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Clinical Features, Predictive Markers and Maternal Fetal Outcomes in an Analysis of Acute Pancreatitis in Pregnancy: A Retrospective Multicenter Study

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Clinical and Experimental Obstetrics & Gynecology
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Background Acute pancreatitis in pregnancy (APIP) is a rare but life-threatening complication for both mother and fetus. The purpose of this study was to describe the etiology, clinical indices, early predictive markers and maternal fetal outcomes of APIP. Methods We retrospectively reviewed 52 APIP cases treated at the 5 tertiary care centers from January 2017 to December 2021 in Guangdong, China. We analyzed the etiology, vital signs, laboratory indices, predictive markers and long-term outcomes of APIP. Results The most common causes of APIP were hypertriglyceridemia (36.5%) and biliary disease (26.9%). Heart rate (HR), white blood cell count, the percentage of blood neutrophils, serum glucose and triglycerides were correlated with the severity of APIP. The ability of HR to predict severe acute pancreatitis (SAP) was highest. There were no maternal deaths reported. The overall fetal mortality rate was 7.7% and 62.5% experienced neonatal asphyxia in SAP. Apgar scores among newborns of mild acute pancreatitis (MAP) were not different. Conclusions The most frequent cause of APIP has changed and hypertriglyceridemia was the most common cause of APIP. The initial HR recorded after admission might be the new predictor of SAP. The severity of APIP was associated with higher risk of neonatal asphyxia. For MAP patients, conservative treatment was also desirable.
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Clin. Exp. Obstet. Gynecol. 2024; 51(12): 275
https://doi.org/10.31083/j.ceog5112275
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Original Research
Clinical Features, Predictive Markers and Maternal Fetal Outcomes in
an Analysis of Acute Pancreatitis in Pregnancy: A Retrospective
Multicenter Study
Jiarong Lun1, Ruirui Li2, Zhongjun Li3, Yuting Ye4, Di Qiu5, Fang He2,* , Jin Jin1,*
1Department of Obstetrics, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, Guangdong, China
2Department of Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, 510140 Guangzhou, Guangdong, China
3Department of Obstetrics, Dongguan People’s Hospital Affiliated to Southern Medical University and Dongguan Key Laboratory of Major Diseases in
Obstetrics and Gynecology, 523058 Dongguan, Guangdong, China
4Department of Obstetrics, Second Clinical Medical College of Jinan University, 518020 Shenzhen, Guangdong, China
5Department of Obstetrics, The First Affiliated Hospital of Jinan University, 510630 Guangzhou, Guangdong, China
*Correspondence: hefangjnu@126.com (Fang He); luckyjinj@163.com (Jin Jin)
Academic Editor: Michael H. Dahan
Submitted: 26 June 2024 Revised: 8 August 2024 Accepted: 2 September 2024 Published: 23 December 2024
Abstract
Background: Acute pancreatitis in pregnancy (APIP) is a rare but life-threatening complication for both mother and fetus. The purpose
of this study was to describe the etiology, clinical indices, early predictive markers and maternal fetal outcomes of APIP. Methods:
We retrospectively reviewed 52 APIP cases treated at the 5 tertiary care centers from January 2017 to December 2021 in Guangdong,
China. We analyzed the etiology, vital signs, laboratory indices, predictive markers and long-term outcomes of APIP. Results: The most
common causes of APIP were hypertriglyceridemia (36.5%) and biliary disease (26.9%). Heart rate (HR), white blood cell count, the
percentage of blood neutrophils, serum glucose and triglycerides were correlated with the severity of APIP. The ability of HR to predict
severe acute pancreatitis (SAP) was highest. There were no maternal deaths reported. The overall fetal mortality rate was 7.7% and 62.5%
experienced neonatal asphyxia in SAP. Apgar scores among newborns of mild acute pancreatitis (MAP) were not different. Conclusions:
The most frequent cause of APIP has changed and hypertriglyceridemia was the most common cause of APIP. The initial HR recorded
after admission might be the new predictor of SAP. The severity of APIP was associated with higher risk of neonatal asphyxia. For MAP
patients, conservative treatment was also desirable.
