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Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial^1,2,3

¹ From the Public Health Research Branch (EC, CR, MT, RMM, and FP), the Department of Obstetrics and Gynecology (PV), and the Direction of Research (FV-O), National Institute of Perinatology, Mexico City, Mexico.

Background: Vitamin C is involved in the synthesis and degradation of collagen and is important for maintenance of the chorioamniotic membranes. Inadequate availability of ascorbic acid during pregnancy has been proposed as a risk factor for premature rupture of the chorioamniotic membranes (PROM).

Objective: The objective of the study was to evaluate the effectiveness of 100 mg vitamin C/d in preventing PROM.

Design: A controlled double-blind trial was performed. Pregnant women (n = 126) in their 20th wk of gestation were invited; 120 accepted and were randomly assigned to 2 groups (100 mg vitamin C/d or placebo). Every 4 wk, plasma and leukocyte vitamin C concentrations were measured, and each subject was evaluated for cervicovaginal infection. The incidence of PROM was recorded for each group as an indicator of the protective effect of vitamin C supplementation.

Results: One hundred nine patients finished the study. Mean plasma vitamin C concentrations decreased significantly throughout the pregnancy in both groups (P = 0.001), and there were no significant differences between groups. Between weeks 20 and 36, mean leukocyte vitamin C concentrations decreased from 17.5 to 15.23 µg/10⁸ cells in the placebo group and increased from 17.26 to 22.17 µg/10⁸ cells in the supplemented group (within- and between-group differences: P = 0.001). The incidence of PROM was 14 per 57 pregnancies (24.5%) in the placebo group and 4 per 52 pregnancies (7.69%) in the supplemented group (relative risk: 0.26; 95% CI: 0.078, 0.837).

Conclusion: Daily supplementation with 100 mg vitamin C after 20 wk of gestation effectively lessens the incidence of PROM.

Key Words: Vitamin C • ascorbic acid • pregnancy • premature rupture of the chorioamniotic membranes • preterm labor • dietary reference intakes • DRIs • Mexico