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Journal of Perinatology (2014) 34, 87–94

& 2014 Nature America, Inc. All rights reserved 0743-8346/14

Acute pancreatitis during pregnancy: a review
G Ducarme1, F Maire2,3, P Chatel4, D Luton4 and P Hammel2,3

This article aims to draw together recent thinking on pregnancy and acute pancreatitis (AP), with a particular emphasis on
pregnancy complications, birth outcomes and management of AP during pregnancy contingent on the etiology. AP during
pregnancy is a rare but severe disease with a high maternal–fetal mortality, which has recently decreased thanks to earlier
diagnosis and some maternal and neonatal intensive care improvement. AP usually occurs during the third trimester or the early
postpartum period. The most common causes of AP are gallstones (65 to 100%), alcohol abuse and hypertriglyceridemia. Although
the diagnostic criteria for AP are not specific for pregnant patients, Ranson and Balthazar criteria are used to evaluate the severity
and treat AP during pregnancy. The fetal risks from AP during pregnancy are threatened preterm labor, prematurity and in utero
fetal death. In cases of acute biliary pancreatitis during pregnancy, a consensual strategy could be adopted according to the
gestational age, and taking in consideration the high risk of recurrence of AP (70%) with conservative treatment and the specific
risks of each treatment. This could include: conservative treatment in first trimester and laparoscopic cholecystectomy in second
trimester. During the third trimester, conservative treatment or endoscopic retrograde cholangiopancreatography with biliary
endoscopic sphincterotomy, and laparoscopic cholecystectomy in early postpartum period are recommended. A multidisciplinary
approach, including gastroenterologists and obstetricians, seems to be the key in making the best choice for the management of
AP during pregnancy.

Journal of Perinatology (2014) 34, 87–94; doi:10.1038/jp.2013.161; published online 19 December 2013
Keywords: acute pancreatitis; management; pregnancy; review

