Authors: Chuankai Lv, Chuanping Xie, Xiaoman Wang, Yakun Liu
Categories: Research, Diagnosis, Infantile appendicitis, Neonatal appendicitis, Ultrasonography, Ultrasound
Authors: Chuankai Lv, Chuanping Xie, Xiaoman Wang, Yakun Liu
Neonatal appendicitis is a rare but critical condition that presents diagnostic challenges due to its nonspecific symptoms and clinical manifestations. Early and accurate diagnosis is crucial for reducing the high mortality rates associated with this condition. Abdominal ultrasonography plays a pivotal role in identifying characteristic signs of appendicitis in neonates. This study aimed to investigate whether neonatal appendicitis can be diagnosed with abdominal ultrasonography by identifying its specific signs.
This study reviewed 20 consecutive cases of neonatal appendicitis confirmed through surgery at a National Medical Center. Preoperative abdominal ultrasonography was analyzed for direct and indirect signs of appendicitis.
Our study included neonates with a mean age of 13.0 ± 7.1 days. The appendix was identifiable in 13 out of 20 cases (65%). The mean outer diameter of the appendix was 4.6 ± 1.8 mm. Eight cases had appendix diameter ≥ 4 mm. Fluid accumulation within the appendiceal cavity was noted in 6 (30%) patients, and peri-appendiceal fluid accumulation was detected in 5 (25%) patients. Ultrasonography revealed appendiceal perforation in 12 out of 16 cases (75%). The indirect signs of neonatal appendicitis included right lower quadrant (RLQ) abscess, pneumoperitoneum, and thickening of the intestinal wall and mesentery in the RLQ.
Most cases of neonatal appendicitis may be diagnosed through abdominal ultrasonography by identifying both direct and indirect signs. Future studies with larger patient cohorts are needed to improve ultrasonographic diagnosis of neonatal appendicitis.
Appendicitis is the most common abdominal surgical emergency in the pediatric population, with more than 70,000 children diagnosed annually in the United States alone [1, 2]. It significantly impacts children’s health and brings substantial economic and disease burdens [3]. Despite its frequent occurrence in children, appendicitis in neonates is exceptionally rare, accounting for only 0.1–0.34% of pediatric appendicitis cases [4, 5]. However, when it does occur in younger patients, the risk of perforation is significantly higher. Perforation rates have been reported as 100% in patients younger than 2 years, 83.3% in patients aged 2–3 years, and 47.3% in patients older than 5 years [6].
The short, conical shape of the neonatal appendix reduces the likelihood of luminal obstruction by stool or lymphoid tissue, which is a common cause of appendicitis in older children and adults [6, 7]. In neonates and older infants, appendicitis presents a unique clinical challenge. It is not only rare, but also often manifests with non-specific symptoms that are difficult to link to this condition and diagnose [8]. The most common clinical manifestations of this disease are fever, vomiting, abdominal distension, diarrhea and lethargy, which are nonspecific and often suspected to be gastroenteritis, necrotizing enterocolitis (NEC), and encephalitis [8, 9]. Moreover, the clinical presentation often varies depending on whether the appendix is perforated [10]. This leads to a higher likelihood of delayed treatment and increased mortality rate. Historically, the mortality rates was 78% from 1901 to 1975, and 23% from 1990 to 2014 in neonatal patients [9, 11].
Ultrasonography has been the first-line work-up when there is a concern for a case of appendicitis in a child. The thin abdominal wall of the newborn may facilitate ultrasound observation of the organs in the abdominal cavity [12]. However, in most reports, ultrasonography could not directly detect or diagnose neonatal appendicitis [13]. Hence, by systematically describing the untrasonographic findings of neonatal appendicitis based on a case series, this study aims to determine whether specific ultrasonographic signs can be used to diagnose neonatal appendicitis, providing a non-invasive diagnostic tool for early and accurate detection.
This is a single-center retrospective study. The study was approved by the Institutional Review Board (IRB) of Beijing Children’s Hospital (approval [2022]-E-183-R; Sep 19, 2022). Due to the retrospective nature of the study, informed consent was waived by the IRB. Our study adheres to the Declaration of Helsinki of 1975 and its later amendments.
Cases with neonatal appendicitis were identified from the institutional database of the National Center for Children’s Health using the International Classification of Diseases, Ninth Revision (ICD-9 540.0, 540.1, 540.9, 541, 542) and International Classification of Diseases, Tenth Revision (ICD-10 K35×, K36, K37).
