What is the management of hypertriglyceridemia (high triglyceride levels) in pregnancy?

Management of Hypertriglyceridemia in Pregnancy

Statins, ezetimibe, and PCSK9 inhibitors must be discontinued ideally 3 months before conception and throughout pregnancy and lactation; if pregnancy occurs while on these medications, stop them immediately and reassure the patient that harm to the fetus is unlikely. 1

Immediate Medication Discontinuation

• All systemically absorbed cholesterol-lowering drugs (statins, ezetimibe, PCSK9 inhibitors) should be stopped immediately upon pregnancy confirmation or ideally 3 months before planned conception. 1
• Statins are not part of the treatment regimen during pregnancy and are not recommended at present. 1
• If a woman becomes pregnant while taking these medications, discontinue them and provide reassurance that fetal harm is unlikely. 1

Risk Stratification and Monitoring

• Monitor triglyceride levels once per trimester in all women at high risk for hyperlipidemia (those with prepregnancy fasting triglycerides >250 mg/dL or 4 mmol/L). 2, 3
• If fasting triglycerides exceed 250 mg/dL during pregnancy, check monthly triglyceride levels and screen for gestational diabetes. 3
• Triglyceride levels physiologically increase during pregnancy, so routine assessment is not necessary unless results will change management (except in homozygous familial hypercholesterolemia). 1

Lifestyle Interventions by Severity

For Triglycerides 250-500 mg/dL:

• Implement a strict low-carbohydrate, low-fat diet with exercise immediately. 3
• Reinforce heart-healthy behaviors including diet, physical activity, and psychological well-being. 1
• Eliminate all added sugars and alcohol completely. 4

For Triglycerides 500-1000 mg/dL:

• Restrict total dietary fat to <20 g/day or <15% of total calories under guidance of a registered dietitian. 3, 4
• Eliminate all added sugars and abstain completely from alcohol. 4
• Consider hospital admission for severe cases requiring intensive monitoring. 2

For Triglycerides >1000 mg/dL:

• Implement extreme dietary fat restriction (<5% of total calories) immediately. 1, 4
• Hospital admission is strongly recommended for intensive management. 2, 5

Pharmacologic Management Algorithm

First-Line Therapy (Triglycerides >500 mg/dL despite lifestyle modifications):

• Prescription omega-3 fatty acids (Lovaza) 4-12 g/day should be initiated as first-line pharmacologic therapy. 3, 6
• High-dose omega-3 fatty acids (up to 12 g/day) have been used successfully to maintain triglycerides <800 mg/dL throughout pregnancy. 6

Second-Line Therapy (Triglycerides remain >500 mg/dL):

• Bile acid sequestrants should be considered, ideally started 3 months before planned pregnancy and continued during pregnancy and lactation. 1
• Monitor for malabsorption of fat-soluble vitamins (particularly vitamin K with INR) and folate when using bile acid sequestrants. 1

Third-Line Therapy (Consider with caution):

• Fibrates (fenofibrate or gemfibrozil) should be considered as second-line therapy only when benefits outweigh unclear teratogenic risks. 3, 5
• Fibrate use during pregnancy has unclear risk-benefit profile and potential teratogenic effects, but may be necessary to prevent pancreatitis. 3
• If fibrates are used, fenofibrate is preferred over gemfibrozil due to better safety profile. 7

Fourth-Line Therapy (Triglycerides >1000 mg/dL or symptomatic pancreatitis):

• Plasmapheresis should be considered early in asymptomatic pregnant women with fasting triglycerides >1000 mg/dL. 3
• Plasmapheresis is indicated for pregnant women with clinical signs of pancreatitis and triglycerides >500 mg/dL despite maximal therapy. 3, 6
• Therapeutic plasma exchange has been used successfully in severe cases. 2, 6

Alternative Therapies (Case reports only):

• Niacin has been used successfully in pregnancy when other treatments failed, titrated to 2000 mg/day to maintain triglycerides <1000 mg/dL. 8
• Niacin is often underutilized due to perceived side effects but may be effective when conventional therapies are inadequate. 8
• Intravenous insulin infusion may be considered in the context of hyperglycemia and severe hypertriglyceridemia. 2, 6
• Subcutaneous heparin has been reported in case series but lacks strong evidence. 6, 5

Special Considerations for High-Risk Patients

• Women with homozygous familial hypercholesterolemia or high-risk heterozygous familial hypercholesterolemia should undergo cardiovascular imaging (CT angiography for coronary disease or echocardiography for aortic stenosis) before planned pregnancy. 1
• In women with homozygous familial hypercholesterolemia and clinical atherosclerotic cardiovascular disease, continued statin use should be considered, particularly after the first trimester if LDL-cholesterol goals are not achieved. 1
• Lipoprotein apheresis should be continued or initiated during pregnancy in women with homozygous familial hypercholesterolemia, especially those with established cardiovascular disease. 1

Critical Pitfalls to Avoid

• Do not delay aggressive intervention when triglycerides exceed 1000 mg/dL—maternal mortality from acute pancreatitis approaches 20%. 3
• Do not continue statins during pregnancy to manage hypertriglyceridemia, as they are contraindicated and ineffective for preventing pancreatitis. 1
• Do not rely solely on lifestyle modifications when triglycerides exceed 500 mg/dL—pharmacologic therapy is mandatory. 3
• Do not overlook screening for gestational diabetes, as poor glycemic control is a primary driver of severe hypertriglyceridemia. 3
• Do not use bile acid sequestrants without monitoring fat-soluble vitamins, particularly vitamin K. 1

Multidisciplinary Team Approach

• Assemble a multidisciplinary team including maternal-fetal medicine, endocrinology, registered dietitian, and potentially nephrology for plasmapheresis. 2, 5
• Most cases of severe hypertriglyceridemia during pregnancy are best managed in consultation with a lipid specialist. 1

Postpartum Management

• Triglyceride levels typically normalize postpartum, but long-term management is essential to prevent recurrence in future pregnancies. 8, 6
• Resume appropriate lipid-lowering therapy after delivery and completion of breastfeeding. 6