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International Journal of Surgery Open 6 (2017) 5e11

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Appendicitis in pregnancy: Difficulties in diagnosis and management. Guidance

for the emergency general surgeon: A systematic review
Arkeliana Tase, MRCS *, Mohamad Fathul Aizat Kamarizan, MBBS, Keshav Swarnkar, FRCS
Department of General Surgery, Royal Gwent Hospital, Cardiff Rd, Newport, NP20 2UB, UK

a r t i c l e i n f o

Article history: 2. Method

Received 5 January 2017
Accepted 11 February 2017 The terms “appendicitis” and “pregnancy” were searched in
Available online 20 February 2017 PubMed, Medline, Embase, HMIC and Cochrane review. The search
included papers published from 2000 onwards. Article selection
was based on relevance to the aims of the study. The exclusion
criteria was papers not relevant to the study aim and not being
available in English language. Given that four different areas were
being reviewed in this study, papers were sub-divided into
different sections depending on the objective it was addressing. No
other review protocol exists. No assumptions or simplifications
were made in this review.
1. Introduction The comparison of imaging modalities was presented in terms
of their sensitivity and specificity as well as their NPV and PPV. The
Abdominal pain in pregnancy presents many challenges to the remainder of the data on surgical management methods was pre-
surgeon and obstetrician due to an altered clinical picture. This sented unchanged from their presentation on the original paper.
paper aims to review recent literature on appendicitis in pregnancy The quality of studies was evaluated by the authors on the basis of
with emphasis on diagnostic difficulties and appropriate in- the aims of the study and the level of evidence presented.
vestigations and management. Compliance with the PRISMA criteria was ensured throughout the
The rationale for the review was the conflicting information study.
regarding the management of appendicitis in pregnancy and the
challenges associated with it. 3. Results & discussion
The review looks in detail at different aspects of assessment and
management of these patients including the differences in pre- The initial literature search identified 7325 overall results. After
sentation, differential diagnoses, investigations, surgery as well as careful review, 42 papers were considered eligible for analysis
complications. based on the requirement set at the start of the study.
The paper presents the different investigation methods
including their shortcomings in confirming the diagnosis. The re- 3.1. Incidence
view looks at the advantage of different imaging modalities with
the final aim of reducing the rate of negative appendicectomies. The incidence of appendicitis in pregnancy is between 1 in 500
An important aspect of this review was the surgical manage- to 1 in 635 pregnancies per year. There is variability in the reported
ment of these patients. In particular we looked at the evidence from incidence [12,26,38]. The diagnosis is confirmed in 1 in 800 to 1 in
the literature with regards to laparoscopic surgery and its safety 1500 pregnancies [10,16,24,26,27]. It accounts for 25% of non-
and benefits. This included adjustments advised by different au- eobstetrical emergencies and is the most common cause of
thors in order to ensure safety and reduce the risk of foetal and abdominal pain requiring surgery during pregnancy [1,4].
maternal complications. The incidence is less compared to non-pregnant women and
greatest in the second trimester of pregnancy (30%, 45% and 25% in
1st, 2nd and 3rd trimester respectively) [19,24,26,37,40,41]. Re-
* Corresponding author. Permanent address: 10 Oliver Court, Ley Farm Close,
Watford, WD25 9BL, UK.
ported possible predictive factors are age over 35 (OR 1.92, 95% CI
E-mail addresses: (A. Tase), 1.65e2.23, p < 0.001) and BMI greater than 30 (OR 1.95, 95% CI
(M.F.A. Kamarizan), (K. Swarnkar). 1.48e2.57, p < 0.001) [2].
2405-8572/© 2017 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://
6 A. Tase et al. / International Journal of Surgery Open 6 (2017) 5e11

