Newborns with hypoxic-ischemic encephalopathy (HIE) may exhibit abnormalities on placental histology. In this phase II clinical trial ancillary study, we hypothesized that placental abnormalities ...correlate with MRI brain injury and with response to treatment.
Fifty newborns with moderate/severe encephalopathy who received hypothermia were enrolled in a double-blind, placebo-controlled trial of erythropoietin for HIE. A study pathologist reviewed all available clinical pathology reports to determine the presence of chronic abnormalities and acute chorioamnionitis. Neonatal brain MRIs were scored using a validated HIE scoring system.
Placental abnormalities in 19 of the 35 (54%) patients with available pathology reports included chronic changes (N = 13), acute chorioamnionitis (N = 9), or both (N = 3). MRI subcortical brain injury was less common in infants with a placental abnormality (26 vs. 69%, P = 0.02). Erythropoietin treatment was associated with a lower global brain injury score (median 2.0 vs. 11.5, P = 0.003) and lower rate of subcortical brain injury (33 vs. 90%, P = 0.01) among patients with no chronic placental abnormality but not in patients whose placentas harbored a chronic abnormality.
Erythropoietin treatment was associated with less brain injury only in patients whose placentas exhibited no chronic histologic changes. Placentas may provide clues to treatment response in HIE.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mild hypoxic-ischemic encephalopathy (HIE) is increasingly recognized as a risk factor for neonatal brain injury. We examined the timing and pattern of brain injury in mild HIE.
This retrospective ...cohort study includes infants with mild HIE treated at 9 hospitals. Neonatal brain MRIs were scored by 2 reviewers using a validated classification system, with discrepancies resolved by consensus. Severity and timing of MRI brain injury (i.e., acute, subacute, chronic) was scored on the subset of MRIs that were performed at or before 8 days of age.
Of 142 infants with mild HIE, 87 (61%) had injury on MRI at median age 5 (IQR 4-6) days. Watershed (23%), deep gray (20%) and punctate white matter (18%) injury were most common. Among the 125 (88%) infants who received a brain MRI at ≤8 days, mild (44%) injury was more common than moderate (11%) or severe (4%) injury. Subacute (37%) lesions were more commonly observed than acute (32%) or chronic lesions (1%).
Subacute brain injury is common in newborn infants with mild HIE. Novel neuroprotective treatments for mild HIE will ideally target both subacute and acute injury mechanisms.
Almost two-thirds of infants with mild HIE have evidence of brain injury on MRI obtained in the early neonatal period. Subacute brain injury was seen in 37% of infants with mild HIE. Neuroprotective treatments for mild HIE will ideally target both acute and subacute injury mechanisms.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
BackgroundPremature infants may lack mature cerebrovascular autoregulatory function and fail to adapt oxygen extraction to decreasing systemic perfusion.MethodsInfants ≤28 weeks of gestational age ...(GA) were recruited. Systemic oxygen saturation (SpO
), mean arterial blood pressure (MABP), and cerebral saturation (near-infrared spectroscopy, SctO
) were measured continuously over the first 72 h. Resulting data underwent error-processing. For each remaining 10 m window, the mean MABP and fractional tissue oxygen extraction (FTOE) were calculated. The infants were divided into two groups (23-25 and 26-28 weeks). The median FTOE at low, medium, and high MABP values (empirically defined within each group based on the 25th and 75th centile) were compared between estimated gestational age (EGA) groups.ResultsSample n=68, mean±SD GA=25.5±1.3 weeks, and birthweight (BW)=823±195 g. The median FTOE in the more preterm group vs. more mature group was statistically different at lower value of MABP (P<0.01) and higher values of MABP (P=0.01), but not at medium values (P=0.55).ConclusionThe more mature group (GA 26-28 weeks) displayed an appropriate increase in oxygen extraction during hypotension, steadily decreasing as MABP increased, suggesting mature autoregulation. An opposite response was noted in the more preterm group, suggesting an inability to mount a compensatory response when BP is outside of the physiologic range.