Volume 70, Number 9

OBSTETRICAL AND GYNECOLOGICAL SURVEY

Copyright 2015 Wolters Kluwer Health,
Inc. All rights reserved.

CME REVIEW ARTICLE

CHIEF EDITORS NOTE: This article is part of a series of continuing education activities in this Journal through which a total
of 36 AMA PRA Category 1 CreditsTM can be earned in 2015. Instructions for how CME credits can be earned appear on the
last page of the Table of Contents.

Gallstone and Severe

Hypertriglyceride-Induced Pancreatitis
in Pregnancy
Mary Ashley Cain, MD,* Jeremy Ellis, MD, Marc A. Vengrove, DO,
Benjamin Wilcox, MD,k Jerome Yankowitz, MD,#
and John C. Smulian, MD, MPH**
*Fellow, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Morsani College of Medicine, University
of South Florida, Tampa, FL; Clinical Assistant Professor, Department of Internal Medicine, Thomas Jefferson University,
Philadelphia; Chief, Division of Endocrinology and Metabolism, Department of Internal Medicine, Lehigh Valley Health,
Allentown, PA; Clinical Assistant Professor, Division of Endocrinology and Metabolism, Morsani College of Medicine, University
of South Florida, Tampa, FL; kDivision of Nephrology, Department of Internal Medicine, Lehigh Valley Health Network,
Allentown, PA; Clinical Assistant Professor of Medicine, #Professor and Chairman, Department of Obstetrics and Gynecology,
Morsani College of Medicine, University of South Florida, Tampa, FL; **Vice Chair, Department of Obstetrics and Gynecology,
Lehigh Valley Health Network, Allentown, PA; and Professor, Department of Obstetrics and Gynecology, Morsani College of
Medicine, University of South Florida, Tampa, FL
Importance: Patients with biliary disease or underlying dyslipidemias are at risk for pancreatitis in pregnancy. Appropriate treatment can decrease the risk of recurrence and perinatal complications. Prevention of severe lipid elevations can prevent the development of pancreatitis in pregnancy.
Objective: To review the pathophysiology, diagnosis and treatment of gallstone and severe hypertriglycerideinduced pancreatitis in pregnancy.
Evidence Acquisition: We performed a literature search regarding pancreatitis, gallstones, hyperlipidemia,
and the treatment of both severe hypertriglyceride-induced pancreatitis and gallstone pancreatitis in pregnancy.
Results: In the setting of acute pancreatitis, removal of the offending agent, either gallstones or serum lipids,
can lead to improved status and decrease recurrence risk.
Conclusions and Relevance: Patients with acute pancreatitis should be treated with analgesia and fluid resuscitation and maintain a nothing-per-os status. In cases of gallstone pancreatitis, removal of the offending
stone through endoscopic retrograde cholangiopancreatography or cholecystectomy can decrease recurrence
risk. Severe hypertriglyceride-induced pancreatitis includes similar management. Lipopheresis may be considered in refractory cases. Patients with severe hypercholesterolemia should maintain a low-fat diet and can continue lipid-lowering agents outside the statin class of medications. Preventing severe dyslipidemia in gestation
can decrease the risk of pancreatitis and improve maternal and neonatal outcomes.
Target Audience: Obstetricians and gynecologists, family physicians
Learning Objectives: After completing this activity, the learner will be better able to diagnose and begin initial
treatment of pancreatitis in pregnancy, explain the physiology of pancreatitis and the association with gallstones
and hyperlipidemia, screen patients for familial hyperlipidemia syndromes, and discuss the various forms of
familial dyslipidemias, potential pregnancy complications, and methods for prevention and treatment of
complications.
The authors has disclosed that the U.S. Food and Drug Administration has not approved the use of the Apheresis apparatus for the
treatment of Lipopheresis as discussed in this article. Please consult
the products labeling for approved information.
All authors and staff in a position to control the content of this
CME activity and their spouses/life partners (if any) have
disclosed that they have no financial relationships with, or

financial interests in, any commercial organizations pertaining

to this educational activity.
Correspondence requests to: Mary Ashley Cain, MD, Division of
Maternal Fetal Medicine, Department of Obstetrics and Gynecology,
College of Medicine, University of South Florida, USF Health South
Tampa Center, 2 Tampa General Circle #6031, Tampa, FL 33606.
E-mail: mcain@health.usf.edu.

