Antenatal N-acetylcysteine to improve outcomes of premature infants with intra-amniotic infection and inflammation (Triple I): randomized clinical trial.
Pediatr Res
; 89(1): 175-184, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-32818949
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Complicaciones Infecciosas del Embarazo
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Acetilcisteína
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Displasia Broncopulmonar
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Recien Nacido Prematuro
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Corioamnionitis
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Nacimiento Prematuro
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
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Guideline
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Infant
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Pregnancy
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Pediatr Res
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos