Objective: To determine if vitamin C in high doses reduces extravascular lung water in women with severe preeclampsia postpartum.
Hypotheses: Vitamin C in the first three days postpartum reduces extravascular lung water assessed by lung ultrasound in patients with severe preeclampsia. Vitamin C in the first three days postpartum reduces urinary levels of oxidative stress biomarkers.
Rationale: Preeclampsia is the leading cause of peripartum pulmonary edema which occurs, at least in part, due to endothelial dysfunction and increased vascular permeability. Oxidative stress contributes significantly to the development of preeclampsia and its clinical course. Vitamin C was proven to be beneficial in reducing vascular permeability in critically ill patients. It has been shown that the use of vitamin C in pregnancy was not effective for primary or secondary prevention of preeclampsia. The effect of vitamin C on preeclampsia postpartum as a tertiary prevention measure, i.e., reducing risks of complications once preeclampsia has already occurred, is not known.
Population: Consecutively admitted patients with singleton pregnancies complicated by severe preeclampsia.
Methods: Single-center, randomized, placebo-controlled, double-blind trial. Thirty-four patients received vitamin C (1.5 g/6 hours) (n = 17) or placebo (n = 17) intravenously at days 1, 2, and 3 postpartum. A lung ultrasound was performed once daily in the first three days following delivery. Echo Comet Score (ECS) was obtained using the 28-rib interspaces technique. Urine was collected on postpartum days 1 and 3. It was analysed for four biomarkers of oxidative stress: dityrosine, 8-hydroxy-2-deoxyguanosine (8- OHdG), 8-isoprostane, and N-epsilon-Hexanoyl-Lysine (HEL). Mann-Whitney-U test was used to compare vitamin C vs placebo groups. A p 䁤 0.05 was considered statistically significant.
Main outcome measures: ECS on day 1 postpartum was the primary outcome studied. ECS on days 2 and 3 postpartum as well as urinary biomarkers of oxidative stress (dityrosine, 8- OHdG, 8-isoprostane, and HEL, normalized for urinary creatinine), on days 1 and 3 postpartum were analyzed as secondary outcomes.
Results: There was no significant difference in ECS on day 1 (median 23 (inter-quartile range (IQR) 21–61) vs 18 (IQR 8–35); p = 0.31). On days 2 and 3, ECS was significantly lower in the vitamin C group compared to the placebo (8 (IQR 3–14) vs 35 (IQR 15–78); p = 0.03 and 5 (IQR 3–10) vs 18 (IQR 18– 44); p = 0.04, respectively). Dityrosine and 8-OHdG values did not differ significantly between the two study groups on day 1 after delivery (p = 0.23 and p = 0.77, respectively), but were significantly lower in the vitamin C group compared to the placebo group on day 3 after delivery (p = 0.04 and p = 0.03, respectively). Values of 8-isoprostane and HEL did not differ significantly between the two study groups on day 1 (p = 0.41 and p = 0.42, respectively), as well as on day 3 after delivery (p = 0.25 and p = 0.24, respectively).
Conclusion: High dose of intravenous vitamin C did not reduce the amount of extravascular lung water or decrease markers of oxidative stress in postpartum patients with severe preeclampsia on day 1 after delivery. It seems, however, it has a delayed effect with a reduction in extravascular lung water detected on ultrasound on days 2 and 3 following delivery and a reduction of urinary levels of dityrosine and 8-OHdG (markers of protein and DNA oxidative damage, respectively) on day 3 after delivery.
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