Valerie Chock
Professor of Pediatrics (Neonatology) and, by courtesy, of Obstetrics and Gynecology (Maternal Fetal Medicine)
Pediatrics - Neonatal and Developmental Medicine
Clinical Focus
- Neonatal-Perinatal Medicine
- Neonatology
Academic Appointments
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Professor - University Medical Line, Pediatrics - Neonatal and Developmental Medicine
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Professor - University Medical Line (By courtesy), Obstetrics & Gynecology - Maternal Fetal Medicine
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Member, Bio-X
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Member, Cardiovascular Institute
Administrative Appointments
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Professor, Division of Neonatal and Developmental Medicine, Stanford University (2005 - Present)
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Associate Director for Neonatal Prenatal Consultation Services, Center for Fetal and Maternal Health, LPCH (2010 - Present)
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Assistant Program Director, Neonatology Fellowship Program, Division of Neonatal and Developmental Medicine, Stanford University (2016 - Present)
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Associate Chief for Clinical Research, Division of Neonatal and Developmental Medicine (2023 - Present)
Honors & Awards
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Stanford Global Health Seed Grant, Stanford Maternal and Child Health Research Institute and Center for Innovation in Global Health (Sept 2023)
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Arline and Pete Harman Endowed Faculty Scholar, Stanford Maternal and Child Health Research Institute (Sept 2020-2023)
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Pediatric Heart Center Research Award, Stanford Pediatric Research Fund-Lucile Packard Foundation for Children's Health (March 2010-March 2012)
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Pilot Early Career Award, Stanford Pediatric Research Fund- Child Health Research Program (Jan 2008-2010)
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NIH Mentored Career Development Award (KL2), Stanford Center for Clinical Translational Education and Research (2009-2011)
Boards, Advisory Committees, Professional Organizations
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Global Health Faculty Fellow, Center for Innovation in Global Health (2023 - Present)
Professional Education
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Fellowship: Stanford Pediatric Hospital Medicine Fellowship (2005) CA
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Medical Education: University of Hawaii at Manoa John A Burns School of Medicine (1998) HI
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Residency: UCSF Pediatric Residency (2001) CA
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Internship: UCSF Pediatric Residency (1999) CA
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Board Certification: American Board of Pediatrics, Pediatrics (2001)
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Board Certification: American Board of Pediatrics, Neonatal-Perinatal Medicine (2005)
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M.S. Epi, Stanford University, Clinical Epidemiology (2011)
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Fellowship, Stanford Lucile Packard Children's Hospital, Neonatology (2005)
Community and International Work
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Reducing Intraventricular Hemorrhage in Premature Infants in Brazil
Ongoing Project
No
Opportunities for Student Involvement
No
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Protecting Newborn Brains: U.S.-Brazil Telemedicine Initiative, Sao Paulo, Brazil
Topic
Neonatal Neurointensive Care
Ongoing Project
Yes
Opportunities for Student Involvement
Yes
Current Research and Scholarly Interests
Neurological monitoring in critically ill infants. Altered hemodynamics in neonates, especially in relation to prematurity, congenital heart disease, and central nervous system injury. Determination of the hemodynamic significance and effects of a patent ductus arteriosus in the preterm infant. Utilizing NIRS (near-infrared spectroscopy) and other technologies for improved monitoring in the NICU.
Clinical Trials
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Brain Oxygenation-II
Not Recruiting
The Brain Oxygenation-II study (BOx-II) is a phase-II, multicenter, single-arm clinical trial evaluating interventions based on near-infrared spectroscopy (NIRS) monitoring of cerebral oxygen saturation in extremely premature infants. Enrolled infants will follow a treatment guideline to maintain cerebral oxygen saturation in a target range within the first 72 hours of life. The primary outcomes will include interventions used to maintain cerebral saturation in target range, rates of cerebral hypoxia and systemic hypoxia, and a composite of death or severe brain injury detected on term-equivalent magnetic resonance imaging.
Stanford is currently not accepting patients for this trial. For more information, please contact Valerie Chock, 650-723-5711.
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Cerebral Oxygenation and Autoregulation in Preterm Infants
Not Recruiting
Premature infants are at high risk for variations in blood pressure and oxygenation during the first few days of life. The immaturity of the premature brain may further predispose these infants to death or the development of neurologic problems. The relationship between unstable blood pressure and oxygen levels and brain injury has not been well elucidated. This study investigates the utility of near-infrared spectroscopy (NIRS), a non-invasive oxygen-measuring device, to identify preterm infants at highest risk for brain injury or death.
Stanford is currently not accepting patients for this trial. For more information, please contact Valerie Chock, MD, 650-723-5711.
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Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants
Not Recruiting
Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment. There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.
Stanford is currently not accepting patients for this trial.
2024-25 Courses
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Independent Studies (5)
- Directed Reading in Pediatrics
PEDS 299 (Aut, Win, Spr, Sum) - Early Clinical Experience
PEDS 280 (Aut, Win, Spr, Sum) - Graduate Research
PEDS 399 (Aut, Win, Spr, Sum) - Medical Scholars Research
PEDS 370 (Aut, Win, Spr, Sum) - Undergraduate Directed Reading/Research
PEDS 199 (Aut, Win, Spr, Sum)
- Directed Reading in Pediatrics
All Publications
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Trends in sex differences in neurodevelopmental outcomes among extremely preterm infants.
Archives of disease in childhood. Fetal and neonatal edition
2024
Abstract
OBJECTIVE: To examine whether changes in survival without moderate or severe neurodevelopmental impairment (NDI) at 18-26 months' corrected age from 1999 to 2018 differed between male and female infants.DESIGN: This retrospective cohort study used data from the NICHD Neonatal Research Network hospitals. Robust Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% CIs for survival without moderate or severe NDI between males and females. Interactions between sex and time were assessed to evaluate temporal differences in the outcome by sex. Variables adjusted for included centre, maternal age, ethnicity/race, gestational age and small for gestational age.PATIENTS: Inborn infants with gestational age of 22-26 weeks at NICHD Neonatal Research Network hospitals from 1999 to 2018.MAIN OUTCOME MEASURE: Change over time in survival without moderate or severe NDI at 18-26 months' corrected age between male and female infants.RESULTS: Of 26 307 infants, 13 045 (49.6%) were male. Survival without moderate or severe NDI declined for both sexes over time, from 32.9% to 30.6% for males and from 47.4% to 40.0% for females, between 1999-2003 and 2014-2018. Males were less likely than females to survive without moderate or severe NDI (aRR=0.80; 95% CI 0.78 to 0.83). Changes in survival without moderate or severe NDI did not differ between males and females.CONCLUSION: There were no differential changes in survival without moderate or severe NDI between male and female infants.
View details for DOI 10.1136/archdischild-2024-327239
View details for PubMedID 39288987
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Neuromonitoring practices for neonates with congenital heart disease: a scoping review.
Pediatric research
2024
Abstract
Neonates with congenital heart disease (CHD) are at risk for adverse neurodevelopmental outcomes. This scoping review summarizes neuromonitoring methods in neonates with CHD. We identified 84 studies investigating the use of near-infrared spectroscopy (NIRS) (n=37), electroencephalography (EEG) (n=20), amplitude-integrated electroencephalography (aEEG) (n=10), transcranial Doppler sonography (TCD) (n=6), and multimodal monitoring (n=11). NIRS was used to evaluate cerebral oxygenation, identify risk thresholds and adverse events in the intensive care unit (ICU), and outcomes. EEG was utilized to screen for seizures and to predict adverse outcomes. Studies of aEEG have focused on characterizing background patterns, detecting seizures, and outcomes. Studies of TCD have focused on correlation with short-term clinical outcomes. Multimodal monitoring studies characterized cerebral physiologic dynamics. Most of the studies were performed in single centers, had a limited number of neonates (range 3-183), demonstrated variability in neuromonitoring practices, and lacked standardized approaches to neurodevelopmental testing. We identified areas of improvement for future research: (1) large multicenter studies to evaluate developmental correlates of neuromonitoring practices; (2) guidelines to standardize neurodevelopmental testing methodologies; (3) research to address geographic variation in resource utilization; (4) integration and synchronization of multimodal monitoring; and (5) research to establish a standardized framework for neuromonitoring techniques across diverse settings. IMPACT: This scoping review summarizes the literature regarding neuromonitoring practices in neonates with congenital heart disease (CHD). The identification of low cerebral oxygenation thresholds with NIRS may be used to identify neonates at risk for adverse events in the ICU or adverse neurodevelopmental outcomes. Postoperative neuromonitoring with continuous EEG screening for subclinical seizures and status epilepticus, allow for early and appropriate therapy. Future studies should focus on enrolling larger multicenter cohorts of neonates with CHD with a standardized framework of neuromonitoring practices in this population. Postoperative neurodevelopmental testing should utilize standard assessments and testing intervals.
View details for DOI 10.1038/s41390-024-03484-x
View details for PubMedID 39183308
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The Future of Neonatal Cerebral Oxygenation Monitoring: Directions After the SafeBoosC-III Trial
JOURNAL OF PEDIATRICS
2024; 270
View details for DOI 10.1018/j.jpeds.2024.114018
View details for Web of Science ID 001227326500001
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Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Reducing Variability in Practice through a Collaborative Telemedicine Initiative.
American journal of perinatology
2024
Abstract
This study aimed to assess the viability of implementing a tele-educational training program in neurocritical care for newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia (TH), with the goal of reducing practice variation. Prospective study including newborns with HIE treated with TH from 12 neonatal intensive care units in Brazil conducted from February 2021 to February 2022. An educational intervention consisting of 12 biweekly, 1-hour, live videoconferences was implemented during a 6-month period in all centers. Half of the centers had the assistance of a remote neuromonitoring team. The primary outcome was the rate of deviations from TH protocol, and it was evaluated during a 3-month period before and after the intervention. Logistic regression via generalized estimating equations was performed to compare the primary and secondary outcomes. Protocol deviations were defined as practices not in compliance with the TH protocol provided. A subanalysis evaluated the differences in protocol deviations and clinical variables between centers with and without neuromonitoring. Sixty-six (39.5%) newborns with HIE were treated with TH during the preintervention period, 69 (41.3%) during the intervention period and 32 (19.1%) after intervention. There was not a significant reduction in protocol deviations between the pre- and postintervention periods (37.8 vs. 25%, p = 0.23); however, a decrease in the rates of missing Sarnat examinations within 6 hours after birth was seen between the preintervention (n = 5, 7.6%) and postintervention (n = 2, 6.3%) periods (adjusted odds ratio [aOR]: 0.36 [0.25-0.52], p < 0.001). Centers with remote neuromonitoring support had significantly lower rates of seizures (27.6 vs. 57.5%; aOR: 0.26 [0.12-0.55], p < 0.001) and significant less seizure medication (27.6 vs. 68.7%; aOR: 0.17 [0.07-0.4], p < 0.001). This study shows that implementing a tele-educational program in neonatal neurocritical care is feasible and may decrease variability in the delivery of care to patients with HIE treated with TH.· Neurocritical care strategies vary widely in low- and middle-income countries.. · Heterogeneity of care may lead to suboptimal efficacy of neuroprotective strategies.. · Tele-education and international collaboration can decrease the variability of neurocritical care provided to infants with HIE..
View details for DOI 10.1055/s-0044-1786720
View details for PubMedID 38714205
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Left Ventricular Strain, Arch Angulation, and Velocity-Time Integral Ratio Improve Performance of a Clinical Pathway for Fetal Diagnosis of Neonatal Coarctation of the Aorta.