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: Post-resuscitation reperfusion following hypoxic-ischemia (HIE) is associated with secondary brain injury in neonates. Objective: To quantify the association between perfusion exceeding ...autoregulatory limits and brain injury. Approach: Continuous mean arterial blood pressure (MABP) and cerebral near-infrared spectroscopy (NIRS) data were prospectively collected from infants with HIE. Cerebral oximetry index (COx) was calculated as a moving correlation coefficient between MABP and NIRS. Upper and lower limits of autoregulation were identified by transition from negative to positive correlation. The proportion of time MABP above (hyperperfusion) and below (hypoperfusion) autoregulatory limits was calculated during therapeutic hypothermia (days 1-3). Main results: Sixteen infants were included; injury was noted in 7/16. There was no significance in hyperperfusion burden between injured and uninjured infants during day one (7% versus 10%, p = 0.88) or two (4% versus 2%, p = 0.88), but there was a marked increase for injured infants on day three (54% versus 14%, p = 0.02). There was a corollary decrease in hypoperfusion for injured versus uninjured infants on day 3 (6% versus 24%, p = 0.05). Significance: HIE infants with brain injury have a late failure of cerebral autoregulation, manifested as a hyperperfusion burden, suggesting pathologic events are active on day 3 of hypothermia. This finding may help to identify infants which might need additional neuroprotection.
Magnetic resonance imaging (MRI) is the gold standard for outcome prediction after hypoxic-ischemic encephalopathy (HIE). Published scoring systems contain duplicative or conflicting elements.
...Infants ≥36 weeks gestational age (GA) with moderate to severe HIE, therapeutic hypothermia treatment, and T1/T2/diffusion-weighted imaging were identified. Adverse motor outcome was defined as Bayley-III motor score <85 or Alberta Infant Motor Scale <10th centile at 12 to 24 months. MRIs were scored using a published scoring system.
Logistic regression (LR) and gradient-boosted deep learning (DL) models quantified the importance of clinical and imaging features. The cohort underwent 80/20 train/test split with fivefold cross validation. Feature selection eliminated low-value features.
A total of 117 infants were identified with mean GA = 38.6 weeks, median cord pH = 7.01, and median 10-minute Apgar = 5. Adverse motor outcome was noted in 23 of 117 (20%).
Putamen/globus pallidus injury on T1, GA, and cord pH were the most informative features. Feature selection improved model accuracy from 79% (48-feature MRI model) to 85% (three-feature model). The three-feature DL model had superior performance to the best LR model (area under the receiver-operator curve 0.69 versus 0.75).
The parsimonious DL model predicted adverse HIE motor outcomes with 85% accuracy using only three features (putamen/globus pallidus injury on T1, GA, and cord pH) and outperformed LR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Hydrogel and gold cup electrodes can be used safely in long-term EEG studies in preterm neonates.•Hydrogel electrodes are non-inferior to gold cup electrodes in terms of replacement frequency and ...recording quality.•Hydrogel electrodes showed a longer uninterrupted recording time than gold cup electrodes.
The objective of this study was to compare gold cup and hydrogel electrodes for frequency of electrode replacement, longevity of the original electrodes after initial placement, recording quality, and skin safety issues in long-term EEG studies in preterm neonates.
We performed a prospective trial with newborns born at ≥23 weeks and ≤30 weeks of gestational age (GA). Two mirror image EEG electrode arrays were utilized on consecutive subjects, where gold cup electrodes alternated with hydrogel electrodes.
Our sample included 50 neonates with mean GA of 27 (±1) weeks. The mean recording time was 84 (±15) hours. No difference was present in the frequency of replacement of either type across the total recording time (p = 0.8). We collected the time at which electrodes were first replaced, and found that hydrogel electrodes showed a longer uninterrupted recording time of 28(±2) hours vs. 20(±2) hours for gold cup electrodes (p = 0.01). Recording quality was similar in either type (p = 0.2). None of the patients experienced significant skin irritation from a discrete electrode.
