The objectives of this prospective cohort study were to identify amplitude-integrated electroencephalography (aEEG) background patterns predictive of severe intracranial hemorrhage. Thirty ventilated ...preterm newborns weighing <1,000 g were assessed by an aEEG cerebral function monitor and ultrasound measurement of cerebral blood flow velocity at time of surfactant administration and tracheal suctioning simultaneously during first 48 hours of life. Birth weight was 624 ± 200 g (mean ± S.D.) and gestational age was 25 ± 2 weeks. Background electrical activity was predominantly discontinuous in 72% of infants. A sharp increase in electrical activity/burst density was observed during surfactant administration and tracheal suctioning in most infants, with a 33.5% increase in mean cerebral blood flow velocity. Burst suppression with low voltage was identified in 57% infants with severe intracranial hemorrhage, whereas no infant without hemorrhage exhibited this pattern ( P = 0.014). We conclude that aEEG low-voltage burst suppression might have useful clinical applications with 100% positive predictive value for severe intracranial hemorrhage.
To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7 weeks of gestational age and to ...assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age.
The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models.
One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age.
Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.
The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD).
A secondary analysis of the PENUT Trial dataset was conducted. ...The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization.
Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD.
We find no support for an increased risk of BPD with iron supplementation.
NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT: Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.
The optimal mode of delivery for extremely low birth weight (ELBW) infants remains unknown. We reviewed the medical records of 374 ELBW infants (gestational age 23-34 weeks) delivered between 1998 ...and 2003 at UAMS. The cesarean section rate was 63.9%. The overall mortality rate was 16.0%. The mortality rate for vaginally delivered infants was 26.7% (36/135) vs. 10% (24/239) for cesarean section (P < .0001). Cesarean delivery was associated with higher odds of survival without severe brain injury (SBI) (OR = 2.33, 95% CI 1.36, 4.00).
IMPORTANCE: Understanding why and how extremely preterm infants die is important for practitioners caring for these infants. OBJECTIVE: To examine risk factors, causes, timing, and circumstances of ...death in a modern cohort of extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort review of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial between December 13, 2013, and September 26, 2016, was conducted. A total of 941 infants born between 24 0/7 and 27 6/7 weeks of gestation enrolled at 19 US sites comprising 30 neonatal intensive care units were included. Data analysis was performed from October 16, 2020, to December 1, 2021. MAIN OUTCOMES AND MEASURES: Risk factors, proximal causes, timing, and circumstances of in-hospital death. RESULTS: Of the 941 enrolled infants, 108 died (11%) before hospital discharge: 38% (n = 41) at 24 weeks’ gestation, 30% (n = 32) at 25 weeks’ gestation, 19% (n = 20) at 26 weeks’ gestation, and 14% (n = 15) at 27 weeks’ gestation. An additional 9 infants (1%) died following hospital discharge. In descending order, the primary causes of death included respiratory distress or failure, pulmonary hemorrhage, necrotizing enterocolitis, catastrophic intracranial hemorrhage, sepsis, and sudden unexplained death. Fifty percent of deaths occurred within the first 10 days after birth. The risk of death decreased with day of life and postmenstrual age such that an infant born at 24 weeks’ gestation who survived 14 days had the same risk of death as an infant born at 27 weeks’ gestation: conditional proportional risk of death, 0.08 (95% CI, 0.03-0.13) vs 0.06 (95% CI, 0.01-0.11). Preterm labor was associated with a decreased hazard of death (hazard ratio HR, 0.45; 95% CI, 0.31-0.66). Infant clinical factors associated with death included birth weight below the tenth percentile for gestational age (HR, 2.11; 95% CI, 1.38-3.22), Apgar score less than 5 at 5 minutes (HR, 2.19; 95% CI, 1.48-3.24), sick appearance at birth (HR, 2.49; 95% CI, 1.69-3.67), grade 2b-3 necrotizing enterocolitis (HR, 7.41; 95% CI, 5.14-10.7), pulmonary hemorrhage (HR, 10.0; 95% CI, 6.76-18.8), severe intracranial hemorrhage (HR, 4.60; 95% CI, 3.24-5.63), and severe sepsis (HR, 4.93; 95% CI, 3.67-7.21). Fifty-one percent of the infants received comfort care before death. CONCLUSIONS AND RELEVANCE: In this cohort study, an association between mortality and gestational age at birth was noted; however, for each week that an infant survived, their risk of subsequent death approximated the risk observed in infants born 1 to 2 weeks later, suggesting the importance of an infant’s postmenstrual age. This information may be useful to include in counseling of families regarding prognosis of survival.
