Electroencephalogram (EEG) signals are often contaminated by the electrocardiogram (ECG) interfer... more Electroencephalogram (EEG) signals are often contaminated by the electrocardiogram (ECG) interference, which affects quantitative characterization of EEG. We propose null-coherence, a frequency-based approach, to attenuate the ECG interference in EEG using simultaneously recorded ECG as a reference signal. After validating the proposed approach using numerically simulated data, we apply this approach to EEG recorded from six newborns receiving therapeutic hypothermia for neonatal encephalopathy. We compare our approach with an independent component analysis (ICA), a previously proposed approach to attenuate ECG artifacts in the EEG signal. The power spectrum and the cortico-cortical connectivity of the ECG attenuated EEG was compared against the power spectrum and the cortico-cortical connectivity of the raw EEG. The null-coherence approach attenuated the ECG contamination without leaving any residual of the ECG in the EEG. We show that the null-coherence approach performs better th...
Objective Collect data from craniofacial surgeons to analyze mandibular distraction osteogenesis ... more Objective Collect data from craniofacial surgeons to analyze mandibular distraction osteogenesis (MDO) protocols, and facial nerve dysfunction (FND) to characterize this common, but poorly documented complication after MDO in infants with Robin Sequence (RS). Design, Setting, and Participants A 16-question anonymous survey designed through REDCap was digitally distributed to members of the American Cleft Palate-Craniofacial Association and International Society of Craniofacial Surgery (ISCFS). Main Outcome Measure(s) Demographic information, MDO perioperative variables, surgeon experience with FND after MDO for patients with RS, and the timing and duration of FND were analyzed. Results Eighty-four responses were collected, with 80 included for analysis. Almost two-thirds of respondent surgeons reported FND as a complication of MDO in patients with RS (51, 63.8%); 58.8% (n = 47) transient FND and 5% (n = 4) with permanent facial nerve palsy only. Both transient and permanent ...
Little is known about parent and family well-being after acute neonatal seizures. In thus study, ... more Little is known about parent and family well-being after acute neonatal seizures. In thus study, we aimed to characterize parent mental health and family coping over the first two years after their child’s neonatal seizures. Parents of 303 children with acute neonatal seizures from nine pediatric hospitals completed surveys at discharge and 12-, 18- and 24-months corrected age. Outcomes included parental anxiety, depression, quality of life, impact on the family, post-traumatic stress and post-traumatic growth. We used linear mixed effect regression models and multivariate analysis to examine relationships among predictors and outcomes. At the two-year timepoint, parents reported clinically significant anxiety (31.5%), depression (11.7%) and post-traumatic stress (23.7%). Parents reported moderately high quality of life and positive personal change over time despite ongoing challenges to family coping. Families of children with longer neonatal hospitalization, functional impairment,...
The aims of this study were to find the normal value of fronto-temporal horn ratio (FTHR) as a ma... more The aims of this study were to find the normal value of fronto-temporal horn ratio (FTHR) as a marker of ventriculomegaly on cranial ultrasound (CUS) in premature newborns and the relation to white matter injury (WMI) and cerebral palsy (CP). This is a retrospective study of newborns admitted between 2011 and 2014. Inclusion criteria were: (1) gestation <29 weeks, (2) birth weight ≤1500 g, (3) referred within 7 days of life, (4) at least two CUS preformed, (5) brain magnetic resonance imaging (MRI) at term age-equivalent. Intraventricular hemorrhage (IVH) grade was identified and FTHR was measured on all CUS. WMI on MRI was evaluated through (1) injury score (Kidokoro 2013) and (2) fractional anisotropy (FA) on the MRI diffusion tensor imaging. CP was estimated using the gross motor function classification system (GMFCS). One hundred neonates met the inclusion criteria: 37 with no IVH, 36 with IVH grade 1–2, and 27 with IVH grade 3–4. The FTHR cut-point of 0.51 had the highest sensitivity and specificity for moderate-to-severe WMI. In the IVH grade 3–4 group, the elevated FTHR correlated with lower FA and higher GMFCS. FTHR is a useful quantitative biomarker of ventriculomegaly in preterm newborns. It may help standardize ventricular measurement and direct intervention. The fronto-temporal horn ratio has the potential to become a standardized tool that can provide an actionable measure to direct intervention for post-hemorrhagic ventricular dilation. This current study will provide the basis of a future clinical trial to optimize intervention timing to decrease the risk of white matter injury in this vulnerable population. The fronto-temporal horn ratio has the potential to become a standardized tool that can provide an actionable measure to direct intervention for post-hemorrhagic ventricular dilation. This current study will provide the basis of a future clinical trial to optimize intervention timing to decrease the risk of white matter injury in this vulnerable population.
