Characterization of "ICU-30": A Binary Composite Outcome for Neonates With Critical Congenital Heart Disease.
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ABSTRACT:
SUBMITTER: Gardner MM
PROVIDER: S-EPMC9238655 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Hypoxic-ischemic white matter brain injury commonly occurs in neonates with critical congenital heart disease. Recent work has shown that longer time to surgery is associated with increased risk for this injury. In this study we investigated changes in perinatal cerebral hemodynamics during the transition from fetal to neonatal circulation to ascertain mechanisms that might underlie this risk. METHODS:Neonates with either transposition of the great arteries (TGA) or hypoplastic left heart syndrome (HLHS) were recruited for preoperative noninvasive optical monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using diffuse optical spectroscopy and diffuse correlation spectroscopy, 2 noninvasive optical techniques. Measurements were acquired daily from day of consent until the morning of surgery. Temporal trends in these measured parameters during the preoperative period were assessed with a mixed effects model. RESULTS:Forty-eight neonates with TGA or HLHS were studied. Cerebral oxygen saturation was significantly and negatively correlated with time, and oxygen extraction fraction was significantly and positively correlated with time. Cerebral blood flow did not significantly change with time during the preoperative period. CONCLUSIONS:In neonates with TGA or HLHS, increasing cerebral oxygen extraction combined with an abnormal cerebral blood flow response during the time between birth and heart surgery leads to a progressive decrease in cerebral tissue oxygenation The results support and help explain the physiological basis for recent studies that show longer time to surgery increases the risk of acquiring white matter injury.
| S-EPMC6166233 | biostudies-literature
Project description:BACKGROUND:Brain microstructural maturation progresses rapidly in the third trimester of gestation and first weeks of life, but typical microstructural development may be influenced by the presence of critical congenital heart disease (CHD). OBJECTIVE:The aim of this study was to investigate the pattern of white matter (WM) microstructural development in neonates with different types of critical CHD. The secondary aim was to examine whether there is an association between WM microstructural maturity and neonatal ischemic brain injury. METHODS:For this prospective, longitudinal cohort study, 74 term born neonates underwent diffusion tensor imaging (DTI) before (N?=?56) and after (N?=?71) cardiac surgery performed <30?days of life for transposition of the great arteries (TGA), single ventricle physiology with aortic arch obstruction (SVP-AO), left- (LVOTO) or right ventricle outflow tract obstruction (RVOTO). Microstructural integrity was investigated by fractional anisotropy (FA) and by mean diffusivity (MD) in 16 white matter (WM) structures in three WM regions with correction for postmenstrual age. Ischemic brain injury was defined as moderate-severe white matter injury or stroke. RESULTS:Before cardiac surgery, the posterior parts of the corona radiata and internal capsule showed significantly higher FA and lower MD compared to the anterior parts. Centrally-located WM structures demonstrated higher FA compared to peripherally-located structures. Neonates with TGA had higher FA in projection-, association- and commissural WM before surgery, when compared to other CHD groups. Neonates with LVOTO showed lower preoperative MD in these regions, and neonates with SVP-AO higher MD. Differences in FA/MD between CHD groups were most clear in centrally located WM structures. Between CHD groups, no differences in postoperative FA/MD or in change from pre- to postoperative FA/MD were seen. Neonatal ischemic brain injury was not associated with pre- or postoperative FA/MD. CONCLUSIONS:Collectively, these findings revealed brain microstructural WM development to follow the same organized pattern in critical CHD as reported in healthy and preterm neonates, from posterior-to-anterior and central-to-peripheral. Neonates with TGA and LVOTO showed the most mature WM microstructure before surgery and SVP-AO the least mature. Degree of WM microstructural immaturity was not associated with ischemic brain injury.