Consecutive patients aged 0 to 28 days who were admitted between December 1, 2007, and January 31, 2023, were eligible candidates. To ensure diagnostic accuracy, we included only cases of appendicitis confirmed by appendectomy, laparotomy, laparoscopic exploration, or autopsy. The exclusion criteria (1) intraoperative or postoperative pathology finding of a normal appendix; (2) diffuse abdominal inflammation where the primary condition could not be confirmed as appendicitis; (3) no abdominal ultrasounography before surgery; (4) no ultrasonographic images or videos in database.
Information regarding demographic data and ultrasound reports was extracted from the electronic medical records. The surgical records, ultrasound reports, and images were checked by two authors to confirm the consistency of the diagnosis. Ultrasound images were extracted from the database of ultrasound department. The review of ultrasound images or videos was conducted by two senior authors with more than 10 years of experience in pediatric ultrasonography. They were not blinded to the clinical diagnosis. Any discrepancy between their conclusions or between their uniform report and the original report were resolved through discussion or with a senior author when necessary. The decisions were made by consensus. Because the diameter of the appendix in four patients was not measured in the original images, it was directly extracted from the reports.
The primary outcome of this study was to assess the diagnostic utility of abdominal ultrasound in detecting neonatal appendicitis. Secondary outcomes included the identification of specific ultrasonographic features, such as the diameter of the appendix and the signs of appendiceal perforation, as well as the correlation between ultrasonographic findings and postoperative pathological diagnoses.
The Philips iU 22 and Hitachi Ascendus color Doppler ultrasound systems, equipped with L12-5 (5–12 MHz) and L74M (5–13 MHz) linear array probes, were employed for neonatal abdominal ultrasonography in our center. Patients were positioned supine for optimal abdominal exposure. The probe was pressed against the abdomen to reveal the intestinal structures. The ileocecum, characterized by its “mushroom” appearance—with the stalk representing the terminal ileum and the cap representing the cecum—is identified on the right side of the abdomen(see Fig. 1A). This “mushroom” serves as an anatomical clue for searching the cecum, and the base of the appendix is located at the terminal end of the cecum. The appendix usually runs parallel to and behind the ileum. If not found around the ileum, a thorough search should be conducted in the right lateral paracolic gutter. The appendix is characterized by its attachment to the cecum, typically appearing coiled, with a blind-ending tip; in cross-section, it appears circular with a diameter generally less than 4 mm(Fig. 1B and D), and longitudinally, it presents as a tubular structure (Fig. 1C); the inner lining is smooth and flat, without swelling of the wall. In our experience, in simple and suppurative appendicitis, the wall of the appendix may be swollen, and in cases of suppurative appendicitis, pus may accumulate in the lumen. In gangrenous appendicitis, the wall may be irregular. In some cases of right lower quadrant abscesses, discontinuity of the appendiceal wall and reduced lumen tension may be observed inside or around the abscess, indicating perforated appendicitis with abscess formation.
Fig. 1Representative ultrasound images of a normal neonatal appendix. (A) Mushroom sign indicates the ileocecum. (B) Cross-sectional view of the appendix shows multiple circular with clear layering, which indicates its coiled shape. (C) Longitudinal view of the proximal part of appendix of another patient. (D) Cross-sectional view of the appendix
Patients with severe abdominal distension were advised to fast for several hours before re-examination if their condition is stable.
Continuous variables were presented as mean and standard deviation (SD) or median and interquartile range (IQR), as appropriate. Categorical variables were expressed as numbers and percentages.
This study included 20 neonates with surgically diagnosed appendicitis. The mean age was 13.0 ± 7.1 days, and 9 patients (45%) were female (Table 1). Preterm births were noted in six (30%) patients, while term births were observed in 13 (65%) patients; the gestational age for one patient was undocumented. The mean birthweight were 3.0 ± 0.7 Kg. The median duration from the onset of symptoms to surgical intervention was 2 (IQR:1–6) days. The majority (80%) had perforated appendicitis, and 6 out of 17 patients (35%) had gangrenous appendicitis. Post-surgical mortality was recorded in one patient (5%). A summary of abdominal ultrasound findings is presented in Table 2.
