Abstract
Objective
Hypertriglyceridemia (HTG) is a rare cause of acute pancreatitis (AP) in pregnancies and has emerged as an aggravating factor of severe pancreatitis. To enhance the diagnosis and management of HTG-induced AP during pregnancy by improving early recognition, optimizing treatment strategies, and minimizing maternal and fetal complications.
Case Report
This is a 29-year-old multigravida woman at a gestational age of 34 weeks and 2 days who presented with sudden abdominal pain and vomiting. She had severe hypertriglyceridemia (7855 mg/dL) and was diagnosed with acute pancreatitis. After an emergency cesarean section, the patient received aggressive hydration, as well as fenofibrate and gemfibrozil as lipid-lowering agents, along with other supportive care. This treatment led to a successful recovery.
Conclusion
The management of HTG-induced AP must consider both maternal and fetal health, with options such as lipid-lowering agents and plasmapheresis being explored, further research was required to ascertain their safety during pregnancy.
Introduction
Acute pancreatitis (AP) is an unusual condition in pregnancy, with an incidence rate of 0.02 %–0.1 % [ ]. The leading causes of AP during pregnancy are primarily gallstone disease and alcohol abuse. Hypertriglyceridemia (HTG) is a rare cause but has recently been recognized as an aggravating factor for severe pancreatitis. The clinical symptoms of AP can sometimes be misdiagnosed as other conditions presenting with abdominal pain during pregnancy. Mądro, A. described several management strategies for AP in a comprehensive review in 2022 [ ]. However, there are no definitive guidelines for the management of hypertriglyceridemia-induced AP.
We present a case of a multigravida woman at a gestational age of 34 weeks and 2 days who was referred to our emergency department due to sudden abdominal pain. The patient received aggressive hydration and lipid-lowering agents after a cesarean section, and she was successfully discharged following treatment.
Case presentation
A 29-year-old female (gravida 3, para 1, spontaneous abortion 1) presented at a gestational age of 34 weeks and 2 days, with gestational diabetes that was diet-controlled. The patient denied any past history of gallbladder stone, hyperlipidemia, or familial hypertriglyceridemia. She experienced sudden left lower abdominal pain, which later became diffuse across the entire abdomen, lasting for one day and accompanied by vomiting and persistent nausea. The patient denied any history of systemic disease, and her family history was unremarkable. She also denied a social history of smoking or alcohol consumption.
The patient was transferred to our emergency department for persisted abdominal pain the next day. At the emergency department, her body temperature was 36.6 °C, blood pressure was 101/62 mmHg, pulse rate was 87 beats per minute, respiratory rate was 20 breaths per minute, and oxygen saturation was 98 % while she was breathing ambient air. Her body height was 162 cm, and her body weight was 68 kg (body mass index: 25.91 kg/m 2 ). Physical examination showed diffused abdominal tenderness (rated 5 out of 10 on the Numeric Rating Scale), without xanthelasma or tendon xanthomas. Pelvic examination presented a closed cervix, with no bloody show or watery discharge. Laboratory tests revealed leukocytosis (15,400/mm 3 ) with neutrophil predominance (87.8 %), anemia (hemoglobin 9.3 g/dL), low hematocrit (27.6 %), hyponatremia (125 mmol/L), slightly decreased calcium (8.5 mg/dL), elevated serum amylase (136 U/L) and lipase (272 U/L), severe hypertriglyceridemia (7855 mg/dL), low albumin (3.1 g/dL), and fasting glucose of 121 mg/dL. Liver function test (AST of 16 U/L and ALT of 6 U/L), hs-CRP, renal function tests, coagulation profile, arterial blood gas parameters and urine analysis showed no significant abnormalities. Nalbuphine 15 mg was administered intravenously for abdominal pain within the first 5 h in the emergency department.
Ultrasonography presented a normal fetal heartbeat, no abdominal aortic aneurysm, and no retroplacental hematoma. Magnetic resonance imaging (MRI) revealed diffuse pancreatic swelling with fluid accumulation around the pancreas and in the left pararenal space ( Fig. 1 ). The patient was diagnosed with acute pancreatitis. We performed an emergency cesarean section immediately after diagnosis. A female infant was delivered, weighing 2390 g, with an Apgar score of 9 at both 1 and 5 min.
