Publications by authors named "Yvonne Wu"

Article Synopsis
  • The study aims to predict the likelihood of death or severe neurodevelopmental impairment (NDI) in neonates with hypoxic-ischemic encephalopathy (HIE) who undergo hypothermia treatment.
  • The research involved 424 neonates from U.S. neonatal intensive care units, tracking their outcomes up to the age of 2 years, with a focus on clinical indicators taken 24 hours after birth.
  • Findings revealed that specific clinical characteristics, including severely abnormal EEG, low pH, and a poor Apgar score, can effectively signal high risk for severe outcomes, offering a high level of specificity and predictive value for clinicians.
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Objective: To determine if chorioamnionitis is associated with an increased risk of adverse 2-year outcomes among infants with hypoxic-ischemic encephalopathy (HIE).

Study Design: This cohort study included all infants with moderate to severe HIE treated with therapeutic hypothermia and enrolled on the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. Clinical chorioamnionitis (CC) was defined as a diagnosis made by a treating obstetrician and histologic chorioamnionitis (HC) was defined as placental inflammation observed on histology.

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Therapeutic hypothermia is an effective therapy for moderate-to-severe hypoxic-ischemic encephalopathy (HIE) in infants born at term or near-term in high-resource settings. Yet there remains a substantial proportion of infants who do not benefit or who will have significant disability despite therapeutic hypothermia. Novel investigational therapies that may confer additional neuroprotection by targeting known pathogenic mechanisms of hypoxic-ischemic brain injury are under development.

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Objective: To assess the relationship between the Sarnat exam, early electroencephalogram (EEG) background, and death or neurodevelopmental impairment (NDI) at age 2 years among neonates with moderate to severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

Study Design: Neonates enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy trial with EEG (n = 463) or amplitude-integrated electroencephalogram (n = 15) reports available on the first day after birth were included in this cohort study. A Sarnat exam was performed between 1 and 6 hours after birth, and neonates were classified into 3 groups of increasing severity based on the number of severe features (none, 1-2, or 3+).

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Background: The High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia demonstrated no neurodevelopmental benefit but was associated with a higher rate of serious adverse events (SAEs). Understanding if targeted Epo plasma exposures were achieved in the HEAL trial and if SAEs were associated with higher exposures would help future therapeutic programs of Epo as a candidate neuroprotective treatment.

Methods: Ancillary study of a subset of HEAL neonates who received Epo (1000 U/kg IV on days 1, 2, 3, 4, and 7) and had plasma drug concentrations measured.

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Article Synopsis
  • * Researchers analyzed data from around 41,000 term births, comparing 374 cases of HIE, 3,056 with fetal acidosis, and 37,546 healthy infants, using a random forest classifier for prediction.
  • * The system showed improved detection rates for HIE (61.8%) and fetal acidosis (48.3%) without increasing false positives in healthy infants, allowing for potential early clinical interventions.
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Importance: Epidural analgesia is used by approximately 70% of birthing persons in the US to alleviate labor pain and is a common cause of elevated temperature in the birthing parent during labor, which, in turn, is associated with adverse neonatal outcomes such as hypoxic-ischemic encephalopathy (HIE).

Objective: To determine whether epidural analgesia is associated with increased risk of HIE after adjusting for the birthing person's maximal temperature before epidural placement and for the propensity to get an epidural.

Design, Setting, And Participants: This retrospective, population-based cohort study was conducted at 15 Kaiser Permanente Northern California hospitals.

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The world urgently needs new sources of clean energy due to a growing global population, rising energy use, and the effects of climate change. Nuclear energy is one of the most promising solutions for meeting the world's energy needs now and in the future. One type of nuclear energy, Low Energy Nuclear Reactions (LENR), has gained interest as a potential clean energy source.

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Background: Both perinatal arterial ischemic stroke (PAIS) and hypoxic-ischemic encephalopathy (HIE) can present with neonatal encephalopathy. We hypothesized that among infants undergoing therapeutic hypothermia, presence of PAIS is associated with a higher risk of seizures and a lower risk of persistent encephalopathy after rewarming.

Methods: We studied 473 infants with moderate or severe HIE enrolled in the HEAL Trial who received a brain MRI.

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Purpose To develop a deep learning algorithm to predict 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy using MRI and basic clinical data. Materials and Methods In this study, MRI data of term neonates with encephalopathy in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial (ClinicalTrials.gov: NCT02811263), who were enrolled from 17 institutions between January 25, 2017, and October 9, 2019, were retrospectively analyzed.

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This article describes the methods used to build a large-scale database of more than 250,000 electronic fetal monitoring (EFM) records linked to a comprehensive set of clinical information about the infant, the mother, the pregnancy, labor, and outcome. The database can be used to investigate how birth outcome is related to clinical and EFM features. The main steps involved in building the database were: (1) Acquiring the raw EFM recording and clinical records for each birth.

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Article Synopsis
  • Infants with hypoxic ischemic encephalopathy (HIE) may have underlying genetic or congenital anomalies, which could influence their health outcomes, but the extent of this impact is not well understood.
  • In a study of 500 infants with HIE, 5% were found to have genetic or congenital anomalies; these infants showed higher rates of death or neurodevelopmental impairment (NDI) compared to those without anomalies.
  • Despite similar severity of HIE, infants with genetic or congenital issues had worse neurological outcomes, including higher instances of cerebral palsy and lower developmental scores at age two.
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Brain extraction, or skull-stripping, is an essential data preprocessing step for machine learning approaches to brain MRI analysis. Currently, there are limited extraction algorithms for the neonatal brain. We aim to adapt an established deep learning algorithm for the automatic segmentation of neonatal brains from MRI, trained on a large multi-institutional dataset for improved generalizability across image acquisition parameters.