Fetal diagnosis and therapy
2024: 1-15
Abstract
Neonatal presentation of coarctation of the aorta (CoA) is a potentially life-threatening condition that is difficult to diagnose in fetal life. We therefore sought to validate and compare novel metrics that may add diagnostic value for fetal CoA, including the diastolic to systolic aortic isthmus VTI ratio (VTId:VTIs), ascending aorta to descending aorta angle (AAo-DAo), transverse aorta to descending aorta angle (TAo-DAo), and LV longitudinal strain (LVS), then to evaluate whether these novel metrics improve specificity to identify fetuses at the highest risk for postnatal CoA without compromising sensitivity.Retrospective cohort study of fetuses followed a prospective clinical pathway and previously classified as mild, moderate, or high-risk for CoA based on standard fetal echo metrics. Novel metrics were retrospectively measured in a blinded manner.Among fetuses with prenatal concern for CoA, VTId:VTIs, AAo-DAo angle, TAo-DAo angle, and LVS were significantly different between surgical and non-surgical cases (p < 0.01 for all variables). In the subgroup of moderate- and high-risk fetuses, the standard high-risk criteria (flow reversal at the foramen ovale or aortic arch) did not discriminate effectively between surgical and non-surgical cases. VTId:VTIs, AAo-Dao angle, Tao-DAo angle, and LVS all demonstrated greater discrimination than standard high-risk criteria, with specificity of 100% and PPV (positive predictive value) of 78-100%.The incorporation of novel metrics added diagnostic value to our clinical pathway for fetal CoA with higher specificity than the previous high-risk criteria. The incorporation of these metrics into the evaluation of fetuses at moderate- or high-risk for surgical CoA may improve prenatal counseling, allow for more consistent surgical planning, and ultimately optimize hospital resource allocation.
View details for DOI 10.1159/000538550
View details for PubMedID 38621375
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Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy.
Journal of perinatology : official journal of the California Perinatal Association
2024
Abstract
Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH).Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined.In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02).Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.
View details for DOI 10.1038/s41372-024-01937-z
View details for PubMedID 38509202
View details for PubMedCentralID 4209658
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The Future of Neonatal Cerebral Oxygenation Monitoring: Directions after the SafeBoosC-III Trial.
The Journal of pediatrics
2024: 114016
View details for DOI 10.1016/j.jpeds.2024.114016
View details for PubMedID 38492916
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Social Determinants of Health and Redirection of Care for Infants Born Extremely Preterm.
JAMA pediatrics
2024
Abstract
Importance: Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding.Objective: To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.Design, Setting, and Participants: This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks' gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic).Main Outcomes and Measures: The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks' gestation, death and neurodevelopmental impairment at 22 to 26 months' corrected age.Results: Of the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type.Conclusions and Relevance: For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.
View details for DOI 10.1001/jamapediatrics.2024.0125
View details for PubMedID 38466268
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Impact of Congenital Heart Disease on the Outcomes of Very Low Birth Weight Infants.
American journal of perinatology
2024
Abstract
OBJECTIVE: To investigate the association of congenital heart disease (CHD) with morbidity and mortality of very low birth weight (VLBW) infants.STUDY DESIGN: This matched case-control study included VLBW infants born at a single institution between 2001 and 2015. The primary outcome was mortality. Secondary outcomes included necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity, and intraventricular hemorrhage. These outcomes were assessed by comparing VLBW-CHDs with control VLBW infants matched by gestational age within a week, birth weight within 500g, sex, and birth date within a year using conditional logistic regression. Multivariable logistic regression analyzed differences in outcomes in the VLBW-CHD group between two birth periods (2001-2008 and 2009-2015) to account for changes in practice.RESULTS: In a cohort of 44 CHD infants matched with 88 controls, the mortality rate was 27% in infants with CHD and 1% in controls (p<0.0001). The VLBW-CHDs had increased BPD; (odds ratio [OR]: 7.70, 95% confidence interval [CI]: 1.96-30.29) and sepsis (OR: 10.59, 95% CI: 2.99-37.57) compared with the control VLBWs. When adjusted for preoperative ventilator use, the VLBW-CHDs still had significantly higher odds of BPD (OR: 6.97, 95% CI: 1.73-28.04). VLBW-CHDs also had significantly higher odds of both presumed and culture-positive sepsis as well as late-onset sepsis than their matched controls. There were no significant differences in outcomes between the two birth periods.CONCLUSION: VLBW-CHDs showed higher odds of BPD, sepsis, and mortality than VLBW infants without CHD. Future research should focus on the increased mortality and specific complications encountered by VLBW infants with CHD and implement targeted strategies to address these risks.KEY POINTS: · Incidence of CHD is higher in preterm infants than in term infants but the incidence of their morbidities is not well described.. · VLBW infants with CHD have higher odds of mortality, bronchopulmonary dysplasia, and sepsis.. · Future research is needed to implement targeted preventive responses..
View details for DOI 10.1055/s-0044-1781460
View details for PubMedID 38408479
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Social distancing and extremely preterm births in the initial COVID-19 pandemic period.
Journal of perinatology : official journal of the California Perinatal Association
2024
Abstract
HYPOTHESIS: Increased social distancing was associated with a lower incidence of extremely preterm live births (EPLB) during the initial COVID-19 pandemic period.STUDY DESIGN: Prospective study at the NICHD Neonatal Research Network sites comparing EPLB (220/7-286/7 weeks) and extremely preterm intrapartum stillbirths (EPIS) rates during the pandemic period (March-July, weeks 9-30 of 2020) with the reference period (same weeks in 2018 and 2019), correlating with state-specific social distancing index (SDI).RESULTS: EPLB and EPIS percentages did not significantly decrease (1.58-1.45%, p=0.07, and 0.08-0.06%, p=0.14, respectively). SDI was not significantly correlated with percent change of EPLB (CC=0.29, 95% CI=-0.12, 0.71) or EPIS (CC=-0.23, 95% CI=-0.65, 0.18). Percent change in mean gestational age was positively correlated with SDI (CC=0.49, 95% CI=0.07, 0.91).CONCLUSIONS: Increased social distancing was not associated with change in incidence of EPLB but was associated with a higher gestational age of extremely preterm births.CLINICALTRIALS:GOV ID: Generic Database: NCT00063063.
View details for DOI 10.1038/s41372-024-01898-3
View details for PubMedID 38388715
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Sample entropy correlates with intraventricular hemorrhage and mortality in premature infants early in life.
Pediatric research
2024
Abstract
Mortality and intraventricular hemorrhage (IVH) are common adverse outcomes in preterm infants and are challenging to predict clinically. Sample entropy (SE), a measure of heart rate variability (HRV), has shown predictive power for sepsis and other morbidities in neonates. We evaluated associations between SE and mortality and IVH in the first week of life.Participants were 389 infants born before 32 weeks of gestation for whom bedside monitor data were available. A total of 29 infants had IVH grade 3 or 4 and 31 infants died within 2 weeks of life. SE was calculated with the PhysioNet open-source benchmark. Logistic regressions assessed associations between SE and IVH and/or mortality with and without common clinical covariates over various hour of life (HOL) censor points.Lower SE was associated with mortality by 4 HOL, but higher SE was very strongly associated with IVH and mortality at 24-96 HOL. Bootstrap testing confirmed SE significantly improved prediction using clinical variables at 96 HOL.SE is a significant predictor of IVH and mortality in premature infants. Given IVH typically occurs in the first 24-72 HOL, affected infants may initially have low SE followed by a sustained period of high SE.SE correlates with IVH and mortality in preterm infants early in life. SE combined with clinical factors yielded ROC AUCs well above 0.8 and significantly outperformed the clinical model at 96 h of life. Previous studies had not shown predictive power over clinical models. First study using the PhysioNet Cardiovascular Toolbox benchmark in young infants. Relative to the generally accepted timing of IVH in premature infants, we saw lower SE before or around the time of hemorrhage and a sustained period of higher SE after. Higher SE after acute events has not been reported previously.
View details for DOI 10.1038/s41390-024-03075-w
View details for PubMedID 38365874
View details for PubMedCentralID 4760862
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Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria.
Pediatric nephrology (Berlin, Germany)
2024
Abstract
Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity.A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups.Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI.AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.
View details for DOI 10.1007/s00467-024-06287-8
View details for PubMedID 38326648
View details for PubMedCentralID 4209658
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Survey of Neonatal Management After Amnioinfusion for Anhydramnios.
JAMA pediatrics
2024
View details for DOI 10.1001/jamapediatrics.2023.6403
View details for PubMedID 38315476
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Renal tissue oxygenation and development of AKI in preterm neonates born < 32 weeks' gestational age in the first week of age.
Journal of perinatology : official journal of the California Perinatal Association
2024
Abstract
OBJECTIVE: To evaluate the relationship between regional renal saturation of oxygen (RrSO2) changes and serum creatinine (SCr) during the first eight days of age for preterm neonates born < 32 weeks' gestational age.DESIGN: Post-hoc analysis of multicenter prospectively measured neonatal RrSO2 values collected during the first 8 days of age in neonates born at < 32 weeks' gestation. Acute kidney injury (AKI) was defined by the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Variables were compared between groups of neonates with and with AKI.RESULTS: One hundred nine neonates were included and 561 SCr values were obtained. Eight participants developed AKI by SCr criteria. A 10-percentage point increase in mean %RrSO2 was associated with a 40% decrease in risk of AKI (95%CI: 9.6-61%; p=0.016).CONCLUSIONS: Increases in mean %RrSO2 in neonates born at < 32 weeks' GA were associated with a decreased risk of AKI. These findings support the design of further prospective trials utilizing RrSO2 monitoring to evaluate new therapies or clinical protocols to prevent and treat neonatal AKI.
View details for DOI 10.1038/s41372-024-01873-y
View details for PubMedID 38233582
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Cerebral Near-Infrared Spectroscopy Use in Neonates: Current Perspectives
RESEARCH AND REPORTS IN NEONATOLOGY
2024; 14: 85-95
View details for DOI 10.2147/RRN.S408536
View details for Web of Science ID 001223165500001
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Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.
The Journal of pediatrics
2023; 266: 113877
Abstract
We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.
View details for DOI 10.1016/j.jpeds.2023.113877
View details for PubMedID 38135028
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Angiotensin-II Use for Refractory Hypotension in an Infant With Bilateral Renal Agenesis.
Pediatrics
2023
Abstract
Infants with congenital bilateral renal agenesis are at significant risk for morbidity and mortality, despite substantial and continuing advances in fetal and neonatal therapeutics. Infants with bilateral renal agenesis may episodically develop severe hypotension that can be refractory to traditional vasopressors. Synthetic angiotensin-II has been successfully used in adult and a few pediatric patients with refractory hypotension but has not been extensively studied in infants. We describe the use of angiotensin-II in treating refractory hypotension in a premature infant with congenital bilateral renal agenesis admitted to the NICU. Within 48 hours, he no longer required other vasopressors. Subsequently, angiotensin-II was gradually weaned and discontinued over 10 days and the patient was ultimately discharged from the hospital. This case demonstrates that angiotensin-II may be a helpful agent to treat refractory hypotension in infants with bilateral renal agenesis.
View details for DOI 10.1542/peds.2023-062128
View details for PubMedID 38098437
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A Population Model of Time-Dependent Changes in Serum Creatinine in (Near)term Neonates with Hypoxic-Ischemic Encephalopathy During and After Therapeutic Hypothermia.
The AAPS journal
2023; 26 (1): 4
Abstract
The objective was to apply a population model to describe the time course and variability of serum creatinine (sCr) in (near)term neonates with moderate to severe encephalopathy during and after therapeutic hypothermia (TH). The data consisted of sCr observations up to 10 days of postnatal age in neonates who underwent TH during the first 3 days after birth. Available covariates were birth weight (BWT), gestational age (GA), survival, and acute kidney injury (AKI). A previously published population model of sCr kinetics in neonates served as the base model. This model predicted not only sCr but also the glomerular filtration rate normalized by its value at birth (GFR/GFR0). The model was used to compare the TH neonates with a reference full term non-asphyxiated population of neonates. The estimates of the model parameters had good precision and showed high between subject variability. AKI influenced most of the estimated parameters denoting a strong impact on sCr kinetics and GFR. BWT and GA were not significant covariates. TH transiently increased [Formula: see text] in TH neonates over the first days compared to the reference group. Asphyxia impacted not only GFR, but also the [Formula: see text] synthesis rate. We also observed that AKI neonates exhibit a delayed onset of postnatal GFR increase and have a higher [Formula: see text] synthesis rate compared to no-AKI patients. Our findings show that the use of [Formula: see text] as marker of renal function in asphyxiated neonates treated with TH to guide dose selection for renally cleared drugs is challenging, while we captured the postnatal sCr patterns in this specific population.
