Elsevier

The Journal of Pediatrics

Volume 168, January 2016, Pages 67-76.e6
The Journal of Pediatrics

Original Article
Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis

https://doi.org/10.1016/j.jpeds.2015.09.076Get rights and content
Under a Creative Commons license
open access

Objective

To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial.

Study design

Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age.

Results

Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted.

Conclusions

In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein.

Trial registration

ClinicalTrials.gov: NCT00724594.

ACA
Anterior cerebral artery
AE
Adverse event
BA
Basilar artery
BG
Basal ganglia
BP
Blood pressure
CBF
Cerebral blood flow
CNS
Central nervous system
CSF
Cerebrospinal fluid
CUS
Cranial ultrasound
DIC
Disseminated intravascular coagulopathy
DOL
Day of life
EEG
Electroencephalogram
FIRS
Fetal inflammatory state
GA
Gestational age
HI
Hypoxic ischemic
HIE
HI encephalopathy
HOL
Hour of life
IL
Interleukin
IL-1Ra
IL-1 receptor antagonist
IVH
Intraventricular hemorrhage
LPS
Lipopolysaccharide
mBP
Mean BP
MCA
Middle cerebral artery
mI
Myoinositol
MRI
Magnetic resonance imaging
MRS
Magnetic resonance spectroscopy
NAA
N-acetylaspartate
NAC
N-acetylcysteine
NEC
Necrotizing enterocolitis
NO
Nitric oxide
PD
Pharmacodynamic
PK
Pharmacokinetics
PT
Prothrombin time
PVL
Periventricular leukomalacia
RcSO2
Regional cerebral oxygenation
SAE
Serious adverse event
TAMX
Time average maximum velocity
VEGF
Vascular endothelial growth factor

Cited by (0)

Supported by the National Institute of Neurological Disorders and Stroke (NS52448). The authors declare no conflicts of interest.