Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

No authors available

The BMJ

May 2011

DOI: 10.1136/bmj.d2901

Citations:47

Influential Citations:2

Interventional (Human) Studies

Enhanced Details

Methods

Pregnant women at high risk of pre-eclampsia (personal history of pre-eclampsia or pre-eclampsia in a first-degree relative) recruited at Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, Mexico City. Study design: randomized, blinded, placebo-controlled clinical trial with three groups (placebo, L-arginine + vitamins, vitamins alone); intention-to-treat analysis. Participants were 14–32 weeks gestation at enrollment; mean age ~28 years; follow-up through delivery; all deliveries at the same hospital.

Intervention

Two Heart Bars daily (35 g each) taken until delivery. L-arginine + antioxidant vitamins group: each bar contains 3.3 g L-arginine plus antioxidant vitamins (Vitamin C 250 mg, Vitamin E 200 IU, Niacin 25 mg, Vitamin B6 2.0 mg, Vitamin B12 4.8 μg, Folate 200 μg); total daily L-arginine: 6.6 g. Antioxidant vitamins alone group: two bars daily containing antioxidant vitamins but no L-arginine. Placebo bars: two bars daily devoid of L-arginine and antioxidant vitamins. Bars indistinguishable in appearance and flavor.

Results

L-arginine plus antioxidant vitamins reduced pre-eclampsia/eclampsia incidence from 30% (placebo) to 13% (L-arginine + vitamins) with an absolute risk reduction of 17% (95% CI 12–21%; P<0.001) and a number needed to treat of about 6. Antioxidant vitamins alone did not significantly reduce risk vs placebo (23% vs 30%; P=0.052). L-arginine + vitamins vs vitamins alone showed a significant additional benefit (P=0.004; ARR 9%). The combination also lowered total preterm delivery (11% vs 20%; P=0.003) and improved some neonatal outcomes (e.g., Apgar scores at 1 and 5 minutes). Authors conclude that L-arginine plus antioxidant vitamins during pregnancy may be a simple, low-cost strategy to reduce pre-eclampsia risk in high-risk populations; antioxidant vitamins alone did not confer protection. Further studies are needed to assess generalizability to low-risk populations and to separate the contributions of L-arginine and antioxidants.

Limitations

Findings apply to a high-risk population and may not generalize to low-risk pregnancies. No arm with L-arginine alone to isolate its effect from antioxidants. Trial powered to detect a large (50%) reduction; may miss smaller differences. Wide enrollment window (14–32 weeks) introduces variability in timing of intervention initiation; further research needed to confirm applicability across different populations.

Abstract

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 the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846. show less