Table 1Characteristics of included patients with neonatal appendicitisItemsPatients(n = 20)Age, (days)^a^13.0 ± 7.1Sex Female, n(%)9 (45) Male, n(%)11 (55)Maturity, n(%) Preterm6 (30) Term13 (65) Unknown1 (5)Gestational age for preterm infants^b^, median (IQR)36 (34.3–36.4)Birthweight, Kg3.0 ± 0.7Symptoms, n(%) Fever9 (45) Abdominal distention14 (70) Diarrhea1 (5) Vomiting6 (30)Laboratory tests WBC count, *10^99.8 (7.9–11.6) Neutrophil count, *10^95.6 (4.3–8.5) CRP, mg/L50 (14–92) Hemoglobin, g/L135 (114–151) Serum albumin, g/L32.6 (25.5–35.7)Days at surgery2 (1–6)Gangrenous appendicitis, n(%)7 (35)Death, n(%)1(5)Perforation, n(%)16 (80)a. Days of suspected symptoms onsetb. Five preterm patients were analyzed
Table 2Summary of abdominal ultrasound finding of neonatal appendicitisUltrasound findingsPatients(n = 20)Days at examination^a^, median (IQR)1.5 (1.0–5.0 )Visible appendix, n(%)13 (65)Invisible appendix, n(%)7 (35)Normal ultrasonographic findings, n(%)0 (0)RLQ abscess or inflammatory lump, n(%)3 (15)Intraperitoneal abscess or inflammatory lump, n(%)4 (20)Amyand’s hernia, n(%)0 (0)Intraperitoneal free gas, n(%)4 (20)Ascites, n(%)10 (50)Depth of ascites, mm18 (8)Pneumatosis intestinalis, n(%)2 (10)RLQ intestinal wall thickening, n(%)6 (30)RLQ mesentery swelling, n(%)4 (20)Diameter of appendix, mm4.6 ± 1.8Thickness of appendiceal wall,^b^ mm1.5 ± 0.5Appendiceal lumen fluid, n(%)6 (30)Appendiceal fecal mass, n(%)1 (5)Periappendicural fluid accumulation, n(%)5 (25)a. From onset of symptoms to ultrasound examinationb. Six patients were included
Ultrasonographic images or dynamic videos were acquired. Typical features are presented in Figs. 2 and 3. The median time from the emergence of symptoms to the ultrasonographic examination was 1.5 (IQR: 1–5) days. The appendix was identifiable in 13 cases (65%), facilitating a direct diagnosis of neonatal appendicitis. The mean outer diameter of the appendix was 4.6 ± 1.8 mm, and the mean thickness of appendiceal wall was 1.5 ± 0.5 mm. The swollen appendix was accompanied by unclear layers of the appendiceal wall (Figs. 2C and 3A, and 3C). Eight out of 11 cases (73%) with measured appendiceal diameter had a diameter ≥ 4 mm (Fig. 2A). In one case, a soft fecal mass was observed within the appendiceal lumen (Fig. 3A). Fluid accumulation within the appendiceal cavity was noted in 6 patients (30%), and peri-appendiceal fluid accumulation was detected in 5 patients (25%) (Fig. 3B and D).
Fig. 2Diagnostic ultrasound images from cases of neonatal appendicitis. (A, B) Images from an 18-day-old girl displaying a swollen, thickened appendix; discontinuity of the proximal appendiceal wall, suggestive of perforation, is marked with an arrow. (C, D) Images from a 23-day-old boy showing a swollen and perforated appendix with indistinct layers (arrow in C); free gas between the abdominal wall and the liver indicative of perforation (arrow in D)
Fig. 3Ultrasound findings in appendicitis cases of a 13-day-old boy (A and B) and a 4-day-old girl (C and D). (A) Longitudinal section of proximal part of appendix in a 13-day-old boy reveals a swelling appendix with unclear layering (yellow arrow) and a fecal mass in the appendiceal lumen (red arrow). (B) Longitudinal section of distal part of appendix shows appendiceal perforation (red arrow) and surrounding abscess (asterisk). (C) The middle part of appendix of 4-day-old girl is swelling with indistinct layering (red arrow). (D) Evidence of appendiceal wall disruption (red arrow) and a periappendiceal hypoechoic abscess (asterisk)
Ultrasound accurately identified appendiceal perforation in 12 out of 16 cases (75%).(Figures 2B and 3B). For the remaining 4 patients, preoperative ultrasounds did not find signs of perforation.