INTRODUCTION time limit using ‘acute pancreatitis’, ‘pregnancy’, ‘surgery’ or

Acute pancreatitis (AP) during pregnancy is a rare disease with ‘management’ as keywords.
an estimated incidence rate of about 1 case per 1000 to 10 000
pregnancies.1–3 The diagnosis of AP is more frequent in
multiparous patients (75%).3,4 AP is rare during the first and DIAGNOSIS OF AP
second trimester of pregnancy (12%), it usually occurs during the The diagnostic criteria for AP are not specific for pregnant
third trimester (50%) or the early postpartum period (38%).3–5 patients. Some standards have been developed in non-pregnant
AP during pregnancy is a severe disease with a high maternal– patients and are often used as a guide to diagnose AP during
fetal mortality rate (37% and 60%, respectively) according to old pregnancy. The disease usually appears during the third trimester
published series of cases, but this has recently decreased thanks to or in the early postpartum period with the association of
earlier diagnosis and some maternal and neonatal intensive care symptoms like upper abdominal pain, nausea or vomiting,
improvement.6–8 Latest studies show rare maternal and fetal anorexia, fever and elevated serum amylase or lipase activities.4
mortalities, around 0 to 3%.1,5,9,10 The diagnosis of AP during pregnancy can be difficult. Pregnancy-
Causes of AP occurring during pregnancy can be different, as linked hematological and biochemical alterations may have an
they are in non-pregnant patients. However, the respective impact on the interpretation of the diagnostic tests (serum amylase
frequency of each cause is different (Table 1). The most common and lipase levels) and the assessment of the AP’s severity (physiologic
identified causes of AP in pregnancy are gallstones (65 to 100%), leukocytosis in pregnant women under 16 000 mm–3, alkaline
alcohol abuse (5 to 10%), idiopathic (15%) and familial hyper- phosphatase can reach to three times normal in normal pregnancy).
triglyceridemia-induced pancreatitis (5%).1,11 An increase in serum amylase and lipase activities should be taken
Given the current uncertainty regarding incidence, manage- into account during pregnancy, as in non-pregnant women, for the
ment and outcome of AP in pregnancy, it is important to establish diagnosis of AP.12 So, an elevated serum amylase and/or a lipase
accurate, generalizable information so that patients can be level higher than three times normal has a good positive predictive
counseled and treated appropriately. This article aims to draw value for the diagnosis of AP in pregnant women. The serum lipase
together recent thinking on AP during pregnancy, with a level has a better sensitivity (94% vs 83%) and specificity (96% vs
particular emphasis on pregnancy complications, birth outcomes 88%) than the serum amylase level to diagnose AP.13
and management of AP during pregnancy contingent on the As well as in non-pregnant patients with AP, the etiological
etiology. We have performed a Pubmed (Medline) search with no investigation based on the assessment data (personal and family
Department of Obstetrics and Gynecology, Centre Hospitalier Departemental, La Roche sur Yon, France; 2Pôle des Maladies de l’Appareil Digestif, Service de Gastroentérologie-
Pancréatologie, Hôpital Beaujon, AP-HP, Clichy, France; 3Inserm U773-CRB3, Université Paris-Diderot, Clichy, France and 4Department of Obstetrics and Gynecology, Hôpital
Beaujon, AP-HP, Université Paris-Diderot, Clichy, France. Correspondence: Dr G Ducarme, Department of Obstetrics and Gynecology, Centre Hospitalier Departemental, 85000
La Roche sur Yon, France.
Received 24 May 2013; revised 21 October 2013; accepted 12 November 2013; published online 19 December 2013
Acute pancreatitis during pregnancy
G Ducarme et al
Table 1. Causes of AP in pregnant women Table 2. Ranson’s criteria for prognosis of acute pancreatitis
Gallstones (65–100%) Ranson’s criteria on admission:
Alcohol abuse (5–10%) Age 455 years
Familial hypertriglyceridemia-induced pancreatitis (5%) White blood cell count 416 000 cells mm–3
Idiopathic (15%) Blood glucose 411 mmol l–1
Drugs-induced AP (thiazide diuretics) (cases) Serum AST 4250 IU l–1
Pancreatitis associated with pregnancy-induced hypertension (cases) Serum LDH 4350 IU l–1
Acute fatty liver of pregnancy associated with AP (cases)
Hyperparathyrodism (cases) Ranson’s criteria after 48 h of admission:
Gene mutations (cases) Hypocalcemia (serum calcium o2.0 mmol l–1)
Cationic trypsinogen (PRSS1) Fall in hematocrit by 410%
CFTR Hypoxemia (PO2 o60 mm Hg)
PSTI Increase in BUN to 41.98 mmol l–1 after IV fluid hydration
PPARG Base deficit (negative base excess) 44 mmol l–1
Sequestration of fluids 46 l
Abbreviations: AP, acute pancreatitis; CFTR, cystic fibrosis transmembrane
conductance regulator; PPARG, peroxisome proliferator-activated receptor Interpretation
gamma; PSTI, pancreatic secretory trypsin inhibitor. If the score X3, severe pancreatitis likely
If the score o3, severe pancreatitis is unlikely
