- Felipe Vadillo-Ortega, professor1,
- Otilia Perichart-Perera, titular researcher2,
- Salvador Espino, associate professor of obstetrics and gynaecology2,
- Marco Antonio Avila-Vergara, associate professor of obstetrics and gynaecology3,
- Isabel Ibarra, associate professor4,
- Roberto Ahued, professor of obstetrics and gynaecology2,
- Myrna Godines, associate professor of obstetrics and gynaecology1,
- Samuel Parry, associate professor and chief of division of maternal-fetal medicine5,
- George Macones, Mitchell and Elaine Yanow professor and head of obstetrics and gynaceology56,
- Jerome F Strauss, professor of obstetrics and gynaecology and dean of School of Medicine7
- 1Department of Experimental Medicine, School of Medicine, Universidad Nacional, Autonoma de Mexico, Torre de Investigacion, 3er Piso, Ciudad Universitaria, Mexico, D F 04510
- 2Instituto Nacional de Perinatologia Isidro Espinosa de los, Reyes, Mexico
- 3Universidad Autonoma de Sinaloa, Mexico
- 4Instituto de Investigaciones Biomedicas, UNAM, Mexico
- 5Department of Obstetrics and Gynaecology, University of Pennsylvania, Philadelphia, PA, USA
- 6Department of Obstetrics and Gynaecology, Washington University, St Louis, MO, USA
- 7Department of Obstetrics and Gynaecology, Virginia Commonwealth University, Richmond, VA, USA
- Correspondence to: F Vadillo-Ortega
- Accepted 28 March 2011
Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.
Design Randomised, blinded, placebo controlled clinical trial.
Setting Tertiary public hospital in Mexico City.
Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.
Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy.
Main outcome measure Development of pre-eclampsia/eclampsia.
Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14).
Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to …