| S-EPMC6350221 | biostudies-literature
Project description:Neonates with congenital heart disease (CHD) display delayed brain development, predisposing them to impaired cerebrovascular autoregulation (CAR) and ischemic brain injury. For this paper, we analyzed the percentage of time with impaired CAR (%time impaired CAR) during the first 72 h after birth, the relation with clinical factors, and survival in 57 neonates with CHD. The primary outcome was a correlation coefficient of cerebral oxygenation (rcSO2) and mean arterial blood pressure (MABP, mmHg) for two hours on a daily basis. The %time impaired CAR ranged from 9.3% of the studied time on day one to 4.6% on day three. Variables associated with more %time impaired CAR were the use of inotropes (day 1, B = 19.5, 95%CI = 10.6-28.3; day 3, B = 11.5, 95%CI = 7.1-16), lower MABP (day 1, B = -0.6, 95%CI = -1.2-0.0), and dextro-transposition of the great arteries (dTGA) (16.2%) compared with other CHD types (2.0-5.0%; day 1, p = 0.022). Survival was not an associated variable. To summarize, impaired CAR was found in CHD neonates in up to 9.3% of the studied time. More evidence is necessary to evaluate an association with inotropes, dTGA, %time impaired CAR, and long-term outcome, further in larger cohorts.
| S-EPMC9688918 | biostudies-literature
Project description:Background and purposeAbnormal cerebral microstructure has been documented in term neonates with congenital heart disease, portending risk for injury and poor neurodevelopmental outcome. Our hypothesis was that preterm neonates with congenital heart disease would demonstrate diffuse cerebral microstructural abnormalities when compared with critically ill neonates without congenital heart disease. A secondary aim was to identify any association between microstructural abnormalities, white matter injury (eg, punctate white matter lesions), and other clinical variables, including heart lesions.Materials and methodsWith the use of tract-based spatial statistics, an unbiased, voxelwise method for analyzing diffusion tensor imaging data, we compared 21 preterm neonates with congenital heart disease with 2 cohorts of neonates without congenital heart disease: 28 term and 27 preterm neonates, identified from the same neonatal intensive care unit.ResultsCompared with term neonates without congenital heart disease, preterm neonates with congenital heart disease had microstructural abnormalities in widespread regions of the central white matter. However, 42% of the preterm neonates with congenital heart disease had punctate white matter lesions. When neonates with punctate white matter lesions were excluded, microstructural abnormalities remained only in the splenium. Preterm neonates with congenital heart disease had similar microstructure to preterm neonates without congenital heart disease.ConclusionsDiffuse microstructural abnormalities were observed in preterm neonates with congenital heart disease, strongly associated with punctate white matter lesions. Independently, regional vulnerability of the splenium, a structure associated with visual spatial function, was observed in all preterm neonates with congenital heart disease.
| S-EPMC4425253 | biostudies-literature
Project description:Recent studies have called into question the benefit of perioperative corticosteroids in children undergoing heart surgery, but have been limited by the lack of placebo control, limited power, and grouping of various steroid regimens together in analysis. We evaluated outcomes across methylprednisolone regimens versus no steroids in a large cohort of neonates.Clinical data from the Society of Thoracic Surgeons Database were linked to medication data from the Pediatric Health Information Systems Database for neonates (?30 days) undergoing heart surgery (2004-2008) at 25 participating centers. Multivariable analysis adjusting for patient and center characteristics, surgical risk category, and within-center clustering was used to evaluate the association of methylprednisolone regimen with outcome.A total of 3180 neonates were included: 22% received methylprednisolone on both the day before and day of surgery, 12% on the day before surgery only, and 28% on the day of surgery only; 38% did not receive any perioperative steroids. In multivariable analysis, there was no significant mortality or length-of-stay benefit associated with any methylprednisolone regimen versus no steroids, and no difference in postoperative infection. In subgroup analysis by surgical-risk group, there was a significant association of methylprednisolone with infection consistent across all regimens (overall odds ratio 2.6, 95% confidence interval 1.3-5.2) in the lower-surgical-risk group.This multicenter observational analysis did not find any benefit associated with methylprednisolone in neonates undergoing heart surgery and suggested increased infection in certain subgroups. These data reinforce the need for a large randomized trial in this population.