None of the patients had normal abdominal findings. Right lower quadrant (RLQ) abscess were identified in 3 patients (15%). Free air in the abdominal cavity was detectable in 4 patients (20%); of these, free air was observed anterior to the liver (Fig. 2D) in 3 cases and in the RLQ with associated fluid collection in one case. Other indirect signs included thickening of the intestinal wall (6 patients) and mesenteric swelling in the RLQ (4 patients).
In three cases, ultrasound findings were inconclusive or non-specific, primarily due to extensive intestinal gas accumulation.
In this retrospective analysis of 20 neonates who underwent preoperative ultrasound examinations, we found that abdominal ultrasonography may be a valuable tool for diagnosing neonatal appendicitis. However, it is crucial for ultrasound physicians to be aware of the possibility of neonatal appendicitis and the characteristics of a normal neonatal appendix. The characteristics of neonatal appendicitis we identified include an appendiceal diameter ≥ 4 mm, blurred layering of the appendiceal wall, the presence of pus within the appendiceal lumen, and peri-appendiceal pus accumulation. Indirect signs of neonatal appendicitis include the presence of an abscess or inflammatory mass confined to the RLQ, thickening of the bowel wall, and mesenteric swelling in the RLQ.
To the best of our knowledge, this is the first article to describe neonatal appendicitis in detail with 20 cases. A detailed description of the normal and abnormal appendix in neonates may help to strengthen the understanding of neonatal appendicitis and promote advances in its early diagnosis through ultrasonography. Unfortunately, we failed to include healthy controls.
Neonatal appendicitis has a propensity to rapidly progress to a life-threatening condition, necessitating early and accurate diagnosis and treatment to reduce mortality rates. The characteristics of neonatal appendicitis has been reported in previous studies [8, 14]. The symptoms are very nonspecific, and the clinical signs are vague within this demographic, complicating the timely diagnosis and emphasizing the need for supportive diagnostic tools, especially abdominal ultrasonography [15, 16].
Ultrasonography has been the first-line work-up when there is concern for appendicitis in a child, with high sensitivity and specificity [17–19] Due to abdominal distention, crying of neonates, and the small size and considerable mobility of the appendix, the neonatal appendix cannot usually be detected [20, 21]. The secondary signs, which include swelling of the periappendiceal mesentery, periappendicular abscess, an incompressble tubular structure containing heterogeneous sludge, and maximum fluid collection in the RLQ, are crucial in suggesting neonatal appendicitis [8, 15]. These features may be frequently suspected as NEC. However, the typical signs of NEC, including pneumatosis intestinalis, portal venous gas, and impaired peristalsis, are seldom seen in neonatal appendicitis [22]. Two of 20 patients had pneumatosis in our reports. Given the rarity and diagnostic challenges of neonatal appendicitis, the role of abdominal ultrasonography in diagnosing neonatal appendicitis warrants further investigation.
Despite the limitations of visualizing the neonatal appendix with ultrasonography, the appendix may be observed in most newborns by reducing the interference of intestinal air through gentle pressure [23, 24]. The ileocecum with a mushroom shape in the RLQ serves as an anatomical marker to indicate the cecum. The appendix typically runs parallel behind the ileum or in the paracolic gutter. The normal features of the appendix in neonates are understudied. Trout et al. reported the normal diameter of appendix in children measured through computed tomography [25]. The mean diameter of appendix in infants 0 to 1 year was less than 4 mm. However, the number of infants included were very limited. Another study of changes in the length and diameter of the normal appendix throughout childhood through appendix specimens reported a mean normal diameter of appendix of 3.7 ± 1.3 mm in children less than 3 years [26]. However, the authors could not actually provide the reasons for appendectomy, and the diameter in specimens may differ from that in vivo. Although the current study did not include normal neonates, most neonates (73%) with appendicitis had an appendix outer diameter ≥ 4 mm. Hence, it is speculated that an appendix outer diameter ≥ 4 mm is suggestive of neonatal appendicitis. Another ultrasonographic feature that is crucial for the diagnosis of neonatal appendicitis if blurred layering of the appendiceal wall. Swollen and blurred appendiceal wall layers often suggest more advanced condition, such as suppurative or gangrenous appendicitis, indicating wall inflammation or perforation [24]. Although not all cases presented with these signs, a combination of these features may increase the diagnostic accuracy [27, 28]. However, these measurements should be used alongside other clinical and ultrasonographic findings and laboratory tests to improve diagnostic accuracy.