Long-term EEG studies can be performed with either gold cup or hydrogel electrodes, validating the safety and quality of both electrode types.
Hydrogel electrodes are a reasonable alternative for use in long-term EEG studies in preterm neonates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Elevated cerebral fractional tissue oxygen extraction (cFTOE) is an adaptation to anemia of prematurity (AOP). cFTOE ≥0.4 is associated with brain injury in infants ≤30 weeks. This longitudinal study ...sought to investigate the utility of cFTOE in the evaluation of AOP.
Infants ≤30 weeks estimated gestational age (EGA) underwent weekly hemoglobin, cerebral saturation, and pulse oximetry recordings from the second through 36 weeks post-menstrual age (PMA). Recordings were excluded if they were under 1 h or if hemoglobin was not measured within 7 days of recording. Mean cFTOE was calculated for each recording. Statistical analysis used linear mixed-effects modeling and receiver operating characteristic analysis.
144 recordings from 39 infants (mean EGA 27.6 ± 2.2 weeks, BW 1139 ± 286 g) were included of whom 39% (15/39) were transfused. The mean recording length was 2.8 ± 1.3 h. There was a significant negative correlation between hemoglobin and cFTOE (R = −0.423, p ≤.001). In a multivariate model, adjusting for EGA, PMA, and patent ductus arteriosus treatment the AUC was 0.821. A critical increase in cFTOE occurred at a hemoglobin level of 9.6 g/dL.
AOP is associated with a critical increase in cFTOE that occurs at a significantly higher hemoglobin level than standard clinical thresholds for transfusion.
•cFTOE, derived from regional cerebral saturations measured using NIRS and pulse oximetry, is a marker of regional tissue oxygen delivery and metabolic activity.•Elevated cFTOE is a known adaptation to anemia, but values ≥0.4 are associated with brain injury in preterm infants.•Current clinical threshold hemoglobin levels for pRBC transfusions in anemia of prematurity are population based and not based on individual patient physiology.•This study identified the threshold for critical oxygen extraction (cFTOE ≥0.4) as 9.6 g/dL in stable preterm infants with anemia of prematurity, significantly higher than current thresholds for transfusion (<8 g/dL).•Longitudinal evaluation of premature infants using concurrent hemoglobin levels and cerebral NIRS may help define patient specific transfusion thresholds of hemoglobin in preterm infants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine the impact of progressive anemia of prematurity on cerebral regional saturation (C-rSO
) in preterm infants and identify the hemoglobin threshold below which a critical decrease (>2SD ...below the mean) in C-rSO
occurs.
In a cohort of infants born ≤30 weeks EGA, weekly C-rSO
data were prospectively collected from the second week of life through 36 weeks post-menstrual age (PMA). Clinically obtained hemoglobin values were noted at the time of recording. Recordings were excluded if they were of insufficient duration (<1 h) or if the hemoglobin was not measured within 7 days. Statistical analysis was performed using a linear mixed effects-model and ROC analysis. ROC analysis was used to determine the threshold of anemia, where C-rSO
critically decreased >2SD below the mean normative value (<55%) in preterm infants.
In total 253 recordings from 68 infants (mean EGA 26.9 ± 2.1 weeks, BW 1025 ± 287 g, 49% male) were included. Approximately 29 out of 68 infants (43%) were transfused during hospitalization. Mixed-model statistical analysis adjusting for EGA, BW, and PMA revealed a significant association between decreasing hemoglobin and C-rSO
(p < 0.01) in transfusion-naive infants but not in transfused infants. In the transfusion naive group, using ROC analysis demonstrated a threshold hemoglobin of 9.5 g/dL (AUC 0.81, p < 0.01) for critical cerebral desaturation in preterm infants.
In transfusion-naive preterm infants, worsening anemia was associated with a progressive decrease in cerebral saturations. Analysis identified a threshold hemoglobin of 9.5 g/dL below which C-rSO
dropped >2SD below the mean.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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