Journal of Neonatal Surgery 2015; 4(1):4

ATHENAS PAGES

Neonatal Appendicitis (Part 1): A Review of 52 cases with

Abdominal Manifestation

V. Raveenthiran*

Department of Pediatric Surgery, Sri Ramasamy Memorial (SRM) Medical College, SRM University, Chennai 603203, India

(Athena stands for abbreviation of Abstracting and Thoughtful Evaluation of Neonatal Articles; but it is also personified by
the contributor. Like Athena of Greek mythology, she distills wisdom from published literature)

No age is free from risk of an attack does not leave behind undigested residue or
Of inflammation in this cul-de-sac fecal pellets. Newborns are least likely to be ex-
- Zeta (Cope Z) Acute abdomen in rhymes
posed to infective agents such as adenoviruses,
which are known to cause lymphoid hyperplas-
Although no age is free from the risk of appen-
ia. Thus, many of the risk factors operating in
dicitis, it is extremely uncommon in newborns.
grown-ups are absent in newborns, which is
Credit of describing the first neonatal case is
why they are least prone for appendicitis. Three
disputed between Diess (1908) [1] and Albrecht
etiological hypotheses abound to explain the
(1905).[2] Although Lillenthal reported a survi-
rare occurrence of neonatal disease. Martin and
vor of scrotal appendicitis in 1908, [2] 45 years
Perrin [6] suggested that obstruction caused by
elapsed before Meigher and Lucas [1] in 1952
Hirschsprung disease could play a role in the
documented the first survivor of abdominal dis-
pathogenesis. Bax et al. [7] proposed that neo-
ease. Another 35 years passed before proving
natal appendicitis (NA) is actually a limited
as to what Sir Zachery Cope remarked as No
form of necrotizing enterocolitis (NEC). The ob-
age really extends into prenatal period. Martin
servation that more than 50% of infants with
- Glen (1986) [3] and Narasimharao et al.
appendicitis are preterm [2] adds strength to
(1987) [4] recorded antenatal appendicitis. A
Baxs theory because 90% of NEC is also found
further 15 years went before hearing about the
in premature babies. Wangensteenian surgeons
first successful laparoscopic appendicectomy in
contemplate etiological role of obstruction due
neonate by Efrati et al. [5] Intrigued by the tar-
to pellet like stool of cystic fibrosis and meconi-
dy progress, Athena looked for a review article
um ileus. But none of the three theories are
to dwell more on this subject. Although Kara-
scientifically proved.
man et.al [2] summarized 141 cases collected
over a century (1901 - 2000), Athena is disap-
Mortality of NA was as high as 78% between
pointed that the entity has largely remained
1901 and 1975. It rapidly declined to 33% dur-
anecdotal and almost all the published reports
ing 1976-84 owing to rapid advances in antibi-
are individual case reports or at the best a
otic therapy, neonatal intensive care and diag-
small series. Therefore, she decided to critically
nostic modalities. Further drop in death rate to
analyze the published data to solve certain un-
28% during 1985-2003 was only a modest im-
answered questions.
provement. [2] These figures cause great con-
cern in the era when corresponding mortality in
Unverified Assumptions
grown-ups is approaching zero per cent. Sever-
Hundred years ago, Wangensteen proved that al factors are incriminated for this high fatality.
appendicitis is caused by luminal obstruction. They include (1) diagnostic and therapeutic de-
Recumbence of newborn and funnel shape of lay due to lack of specific clinical features and
fetal appendix are said to protect against ap- rarity of the disease; (2) early perforation due to
pendicular blockage. Milk, unlike adult food, fragility of neonatal appendix; (3) poorly walled

* Corresponding Author EL-MED-Pub Publishers.