In most previous studies, the appendix was not detectable. A recent systematic review showed that 11 of 81 small infants (14%) within 3 months of age with abdominal appendicitis were diagnosed with appendicitis by ultrasound [13]. In the current study, 13 cases (65%) had visible appendix. The discrepancy may derived from publication bias, as most previous studies were case reports. Cases with typical appendiceal features may be missed.
The perforation rate in neonatal appendicitis is very high [8, 9]. In a previous study, the perforation rate reached 80%, which is higher than that in older infants over 28 days (63.9%).^8^ The high perforation rate may contributed to the thinner appendiceal wall in neonates than that in older infants and children, as the thickness of appendiceal increases with age [25]. It is noteworthy that although both ultrasound and surgery revealed that perforation occurred early, only 4 patients with perforation exhibited the classic perforation sign of pneumoperitoneum. This may be attributed to the small amount of gas spilled out through the perforation. Discontinuities in the appendiceal wall are detectable on ultrasound, and although this feature is not easy to detect, its sensitivity in diagnosing perforation reached 100%. Abscesses, cloudy effusions (pus accumulation), intestinal adhesions, and intestinal interstitial fluid confined to or most prominently in the right lower abdomen are also suggestive of appendicitis. However, perforation and peritonitis cannot be attributed solely to appendicular perforation.
An important indirect feature of neonatal appendicitis is the presence of an abscess or effusion in the right lower abdomen. In a report by Cui et al., 10 of 12 neonates with appendicitis had fluid lesions in the right lower abdomen [29]. Most of our patients also had either a periappendiceal confined effusion (pus accumulation) or an interstitial effusion in the right lower abdomen. The prevailing belief is that the infant’s underdeveloped greater omentum and immune system contribute to challenges in localizing the inflammation. Based on the presence of RLQ abscess, it appears that the patient’s immunity is a bit stronger than we assumed. Of course, this fluid confined to the right lower abdomen could be the result of survivor bias, or it could be attributed to the powerful antibiotics. In our experience, a difficult to interpret RLQ mass could be appendicular abscess. When inflammatory changes are detected in the RLQ, the high suspicion of neonatal appendicitis should be taken seriously.
The most common etiology for appendicitis is luminal obstruction from lymphoid follicle hyperplasia, fecaliths, or parasites [30]. However, the chance of luminal obstruction in newborns is minimal, because they have much less prominent lymphoid tissue and funnel-shaped lumen of the appendix. These features make neonatal appendix less susceptible to luminal obstruction. Only one patients had a soft fecal mass in the appendiceal lumen, without signs of obstruction.
This study has several limitations. First, this study is a retrospective analysis of confirmed and operated cases. We did not include cases with positive ultrasonographic findings but did not undergo appendectomy, nor cases that did not undergo ultrasonography. This exclusion introduces selection bias and could overestimate the diagnostic value of ultrasound in identifying neonatal appendicitis. Additionally, it limits the generalizability of our findings. The cohort’s location and specific characteristics, such as patient demographics or institutional practices, may also limit the generalizability of these findings to broader populations. Second, the ultrasound reports, images, and videos were searched from the database of ultrasound department. Some patients had missing images but detailed reports. We could not retrospectively analyse the key features of neonatal appendicitis in these cases. Third, we did not analyze cases whose ultrasound findings suggested appendicitis but the diagnosis was not confirmed during surgery. This could result in an overestimation of the diagnostic value of ultrasound, as similar findings may occur in other abdominal conditions. Fourth, the limited number of patients hampers our ability to establish ultrasonographic criteria for neonatal appendicitis. Moreover, given the lack of diagnostic accuracy metrics such as sensitivity and specificity, we could not evaluated the diagnostic accuracy of abdominal ultrasound. It is important to be aware for future studies that the sensitivity and specificity of ultrasound in diagnosing this condition may be affected by the low prevalence of this condition, as lower prevalence can lead to a higher likelihood of false positives or false negatives.
Our findings demonstrate that neonatal appendicitis may be diagnosed through abdominal ultrasonography by identifying both direct and indirect signs. These signs include an appendix diameter of 4 mm or more, blurred layering of the appendiceal wall, the presence of pus within or surrounding the appendix, and evidence of a RLQ abscess. Future studies with larger patient cohorts are needed to validate these findings and to fully assess the reliability of ultrasound in this context.