| S-EPMC3269116 | biostudies-literature
Project description:ObjectivesTo develop a population pharmacokinetic model for IV phenobarbital in neonates following cardiac surgery and perform simulations to identify optimal dosing regimens.DesignRetrospective single-center pharmacokinetic study.SettingCardiac ICU at Children's Hospital of Philadelphia.PatientsConsecutive neonates who received greater than or equal to one dose of IV phenobarbital and had greater than or equal to one phenobarbital concentration drawn per standard of care from June 15, 2012, to October 15, 2018.InterventionsNone.Measurements and main resultsA population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Simulations were performed using the final model variables. Optimal phenobarbital loading doses were determined based on attainment of peak and maintenance concentrations between 20 and 40 mg/L. A total of 37 neonates contributed 159 pharmacokinetic samples. The median (range) weight, postmenstrual age, and postnatal age were 3.2 kg (1.3-3.8), 39 2/7 weeks (28 2/7 to 42 6/7), and 5 days (0-26 d), respectively. Twelve patients (32%) were on extracorporeal membrane oxygenation. An one-compartment model best described the data. The final population pharmacokinetic model included (1) weight and postnatal age for clearance and (2) weight, extracorporeal membrane oxygenation, and albumin for volume of distribution. In neonates not on extracorporeal membrane oxygenation, loading doses of 30 and 20 mg/kg reached goal concentration with albumin values less than or equal to 3 and 3.5 mg/dL, respectively. Loading doses of 30 mg/kg reached goal concentration on extracorporeal membrane oxygenation regardless of albumin values. Maintenance doses of 4-5 mg/kg/d reached goal concentration in all neonates.ConclusionsIn neonates following cardiac surgery, phenobarbital clearance increased with postnatal age. Volume of distribution increased with extracorporeal membrane oxygenation and lower albumin values. Loading doses of 30 mg/kg on extracorporeal membrane oxygenation and 20-30 mg/kg without extracorporeal membrane oxygenation were needed to reach goal concentration based on simulations.
| S-EPMC7416482 | biostudies-literature
Project description:Vocal fold motion impairment (VFMI) is a known risk factor following congenital heart surgery (CHS). The impact of this diagnosis on utilization and outcomes is unknown.To evaluate the cost, postprocedure length of stay (PPLOS), and outcomes for neonates with VFMI after CHS.A cross-sectional analysis of the 2012 Kids' Inpatient Database (KID) of neonates who underwent CHS was carried out. The KID is an administrative data set of patients, aged 20 years or younger, and contains data on more than 10 million hospitalizations from 44 states. The KID is limited to inpatient hospitalization and contains discharge summary level of data. Patients were limited to those who were born during the hospitalization and those who were aged 28 days or younger at the time of admission for CHS. A weighted total of 4139 neonates who underwent CHS were identified, of which 3725 survived. The proportion of neonates diagnosed with VFMI was 264 (6.92%) of 3725.Congenital heart surgery.Cost of inpatient hospital stay, postprocedure length of stay, odds of pneumonia, gastrostomy tube placement, and tracheostomy tube placement. Risk-adjusted generalized linear models examined differences in cost and PPLOS between neonates who underwent CHS and were diagnosed with VFMI and those who were not. Risk-adjusted logistic regression compared the odds of selected outcomes (gastrostomy, tracheostomy, pneumonia). Models were weighted to provide national estimates.Of 3725 neonates (aged 0-28 days), 2203 (59.1%) were male and 1517 (40.7%) were female. Neonates diagnosed with VFMI had significantly higher total cost by $34 000 (95% CI, 2200-65 000) and PPLOS by 9.1 days (95% CI, 4.6-13.7) compared with those who did not. When PPLOS was included as a covariate in the model for cost, presence of VFMI was no longer significant. There were no differences in odds of pneumonia, gastrostomy, or tracheostomy.Vocal fold motion impairment after CHS was associated with significant increases in cost owing to increased PPLOS. These findings provide a foundation to further investigate standardized screening for VFMI following CHS; early identification and treatment may decrease cost and PPLOS.
