduction section, only the superiority of antibiotic therapy was emphasized, and the study highlighting surgery was not emphasized. I recommend that this study with good surgical results be emphasized in this section.

Response: We have revised this section accordingly and added them.

Discussion section: ‘’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, doi: 10.1111/ans.17443)}
I suggest adding an additional reference at the end of this sentence. Our work on this subject is up-to-date and has received many references in a short time (Peksöz et al., 2022¹).

Response: We have added the reference.

Discussion section: "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"

Response: We have revised the article accordingly.

Disadvantages of LA were mentioned in your article, but Laparascopic appendectomy has been routinely applied in pregnant women today. Although the subject of your study is antibiotic treatment or surgical treatment, this current information should be renewed and reviewed. An important study demonstrated the superiority of LA. ‘’Compared with OA, LA was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that LA shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with OA in pregnant women with suspected appendicitis’’ (Lee et al., 2019²).

Response: We have revised the article accordingly.
Dear Reviewer, we thank you for your kind review and insightful notes. We have revised the manuscript accordingly.

In the Abstract section, the complications which are seen more in the results section should be mentioned a little bit. This can be difficult to do, but when researchers read the articles, they read the abstract first. It is important to provide this information in order for the study to be more effective.

Response: We have revised the abstract accordingly and added more information about the complications in the abstract.

Keywords should be rewritten, comments; Add 'antibiotic therapy' instead of 'Antibiotic'. Add 'Pregnancy' instead of 'pregnant', and, add outcomes or complications words.

Response: We have revised the keywords accordingly.

In your article, it was emphasized that the treatment of acute appendicitis in pregnant women is controversial, but in the introduction section, only the superiority of antibiotic therapy was emphasized, and the study highlighting surgery was not emphasized. I recommend that this study with good surgical results be emphasized in this section.

Response: We have revised this section accordingly and added them.

Discussion section: ‘’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, doi: 10.1111/ans.17443)}
I suggest adding an additional reference at the end of this sentence. Our work on this subject is up-to-date and has received many references in a short time (Peksöz et al., 2022¹).

Response: We have added the reference.

Discussion section: "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"

Response: We have revised the article accordingly.

Disadvantages of LA were mentioned in your article, but Laparascopic appendectomy has been routinely applied in pregnant women today. Although the subject of your study is antibiotic treatment or surgical treatment, this current information should be renewed and reviewed. An important study demonstrated the superiority of LA. ‘’Compared with OA, LA was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that LA shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with OA in pregnant women with suspected appendicitis’’ (Lee et al., 2019²).

Response: We have revised the article accordingly.
Competing Interests: None Close
Report a concern

Comments on this article Comments (0)

Version 2

VERSION 2 PUBLISHED 16 Feb 2023

Open Peer Review

Reviewer Status

Reviewer Reports

	Invited Reviewers
	1	2	3
Version 2 (revision) 06 Sep 23	read	read	read
Version 1 16 Feb 23	read

Rıfat Peksöz, Ataturk University, Erzurum, Turkey
kumar Hari Rajah, Taylors University School of Medicine and Health Science, Selangor, Malaysia
Goran Augustin, University of Zagreb, Zagreb, Croatia

Comments on this article

All Comments(0)

Add a comment

Browse by related subjects

Back to all reports

Reviewer Report

8 Views

08 Jul 2024 | for Version 2

Goran Augustin, University of Zagreb, Zagreb, Croatia

8 Views Cite this report Responses(0)

Approved With Reservations

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

I cannot comment. A qualified statistician is required.
Are the conclusions drawn adequately supported by the results presented in the review?

Yes
If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.)

Not applicable

References

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Abdominal surgery

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

4 Views

24 Jun 2024 | for Version 2

kumar Hari Rajah, Taylors University School of Medicine and Health Science, Selangor, Malaysia

4 Views Cite this report Responses(0)

Approved

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes
If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.)

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

general surgery and gastroenterology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

6 Views

26 Sep 2023 | for Version 2

Rıfat Peksöz, Department of General Surgery, Faculty of Medicine, Ataturk University, Erzurum, Erzurum, Turkey

6 Views Cite this report Responses(0)

Approved

Necessary revisions have been made. I wish success to the authors.