View details for DOI 10.1208/s12248-023-00851-0
View details for PubMedID 38051395
View details for PubMedCentralID 7906350
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Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants: A Secondary Near-Infrared Spectroscopy Study of the Transfusion of Prematures Randomized Clinical Trial (TOP NIRS).
JAMA network open
2023; 6 (9): e2334889
Abstract
Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes.To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age.This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022.Near-infrared spectroscopy monitoring of Csat and Msat.Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score <85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment.A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower-hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher-hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs -0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03).In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia.ClinicalTrials.gov Identifier: NCT01702805.
View details for DOI 10.1001/jamanetworkopen.2023.34889
View details for PubMedID 37733345
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Use of term reference infants in assessing the developmental outcome of extremely preterm infants: lessons learned in a multicenter study.
Journal of perinatology : official journal of the California Perinatal Association
2023
Abstract
Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics.Impairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers.Term Reference (under the Generic Database Study): NCT00063063.
View details for DOI 10.1038/s41372-023-01729-x
View details for PubMedID 37542155
View details for PubMedCentralID 3796892
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Renal Oxygen Saturations and Acute Kidney Injury in the Preterm Infant with Patent Ductus Arteriosus.
American journal of perinatology
2023
Abstract
OBJECTIVE: Decreased near-infrared spectroscopy (NIRS) measures of renal oxygen saturation (Rsat) have identified preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA). NIRS may further identify infants at risk for acute kidney injury (AKI) in a population with concern for hsPDA.DESIGN: Review of infants ≤29 weeks gestation undergoing NIRS and echocardiography due to concern for hsPDA. The hsPDA was defined by two of the following: moderate-large size, left to right shunt, aortic flow reversal, left atrial enlargement. AKI was defined by neonatal modified Kidney Disease Improving Global Outcomes (KDIGO). Rsat and cerebral saturation (Csat), averaged over 1 hour, were evaluated for the 24 hour period around echocardiography.RESULT: Among 77 infants, 29 (38%) had AKI by neonatal modified KDIGO criteria. hsPDA was found on echocardiography in 59 (77%). There were no differences in hsPDA in infants with and without AKI (p=0.1). Rsat was not associated with AKI (p=0.3). Infants on dopamine had less Rsat variability (p<0.01).CONCLUSION: Rsat prior to echocardiography did not discriminate AKI in this cohort of preterm infants at risk for hsPDA, however data may not capture optimal timing of Rsat measurement before AKI.
View details for DOI 10.1055/a-2130-2269
View details for PubMedID 37459881
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Cerebral oxygen saturation in neonates: a bedside comparison between neonatal and adult NIRS sensors.
Pediatric research
2023
Abstract
The majority of neonatal NIRS literature recommends target ranges for cerebral saturation (rScO2) based on data using adult sensors. Neonatal sensors are now commonly used in the neonatal intensive care unit (NICU). However, there is limited clinical data correlating these two measurements of cerebral oxygenation.A prospective observational study was conducted in two NICUs between November 2019 and May 2021. An adult sensor was placed on infants undergoing routine cerebral NIRS monitoring with a neonatal sensor. Time-synchronized rScO2 measurements from both sensors, heart rate, and systemic oxygen saturation values were collected over 6 h under varying clinical conditions and compared.Time-series data from 44 infants demonstrated higher rScO2 measurements with neonatal sensors than with adult sensors; however, the magnitude of the difference varied depending on the absolute value of rScO2 (Adult = 0.63 × Neonatal + 18.2). While there was an approximately 10% difference when adult sensors read 85%, readings were similar when adult sensors read 55%.rScO2 measured by neonatal sensors is typically higher than measured by adult sensors, but the difference is not fixed and is less at the threshold indicative of cerebral hypoxia. Assuming fixed differences between adult and neonatal sensors may lead to overdiagnosis of cerebral hypoxia.In comparison to adult sensors, neonatal sensors rScO2 readings are consistently higher, but the magnitude of the difference varies depending on the absolute value of rScO2. Marked variability during high and low rScO2 readings was noted, with approximately 10% difference when adult sensors read 85%, but nearly similar (58.8%) readings when adult sensors read 55%. Estimating fixed differences of approximately 10% between adult and neonatal probes may lead to an inaccurate diagnosis of cerebral hypoxia and result in subsequent unnecessary interventions.
View details for DOI 10.1038/s41390-023-02705-z
View details for PubMedID 37391490
View details for PubMedCentralID 4283997
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Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial: A Secondary Analysis of a Randomized Clinical Trial.
JAMA network open
2023; 6 (5): e2315315
Abstract
Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death.To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death.This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023.Infants were randomized to 10 days of hydrocortisone or placebo treatment.Infants' baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up.Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4.In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death.ClinicalTrials.gov Identifier: NCT01353313.
View details for DOI 10.1001/jamanetworkopen.2023.15315
View details for PubMedID 37256621
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Newer indications for neuromonitoring in critically ill neonates.
Frontiers in pediatrics
2023; 11: 1111347
Abstract
Continuous neuromonitoring in the neonatal intensive care unit allows for bedside assessment of brain oxygenation and perfusion as well as cerebral function and seizure identification. Near-infrared spectroscopy (NIRS) reflects the balance between oxygen delivery and consumption, and use of multisite monitoring of regional oxygenation provides organ-specific assessment of perfusion. With understanding of the underlying principles of NIRS as well as the physiologic factors which impact oxygenation and perfusion of the brain, kidneys and bowel, changes in neonatal physiology can be more easily recognized by bedside providers, allowing for appropriate, targeted interventions. Amplitude-integrated electroencephalography (aEEG) allows continuous bedside evaluation of cerebral background activity patterns indicative of the level of cerebral function as well as identification of seizure activity. Normal background patterns are reassuring while abnormal background patterns indicate abnormal brain function. Combining brain monitoring information together with continuous vital sign monitoring (blood pressure, pulse oximetry, heart rate and temperature) at the bedside may be described as multi-modality monitoring and facilitates understanding of physiology. We describe 10 cases in critically ill neonates that demonstrate how comprehensive multimodal monitoring provided greater recognition of the hemodynamic status and its impact on cerebral oxygenation and cerebral function thereby informing treatment decisions. We anticipate that there are numerous other uses of NIRS as well as NIRS in conjunction with aEEG which are yet to be reported.
View details for DOI 10.3389/fped.2023.1111347
View details for PubMedID 37187586
View details for PubMedCentralID PMC10175818
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Early Life Outcomes in Relation to Social Determinants of Health for Children Born Extremely Preterm.
The Journal of pediatrics
2023: 113443
Abstract
To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm.This is a cohort study of infants born at 22-26 weeks' gestation in NICHD Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by three maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death post-discharge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and two SDOH (eg, group comparisons by education adjusted for insurance and race).Of 7438 children, 5442 (73%) had at least one risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% confidence interval (CI) 0.06-0.68) and readmission more likely (adjusted odds ratio (aOR) 1.27, 95% CI 1.12-1.43) for infants whose mothers had public/no insurance versus private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CI 1.86-3.00) and death five times as likely (aOR 5.22, 95% CI 2.54-10.73) for infants with three risk-associated SDOH compared with those with none.Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death post-discharge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.
View details for DOI 10.1016/j.jpeds.2023.113443
View details for PubMedID 37105408
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Correction To: Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia.
Pediatric research
2023
View details for DOI 10.1038/s41390-023-02581-7
View details for PubMedID 37045947
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Optimal neuromonitoring techniques in neonates with hypoxic ischemic encephalopathy.
Frontiers in pediatrics
2023; 11: 1138062
Abstract
Neonates with hypoxic ischemic encephalopathy (HIE) are at significant risk for adverse outcomes including death and neurodevelopmental impairment. Neuromonitoring provides critical diagnostic and prognostic information for these infants. Modalities providing continuous monitoring include continuous electroencephalography (cEEG), amplitude-integrated electroencephalography (aEEG), near-infrared spectroscopy (NIRS), and heart rate variability. Serial bedside neuromonitoring techniques include cranial ultrasound and somatic and visual evoked potentials but may be limited by discrete time points of assessment. EEG, aEEG, and NIRS provide distinct and complementary information about cerebral function and oxygen utilization. Integrated use of these neuromonitoring modalities in addition to other potential techniques such as heart rate variability may best predict imaging outcomes and longer-term neurodevelopment. This review examines available bedside neuromonitoring techniques for the neonate with HIE in the context of therapeutic hypothermia.
View details for DOI 10.3389/fped.2023.1138062
View details for PubMedID 36969281
View details for PubMedCentralID PMC10030520
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Renal oximetry for early acute kidney injury detection in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia.
Pediatric nephrology (Berlin, Germany)
2023
Abstract
BACKGROUND: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI).METHODS: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (<33% on day 3 of life,<40% on day 5, and<46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2-Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI.RESULTS: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P<0.001). Rsat>70% had a fair predictive performance for AKI at 48-84 HOL (AUC 0.71-0.79). RFTOE≤25 had a good predictive performance for AKI at 42-66 HOL (AUC 0.8-0.83). The final statistical model with the best fit to predict AKI (AUC=0.88) included RFTOE at 48 HOL (P=0.012) and pH of the infants' first postnatal blood gas (P=0.025).CONCLUSIONS: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. A higher resolution version of the Graphical abstract is available as Supplementary information.
View details for DOI 10.1007/s00467-023-05892-3
View details for PubMedID 36786860
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Investigating the association between renal tissue oxygenation and development of AKI in preterm neonates
SPRINGER. 2023: S16-S17
View details for Web of Science ID 001043123300017
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Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia.
Pediatric research
2023
Abstract
Inhaled nitric oxide (iNO) is widely used for the management of infants with congenital diaphragmatic hernia (CDH); however, evidence of benefit is limited.This is a multicenter cohort study using data from the Congenital Diaphragmatic Hernia Study Group between 2015 and 2020. The impact of early iNO use in the first 3 days of life prior to ECLS use on mortality or ECLS use was explored using multivariate logistic regression models and subgroup analyses.Of the 1777 infants, 863 (48.6%) infants received early iNO treatment. Infants receiving iNO had lower birth weight, larger defect size, more severe pulmonary hypertension, and abnormal ventricular size and function. After controlling for these factors, early iNO use was associated with increased mortality (aOR 2.06, 95% CI 1.05-4.03, P = 0.03) and increased ECLS use (aOR 3.44, 95% CI 2.11-5.60, P < 0.001). Subgroup analyses after stratification by echocardiographic characteristics and defect size revealed no subgroup with a reduction in mortality or ECLS use.Use of iNO in the first 3 days of life prior to ECLS was not associated with a reduction in mortality or ECLS use in either the regression models or the subgroup analyses. The widespread use of iNO in this vulnerable population requires reconsideration.Evidence to support widespread use of iNO for infants with congenital diaphragmatic hernia is limited. The use of iNO in the first 3 days of life was associated with significantly increased mortality and ECLS use. Stratification by echocardiographic characteristics and defect size did not reveal a subgroup that benefited from iNO. Even the subset of patients with R-to-L shunts at both ductal and atrial levels, a surrogate for elevated pulmonary arterial pressures in the absence of significantly decreased LV compliance, did not benefit from early iNO use. Early iNO therapy was of no benefit in the management of acute pulmonary hypertension in infants with congenital diaphragmatic hernia, supporting reconsideration of its use in this population.
View details for DOI 10.1038/s41390-023-02491-8
View details for PubMedID 36725908
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Editorial: Advances in the use of neuromonitoring in newborns.
Frontiers in pediatrics
2023; 11: 1215991
View details for DOI 10.3389/fped.2023.1215991
View details for PubMedID 37284291
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Neuromonitoring in neonatal critical care part I: neonatal encephalopathy and neonates with possible seizures.