Score 0–2: 2% mortality
history, alcohol consumption and drugs), blood tests (white cell Score 3–4: 15% mortality
count, liver enzyme concentrations guide to the presence of Score 5–6: 40% mortality
cholelithiasis) and imaging is necessary to orientate, evaluate the Score 7–8: 100% mortality
severity and treat AP during pregnancy. Abbreviation: AST, aspartate aminotransferase; BUN, blood urea nitrogen;
Abdominal ultrasound is safe and it has higher sensitivity than IV, intravenous; LDH, lactate dehydrogenase.
computerized tomography for detecting gallstones in cases of AP.
Magnetic resonance imaging (MRI) is an accurate technique for
detecting the cause of acute abdominal and pelvic pain during and the perinatal mortality was 3.6%.1 Patients who developed AP
pregnancy and should be considered for pancreas screening during the first trimester had the lowest percentage of term
during pregnancy after sonographically indeterminate findings.14 pregnancy (60%) and the highest risks of fetal loss (20%) and
MRI can provide information on AP and its complications (edema, preterm delivery (16%).24 Sun et al.10 compared maternal–fetal risk
pseudocysts or hemorrhagic pancreatitis), and it can also help to between 18 pregnancies complicated by severe AP and 51
determine whether the main pancreatic duct is clear or not when pregnancies with mild AP. They concluded that miscarriages and
persistent cholestasis occurs. MRI has also the advantage of not preterm infants contributed to fetal loss in the ‘mild’ group, while
causing any fetal toxicity even when gadolinium contrast media is fetal death and stillbirth contributed in the ‘severe’ group. Cases of
used, while iodinated contrast medium during computerized acute biliary pancreatitis were associated with better perinatal
tomography could induce fetal hypothyroidism.15–19 Overall, outcomes than non-biliary causes.1
both sensitivity and negative predictive value for the diagnosis
of choledocholithiasis are lower than those of endoscopic
ultrasonography. However, their non-invasive nature and the ACUTE BILIARY PANCREATITIS
absence of general anesthesia lead to prefer them as first choice Epidemiology
tests in pregnant patients.20
Elevated progesterone levels induce biliary hypotonia, increasing
the pressure of the sphincter of Oddi—which leads to bile stasis—
EVALUATION OF SEVERITY and the impregnation of estrogen changes the composition of
bile, which becomes more lithogenic.23 Therefore, the risk of
Ranson and Balthazar criteria for the classification of AP’s severity biliary sludge and stones increases throughout pregnancy. The
in non-pregnant patients have been developed (Table 2) and are main independent risk factor for gallstones is pre-pregnancy
often used as a guide to evaluate the disease’s severity and treat it obesity.3,25 high-density lipoprotein cholesterol was also inversely
during pregnancy.21 In addition to abdominal ultrasound, MRI has associated with incidental gallbladder lithiasis.25
shown to be as effective as computerized tomography for staging The incidence of biliary manifestations during pregnancy (colic,
AP using the Balthazar severity index.22 If there is no problem for acute cholecystitis, cholangitis or biliary AP) is from 0.05 to 8%.
the differential diagnosis, it is strongly recommended to perform During pregnancy, cholelithiasis is the most common cause of AP
an evaluation using imaging at least 48 h after the beginning of accounting for 65 to 100% of cases.4,23,26 In a prospective study of
pain (Figure 1), as too early staging may underestimate the over 3000 patients who had ultrasound examination throughout
severity of an AP.13 In the literature, severe AP (scoreX3) during the pregnancy, the authors showed a cumulative incidence of
pregnancy are mainly due to gallstone migration or to hyper- sludge or gallstones in early postpartum in 10.2%, with biliary
glyceridemia.10,23 sludge in 5.1%, stones in 2.8% and gallstones in patients with pre-
existing sludge in 2.3%.25 A symptomatic biliary complication
occurred in 1.2% of the pregnant women. The variability of the
reported incidence is related to a center effect and the sensitivity
The fetal risks from AP during pregnancy are threatened preterm of the techniques used for the lithiasis diagnosis (microlithiasis are
labor, prematurity and in utero fetal death. Previously reported frequent during pregnancy and only endoscopic ultrasonography
high perinatal mortality rates secondary to AP are due to neonatal has a high sensitivity for the diagnosis).
deaths after preterm delivery. In recent series, perinatal mortality
rates were improved, mainly because 74% of the infants were
delivered in term.4 A large retrospective study including 101 cases Treatments
of pancreatitis (89 AP and 12 chronic pancreatitis) affecting The particularity of the acute biliary pancreatitis during preg-
among 305 101 deliveries in 10 years showed no maternal death, nancy is its high recurrence rate, around 70% (90% during