www.obgynsurvey.com | 577

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24

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Obstetrical and Gynecological Survey

PANCREATITIS IN PREGNANCY
Acute pancreatitis in pregnancy is rare, occurring
in approximately 1 per 3000 pregnancies.1,2 Significant
maternal morbidity can occur including intensive care
admission, metabolic disturbances, sepsis, pancreatic
necrosis, and hypovolemic shock.3 Rates of preterm delivery, fetal distress, and demise are increased in pregnancies with pancreatitis.13 Older reports regarding
pancreatitis in pregnancy found maternal and perinatal
death rates as high as 20% and 50%, respectively.1
More recent reports show no maternal deaths and lower
perinatal death rates of 3.6% to 10%.1,2 These improvements in perinatal outcomes are likely due to improvements in maternal and perinatal care.
Biliary issues cause the majority of pancreatitis cases
complicating pregnancy, followed by alcohol-related
disease.1,2
Diagnosis
Diagnostic criteria for pancreatitis include severe
epigastric pain; specific findings on imaging either
through computed tomography (CT), magnetic resonance imaging, or ultrasound; and serum amylase or lipase at 3 times the normal values.4,5 Patients must meet
2 of these 3 criteria for definitive diagnosis.6 Diagnosis
of pancreatitis complicating pregnancy should include
these same criteria. The location of pancreatic pain
and lipase or amylase values should not be altered in
pregnancy and can therefore reliably lead to the diagnosis of pancreatitis. Imaging through abdominal ultrasound confers no risk of radiation to the fetus and can
identify gallstones in cases of gallstone pancreatitis.5
This form of imaging may limit the identification of
common bile duct stones and biliary sludge.5,7 Because
of the risk of radiation exposure and availability of
alternative options, CT is not indicated for the diagnosis of pancreatitis in pregnancy.8 In addition, CT imaging cannot identify necrotizing pancreatitis early in
the disease process, limiting the modalitys utility in
addressing disease severity in both pregnant and nonpregnant patients.4 Endoscopic ultrasound (EUS) requires sedation but involves no radiation risk and is
sensitive for the identification of common bile duct
stones and biliary sludge. This modality may be used
along with therapeutic endoscopic retrograde cholangiopancreatography (ERCP) to remove the offending
stones.4,5,8 Although ERCP involves radiation exposure, abdominal shielding decreases radiation-related
risk, and recent reviews demonstrate the safety of
the procedure for therapeutic purposes in pregnancy.9
If indicated ERCP can be completed during the same
sedation as the diagnostic EUS. Magnetic resonance

cholangiopancreatography involves no radiation exposure and can be used to identify common bile duct stones
as well as identifying pseudocysts and walled-off necrosis.4,5 Magnetic resonance cholangiopancreatography
and EUS provide safer alternatives to ERCP and CT imaging for diagnostic purposes among pregnant pancreatitis patients. Pregnant patients presenting with abdominal
pain and elevated serum markers do not require imaging to confirm the diagnosis of pancreatitis.10
Severity
Developed in 1992 and revised in 2012, the Atlanta
classifications describe disease severity among nonpregnant pancreatitis patients and provide a standard
guideline for discussion of the disease.6,10 Acute interstitial pancreatitis consists of edema and enlargement
of the pancreas. In contrast, 5% to 10% of patients will
develop necrotic pancreatitis in which the pancreatic
and peripancreatitic tissues necrose, leading to altered
perfusion and in some cases infection. Signs of necrosis
are not apparent on early CT imaging. If necessary, CT
to define the subtype of pancreatitis should be delayed
until after the first week of symptoms.4,10 Infected necrosis typically develops 1 week after initial symptoms
and leads to extraluminal gas on CT imaging and positive findings on fine-needle aspirate.10 Infected necrosis
in pancreatitis confers an increase in morbidity and
mortality.6,10
The revised classifications also describe persistent organ failure as more than 48 hours and transient as less
than 48 hours. Multiorgan failure involves 3 systems,
cardiovascular, renal, and respiratory, and uses the
modified Marshall scoring system to assess the disease.10,11 Because of physiologic changes of pregnancy
and lack of research in a pregnant population, this system will not likely be accurate in assessing severity
among pregnant patients. The revised classifications
define local complications as pancreatic pseudocysts,
peripancreatitc fluid, necrosis, and walled-off necrosis,
whereas systemic complications are exacerbations of
preexisting disease.10 The early phase occurs with local
inflammation and typically persists no longer than
2 weeks. The presence of local complications defines
the later phase and occurs only in severe cases.10
Using these definitions, the revised Atlanta classifications define pancreatitis as mild, no organ failure
and no local or systemic complications; moderately severe, transient organ failure and/or local or systemic
complications without persistent organ failure; and
severe, persistent organ failure either single organ or
multiorgan.6,10 These definitions assist providers in addressing a patients mortality risk as the risk increases

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

Gallstone and Pancreatitis in Pregnancy CME Review Article

with increasing severity. While these classifications may

be extrapolated to the pregnant population, no research
exists regarding the risk of mortality and perinatal
morbidities based on these groupings.
Risk Factors
Biliary issues cause the majority of pancreatitis cases
complicating pregnancy, followed by alcohol-related
disease.1,2 Severe hypertriglyceridemia (SHTG)induced
pancreatitis accounts for about 4% to 30% of all cases
of pancreatitis in pregnancy, with 1 case series reporting
a rate as high as 50%.13 Alcohol-induced pancreatitis
occurs in 12% of patients and may prove difficult to diagnose because of the patients reluctance to endorse alcohol abuse.2,12 Less frequent causes of pancreatitis in
pregnancy include cystic fibrosis and hypercalcemia
due to hyperparathyroidism.12 Smoking and medications including erythromycin, sulfasalazine, acetaminophen, and steroids confer additional risk of pancreatitis
in nonpregnant patients.13,14
GALLSTONE PANCREATITIS IN
PREGNANCY
Pregnancy leads to an increase in biliary sludge
and gallstone formation. Because of slowing of gallbladder emptying and increases in hepatic bile cholesterol secretion, the risk of gallstones increases during
pregnancy with further increases at each subsequent
pregnancy.5 Progesterone causes relaxation of the gallbladders smooth muscle, increasing biliary stasis and
gallstone formation.12 Obesity, parity, and insulin resistance further increase the risk of gallstones.15 Gallstone
pancreatitis occurs when gallstones obstruct the pancreatic duct.6 Following obstruction, the pancreatic
enzyme trypsinogen prematurely activates to trypsin,
leading to autodigestion of pancreatic acinar cells.6,16
The autodigestive process causes inflammation and
subsequent macrophage and cytokine release.6 The inflammatory process can range in severity from mild
edema to a necrosis of the pancreatic tissue. Further inflammation may lead to sepsis and multiorgan dysfunction.6,17 A failure in the intestinal barrier is a possible
cause of sepsis among patients with severe pancreatitis.17 Mortality increases from less than 3% to greater
than 15% among patients with necrotic pancreatitis.
Mortality rates rise further if necrotic pancreatic tissue
becomes infected.17,18