Ranson criteria for pancreatitis at admission scored zero points, while the criteria assessed 48 h later scored three points, indicating non-severe AP with a predicted mortality of 15 %. After delivery, we initiated combined care with the gastroenterology department for the management of acute pancreatitis. The patient recieved aggressive intravenous hydration with lactated Ringer’s solution and 20 % albumin (2 bottles over 3 days) to address hypoalbuminemia. She experienced mild shortness of breath due to more hydration being given. Chest X-ray revealed bilateral pleural effusion ( Fig. 2 ). We closely monitored her respiratory pattern and provided oxygen therapy. The patient remained NPO from the time of her arrival in the emergency department. Six hours after the cesarean section, her abdominal pain had progressively improved, and she was started on an oral clear liquid diet. Since she tolerated it well, oral feeding with a low-fat soft diet was introduced on the 5th day of admission. She was administered flomoxef as an antibiotic to prevent necrotizing pancreatitis. Gemfibrozil (300 mg twice daily) were given for hypertriglyceridemia on the first day, but we switched to fenofibrate (200 mg per day) due to the risk of gemfibrozil-induced severe rhabdomyolysis [ ]. We closely monitored her electrolytes in case of hypocalcemia, and her blood glucose remained within the normal range.
During hospitalization, symptoms such as epigastric tenderness and abdominal fullness improved. By the 8th day, laboratory tests showed a decline in serum TG to 667 mg/dL, along with decreases in serum amylase (83 U/L) and lipase (117 U/L). The complete blood count revealed no significant abnormalities. The patient was discharged on the 9th day, with no complications noted during outpatient follow-up.
Discussion
Diagnosis of AP in pregnancy
The maternal mortality rate of AP has been reported to be 37 %, with a fetal mortality rate of 60 % [ ]. Given the high mortality associated with AP, early diagnosis during pregnancy is critical. When a patient presents with an acute abdomen, AP must be clearly differentiated from peritonitis, placental abruption, uterine rupture and other obstetric complications [ ]. Elevating serum TG in AP patients are independently associated with persistent organ failure [ ]. Serum TG between 750 and 1000 mg/dL are required to induce acute pancreatitis [ ].
The American College of Obstetricians and Gynecologists (ACOG) suggests that female patients undergo annual lipid assessment before becoming pregnant, and that pregnant patients complete a lipid profile and screening for gestational diabetes at the first prenatal visit. It is also recommended that lipid profiles be monitored every trimester, or within 6 weeks if there is medical intervention for dyslipidemia [ ]. Wiznitzer et al. demonstrated in a population-based study that serum TG levels peak during the third trimester, though they do not exceed 250 mg/dL even at their highest [ ]. For patients whose serum TG levels exceed 250 mg/dL, monthly TG measurements are suggested [ ]. Overall, we recommend closely monitoring serum TG levels in high-risk patients for prevention, and for those diagnosed with AP, early lipid panel assessment is crucial to confirm a correlation with hypertriglyceridemia.
Management of hypertriglyceridemia-induced AP
Management of HTG-induced AP must consider both maternal and fetal health. In patients with gestational hypertriglyceridemia, maternal complications can include hyperviscosity syndrome, pre-eclampsia, and an increased risk of hyperlipoproteinemia. Fetal complications may include macrosomia, preterm labor, prematurity, or even fetal death [ ]. Conservative treatment is recommended for patients with AP during the first trimester, including adequate hydration, antispasmodics, analgesics and correction of electrolyte imbalances [ ]. If the patient’s condition worsens despite 24–48 h of intensive treatment, or if the course of AP is severe, termination of the pregnancy should be considered [ ].
Termination of pregnancy has to be determined by obstetricians and gastroenterologists with the patient’s consent. Indications for pregnancy termination include confirmed stillbirth or the need for fetal-toxic drugs to treat pancreatitis. The methods of pregnancy termination can include cesarean section, preterm or full-term natural delivery, and abortion [ ]. In this case, the patient was in the third trimester, and we performed an emergency cesarean section following the diagnosis due to her deteriorating condition.
Initial management of hypertriglyceridemia-related AP is similar to that for other causes of AP [ ]. Patients should remain NPO for bowel rest, receive adequate pain control, and undergo aggressive intravenous hydration (250–500 ml per hour of isotonic crystalloid solution, with lactated Ringer’s solution preferred during the first 24–48 h [ ]). According to the former FDA pregnancy categories, certain pain medications are contraindicated for pregnant patients due to potential adverse effects. Nonsteroidal anti-inflammatory drugs (all category D in the third trimester), aspirin (category D in the third trimester), metamizole (category C in the first and second trimesters; category D in the third trimester), and opioids (mostly category C during pregnancy) should be used with caution [ ]. Oxygen therapy may be provided if necessary. Patients should start a low-fat diet (with less than 20 % of total calories derived from fat), and omega-3 fatty acid supplements may be effective in preventing hyperlipidemia-induced pancreatitis during pregnancy [ ]. Once pain is well controlled, patients can begin with oral clear liquids and gradually progress to a low-fat diet if tolerated [ ]. Oral feeding with a low-fat diet typically starts within a week after admission for patients with mild AP [ ]. A randomized controlled trial indicated that nasogastric tube feeding within 24 h of admission reduces abdominal pain and the risk of oral food intolerance in patients with mild to moderate AP compared to remaining NPO [ ].