OBJECTIVE To characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born at ... more OBJECTIVE To characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born at term and preterm. For term infants, to compare seizure severity and treatment response for multi-site vs single-site ICH and hypoxic-ischemic encephalopathy (HIE) with vs. without ICH. STUDY DESIGN We studied 112 newborn infants with seizures attributed to ICH, and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multi-site vs. single-site ICH and HIE with vs. without ICH. RESULTS ICH was a more common seizure etiology in infants born preterm vs. term (27% vs. 10%, p<0.001). Most infants had subclinical seizures (74%) and an incomplete response to initial antiseizure medication (ASM) (68%). In infants born term, multi-site ICH was associated with more subclinical seizures than single-site ICH (93% vs. 66%, p=0.05) and an incomplete response to the initial ASM (100% vs. 66%, p=0.02). Status epilepticus was more common in HIE with ICH vs. HIE alone (38% vs. 17%, P = .05). CONCLUSIONS Seizure severity was higher and treatment response was lower among infants born term with complicated ICH. These data support the use of continuous video electroencephalogram monitoring to accurately detect seizures and a multi-step treatment plan that considers early use of multiple ASMs, particularly with parenchymal and high-grade intraventricular hemorrhage and complicated ICH.
Neonatal-onset urea cycle disorders (UCDs) may result in hyperammonemic (HA) encephalopathy prese... more Neonatal-onset urea cycle disorders (UCDs) may result in hyperammonemic (HA) encephalopathy presenting with several neurologic sequelae including seizures, coma, and death. However, no recommendations are given in how and when neurodiagnostic studies should be used to screen or assess for these neurologic complications. We present a case of carbamoyl phosphate synthetase 1 (CPS1) deficiency in a newborn female in which electroencephalogram monitoring to assess encephalopathy and seizures, and magnetic resonance imaging measurements of brain metabolites were used to guide care during her hyperammonemic crisis. Her neurologic course and response to treatment characterizes the significant neurologic impact of HA encephalopathy. Our group herein proposes a clinical neurodiagnostic pathway for managing acute HA encephalopathy.
OBJECTIVE To examine the frequency of placental abnormalities in a multicenter cohort of newborn ... more OBJECTIVE To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE), and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE. STUDY DESIGN Infants born at ≥ 36 weeks of gestation (n=500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system. RESULTS Complete placental pathologic examination was available for 321/500 (64%) trial participants. Placental abnormalities were identified in 273/321 (85%) and were more common in infants ≥ 40 weeks of gestation (93% vs. 81%, p=0.01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs. -14.3, p=0.049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs. 38.0, p<0.001) and higher rates of clinically diagnosed chorioamnionitis (25% vs 2%, P < .001) than those without acute abnormalities. CONCLUSION Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.
Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half ... more Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half of neonates treated with therapeutic hypothermia for NE have EEG-confirmed seizures. These seizures are best identified with continuous EEG monitoring, as clinical diagnosis leads to under-diagnosis of subclinical seizures and over-treatment of events that are not seizures. High seizure burden, especially status epilepticus, is thought to augment brain injury. Treatment, therefore, is aimed at minimizing seizure burden. Phenobarbital remains the mainstay of treatment, as it is more effective than levetiracetam and easier to administer than fosphenytoin. Emerging evidence suggests that, for many neonates, it is safe to discontinue the phenobarbital after acute seizures resolve and prior to hospital discharge.
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2020
ObjectiveNeonates with seizures have a high risk of mortality and neurological morbidity. We aime... more ObjectiveNeonates with seizures have a high risk of mortality and neurological morbidity. We aimed to describe the experience of parents caring for neonates with seizures.DesignThis prospective, observational and multicentre (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. At the time of hospital discharge, parents answered six open-ended response questions that targeted their experience. Responses were analysed using a conventional content analysis approach.Results144 parents completed the open-ended questions (732 total comments). Four themes were identified. Sources of strength: families valued medical team consensus, opportunities to contribute to their child’s care and bonding with their infant. Uncertainty: parents reported three primary types of uncertainty, all of which caused distress: (1) the daily uncertainty of the intensive care experience; (2) concerns about their child’s uncertain future and (3) lack of consensus between ...