3.2. Presentation trimester accordingly. All patients presented with abdominal pain
(60.9% in RIF, 13% in RUQ) [16]. Another study also reported highest
Patients commonly present with right lower quadrant pain on incidence in second trimester with 51.7% (n ¼ 15) of cases pre-
all stages of pregnancy. The increase in uterine volume in the third senting with RIF pain. In this study, all patients in third trimester
trimester can result in migration of the appendix a few cm caudally. and 50% of patients in second trimester showed cephalic distribu-
This may lead to pain shifting to right flank or upper quadrant tion of pain in right flank [23].
[1,10,19,26]. The appendix displacement stops contact with omen-
tum which results in higher rates of peritonitis especially in the
3.3. Differential diagnosis
third trimester [1,26]. This is due to foetal membranes not able to
block the inflammatory process. Reluctance to operate may also
In all pregnant women with lower abdominal pain, ectopic
affect rates of peritonitis [26].
pregnancy should be ruled out. Nausea and vomiting of pregnancy
Recent studies (Table 1) describe pain in right lower quadrant as
is not associated with abdominal pain. Round ligament pain is not
the most common presenting symptom (86%e100%, 80%e85% and
progressive or associated with other symptoms [26]. Other
60%e85% on 1st, 2nd and 3rd trimester accordingly) [24,31,41]. A
gynaecological differentials are ovarian torsion and fibroid degen-
typical picture is however only present in 50e60% of cases and
eration [8,16,41].
right lower quadrant pain is also the most common symptom in
Pyelonephritis is more common during pregnancy [23]. Renal
non-appendicitis pain [4,24].
stones and hydronephrosis may be present in patients with a
In addition, pregnancy is associated with physiological leuco-
previous history [8]. Pre-eclampsia and HELLP syndrome in the 2nd
cytosis (16 900 cells/mL in 3rd trimester). Thus, biochemical find-
trimester are associated with nausea, vomiting, RUQ, epigastric
ings are unreliable [10,19,26]. Nausea, vomiting and anorexia are
pain and hypertension but rarely fever [26,41].
common and indistinguishable from pregnancy related symptoms
Premature detachment of placenta and uterine rupture present
with lower abdominal pain, vaginal bleeding, changes in foetal
Terzi A et al. (2010) reported that 17.3% (n ¼ 8), 56.5% (n ¼ 26)
heart rate and uterine stiffness differing them from appendicitis
and 26% (n ¼ 12) presented with appendicitis in 1st, 2nd and 3rd

Table 1
Baseline characteristics of study group.

Reference Year No of patients Pain location Trimester No of women Perforation

1st 2nd 3rd Open Laparoscopic

Abbasi N et al. [1] 2014 7114 OD 2.0 OD 0.5 20.3%

48.1% 46.1% OR 1.3
Brown JJS et al. [4] 2008 450 RLQ PPV 61.7
PPV% 58.1, NPV% 36.6 NPV 49.6
PPV% 61.8, NPV% 43.2
Flexer S M et al. [10] 2014 38 articles
Jung SJ et al. [16] 2012 25 RLQ -68% 40% 56% 4% 84% (n ¼ 21) 16% (n ¼ 4)
Periumbilical e 28%
RUQ e 4%
Mourad J et al. [24] 2000 67 RLQ 25% 40% 34% 12%
n1 ¼ 12. n2 ¼ 15, n3 ¼ 11
Sharma A K et al. [31] 2012 15 RLQ 20% 40% 40% 13% (n ¼ 2)
n1 ¼ 2 (100%) (n ¼ 2) (n ¼ 6) (n ¼ 6)
n2 ¼ 4 (80%)
n3 ¼ 3 (60%)
Neto A H F et al. [25] 2014 68 articles RLQ ¼ 75% 14-43%
RUQ ¼ 20%
Wei P L et al. [37] 2012 908 n ¼ 780 n ¼ 85 n ¼ 43
Wilasrusmee C et al. 2012 3415 n ¼ 2816 n ¼ 599
[38] (11 studies)
Zingone F et al. [42] 2015 362,219 n ¼ 60 n ¼ 80 n ¼ 42
(156 during
88 post partum)
Miloudi N et al. [23] 2012 29 RLQ en ¼ 24 32% 42% 26% n ¼ 11 n ¼ 18 (n ¼ 2 n¼5
n1 ¼ 7, n2 ¼ 15, n3 ¼ 7 n1 ¼ 2, n2 ¼ 4, n3 ¼ 5 converted)
n1 ¼ 4, n2 ¼ 11, n3 ¼ 1
Ito K et al. [15] 2012 87 n ¼ 29 n ¼ 47 n ¼ 11
Terzi A et al. [33] 2010 46 RLQ (n ¼ 28) 17.3% 56.5% 26%
RUQ (n ¼ 6)
Generalized (n ¼ 5)
Kazim S F et al. [18] 2009 38 RLQ (n ¼ 33) 86.8% 30% 37% 34% 97% (n ¼ 37) 16% (n ¼ 6)
RUQ (n ¼ 2) 5.3%
Generalized (n ¼ 3) 7.9%
Machado N O et al. [20] 2009 26 RLQ (n ¼ 14) n¼6 n ¼ 20
Rt flank (n ¼ 2)
Central (n ¼ 4)
Peled Y et al. [28] 2014 85 69% (n ¼ 59) 31% (n ¼ 26) n ¼ 11
Peled Y et al. [28] 2014 85 69% (n ¼ 59) 31% (n ¼ 26) n ¼ 11

