Preeclampsia is a pregnancy-specific hypertensive disorder characterized by new-onset hypertension and proteinuria occurring after 20 weeks of gestation. It is a major cause of maternal and perinatal morbidity and mortality worldwide, particularly in low- and middle-income countries (1). The global incidence of preeclampsia is estimated to be around 2-8% of all pregnancies, contributing significantly to preterm birth, intrauterine growth restriction, and adverse maternal outcomes (2,3). Despite advancements in obstetric care, effective prevention strategies remain limited.

Low-dose aspirin has been recommended as a preventive measure for preeclampsia among high-risk women due to its antiplatelet effects, which help reduce placental ischemia and endothelial dysfunction, key contributors to preeclampsia development (4). The American College of Obstetricians and Gynecologists (ACOG) recommends initiating low-dose aspirin (81 mg/day) between 12 and 28 weeks of gestation for women at high risk of developing preeclampsia (5). Multiple studies have demonstrated the efficacy of low-dose aspirin in reducing the incidence of preeclampsia and associated complications when administered early in pregnancy (6,7).

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have gained attention for their anti-inflammatory, antioxidant, and vasodilatory properties, which may play a role in preventing preeclampsia (8). Several observational studies have suggested that omega-3 fatty acid supplementation may reduce the risk of preeclampsia by modulating inflammatory pathways and improving endothelial function (9,10). However, findings from randomized controlled trials have been inconsistent, with some studies reporting no significant benefit from omega-3 supplementation alone (11,12).

The combination of low-dose aspirin and omega-3 fatty acids presents a potentially synergistic approach for preventing preeclampsia by targeting multiple pathophysiological pathways. This study aims to evaluate the efficacy of low-dose aspirin, omega-3 fatty acids, and their combination in preventing preeclampsia among high-risk pregnant women. The findings of this study could provide valuable insights into optimizing preventive strategies for preeclampsia and improving maternal and neonatal outcomes.

The study included 300 pregnant women aged between 18 and 40 years, identified as high-risk for preeclampsia based on established criteria, including a history of preeclampsia, chronic hypertension, multiple gestations, diabetes mellitus, or autoimmune disorders. Pregnant women with known hypersensitivity to aspirin or omega-3 fatty acids, severe hepatic or renal impairment, or other contraindications to these interventions were excluded.

Randomization and Group Allocation: Participants were randomly assigned into three groups using a computer-generated randomization sequence:

• Group A (Low-Dose Aspirin Group): Received low-dose aspirin (81 mg/day).
• Group B (Omega-3 Fatty Acids Group): Received omega-3 fatty acids (1 g/day).
• Group C (Combination Group): Received a combination of low-dose aspirin (81 mg/day) and omega-3 fatty acids (1 g/day).

Randomization codes were sealed in opaque envelopes and assigned by an independent investigator to ensure allocation concealment.

Intervention Protocol: The interventions were initiated between 12 and 16 weeks of gestation and continued until delivery. Compliance was monitored through regular follow-up visits every 4 weeks, where participants were asked to return unused medications and report adverse events, if any.

Outcome Measures: The primary outcome was the incidence of preeclampsia, defined according to the American College of Obstetricians and Gynecologists (ACOG) criteria as new-onset hypertension (≥140/90 mmHg) and proteinuria (≥300 mg/24 hours) occurring after 20 weeks of gestation.
The secondary outcomes included the incidence of gestational hypertension (hypertension without proteinuria), maternal adverse events (such as gastrointestinal symptoms, bleeding complications, and allergic reactions), and neonatal outcomes (including birth weight, Apgar scores, and admission to the neonatal intensive care unit).

Data Collection: Baseline demographic and clinical characteristics were recorded during the initial visit. Blood pressure measurements and urine analysis were performed at each follow-up visit. Neonatal outcomes were assessed immediately after delivery. Data were collected using a structured proforma and entered into a secure database.

Statistical Analysis: Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 27.0. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. Differences between groups were analyzed using one-way analysis of variance (ANOVA) for continuous variables and the chi-square test for categorical variables. A p-value of <0.05 was considered statistically significant.

