Vitamin C and vitamin E in pregnant women at risk of pre-eclampsia

Lucilla Poston and colleagues1Poston L Briley AL Seed PT Kelly FJ Shennan AH Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.Lancet. 2006; 367: 1145-1154Summary Full Text Full Text PDF PubMed Scopus (623) Google Scholar provide clinical evidence to support our concern that, owing to its non-antioxidant pleiotropic effects, exogenous vitamin E could interfere with the physiological progression of pregnancy—ie, Th1 to Th2 transition at the fetal-maternal interface.2Banerjee S Chambers AE Campbell S Is vitamin E a safe prophylaxis for preeclampsia?.Am J Obstet Gynecol. 2006; 194: 1228-1233Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar Poston and colleagues show that dietary intake of vitamin E in the second and third trimesters of pregnancy does not prevent the development of pre-eclampsia irrespective of the nature of risk at enrolment. Moreover, a significantly increased incidence of early-onset pre-eclampsia, low birthweight, and stillbirth in the vitamin-E-treated groups suggests a detrimental effect on the fetoplacental unit. We have additional concerns that the fetal immune development in treated groups could be directly influenced by a potential interferon gamma mimic such as a vitamin E.2Banerjee S Chambers AE Campbell S Is vitamin E a safe prophylaxis for preeclampsia?.Am J Obstet Gynecol. 2006; 194: 1228-1233Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar As a consequence of this, we believe that VIP and ongoing vitamin E trials in human pregnancy3Fraser WD Audibert F Bujold E Leduc L Xu H Boulvain M Julien P The vitamin E debate: implications for ongoing trials of pre-eclampsia prevention.Br J Obstet Gynaecol. 2005; 112: 684-688Crossref Scopus (19) Google Scholar will remain incomplete until the children born to mothers enrolled in these trials are monitored for clinical manifestations of atopic disorders such as asthma, wheezing, and eczema at least up to 2 years of age. Given the initial optimistic publicity surrounding vitamin E trials, we believe that the public should be warned about the likely adverse effects of pregnant women taking vitamin E supplements. It is important to note that the case for vitamin E prophylaxis for pre-eclampsia before the commencement of the VIP trial (Aug 6, 2003) and other multinational trials3Fraser WD Audibert F Bujold E Leduc L Xu H Boulvain M Julien P The vitamin E debate: implications for ongoing trials of pre-eclampsia prevention.Br J Obstet Gynaecol. 2005; 112: 684-688Crossref Scopus (19) Google Scholar was neither indicated nor contraindicated on the basis of substantial clinical investigation. Marshall Lindhheimer and Baha Sibai point out in their associated Comment4Lindheimer ML Sibai BM Antioxidant supplementation in pre-eclampsia.Lancet. 2006; 367: 1119-1120Summary Full Text Full Text PDF PubMed Scopus (22) Google Scholar that experimental evidence supporting the concept that excess reactive oxygen species (ROS) is a primary cause of pre-eclampsia is circumstantial. Moreover, the discovery2Banerjee S Chambers AE Campbell S Is vitamin E a safe prophylaxis for preeclampsia?.Am J Obstet Gynecol. 2006; 194: 1228-1233Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 5Lambeth JD NOX enzymes and the biology of reactive oxygen.Nat Rev Immunol. 2004; 4: 181-189Crossref PubMed Scopus (2530) Google Scholar of non-phagocytic ROS systems in the human placenta points towards the physiological necessity of early hypoxic development of the human embryo and placenta. We declare that we have no conflict of interest. Vitamin C and vitamin E in pregnant women at risk of pre-eclampsia – Authors' replyWe agree with Stephen Wood that bias through differences in methods of data acquisition could explain heterogeneity among trials. However, our two trials1,2 used identical methods for diagnosis. As stated in the first, “Data were collected and laboratory analyses carried out without awareness of allocation. Three clinicians assessed the masked data”. Indeed this was the same committee that was involved in the larger multicentre study. Incorrect diagnosis in the first study is therefore not a likely explanation for the different outcomes. Full-Text PDF