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Objective: To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM).

Study Design: This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures.

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Article Synopsis
  • The study aimed to compare outcomes in infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH) using esophageal vs rectal temperature monitoring.
  • Of the 500 infants analyzed, there were no significant differences in rates of death or neurodevelopmental impairment (NDI) between the two monitoring methods.
  • However, infants monitored rectally had lower odds of experiencing overcooling and hypotension compared to those monitored esophageally, indicating potential benefits of rectal monitoring.*
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Article Synopsis
  • Advances in perinatal and neonatal care have improved the survival rates of preterm infants, shifting the focus to enhancing long-term neurological outcomes.
  • Current therapies like antenatal steroids show short-term benefits, but there's little evidence for long-term neurodevelopmental improvement, necessitating further research into effective neuroprotective strategies.
  • Promising treatments under investigation include multipotential stem cells and anti-inflammatory therapies, while immediate care methods that nurture brain health in NICUs are crucial for fostering neuroplasticity.
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Article Synopsis
  • This study focuses on improving the detection of fetuses at risk for fetal acidosis or hypoxic-ischemic encephalopathy (HIE) during labor by analyzing fetal heart rate (FHR) and uterine pressure (UP) signals.
  • A random forest classifier was developed to give intervention recommendations based on feature data from FHR and UP collected in 20-minute intervals, showing a significant increase in identifying at-risk babies well before delivery.
  • The system identified more cases of HIE and acidosis, suggesting early intervention opportunities that could lower HIE rates, despite a slight rise in cesarean section rates among healthy births.
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  • The study investigates the effects of selective serotonin reuptake inhibitors (SSRIs) taken by pregnant women after 20 weeks on neonatal adaptation, which can be delayed in infants exposed to these medications.
  • Conducted on a large population of 280,090 infants born in Northern California from 2011 to 2019, it found that 11.2% of infants exposed to SSRIs experienced delayed adaptation compared to 4.4% in non-exposed infants.
  • The research suggests a significant, dose-dependent relationship between SSRI use in late pregnancy and delayed neonatal adaptation, especially with certain SSRIs like escitalopram and fluoxetine having the highest associated risks.
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Objective: To study the association between the Sarnat exam (SE) performed before and after therapeutic hypothermia (TH) and outcomes at 2 years in infants with moderate or severe hypoxic-ischaemic encephalopathy (HIE).

Design: Secondary analysis of the igh-dose rythropoietin for sphyxia and Encephaopathy Trial. Adjusted ORs (aORs) for death or neurodevelopmental impairment (NDI) based on SE severity category and change in category were constructed, adjusting for sedation at time of exam.

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Background: Maternal inflammation can result from immune dysregulation and metabolic perturbations during pregnancy. Whether conditions associated with inflammation during pregnancy increase the likelihood of autism spectrum disorder (ASD) or other neurodevelopmental disorders (DDs) is not well understood.

Methods: We conducted a case-control study among children born in California from 2011 to 2016 to investigate maternal immune-mediated and cardiometabolic conditions during pregnancy and risk of ASD ( = 311) and DDs ( = 1291) compared with children from the general population ( = 967).

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Nulliparous pregnancies, those where the mother has not previously given birth, are associated with longer labors and hence expose the fetus to more contractions and other adverse intrapartum conditions such as chorioamnionitis. The objective of the present study was to test if accounting for nulliparity could improve the detection of fetuses at increased risk of developing hypoxic-ischemic encephalopathy (HIE). During labor, clinicians assess the fetal heart rate and uterine pressure signals to identify fetuses at risk of developing HIE.

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Article Synopsis
  • The study aimed to investigate whether the time it takes for infants with hypoxic-ischemic encephalopathy (HIE) to reach a target temperature affects their risk of death or neurodevelopmental impairment (NDI) by the age of 2.
  • It involved 500 infants treated with therapeutic hypothermia, categorizing them into early (≤4 hours) and late (>4 hours) target temperature groups, but results showed no significant differences in mortality or NDI between the two groups.
  • Ultimately, the findings suggest that the timing of reaching target temperature does not independently impact outcomes, as both groups had similar neurodevelopmental scores among survivors.
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Introduction: Erythropoietin (Epo) is a putative neuroprotective therapy that did not improve overall outcomes in a phase 3 randomized controlled trial for neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). However, HIE is a heterogeneous disorder, and it remains to be determined whether Epo had beneficial effects on a subset of perinatal brain injuries.

Methods: This study was a secondary analysis of neuroimaging data from the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, which was conducted from 2016 to 2021 at 17 sites involving 23 US academic medical centers.

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Background: Recent studies suggest that the incidence of perinatal hypoxic-ischemic encephalopathy (HIE) may be increasing in developed countries. However, this observed increase may be due to increased ascertainment and increased treatment with therapeutic hypothermia rather than an increase in disease burden. In a US population-based cross-sectional study, we determined the incidence of perinatal HIE over time.

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