*. n1 ¼ number on first trimester, n2 ¼ number on second trimester, n3 ¼ number on third trimester.

A. Tase et al. / International Journal of Surgery Open 6 (2017) 5e11 7

Lastly, uterine vein thrombophlebitis post partum presents with levels of positive and negative predictive values reported are 88.2%
right lower abdominal pain if the right vein is affected [26]. and 100% respectively. This varies between studies and affected by
gestational age [8,21]. The rate of indeterminate findings is 88e97%
3.4. Investigations in women above 16 weeks gestation [10]. Other studies have re-
ported non diagnostic findings in 63% and confirmed appendicitis
The investigation is both biochemical and radiological. in 34% of cases. It has a sensitivity of 20% and specificity of 100%
3.4.1. Biochemical The American College of Radiology criteria, recommends graded
White cell count and C-reactive protein levels are physiologi- compression USS as the initial imaging in first and second trimester
cally raised with increasing gestational age thus findings are non- of pregnancy. In indeterminate cases, MRI is the next imaging
diagnostic [19,22,33,40]. Some authors propose that these param- modality. MRI has the advantage of identifying other diagnoses in
eters in conjunction with lymphocyte count, neutrophil to the absence of ionising radiation [7,8,10,26,39]. Oral contrast using
lymphocyte ratio and platelet to lymphocyte ratio are useful in gadolinium is not advised as it crosses the placenta with unknown
diagnosis with a high sensitivity and specificity [37,40]. consequences to the foetus [8]. MRI scan has a NPV of 97%e100%
New markers such as IL-1 and IL10, bilirubin, procalcitonin and and a PPV of 98.7%e100%. Late stages of pregnancy present chal-
calprotectin are being studied for their diagnostic accuracy [21]. lenges to interpretation of MRI scans [8,14]. It has a sensitivity of
90e100% and a specificity of 94e98% in identifying appendicitis
3.4.2. Radiological [8,10]. It is associated with a 0e7% rate of negative laparotomy and
In pregnancy, USS and MRI are most commonly used. Use of CT 8% perforation rate [8,9].
scanning is also reported with limited usage due to associated ra- CT is indicated if MRI is contraindicated due to pacemaker or
diation. Imaging is critical in reducing the rate of negative appen- other non-compatible devices and USS scan in non-diagnostic
dicectomy [16]. Table 2 shows a breakdown of the imaging [8,39]. Whilst very reliable in diagnosing appendicitis, the effects
modalities as discussed in different studies. of radiation exposure to the foetus are linked with double the risks
USS is easily accessible but has variable accuracy. The highest of development of childhood cancers [10]. If considering its use, it

Table 2
Advised Investigations on individual studies and their effectiveness.