The objective was to examine the discriminatory ability of electroencephalogram (EEG) delta power... more The objective was to examine the discriminatory ability of electroencephalogram (EEG) delta power in neonates with hypoxic-ischemic encephalopathy (HIE) with well-defined outcomes. Prolonged continuous EEG recordings from term neonates with HIE during therapeutic hypothermia enrolled in a prospective observational study were examined. Adverse outcome was defined as death or severe brain injury by magnetic resonance imaging (MRI); favorable outcome was defined as normal or mild injury by MRI. Neonates were stratified by Sarnat grade of encephalopathy at admission. EEG was partitioned into 10-minute nonoverlapping artifact- and seizure-free epochs. Delta power was calculated and compared between the groups using receiver operating characteristic (ROC) analyses and Wilcoxon rank-sum tests. An area under the ROC curve >0.7 with P
Objective: To examine the frequency and types of placental pathology observed in encephalopathic ... more Objective: To examine the frequency and types of placental pathology observed in encephalopathic newborns presenting for therapeutic hypothermia. Study Design: Between May 2006 and April 2010, 140 term newborns with neonatal encephalopathy were admitted for cooling. The presence or absence of recognized asphyxial ("sentinel") birth events was noted. Placental pathology was categorized as vascular, inflammatory, or other. Result: Placental surgical pathology reports were available for 100 newborns, of whom 51% had sentinel events. Abnormalities were reported in 51% of placentas, 29% with and 73% without sentinel events (p = 0.0001). Inflammatory pathology was more frequent in infants without sentinel events (43% vs. 14%, p = 0.0016), especially in infants with pH below 7.0 (p = 0.012). Conclusion: Placental pathology was common in infants with neonatal encephalopathy admitted for therapeutic hypothermia, especially in those with no clinically recognized sentinel birth events. Severe acidosis was often observed in infants without sentinel events who had inflammatory placental pathology.
Electroencephalogram (EEG) signals are often contaminated by the electrocardiogram (ECG) interfer... more Electroencephalogram (EEG) signals are often contaminated by the electrocardiogram (ECG) interference, which affects quantitative characterization of EEG. We propose null-coherence, a frequency-based approach, to attenuate the ECG interference in EEG using simultaneously recorded ECG as a reference signal. After validating the proposed approach using numerically simulated data, we apply this approach to EEG recorded from six newborns receiving therapeutic hypothermia for neonatal encephalopathy. We compare our approach with an independent component analysis (ICA), a previously proposed approach to attenuate ECG artifacts in the EEG signal. The power spectrum and the cortico-cortical connectivity of the ECG attenuated EEG was compared against the power spectrum and the cortico-cortical connectivity of the raw EEG. The null-coherence approach attenuated the ECG contamination without leaving any residual of the ECG in the EEG. We show that the null-coherence approach performs better th...
Objective Collect data from craniofacial surgeons to analyze mandibular distraction osteogenesis ... more Objective Collect data from craniofacial surgeons to analyze mandibular distraction osteogenesis (MDO) protocols, and facial nerve dysfunction (FND) to characterize this common, but poorly documented complication after MDO in infants with Robin Sequence (RS). Design, Setting, and Participants A 16-question anonymous survey designed through REDCap was digitally distributed to members of the American Cleft Palate-Craniofacial Association and International Society of Craniofacial Surgery (ISCFS). Main Outcome Measure(s) Demographic information, MDO perioperative variables, surgeon experience with FND after MDO for patients with RS, and the timing and duration of FND were analyzed. Results Eighty-four responses were collected, with 80 included for analysis. Almost two-thirds of respondent surgeons reported FND as a complication of MDO in patients with RS (51, 63.8%); 58.8% (n = 47) transient FND and 5% (n = 4) with permanent facial nerve palsy only. Both transient and permanent ...