 Neonatal Appendicitis (Part 1): A Review of 52 cases with Abdominal Manifestation

off infection due to underdeveloped omentum; and appendix. She excluded 5 neonates re-
(4) immature immune system and (5) limited ported in non-English articles,[8-11] 2 patients
physiological reserve of preterm babies. All who were actually treated prior to 1990 [12]
these assumptions have not been subjected to and one [13] of the duplicate publications. [2,
rigorous scientific testing. 13] Definitions of neonatology terms were simi-
lar to that of WHO convention. However, infants
Unanswered questions who had disease onset during neonatal period
but presented later than 28 days were also in-
Foregoing hypothetical assumptions made cluded. Athena could collect 52 cases of neona-
Athena inquisitive of the following concerns: tal appendicitis treated and reported between
1990 January and 2014 December.[1,2,5,12,
1. Is there a causal relationship between 14-50]
NA and Hirschsprungs disease?
2. How often is cystic fibrosis or meconi- Geographic Distribution
um ileus associated with NA?
Athena found that maximum number of cases
3. Is NA a form of NEC? How often are the have been reported from India (n=10), which is
risk factors of NEC seen in NA? followed by Turkey (n=8), USA (n=5), UK (n=4),
4. What is the current mortality of NA? Is and Canada (n=4). The high incidence in India
it unusually high? does not appear to be due to her global first-
rank in preterm population. [51] This impres-
5. Is the mortality affected by gestational
maturity, diagnostic delay or perfora- sion is supported by the fact that only one case
tion? has been described from China, [31] which is in
the second position of preterm census. Further
6. Does the perforation occur early and is there are no reports from Nigeria, Indonesia,
there a correlation between it and Malawi and Congo, which are in successive po-
therapeutic delay? sition of having the highest preterm birth rate.
7. How often the infection or perforation Therefore, Athena concludes the skewed distri-
is effectively walled off? bution could be a phenomenon of publication
bias or genetic susceptibility.
8. Is there a clue for early diagnosis?
9. Which is the most useful investigation? Sex Ratio
10. Is a particular group of neonates more
vulnerable to NA than others? Karaman et al. [2] showed a clear male prepon-
derance with a male: female ratio of 3:1. But
Athena finds a narrowing gap in sex ratio with
56% in males and 40% in females. (Table 1) It
Athenas Plot
is not clear if the change is due to selection bi-
as or due to an alteration in the disease pat-
Athena is not for mixing apples and oranges.
tern. The latter appears to be plausible because
Clubbing the current literature with that of re-
Karaman et al had also shown a similar trend.
mote past is meaningless because of the signifi-
While analyzing the data of 3 time-intervals
cant advancements made recently. Therefore,
namely 1909-75, 1976-84 and 1985-2003, they
Athena restricted her analysis to reports pub-
calculated male: female proportion as 60:27,
lished during the last 25 years (1990 - 2014).
60:40 and 50:36 respectively.
Inflammed appendix in hernial sac (Amyand
hernia) has a totally different outlook from that
Gestational Maturity
of the abdominal disease. Hence, Athena ex-
cluded Amyand hernia and intends to examine Traditionally, preterm neonates are considered
it separately. She searched Pubmed, Google to be more vulnerable for appendicitis. Nearly
Scholar, Embase, Indmed and AJOL using a 52% were premature babies in Karamans re-
keyword combination of neonate, newborn

Journal of Neonatal Surgery Vol. 4(1); 2015

 Neonatal Appendicitis (Part 1): A Review of 52 cases with Abdominal Manifestation

view [2]. But Athena finds term infants being lar perforation due to congenital megacolon. [6]
more affected than preterm (48% vs. 37%). This This could not be verified because fine details of
is corroborated by the fact that an equal pro- appendicular histology are not usually included
portion of the neonates were having optimal in published case reports. For these reasons,
and suboptimal birth weight. (Table 1) These coincidence of colonic aganglionosis and NA
observations strengthen the hypothesis that the will remain a clinical curiosity rather than a
disease pattern is changing over the time. scientific fact.

