Survival and Neurodevelopmental Outcomes in Congenital Diaphragmatic Hernia Patients with Single versus Repeat Extracorporeal Membrane Oxygenation Runs.

OBJECTIVE: We describe the survival and neurodevelopmental outcomes of congenital diaphragmatic hernia (CDH) patients who received single and repeat extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: This is a retrospective single-center study comparing neurodevelopmental outcomes in CDH patients who were managed without ECMO, who received one ECMO run, and those who received two ECMO runs. Neurodevelopmental testing was performed utilizing the Bayley Scales of Infant Development-III. RESULTS: There were 68 neonates identified with CDH from January 2011 to June 2019: 30 did not receive ECMO, 29 received single ECMO run, and 9 received two ECMO runs. Survival of ECMO patients was 50%, with 48% of single run and 57% of repeat run patients surviving to discharge. Second-run ECMO patients had increased median ventilator days (60 vs. 33, p = 0.04) and increased median length of hospital stay (159 vs. 89, p = 0.01). Neurodevelopmental testing via Bayley Scales of Infant Development-III was performed on 74% of survivors at the mean age of 24 months. CDH neonates who underwent ECMO (single or repeat runs) were more likely to have lower cognitive, language, and motor composite scores as compared with CDH neonates who had not required ECMO. Motor composite scores were significantly lower in repeat ECMO run neonates as compared with single ECMO run (72 + 6 vs. 85 + 4, p = 0.0003), but there were no further deficits noted in language or cognitive domains. CONCLUSION: Survival after a second ECMO run in CDH is possible, although with increased ventilator days and increased length of hospitalization. We also find further deficits in motor outcomes in the second-run ECMO group compared with single-run ECMO. Our findings do not preclude a second ECMO run, but rather inform our counseling to families and reinforce the need for close neurodevelopmental follow-up for these patients. KEY POINTS: · A repeat ECMO run is associated with further neurodevelopmental deficits in the motor domain.. · Survival is possible after repeat ECMO and is associated with increased length of hospital stay.. · Neurodevelopmental follow-up is critical for all CDH ECMO patients..

Cerebellar hemorrhage: a 10-year evaluation of risk factors.

Background: While cerebellar hemorrhage (CH) has been linked with adverse neurodevelopmental outcome in preterm infants, it remains under-recognized and the underlying mechanisms are not fully understood.Objective: To determine risk factors for CH in premature infants.Methods: A retrospective cohort study included all inborn infants ≤ 30 weeks EGA admitted to the NICU from 2007 to 2016. Comprehensive perinatal and clinical factors were collected. CH size, sidedness, and symmetry were noted. Factors associated with CH were evaluated using univariate and multivariate logistic regression.Results: Of the 352 identified infants, 69 (20%) had CH. Those with CH were born at earlier EGA, received less antenatal steroids, more frequently had an admission temperature <36 °C, had more severe lung disease, received more inotropes, and had higher rates of intraventricular hemorrhage (IVH). In the regression model, low admission temperature (OR = 3.5), inotrope exposure (OR = 2.6), chorioamnionitis (OR = 2.3), and increased ventilator days (OR = 1.02) were associated with increased risk, while antenatal steroids (OR = 0.3) and male sex (OR = 0.5) were associated with decreased risk. Imaging modality at first diagnosis was split between ultrasound and MRI (52 versus 48%). Median age at diagnosis was 4 d; 52% of cases were unilateral, and size was punctate, small, and large in 23, 45, and 32% of cases, respectively.Conclusions: CH is common in premature infants and can be diagnosed using ultrasound or MRI. Clinically modifiable risk factors have been identified and should serve as the basis for improved clinical strategies in temperature, ventilator, and blood pressure management.

Central versus Low-Lying Umbilical Venous Catheters: A Multicenter Study of Practices and Complications.

OBJECTIVES: Conventional neonatology practice is to place umbilical venous catheters (UVCs) in central position and to limit the use of low-lying catheters. Our objectives were to describe the practices and complications associated with UVCs and to evaluate the type of infusates used with either UVC position. STUDY DESIGN: A retrospective chart review was performed at four neonatal intensive care units to identify neonates who underwent UVC placement over a 2-year period. Infant demographics, UVC position, catheter days, fluid and medication characteristics, and specific complications were extracted. RESULTS: A total of 2,011 neonates who underwent UVC placement were identified during the 2-year period. Of these, 641 UVCs (31.9%) were identified in the low-lying position. Centrally positioned UVCs were associated with lower gestational age and were left in situ for a longer duration than low-lying UVCs. Infusions of hyperosmolar solutions and vasopressors were significantly higher in central UVCs, though they were used in a significant number of low-lying UVCs. Complications, while not statistically different, were three times higher in low-lying UVCs. CONCLUSION: Despite conventional teaching, low-lying UVCs were used in nearly one-third of infants in this cohort. Parenteral nutrition, antibiotics, and vasopressors were infused through central and low-lying UVCs. There was no statistically significant difference in complication rates between UVC positions.

Necrotizing enterocolitis leads to disruption of tight junctions and increase in gut permeability in a mouse model.

BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants. Neonates weighing <1500 grams are at the highest risk for acquiring NEC, with a prevalence of nearly 7-10%, mortality up to 30%, and several long-term complications among survivors. Despite advancements in neonatal medicine, this disease remains a challenge to treat. The aim of this study is to investigate the effect of NEC on gut epithelial tight junctions and its barrier function using a NEC mouse model. METHODS: Three-day old C57BL/6 mouse pups were fed with Esbilac formula every 3 hours and then subjected to hypoxia twice daily followed by cold stress. Dam fed pups from the same litters served as controls. Pups were observed and sacrificed 96 hours after the treatments and intestines were removed for experiments. The successful induction of NEC was confirmed by histopathology. Changes in tight junction proteins in NEC intestines were studied by western blotting and immunofluorescent microscopy using specific protein markers. The gut leakage in NEC was visualized using biotin tracer molecules. RESULTS: Our study results demonstrate that we induced NEC in >50% of experimental pups, pups lost nearly 40% of weight and their intestines showed gross changes and microscopic changes associated with NEC. There were inflammatory changes with loss of tight junction barrier function and disruption of tight junction claudin proteins in the intestines of NEC mouse model. We have demonstrated for the first time that NEC intestines develop increased leakiness as visualized by biotin tracer leakage. CONCLUSIONS: NEC leads to breakdown of epithelial barrier due to changes in tight junction proteins with increased leakiness which may explain the transmigration of microbes and microbial products from the gut lumen into the blood stream leading to sepsis like signs clinically witnessed.

A Web-Based Calculator for the Prediction of Severe Neurodevelopmental Impairment in Preterm Infants Using Clinical and Imaging Characteristics.

Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe neurodevelopmental outcomes from normal-moderate outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation and who had MRI imaging at term-equivalent age and neurodevelopmental testing at 18⁻24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage) and clinical factors that were strongly predictive of an outcome were investigated. A binary logistic regression model was then generated from the composite of clinical and imaging components. A total of 154 infants were included (mean gestational age = 26.1 ± 1.8 weeks, birth weight = 889.1 ± 226.2 g). The final model (imaging score + ventilator days + delivery mode + antenatal steroids + retinopathy of prematurity requiring surgery) had strong discriminatory power for severe disability (AUC = 0.850), with a PPV (positive predictive value) of 76% and an NPV (negative predictive value) of 90%. Available as a web-based tool, it can be useful for prognostication and targeting early intervention services to infants who may benefit the most from such services.

Divergent risk factors for cerebellar and intraventricular hemorrhage.

OBJECTIVE: To identify whether intraventricular hemorrhage (IVH) and cerebellar hemorrhage (CH) have common or divergent risk factors. STUDY DESIGN: This is a retrospective cross-sectional cohort of infants including all infants born <30 weeks from 2007 to 2016. Comprehensive perinatal and clinical factors were extracted from the medical record. Outborn infants, infants with major congenital anomaly, those transferred prior to discharge, and those with mixed or no brain injury were excluded. The remaining infants were divided into two groups: IVH only and CH only. Continuous variables were evaluated with the Wilcoxon-Mann-Whitney test, and categorical variables were evaluated with Fisher's exact test. Multinomial logistic regression was used to identify factors which predispose infants towards injury type more than another, holding other factors constant. RESULTS: In total, 127 infants were included (CH n = 27, IVH n = 100). Compared to those with IVH, infants with CH were of lower EGA (p = 0.03), lower birth weight (p = 0.01), more often of multiple gestation (p = 0.03), more frequently born emergently (p = 0.03), had a greater number of ventilator days (p = 0.03), received postnatal steroids more often (p = 0.02), had a greater incidence of hemodynamically significant patent ductus arteriosus (PDA), and less frequently had pulmonary hemorrhage (p = 0.04). In multinomial regression analysis, three factors were identified which favored CH over IVH: multiple gestation (RR 4.70, 95% CI 1.56-14.21, p < 0.01), chorioamnionitis (RR 3.18, 95% CI 1.13-8.92, p = 0.03), and emergent delivery (RR 4.14, 95% CI 1.48-11.55, p < 0.01). Only advancing gestational favored IVH over CH (RR 0.74, 95% CI 0.65-0.85, p < 0.01). CONCLUSIONS: IVH and CH have unique risk factors. These results highlight the need to tailor neuroimaging surveillance to specific patient risk factors.

Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case-control study.

OBJECTIVE: To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. PATIENTS AND METHODS: A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. RESULTS: Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. CONCLUSION: In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain.

The potential utility of non-invasive imaging to monitor restoration of bladder structure and function following subtotal cystectomy (STC).

BACKGROUND: Restoration of normal bladder volume and function (i.e., bioequivalent bladder) are observed within 8 weeks of performing subtotal cystectomy (STC; removal of ~70 % of the bladder) in 12-week old rats. For analysis of bladder function in rodents, terminal urodynamic approaches are largely utilized. In the current study, we investigated the potential for Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans to noninvasively track restoration of structure and function following STC. METHODS: Twelve week old female Fisher F344 rats underwent STC and were scanned via CT and/or MRI 2, 4, 8, and 12 weeks post-STC, followed by urodynamic testing. After euthanasia, bladders were excised for histological processing. RESULTS: MRI scans demonstrated an initial decline followed by a time-dependent increase to normal bladder wall thickness (BWT) by 8 weeks post-STC. Masson's trichrome staining showed a lack of fibrosis post-STC, and also revealed that the percent of smooth muscle in the bladder wall at 2 and 4 weeks positively correlated with pre-operative baseline BWT. Moreover, increased BWT values before STC was predictive of improved bladder compliance at 2 and 4 weeks post-STC. Cystometric studies indicated that repeated MRI manipulation (i.e. bladder emptying) apparently had a negative impact on bladder capacity and compliance. A "window" of bladder volumes was identified 2 weeks post-STC via CT scanning that were commensurate with normal micturition pressures measured in the same animal 6 weeks later. CONCLUSIONS: Taken together, the data indicate some limitations of "non-invasive" imaging to provide insight into bladder regeneration. Specifically, mechanical manipulation of the bladder during MRI appears to negatively impact the regenerative process per se, which highlights the importance of terminal cystometric studies.