Antioxidants for preventing pre-eclampsia.

Systematic review and meta-analysis of randomized trials in pregnant women at low, moderate, or high risk of pre-eclampsia. Women with established pre-eclampsia were excluded, and most trials enrolled singleton pregnancies in mid-pregnancy, often before 20 weeks' gestation.

Oral antioxidant supplementation during pregnancy, most commonly vitamin C 1000 mg plus vitamin E 400 IU daily, with other trials using lycopene, selenium, red palm oil containing a tocotrienol-rich fraction, or multivitamin regimens. Interventions were generally started in mid-pregnancy or before 20 weeks' gestation and continued until delivery or late pregnancy; one regimen also included fish oil.

Routine antioxidant supplementation in pregnancy did not clearly prevent pre-eclampsia. The pooled effect for pre-eclampsia was RR 0.73, 95% CI 0.51 to 1.06 across nine trials and 5446 women, with no clear benefit for severe pre-eclampsia, small-for-gestational-age birth, or baby death. Antioxidants were associated with more antihypertensive therapy (RR 1.77, 95% CI 1.22 to 2.57) and more antenatal hospital admission for hypertension (RR 1.54, 95% CI 1.00 to 2.39); preterm birth also trended slightly higher (RR 1.10, 95% CI 0.99 to 1.22). Small single-trial signals suggested possible benefit for lycopene and for vitamin C plus E combined with aspirin and fish oil, but the authors concluded that routine antioxidant supplementation is not supported by current evidence.

The evidence base was heterogeneous, with different antioxidants, doses, cointerventions, and starting times across mostly small trials. Several favorable subgroup findings came from single, limited studies, some outcomes had variable denominators or interim analyses, and long-term infant or maternal outcomes were not reported. Overall certainty is limited by indirectness and inconsistent trial quality.