| S-EPMC5876821 | biostudies-other
Project description:ObjectivesThe primary objective was to compare the volume of distribution (Vd), clearance (CL), elimination rate (Ke), and half-life (t½) of amikacin in neonates with cyanotic defects, acyanotic defects, and controls, adjusted for gestational and postnatal age. Secondary objectives were to compare the incidence of acute kidney injury (AKI) between controls and the congenital heart disease (CHD) group and to identify potential risk factors.MethodsThis retrospective cohort study included neonates receiving amikacin from January 1, 2013 to August 31, 2016. Patients were excluded if concentrations were not appropriately obtained or if AKI or renal anomalies were identified prior to amikacin initiation. Congenital heart disease was classified as acyanotic or cyanotic. Patients with CHD were matched 1:1 with non-CHD controls according to postmenstrual age. Bivariate analyses were performed using Wilcoxon-Mann-Whitney test, Pearson χ2 tests, or Fisher exact as appropriate with a p value <0.05. Regression analyses included logistic and analysis of covariance.ResultsFifty-four patients with CHD were matched with 54 controls. Median (IQR) postnatal age (days) at amikacin initiation significantly differed between CHD and controls, 3.0 (1.0-16.0) versus 1.0 (1.0-3.0), p = 0.016. After adjusting for gestational and postnatal age, there was no difference in the mean (95% CI) Vd (L/kg) and CL (L/kg/hr) between CHD and controls, 0.47 (0.44-0.50) versus 0.46 (0.43-0.49), p = 0.548 and 0.05 (0.05-0.05) versus 0.05 (0.05-0.05), p = 0.481, respectively. There was no difference in Ke or t½ between groups. There was no difference in AKI between the CHD and controls, 18.5% versus 9.3%, p = 0.16.ConclusionsClinicians should consider using standard amikacin dosing for neonates with CHD and monitor renal function, since they may have greater AKI risk factors.
| S-EPMC8139570 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-06-22 | GSE203275 | GEO
Project description:BackgroundThe early life gut microbiome is crucial in maintaining host metabolic and immune homeostasis. Though neonates with critical congenital heart disease (CCHD) are at substantial risks of malnutrition and immune imbalance, the microbial links to CCHD pathophysiology remain poorly understood. In this study, we aimed to investigate the gut microbiome in neonates with CCHD in association with metabolomic traits. Moreover, we explored the clinical implications of the host-microbe interactions in CCHD.MethodsDeep metagenomic sequencing and metabolomic profiling of paired fecal samples from 45 neonates with CCHD and 50 healthy controls were performed. The characteristics of gut microbiome were investigated in three dimensions (microbial abundance, functionality, and genetic variation). An in-depth analysis of gut virome was conducted to elucidate the ecological interaction between gut viral and bacterial communities. Correlations between multilevel microbial features and fecal metabolites were determined using integrated association analysis. Finally, we conducted a subgroup analysis to examine whether the interactions between gut microbiota and metabolites could mediate inflammatory responses and poor surgical prognosis.ResultsGut microbiota dysbiosis was observed in neonates with CCHD, characterized by the depletion of Bifidobacterium and overgrowth of Enterococcus, which was highly correlated with metabolomic perturbations. Genetic variations of Bifidobacterium and Enterococcus orchestrate the metabolomic perturbations in CCHD. A temperate core virome represented by Siphoviridae was identified to be implicated in shaping the gut bacterial composition by modifying microbial adaptation. The overgrowth of Enterococcus was correlated with systemic inflammation and poor surgical prognosis in subgroup analysis. Mediation analysis indicated that the overgrowth of Enterococcus could mediate gut barrier impairment and inflammatory responses in CCHD.ConclusionsWe demonstrate for the first time that an aberrant gut microbiome associated with metabolomic perturbations is implicated in immune imbalance and adverse clinical outcomes in neonates with CCHD. Our data support the importance of reconstituting optimal gut microbiome in maintaining host metabolic and immunological homeostasis in CCHD. Video Abstract.
| S-EPMC9801562 | biostudies-literature