Reference Year No of patients Primary USS MRI CT Comments


Neto A H F et al [26] 2014 68 articles USS Sensitivity 67 Sensitivity 91% Sensitivity 85.7% CT indicated when
e100% (95% CI 54e99%) (95% CI 63.7e96%) MRI is inconclusive
Specificity 86e96% Specificity 98% (95% Specificity 97.4% or unavailable
CI 87e99%) (95% CI 86.2-99.9%)
Yan J et al [39] 2012 1 USS Graduated Useful in
compression differentiating
technique between
appendicitis and
other differentials
Israel G M et al [14] 2008 33 USS followed 1/5 confirmed 4/5 confirmed MRI able to suggest
n¼5 by MRI 2/5 indeterminate 1/5 indeterminate alternative
confirmed 1/0 negative USS diagnoses
Dewhurst C et al [8] 2013 56 papers NPV of non Sensitivity 90 MRI preferred in
visualised appendix e100% 2nd and 3rd
90% Specificity 94e98% trimesters
2% of appendix A normal appendix
visualised on MRI excludes
Burke L M B et al [5] 2015 709 MRI 49.5% of pts had Sensitivity 96.8%
USS Specificity 99.2%
90.6% non NPV 99.5%, PPV
diagnostic 92.4%
Flexer S M et al [10] 2014 38 papers USS followed 7e96% Sensitivity 50e95% 8% negative
by MRI indeterminate Specificity 93 appendicectomy
findings e100% rate
Radiation linked to
doubled risk of
childhood cancer
Negoi I e al [25] 2015 8 USS 75% identified Advised in
appendicitis (n ¼ 6) indeterminate
cases but not used
Ito K et al [15] 2012 87 USS then CT 24% identified Not used Used in 20%
appendicitis Correct diagnosis in
(n ¼ 21) 66.7%
Terzi A et al [33] 2010 46 Uss Sensitivity 37.5%
Specificity 66.66%
PPV 88.23%, NPV
Kazim S F et al [18] 2009 38 Uss Identified
appendicitis in
n¼15 (39.5%)
8 A. Tase et al. / International Journal of Surgery Open 6 (2017) 5e11