579

aggressive fluid resuscitation. If not monitored carefully,

overtreatment can lead to pulmonary edema, and undertreatment increases the patients mortality risk.19 Fluid
therapy in a pregnant population must be carefully monitored, and no current evidence exists on the most
appropriate rate of resuscitation for treatment of acute
pancreatitis in pregnancy. Enteral nutritional therapy
avoids complications associated with parental therapy including catheter-related infection. Pregnant patients are at
greater risk of catheter-related complications than nonpregnant patients.5 Studies involving nonpregnant patients with pancreatitis found a trend toward nasojejunal
enteral therapy and decreased organ failure over parental
therapy. Often more practical than nasojejunal feeding,
nasogastric feeding avoids the complications associated
with parenteral therapy and may be used to treat pancreatitis in both the pregnant and nonpregnant populations.12,20 Among patients with mild pancreatitis, oral
feeding may begin upon cessation of clinical symptoms.6
Pancreatitis patients with cholangitis, infected necrosis, or
sepsis require treatment with an initial pregnancy-safe,
broad-spectrum antibiotic regimen. The physician can
then tailor the antibiotics to the causative organism following identification through cultures.5 Prophylactic antibiotics are not indicated in the treatment of pancreatitis.6
In cases of gallstone pancreatitis, treatment must
address the underlying cause of gallbladder disease. Patients with mild pancreatitis and no evidence of infection should undergo cholecystectomy. Removal of the
gallbladder decreases recurrence rates and improves
outcomes in both the pregnant and nonpregnant
populations.5,2124 Reports demonstrate the safety of
cholecystectomy in every trimester.24,25 Because of the
completion of organogenesis, lower spontaneous abortion rates, and smaller uterine size, the second trimester
may be the ideal time for laparoscopic cholecystectomy.25 Among patients with severe pancreatitis, common bile duct stones, suspected cholangitis, or a prior
cholecystectomy, ERCP with sphincterotomy allows
for removal of the offending stone.23
The rarity of the disease among pregnant patients
creates challenges in the development of pregnancyspecific guidelines for gallstone pancreatitis. Treatment
and diagnostic guidelines from the nonpregnant literature guide current management options. Recent increasing evidence supports the use of cholecystectomy or
ERCP at time of diagnosis to decrease recurrence rates
and improve outcomes in pregnancy.

Treatment of Gallstone Pancreatitis in Pregnancy

Conservative treatment of pancreatitis includes pain
control, fluid resuscitation, and nutrition therapy. Initial treatment among nonpregnant patients includes

SHTG PANCREATITIS IN PREGNANCY

As with all cases of pancreatitis in pregnancy, the incidence of SHTG-induced pancreatitis increases with

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Obstetrical and Gynecological Survey

increasing gestational age.13,22 Severe hypertriglyceridemiaassociated pancreatitis further increases the rates of preterm
delivery and fetal demise, with 1 small report showing
60% versus 14% fetal demise rates with SHTG versus
gallstone pancreatitis, respectively.3
The mechanisms by which SHTG induces acute pancreatitis have yet to be fully elucidated. One theory
suggests that spontaneous hydrolysis of triglycerides
by lipase from pancreatic acinar cells results in increased concentrations of free fatty acids. These unbound fatty acids in sufficient quantities are cellular
toxins and result in acinar cell and capillary injury.
High concentrations of chylomicrons increase serum
viscosity, resulting in capillary plugging in the pancreas. The blocked capillaries create an ischemic environment, resulting in pancreatic autodigestion causing
pancreatitis.4
Lipid Physiology in Pregnancy
All pregnancies experience a physiologic increase
in triglyceride and total cholesterol levels during pregnancy.26 Levels of both substances are in reference
ranges in the first trimester and rise throughout pregnancy with cholesterol increasing by 50% and triglycerides 2- to 4-fold.26,27 Estrogen, progesterone, and
human placental lactogen mediate these changes.27,28
The placenta uses cholesterol for steroid synthesis,
and fatty storage occurs in preparation for rapid fetal
growth. Physiologic increases in triglycerides and cholesterol do not typically exceed 332 and 335 ng/mL,
respectively.26 Severe hypertriglyceridemia, defined as
triglyceride level exceeding 1000 ng/mL, occurring in
pregnancy is pathologic. Extreme elevations in triglycerides increase the patients risk for pancreatitis as well
as hyperlipoproteinemia later in life.27
Familial Hyperlipidemias
Familial hyperlipidemias can result in elevations
of triglycerides, cholesterol, or both. Familial hypertriglyceridemia (Fredrickson type IV) is an autosomal
dominant disease that is associated with baseline
triglyceride levels of 200 to 400 mg/dL. Pregnancy,
estrogen-containing oral contraceptive pills, and alcohol abuse can precipitate severe elevations.29
Many patients who present with SHTG have a combination of elevated chylomicrons and triglycerides
(Fredrickson type V). These patients have an underlying disorder of triglyceride metabolism that becomes
exacerbated by a secondary factor such as pregnancy, uncontrolled diabetes, hypothyroidism, nephrotic syndrome, or alcohol abuse. Drugs such as oral