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

My areas of expertise are general surgery, especially acute appendicitis. Surgery interest: (General surgery, Gastrointestinal diseases): Emergencies in general surgery, ERCP, Endoscopy-colonoscopy, endoscopic interventions, colo-rectal diseases (colorectal cancers, diverticülitis), stomach diseaes (gastric cancer), gastrointestinal cancers, open or laparoscopic hernias (groin hernias, incisional, umbilical), anorectal diseases (pilonidal sinüs, hemorrhoid, anal fissure, perianal fistüla...), gallbladder surgery, spleen surgery, bariatric surgery (morbid obesity), nissen fundoplication.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

14 Views

01 Sep 2023 | for Version 1

Rıfat Peksöz, Department of General Surgery, Faculty of Medicine, Ataturk University, Erzurum, Erzurum, Turkey

14 Views Cite this report Responses(1)

Approved With Reservations

In the Abstract section, the complications which are seen more in the results section should be mentioned a little bit. This can be difficult to do, but when researchers read the articles, they read the abstract first. It is important to provide this information in order for the study to be more effective.
Keywords should be rewritten, comments; Add 'antibiotic therapy' instead of 'Antibiotic'. Add 'Pregnancy' instead of 'pregnant', and, add outcomes or complications words.
In your article, it was emphasized that the treatment of acute appendicitis in pregnant women is controversial, but in the introduction section, only the superiority of antibiotic therapy was emphasized, and the study highlighting surgery was not emphasized. I recommend that this study with good surgical results be emphasized in this section.
Discussion section: ‘’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, doi: 10.1111/ans.17443)}
I suggest adding an additional reference at the end of this sentence. Our work on this subject is up-to-date and has received many references in a short time (Peksöz et al., 2022¹).
Discussion section: "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"
Disadvantages of LA were mentioned in your article, but Laparascopic appendectomy has been routinely applied in pregnant women today. Although the subject of your study is antibiotic treatment or surgical treatment, this current information should be renewed and reviewed. An important study demonstrated the superiority of LA. ‘’Compared with OA, LA was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that LA shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with OA in pregnant women with suspected appendicitis’’ (Lee et al., 2019²).

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Partly
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes

References

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Respond to this report

Responses (1)

Author Response

06 Oct 2023

Valeska Candrawinata, Faculty of Medicine, Pelita Harapan University, Tangerang, 15811, Indonesia

Dear Reviewer, we thank you for your kind review and insightful notes. We have revised the manuscript accordingly.

In the Abstract section, the complications which are seen more in the results section should be mentioned a little bit. This can be difficult to do, but when researchers read the articles, they read the abstract first. It is important to provide this information in order for the study to be more effective.

Response: We have revised the abstract accordingly and added more information about the complications in the abstract.

Keywords should be rewritten, comments; Add 'antibiotic therapy' instead of 'Antibiotic'. Add 'Pregnancy' instead of 'pregnant', and, add outcomes or complications words.

Response: We have revised the keywords accordingly.

In your article, it was emphasized that the treatment of acute appendicitis in pregnant women is controversial, but in the introduction section, only the superiority of antibiotic therapy was emphasized, and the study highlighting surgery was not emphasized. I recommend that this study with good surgical results be emphasized in this section.

Response: We have revised this section accordingly and added them.

Discussion section: ‘’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, doi: 10.1111/ans.17443)}
I suggest adding an additional reference at the end of this sentence. Our work on this subject is up-to-date and has received many references in a short time (Peksöz et al., 2022¹).

Response: We have added the reference.

Discussion section: "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"

Response: We have revised the article accordingly.

Disadvantages of LA were mentioned in your article, but Laparascopic appendectomy has been routinely applied in pregnant women today. Although the subject of your study is antibiotic treatment or surgical treatment, this current information should be renewed and reviewed. An important study demonstrated the superiority of LA. ‘’Compared with OA, LA was associated with lower wound infection rates and shorter LOS. Based on our results and recent literatures, we suggest that LA shows non-inferior safety with respect to pregnancy outcomes but superior with regard to surgical outcomes compared with OA in pregnant women with suspected appendicitis’’ (Lee et al., 2019²).

Response: We have revised the article accordingly.