needs to be thoroughly discussed with the patient. experience and operative findings. They concluded that laparos-
Early exploration prior to imaging has been challenged due to a copy is safe even in the third trimester of pregnancy [32].
higher negative appendicectomy rate in pregnant patients (36% vs
14%, p < 0.001). In up to 87% of cases no cause for the pain is found 3.5.2. Laparotomy/open appendicectomy
[15]. Laparotomy is a well established approach. Studies have shown
that it is twice more common in pregnancy compared to non-
3.5. Management pregnant women (p < 0.001) [1]. The advice is a transverse inci-
sion through McBurney's point or through the point of maximum
There is little evidence on safety of medical management of tenderness. In unclear cases, a lower midline incision is recom-
appendicitis. It is not advisable in pregnancy due to poor outcomes mended through which a caesarean section can also be carried out.
and complications. One study showed greater rates of septic shock, The surgical approach used depends on the patient's physical status
venous thromboembolism and peritonitis after conservative man- especially their BMI, gestational age and the choice of the on call
agement [1,10,13,20]. The risk of foetal loss is increased to 36% in surgeon as guided by their experience [23].
perforated vs 1.5% in non-perforated cases [13].
Surgical options include open and laparoscopic approach. 3.6. Complications
Complication rates are related to the underlying diagnosis and
maternal factors rather than surgical approach [30]. Table 3 gives a 3.6.1. Foetal complications
breakdown of the reviewed evidence. Appendicitis in pregnancy is related to babies with lower birth
weight and small for gestational age. This is more common in 1st
3.5.1. Laparoscopy and 2nd trimesters whilst preterm labour is more common in the
The outcomes of laparoscopy during pregnancy vary signifi- 1st and 3rd trimesters. Congenital anomalies can occur in the 1st
cantly between different studies. Most recent studies show no trimester and surgery in 3rd trimester is associated with early
difference between it and the open approach. Some authors report delivery [10,16,37].
a higher incidence of preterm delivery (<37 weeks gestation) and a Risk of foetal loss is between 3 and 15% in women with
higher rate of foetal loss (6% vs 3% with open surgery) with lapa- complicated appendicitis in their 1st trimester. This can be as high
roscopy [1]. as 20e37% and associated with a delivery rate of 15e45%
Main concerns with laparoscopy in pregnancy are foetal acidosis [34,35,38].
and issues with maternal ventilation. Maximum CO2 pressures of Cases of delayed diagnosis are associated with foetal mortality
12 mmHg are recommended. In addition, trocar location should be of up to 35e55% in patients with perforated appendix compared to
based on location of the gravid uterus. TED stockings and flowtrons 1.5% in noneperforated cases [8,17]. Long term data on this is
should be used both pre and post operatively. A left lateral tilt of however limited [26].
15e30 is suggested to reduce pressure on the inferior vena cava McGory ML et al. (2007) found a higher rate of negative ap-
and aorta. These modifications can minimise the reduction of blood pendicectomy in pregnant women (23% vs 18%, p < 0.05). (Table 4
flow to the uterus thus reduce foetal hypoxia and risk of premature shows the rates of negative appendicectomy reported in the liter-
labour [9,10]. Some authors advice diagnostic laparoscopy if diag- ature). The study showed that laparoscopy had a higher rate of
nosis is unclear with conversion to open in the third trimester [10]. foetal loss compared to open appendicectomy (odds ratio 2.31)
Other modifications suggested are avoidance of cervix instru- [22]. Pre-term labour is highest in the first week following surgery
mentation, use of open techniques or use of a Hasson technique for which suggests that both appendicitis and surgical complications
the first port [20,26]. One study reported insertion of a 10 mm first lead to preterm contractions [25,41].
port just below the xiphoid with other ports inserted under direct
vision. The authors concluded that laparoscopy is safe in the third 3.6.2. Maternal complications
trimester if adjustments are made to the technique [9]. Incidence of perforation of appendix is 20.3%e43% (16,1%e19%
Machado NO et al. (2009) suggested placing the initial port in in the general population) in pregnancy. It is highest in the third
the midline approximately 2 cm above the superior level of the trimester and gives rise to pelvic collections, wound infection and
uterus followed by two other ports in left lower and right upper sepsis [15,20,38,41]. This risk increases with gestational age and
quadrant. This could be used in all trimesters of pregnancy with rates of perforation are 8.7%, 12.5% and 26.1% for each trimester
lower rates of intraoperative complications. The rate of foetal loss respectively [1,10,27] Multivariate analyses showed that abscess
was almost 6% which is higher than after open appendicectomy development is related to diagnosis rather than surgical approach
[20]. A systematic review of 25 studies compared open to lapa- [29]. A delay in surgery by more than 24 h s is related to 66%
roscopy however in the absence of strong evidence, no preferred incidence of perforation [20]. Other complications are ileus and
surgical approach could be recommended [36]. respiratory infections [16,42].
Other studies reported a higher post-operative complication
rate following open surgery (25% vs 3.8%, p < 0.009). No statistical 4. Conclusion
significance was found in perioperative obstetric or neonatal out-
comes. The hospital stay for the laparoscopic group was higher Pregnant women with suspected appendicitis should be inves-
mainly for foetal surveillance [32]. tigated and managed without delay. A multidisciplinary approach
The American society of gastrointestinal and endoscopic sur- is to the best interest of the patient. Important differential di-
geons (SAGES) reviewed many aspects of care from multiple large agnoses should be ruled out. Imaging investigations are essential
trials [32]. Level 1 evidence from their review demonstrated that and include USS followed by MRI whilst biochemical tests are non-
laparoscopic appendicectomy offers a shorter hospital stay. The diagnostic.
difference between open and laparoscopic approaches was higher Surgical management is planned based on the surgeon's skills
wound infections in the open approach but higher deep pelvic and experience. Patient factors such as BMI, gestational age,
abscess rates after laparoscopy. Later studies however showed no trimester of pregnancy and previous abdominal surgery should be
difference between the approaches. The conversion to open surgery considered. Both open and laparoscopic approaches can be suc-
varied between 0 and 27% depending on the surgeon's decision, cessful in the right hands. Modifications to the laparoscopic
A. Tase et al. / International Journal of Surgery Open 6 (2017) 5e11 9

Table 3
Management and complications as per individual studies.

Reference Year No of Management Risk of Maternal complications Foetal complications Hospital stay
patients perforation/
Surgery Conservative

