期刊
PEDIATRIC RESEARCH
卷 89, 期 1, 页码 175-184出版社
SPRINGERNATURE
DOI: 10.1038/s41390-020-01106-w
关键词
-
类别
资金
- Division of Maternal-Fetal Medicine, Yale University Department of Obstetrics, Gynecology, and Reproductive Sciences
- Yale New Haven Hospital
- National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [R01 HD047321]
- NICHD [R01 HD0880833]
The study suggests that prenatal administration of NAC to pregnant women can reduce the incidence of preterm birth and adverse outcomes for newborns. Newborns exposed to NAC showed significantly improved status at birth, required less intensive resuscitation, and had a lower risk of developing severe morbidities compared to those exposed to placebo.
Background Intrauterine infection and/or inflammation (Triple I) is an important cause of preterm birth (PTB) and adverse newborn outcomes.N-acetylcysteine (NAC) is a Food and Drug Administration (FDA)-approved drug safely administered to pregnant women with acetaminophen toxicity. Methods We conducted a single-center, quadruple-blind, placebo-controlled trial of pregnant women with impending PTB due to confirmed Triple I. Participants (n = 67) were randomized to an intravenous infusion of NAC or placebo mimicking the FDA-approved regimen. Outcomes included clinical measures and mechanistic biomarkers. Results Newborns exposed to NAC (n = 33) had significantly improved status at birth and required less intensive resuscitation compared to placebo (n = 34). Fewer NAC-exposed newborns developed two or more prematurity-related severe morbidities [NAC: 21% vs. placebo: 47%, relative risk, 0.45; 95% confidence interval (CI) 0.21-0.95] with the strongest protection afforded against bronchopulmonary dysplasia (BPD, NAC: 3% vs. placebo: 32%, relative risk, 0.10; 95% CI: 0.01-0.73). These effects were independent of gestational age, birth weight, sex, or race. Umbilical cord plasma NAC concentration correlated directly with cysteine, but not with plasma or whole blood glutathione. NAC reduced the placental expression of histone deacetylase-2, suggesting that epigenetic mechanisms may be involved. Conclusions These data provide support for larger studies of intrapartum NAC to reduce prematurity-related morbidity. Impact In this randomized clinical trial of 65 women and their infants, maternal intravenous NAC employing the FDA-approved dosing protocol resulted in lower composite neonatal morbidity independent of gestational age, race, sex, and birthweight. Administration of NAC in amniocentesis-confirmed Triple I resulted in a remarkably lower incidence of BPD. As prior studies have not shown a benefit of postnatal NAC in ventilated infants, our trial highlights the critical antenatal timing of NAC administration. Repurposing of NAC for intrapartum administration should be explored in larger clinical trials as a strategy to improve prematurity-related outcomes and decrease the incidence of BPD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据