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

ABSTRACT: 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.

SUBMITTER: Jenkins DD

PROVIDER: S-EPMC4698030 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Jenkins Dorothea D DD Wiest Donald B DB Mulvihill Denise M DM Hlavacek Anthony M AM Majstoravich Sarah J SJ Brown Truman R TR Taylor Joseph J JJ Buckley Jason R JR Turner Robert P RP Rollins Laura Grace LG Bentzley Jessica P JP Hope Kathryn E KE Barbour Andrew B AB Lowe Danielle W DW Martin Renee H RH Chang Eugene Y EY

The Journal of pediatrics 20151103

<h4>Objective</h4>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.<h4>Study design</h4>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. Postn ...[more]

PMID: 26545726

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Project description:BackgroundIn 2019, 1 of 6 births was affected by gestational diabetes mellitus (GDM) globally. GDM results in adverse maternal, fetal, and neonatal outcomes in the short and long term, such as pregnancy and birth complications, type 2 diabetes, metabolic syndrome, and cardiovascular disease. In the context of "transgenerational programming," diabetes mellitus during pregnancy can contribute to "programming" errors and long-term consequences for the child. Therefore, early therapy strategies are required to improve the clinical management of GDM. The interest in digital therapy approaches, such as telemetry, has increased because they are promising, innovative, and sustainable.ObjectiveThis study aimed to assess the current evidence regarding the clinical effectiveness of telemetric interventions in the management of GDM, addressing maternal glycemic control, scheduled and unscheduled visits, satisfaction, diabetes self-efficacy, compliance, maternal complications in pregnancy and childbirth, as well as fetal and neonatal outcomes.MethodsMedline via PubMed, Web of Science Core Collection, Embase, Cochrane Library, and CINAHL databases were systematically searched from January 2008 to April 2020. We included randomized controlled trials, systematic reviews, meta-analyses, and clinical trials in English and German. Study quality was assessed using "A MeaSurement Tool to Assess systematic Reviews" and "Effective Public Health Practice Project."ResultsOur search identified 1116 unique studies. Finally, we included 11 suitable studies (including a total of 563 patients and 2779 patient cases): 4 systematic reviews or meta-analyses (1 of high quality and 3 of moderate quality), 6 randomized controlled trials (2 of high quality and 4 of moderate quality), and 1 low-quality nonrandomized controlled trial. We classified 4 "asynchronous interventions" and 3 "asynchronous and real-time interventions." Our findings indicate that telemetric therapy clearly improves glycemic control and effectively reduces glycated hemoglobin A1c levels. Furthermore, in 1 study, telemetry proved to be a significant predictor for a better glycemic control (hazard ratio=1.71, 95% CI 1.11-2.65; P=.02), significantly fewer insulin titrations were required (P=.04), and glycemic control was achieved earlier. Telemetric therapy significantly reduced scheduled and unscheduled clinic visits effectively, and women were highly satisfied with the treatment (P<.05). From fetal and neonatal short-term outcomes, some improving tendencies in favor of telemetry were determined. No long-term outcomes were detected.ConclusionsTelemetric interventions clearly improved glycemic control, notably glycated hemoglobin A1c levels, and reduced scheduled and unscheduled clinic visits effectively, which reinforces this digital approach in the treatment of GDM.

Project description:OBJECTIVES:No information exists about whether fetal inflammatory-response(FIR), early-onset neonatal sepsis(EONS) and chorioamnionitis(an advanced-stage of maternal inflammatory-response in extraplacental membranes) continuously increase according to the progression of inflammation in umbilical-cord(UC). The objective of current-study is to examine this-issue. METHODS:Study-population included 239singleton pregnant-women(gestational-age[GA] at delivery: 21.6~36weeks) who had inflammation in extraplacental membranes or chorionic plate (CP) and either preterm-labor or preterm-PROM. We examined FIR, and the frequency of fetal inflammatory-responses syndrome(FIRS), proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC. The progression of inflammation in UC was divided with a slight-modification from previously reported-criteria as follows: stage0, inflammation-free UC; stage-1: umbilical phlebitis only; stage-2: involvement of at least one UA and either the other UA or UV without extension into WJ; stage-3: the extension of inflammation into WJ. FIR was gauged by umbilical-cord-plasma(UCP) CRP concentration(ng/ml) at birth, and FIRS was defined as an elevated UCP CRP concentration at birth(?200ng/ml). RESULTS:Stage-0, stage-1, stage-2 and stage-3 of inflammation in UC were present in 48.1%, 15.5%, 6.7%, and 29.7% of cases. FIR continuously increased according to the progression of inflammation in UC(Kruskal-Wallis test,P<0.001; Spearman-rank-correlation test,P<0.000001,r = 0.546). Moreover, there was a significant and stepwise increase in the frequency of FIRS, proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC(each for P<0.000005 in both chi-square test and linear-by-linear-association). Multiple logistic-regression analysis demonstrated that the more advanced-stage in the progression of inflammation in UC(i.e., stage-1 vs. stage-2 vs. stage-3), the better predictor of suspected-EONS (Odds-ratio[OR]3.358, 95%confidence-interval[CI]:1.020-11.057 vs. OR5.147, 95%CI:1.189-22.275 vs. OR11.040, 95%CI:4.118-29.592) and chorioamnionitis(OR6.593, 95%CI:2.717-15.999 vs. OR16.508, 95%CI:3.916-69.596 vs. OR20.167, 95%CI:8.629-47.137). CONCLUSION:FIR, EONS and chorioamnionitis continuously increase according to the progression of inflammation in UC among preterm-gestations with inflammation in extraplacental membranes or CP. This finding may suggest that funisitis(inflammation in UC) is both qualitatively and quantitatively histologic-counterpart of FIRS, and a surrogate-marker for chorioamnionitis.

Dataset Information

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

Publications

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

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