Little is known about parent and family well-being after acute neonatal seizures. In thus study, ... more Little is known about parent and family well-being after acute neonatal seizures. In thus study, we aimed to characterize parent mental health and family coping over the first two years after their child’s neonatal seizures. Parents of 303 children with acute neonatal seizures from nine pediatric hospitals completed surveys at discharge and 12-, 18- and 24-months corrected age. Outcomes included parental anxiety, depression, quality of life, impact on the family, post-traumatic stress and post-traumatic growth. We used linear mixed effect regression models and multivariate analysis to examine relationships among predictors and outcomes. At the two-year timepoint, parents reported clinically significant anxiety (31.5%), depression (11.7%) and post-traumatic stress (23.7%). Parents reported moderately high quality of life and positive personal change over time despite ongoing challenges to family coping. Families of children with longer neonatal hospitalization, functional impairment,...
The aims of this study were to find the normal value of fronto-temporal horn ratio (FTHR) as a ma... more The aims of this study were to find the normal value of fronto-temporal horn ratio (FTHR) as a marker of ventriculomegaly on cranial ultrasound (CUS) in premature newborns and the relation to white matter injury (WMI) and cerebral palsy (CP). This is a retrospective study of newborns admitted between 2011 and 2014. Inclusion criteria were: (1) gestation <29 weeks, (2) birth weight ≤1500 g, (3) referred within 7 days of life, (4) at least two CUS preformed, (5) brain magnetic resonance imaging (MRI) at term age-equivalent. Intraventricular hemorrhage (IVH) grade was identified and FTHR was measured on all CUS. WMI on MRI was evaluated through (1) injury score (Kidokoro 2013) and (2) fractional anisotropy (FA) on the MRI diffusion tensor imaging. CP was estimated using the gross motor function classification system (GMFCS). One hundred neonates met the inclusion criteria: 37 with no IVH, 36 with IVH grade 1–2, and 27 with IVH grade 3–4. The FTHR cut-point of 0.51 had the highest sensitivity and specificity for moderate-to-severe WMI. In the IVH grade 3–4 group, the elevated FTHR correlated with lower FA and higher GMFCS. FTHR is a useful quantitative biomarker of ventriculomegaly in preterm newborns. It may help standardize ventricular measurement and direct intervention. The fronto-temporal horn ratio has the potential to become a standardized tool that can provide an actionable measure to direct intervention for post-hemorrhagic ventricular dilation. This current study will provide the basis of a future clinical trial to optimize intervention timing to decrease the risk of white matter injury in this vulnerable population. The fronto-temporal horn ratio has the potential to become a standardized tool that can provide an actionable measure to direct intervention for post-hemorrhagic ventricular dilation. This current study will provide the basis of a future clinical trial to optimize intervention timing to decrease the risk of white matter injury in this vulnerable population.
OBJECTIVE To characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born at ... more OBJECTIVE To characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born at term and preterm. For term infants, to compare seizure severity and treatment response for multi-site vs single-site ICH and hypoxic-ischemic encephalopathy (HIE) with vs. without ICH. STUDY DESIGN We studied 112 newborn infants with seizures attributed to ICH, and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multi-site vs. single-site ICH and HIE with vs. without ICH. RESULTS ICH was a more common seizure etiology in infants born preterm vs. term (27% vs. 10%, p<0.001). Most infants had subclinical seizures (74%) and an incomplete response to initial antiseizure medication (ASM) (68%). In infants born term, multi-site ICH was associated with more subclinical seizures than single-site ICH (93% vs. 66%, p=0.05) and an incomplete response to the initial ASM (100% vs. 66%, p=0.02). Status epilepticus was more common in HIE with ICH vs. HIE alone (38% vs. 17%, P = .05). CONCLUSIONS Seizure severity was higher and treatment response was lower among infants born term with complicated ICH. These data support the use of continuous video electroencephalogram monitoring to accurately detect seizures and a multi-step treatment plan that considers early use of multiple ASMs, particularly with parenchymal and high-grade intraventricular hemorrhage and complicated ICH.
Neonatal-onset urea cycle disorders (UCDs) may result in hyperammonemic (HA) encephalopathy prese... more Neonatal-onset urea cycle disorders (UCDs) may result in hyperammonemic (HA) encephalopathy presenting with several neurologic sequelae including seizures, coma, and death. However, no recommendations are given in how and when neurodiagnostic studies should be used to screen or assess for these neurologic complications. We present a case of carbamoyl phosphate synthetase 1 (CPS1) deficiency in a newborn female in which electroencephalogram monitoring to assess encephalopathy and seizures, and magnetic resonance imaging measurements of brain metabolites were used to guide care during her hyperammonemic crisis. Her neurologic course and response to treatment characterizes the significant neurologic impact of HA encephalopathy. Our group herein proposes a clinical neurodiagnostic pathway for managing acute HA encephalopathy.