contraceptives, oral estrogen replacement, tamoxifen,

-blockers, glucocorticoids, and some of the HIVantiretroviral agents can cause SHTG in susceptible individuals. These patients can also present with pancreatitis
and eruptive xanthomas.29
Emerging in early childhood or infancy, familial chylomicronemia causes severe elevations in triglycerides,
often more than 1000 mg/dL. Very large accumulations of chylomicrons due to a complete deficiency
of lipoprotein lipase or its cofactor apoprotein C-II
characterize this rare autosomal recessive disorder.30
These patients demonstrate hepatosplenomegaly and
xanthomas and will likely be diagnosed prior to reproductive age.29
In addition, familial combined hyperlipidemia has a
complex mode of inheritance, which has not been fully
elucidated. It is a very common disorder and can present with isolated levels of cholesterol (Fredrickson 2a),
triglycerides (Fredrickson 4), or a combination of elevated cholesterol and triglycerides (Fredrickson 2b).
High plasma levels of apoprotein B help confirm the diagnosis.31 Fredrickson 2b is also associated with a family history of early-onset cardiovascular disease.29 The
normal changes in lipid metabolism during pregnancy
coupled with underlying defects in very low-density lipoprotein clearance predispose a patient with familial
hyperlipidemia to SHTG and pancreatitis.27
In contrast, familial hypercholesterolemia syndromes
lead to elevations only in cholesterol and do not cause
triglyceride disturbances. A defect in the low-density lipoprotein (LDL) receptor disrupts the cells ability to
internalize and catabolize LDL particles, leading to severe elevations in serum cholesterol.32 Associated with
more than 1600 LDL receptor mutations, mutations in
apolipoprotein B and proprotein convertase subtilisin/
kexin 9 can lead to similar phenotypes.32 The heterozygous form of the disease occurs in approximately 1 per
500 individuals.33 Total cholesterol values range from
350 to 500 mg/dL at baseline; patients often present
with early-onset cardiovascular disease, cholesterol
xanthomas, and a family history of early cardiovascular disease or death.32 The homozygous form of disease leads to total cholesterol levels between 650 and
1000 mg/dL. Homozygous familial hypercholesterolemia leads to tendon xanthomas and cardiovascular
disease in childhood and occurs in 1 per 1 million individuals. 33 The hypercholesterolemia syndromes
do not typically cause elevations in triglycerides and
therefore are not considered a major risk factor for
hypertriglyceride-induced pancreatitis in pregnancy. Interestingly, recent evidence suggests an association between aberrations in cholesterol levels in pregnancy and
risk of hypertensive syndromes of pregnancy.34,35

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Gallstone and Pancreatitis in Pregnancy CME Review Article

