Revisiting the Role of Omega-3 Fatty Acids in Preeclampsia: A Systematic Review and Meta-Analysis

Abstract Context Preeclampsia remains one of the major causes of neonatal and maternal morbidity. Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), can influence placental function and vascular health, potentially affecting preeclampsia risk. Objective The objective of this review was to systematically evaluate and quantitatively synthesize evidence on maternal DHA levels in women with preeclampsia compared with normotensive controls. Data Sources A systematic search was conducted across the PubMed, Scopus, and Cochrane Library databases to identify to identify eligible studies published between January 1990 and February 2026. Data Extraction We extracted data on study characteristics, sample details, gestational timing, and omega-3 fatty acid levels from each included study. Data Analysis A random-effects model was used to calculate standardized mean differences (SMDs). Six pre-specified subgroup analyses and a leave-one-out sensitivity analysis were conducted to investigate sources of heterogeneity. Certainty of evidence was assessed using the GRADE framework. The primary pooled analysis demonstrated lower DHA levels in women with preeclampsia compared with normotensive controls (SMD = −0.20; 95% CI: −0.57 to 0.17; P = .289; I² = 89.05%). A pre-specified sensitivity analysis excluding 2 methodologically outlying studies yielded an exploratory significant effect (SMD = −0.24; 95% CI: −0.39 to −0.09; P = .002; I² = 29.1%). Across 6 subgroup analyses, significant negative associations were observed in Indian, Gas Chromatography–Flame Ionization Detection (GC-FID), cross-sectional, and at-delivery subgroups, with the largest effect size being observed in early pregnancy studies (SMD = −0.42). The certainty of the evidence was rated Very Low for all outcomes. Conclusion Lower DHA levels are consistently associated with preeclampsia across diverse populations; however, Very Low certainty of evidence precludes causal conclusions. The directional consistency, particularly in early pregnancy, warrants investigation through prospective longitudinal studies with standardized protocols and dietary confounder control. Systematic Revivew Registration PROSPERO registration No. CRD420261378084.