Journal of Perinatology (2014), 87 – 94 & 2014 Nature America, Inc.

Acute pancreatitis during pregnancy
G Ducarme et al

Figure 1. Non-enhanced abdominal magnetic resonance imaging (MRI) in a woman who presented an acute pancreatitis at 37 weeks
gestation. Non-enhanced abdominal MRI showing the extent of necrosis in contact with the tail of the pancreas, around the kidneys and in
the parietocolic folds (arrows, a, b), the gallbladder with no parietal thickening and no visible gallstone, and the diffuse enlargement of the
pancreas with heterogeneous attenuation of pancreatic parenchyma (arrows, c, d).

hospitalization) vs 20% to 30% in the general population.6,27,28 Open cholecystectomy or laparoscopic cholecystectomy?. The
Management should consider both maternal and fetal risks conti- literature review identified 20 studies (197 patients) describing
ngent on the treatment: irradiation during endoscopic retrograde laparoscopic cholecystectomy during pregnancy, excluding small
cholangiopancreatography (ERCP) with biliary endoscopic sphinc- series of o5 patients.9 The procedure was performed more often
terotomy, general anesthesia and laparoscopy. during the second trimester of pregnancy without any maternal
Surgery? A review included 12 studies, concerning 113 patients Four retrospective studies have compared open cholecystec-
with confirmed gallstone-induced AP during pregnancy, compar- tomy vs laparoscopic cholecystectomy.30–33 These studies did
ing conservative with surgical treatment.9 No maternal deaths not show any significant difference in maternal and fetal
were reported in either group. Maternal morbidity, fetal morbidity outcome. One fetal death occurred in the laparoscopic chole-
and mortality were low and not significantly different between the cystectomy group, compared with two in the open-surgery group
two groups. However, in 12 reports about biliary pancreatitis, the (P ¼ 0.41). There were 6 out of 89 (6.74%) preterm deliveries in the
authors reported a trend toward higher rate of fetal mortality laparoscopic cholecystectomy group compared with 2 out of 69
(8.0% vs 2.6%, P ¼ 0.28) in the conservative group, suggesting the (2.90%) in the open-surgery group (P ¼ 0.27).9
need for earlier cholecystectomy (and biliary tract clearance when No study has specifically evaluated the fetal risk associated
necessary) during pregnancy. with intraoperative opacification of the biliary tract. This tech-
Recently, Othman et al.29 published a retrospective study in a nique should be limited in case of suspected choledocholi-
tertiary-care referral hospital. A total of 112 patients who thiasis, using a preoperative MRI or an intraoperative ultrasound
had complications related to gallstones during pregnancy was imaging.
reported and classified into three groups: conservative treatment, In addition to the more commonly recognized benefits of
laparoscopic cholecystectomy and ERCP. The number of emer- laparoscopy, comparing laparotomy (duration of postoperative
gency department visits, recurrent biliary symptoms and the hospital stay, quicker return transit, lower risk of postoperative
number of hospitalizations were significantly higher in the conser- venous thrombosis by early mobilization), there is a shorter
vative treatment group compared with the active intervention duration of sedation (responsible for fetal respiratory depression),
group (cholecystectomy and/or ERCP). The authors concluded that and a reduced incision size and uterine manipulation, which is the
ERCP and laparoscopic cholecystectomy can be safe alternative most associated factor with a risk of preterm delivery. Precautions
approaches during pregnancy. are recommended to avoid high intraperitoneal pressures: to favor