Keywords: acute pancreatitis in pregnancy; clinical predictors; etiology; long-term prognosis
1. Introduction
Acute pancreatitis in pregnancy (APIP) is a life-
threatening complication affecting both mother and fetus,
with an incidence of approximately 1 in 1000–10,000 preg-
nancies [1]. Due to its atypical presentations and rapid clin-
ical changes, APIP is easily misdiagnosed and missed by
clinicians, resulting in serious adverse maternal and neona-
tal outcomes. Over the past decades, the APIP-associated
mortality rate was high for the mother and fetus, reaching
20% and 50%, respectively [2,3]. As a consequence of ad-
vances in medical knowledge and technology and progress
in neonatal intensive care, recent study has reported a de-
cline in maternal and fetal mortality [4].
Until recently, most APIP studies involved small,
single-center investigations with a long reference time-
period [5,6 as such, conclusions may not be generaliz-
able to all patients and all areas. Some larger scale stud-
ies have been recently published to describe the clinical
features, predictive indicators and pregnancy outcomes of
APIP, which provides solid data for further research [79],
although some of these studies focused on only one aspect
of the disease with the data spanning a period of ten years.
In this study, we conducted a retrospective review of 52
cases of APIP treated at 5 tertiary care centers in Guang-
dong, China, from January 2017 to December 2021. All
are specialist centers for critical maternal treatment, and
preferentially receive referrals from surrounding hospitals,
making them ideal sources for collecting data on APIP pa-
tients. Our aim was to describe and update the current data
regarding the etiology, clinical features and maternal fetal
outcomes of APIP. Additionally, we sought to investigate
early predictive markers for severe acute pancreatitis (SAP)
and long-term pregnancy outcomes.
2. Materials and Methods
2.1 Patients and Clinical Data
This research was conducted as a retrospective, cross-
sectional, multicenter study involving patients hospitalized
with APIP in Guangdong Province, China: Nanfang Hos-
pital, Southern Medical University, The Third Affiliated
Hospital of Guangzhou Medical University, The First Af-
filiated Hospital of Jinan University, Dongguan People’s
Hospital, and Shenzhen People’s Hospital. Four other hos-
pitals agreed to be involved in study. We utilized data of
Fig. 1. The flow chart of the study. APIP, acute pancreatitis in pregnancy.
pregnant patients attending the hospitals from January 2017
to December 2021. The criterion for inclusion was acute
pancreatitis diagnosed during pregnancy. Patients meeting
the following criteria were excluded: (1) readmission (only
included first-time record); (2) pregnancy was terminated
prior to admission to hospital; (3) length of more than 7 d
from APIP onset to admission; (4) serious comorbidities;
and (5) more than 5 missing data of candidate variables.
Data were collected through electronic medical
records (EMR); this included maternal age, etiology of
acute pancreatitis (AP), disease severity, gestational age at
AP onset and delivery, clinical features and complications,
diagnostic tests, maternal and fetal outcomes, vital signs,
and laboratory test data within 24 h of admission. All data
reflected the first inpatient examination following admis-
sion.
2.2 APIP Diagnosis and Definition
The classification and diagnostic criteria for APIP
were determined according to the Atlanta Criteria and Clin-
ical practice guidelines [10,11]. To diagnose acute pan-
creatitis, at least 2 of the following 3 criteria must be
met: (1) abdominal pain consistent with acute pancre-
atitis; (2) serum lipase and/or amylase at least 3 times
higher than the upper normal limit; and (3) radiological ev-
idence indicating acute pancreatitis. Mild acute pancreati-
tis (MAP) was defined as AP without organ dysfunction
or localized/generalized complications. Moderately severe
acute pancreatitis (MSAP) was defined as AP with transient
(within 48 h) organ dysfunction or localized/generalized
complications. Severe acute pancreatitis (SAP) was defined
as AP with persistent (more than 48 h) organ dysfunction
or localized/generalized complications. Organ dysfunc-
tion was assessed based on the modified Marshall score,
while local complications comprised acute peripancreatic
fluid collection, pancreatic pseudocyst, acute necrosis, and
walled-off necrosis. By etiology, APIP could be catego-
rized into acute biliary pancreatitis, hypertriglyceridemic
pancreatitis (HTGP), or other types of pancreatitis. Acute
biliary pancreatitis was diagnosed by radiological evidence
of abdominal ultrasonography, such as gallstones or sludge
in the biliary tree or the gallbladder [12]. Hypertriglyc-
eridemic pancreatitis was diagnosed with either a serum
triglyceride 11.3 mmol/L or serum triglyceride between
5.65 and 11.3 mmol/L with a lipid turbidity appearance af-
ter excluding biliary, alcohol or medication factors [11].
