Buhimschi CS, Bahtiyar MO, Zhao G, et al. - N-acetylcysteine (NAC) is a Food and Drug Administration (FDA)-approved drug for intrauterine infection and/or inflammation (Triple I), an important cause of preterm birth (PTB) and adverse newborn outcomes, that could be safely administered to pregnant women with acetaminophen toxicity. Researchers here examined clinical measures and mechanistic biomarkers in women (n = 67) randomized to an intravenous infusion of NAC or placebo mimicking the FDA-approved regimen in a single-center, quadruple-blind, placebo-controlled trial of pregnant women with impending PTB due to confirmed Triple I. Newborns exposed to NAC had significantly improved status at birth and required less intensive resuscitation, along with less frequent development of two or more prematurity-related severe morbidities with the strongest protection afforded against bronchopulmonary dysplasia. Observations suggest direct correlation of umbilical cord plasma NAC concentration with cysteine, but not with plasma or whole blood glutathione. The placental expression of histone deacetylase-2 reduced with NAC, suggesting the involvement of epigenetic mechanisms. As benefits of postnatal NAC in ventilated infants have been reported in prior studies, this trial highlights the critical antenatal timing of NAC administration.