Women who develop disorders during pregnancy

associated with abnormal cholesterol and triglycerides such as pancreatitis and preeclampsia should be
screened for familial syndromes and underlying dyslipidemia. Simple screening methods including a detailed
family history, serum lipids, and physical examination
can identify those women who require further evaluation for familial syndromes. Finally, patients with
known risk factors for hypertriglyceridemia such as diabetes mellitus, obesity, and alcoholism may experience
severe gestational hyperlipidemia.27 These severe elevations can also lead to adverse pregnancy outcomes
and pancreatitis.
Treatment of Severe Hyperlipidemia
Because lipoprotein levels are not routinely measured
in pregnancy, SHTG may go unrecognized until an
acute pancreatitis episode. Therapy to improve severely
elevated triglyceride levels in pregnancy is expected
to decrease the risk of pancreatitis.28 Effective treatments for SHTG include fat-restricted diet, omega-3
fatty acid supplementation, and oral therapy such as niacin and fenofibrates. Omega-3 fatty acid supplementation can lower serum triglyceride levels 20% to 50%.36
Doses equal to or greater than 3 g/d of eicosapentaenoic acid/docosahexaenoic acid are needed to achieve
these reductions, and these high doses may be difficult
to tolerate.
Fibrates, a category C medication, work to raise highdensity lipoprotein and lower triglycerides through upregulation of lipoprotein lipase metabolism.28 Niacin,
also a category C medication with no known reports
of teratogenicity, reduces hepatic synthesis of triglycerides, decreases cholesterol transport out of the liver, and
reduces free fatty acid degradation in hepatocytes.28
Treatment for hypercholesterolemia outside pregnancy usually consists of a statin medication. Bile acid
sequestrants and ezetimibe, both of which lower intestinal absorption of cholesterol and are pregnancy category C, may be added to statin therapy if warranted
by disease severity.28 The statin class of medications
lowers cholesterol by 20% to 60% through the inhibition of HMG-CoA reductase. These medications are
considered pregnancy category X because of theoretical
concerns of altered fetal cholesterol synthesis. At least 1
case-control study reported no statistically significant
increases in teratogenicity among statin-exposed pregnancies37 A review of the literature found evidence
regarding the effects of statin exposure in pregnancy
was limited by confounders, small samples, recall bias,
and ethical limitations.38 Although statins will not decrease triglyceride levels among patients at risk for

581

pancreatitis, these medications theoretically could improve outcomes in women with significantly elevated
cholesterol levels who are at risk for adverse pregnancy
outcomes. Based on the current level of evidence, patients requiring routine statin medications should discontinue these treatments prior to conception and restart
following pregnancy and lactation. Physicians should
encourage patients with a history of hyperlipidemia
prior to pregnancy to maintain some form of treatment in an effort to prevent severe pathologic lipid
elevations.
Treatment of SHTG-Induced Pancreatitis
Treatments for SHTG pancreatitis include diet restriction, pain control, aggressive hydration, and therapeutic
plasma exchange (TPE). Physiologic increases in lipoproteins reverse following delivery, reaching normal
levels at approximately 6 weeks postpartum.28 For these
pregnancies at term, delivery may be considered in an
effort to improve SHTG and lead to resolution of the
acute pancreatitis episode. Treatment for acute SHTG
pancreatitis in pregnancies remote from term requires
aggressive therapy to prevent iatrogenic preterm delivery
and maternal and fetal mortality.
Lipopheresis, or TPE, leads to rapid improvement of
marked hypertriglyceridemia. This apheresis procedure can be utilized for the direct removal of excessive
triglycerides from the serum, thus reducing continued
pancreatic inflammation and damage.39 The exchange
of plasma requires reliable venous access, typically
through a central venous catheter designed to withstand significant flow and pressures (such as a typical
dialysis catheter) with radiographic confirmation of
placement. Three modalities of lipopheresis are available:
discontinuous-flow centrifugation, continuous-flow centrifugation, and plasma filtration. Centrifugation processes rely on separation of molecules based on
molecular weight, whereas plasma filtration utilizes
highly selective filters targeting specific blood constituents. The mechanical action of lipopheresis removes
the patients lipemic blood, filters and removes the
offending materials, and returns a cleaned blood
to the patient.40 Supplemental albumin, often in conjunction with normal saline, replaces filtered volume.
Unfractionated heparin infusion prevents clotting in
the apheresis apparatus and facilitates triglyceride
reductions.41
A single session of lipopheresis reduces triglyceride levels by up to 70% and can lead to marked clinical improvement.42 Larger volume exchanges can cause
more precipitous decreases in serum triglycerides.
Early, rapid correction of excessive triglycerides gives

