Role of Vitamin C Supplementation in the Prevention of Premature Rupture of Membranes (PROM) and Preterm PROM: A Systematic Review and Meta-Analysis.

Vitamin C is a micronutrient assumed to have effects on the occurrence of "preterm premature rupture of membranes" (PPROM) and "premature rupture of membranes" (PROM). The objective of this review was to find the pooled incidence of PROM and/or PPROM between subgroups in relation to dose, mode of therapy (monotherapy vs. combination therapy) and history of PROM/PPROM in previous pregnancies. A search was conducted in the electronic databases (PubMed, Google Scholar, Scopus) from inception to November 2022, using the search terms "Vitamin C", "Ascorbic acid", "preterm premature rupture of membrane" and "premature rupture of membrane". The lists of references of all the selected eligible articles were also searched to find studies of interest. A total of nine randomized controlled trials (published in English) with 16,076 participants involving the supplementation of vitamin C during pregnancy were picked up for analysis. Data management was done using the Review Manager (RevMan 5.3). A statistical test for publication bias was done in jamovi, version 2.3.18. In comparison to placebo, vitamin C supplementation was not found to be significantly effective in preventing the occurrence of PPROM/PROM. However, a low dose of vitamin C and the monotherapy mode of administration significantly decreased the occurrence of PPROM/PROM. Vitamin C has significant beneficial effects in women with a history of PROM in a previous pregnancy. Hence, we conclude that vitamin C administered as monotherapy in low doses (preferably 100 mg/day) has definite benefits in preventing the occurrence of PROM/PPROM with greater advantages seen in those with a history of similar complications in a previous pregnancy.