Vitamin C supplementation in pregnancy

Alice Rumbold, Erika Ota, Chie Nagata, Sadequa Shahrook, Caroline A Crowther

Vitamin C supplementation may help reduce the risk of pregnancy complications such as pre-eclampsia, intrauterine growth restriction and maternal anaemia. There is a need to evaluate the efficacy and safety of vitamin C supplementation in pregnancy. To evaluate the effects of vitamin C supplementation, alone or in combination with other separate supplements on pregnancy outcomes, adverse events, side effects and use of health resources. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies. All randomised or quasi-randomised controlled trials evaluating vitamin C supplementation in pregnant women. Interventions using a multivitamin supplement containing vitamin C or where the primary supplement was iron were excluded. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Twenty-nine trials involving 24,300 women are included in this review. Overall, 11 trials were judged to be of low risk of bias, eight were high risk of bias and for 10 trials it was unclear. No clear differences were seen between women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control for the risk of stillbirth (risk ratio (RR) 1.15, 95% confidence intervals (CI) 0.89 to 1.49; 20,038 participants; 11 studies; I² = 0%; moderate quality evidence), neonatal death (RR 0.79, 95% CI 0.58 to 1.08; 19,575 participants; 11 studies; I² = 0%), perinatal death (average RR 1.07, 95% CI 0.77 to 1.49; 17,105 participants; seven studies; I² = 35%), birthweight (mean difference (MD) 26.88 g, 95% CI -18.81 to 72.58; 17,326 participants; 13 studies; I² = 69%), intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06; 20,361 participants; 12 studies; I² = 15%; high quality evidence), preterm birth (average RR 0.99, 95% CI 0.90 to 1.10; 22,250 participants; 16 studies; I² = 49%; high quality evidence), preterm PROM (prelabour rupture of membranes) (average RR 0.98, 95% CI 0.70 to 1.36; 16,825 participants; 10 studies; I² = 70%; low quality evidence), term PROM (average RR 1.26, 95% CI 0.62 to 2.56; 2674 participants; three studies; I² = 87%), and clinical pre-eclampsia (average RR 0.92, 95% CI 0.80 to 1.05; 21,956 participants; 16 studies; I² = 41%; high quality evidence).Women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control were at decreased risk of having a placental abruption (RR 0.64, 95% CI 0.44 to 0.92; 15,755 participants; eight studies; I² = 0%; high quality evidence) and had a small increase in gestational age at birth (MD 0.31, 95% CI 0.01 to 0.61; 14,062 participants; nine studies; I² = 65%), however they were also more likely to self-report abdominal pain (RR 1.66, 95% CI 1.16 to 2.37; 1877 participants; one study). In the subgroup analyses based on the type of supplement, vitamin C supplementation alone was associated with a reduced risk of preterm PROM (average RR 0.66, 95% CI 0.48 to 0.91; 1282 participants; five studies; I² = 0%) and term PROM (average RR 0.55, 95% CI 0.32 to 0.94; 170 participants; one study). Conversely, the risk of term PROM was increased when supplementation included vitamin C and vitamin E (average RR 1.73, 95% CI 1.34 to 2.23; 3060 participants; two studies; I² = 0%). There were no differences in the effects of vitamin C on other outcomes in the subgroup analyses examining the type of supplement. There were no differing patterns in other subgroups of women based on underlying risk of pregnancy complications, timing of commencement of supplementation or dietary intake of vitamin C prior to trial entry. The GRADE quality of the evidence was high for intrauterine growth restriction, preterm birth, and placental abruption, moderate for stillbirth and clinical pre-eclampsia, low for preterm PROM. The data do not support routine vitamin C supplementation alone or in combination with other supplements for the prevention of fetal or neonatal death, poor fetal growth, preterm birth or pre-eclampsia. Further research is required to elucidate the possible role of vitamin C in the prevention of placental abruption and prelabour rupture of membranes. There was no convincing evidence that vitamin C supplementation alone or in combination with other supplements results in other important benefits or harms.