A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Vitamins C and E and the risks of preeclampsia and perinatal complications. Vitamin D supplementation in pregnancy: a controlled trial of two methods. Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial. Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. Vitamin a status of pregnant women and effect of post partum vitamin a supplementation. Maternal administration of vitamin K does not improve the coagulation profile of preterm infants.
In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour. Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.
                We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .
                Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).
                Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy. Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.
                We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.
                Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).
                Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).
                Copyright 2006 Massachusetts Medical Society. A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region. We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women.
                Women at risk for preeclampsia (previous preeclampsia, chronic hypertension, pregestational diabetes, or multifetal gestation) were recruited at 14 to 20 weeks' gestation and randomly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins. The primary outcome was the occurrence of preeclampsia. An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50% reduction in the rate of preeclampsia.
                Funding was terminated after 109 women had been recruited; 9 were lost to follow-up or withdrew. We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies. The rate of preeclampsia was not different: 17.3% in women who received supplemental vitamins C and E, versus 18.8% in the placebo group. Assuming a baseline rate of preeclampsia in the placebo group between 15% and 20%, we can estimate that 500 to 950 women in each arm will be required to show a clinically important reduction in the rate of preeclampsia.
                The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated. Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm. The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival.
                The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age.
                Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age.
                A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively.
                Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal. To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates.
                Randomised, placebo controlled, two by two factorial trial.
                Bissau, Guinea-Bissau.
                1717 low birthweight neonates born at the national hospital.
                Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months.
                Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo.
                No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation being 0.74 (95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau, the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 (95% CI 0.87 to 1.33); 0.80 (95% CI 0.58 to 1.10) in boys and 1.41 (95% CI 1.04 to 1.90) in girls (P=0.01 for interaction between neonatal vitamin A and sex).
                The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that, overall, it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau. Worryingly, the trials show that vitamin A supplementation at birth can be harmful in girls. Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects. Trial registration ClinicalTrials.gov NCT00168610. To assess the Vitamin A status of pregnant women in their third trimester using maternal serum retinol levels as the indicator; and (ii) To assess the impact of postpartum Vitamin A supplementation on the Vitamin A status of exclusively breastfed infants.
                Prospective randomized single blind controlled study.
                Teaching Hospital.
                109 apparently healthy primi and second gravida women registered at the antenatal clinic were included in the study and followed up for three months postpartum. Serum retinol levels of pregnant mothers in their third trimester (35-37 weeks) and cord blood levels after delivery were estimated. Mothers were then assigned to two groups. The experimental group included 53 mothers who received a single dose of 2 lakh units of Vitamin A orally. The control group had 56 mothers who did not receive Vitamin A. Mothers and infants were followed up for three months. The serum retinol of infants and the breast milk retinol levels were estimated at the end of three months and the results were compared. The growth of the infants was also monitored.
                Subclinical Vitamin A deficiency was seen in 29.67% of pregnant women. At the end of three months, 69.6% of mothers in the control group had breast milk retinol levels below 30 mg/dl, as opposed to 36.1% in the experimental group. Forty five per cent of infants in the control group had subclinical vitamin A deficiency compared to none in the experimental group. There was no difference in the growth of infants in the two groups. However, the infant serum and the breast milk retinol levels were significantly higher in the supplemented group.
                There is a high prevalence of inapparent Vitamin A deficiency (29.7%) in pregnant women in their third trimester from lower socio-economic strata. Postpartum Vitamin A supplementation had a beneficial impact on the infant serum retional and the breast milk retinol level but no effect on infant growth. The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.
The data are too few to say if vitamin C supplementation either alone or in combination with other supplements is beneficial during pregnancy. Preterm birth may have been increased with vitamin C supplementation.
[Note: The 32 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]