& 2014 Nature America, Inc. Journal of Perinatology (2014), 87 – 94

Acute pancreatitis during pregnancy
G Ducarme et al
the left lateral decubitus position to minimize aorto-caval HYPERTRIGLYCERIDEMIA
compression; to avoid rapid changes in position; and to use Epidemiology
electrocoagulation with caution.9,34 Hypertriglyceridemia in pregnant patients can occur on pre-
existing dyslipidemia, associated with others diseases (hyperten-
Time for surgery?. Another important question is when the sion, diabetes and alcoholism), or without any predisposing factor.
best moment for surgery is if the situation allows elective Triglycerides concentration rises gradually, 2.5-fold over pre-
choice in pregnant woman. Laparoscopic cholecystectomy pregnancy levels, reaching a peak during the third trimester to
appears to be a safe procedure during all trimesters but it is as high as almost twice the non-pregnant values. That’s why the
best carried out during the second trimester because the fetus AP occurs more often during the third trimester of pregnancy.
has completed the organogenesis and the uterus is not too Lipids decrease gradually during postpartum to regain pre-
large. Laparoscopic cholecystectomy should be proposed as pregnancy level in 6 weeks.52,53 These changes are related to an
soon as the technical conditions for surgery are possible with- increasing hepatic synthesis of very low-density lipoproteins and a
out major maternal–fetal morbidity (that is, concomitant chole- reduction in the activity of lipoprotein lipase in relation to the high
cystitis).35–37 levels of estrogen.53 Factors favoring dyslipidemia disturbances
are excessive weight gain, diabetes, alcohol consumption, drugs
Role of ERCP. ERCP has become an invaluable diagnostic and (steroids, diuretics and beta-blockers) and latent genetic
therapeutic tool for biliary and pancreatic disorders. The indica- abnormalities (lipoprotein lipase, apoC2 or apoE). Experimental
tions for ERCP with biliary endoscopic sphincterotomy are models of isolated dog pancreas have shown direct toxicity of
choledocholithiasis associated with AP, and prevention of triglycerides.54
recurrence of AP during the third trimester of pregnancy. Many Pregnancy, especially in the third trimester, can deregulate
studies have reported the results of ERCP during pregnancy and controlled lipid levels in women with familial hypertriglyceridemia
all have shown the absence of serious complications for the and it may lead to AP and significant morbidity in both mother
mother and the fetus.38–46 The risk of induced AP with ERCP is and fetus. Familial severe hypertriglyceridemia (levels 410 g l–1) is
around 5% without serious form if the procedure is done by an a known cause of AP during pregnancy. The incidence of familial
experienced surgeon. The risk of fetal complications related to hypertriglyceridemia-induced pancreatitis is estimated at 1/25 000
ERCP has shown to be o5%.47 pregnancies.55,56
The main concern about performing ERCP during pregnancy
centers on radiation exposure to the fetus during fluoroscopy.
Therapeutic ERCP is associated with significantly higher radiation Treatment
exposure than diagnostic ERCP. Average effective dose A history of familial hypertriglyceridemia requires bio-
was 3.1 mSv for diagnostic and 12.4 mSv for therapeutic logical monitoring for pregnancy-related hypertriglyceridemia in
ERCP.48,49 Published series on estimated dose exposure to those patients with a pre-pregnancy fasting triglyceride level
fetus during ERCP have ranged from 0.1 to 3 mSv, which is 44 mmol l–1. A serum triglyceridemia level over 10 g l–1 is an
significantly lower than the threshold dose required for fetal identifiable risk factor for complications.57,58 The mainstay
malformation (5 mSv during pregnancy), otherwise known as the treatment, including dietary restriction of fat and lipid-lowering
deterministic effect.47,50 Studies concerning nonradiation ERCP agents when triglyceride level increases to 410 g l–1, effectively
using wire-guided biliary cannulation and choledochoscopy have prevents further episodes of hypertriglyceridemia-induced AP
been published and the authors have concluded that this during pregnancy.59
technique is a safe and effective treatment for symptomatic In the non-pregnant population, plasma exchange is proven to
choledocholithiasis during pregnancy.43,44 The fetal risks from be a safe and useful management method in cases of severe
performing ERCP during pregnancy must therefore be weighed hypertriglyceridemia where conventional drug treatment has
against the risks to the fetus and the patient in the absence of failed.60,61 It can quickly clear triglycerides from plasma, both
intervention. by lipid epuration and by compensation using fresh frozen
plasma and lipoprotein lipase adjunction.62 There are very few
Therapeutic strategy. No standardized guidelines have been data on the efficacy of plasma exchange in pregnant patients,
published concerning the most effective management of acute based on clinical cases or short series.52,56,63 A short series
biliary pancreatitis in pregnant women to reduce maternal and reported a mean removal rate during a single plasma exchange
neonatal mortality and morbidity. for triglyceride of around 66 and 83% after the second in 17 non-
A recent multimodal approach to acute biliary pancreatitis pregnant patients with hypertriglyceridema-induced pancreatitis.62
during pregnancy has been published.51 The authors reported Technical variants are numerous and involve centrifugation
seven pregnant women who were managed by using magnetic or filtration supplemented or not by immunoadsorption
resonance cholangiopancreatography, ERCP and sphincterotomy (Ac anti-apoB), precipitation (heparin-induced extracorporeal
followed by laparoscopic cholecystectomy. They concluded that low-density lipoprotein precipitation) or by adsorption on
this active management of acute biliary pancreatitis provides dextran. They all share a high production cost and require high
definite treatment and seems to put both mother and fetus at technology.
lower risk than presumed. Other treatment options including combined heparin and
Finally, according to the high risk of recurrence of AP (70%) with insulin infusions have been described in the context of hyper-
conservative treatment and the specific risks of each treatment, triglyceridemia-induced AP.64–67 The clinical data of these
and although there are no randomized studies, consensual publications have shown pain relief and a reduction of triglyce-
strategy according to the gestational age could be adopted rides below 10 g l–1 in 24 to 48 h. These results were comparable to
(Table 3): those obtained with plasma exchange.
In conclusion, no standardized guidelines have been published
- First trimester: conservative treatment and laparoscopic chole- concerning the most effective management of hypertriglyceride-
cystectomy during second trimester. mia-induced AP during pregnancy. Therapy should include a
- Second trimester: laparoscopic cholecystectomy. multidisciplinary team to address dietary fat restriction, appro-
- Third trimester: conservative treatment or ERCP with biliary priate nutritional supplements and possible medications when
endoscopic sphincterotomy, and laparoscopic cholecystectomy needed. Therapeutic plasma exchange and/or other treat-
in the early postpartum period. ment options including combined parenteral heparin and insulin