Trimester categorization was defined as first trimester (1–
13+6 weeks), second trimester (14–27+6 weeks), and third
trimester (from 28 weeks to delivery). Early and moder-
ately preterm birth was defined as birth at <34 weeks of
gestation but 28 completed weeks. Extremely preterm
birth was defined as birth at <28 weeks of gestation. Fetal
loss included spontaneous or induced abortion, intrauterine
fetal death or stillbirth. Neonatal asphyxia was defined as
an Apgar score of <8.
2.3 Statistical Analysis
We conducted all data analyzes using IBM SPSS 25.0
(IBM Corp., Armonk, NY, USA). We excluded variables
with >10% missing data. If variables had missing data ac-
counting for <10%, the missing data with normal distribu-
tion was replaced by mean and skewed distribution by me-
dian. Continuous variables that followed a normal distribu-
tion were reported as mean ±standard deviation (SD) and
differences between groups were assessed using Student’s
ttests or one-way analyses of variance. Frequencies (%)
are utilized to present categorical variables and differences
between groups were assessed using Chi-squared tests or
Fisher exact tests, as appropriate. Non-normally distributed
continuous variables are presented as median (inter-quartile
range, IQR) and were compared using non-parametric tests.
The accuracy of biomarkers to predict SAP was assessed via
receiver operating characteristic (ROC) curves. Logistic re-
gression analysis was performed to determine independent
predictors of SAP. The pvalue was compared with the area
under the curve (AUC) with 0.5, and sensitivity and speci-
ficity were computed to assess diagnostic value. pvalues
<0.05 were deemed statistically significant.
2
Table 1. General information of APIP patients by different severity.
MAP MSAP SAP pvalue
Individuals (n) 35 9 8
Age, years 31.46 ±6.31 28.78 ±4.52 28.38 ±3.96 0.250
BMI, kg/m226.45 ±3.90 27.49 ±4.70 28.43 ±3.94 0.422
Gestation weeks on admission (weeks) 31.71 (7.57) 36.43 (5.79) 31.43 (4.14) 0.056
Trimester of pregnancy on admission (n) 0.655
1st Trimester 2 0 0
2nd Trimester 7 0 1
3rd Trimester 26 9 7
Etiology (n) 0.104
Hyperlipidaemia 11 2 6
Biliary diseases 12 2 0
Others 12 5 2
Inpatient information
Hospital stay, days 10 (7) 12 (14) 16.5 (13) 0.025
Patients transferred to ICU (n) 10 4 7 0.008
Daily hospital charges, RMB (n) 0.023
<1000 6 1 1
1000–4999 23 4 1
5000–9999 5 3 4
10,000 1 1 2
Abbreviations: BMI, body mass index; ICU, intensive care unit; APIP, acute pancreatitis in pregnancy;
MAP, mild acute pancreatitis; MSAP, moderately severe acute pancreatitis; SAP, severe acute pancre-
atitis. December 31, 2021 exchange rate, 6.378 RMB = 1 US dollar (State Administration of Foreign
Exchange, China, 2021).
Fig. 2. Receiver operating characteristic (ROC) curve of clin-
ical indicators for predicting SAP. SAP, severe acute pancreati-
tis; WBC, blood cell count; Neu%, blood neutrophil percentage;
TG, triglycerides; HR, heart rate
3. Results
3.1 Demographics
During the study period, a total of 56 APIP patients
were reviewed. According to the inclusion and exclu-
sion criteria, we enrolled 52 pregnant patients in this study
(Fig. 1). The mean maternal age was 30.5 ±5.8 years. The
average height was 157.0 ±5.0 cm and the body mass in-
dex (BMI) was 26.9 ±4.0 kg/m2. The median gestational
age was 32.0 (7.0) weeks. Most patients (80.8%) were diag-
nosed with APIP in the third trimester; 8 patients had APIP
during the second trimester and 2 during the first trimester.
Hypertriglyceridemia (36.5%) and biliary diseases (26.9%)
were the most common causes of APIP. MAP occurred in
67.3%, 17.3% were MSAP, and 15.4% were SAP (Table 1).