Pediatric research
2022
Abstract
The blooming of neonatal neurocritical care over the last decade reflects substantial advances in neuromonitoring and neuroprotection. The most commonly used brain monitoring tools in the neonatal intensive care unit (NICU) are amplitude integrated EEG (aEEG), full multichannel continuous EEG (cEEG), and near-infrared spectroscopy (NIRS). While some published guidelines address individual tools, there is no consensus on consistent, efficient, and beneficial use of these modalities in common NICU scenarios. This work reviews current evidence to assist decision making for best utilization of neuromonitoring modalities in neonates with encephalopathy or with possible seizures. Neuromonitoring approaches in extremely premature and critically ill neonates are discussed separately in the companion paper. IMPACT: Neuromonitoring techniques hold promise for improving neonatal care. For neonatal encephalopathy, aEEG can assist in screening for eligibility for therapeutic hypothermia, though should not be used to exclude otherwise eligible neonates. Continuous cEEG, aEEG and NIRS through rewarming can assist in prognostication. For neonates with possible seizures, cEEG is the gold standard for detection and diagnosis. If not available, aEEG as a screening tool is superior to clinical assessment alone. The use of seizure detection algorithms can help with timely seizures detection at the bedside.
View details for DOI 10.1038/s41390-022-02393-1
View details for PubMedID 36476747
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Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates.
Pediatric research
2022
Abstract
Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. IMPACT: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication. For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury. Continuous multimodal monitoring as well as monitoring of sleep, sleep-wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care.
View details for DOI 10.1038/s41390-022-02392-2
View details for PubMedID 36434203
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Rescaling Creatinine Centiles in Neonates Treated with Therapeutic Hypothermia for Neonatal Encephalopathy.
Neonatology
2022: 1-3
View details for DOI 10.1159/000526738
View details for PubMedID 36183691
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Altered biventricular function in neonatal hypoxic-ischaemic encephalopathy: a case-control echocardiographic study.
Cardiology in the young
2022: 1-10
Abstract
BACKGROUND: In newborns with hypoxic-ischaemic encephalopathy, more profound altered right and left ventricular function has been associated with mortality or brain injury. Mechanisms underlying cardiac dysfunction in this population are thought to be related to the persistence of increased pulmonary vascular resistance and myocardial ischaemia. We sought to compare cardiac function in newborns with hypoxic-ischaemic encephalopathy to controls using echocardiography.METHODS: We did a retrospective case-control study with moderate or severe hypoxic-ischaemic encephalopathy between 2008 and 2017. Conventional and speckle-tracking echocardiography measures were extracted to quantify right and left ventricular systolic and diastolic function. Fifty-five newborns with hypoxic-ischaemic encephalopathy were compared to 28 controls.RESULTS: Hypoxic-ischaemic encephalopathy newborns had higher estimated systolic pulmonary pressure (62.5 ± 15.0 versus 43.8 ± 17.3 mmHg, p < 0.0001) and higher systolic pulmonary artery pressure/systolic blood pressure ratio [101 ± 16 (iso-systemic) versus 71 ± 27 (2/3 systemic range) %, p < 0.0001]. Tricuspid annular plane systolic excursion was decreased (7.5 ± 2.2 versus 9.0 ± 1.4 mm, p = 0.002), E/e' increased (7.9 ± 3.3 versus 5.8 ± 2.0, p = 0.01), and right ventricle-myocardial performance index increased (68.1 ± 21.5 versus 47.8 ± 9.5, p = 0.0001) in hypoxic-ischaemic encephalopathy. Conventional markers of left ventricle systolic function were similar, but e' velocity (0.059 ± 0.019 versus 0.070 ± 0.01, p = 0.03) and left ventricle-myocardial performance index were statistically different (77.9 ± 26.2 versus 57.9 ± 11.2, p = 0.001). The hypoxic-ischaemic encephalopathy group had significantly altered right and left ventricular deformation parameters by speckle-tracking echocardiography. Those with decreased right ventricle-peak longitudinal strain were more likely to have depressed left ventricle-peak longitudinal strain.CONCLUSION: Newborns with hypoxic-ischaemic encephalopathy have signs of increased pulmonary pressures and altered biventricular systolic and diastolic function.
View details for DOI 10.1017/S1047951122002839
View details for PubMedID 36065722
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Association of Antenatal Steroid Exposure at 21 to 22 Weeks of Gestation With Neonatal Survival and Survival Without Morbidities.
JAMA network open
2022; 5 (9): e2233331
Abstract
Importance: The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials.Objective: To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids.Design, Setting, and Participants: This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of Child Health and Human Development Neonatal Research Network. Infants who did not receive intensive care and infants with antenatal steroid exposure after GA 22 6/7 weeks were excluded.Exposure: Infants were classified as having no, partial, or complete exposure to antenatal steroids.Main Outcomes and Measures: The primary outcome was survival to discharge. The main secondary outcome was survival without major neonatal morbidity. The associations of differential exposures to antenatal steroids with outcomes were evaluated using logistic regression, adjusting for GA, sex, race, maternal education, small for GA status, mode of delivery, multiple birth, prolonged rupture of membranes, year of birth, and Neonatal Research Network center.Results: A total of 431 infants (mean [SD] GA, 22.6 [0.5] weeks; 232 [53.8%] boys) were included, with 110 infants (25.5%) receiving no antenatal steroids, 80 infants (18.6%) receiving partial antenatal steroids, and 241 infants (55.9%) receiving complete antenatal steroids. Seventeen infants were exposed to antenatal steroids at GA 21 weeks. Among infants exposed to complete antenatal steroids, 130 (53.9%) survived to discharge, compared with 30 infants (37.5%) with partial antenatal steroid exposure and 239 infants (35.5%) with no antenatal steroids. Infants born after complete antenatal steroid exposure, compared with those without antenatal steroid exposure, were more likely to survive to discharge (adjusted odds ratio [aOR], 1.95 [95% CI, 1.07-3.56]) and to survive without major morbidity (aOR, 2.74 [95% CI, 1.19-6.30]).Conclusions and Relevance: In this retrospective cohort study, among infants born between GA 22 0/7 and 23 6/7 weeks who received intensive care, exposure to a complete course of antenatal steroids at GA 22 6/7 weeks or less was independently associated with greater odds of survival and survival without major morbidity. These data suggest that the use of antenatal steroids in patients at GA 22 6/7 weeks or less could be beneficial when active treatment is considered.
View details for DOI 10.1001/jamanetworkopen.2022.33331
View details for PubMedID 36156145
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A phase-II clinical trial of targeted cerebral near infrared spectroscopy using standardized treatment guidelines to improve brain oxygenation in preterm infants (BOx-II): A study protocol.
Contemporary clinical trials
2022: 106886
Abstract
BACKGROUND: Mortality and brain injury are common adverse outcomes in infants born <28 weeks. Conventional pulse oximetry may not detect subclinical changes prior to deterioration and fails to detect changes within the brain. Increasing evidence supports the use of cerebral near-infrared spectroscopy (NIRS) in the early care of preterm infants, yet the impact of specific interventions on cerebral oxygenation and the relationship between cerebral hypoxia and brain injury on MRI remain to be determined.METHODS/DESIGN: 100 infants <28 completed weeks of gestation will be recruited for a prospective, multicenter intervention trial. After informed consent, infants will undergo cerebral NIRS monitoring starting within 6 h of birth and continuing through 72 h. Infants with persistent cerebral desaturation will receive interventions following a standard treatment algorithm selected by the provider based on the patient's clinical condition. Providers will record the timing and choice of intervention(s) and term equivalent brain MRI will be performed for survivors. There are three objectives of this study: 1) to identify the relationship between cerebral hypoxia burden and brain injury on term-equivalent MRI. 2) to identify most common interventions after cerebral hypoxia, and 3) to quantify frequency of occult cerebral hypoxia events.DISCUSSION: There is increasing evidence for the role of early cerebral NIRS monitoring in the neuroprotective care of preterm infants. This phase-II trial will provide essential data to improve the intervention approach, model the effect size of interventions on a wider extent of brain injury, and quantify the discrepancy between measurements of systemic and cerebral hypoxia.
View details for DOI 10.1016/j.cct.2022.106886
View details for PubMedID 35995129
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Image-based prenatal predictors of postnatal survival, extracorporeal life support, and defect size in right congenital diaphragmatic hernia.
Journal of perinatology : official journal of the California Perinatal Association
2022
Abstract
To determine the association between prenatal ultrasound (US) and magnetic resonance imaging (MRI) characteristics in right congenital diaphragmatic hernia (RCDH) with postnatal outcome.CDH Study Group data were reviewed for all RCDH infants (n = 156) born between 2015 and 2019. Prenatal US and MRI lung size measurements were correlated with survival, extracorporeal life support (ECLS), and defect size.Overall survival was 64.1%. ECLS was required in 40.4%. US and MRI-based prenatal assessment of pulmonary hypoplasia does not predict survival. Prenatal measurement of lung size using either US or MRI correlates with ECLS use. Only MRI-based measures of lung size are associated with defect size.Image-based prenatal predictors of survival, ECLS, and defect size are of limited value in RCDH. Extrapolation of prenatal survival and morbidity indicators from left to right-sided CDH is not appropriate. There is an urgent need to develop RCDH prenatal prediction models.
View details for DOI 10.1038/s41372-022-01470-x
View details for PubMedID 35922665
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Serum Creatinine Patterns in Neonates Treated with Therapeutic Hypothermia for Neonatal Encephalopathy.
Neonatology
2022: 1-9
Abstract
INTRODUCTION: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates.METHODS: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ≥0.3 mg/dL within 48 h, or ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort.RESULTS: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th-25th-50th-75th-90th-95th) PNA centiles (day 1-10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2-14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr).CONCLUSIONS: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies.
View details for DOI 10.1159/000525574
View details for PubMedID 35797956
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Spinal Muscular Atrophy Type 1: Fetal Diagnosis, Prenatal Coordination, and Postnatal Management in the Era of Novel Therapies.
NeoReviews
2022; 23 (7): e520-e526
View details for DOI 10.1542/neo.23-7-e520
View details for PubMedID 35773512
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Ductus arteriosus and the preterm brain.
Archives of disease in childhood. Fetal and neonatal edition
2022
Abstract
As the approach to the patent ductus arteriosus (PDA) in the preterm infant remains controversial, the potential consequences of a significant ductal shunt on the brain should be evaluated. In this population at high risk of adverse outcomes, including intraventricular haemorrhage and white matter injury, as well as longer-term neurodevelopmental impairment, it is challenging to attribute sequelae to the PDA. Moreover, individual patient characteristics including gestational age and timing of PDA intervention factor into risks of brain injury. Haemodynamic assessment of the ductus combined with bedside neuromonitoring techniques improve our understanding of the role of the PDA in neurological injury. Effects of various PDA management strategies on the brain can similarly be investigated. This review incorporates current understanding of how the PDA impacts the developing brain of preterm infants and examines modalities to measure these effects.
View details for DOI 10.1136/archdischild-2022-324111
View details for PubMedID 35732482
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Association between multi-organ dysfunction and adverse outcome in infants with hypoxic ischemic encephalopathy.
Journal of perinatology : official journal of the California Perinatal Association
2022
Abstract
OBJECTIVE: To evaluate multi-organ dysfunction (MOD) in newborns treated with therapeutic hypothermia (TH) for hypoxic ischemic encephalopathy (HIE), and to compare MOD in those with normal/mild magnetic resonance imaging (MRI) findings to those with moderate to severe MRI findings or death.STUDY DESIGN: Retrospective single-center observational study of infants treated with TH. A total of 16 parameters across 7 organ systems were analyzed. Primary outcome was death or moderate to severe brain injury on MRI.RESULT: Of 157 infants treated with TH, 77% had ≥2 organ systems with dysfunction. The number of organ systems with dysfunction was strongly associated with death or moderate-to-severe brain injury (p<0.0001). Hematologic (68%) and hepatic (65%) dysfunction were most common. Neurologic and renal dysfunction were most strongly associated with the primary outcome (OR 13.5 [6.1-29.8] and 11.2 [4.1-30.3], respectively), while pulmonary hypertension was not.CONCLUSION: MOD is prevalent in infants undergoing TH for HIE, and the association between MOD and adverse outcomes may impact clinical care and counseling.
View details for DOI 10.1038/s41372-022-01413-6
View details for PubMedID 35578019
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Early brain and abdominal oxygenation in extremely low birth weight infants.
