A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended acetylsalicylic acid, 75 to 162 mg daily, and calcium for women with low calcium intake, to prevent preeclampsia in women at high risk.
A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended against antioxidant supplementation, dietary salt restriction, and modification of physical activity to prevent preeclampsia.
A 2010 Cochrane review of calcium supplementation in pregnancy to prevent hypertensive disorders included 13 randomized trials with 15,730 participants. Calcium supplementation was associated with a reduced risk for preeclampsia (RR, 0.45 [CI, 0.31 to 0.65]). The greatest reduction in risk was for women at high risk (RR, 0.22 [CI, 0.12 to 0.42]) and those with low baseline dietary calcium intake (RR, 0.36 [CI, 0.20 to 0.65]) (6).
A 2008 Cochrane review of antioxidants to prevent preeclampsia included 10 trials involving 6533 women. Included studies compared one or more antioxidants with either placebo or no antioxidants during pregnancy. There was no significant difference in rates of preeclampsia between antioxidant and control groups (RR, 0.73 [CI, 0.51 to 1.06]) (7).
A 2007 meta-analysis of vitamin C or E for the prevention of preeclampsia included four randomized trials (4680 women). No difference in the diagnosis of preeclampsia was found (vitamin group, 11%, vs. placebo group, 11.4%; RR, 0.97 [CI, 0.82 to 1.13]) (8).
A 2013 systematic review of the association between maternal levels of 25-hydroxy vitamin D and pregnancy outcomes included 31 observational studies. Insufficient serum levels of 25-hydroxy vitamin D were associated with preeclampsia (pooled OR, 1.79 [CI, 1.25 to 2.58]) (9).
A 2012 Cochrane review of vitamin D supplementation during pregnancy included 6 trials with 1023 participants, only one of which reported rates of preeclampsia. Women taking calcium plus vitamin D had similar rates of preeclampsia to those taking placebo (RR, 0.67 [CI, 0.33 to 1.35]). However, women receiving vitamin D had lower rates of low birthweight (<2500 grams) than women receiving no treatment or placebo (RR, 0.48 [CI, 0.23 to 1.01]) (10).
A randomized trial compared supplementation with medical food bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo in 450 pregnant women at high risk for preeclampsia. The incidence of preeclampsia was lower in the L-arginine plus antioxidant vitamins group compared with placebo (absolute risk reduction, 0.17 [CI, 0.12 to 0.21]; P<0.001) and compared with antioxidant vitamins alone (absolute risk reduction, 0.09 [CI, 0.05 to 0.14]; P=0.004). Antioxidant vitamins alone did not reduce preeclampsia compared with placebo (11).
A prospective cohort study evaluated the impact of daily multivitamin use in 1835 pregnant patients at less then 16 weeks' gestation. Patients were divided into two groups: those regularly using (n=860) and those not regularly using multivitamins daily in the past 6 months. When adjusted for multiple demographic factors, there was a significant difference in the risk for preeclampsia between regular users and nonusers of multivitamins (4.4% in nonusers and 3.8% in users; OR, 0.55 [CI, 0.32 to 0.95]) (12).
A randomized trial compared 1000 mg of vitamin C plus 400 IU of vitamin E (alpha-tocopherol) to matched placebo daily until delivery in 762 pregnant women with type 1 diabetes. The incidence of preeclampsia was similar in the vitamin (15%; n=57) and placebo (19%; n=70) groups (RR, 0.81 [CI, 0.59 to 1.12]) (13).
In a multicenter, randomized, double-blind trial, 10,154 nulliparous women who were at low risk for preeclampsia were randomly assigned to begin daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the ninth and sixteenth weeks of pregnancy. Rates of the primary outcome (severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or perinatal death) did not differ in the vitamin and placebo groups (6.1% and 5.7%, respectively; RR, 1.07 [CI, 0.91 to 1.25]) or in the rates of preeclampsia (7.2% and 6.7%, respectively; RR, 1.07 [CI, 0.93 to 1.24]) (14).
In a multinational, multicenter, randomized, controlled, double-blind trial organized by the World Health Organization, 1365 pregnant women with low nutritional status who were between 14 and 22 weeks' gestation were randomly assigned to receive 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily until delivery. Supplementation was not associated with a reduction in preeclampsia (RR, 1.0 [CI, 0.9 to 1.3]), eclampsia (RR, 1.5 [CI, 0.3 to 8.9]), or gestational hypertension (RR, 1.2 [CI, 0.9 to 1.7]). Low birthweight (RR, 0.9 [CI, 0.8 to 1.1]), small size for gestational age (RR, 0.9 [CI, 0.8 to 1.1]), and perinatal deaths (RR, 0.8 [CI, 0.6 to 1.2]) were also unaffected (15).
A randomized trial compared daily vitamins C and E with placebo in 739 patients at increased risk for preeclampsia. Rates of preeclampsia were similar in the vitamin (13.8%) and placebo (15.6%) groups (RR, 0.87 [CI, 0.61 to 1.25]) (16).
A planned analysis for secondary outcome of the same trial showed an increased risk for premature rupture of the membranes (RR, 1.89 [CI, 1.11 to 3.23]; P=0.015) in the vitamin group (17).
A randomized, controlled trial of 1877 nulliparous women assigned to daily supplementation (n=935) with vitamin C, 1000 mg/d, and vitamin E, 400 IU/d, or placebo (n=942) from 14 to 22 weeks' gestation until delivery showed no significant difference in the risk for preeclampsia (6% in the multivitamin group and 5% in the placebo group; RR, 1.20 [CI, 0.82 to 1.75]) (18).
A randomized, controlled trial of 2410 pregnant women at increased risk for eclampsia assigned to supplementation (n=1199) with vitamin C, 100 mg/d, and vitamin E, 400 IU/d, or placebo (n=1205) from the second trimester of pregnancy until delivery showed no significant difference in the risk for preeclampsia (15% in the supplementation group and 16% in the placebo group; RR, 0.97 [CI, 0.80 to 1.17]) (19).
In a randomized, controlled trial in a population with endemic vitamin D deficiency, supplementation of 2000 and 4000 IU/day of vitamin D appeared safe in pregnancy, and a dose of 4000 IU/day appeared to be the most effective in optimizing serum 25-hydroxy vitamin D concentrations in mothers and their infants (20).
In a double-blind, randomized, controlled trial including 350 women, vitamin D supplementation of 4000 IU/day during pregnancy was safe and most effective in achieving sufficiency in all women and their neonates regardless of race (21).