3.2 Clinical APIP Data
We compared the clinical data according to the sever-
ity of APIP, including baseline clinical data, vital signs, in-
hospital information (duration of hospital stay, daily hospi-
talization charges), and commonly used laboratory indices
(Tables 1,2). At baseline, the 3 groups were similar in age,
BMI, gestational weeks, and etiology. Hospital length-of-
stay and daily charges showed a positive correlation with
the severity of APIP. SAP had the highest rate (87.5%) of
transfer to the intensive care unit (ICU). Heart rate (HR),
white blood cell count (WBC), blood neutrophil percentage
(Neu%), serum glucose, and triglycerides were correlated
with the severity of APIP.
3.3 Biomarker Prediction of SAP
We found that some clinical indicators were signifi-
cantly different between the 3 groups (Table 2), so we con-
3
Table 2. Clinical indices of APIP patients by different severity.
MAP (n = 35) MSAP (n = 9) SAP (n = 8) pvalue
Vital signs
SBP, mmHg 112 (11) 118 (17) 137 (37) 0.115
DBP, mmHg 74 (9) 73 (14) 69 (23) 0.958
Temp, °C 36.7 (0.4) 36.5 (0.5) 36.6 (0.7) 0.825
HR, bpm 93 ±13 92 ±14 121 ±11 <0.001
Laboratory test data
WBC, ×109/L 11.20 ±5.22 10.26 ±4.58 17.16 ±5.53 0.011
Neu% 79.9 ±11.7 74.2 ±15.0 89.9 ±2.9 0.024
HCT, L/L 0.32 ±0.03 0.33 ±0.04 0.30 ±0.04 0.107
CRP, mg/L 30.0 (49.1) 39.1 (152.3) 123.4 (199.9) 0.100
K, mmol/L 3.77 ±0.41 3.67 ±0.22 3.76 ±0.49 0.799
Ca, mmol/L 2.12 ±0.14 2.15 ±0.13 2.07 ±0.19 0.556
Glu, mmol/L 5.70 (2.83) 5.40 (2.43) 8.70 (5.26) 0.016
Amylase, U/L 161.1 (218.8) 122.0 (544.9) 89.8 (382.0) 0.577
ALT, U/L 14.9 (16.8) 7.3 (9.7) 9.6 (7.8) 0.220
AST, U/L 19.4 (17.5) 19.9 (16.1) 21.5 (13.5) 0.993
ALB, g/L 31.7 ±4.2 32.7 ±3.2 30.2 ±3.3 0.433
TBil, µmol/L 10.81 (9.70) 9.66 (11.10) 7.86 (10.70) 0.648
DBil, µmol/L 3.85 (6.08) 5.37 (6.10) 4.99 (6.64) 0.515
Cr, µmol/L 44.4 ±15.7 46.9 ±8.7 36.2 ±11.3 0.261
TG, mmol/L 2.33 (4.80) 3.07 (3.30) 15.48 (41.12) 0.016
TC, mmol/L 5.70 (4.09) 6.19 (4.94) 11.57 (20.07) 0.087
Abbreviations: SBP, systolic pressure; DBP, diastolic pressure; HR, heart rate; WBC,
white blood cell count; Neu%, blood neutrophil percentage; HCT, hematocrit; CRP, C-
reactive protein; K, serum potassium; Ca, total calcium; Glu, serum glucose; ALT, ala-
nine aminotransferase; AST, aspartate aminotransferase; ALB, seralbumin; TBil, total
bilirubin; DBil, direct bilirubin; Cr, creatinine; TG, triglycerides; TC, total cholesterol.
Table 3. Clinical indicators for predicting SAP.