Table 1: Demographic pattern of neonatal ap- Table 2: Clinical features of Neonatal appendicitis
pendicitis
Clinical Feature n (%)
Demographic description n (%)

Non-specific Features
Sex Ratio
Male 29 56% Abdominal distension 42 89%
Female 21 40% Vomiting 28 54%
Unspecified 1 4% Abdominal tenderness 25 48%
Feed refusal 22 42%
Birth weight Fever 16 31%
1000 - 1499 g 6 12%
1500 - 2499 g 6 12% Restlessness 10 19%
2500 - 3500 g 15 29% Lethargy 9 17%
> 3500 g 5 10% Dehydration 9 17%
Unspecified 20 39% Constipation 8 15%
Tachypnea 8 15%
Maturity Shock 6 12%
Preterm 19 37% Tachycardia 6 12%
Term 25 48%
Unspecified 8 15% Hematochezia 4 8%
Diarrhea 2 4%
Mode of Delivery Hypothermia 2 4%
Vaginal delivery 16 31% Hydrocele 2 4%
Cesarean 15 29% Apnea 1 2%
Unspecified 21 40% Convulsions 1 2%
Cyanosis 1 2%
Skin Rashes 1 2%

Specific indicators
Etiological role of Co-morbidity & Risk fac-
tors RIF Erythema 7 14%
RIF Lump 6 12%
RIF Edema 2 4%
Athena could not find a single report of cystic
RIF Tenderness 1 2%
fibrosis or meconium ileus in NA. Even Kara- Air in appendix lumen 1 2%
man, [2] over a period of 100 years, could find Free air in RIF 1 2%
only one case of cystic fibrosis in 128 NA. * Stool occult blood was positive in another 4 cases
RIF Right iliac fossa
Therefore, the alleged correlation between the
two pathologies appears to a medical myth.
Generalized peritonitis and intestinal conges-
Athenas series had only 4 cases of Hirsch- tion of perforated appendicitis is difficult to dis-
sprung disease co-existing with inflammed ap- tinguish from that of NEC. Athena noted that
pendix. None of them had features of enterocol- one or more risk factors of NEC were present in
itis of megacolon. Prior to 1990, this combina- 23 (44%) neonates suffering from appendicitis.
tion has been reported in only 9 neonates [44] Peri-natal or pre-morbid asphyxia was reported
but not in older children. Sarioglu et al. [44] in as many as 17 (33%) instances. Prolonged
over a period of 18 years, picked up 2 NA rupture of membrane, chorio-amnionitis and
among 302 neonates with Hirschsprungs dis- maternal sepsis were present in 7 (13%) cases.
ease. Extreme rarity of the association pre- Serious congenital heart disease (n=3) and ma-
cludes any meaningful analysis. Periappendici- ternal smoking (n=1) were also noted. There-
tis without transmural infiltration of neutro- fore, the claim of NA being a form of NEC has
phils is said to be characteristic of appendicu- some substance and it deserves further investi-

Journal of Neonatal Surgery Vol. 4(1); 2015

 Neonatal Appendicitis (Part 1): A Review of 52 cases with Abdominal Manifestation