Journal of Perinatology (2014), 87 – 94 & 2014 Nature America, Inc.

Acute pancreatitis during pregnancy
G Ducarme et al
Table 3. Algorithm of treatment in acute biliary pancreatitis in pregnant women

infusions in severe cases are effective approaches to treat and possible medications when needed. Termination of preg-
gestational hypertriglyceridemia-induced AP. Termination of nancy would be discussed according to the term and the severity
pregnancy (induction of labor or cesarean section) would be of the recurrence of AP. The early application of treatments in
discussed according to the term and the severity of the AP. parturient women with chronic alcoholic pancreatitis may improve
The early application of treatments in parturient women with the clinical course.
hypertriglyceridemia-induced AP may improve the clinical
As in non-pregnant patients, drug-induced AP may occur and it
ALCOHOL should be systematically explored in the examination. In the litera-
Chronic alcoholic consumption is a rare cause of AP during ture, thiazide diuretics are the most common drugs implicated in
pregnancy, estimated at 5 to 10%. Alcohol and chronic alcoholic the occurrence of AP during pregnancy.69
pancreatitis before pregnancy were associated with increased
rates of recurrence of AP and preterm delivery (66.7% vs 18.6% in
case of simple gallstone pancreatitis).1,68 PANCREATITIS ASSOCIATED WITH PREGNANCY-INDUCED
No standardized guidelines have been published concerning HYPERTENSION
the most effective management of chronic alcoholic pancreatitis Pancreatitis associated with pregnancy-induced hypertension
during pregnancy. Therapeutic strategy should include a multi- is exceptional. Severe preeclampsia may cause widespread
disciplinary team to address appropriate nutritional supplements, end-organ damage with abnormalities of the microcirculation

& 2014 Nature America, Inc. Journal of Perinatology (2014), 87 – 94

Acute pancreatitis during pregnancy
G Ducarme et al
involving brain, liver, kidney and circulatory systems, and it may CONCLUSION
affect the gastrointestinal system, resulting in a concomitant AP during pregnancy is a rare but severe disease. There is no
pancreatic ischemia and severe necrotizing AP.70–72 Haukland consensus in the literature regarding the management of AP
et al.73 showed in 13 patients with severe preeclampsia that mean during pregnancy. Traditionally conservative, the treatment of
serum concentration of amylase was statistically significantly biliary lithiasis depends on the symptoms. A multidisciplinary
higher than the corresponding mean serum concentrations in approach, including gastroenterology and obstetric care, seems to
30 normal pregnancies (1.6 vs 1.1 mmol l–1). be a key in making the best choice for management of AP during
Acute fatty liver of pregnancy is a rare condition occurring in the CONFLICT OF INTEREST
third trimester of pregnancy, characterized by nausea, vomiting, The authors declare no conflict of interest.
abnormal and moderate hyperbilirubinemia. It may be compli-
cated by renal and acute liver failure, respiratory distress,
coagulopathy and rarely pancreatitis. Twelve cases of acute fatty AUTHOR CONTRIBUTIONS
liver of pregnancy associated with AP have been reported with a GD, FM and PC were the main contributors to the conception, manuscript
high maternal mortality rate (17%).74 design and preparation of the manuscript. DL and PH advised on the original
design and reviewed the manuscript.

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