Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial
Felipe Vadillo-Ortega, professor,1 Otilia Perichart-Perera, titular researcher,2 Salvador Espino, associate professor of obstetrics and gynaecology,2 Marco Antonio Avila-Vergara, associate professor of obstetrics andgynaecology,3 Isabel Ibarra, associate professor,4 Roberto Ahued, professor of obstetrics and gynaecology,2 Myrna Godines, associate professor of obstetrics and gynaecology,1 Samuel Parry, associate professor and chief of division of maternal-fetal medicine,5 George Macones, Mitchell and Elaine Yanow professor and head of obstetrics and gynaceology,5,6 Jerome F Strauss, professor of obstetrics andgynaecology and dean of School of Medicine7
1 Department of Experimental Medicine, School of Medicine, Universidad Nacional, Autonoma de Mexico, Torre de Investigacion, 3er Piso, Ciudad Universitaria, Mexico, D F 04510 2 Instituto Nacional de Perinatologia Isidro Espinosa de los, Reyes, Mexico 3 Universidad Autonoma de Sinaloa, Mexico 4 Instituto de Investigaciones Biomedicas, UNAM, Mexico 5Department of Obstetrics and Gynaecology, University of Pennsylvania, Philadelphia, PA, USA 6 Department of Obstetrics and Gynaecology, Washington University, St Louis, MO, USA 7 Department of Obstetrics and Gynaecology, Virginia Commonwealth University, Richmond, VA, USA Correspondence to: F VadilloOrtega firstname.lastname@example.org
Cite this as: BMJ 2011;342:d2901 doi:10.1136/bmj.d2901
ABSTRACTObjective 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 previouspregnancy complicated by pre-eclampsia, or preeclampsia 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 measureDevelopment 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; P300 mg/24 hours) presenting after 20 weeks of gestation in women known to bepreviously normotensive. We defined eclampsia as non-epileptic convulsions. We defined mild pre-eclampsia as when hypertension and proteinuria were present but no evidence of systemic organ damage was detectable. Severe preeclampsia was detected when proteinuria was above 2.0 g/24 hours, blood pressure was ≥160/110 mm Hg, or both. We also assessed several neonatal end points, including preterm birth (bornbefore 37 weeks of gestation), birth weight, small for gestational age (according to institutional charts), and Apgar scores. We based the sample size calculation on consideration of all three two way comparisons (placebo v antioxidant vitamins alone, placebo v antioxidant vitamins plus L-arginine, and antioxidant vitamins plus L-arginine v antioxidant vitamins alone), assuming a 50% proportionalreduction in pre-eclampsia in any group compared with placebo, an α error of 0.05, a β error of 0.2, and a 1:1:1 allocation ratio. We used a Bonferroni correction so that a test specific error (α) of 0.016 (0.05/3) was used for significance testing of all primary two way comparisons. We also used the α error of 0.016 in our sample size estimation. We assumed a prevalence of preeclampsia in the...