Dietary supplements and drugs for preeclampsia prophylaxis

Abstract

Pre-eclampsia (PE) is a major cause of mortality and morbidity during pregnancy. Many different strategies to prevent PE have been investigated in randomized controlled trials, but none have been found to be widely effective and this is not surprising given the complexities in pathogenesis. Low-dose aspirin, diminishing platelet thromboxane synthesis, seems to prevent or delay PE. A meta-analysis of individual patient data from 32,217 women (PARIS collaborative group) asses that low-dose aspirin during pregnancy is associated with moderate reduction in the relative risk of PE (RR 0.90 95%CI 0.84–0.97), of birth before 34 weeks’ gestation (RR 0.90 95%CI 0.83–0.98), and of having a pregnancy with a serious adverse outcome (RR 0.90 95%CI 0.85–0.96). This effect seems to be more significant in women at high risk of developing PE. Regarding diet and nutrients, there does not appear to be any clear benefit for prevention of PE from routine dietary supplementation. There is high quality evidence that vitamin C and vitamin E are not effective for prevention or treatment of PE. Actually a meta-analyses found that supplementation with these antioxidants is associated with a slightly increased risk of gestational hypertension and premature rupture of membranes. Also there is not enough high-quality evidence to show that dietary magnesium or omega-3 fatty acids supplementation during pregnancy is beneficial. Calcium supplementation instead appears to reduce the risk of PE and the rare occurrence of the composite outcome ’death or serious morbidity’ specially in women with a low baseline calcium intake. Some studies assess that preeclamptic women may be deficient in nitric oxide, which mediates vasodilatation and inhibits platelet aggregation. For this reason NO donors, such as isosorbide dinitrate, glyceryl trinitrate and S-Nitroglutathione, were used in some trials as treatment in preeclamptic women. Despite the reduction in blood pressure and in uterine artery pulsatility index, these substances were rarely used in clinical practice because of adverse effects such as headache or preoxynitrite production. Also l -arginine, the substrate for synthesis of nitric oxide, has been investigated as a mean of preventing PE. Even though a dysfunction of the l -arginine-NO pathway that seems to be present in preeclamptic women, l -arginine load appears to be associated with increased nitric oxide (NO) production, hypotension and reduction of PE/eclampsia rate. Also in obese women there is a dysfunction of the l -arginine-NO pathway that causes a decrease of endothelial-dependent vasodilatation. In these women a l -arginine supplement could be helpful. Conclusion Aspirin proven to be of some help provided dose and timing are adequate. Impact on PE is limited, and its use is better in high-risk. Calcium supply could be helpful in population with low dietary intake. l -Arginine supplementation is worth to receive the same attention aspirin had also considering that biological activity seems wider. Actual evidences are more robust than the ones that allows wasting time and money for Vitamins C and E.