Pediatric research
2022
Abstract
BACKGROUND: Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined.METHODS: A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables.RESULTS: In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p<0.001).CONCLUSION: Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population.IMPACT: Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.
View details for DOI 10.1038/s41390-022-02082-z
View details for PubMedID 35513716
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Renal oxygenation measured by near-infrared spectroscopy in preterm neonates in the first week.
Pediatric research
2022
Abstract
OBJECTIVE: To describe renal regional saturation of oxygen (RrSO2) values during the first week of life for preterm neonates born at <32 weeks gestational age (GA).METHODS: RrSO2 values recorded over the first week of life using near-infrared spectroscopy were retrospectively analyzed in this two-center cohort study of preterm infants without known congenital anomalies of the kidney.RESULTS: A cohort of 109 neonates with a median GA of 26.9 weeks and a median of 120 (IQR: 87-141) hours of continuous RrSO2 monitoring were included. Separately fitted trends in RrSO2 did not differ (p=0.52) between sites and demonstrated a consistent decrease in RrSO2 by 20 points (95% CI: 9.6-30.1) during the first 60h of life, followed by a stabilization of RrSO2 thereafter. RrSO2 baseline trends increased by 2.1 (95% CI: 0.8-3.3) percentage points for each additional week GA between 24 and 32 weeks GA.CONCLUSIONS: Despite differences in adjusted RrSO2 values between sites, profiles over time are consistent, allowing for the determination of RrSO2 trajectories in preterm infants. This expected pattern of RrSO2 changes in the first week may help guide future investigations and interventions to identify and reduce kidney injury in the preterm neonate.IMPACT: Renal regional saturation of oxygen (RrSO2) slowly decreases during the first 60h of age in <32-week preterm neonates. While site differences were identified with respect to absolute values, RrSO2 trends from two different centers were not different. Lower gestational age neonates have lower RrSO2 levels during the first week.
View details for DOI 10.1038/s41390-022-02036-5
View details for PubMedID 35354931
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Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.
The New England journal of medicine
2022; 386 (12): 1121-1131
Abstract
BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age.RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups.CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).
View details for DOI 10.1056/NEJMoa2114897
View details for PubMedID 35320643
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The impact of prematurity and associated comorbidities on clinical outcomes in neonates with congenital heart disease.
Seminars in perinatology
2022: 151586
Abstract
Prematurity is a common risk factor in children, affecting approximately 10% of live births, globally. It is more common in children with critical congenital heart disease (CCHD) and carries important implications in this group of patients. While outcomes have been improving over the years, even late preterm birth is associated with worse outcomes in children born with critical congenital heart disease compared to those without. Infants with both prematurity and CCHD are at particularly high risk for important comorbidities, including: necrotizing enterocolitis, intraventricular hemorrhage, white matter injury, neurodevelopmental anomalies and retinopathy of prematurity. Lesion-specific intensive care management of these infants, interventional and peri-operative management specifically tailored to their needs, and multidisciplinary care all have the potential to improve outcomes in this challenging group.
View details for DOI 10.1016/j.semperi.2022.151586
View details for PubMedID 35525603
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Near-Infrared Spectroscopy as a Hemodynamic Monitoring Tool during Neonatal Extracorporeal Life Support: A Case Series.
The journal of extra-corporeal technology
2022; 54 (1): 61-66
Abstract
Near-infrared spectroscopy (NIRS) is a non-invasive clinical tool allowing for real-time, continuous measurement of regional tissue oxygenation (rSO2); though predominantly used for neuromonitoring, it also has the potential for early detection of hemodynamic compromise in the patients on extracorporeal life support (ECLS). The authors present two cases of neonates for whom continuous monitoring of multisite rSO2 with NIRS provided the first indication of a significant compromise in hemodynamic status from catastrophic hemorrhagic complications while on ECLS ahead of conventional ECLS monitoring parameters. Routine NIRS monitoring of neonates on ECLS has utility for ongoing assessment of hemodynamic status and can be used for early detection of complications leading to impaired tissue perfusion.
View details for DOI 10.1182/ject-61-66
View details for PubMedID 36380823
View details for PubMedCentralID PMC9639685
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Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018.
JAMA
1800; 327 (3): 248-263
Abstract
Importance: Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity.Objective: To review survival, in-hospital morbidities, care practices, and neurodevelopmental and functional outcomes at 22-26 months' corrected age for extremely preterm infants.Design, Setting, and Participants: Prospective registry for extremely preterm infants born at 19 US academic centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. The study included 10 877 infants born at 22-28 weeks' gestational age between January 1, 2013, and December 31, 2018, including 2566 infants born before 27 weeks between January 1, 2013, and December 31, 2016, who completed follow-up assessments at 22-26 months' corrected age. The last assessment was completed on August 13, 2019. Outcomes were compared with a similar cohort of infants born in 2008-2012 adjusting for gestational age.Exposures: Extremely preterm birth.Main Outcomes and Measures: Survival and 12 in-hospital morbidities were assessed, including necrotizing enterocolitis, infection, intracranial hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia. Infants were assessed at 22-26 months' corrected age for 12 health and functional outcomes, including neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices.Results: The 10 877 infants were 49.0% female and 51.0% male; 78.3% (8495/10848) survived to discharge, an increase from 76.0% in 2008-2012 (adjusted difference, 2.0%; 95% CI, 1.0%-2.9%). Survival to discharge was 10.9% (60/549) for live-born infants at 22 weeks and 94.0% (2267/2412) at 28 weeks. Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. All in-hospital morbidities were more likely among infants born at earlier gestational ages. Overall, 8.9% (890/9956) of infants had necrotizing enterocolitis, 2.4% (238/9957) had early-onset infection, 19.9% (1911/9610) had late-onset infection, 14.3% (1386/9705) had severe intracranial hemorrhage, 12.8% (1099/8585) had severe retinopathy of prematurity, and 8.0% (666/8305) had severe bronchopulmonary dysplasia. Among 2930 surviving infants with gestational ages of 22-26 weeks eligible for follow-up, 2566 (87.6%) were examined. By 2-year follow-up, 8.4% (214/2555) of children had moderate to severe cerebral palsy, 1.5% (38/2555) had bilateral blindness, 2.5% (64/2527) required hearing aids or cochlear implants, 49.9% (1277/2561) had been rehospitalized, and 15.4% (393/2560) required mobility aids or other supportive devices. Among 2458 fully evaluated infants, 48.7% (1198/2458) had no or mild neurodevelopmental impairment at follow-up, 29.3% (709/2419) had moderate neurodevelopmental impairment, and 21.2% (512/2419) had severe neurodevelopmental impairment.Conclusions and Relevance: Among extremely preterm infants born in 2013-2018 and treated at 19 US academic medical centers, 78.3% survived to discharge, a significantly higher rate than for infants born in 2008-2012. Among infants born at less than 27 weeks' gestational age, rehospitalization and neurodevelopmental impairment were common at 2 years of age.
View details for DOI 10.1001/jama.2021.23580
View details for PubMedID 35040888
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Duration of noninvasive respiratory support and risk for bronchopulmonary dysplasia or death
JOURNAL OF PERINATOLOGY
2022
Abstract
To determine whether the duration of noninvasive respiratory support exposure is associated with bronchopulmonary dysplasia (BPD) or death in preterm infants.Multicenter, retrospective study of infants born at <29 weeks' gestation. The association between days on noninvasive respiratory support and BPD or death was determined using instrumental variable techniques and generalized propensity score matching to account for potential confounding by illness severity.Among 6268 infants 36% developed BPD or died. The median duration of noninvasive respiratory support was 18 days. There was inconsistency in the association between noninvasive support and BPD or death when analyzed by instrumental variable techniques (Average Marginal Effect -0.37; 95% CI -1.23 to 0.50) and generalized propensity score matching (Average Marginal Effect 0.46; 95% CI 0.33 to 0.60).Findings on the association between duration of exposure to noninvasive respiratory support and the development of BPD or death were inconclusive. CLINICALTRIALS.Generic Database:NCT00063063.
View details for DOI 10.1038/s41372-021-01269-2
View details for Web of Science ID 000742796200001
View details for PubMedID 35034096
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Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study.
JAMA neurology
2021
Abstract
Importance: Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce.Objective: To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy.Design, Setting, and Participants: This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years' follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020.Interventions: Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity.Main Outcomes and Measures: The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes.Results: A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (kappa, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P=.001; group B, 21% vs 10%; P=.03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center.Conclusions and Relevance: Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk.Trial Registration: ClinicalTrials.gov Identifier: NCT01192776.
View details for DOI 10.1001/jamaneurol.2021.3723
View details for PubMedID 34661629
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In-Hospital Morbidities for Neonates With Congenital Diaphragmatic Hernia: The Impact of Defect Size and Laterality.
The Journal of pediatrics
2021
Abstract
OBJECTIVE: To determine in-hospital morbidities for neonates with right-sided congenital diaphragmatic hernia (R-CDH) compared with those with left-sided defects (L-CDH) and to examine the differential effect of laterality and defect size on morbidities.STUDY DESIGN: This retrospective, multicenter, cohort study from the international Congenital Diaphragmatic Hernia Study Group (CDHSG) registry collected data from neonates with CDH surviving until hospital discharge from 90 neonatal intensive care units between 1/1/2007 and 7/31/2020. Major pulmonary, cardiac, neurologic, and gastrointestinal morbidities were compared between neonates with L-CDH and R-CDH, adjusted for prenatal and postnatal factors using logistic regression.RESULTS: Of 4123 survivors with CDH, those with R-CDH (n=598, 15%) compared with those with L-CDH (n=3525, 85%) had increased odds of pulmonary (1.7, 95% CI 1.4-2.2, P < .0001), cardiac (1.4, 95% CI 1.1-1.8, p=0.01), gastrointestinal (1.3, 95% CI 1.1-1.6, p=0.01), and multiple (1.6, 95% CI 1.2-2.0, p<0.001) in-hospital morbidities, with greater likelihood of morbidity with increasing defect size. There was no difference in neurologic morbidities between groups.CONCLUSION: Neonates with R-CDH and larger defect size are at increased risk for in-hospital morbidities. Counseling and clinical strategies should incorporate knowledge of these risks, and approach to neonatal R-CDH should be distinct from current practices targeted to L-CDH.
View details for DOI 10.1016/j.jpeds.2021.09.001
View details for PubMedID 34506854
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Cardiac Dysfunction in Neonatal HIE Is Associated with Increased Mortality and Brain Injury by MRI.
American journal of perinatology
2021
Abstract
OBJECTIVE: Describe the association between cardiac dysfunction and death or moderate-to-severe abnormalities on brain magnetic resonance imaging (MRI) in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE).STUDY DESIGN: Retrospective study in neonates with moderate or severe HIE undergoing therapeutic hypothermia between 2008 and 2017. Primary outcome was death or moderate-to-severe brain injury using the Barkovich score. Conventional and speckle-tracking echocardiography measures were extracted from available echocardiograms to quantify right (RV) and left (LV) ventricular functions.RESULTS: A total of 166 newborns underwent therapeutic hypothermia of which 53 (36.5%) had echocardiography performed. Ten (19%) died prior to hospital discharge, and 11 (26%) had moderate-to-severe brain injury. There was no difference in chronologic age at echocardiography between the normal and adverse outcome groups (22 [±19] vs. 28 [±21] hours, p=0.35). Cardiac findings in newborns with abnormal outcome included lower systolic and diastolic blood pressure (BP) at echocardiography (p=0.004) and decreased tricuspid annular plane systolic excursion (a marker of RV systolic function; p=0.01), while the ratio of systolic pulmonary artery (PA) pressure to systolic BP indicated isosystemic pressures (>2/3 systemic) in both groups. A multilogistic regression analysis, adjusting for weight and seizure status, indicated an association between abnormal outcome and LV function by longitudinal strain, as well as by ejection fraction.CONCLUSION: Newborns who died or had moderate-to-severe brain injury had a higher incidence of cardiac dysfunction but similar PA pressures when compared with those who survived with mild or no MRI abnormalities.KEY POINTS: · Newborns with HIE with functional LV/RV dysfunction are at risk for death or brain injury.. · All neonates with HIE had elevated pulmonary pressure, but neonates with poor outcome had RV dysfunction.. · When evaluating newborns with HIE by echocardiography, beyond estimation of pulmonary pressure, it is important to assess biventricular function..