Tendinopathy has been broadly characterized as alterations in cell proliferation, extracellular matrix turnover/synthesis, and inflammatory alterations. However, the underlying glucose metabolism ...pathways which contribute to these responses have not been well explored. The potential link between glucose metabolism and tendon pathology is interesting from a global standpoint since the development of spontaneous tendinopathy is associated with systemic metabolic disorders including diabetes mellitus. Therefore, the overarching goal of this study was to understand the potential pathogenic role of glucose metabolism‐driven mechanisms in the development of tendinopathy. To test this, we have utilized an untargeted metabolomics approach to discover pathways which may be altered following tendinopathic injury and treadmill running in an established murine model of TGF‐β1 induced tendinopathy. While specific tendon glucose alterations were not observed via metabolomics or 18F‐fluoroeoxyglucose (FDG) positron emission tomography/microcomputed tomography imaging (18F‐FDG PET/CT), metabolites including creatinine, D‐chiro‐inositol, and lipids were dysregulated following tendon injury. As novel pathways for manipulation, the creatine pathway, myo‐inositol pathway, and lipid signaling may lead to the development of enhanced preventative strategies and therapeutic options for all patients who suffer from tendon‐related injuries.
The chain of events surrounding the initiation and intensification of the last glacial cycle remain relatively poorly understood. In particular, the role of Southern Ocean paleocirculation changes is ...poorly constrained, in part, owing to a paucity of sedimentary records from this region. In this study we present multiproxy data – including neodymium isotope and sortable silt measurements – for paleocirculation changes within the deep (3167 m water depth) Indian sector of the Southern Ocean from a new sediment core, TT1811-34GGC (41.718°S, 80.163°E). We find a tight coupling between circulation changes, Antarctic climate, and atmospheric CO2 concentrations throughout the last 118,000 years, even during the initial stages of glacial inception of Marine Isotope Stage (MIS) 5.4 to 5.1. We find that periods of cooling correspond to reductions in the entrainment of North Atlantic-sourced waters within the deep Southern Ocean, as evidenced by more radiogenic neodymium isotope values of deep water bathing our core site. Cooling also corresponds to generally slower bottom water flow speeds, as indicated by finer sortable silt size fractions. A reduction in entrainment of North-Atlantic sourced waters occurred during MIS 5.4–5.1, when Atlantic circulation was strong, suggesting a Southern hemisphere control on paleocirculation changes at that time. We hypothesise that expanded Southern Ocean sea-ice during MIS 5.4 increased the density of the deep Southern Ocean, reducing the ability of Atlantic-sourced waters to mix into Lower Circumpolar Deep Water. This led to an expanded contribution of Pacific Deep Water within the lower circulation cell and increased stratification within the deep Southern Ocean. These paleocirculation changes can help account for the reduction in atmospheric CO2 across the MIS 5.5 to 5.4 transition, and in doing so help explain the chain of events surrounding the decent into the last glacial period.
•Proportion of NADW mixing into LCDW reduced during the last glacial period.•A reduction in NADW within LCDW is observed during early stages of glacial inception during MIS 5.4•Increased stratification within Southern Ocean early during the last glacial cycle is inferred.•Physical circulation changes within the Southern Ocean may play a role in initiation of glaciation.
Dopamine, by acting upon D1 and D2 dopamine receptors located on striatonigral and striatopallidal neurons, respectively, has been postulated to inhibit output from the substantia nigra pars ...reticulata (SNpr) and internal pallidal segment (GPi). The inhibition of the SNpr/GPi should, in turn, disinhibit the thalamus to facilitate movement. The present study tests this prediction in intact (unlesioned) rats by attempting to correlate changes in the single unit activities of SNpr neurons with motor (i.e. behavioral) responses in the 20–30 min after infusions of
d-amphetamine into the striatum. Unilateral injections of amphetamine (20 μg/μl) into either the dorsal-rostral, central, or ventral-lateral striatum failed to appreciably alter behavior and, in parallel electrophysiological studies, failed to consistently or significantly alter the activities of SNpr neurons in either chloral hydrate-anesthetized rats or awake locally anesthetized rats. However, when amphetamine was infused bilaterally into the ventral-lateral striatum (VLS; 20 μg/μl per side), a robust behavioral activation ensued (increased locomotor activity, oral movements, and sniffing) with an onset ranging from immediate to 20 min post-infusion and persisting for at least 40 min. In parallel studies, bilateral amphetamine infusions into VLS also caused changes in the firing frequency of a majority of SNpr neurons. However, the changes in firing were extremely variable and, contrary to expectation, the net population response of SNpr neurons was an increase in firing which corresponded in time with the period of peak behavioral activation. These results show that (i) bilateral but not unilateral activation of striatal dopamine receptors is needed to elicit behavioral and electrophysiological output from the basal ganglia, and (ii) motor activation is apparently not signaled by a generalized inhibition of SNpr firing, as is predicted by the basal ganglia model.
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