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582

Obstetrical and Gynecological Survey

the greatest therapeutic benefit in severe pancreatitis.43

Treatment sessions should continue until reaching a target triglyceride level of less than 500 mg/dL. Most patients demonstrate marked symptomatic relief with 2
to 3 plasma exchanges.41,44 Standard pharmacological
treatments should not be withheld or delayed when considering plasmapheresis.
Lipopheresis is an invasive procedure with potential adverse effects. The large volume shifts necessary for therapeutic exchange may result in transient
hypotension, nausea, vomiting, and other vasovagal symptoms.45 Transient hypotension decreases
placental blood flow in pregnancy and can lead to
nonreassuring fetal status. Appropriate volume resuscitation ameliorates these symptoms. Sequestration
of calcium by citrate reduces ionized calcium levels,
and prophylactic calcium supplementation may be
necessary to avoid cardiac arrhythmias.46 Reduced
fibrinogen levels and coagulation factors during lipopheresis may cause coagulopathy and bleeding
complications.47 Interrupting the delicate balance of
coagulation in pregnancy can lead to massive hemorrhage and devastating maternal and fetal outcomes.
Plasma exchange can also cause anaphylactic reactions due to a reaction to immunoglobulin A during
the exchange, resulting in serious morbidity and
mortality.48
There are few reports of lipopheresis to treat SHTG
and hypertriglyceridemia-induced pancreatitis in pregnancy.41,49,50 Because of the rarity of disease, there
are no randomized controlled trials evaluating the use
of lipopheresis in the setting of SHTG pancreatitis.
Mild to moderate cases of SHTG-induced pancreatitis
can be treated initially with pain control, diet restriction,
and volume resuscitation. Insulin infusions with glucose solution may help in some cases. In severe cases,
remote from delivery, lipopheresis should be considered to prevent maternal and perinatal morbidity
and mortality. In these situations, the benefits of resolution of pancreatitis outweigh the theoretical risks
of lipopheresis. Sivakumaran et al50 reported a case of
familial hypertriglyceridemia in which lipopheresis
was used to prevent SHTG and pancreatitis. This
case required 13 total plasma exchanges to maintain
triglyceride levels less than 1000 ng/mL. Bildirici
et al51 reported a case of SHTG-induced pancreatitis
in the third trimester treated with TPE 3 times over
5 days resulting in resolution of the disease and no adverse maternal, fetal, or neonatal outcomes. Severe
hypertriglyceridemia-induced pancreatitis causes significant maternal and perinatal morbidity. Although
the rarity of this form of pancreatitis limits a careful evaluation of all treatment options, lipopheresis

appears to be a useful tool in treating this potentially

morbid condition.
Fetal Effects of Maternal Hyperlipidemia
In addition to the risk for preterm delivery from maternal hypertensive disorders or the effects of pancreatitis, fetal exposure to severe maternal dyslipidemia may
be detrimental to the health of the child. Aortic evaluation at autopsy of young adults and children noted
significantly increased rate of fatty streak formation
among those children born to mothers with known hypercholesterolemia.52 The same group also evaluated
maternal and neonatal cholesterol levels and noted significant correlations when the fetus was born at less
than 6 months of age (r = 0.88, P < 0.01). The same correlation was not seen for fetuses delivered at term. The
elevated cholesterol levels in the early fetuses may be
due to an early effect that is not seen at later gestational
ages.53 In addition, children with maternally inherited
familial hypercholesterolemia demonstrate higher cholesterol levels than do those with paternally inherited
disease.54 The findings from these studies emphasize
the importance of optimizing maternal lipid status during pregnancy.
CONCLUSIONS
Both biliary disease and severe lipid elevations are
risk factors for pancreatitis. Pregnancy can cause exacerbations in these risk factors leading to pancreatitis.
Pregnancy should not alter disease recognition and
treatment. Patients presenting with gallstone disease
may undergo ERCP or cholecystectomy safely in pregnancy. Those patients with SHTG pancreatitis should
undergo a complete family history as they likely suffer
from a familial syndrome, which may be previously undiagnosed. Treatment of pancreatitis through removal
of the offending stone or serum lipids can lead to more
rapid improvement, decrease recurrence rates, and improve perinatal outcomes.
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