View details for DOI 10.1055/s-0041-1735618
View details for PubMedID 34492719
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End-organ saturations correlate with aortic blood flow estimates by echocardiography in the extremely premature newborn - an observational cohort study.
BMC pediatrics
2021; 21 (1): 312
Abstract
BACKGROUND: Near-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO.METHODS: Newborns <29weeks' gestation (2013-2017) underwent routine NIRS monitoring. Csat, Rsat and systemic saturation at the time of ECHO were retrospectively analyzed and compared with Doppler markers of aortic flow. Renal and cerebral fractional tissue oxygen extraction (rFTOE and cFTOE, respectively) were calculated. Mixed effects models evaluated the association between NIRS and Doppler markers.RESULTS: Forty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3±3.8weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE.CONCLUSIONS: NIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.
View details for DOI 10.1186/s12887-021-02790-1
View details for PubMedID 34253175
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Cerebral saturation reflects anterior cerebral artery flow parameters by Doppler ultrasound in the extremely premature newborn.
Journal of perinatology : official journal of the California Perinatal Association
2021
Abstract
BACKGROUND: Near-infrared spectroscopy measures cerebral saturation (Csat), although correlation with cerebral blood flow remains unclear in premature newborns at risk for intraventricular hemorrhage (IVH).OBJECTIVES: Compare Doppler markers of anterior cerebral artery (ACA) flow with Csat obtained during head ultrasound (HUS).METHOD: Newborns <29 weeks (2013-2017) underwent Csat monitoring with clinical acquisition of HUS. ACA Doppler markers were measured (with and without pressure) and Resistive Index (RI) was calculated. Mixed effects models evaluated the association between Csat and Doppler markers.RESULTS: 98 neonates with 175 Csat-HUS observations were analyzed. Age at birth was 26.2±1.5 weeks, with post-menstrual age of 26.9±1.7 weeks at HUS. Csat was associated with RI without pressure (p=0.045), RI with pressure (p=0.019), and peak systolic velocity with pressure (p=0.036). Severe IVH (n=27 [15%]) was associated with lower Csat (60±11% vs 68±9%, p=0.01).CONCLUSION: Csat was associated with ACA Doppler measurements in extremely premature neonates.
View details for DOI 10.1038/s41372-021-01145-z
View details for PubMedID 34247188
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Fluid management, electrolytes imbalance and renal management in neonates with neonatal encephalopathy treated with hypothermia.
Seminars in fetal & neonatal medicine
2021: 101261
Abstract
Kidney dysfunction and acute kidney injury (AKI) frequently accompanies neonatal encephalopathy and contributes to neonatal morbidity and mortality. While there are currently no proven therapies for the treatment of AKI, understanding the pathophysiology along with early recognition and treatment of alterations in fluid, electrolyte and metabolic homeostasis that accompany AKI offer opportunity to reduce associated morbidity. Promising new tests and technologies, including urine and serum biomarkers and renal near-infrared spectroscopy offer opportunities to improve diagnosis and monitoring of neonates at risk for kidney injury. Furthermore, recent advances in neonatal kidney supportive therapies such as hemofiltration and hemodialysis may further improve outcomes in this population. This chapter provides an overview of disorders of fluid balance, electrolyte homeostasis and kidney function associated with neonatal encephalopathy and therapeutic hypothermia. Recommendations for fluid and electrolyte management based upon published literature and authors' opinions are provided.
View details for DOI 10.1016/j.siny.2021.101261
View details for PubMedID 34140246
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Neonatal NIRS monitoring: recommendations for data capture and review of analytics.
Journal of perinatology : official journal of the California Perinatal Association
2021
Abstract
Brain injury is one of the most consequential problems facing neonates, with many preterm and term infants at risk for cerebral hypoxia and ischemia. To develop effective neuroprotective strategies, the mechanistic basis for brain injury must be understood. The fragile state of neonates presents unique research challenges; invasive measures of cerebral blood flow and oxygenation assessment exceed tolerable risk profiles. Near-infrared spectroscopy (NIRS) can safely and non-invasively estimate cerebral oxygenation, a correlate of cerebral perfusion, offering insight into brain injury-related mechanisms. Unfortunately, lack of standardization in device application, recording methods, and error/artifact correction have left the field fractured. In this article, we provide a framework for neonatal NIRS research. Our goal is to provide a rational basis for NIRS data capture and processing that may result in better comparability between studies. It is also intended to serve as a primer for new NIRS researchers and assist with investigation initiation.
View details for DOI 10.1038/s41372-021-00946-6
View details for PubMedID 33589724
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Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia.
The Journal of pediatrics
2021
Abstract
To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia.We performed a multicenter prospective observational study of 64 neonates. Urine was obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin 18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), insulin like growth factor binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO AKI criteria.AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use (median [IQR], 2[0-5] days vs. 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; p=0.012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs only yielded a fair prediction. KIM-1 had the best predictive performance across time points with an AUC (SE) of 0.79 (0.11) at 48 HOL. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 HOL.Urine NGAL, KIM-1, and IL-18 were elevated in neonates with HIE receiving TH who developed AKI. However, wide variability and unclear cut off levels make their clinical utility unclear.
View details for DOI 10.1016/j.jpeds.2021.08.090
View details for PubMedID 34547334
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Blood pressure goals: Is cerebral saturation the new mean arterial pressure?
American journal of perinatology
2021
Abstract
To correlate hypotension and cerebral saturation from near-infrared spectroscopy (cNIRS) in neonates on dopamine.Retrospective review of neonates receiving dopamine between August 2018-2019 was performed. Hypotension thresholds included mean arterial pressure (MAP) of postmenstrual age (PMA) ± 5mmHg, 30mmHg, and gestational age (GA) ± 5mmHg. Time below threshold MAP was compared to time with cerebral hypoxia (cNIRS <55%).Hypotension occurred 6-33% of time on dopamine in 59 cases. Hypotension did not correlate with abnormal cNIRS overall, within PMA subgroups, or by outcomes. Hypotensive periods with MAP
View details for DOI 10.1055/a-1704-1851
View details for PubMedID 34814195
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Prolonged Ductal Patency in Preterm Infants: Does It Matter?
The Journal of pediatrics
2020
View details for DOI 10.1016/j.jpeds.2020.10.059
View details for PubMedID 33130156
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Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.
Pediatric research
2020
Abstract
BACKGROUND: Theophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies.METHODS: A population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review. Aminophylline (intravenous salt form of theophylline) was given per institutional standard of care for low urine output and/or rising serum creatinine (5mg/kg intravenous (i.v.) load then 1.8mg/kg i.v. q6h). The ability of different dosing regimens to achieve target concentrations (4-10mg/L) associated with clinical response was examined.RESULTS: Birth weight was a significant predictor of theophylline clearance and volume of distribution (p<0.05). The median half-life was 39.5h (range 27.2-50.4). An aminophylline loading dose of 7mg/kg followed by 1.6mg/kg q12h was predicted to achieve target concentrations in 84% of simulated neonates.CONCLUSIONS: In neonates with HIE undergoing hypothermia, theophylline clearance was low with a 50% longer half-life compared to full-term normothermic neonates without HIE. Dosing strategies need to consider the unique pharmacokinetic needs of this population.IMPACT: Theophylline is a potential renal-protective therapy in neonates with HIE undergoing therapeutic hypothermia; however, the pharmacokinetics and dose needs in this population are not known.Theophylline clearance was low in neonates with HIE undergoing therapeutic hypothermia with a 50% longer half-life compared to full-term normothermic neonates without HIE.As theophylline is advanced in clinical development, dosing strategies will need to consider the unique pharmacokinetic needs of neonates with HIE undergoing therapeutic hypothermia.Fig. 1INDIVIDUAL PREDICTED THEOPHYLLINE CONCENTRATIONS IN NEONATES WITH HIE RECEIVING HYPOTHERMIA BASED ON THE FINAL PHARMACOKINETIC MODEL AS COMPARED TO THE OBSERVED MEASURED CONCENTRATIONS.: DBS dried blood samples measured as part of a prospective study, plasma samples measured as part of clinical care.Fig. 2Relationship between the average theophylline concentration over the first 24h of treatment (Cavg,24) and (a) change in urine output (∆UOP) 24h after the start of treatment and (b) change in serum creatinine (∆SCr) 48h after the start of treatment.Fig. 3Predicted theophylline concentration-time course after aminophylline using (a) dosing strategy used in clinical care during the study time period (loading dose 5mg/kg, followed by 1.8mg/kg every 6h) and (b) optimized dosing strategy (loading dose 7mg/kg, followed by 1.6mg/kg every 12h). Each dosing strategy was simulated in 3000 neonates using the final population pharmacokinetic model. Solid line represents the median and dashed lines represent the 10th and 90th percentile. Shaded area represents targeted concentration range of 4-10mg/L.
View details for DOI 10.1038/s41390-020-01140-8
View details for PubMedID 32919393
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Aminophylline for renal protection in neonatal hypoxic-ischemic encephalopathy in the era of therapeutic hypothermia.
Pediatric research
2020
Abstract
BACKGROUND: Neonates with hypoxic-ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied.METHODS: A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum creatinine (SCr). Comparisons were also made to control neonates matched for hours of life who were cooled but unexposed to aminophylline.RESULTS: Sixteen neonates cooled for HIE received aminophylline starting at 25±14h of life. Within 12h of starting aminophylline, UOP increased by 2.6±1.9mL/kg/h. SCr declined by 0.4±0.2mg/dL in survivors over the first 4 days. When compared to control neonates, UOP increase was greater in the aminophylline group (p<0.001). SCr declined in survivors in both groups, although baseline SCr was higher in the aminophylline group.CONCLUSIONS: Aminophylline use in neonates with HIE undergoing hypothermia was associated with an increase in UOP and a decline in SCr. A randomized trial will be needed to establish a potential renal protective role of aminophylline.IMPACT: The renal protective effect of aminophylline in neonates with HIE has not yet been studied in the context of therapeutic hypothermia.Aminophylline exposure in neonates cooled for HIE was associated with increased UOP and a similar decline in SCr when compared to control infants unexposed to aminophylline.Improved renal function after receiving aminophylline in this observational cohort study suggests the need for future randomized trials to establish the potential benefit of aminophylline in the HIE population undergoing hypothermia.
View details for DOI 10.1038/s41390-020-0999-y
View details for PubMedID 32503030
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NIRS improves hemodynamic monitoring and detection of risk for cerebral injury: cases in the neonatal intensive care nursery
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
2020; 33 (10): 1802–10
View details for DOI 10.1080/14767058.2018.1528223
View details for Web of Science ID 000519294200026
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Behavior Profiles at 2Years for Children Born Extremely PretermwithBronchopulmonary Dysplasia.
The Journal of pediatrics
2020
Abstract
OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).STUDY DESIGN: We studied children born at 22-26weeks of gestation and assessed at 22-26months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P<.001) and pervasive developmental problems (P<.001) increased with worsening BPD grade. Sleep problems (P=.008) and aggressive behavior (P=.023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values<.05).CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.
View details for DOI 10.1016/j.jpeds.2019.12.028
View details for PubMedID 32008764
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Simultaneous Near-Infrared Spectroscopy (NIRS) and Amplitude-Integrated Electroencephalography (aEEG): Dual Use of Brain Monitoring Techniques Improves Our Understanding of Physiology
FRONTIERS IN PEDIATRICS
2020; 7: 560
Abstract
Continuous brain monitoring tools are increasingly being used in the neonatal intensive care unit (NICU) to assess brain function and cerebral oxygenation in neonates at high risk for brain injury. Near infrared spectroscopy (NIRS) is useful in critically ill neonates as a trend monitor to evaluate the balance between tissue oxygen delivery and consumption, providing cerebral and somatic oximetry values, and allowing earlier identification of abnormalities in hemodynamics and cerebral perfusion. Amplitude-integrated electroencephalography (aEEG) is a method for continuous monitoring of cerebral function at the bedside. Simultaneous use of both monitoring modalities may improve the understanding of alterations in hemodynamics and risk of cerebral injury. Several studies have described correlations between aEEG and NIRS monitoring, especially in infants with hypoxic-ischemic encephalopathy (HIE), but few describe the combined use of both monitoring techniques in a wider range of clinical scenarios. We review the use of NIRS and aEEG in neonates and describe four cases where abnormal NIRS values were immediately followed by changes in brain activity as seen on aEEG allowing the impact of a hemodynamic disturbance on the brain to be correlated with the changes in the aEEG background pattern. These four clinical scenarios demonstrate how simultaneous neuromonitoring with aEEG and NIRS provides important clinical information. We speculate that routine use of these combined monitoring modalities may become the future standard for neonatal neuromonitoring.