A total of 300 high-risk pregnant women were enrolled in the study and randomly assigned to three groups: Group A (Low-Dose Aspirin, n = 100), Group B (Omega-3 Fatty Acids, n = 100), and Group C (Combination of Low-Dose Aspirin and Omega-3 Fatty Acids, n = 100). The baseline characteristics of participants were similar across all groups (Table 1).

Table 1: Baseline Characteristics of Study Participants

The incidence of preeclampsia was significantly lower in Group C (8%) compared to Group A (15%) and Group B (12%) (p = 0.03). The results indicate a relative risk reduction of 46.7% in Group C compared to Group A, and 33.3% compared to Group B (Table 2).

Table 2: Incidence of Preeclampsia and Gestational Hypertension

Neonatal outcomes, including birth weight and Apgar scores, were also improved in the combination group (Group C) compared to the other groups (Table 3).

Table 3: Neonatal Outcomes

The combination therapy of low-dose aspirin and omega-3 fatty acids (Group C) demonstrated better outcomes in reducing the incidence of preeclampsia and gestational hypertension, as well as improving neonatal birth weights and Apgar scores (Tables 2 and 3).

The findings of this randomized controlled trial suggest that the combination of low-dose aspirin and omega-3 fatty acids significantly reduces the incidence of preeclampsia and gestational hypertension in high-risk pregnant women compared to either intervention alone. Furthermore, neonatal outcomes, particularly birth weight and Apgar scores, were notably better in the combination therapy group, indicating a potential synergistic effect.

Low-dose aspirin has been well-documented for its efficacy in reducing the risk of preeclampsia by inhibiting platelet aggregation and improving placental blood flow through its anti-inflammatory and antithrombotic properties (1,2). Previous studies have demonstrated that the administration of low-dose aspirin, particularly when initiated before 16 weeks of gestation, effectively reduces the incidence of preeclampsia among high-risk women (3). Our findings align with these studies, as participants receiving low-dose aspirin alone (Group A) experienced a lower incidence of preeclampsia than previously reported rates in high-risk populations (4).

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been proposed to have protective effects against preeclampsia due to their anti-inflammatory, vasodilatory, and endothelial-stabilizing properties (5,6). Although some studies have reported no significant benefit of omega-3 supplementation alone in preventing preeclampsia (7), others have shown reduced incidence rates and improved maternal outcomes, particularly when administered in adequate dosages and for extended durations (8,9).

The combination of low-dose aspirin and omega-3 fatty acids demonstrated superior efficacy in our study, reducing the incidence of preeclampsia to 8% compared to 15% and 12% in the aspirin-only and omega-3-only groups, respectively. The enhanced efficacy may be attributed to the complementary mechanisms of action of the two interventions. While aspirin primarily targets platelet aggregation and placental blood flow, omega-3 fatty acids reduce systemic inflammation and improve endothelial function, providing a more comprehensive approach to preeclampsia prevention (10,11).

The improvement in neonatal outcomes observed in the combination group further supports the potential benefits of dual therapy. Improved birth weights and higher Apgar scores in Group C are consistent with previous studies indicating that adequate omega-3 fatty acid intake during pregnancy is associated with enhanced fetal growth and development (12,13). Additionally, the observed reduction in gestational hypertension in Group C suggests that the combination therapy may also be effective in preventing other hypertensive disorders of pregnancy (14,15).

Limitations of the study:

Despite the promising findings, some limitations must be acknowledged. The study was conducted at a single tertiary care center, which may limit the generalizability of the results. Additionally, the duration of follow-up was limited to the pregnancy period, and long-term outcomes for both mothers and infants were not assessed. Furthermore, adherence to the interventions was monitored only through self-reports and return of unused medication, which may have introduced reporting bias. Future studies with larger sample sizes, multi-center designs, and extended follow-up periods are warranted to confirm these findings and establish standardized guidelines for the combined use of low-dose aspirin and omega-3 fatty acids in high-risk pregnancies. Additionally, exploring the optimal dosage and timing of intervention initiation could further enhance the efficacy of this preventive approach.

This study concluded that combination of low-dose aspirin and omega-3 fatty acids seems to be more effective in reducing the incidence of preeclampsia and gestational hypertension compared to either intervention alone. This combined approach may be a favourable strategy for preventing preeclampsia in high-risk pregnant women. Further large-scale studies are necessary to confirm these findings.

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