OBJECTIVE To examine the frequency of placental abnormalities in a multicenter cohort of newborn ... more OBJECTIVE To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE), and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE. STUDY DESIGN Infants born at ≥ 36 weeks of gestation (n=500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system. RESULTS Complete placental pathologic examination was available for 321/500 (64%) trial participants. Placental abnormalities were identified in 273/321 (85%) and were more common in infants ≥ 40 weeks of gestation (93% vs. 81%, p=0.01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs. -14.3, p=0.049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs. 38.0, p<0.001) and higher rates of clinically diagnosed chorioamnionitis (25% vs 2%, P < .001) than those without acute abnormalities. CONCLUSION Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.
Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half ... more Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half of neonates treated with therapeutic hypothermia for NE have EEG-confirmed seizures. These seizures are best identified with continuous EEG monitoring, as clinical diagnosis leads to under-diagnosis of subclinical seizures and over-treatment of events that are not seizures. High seizure burden, especially status epilepticus, is thought to augment brain injury. Treatment, therefore, is aimed at minimizing seizure burden. Phenobarbital remains the mainstay of treatment, as it is more effective than levetiracetam and easier to administer than fosphenytoin. Emerging evidence suggests that, for many neonates, it is safe to discontinue the phenobarbital after acute seizures resolve and prior to hospital discharge.
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2020
ObjectiveNeonates with seizures have a high risk of mortality and neurological morbidity. We aime... more ObjectiveNeonates with seizures have a high risk of mortality and neurological morbidity. We aimed to describe the experience of parents caring for neonates with seizures.DesignThis prospective, observational and multicentre (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. At the time of hospital discharge, parents answered six open-ended response questions that targeted their experience. Responses were analysed using a conventional content analysis approach.Results144 parents completed the open-ended questions (732 total comments). Four themes were identified. Sources of strength: families valued medical team consensus, opportunities to contribute to their child’s care and bonding with their infant. Uncertainty: parents reported three primary types of uncertainty, all of which caused distress: (1) the daily uncertainty of the intensive care experience; (2) concerns about their child’s uncertain future and (3) lack of consensus between ...
The objective was to examine the discriminatory ability of electroencephalogram (EEG) delta power... more The objective was to examine the discriminatory ability of electroencephalogram (EEG) delta power in neonates with hypoxic-ischemic encephalopathy (HIE) with well-defined outcomes. Prolonged continuous EEG recordings from term neonates with HIE during therapeutic hypothermia enrolled in a prospective observational study were examined. Adverse outcome was defined as death or severe brain injury by magnetic resonance imaging (MRI); favorable outcome was defined as normal or mild injury by MRI. Neonates were stratified by Sarnat grade of encephalopathy at admission. EEG was partitioned into 10-minute nonoverlapping artifact- and seizure-free epochs. Delta power was calculated and compared between the groups using receiver operating characteristic (ROC) analyses and Wilcoxon rank-sum tests. An area under the ROC curve >0.7 with P
Objective: To examine the frequency and types of placental pathology observed in encephalopathic ... more Objective: To examine the frequency and types of placental pathology observed in encephalopathic newborns presenting for therapeutic hypothermia. Study Design: Between May 2006 and April 2010, 140 term newborns with neonatal encephalopathy were admitted for cooling. The presence or absence of recognized asphyxial ("sentinel") birth events was noted. Placental pathology was categorized as vascular, inflammatory, or other. Result: Placental surgical pathology reports were available for 100 newborns, of whom 51% had sentinel events. Abnormalities were reported in 51% of placentas, 29% with and 73% without sentinel events (p = 0.0001). Inflammatory pathology was more frequent in infants without sentinel events (43% vs. 14%, p = 0.0016), especially in infants with pH below 7.0 (p = 0.012). Conclusion: Placental pathology was common in infants with neonatal encephalopathy admitted for therapeutic hypothermia, especially in those with no clinically recognized sentinel birth events. Severe acidosis was often observed in infants without sentinel events who had inflammatory placental pathology.
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