Negoi I e al [25] 2015 8 100% performed Not advised Nil nil

Flexer S M et al. [10] 2014 38 Treatment- surgical Not advised
papers Open or
Equally advised
Neto A H F et al. [26] 2014 68 If diagnosis certain Not advised 14-43% Risk of foetal loss 1.5%
articles e laparotomy (36% in perforated cases)
If diagnosis Premature delivery 4%
uncertain e (11% perforated cases)
laparoscopy with
Abbasi N et al. [1] 2014 7114 Open e 48.1%, OD 5.8% 20.3% Ileus 5.3% Post op stay >3 days
2.0 (95% CI 1.9e2.1) (n ¼ 413) Conservative Pneumonia 1.1% (2.6% with 45.5%
Laparoscopic e 28.8% peritonitis) 82.4% in peritonitis
46.1%, OD 0.5 (95% Open - 19.8% Haemorrhage/haematoma
CI 0.5e0.5) 0.2% (0.2% with peritonitis)
Venous thromboembolism
0.4% (0.6% with peritonitis)
Jung SJ et al. [16] 2012 25 Open 84% (n ¼ 21) Not advised Wound infection ¼ 2 (open) Spontaneous abortion Open (mean 6.7 days)
Laparoscopic 16% n ¼ 0 (Lap) n¼1 Lap (mean 3.8days)
(n ¼ 4)
Wei P L et al. [37] 2012 908 5.8% (n ¼ 53) Low birth weight 12%
Preterm birth 11.6%
Small for gestational age
Miloudi N et al. [23] 2012 29 Open 38% (n ¼ 11) Not 17% (n ¼ 5)
Laparoscopic 55.2% practiced
(n ¼ 16)
Converted to open
6.8% (n ¼ 2)
Sadot E et al. [30] 2009 65 Open 26% (n ¼ 17) Not advised Nil No difference between Open 4.2 days
Laparoscopic 74% open and lap on foetal Lap 3.4 days
(n ¼ 48) outcome (p ¼ 0.001)
1st trimester e
100% laparoscopic
(p < 0.001)
2nd trimester e
73% lap, 27% open
3rd trimester e 71%
lap, 29% open
Abbasi N et al. [2] 2014 1203 Open 60.3% 9.1% 27% Antepartum haemorrhage Pre-term delivery
Laparoscopically n ¼ 10 (0.83%) n ¼ 213 (17.71%)
30.7% Abruption placentae n ¼ 26 Intrauterine death
(2.16%) n ¼ 12 (1%)
Zainuddin Z R B et al. 2014 31 Perforated appendix risk e Foetal loss risk 1.5e9%
[41] papers up to 43% Consequences of
Wilasrumee C et al. 2012 3415 Open (n ¼ 2816) None Wound infection e RR 0.91 Preterm labour RR 1.4
[38] 11 Laparoscopic (0.12e7.18) (0.68e3.06)
studies (n ¼ 599) Foetal loss RR 1.91 (1.31
Pastore P A et al. 2006 2 N ¼ 1 foetal loss 7 days
[27] post laparotomy
MCGory M L et al. 2007 3133 Negative appendicectomy Non complicated
[22] rate 23% appendicitis
Foetal loss 2% p < 0.05
Early delivery 4%
p < 0.05
Complicated appendicitis
Foetal loss 6% p < 0.05
Early delivery % p < 0.05
Ito K et al. [15] 2012 87 Wound infection n ¼ 2 Foetal loss n ¼ 3 Non perforated 3 days
Abscess n ¼ 1 [1e11]
Bowel obstruction n ¼ 1 Perforated 4 days [2
DVT/PE n ¼ 1 e12]
Terzi A et al. [33] 2010 46 Wound infection n ¼ 50 Pre-term delivery n ¼ 1
Kazim S F et al. [18] 2009 38 Open (n ¼ 37) 97% Wound infection (n ¼ 3) 8% Pre-term delivery n ¼ 3
Intraabdominal abscess (8%)
(n ¼ 1) 3% Foetal loss n ¼ /1
PE (n ¼ 2)

OR ¼ odds ratio, RR ¼ relative risk.

10 A. Tase et al. / International Journal of Surgery Open 6 (2017) 5e11

Table 4
Negative appendicectomy rate.

Reference Year of publication Rate of negative appendicectomy

Machado N O et al. [20] 2009 19.2% (n ¼ 5)

Ito K et al. [15] 2012 36%
Zingone F et al. [42] 2015 n1 ¼ 17.4%, n2 ¼ 26.2%, n3 ¼ 7.1%
Wilasrusmee C et al. [38] 2012 12-24%
Neto A H F et al. [26] 2015 20-35%
Sharma A K et al. [31] 2012 20% (n ¼ 3)
Mourad J et al. [24] 2000 33%, (n1 ¼ 3, n2 ¼ 5, n3 ¼ 7)

n1 ¼ Number on 1st trimester, n2 ¼ Number on 2nd trimester, n3 ¼ Number on 3rd trimester.

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