gation. A well designed animal study is indicat- tients with perforation. Correct pre-operation
ed to know as to why NEC changes are con- diagnosis was possible in 2 instances when the
fined to the appendix. free gas was seen in RIF or inside the appen-
dicular lumen. Plain radiographs, although not
Clinical Diagnosis diagnostic of appendicitis, are helpful in detect-
ing complications.
Definitive diagnosis was made clinically in 3
neonates and at autopsy in 2 infants. All others Perforation and Walling off Infection
were diagnosed retrospectively after sur-
gical exploration. Diagnostic role of laparoscopy Approximately 85% of the infants had appen-
seems to be underutilized because only 5 cases dicular perforation at laparotomy. The mean
have been described so far. [5,20,34,42] Ab- delay between the onset of symptoms and de-
dominal distension (89%), vomiting (54%), ab- finitive therapy was 8 3.5 days in uncompli-
dominal tenderness (48%), restlessness or leth- cated cases and 3.3 3 days in perforated ap-
argy (36%) and fever (31%) were the most pendices. Using Students t-test, Athena found
common symptoms. [Table 2] Admittedly, they the difference be statistically significant (P =
are non-specific and hence may not narrow 0.044). Usually perforation is expected to be
down the clinical diagnosis. Contrary to general more common when there is inordinate delay.
belief 18 of the neonates (35%) had one or more Therefore, the paradox of shorter delay in per-
localizing signs. Interestingly only 3 of them foration group necessitated further dissection
(17%) were correctly diagnosed prior to laparot- of data by compartmentalizing pre-hospital
omy. The high rate of misdiagnosis despite the procrastination and post-admission delay. The
presence of localizing sign attests the old prov- mean delay between admission to NICU for ab-
erb, Eyes cant see what the mind does not dominal symptoms and definitive treatment
know. Signs of perforated appendix such as was also significantly longer in uncomplicated
flank erythema or edema, palpable mass and group (5.3 3.2 days) than in perforation group
tenderness are also seen in NEC. Understanda- (1.8 2.3 days). However, the mean duration of
bly, the most common misdiagnosis was NEC pre-hospital symptoms did not differ signifi-
in 32% cases. Nevertheless on careful analysis, cantly between the two groups (1.7 2.3 vs 2.7
Athena found that these signs when occurring 0.6 days in perforated and non-perforated
exclusively in RIF indicate appendicitis rather groups respectively). From this analysis Athena
than NEC. infers that diagnostic delay did not increase the
perforation rate. Conversely, neonates with ap-
Most useful Investigation pendicular perforation were diagnosed and
treated earlier than those without it. Even in
Leukocyte count and ultrasonography (USG)
the absence of correct clinical diagnosis, perfo-
showed poor yield. Free fluid or mass in RIF
ration - as indicated by pneumoperitoneum -
(8%) demonstrated by USG are useful but not
appears to have prompted surgical exploration.
conclusive of appendicitis. On the other hand,
As a note of caution, Athena is also aware that
USG distracted the clinical attention towards
the statistics may be deceptively fallacious due
coincidental cystic lesions. Actually, a few in-
to extremely small sample size.
fants had undergone laparotomy for suspected
hydronephrosis [14] or duplication cyst [39,42] The present analysis confirms the traditional
based on the USG reporting and the correct view that infection of perforated appendix is
diagnosis turned out to be an intra-operative poorly walled off in newborn. Appendicular ab-
surprise. Sepsis screening such as C-reactive scess and mass formation were noted in only 9
protein and blood culture were positive in only (17%) infants. However, this account may be
27% of cases. misleading because in 64% of published reports
a specific description of operation finding is
Pneumoperitoneum is the single most useful
missing.
sign which was seen in 23 of the 44 (52%) pa-

Journal of Neonatal Surgery Vol. 4(1); 2015

 Neonatal Appendicitis (Part 1): A Review of 52 cases with Abdominal Manifestation

Mortality Recently Bengtsson and Houten [53] introduced

a new term neonatal appendicopathy which in-
Athena computed a disturbingly high mortality cludes primary-, secondary- and peri appendi-
of 23 per cent even in this modern era. The citis. Although Athena concurs with the au-
death rate was not affected by sex of the infant, thors on the practical difficulties of distinguish-
birth weight, gestational maturity, mode of de- ing true appendicitis from inflammation of ap-
livery or any of the individual symptoms. One pendix secondary to NEC, she is reluctant to
would expect mortality of perforated appendici- buy the authors arguments and the proposed
tis be greater than that of uncomplicated cases. terminologies. For example, periappendicitis is
Perplexingly, only 8 out of 44 neonates (18%) in fact secondary appendicitis. Inflamed appen-
with perforation died while 4 out of 7 (57%) dix in hernia sac is a unique clinical presenta-
without perforation expired. Using 2-tailed tion rather than secondary appendicitis.
Fishers exact test, Athena found the difference
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 Neonatal Appendicitis (Part 1): A Review of 52 cases with Abdominal Manifestation

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Contributed By:

V. Raveenthiran
Department of Pediatric Surgery, SRM Medical College & Hospital SRM University, Chennai, India.
E mail: [email protected]

Submitted on: 05-01-2015

Accepted on: 07-01-2015
Conflict of interest: The author is an Editor of the journal. But he did not take part in the evaluation or decision making
of this manuscript. The manuscript has been independently handled by two other editors.
Source of Support: Nil

Journal of Neonatal Surgery Vol. 4(1); 2015