Variables AUC 95% CI pvalue Cut-off Sensitivity Specificity
WBC 0.813 0.646–0.979 0.005 12.65 0.875 0.750
Neu% 0.824 0.705–0.943 0.004 87.65 0.875 0.723
Glucose 0.820 0.657–0.983 0.004 6.395 0.875 0.705
TG 0.827 0.707–0.946 0.004 3.88 1.000 0.614
HR 0.950 0.882–1.000 <0.001 112 0.875 0.932
Abbreviations: AUC, area under the receiver operating characteristic curve; 95% CI,
95% confidence interval.
structed receiver operating characteristic (ROC) curves to
compare the values of the indicators to predict SAP and
identify cut-off values (Fig. 2). The area under the curve
(AUC) and the optimal cut-off values are summarized in
Table 3. HR had the greatest ability to predict SAP (AUC
= 0.950, p<0.001). In order to further explore the clinical
significance of these indicators, logistic regression analysis
was performed. As shown in Table 4, univariate analysis re-
vealed that all 5 indicators were related to SAP. However,
adjusted for other variables except themselves, only HR
(odds ratio (OR) = 1.274, 95% confidence interval (95%
CI): 1.024–1.585, p= 0.030) was the independent factor
for predicting SAP by multivariate analysis.
3.4 Maternal and Fetal Outcomes
As shown in Table 5, the overall fetal mortality rate
was 7.7% (4/52). Four fetal losses were all in MAP; 3 in-
volved induced abortion due to concerns about the disease
or medications affecting pregnancy and 1 experienced an
intrauterine demise of unknown origin (the woman only ac-
cepted the test for therapeutic purposes). Early and moder-
ately preterm births occurred in 26.9% (14/52) and 1.9%
(1/52) were extremely preterm births (at 27.9 weeks). Of
all live births, 7 newborns were diagnosed with neonatal
asphyxia. Thirteen patients with MAP were able to con-
tinue with their pregnancy on discharge. Further-more, we
followed up 6 long-term outcomes of the 13 patients from
their EMR. The median gestational age of these 6 women
4
Table 4. Logistic regression analysis of clinical indicators for predicting SAP.
Variables Univariate analysis Multivariate analysis
Coefficient pvalue OR (95% CI) Coefficient pvalue OR (95% CI)
WBC 0.192 0.010 1.212(1.047–1.403) –0.114 0.495 0.892 (0.644–1.237)
Neu% 0.201 0.041 1.222 (1.008–1.481) 0.396 0.254 1.486 (0.752–2.934)
Glucose 0.426 0.010 1.531 (1.109–2.114) 0.264 0.556 1.303 (0.541–3.138)
TG 0.038 0.030 1.039 (1.004–1.075) 0.036 0.441 1.037 (0.946–1.137)
HR 0.202 0.004 1.224 (1.068–1.402) 0.242 0.030 1.274 (1.024–1.585)
Abbreviations: OR, odds ratio; 95% CI, 95% confidence interval.
Table 5. Maternal fetal outcomes by different severity.
Total number, n (%) MAP (n = 35) MSAP (n = 9) SAP (n = 8)
Continued pregnancy 13 (37.1%) 0 (0.0%) 0 (0.0%)
Total life birth 18 (51.4%) 9 (100.0%) 8 (100.0%)
Cesarean birth 15 (42.9%) 9 (100.0%) 8 (100.0%)
Vaginal birth 3 (8.6%) 0 (0.0%) 0 (0.0%)
Early and moderately preterm birth 6 (17.1%) 3 (33.3%) 5 (62.5%)
Extremely preterm birth 0 (0.0%) 0 (0.0%) 1 (12.5%)
Total fetal loss 4 (11.5%) 0 (0.0%) 0 (0.0%)
Spontaneous abortion 0 (0.0%) 0 (0.0%) 0 (0.0%)
Artificial abortion 3 (8.6%) 0 (0.0%) 0 (0.0%)
Intrauterine fetal death 1 (2.9%) 0 (0.0%) 0 (0.0%)
Stillbirth 0 (0.0%) 0 (0.0%) 0 (0.0%)
Neonatal asphyxia 1 (2.9%) 1 (11.1%) 5 (62.5%)
Table 6. Apgar score of living neonates in MAP.
Number Apgar
1 min 5 min 10 min
Group A 18 10 (2.0) 10 (0.0) 10 (0.0)
Group B 6 9 (0.0) 9 (1.0) 10 (0.0)
pvalue - 0.454 0.177 0.871
Group A: the newborns in MAP who were delivered during
admission due to APIP; Group B: the 6 newborns in a con-
tinuing pregnancy.
was 39.7 (7.7) weeks. We defined the newborns in MAP
who were delivered during admission due to APIP as group
A, and the 6 newborns in a continuing pregnancy as group
B. There was no statistical difference in Apgar scores be-
tween the two newborn groups (Table 6).