View details for DOI 10.3389/fped.2019.00560
View details for Web of Science ID 000510920400001
View details for PubMedID 32039117
View details for PubMedCentralID PMC6985148
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Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.
The New England journal of medicine
2020; 383 (27): 2639–51
Abstract
Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).
View details for DOI 10.1056/NEJMoa2020248
View details for PubMedID 33382931
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Cerebral Oxygenation and Autoregulation in Preterm Infants (Early NIRS Study).
The Journal of pediatrics
2020
Abstract
To determine if decreased cerebral oxygenation or altered cerebral autoregulation as measured by near-infrared spectroscopy (NIRS) in the first 96 postnatal hours is associated with an increased risk of death or severe neuroradiographic abnormalities in very preterm infants.The Early NIRS prospective, multi-center study enrolled very preterm infants with birth weight <1250 g from 6 tertiary neonatal intensive care units. Mean arterial blood pressure (MAP) and cerebral oxygen saturation (Csat) were continuously monitored using a neonatal sensor until 96 hours of age. Moving window correlations between Csat and MAP determined time periods with altered cerebral autoregulation, and percentiles of correlation were compared between infants with and without the adverse outcome of mortality or severe neuroradiographic abnormalities by early cranial ultrasound.Of 103 subjects with mean gestational age of 26 weeks, 21 (20%) died or had severe neuroradiographic abnormalities. Infants with adverse outcomes had a lower mean Csat (67 ± 9%) compared with those without adverse outcomes (72 ± 7%, P = .02). Csat <50% was identified as a cut-point for identifying infants with adverse outcome (AUC =0.76). Infants with adverse outcomes were more likely to have significant positive or negative correlations between Csat and MAP, indicating impaired cerebral autoregulation (p=0.006).Early NIRS monitoring may detect periods of lower cerebral oxygenation and altered cerebral autoregulation, identifying preterm infants at risk for mortality or neuroradiographic injury. Improved understanding of the relationship between altered hemodynamics and cerebral oxygenation may inform future strategies to prevent brain injury.
View details for DOI 10.1016/j.jpeds.2020.08.036
View details for PubMedID 32818482
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Renal Tissue Oxygenation Monitoring-An Opportunity to Improve Kidney Outcomes in the Vulnerable Neonatal Population.
Frontiers in pediatrics
2020; 8: 241
Abstract
Adequate oxygenation of the kidney is of critical importance in the neonate. Non-invasive monitoring of renal tissue oxygenation using near-infrared spectroscopy (NIRS) is a promising bedside strategy for early detection of circulatory impairment as well as recognition of specific renal injury. As a diagnostic tool, renal NIRS monitoring may allow for earlier interventions to prevent or reduce injury in various clinical scenarios in the neonatal intensive care unit. Multiple studies utilizing NIRS monitoring in preterm and term infants have provided renal tissue oxygenation values at different time points during neonatal hospitalization, and have correlated measures with ultrasound and Doppler flow data. With the establishment of normal values, studies have utilized renal tissue oxygenation monitoring in preterm neonates to predict a hemodynamically significant patent ductus arteriosus, to assess response to potentially nephrotoxic medications, to identify infants with sepsis, and to describe changes after red blood cell transfusions. Other neonatal populations being investigated with renal NIRS monitoring include growth restricted infants, those requiring delivery room resuscitation, infants with congenital heart disease, and neonates undergoing extracorporeal membrane oxygenation. Furthermore, as the recognition of acute kidney injury (AKI) and its associated morbidity and mortality in neonates has increased over the last decade, alternative methods are being investigated to diagnose AKI before changes in serum creatinine or urine output occur. Studies have utilized renal NIRS monitoring to diagnose AKI in specific populations, including neonates with hypoxic ischemic encephalopathy after birth asphyxia and in infants after cardiac bypass surgery. The use of renal tissue oxygenation monitoring to improve renal outcomes has yet to be established, but results of studies published to date suggest that it holds significant promise to function as a real time, early indicator of poor renal perfusion that may help with development of specific treatment protocols to prevent or decrease the severity of AKI.
View details for DOI 10.3389/fped.2020.00241
View details for PubMedID 32528917
View details for PubMedCentralID PMC7247835
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Influence of enteral feeding and anemia on tissue oxygen extraction after red blood cell transfusion in preterm infants.
Transfusion
2020
Abstract
Understanding factors that impact tissue oxygen extraction may guide red blood cell (RBC) transfusion decision making in preterm infants. Our objective was to assess the influence of enteral feeding and anemia on cerebral and mesenteric oxygen saturation (Csat and Msat) and fractional tissue oxygen extraction (cFTOE and mFTOE) over the entire time course of RBC transfusion.Preterm, very low-birth-weight infants receiving RBC transfusions at a single center were enrolled. Near-infrared spectroscopy sensors measured Csat and Msat levels from an hour before transfusion to 24 hours after. During this period, changes in Csat, Msat, cFTOE, and mFTOE were described, and their association with enteral feeding status and pretransfusion degree of anemia were assessed using generalized estimating equations.RBC transfusion data from 31 preterm infants were included. Infants receiving enteral feeds exhibited lower pretransfusion Msat. Infants with pretransfusion hematocrit greater than 30% exhibited higher pretransfusion Csat and lower pretransfusion cFTOE. Such differences in baseline measurements persisted through 24 hours after transfusion. However, no statistically significant differences in oxygenation measures over time by enteral feeding or anemia status were identified.Compared to NPO, enteral feeding was associated with lower Msat; anemia (hematocrit ≤30%) was associated with lower Csat and higher cFTOE. Over the time course of RBC transfusion, trajectories of Csat, Msat, cFTOE and mFTOE did not differ by enteral feeding or anemia status.
View details for DOI 10.1111/trf.15680
View details for PubMedID 31984520
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Intraventricular hemorrhage and white matter injury: is persistent cerebral desaturation a missing link?
Pediatric research
2020
View details for DOI 10.1038/s41390-020-01294-5
View details for PubMedID 33247218
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Prenatally diagnosed omphalocele: characteristics associated with adverse neonatal outcomes.
Journal of perinatology : official journal of the California Perinatal Association
2019
Abstract
OBJECTIVE: To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases.STUDY DESIGN: Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed.RESULTS: Out of 63 fetal cases, 33 were live-born, >50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach toomphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3-422), p=0.006).CONCLUSION: Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.
View details for DOI 10.1038/s41372-019-0410-1
View details for PubMedID 31227786
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Differences in patient characteristics and care practices between two trials of therapeutic hypothermia
PEDIATRIC RESEARCH
2019; 85 (7): 1008–15
View details for DOI 10.1038/s41390-019-0371-2
View details for Web of Science ID 000468524800020
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Near-Infrared Spectroscopy in the Diagnostic Evaluation of Mitochondrial Disorders: A Neonatal Intensive Care Unit Case Series
JOURNAL OF PEDIATRICS
2019; 208: 282–86
View details for DOI 10.1016/j.jpeds.2019.01.022
View details for Web of Science ID 000465236700050
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Differences in patient characteristics and care practices between two trials of therapeutic hypothermia.
Pediatric research
2019
Abstract
BACKGROUND: The Induced Hypothermia (IH) and Optimizing Cooling (OC) trials for hypoxic-ischemic encephalopathy (HIE) had similar inclusion criteria. The rate of death/moderate-severe disability differed for the subgroups treated with therapeutic hypothermia (TH) at 33.5°C for 72h (44% vs. 29%, unadjusted p=0.03). We aimed to evaluate differences in patient characteristics and care practices between the trials.METHODS: We compared pre/post-randomization characteristics and care practices between IH and OC.RESULTS: There were 208 patients in the IH trial, 102 cooled, and 364 in the OC trial, 95 cooled to 33.5°C for 72h. In OC, neonates were less ill, fewer had severe HIE, and the majority were cooled prior to randomization. Differences between IH and OC were observed in the adjusted difference in the lowest PCO2 (+3.08mmHg, p=0.005) and highest PO2 (-82.7mmHg, p<0.001). In OC, compared to IH, the adjusted relative risk (RR) of exposure to anticonvulsant prior to randomization was decreased (RR 0.58, (0.40-0.85), p=0.005) and there was increased risk of exposure during cooling to sedatives/analgesia (RR 1.86 (1.21-2.86), p=0.005).CONCLUSION: Despite similar inclusion criteria, there were differences in patient characteristics and care practices between trials. Change in care practices over time should be considered when planning future neuroprotective trials.
View details for PubMedID 30862961
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Near-Infrared Spectroscopy in the Diagnostic Evaluation of Mitochondrial Disorders: A Neonatal Intensive Care Unit Case Series.
The Journal of pediatrics
2019
Abstract
We assessed the utility of near-infrared spectroscopy to evaluate neonates with mitochondrial disorders. We observed abnormally high cerebral oxygen saturation levels indicating insufficient tissue oxygen utilization. We propose that near-infrared spectroscopy may be an additional tool in the diagnostic evaluation of a suspected mitochondrial disorder.
View details for PubMedID 30853194
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Birth Location of Infants with Critical Congenital Heart Disease in California
PEDIATRIC CARDIOLOGY
2019; 40 (2): 310–18
View details for DOI 10.1007/s00246-018-2019-0
View details for Web of Science ID 000460553100007
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Immediate Postnatal Ventricular Performance Is Associated with Mortality in Hypoplastic Left Heart Syndrome
PEDIATRIC CARDIOLOGY
2019; 40 (1): 168–76
View details for DOI 10.1007/s00246-018-1974-9
View details for Web of Science ID 000456807300022
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Birth Location of Infants with Critical Congenital Heart Disease in California.
Pediatric cardiology
2018
Abstract
The American Academy of Pediatrics classifies neonatal intensive care units (NICUs) from level I to IV based on the acuity of care each unit can provide. Birth in a higher level center is associated with lower morbidity and mortality in high-risk populations. Congenital heart disease accounts for 25-50% of infant mortality related to birth defects in the U.S., but recent data are lacking on where infants with critical congenital heart disease (CCHD) are born. We used a linked dataset from the Office of Statewide Health Planning and Development to access ICD-9 diagnosis codes for all infants born in California from 2008 to 2012. We compared infants with CCHD to the general population, identified where infants with CCHD were born based on NICU level of care, and predicted level IV birth among infants with CCHD using logistic regression techniques. From 2008 to 2012, 6325 infants with CCHD were born in California, with 23.7% of infants with CCHD born at a level IV NICU compared to 8.4% of the general population. Level IV birth for infants with CCHD was associated with lower gestational age, higher maternal age and education, the presence of other congenital anomalies, and the diagnosis of a single ventricle lesion. More infants with CCHD are born in a level IV NICU compared to the general population. Future studies are needed to determine if birth in a lower level of care center impacts outcomes for infants with CCHD.
View details for PubMedID 30415381
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Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly
JOURNAL OF PERINATOLOGY
2018; 38 (11): 1444–52
View details for DOI 10.1038/s41372-018-0208-6
View details for Web of Science ID 000449174800002
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Development of a NeuroNICU with a Broader Focus on All Newborns at Risk of Brain Injury: The First 2 Years
AMERICAN JOURNAL OF PERINATOLOGY
2018; 35 (12): 1197–1205
View details for DOI 10.1055/s-0038-1646954
View details for Web of Science ID 000445491700012
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NIRS improves hemodynamic monitoring and detection of risk for cerebral injury: cases in the neonatal intensive care nursery.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
2018: 1–191
Abstract
Near-infrared spectroscopy (NIRS) monitoring provides a noninvasive, bedside measure of cerebral and somatic oxygenation in neonates at risk for hemodynamic instability and brain injury. This technology has been increasingly utilized in the neonatal intensive care unit, however clinicians perceive a lack of evidence for the added value of NIRS monitoring. We present six clinical scenarios illustrating the value of NIRS monitoring for the diagnosis and management of critically ill newborns.
