Narrative review on managing hypertriglyceridemia in pregnancy, including olezarsen and volanesorsen

Pregnancy induces profound metabolic adaptations, including marked rises in lipid concentrations. Triglyceride levels may increase by 100–300% compared with pre-pregnancy values, and in some women this physiological response exceeds the adaptive range. Although triglyceride elevation alone does not necessarily increase the risk of complications, higher triglyceride levels have been linked to maternal disorders such as preeclampsia, gestational hypertension, and acute pancreatitis, as well as adverse fetal outcomes, including abnormal birth weight and preterm delivery. Management of hypertriglyceridemia in pregnancy is challenging due to limited pharmacologic options and the need to ensure fetal safety. A personalized, multidisciplinary strategy—based on a low-fat diet, weight optimization, and regular physical activity—remains first-line therapy. In severe hypertriglyceridemia with imminent pancreatitis risk, rapid interventions such as pharmacotherapy or therapeutic plasma exchange are required to promptly reduce triglyceride levels. Novel agents targeting apolipoprotein C-III (olezarsen, volanesorsen) can lower triglycerides by 40–70%, but their safety in pregnancy is not established. While olezarsen is not recommended, two case reports describe successful and safe use of volanesorsen in pregnant women with familial chylomicronemia syndrome under close monitoring. This narrative review synthesizes current evidence on the pathophysiology, prognostic implications, and management of hypertriglyceridemia in pregnancy, emphasizing early risk identification, first-trimester lipid assessment, and individualized treatment aligned with the updated ESC/EAS guidelines.