View more View less

Competing Interests

None

Alongside their report, reviewers assign a status to the article:

Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions

[1] 1. Abbasi N, Patenaude V, Abenhaim HA: Evaluation of obstetrical and fetal outcomes in pregnancies complicated by acute appendicitis. Arch. Gynecol. Obstet. 2014; 290(4): 661–667. PubMed Abstract | Publisher Full Text

[2] 2. Andersen B, Nielsen TF: Appendicitis in pregnancy, Diagnosis, management and complications. Acta Obstet. Gynecol. Scand. 1999; 78(9): 758–762. Publisher Full Text

[3] 3. Mourad J, Elliott JP, Erickson L, et al.: Appendicitis in pregnancy: New information that contradicts long-held clinical beliefs. Am. J. Obstet. Gynecol. 2000; 182(5): 1027–1029. PubMed Abstract | Publisher Full Text

[4] 4. Di Saverio S, Podda M, De Simone B, et al.: Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J. Emerg. Surg. 2020; 15(1): 27. PubMed Abstract | Publisher Full Text | Free Full Text

[5] 5. Il JJ, Park HC, Kim MJ, et al.: Outcomes of Antibiotic Therapy for Uncomplicated Appendicitis in Pregnancy. Am. J. Med. 2017; 130(12): 1467–1469. PubMed Abstract | Publisher Full Text

[6] 6. Liu J, Ahmad M, Wu J, et al.: Antibiotic is a safe and feasible option for uncomplicated appendicitis in pregnancy - A retrospective cohort study. Asian J. Endosc. Surg. 2021; 14(2): 207–212. PubMed Abstract | Publisher Full Text

[7] 7. Nakashima M, Takeuchi M, Kawakami K: Clinical Outcomes of Acute Appendicitis During Pregnancy: Conservative Management and Appendectomy. World J. Surg. 2021; 45(6): 1717–1724. PubMed Abstract | Publisher Full Text

[8] 8. Ashbrook M, Cheng V, Sandhu K, et al.: Management of Complicated Appendicitis during Pregnancy in the US. JAMA Netw. Open. 2022; 5(4): E227555. PubMed Abstract | Publisher Full Text | Free Full Text

[9] 9. Chakraborty J, Kong JC, Su WK, et al.: Safety of laparoscopic appendicectomy during pregnancy: a systematic review and meta-analysis. ANZ J. Surg. 2019; 89(11): 1373–1378. PubMed Abstract | Publisher Full Text

[10] 10. Sallinen V, Akl EA, You JJ, et al.: Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br. J. Surg. 2016; 103(6): 656–667. PubMed Abstract | Publisher Full Text | Free Full Text

[11] 11. Poprom N, Numthavaj P, Wilasrusmee C, et al.: The efficacy of antibiotic treatment versus surgical treatment of uncomplicated acute appendicitis: Systematic review and network meta-analysis of randomized controlled trial. Am. J. Surg. 2019; 218(1): 192–200. PubMed Abstract | Publisher Full Text

[12] 12. Abbasi N, Patenaude V, Abenhaim HA: Management and outcomes of acute appendicitis in pregnancy - Population-based study of over 7000 cases. BJOG Int. J. Obstet. Gynaecol. 2014; 121(12): 1509–1514. PubMed Abstract | Publisher Full Text

[13] 13. Vasileiou G, Eid AI, Qian S, et al.: Appendicitis in Pregnancy: A post-hoc analysis of an EAST multicenter study. Surg. Infect. 2020; 21(3): 205–211. PubMed Abstract | Publisher Full Text

[14] 14. Yang J, Wen SW, Krewski D, et al.: Association of treatments for acute appendicitis with pregnancy outcomes in the United States from 2000 to 2016: Results from a multi-level analysis. PLoS One. 2021; 16(12 December): e0260991. PubMed Abstract | Publisher Full Text | Free Full Text

[15] 15. Peeters T, Martens S, D’Onofrio V, et al.: An observational study of innate immune responses in patients with acute appendicitis. Sci. Rep. 2020; 10(1): 17352. PubMed Abstract | Publisher Full Text | Free Full Text

[16] 16. Peksöz R, Dişçi E, Kaya A, et al.: Significance of laboratory parameters in diagnosing acute appendicitis during pregnancy. ANZ J. Surg. 2022; 92 (1-2): 121–127. PubMed Abstract | Publisher Full Text