4. Discussion
APIP is a rare type of acute pancreatitis and remains
a challenging clinical problem. Maternal physiological
changes that occur during pregnancy make the condition
more complicated. In our retrospective study, we analyzed
52 APIP cases from Guangdong Province, China admitted
from 2017 to 2021. We aimed to provide an update of clini-
cal disease features and to identify the best predictors for the
severity of APIP. The majority of APIP (81.25%) occurred
in the third trimester, which is also consistent with previ-
ous studies [7,13]. In addition, the incidence of MSAP and
SAP increased during the third trimester, indicating that the
incidence and severity of APIP increased as the pregnancy
progressed.
In our study, the most frequent cause of APIP was
hyperlipidaemia, followed by biliary disease. During nor-
mal pregnancy, multiple changes in the levels of hormones
during pregnancy cause adaptive changes in carbohydrate
and lipid metabolism. In women with an altered lipopro-
tein metabolism, these changes cause marked hypertriglyc-
eridemia [1,14]. Additionally, in the context of hyperlipi-
demia, a physiologic hypercoagulable state during preg-
nancy and fat emboli in the pancreatic vessels may com-
bine to impair pancreatic microcirculation, in turn leading
to pancreatic damage and acute pancreatitis [15]. However,
in China, hyperlipidemia is not the leading cause of APIP.
According to the findings of a previous meta-analysis con-
ducted by investigators from our hospital [16], the most
common cause of APIP was biliary disease. This changed
after 2009, with more pregnancy-associated hypertriglyc-
eridemic pancreatitis being reported and hyperlipidaemia
has become the main trigger of APIP, with a rate of 37%.
These changes may stem from the rapid growth of the Chi-
nese economy, improved living standards, and changes in
diet during pregnancy. Marked changes in the etiology of
APIP have also been reported in studies from different re-
gions around the world [4,1725] (Table 7, Ref. [4,16
25]), suggesting that ethnic or environmental factors might
affect the pathogenesis of APIP. It is commonly accepted
that biliary disease is the most common etiology for APIP
5
Table 7. Etiologies of APIP from different regions.
Area Etiologies
Biliary disease
(%)
Hyperlipidemia
(%)
Asia
China [16] 33.00 37.00
India [1719] 53.80 19.20
South Korea [25] 0.00 100.00
America
The United State [4] 88.00 0.00
Canada [20] 65.80 0.91
French Guiana [21] 40.00 -1
Europe
Italy [22] 38.20 -2
Spain [23] 84.20 5.30
Turkey [24] 54.50 33.30
1missing data, blood lipid profiles were not examined in study.
2missing data, only acute biliary pancreatitis was provided in
study.
in Europe, North America, and India [24,26,27]. During
pregnancy, elevated progesterone levels can alter gallblad-
der motility, leading to bile stasis. Additionally, high es-
trogen levels can modify the composition of bile, making it
more lithogenic. These changes may increase the risk of de-
veloping AP [22,28]. However, hyperlipidemia is the ma-
jor causal factor in East Asian countries such as China and
South Korea. One reason for this phenomenon may stem
from a lower prevalence of gallstones in Asian countries
compared to western countries [24,27]. In addition, there
are recognized ethnic differences in the levels of baseline
triglycerides; these are highest in East Asians, followed by
Caucasians, and lowest in South Asians and African Amer-
icans [29]. However, we also observed from Table 7that
APIP etiologies differ between countries and regions on the
same continent, even in the context of similar geographical
and racial factors. As such, lifestyle factors such as diet
may play a critical role in the pathogenesis of APIP.
As demonstrated in our study, SAP mostly occurred
during the second and third trimesters and was associated
with a high proportion of adverse maternal-fetal outcomes.
