Effects of the Supplementation of N-acetylcysteine on Redox Imbalance, Cytokine Levels, and Perinatal Outcomes in Pregnant Women with Preeclampsia: A Double-Blind, Randomized, Placebo-Controlled Pilot Study

Abstract

Background/Objectives: This study aimed to evaluate the effects of oral administration of N-acetylcysteine (NAC) in pregnant women with preeclampsia (PE), using serum markers of redox imbalance and cytokine levels and perinatal outcomes. Methods: A double-blind, randomized, placebo-controlled pilot study was carried out from 2021 to 2023. The study was retrospectively registered with REBEC (Brazilian Clinical Trials Registry). After screening, women were randomized into 2 groups according to the type of supplementation: 600 mg of NAC (NAC group) or capsules containing 2% colloidal silicon dioxide and 98% microcrystalline cellulose (placebo group) until delivery. Blood samples were collected to quantify biomarkers of redox imbalance and cytokine levels. Questionnaires containing socioeconomic, clinical, obstetric, and anthropometric data were applied. Results: A total of 51 pregnant women with PE were included (26 in the placebo group and 25 in the NAC group). The use of NAC was associated with a higher gestational age at birth (GA) of the conceptus (placebo group: 37.39 weeks ± 1.96 SD vs. NAC group: 38.45 weeks ± 1.51 SD; p = 0.044). A moderate effect size was observed for this variable (Cohen’s d = 0.52). However, treatment allocation (NAC vs. control) was not independently associated with gestational age at birth after adjustment for covariates (F(1,28) = 0.144; p = 0.707; η2p = 0.005). The adjusted mean difference between groups was 0.92 weeks (95% CI: −0.16 to 2.00). No other significant effects on redox and inflammatory markers were identified using NAC. Conclusions: NAC supplementation did not impact the mode of delivery between the NAC and placebo groups. As a secondary exploratory finding, a possible trend toward prolonged gestational age was observed in the NAC group; however, this result should be interpreted with caution, given the exploratory nature of the analysis, the neutrality of the primary outcome, and the limited sample size.