Lipid-lowering treatment for pregnancies
There are several lipid-lowering agents that should be considered. Insulin effectively regulates lipoprotein lipase (LPL) activity, leading to a reduction in serum TG levels. Thuzar et al. reported that serum TG levels decreased by 87 % within 24 h in patients managed with intravenous insulin and fasting, compared to a 40 % reduction in those treated with intravenous insulin alone and a 23 % reduction with subcutaneous insulin [ ]. The monotherapy of heparin remains controversial. Several case studies have demonstrated a synergistic effect from the combination of heparin and insulin, making it a first-line therapy for severe hypertriglyceridemia [ ]. High doses of niacin are not recommended for pregnant patients due to the risk of harm to the unborn fetus and potential side effects, including flushing and dysglycemia. However, a few case reports have described the use of niacin in the first trimester of pregnancy without any fetal adverse effects [ ]. In July 2021, the US Food and Drug Administration (FDA) requested the removal of the contraindication against statin use during pregnancy. Statins may be permitted for severe LDL-C increases when the obstetrician and gastroenterologist determine that the benefits outweigh the risks [ ]. However, it is important to note that the FDA still does not recommend the routine use of statins in pregnant patients.
Fibrates are peroxisome proliferator-activated receptor alpha (PPARα) activators that can enhance LPL activity and reduce apolipoprotein C3, leading to increased lipolysis and decreased triglyceride levels. However, the use of fibrate during pregnancy is limited due to animal studies showing skeletal and teratogenic effects [ ]. Fibrates are classified as category C under the former FDA pregnancy risk categories, and there are insufficient studies on their use in humans. Fibrates should only be used if the potential benefits justify the associated risks. One case reported the successful use of fenofibrate to manage hypertriglyceridemia in a third-trimester pregnant patient without adverse complications [ ]. Another case report indicated that the use of gemfibrozil during pregnancy is justified, as the consequences of untreated hypertriglyceridemia far outweigh the potential risks associated with gemfibrozil [ ]. Major congenital abnormalities are most likely to occur between 5 and 14 weeks of gestation (during the first trimester), so fibrates are recommended only for pregnancies after embryogenesis if necessary. Nonetheless, there has been a case report of a successful pregnancy in a patient who used fenofibrate during the first trimester [ ]. Further experience and research are needed to confirm the safety of fibrates in pregnant patients.
Plasmapheresis is another treatment option for severe hypertriglyceridemia. Wind et al. summarized 25 studies involving 67 pregnancies treated with apheresis for hypertriglyceridemic pancreatitis, recommending lipoprotein apheresis (LA) as a second-line therapy for pregnant patients with HTG-induced AP [ ]. The most common side effect of therapeutic plasma exchange (TPE) is maternal hypotension. To maintain hemodynamic stability, adequate saline infusion is essential during TPE. For patients in the second and third trimesters, lying on the left side is recommended to prevent compression of the inferior vena cava [ ].
Conclusion
We presented a successful case of a 29-year-old pregnant woman with HTG-induced AP, who was treated with aggressive hydration, fenofibrate and gemfibrozil as lipid-lowering agents, and supportive care such as analgesics and oxygen therapy. Initial management of HTG-induced AP follows standard principles of fasting, pain control, and aggressive intravenous hydration. Low-fat diets and omega-3 fatty acid supplements may be beneficial. Several lipid-lowering agents, including insulin, heparin, niacin, and statins, can effectively reduce serum TG levels. The choice of medication depends on the patient’s condition and safety considerations during pregnancy. Fibrates, such as fenofibrate and gemfibrozil, have shown promise in reducing TG levels in pregnant patients, although more research is needed to confirm their safety. Plasmapheresis, specifically lipoprotein apheresis, is considered a second-line therapy for severe HTG-induced AP during pregnancy. AP during pregnancy requires a multidisciplinary approach, involving obstetricians and gastroenterologists, to provide timely and individualized care.
Declaration of competing interest
The authors have no conflicts of interest relevant to this article.
References
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