Other studies also support the link between APIP sever-
ity and higher risks of poor maternal and fetal outcomes
[5,7,30]. Approximately 5–10% of acute pancreatitis pa-
tients will develop severe acute pancreatitis in the general
population in China [11], while there was 15.4% SAP in
pregnant patients in our study. We also found a significant
positive correlation between disease severity, daily health-
care costs and the duration of stay in the hospital. SAP
showed the highest rate of transfer to the ICU. Thus, SAP
imparted significant financial strains on the family and in-
creased healthcare burdens on an already stressed health
system. We suggest the following possible reasons for the
adverse effects of SAP. There is an inevitable delay in di-
agnosis, particularly in patients with SAP compared with
those with MAP [30]. The most common initial symptoms
of APIP, such as epigastric pain, nausea, and vomiting dur-
ing mid to late gestation are likely to be ascribed to the
pregnancy, leading to misdiagnoses and delayed treatments
[5,31]. SAP requires significant medical resources, thus in-
curring high treatment costs; these are likely to be higher
if multiple rounds of testing are required and treatment is
delayed. Thus, early recognition and prompt treatment of
APIP are vitally important.
The majority of previous retrospective studies only
summarized and reported the clinical features of APIP
[5,7,32]. In addition, most studies into the early predictors
of SAP have focused only on acute pancreatitis in the non-
pregnant population, such as the association of neutrophil–
lymphocyte ratio (NLR), red cell distribution width (RDW),
and C-reactive protein (CRP) with AP [33,34]. Only a few
studies have collected routine laboratory tests after APIP
onset to evaluate the predictive values of these tests on
APIP severity [9,15]. From that study, lactate dehydroge-
nase (LDH) and RDW was able to predict SAP early, and
low serum triglycerides (<4.72 mmol/L) can be used to pre-
dict MAP. We observed that pleural effusion, confirmed by
echocardiography, has been identified as an independent
predictor of the severity of AP in the general population,
according to a prospective observational study [35]. But
unfortunately, the echocardiography data in our study were
limited, as echocardiography is not routinely performed on
APIP patients in our hospitals. In our study, we analyzed
common vital signs including blood pressure (BP), HR, and
relative risk (RR) against the severity of APIP, which had
not been previously done. Vital signs are objective and can
be readily obtained from a simple assessment, thereby pro-
viding clinicians an efficient tool to evaluate the patient’s
condition. By analyzing HR between the clinical groups,
we found that HR may offer a simple and feasible indicator
for the early prediction of SAP. As shown in Table 3, HR
could predict SAP with a cut-off value of 112 beats/min; it
was the best of the tested markers. Further, we found the
diagnostic specificity of HR to be 0.932 in our study, which
was higher than the risk score (0.828) calculated by Jin Di
et al. [9], while the diagnostic sensitivity was equivalent in
both studies. According to the multivariate analysis results,
HR was the only independent factor for predicting SAP in
our study. Previously, Khoueiry et al. [36] conducted a
retrospective study of patients with pericardial effusion and
observed that HR is associated with CRP levels. Hamaad
et al. [37] studied the relationship between HR and inflam-
masome activation among 100 patients with acute coronary
syndrome and concluded that increased heart rate correlated
with the level of inflammation [37]. In addition, Torpy et
al. [38] administered interleukin-6 (IL-6, 3 µg/kg of body
weight) via subcutaneous injection to healthy individuals
and observed a HR increase. The HR began to increase sig-
nificantly compared with baseline at 90 minutes after IL-6
injection, and the maximum effect was seen at 360 minutes
after injection [38]. The above indicated that cytokines can
increase HR. According to literature reports, the pathogene-
6
sis of cardiac manifestations in acute pancreatitis in the non-
pregnant population (such as hypotension and tachycardia)
was secondary to hypovolemia, metabolic disturbances and
cytokines [39]. In our study, we observed that there was no
statistical difference in blood pressure, hematocrit (HCT)
and serum electrolytes among the 3 types of APIP. To some
extent, we could consider that the pro-inflammatory cy-
tokines play a major role at least in initial stages of APIP.
We speculate that increased heart rate on admission can re-
flect the severity of inflammation in APIP, which is an in-
flammatory disease. SAP has a very strong positive corre-
lation with systemic inflammatory responses, so the early
increases in HR might help to predict SAP development.
So far, studies correlating HR and APIP remain rare, but
our findings provide a new direction for larger studies in
the future.
The complexities of managing APIP arise from the
decision-making involved in the timing and route of preg-
nancy termination. There are currently no standardized
guidelines to instruct the diagnosis and treatment of APIP.