[17] 17. Abu-Raya B, Michalski C, Sadarangani M, et al.: Maternal Immunological Adaptation During Normal Pregnancy. Front. Immunol. 2020; 11: 11. PubMed Abstract | Publisher Full Text | Free Full Text

[18] 18. Carstens AK, Fensby L, Penninga L: Nonoperative Treatment of Appendicitis during Pregnancy in a Remote Area. Am. J. Perinatol. Rep. 2018; 08(01): e37–e38. PubMed Abstract | Publisher Full Text | Free Full Text

[19] 19. Loftus TJ, Brakenridge SC, Croft CA, et al.: Successful nonoperative management of uncomplicated appendicitis: predictors and outcomes. J. Surg. Res. 2018; 222: 212–218.e2. PubMed Abstract | Publisher Full Text | Free Full Text

[20] 20. Shindoh J, Niwa H, Kawai K, et al.: Predictive factors for negative outcomes in initial non-operative management of suspected appendicitis. J. Gastrointest. Surg. 2010; 14(2): 309–314. PubMed Abstract | Publisher Full Text

[21] 21. Tsai MC, Lin HC, Lee CZ: Diabetes increases the risk of an appendectomy in patients with antibiotic treatment of noncomplicated appendicitis. Am. J. Surg. 2017; 214(1): 24–28. PubMed Abstract | Publisher Full Text

[22] 22. Kave M, Parooie F, Salarzaei M: Pregnancy and appendicitis: A systematic review and meta-analysis on the clinical use of MRI in diagnosis of appendicitis in pregnant women. World J. Emerg. Surg. 2019; 14(1): 37. PubMed Abstract | Publisher Full Text | Free Full Text

[23] 23. Baruch Y, Canetti M, Blecher Y, et al.: The diagnostic accuracy of ultrasound in the diagnosis of acute appendicitis in pregnancy. J. Matern. Neonatal Med. 2020; 33(23): 3929–3934. PubMed Abstract | Publisher Full Text

[24] 24. Konrad J, Grand D, Lourenco A: MRI: first-line imaging modality for pregnant patients with suspected appendicitis. Abdom. Imaging. 2015; 40(8): 3359–3364. PubMed Abstract | Publisher Full Text

[25] 25. Lee SH, Lee JY, Choi YY, et al.: Laparoscopic appendectomy versus open appendectomy for suspected appendicitis during pregnancy: a systematic review and updated meta-analysis. BMC Surg. 2019; 19(1): 41. PubMed Abstract | Publisher Full Text | Free Full Text

[26] 26. Ball E, Waters N, Cooper N, et al.: Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG). Facts, Views Vis. ObGyn. 2019; 11(1): 5–25. PubMed Abstract Reference Source

[27] 27. Zingone F, Sultan AA, Humes DJ, et al.: Risk of acute appendicitis in and around pregnancy a population-based cohort study from england. Ann. Surg. 2015; 261(2): 332–337. PubMed Abstract | Publisher Full Text

[28] 28. Candrawinata VS, Hanafi RV, Baskoro BA, et al.: Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis. [Dataset]. Zenodo. 2022. Publisher Full Text

Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis

Abstract

Keywords

Revised Amendments from Version 1

Introduction

Methods

Database and literature search

Study selection/design

Data extraction

Statistical analysis

Results

Figure 1. PRISMA flow diagram.

Study characteristics

Table 1. Characteristics of included studies.

Table 2. Risk of bias assessment The Risk of Bias in Non-Randomized Studies – of Interventions (ROBINS-I) tool.

Preterm delivery

Figure 2. Forest plot showing preterm delivery between antibiotic and surgery group.

Fetal loss

Figure 3. Forest plot showing fetal loss between antibiotic and surgery group.

Maternal death

Complications

Figure 4. Forest plot showing complications between antibiotic and surgery group.

Sensitivity analysis

Figure 5. Forest plot showing the sensitivity analysis for fetal loss (A) and complications (B) between antibiotic and surgery group.

Certainty of evidence

Table 3. Certainty of evidence.

Discussion

Conclusion

Data availability

Underlying data

Extended data

Reporting guidelines

References

Comments on this article Comments (0)

Open Peer Review

Comments on this article Comments (0)

Open Peer Review

Reviewer Status

Reviewer Reports

Comments on this article

Browse by related subjects

Competing Interests Policy

Stay Updated