Luo et al. [7] provided some recommendations for indica-
tors for the termination of pregnancy: (1) when organ dys-
function exists, continuing pregnancy might aggravate the
disease; (2) during the first two trimesters of pregnancy,
clinical medications might affect the growth of the fetus;
(3) fetal development is basically mature (after 37 weeks),
systemic inflammation response syndrome (SIRS) caused
by APIP and clinical medications might increase the risk of
fetal death [7]. At our medical center, a multidisciplinary
team, including obstetrics, hepatobiliary surgery, gastroen-
terology and ICU, would be constructed to assess the med-
ical condition of APIP and decide whether to terminate
pregnancy. Consistent with the conclusion of other stud-
ies [5,13], in this study, adverse outcomes occurred more
frequently among pregnant patients diagnosed with MSAP
and SAP, compared to MAP. Therefore, early diagnosis and
timely treatment for MSAP and SAP should confer marked
benefits. Conservative management is suggested for pa-
tients with MAP [40], implying that continuation of preg-
nancy for MAP after conservative treatment would be safe.
Though multidisciplinary consultation has done to assess
medical condition and provide personalized treatment op-
tions, some pregnant women will still request induction out
of concerns about their medical condition and fetal toxic-
ity arising from the drug treatments. Long-term outcomes
for continued pregnancy in MAP have not been previously
reported. In this study, we recorded outcomes from 6 long-
term cases of continued pregnancy in MAP and the HRs of
these 6 pregnant patients were all <112 beats/min, match-
ing our result. Nearly all these pregnancies continued to
term. In the comparison between group A and B, we found
no difference in the Apgar scores, demonstrating that the
long-term MAP prognosis was comparable. Thus, clini-
cal therapeutic guidance for MAP patients may not need
to be radical. Trying to prolong pregnancy for MAP could
reduce early termination of pregnancy which was unneces-
sary, especially preterm births. But due to the rapid changes
in APIP, these patients should be closely monitored to avoid
disease progression.
This study has some limitations. Firstly, a retrospec-
tive study has inherent limitations. We could investigate as-
sociations but could not infer causation. Secondly, there is
no available guideline to provide standard management of
APIP. Guideline of acute pancreatitis was used to identify
APIP, which might limit the generalization of the results. In
addition, this study consisted of a small sample size. Due
to the low incidence of APIP, to recruit a large number of
study patients is quite difficult. Besides, the recruitment of
patients from tertiary hospitals might lead to selection bias.
However, this is currently the largest cohort in order to in-
vestigate APIP in Guangdong Province.
5. Conclusions
APIP is a rare but severe disease that potentially
threatens maternal and fetal wellbeing. Hypertriglyc-
eridemia was the most common etiology of APIP, suggest-
ing that a greater focus should be given to nutrition and
metabolic health in pregnant patients. The severity of APIP
was correlated with a higher risk of poor outcomes, sug-
gesting that a specific and sensitive marker to predict SAP
is required. HR recorded after admission may be a predic-
tor of APIP. For APIP patients, it is important to consider
the most appropriate timing for pregnancy termination, but
for MAP patients, conservative treatment is a likely option.
More research is required to elucidate the etiology, clinical
predictors, and treatments of APIP.
Availability of Data and Materials
The datasets used and analyzed during the current
study are available from the corresponding author on rea-
sonable request.
Author Contributions
JL, JJ and FH conceived and designed the project. JL,
RL, ZL, YY and DQ collected the data. JL and RL analyzed
and interpreted the data. JL drafted the manuscript. All au-
thors read and approved the final manuscript. All authors
contributed to editorial changes in the manuscript. All au-
thors have participated sufficiently in the work and agreed
to be accountable for all aspects of the work.
Ethics Approval and Consent to Participate
The study was conducted in accordance with the Dec-
laration of Helsinki. The study protocol was approved by
the Institutional Review Board of the Nanfang Hospital,
Southern Medical University (approval No. NFEC-2022-
247). The records and data did not include identifying pa-
tient information and the analysis was based on retrospec-
tive record review, so individual informed consent was not
7
required. The informed consent has been exempted by the
Institutional Review Board of the Nanfang Hospital, South-
ern Medical University.
Acknowledgment
We are grateful to the hospital collaborators for assis-
tance in data collection.
Funding
This study was supported by Clinical Research Fun-
dation of Nanfang Hospital, Southern Medical University
(2019CR014).
Conflict of Interest
The authors declare no conflict of interest.
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