View details for PubMedID 30244630
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Immediate Postnatal Ventricular Performance Is Associated with Mortality in Hypoplastic Left Heart Syndrome.
Pediatric cardiology
2018
Abstract
Right ventricular (RV) function as assessed by deformation has been evaluated prenatally and after palliation in hypoplastic left heart syndrome (HLHS). However, limited data exist about the immediate postnatal cardiac adaptation and RV function in HLHS. We compared echocardiographic measures of cardiac performance in HLHS versus controls in their first week of life. As a secondary objective, we evaluated if markers at the first echocardiogram were associated with mid- and long-term outcomes. Clinical and echocardiographic data of patients with HLHS between 2013 and 2016 were reviewed. The study population was matched with controls whose echocardiograms were obtained due to murmur or rule out coarctation. Speckle-tracking echocardiography was used to assess deformation. Thirty-four patients with HLHS and 28 controls were analyzed. Age at echocardiogram was similar between HLHS and controls. The RV of HLHS was compared to both RV and left ventricle (LV) of controls. HLHS deformation parameters [RV peak global longitudinal strain (GLS), global longitudinal strain rate (GLSR)] and tricuspid annular plane systolic excursion (TAPSE) were decreased compared to RV of controls. The LV-fractional area change, peak GLS, GLSR, circumferential strain, and strain rate of controls were higher than the RV of HLHS. Calculated cardiac output (CO) was higher in the HLHS group (592 vs. 183mL/kg/min, p=0.0001) but similar to the combined LV and RV output of controls. Later mortality or cardiac transplantation was associated with the RV CO and RV stroke distance at initial echocardiogram. Cox proportional hazard regression determined that restriction at atrial septum, decreased initial RV stroke distance and decreased TAPSE had a higher risk of death or cardiac transplantation. TAPSE and RV stroke distance by velocity time integral had adequate inter-reader variability by Bland-Altman plot and Pearson's correlation. Our study found that the HLHS RV deformation is decreased in the early postnatal period when compared to both LV and RV of controls, but deformation was not associated with mid- and long-term outcomes. Later mortality or cardiac transplantation was associated with decreased initial stroke distance and cardiac output. Early evaluation of patients with HLHS should include an assessment of stroke distance and future research should evaluate its implication in management strategies.
View details for PubMedID 30178190
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Renal Saturation and Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
JOURNAL OF PEDIATRICS
2018; 200: 232-+
View details for DOI 10.1016/j.jpeds.2018.04.076
View details for Web of Science ID 000442390400038
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Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly.
Journal of perinatology : official journal of the California Perinatal Association
2018
Abstract
OBJECTIVE: Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM).STUDY DESIGN: Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children's Hospital Stanford 1/1/2009-6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated.RESULTS: A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related.CONCLUSION: Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.
View details for PubMedID 30158676
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Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease
JOURNAL OF PERINATOLOGY
2018; 38 (6): 658–64
View details for DOI 10.1038/s41372-018-0093-z
View details for Web of Science ID 000437240700009
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Renal Saturation and Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia.
The Journal of pediatrics
2018
Abstract
OBJECTIVE: To investigate the range of renal near-infrared spectroscopy (NIRS) measures in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) and to determine the association between renal NIRS measures and the development of acute kidney injury (AKI).STUDY DESIGN: A retrospective chart review was conducted of neonates with moderate to severe HIE who received therapeutic hypothermia at a tertiary care center from 2014 to 2016. Neonates had routine continuous NIRS monitoring of cerebral and renal saturation (Rsat) as part of their clinical care for 72hours of cooling and until 24hours after rewarming. The outcome of AKI was defined by an abnormal rate of decline of serum creatinine over the first 5 days of life. Mixed effects models determined the association between renal NIRS measures and AKI over time.RESULTS: Of 38 neonates with HIE undergoing cooling, 15 (39%) developed AKI. Rsat was lower than cerebral saturation during cooling (P<.01), but Rsat increased over time after rewarming, while renal oxygen extraction levels decreased (P<.0001). Neonates with AKI had higher Rsat levels (P<.01) compared with those without AKI after 24hours of life. Using receiver operating characteristic curves, Rsat >75% by 24-48hours predicted AKI with a sensitivity of 79% and specificity of 82% (area under the receiver operating characteristic curve=0.76).CONCLUSIONS: Throughout cooling, neonates with AKI had higher Rsat measures than those without AKI. These differences may reflect lower oxygen extraction by the injured kidney. NIRS monitoring of Rsat may identify neonates with HIE at risk of developing AKI.
View details for PubMedID 29866591
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Development of a NeuroNICU with a Broader Focus on All Newborns at Risk of Brain Injury: The First 2 Years.
American journal of perinatology
2018
Abstract
OBJECTIVE: Many critically ill neonates have an existing brain injury or are at risk of neurologic injury. We developed a "NeuroNICU" (neurologic neonatal intensive care unit) to better provide neurologically focused intensive care.STUDY DESIGN: Demographic and clinical variables, services delivered, and patient outcomes were recorded in a prospective database for all neonates admitted to the NeuroNICU between April 23, 2013, and June 25, 2015.RESULTS: In total, 546 neonates were admitted to the NeuroNICU representing 32% of all NICU admissions. The most common admission diagnoses were congenital heart disease (30%), extreme prematurity (18%), seizures (10%), and hypoxic-ischemic encephalopathy (9%). Neuromonitoring was common, with near-infrared spectroscopy used in 69%, amplitude-integrated electroencephalography (EEG) in 45%, and continuous video EEG in 35%. Overall, 43% received neurology or neurosurgery consultation. Death prior to hospital discharge occurred in 11%. Among survivors, 87% were referred for developmental follow-up, and among those with a primary neurologic diagnosis 57% were referred for neurology or neurosurgical follow-up.CONCLUSION: The NeuroNICU-admitted newborns with or at risk of brain injury comprise a high percentage of NICU volume; 38% had primary neurologic diagnoses, whereas 62% had medical diagnoses. We found many opportunities to provide brain focused intensive care, impacting a substantial proportion of newborns in our NICU.
View details for PubMedID 29702712
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Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease.
Journal of perinatology : official journal of the California Perinatal Association
2018
Abstract
OBJECTIVE: Multicystic dysplastic kidney (MCDK) is one of the most common anomalies detected by prenatal ultrasound. Our objective was to identify factors associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK STUDY DESIGN: A retrospective review of prenatally diagnosed MCDK (1 January 2009 to 30 December 2014) from a single academic center was conducted. The primary outcome was death or need for dialysis among live-born infants. Associations between prenatal characteristics and outcome were analyzed by Fisher's exact test and Mann-Whitney test.RESULTS: A total of 53 cases of prenatally suspected MCDK were included, of which 46 cases were live-born and confirmed postnatally (38 survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral MCDK, contralateral renal anomalies, and anhydramnios were significantly associated with death or need for dialysis (all p<0.0001).CONCLUSIONS: Prenatally identified findings are associated with adverse neonatal outcome, and can guide counseling and management planning. In the absence of significant associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal course.
View details for PubMedID 29572458
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End-Organ Saturation Differences in Early Neonatal Transition for Left-versus Right-Sided Congenital Heart Disease
NEONATOLOGY
2018; 114 (1): 53–61
Abstract
For neonates with congenital heart disease (CHD), left-sided (LL) and right-sided (RL) single ventricular physiologies (LL, hypoplastic left heart syndrome; RL, tricuspid atresia or pulmonary atresia with intact ventricular septum) may demonstrate distinct changes in tissue saturation in the first 72 h of life. Near-infrared spectroscopy (NIRS) can measure regional cerebral saturation (Csat) and renal saturation (Rsat) to clarify differences between LL and RL over time.Our primary objective was to measure changes in Csat and Rsat in the first 72 h of life using NIRS between CHD infants with LL compared to RL. The secondary objective was to correlate NIRS values to an echocardiographic marker of perfusion.Newborns with hypoplastic left heart syndrome, tricuspid atresia, and pulmonary atresia with intact ventricular septum from 2013 to 2016 underwent routine NIRS monitoring. Csat, Rsat, and systemic saturations (SpO2) in the first 72 h of life were retrospectively analyzed and the echocardiographic descending aorta velocity time integral (VTI) was measured. Mixed effects models compared differences over time between LL and RL.The final cohort included 13 LL, 12 RL, and 4 controls. Csat decreased for RL compared to LL (p = 0.005), while Rsat decreased for both (p = 0.008). Over time, SpO2 increased for LL but decreased for RL (p = 0.046). Compared to the controls, infants with CHD had lower Csat, lower Rsat, and lower SpO2. The descending aorta VTI was correlated with Rsat (R2 = 0.24, p = 0.02).NIRS Csat measures were better preserved in LL compared to RL. Rsat decreased in both groups through time. The correlation between the descending aorta VTI and Rsat suggests an association between NIRS measures of renal saturation and renal perfusion.
View details for PubMedID 29649824
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Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy A Randomized Clinical Trial
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
2017; 318 (16): 1550–60
Abstract
Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours.To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy.A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size.Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C).The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization.Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively.Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness.clinicaltrials.gov Identifier: NCT00614744.
View details for PubMedID 29067428
View details for PubMedCentralID PMC5783566
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Changing Management of the Patent Ductus Arteriosus: Effect on Neonatal Outcomes and Resource Utilization.
American journal of perinatology
2017
Abstract
Objective This historical cohort study investigated how a shift toward a more conservative approach of awaiting spontaneous closure of the patent ductus arteriosus (PDA) in preterm infants has affected neonatal outcomes and resource utilization. Methods We retrospectively studied very low birth weight infants diagnosed with a PDA by echocardiogram (ECHO) in 2006-2008 (era 1), when medical or surgical PDA management was emphasized, to those born in 2010-2012 (era 2) when conservative PDA management was encouraged. Multiple regression analyses adjusted for gestational age were performed to assess differences in clinical outcomes and resource utilization between eras. Results More infants in era 2 (35/89, 39%) compared with era 1 (22/120, 18%) had conservative PDA management (p < 0.01). Despite no difference in surgical ligation rate, infants in era 2 had ligation later (median 24 vs. 8 days, p < 0.0001). There was no difference in clinical outcomes between eras, while number of ECHOs per patient was the only resource measure that increased in era 2 (median 3 vs. 2 ECHOs, p = 0.003). Conclusion In an era of more conservative PDA management, no increase in adverse clinical outcomes or significant change in resource utilization was found. Conservative PDA management may be a safe alternative for preterm infants.
View details for DOI 10.1055/s-0037-1601442
View details for PubMedID 28376547
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Prediction of neonatal respiratory distress in pregnancies complicated by fetal lung masses.
Prenatal diagnosis
2017
Abstract
The objective of this article is to evaluate the utility of fetal lung mass imaging for predicting neonatal respiratory distress.Pregnancies with fetal lung masses between 2009 and 2014 at a single center were analyzed. Neonatal respiratory distress was defined as intubation and mechanical ventilation at birth, surgery before discharge, or extracorporeal membrane oxygenation (ECMO). The predictive utility of the initial as well as maximal lung mass volume and congenital pulmonary airway malformation volume ratio by ultrasound (US) and magnetic resonance imaging (MRI) was analyzed.Forty-seven fetal lung mass cases were included; of those, eight (17%) had respiratory distress. The initial US was performed at similar gestational ages in pregnancies with and without respiratory distress (26.4 ± 5.6 vs 22.3 ± 3 weeks, p = 0.09); however, those with respiratory distress had higher congenital volume ratio at that time (1.0 vs 0.3, p = 0.01). The strongest predictors of respiratory distress were maximal volume >24.0 cm(3) by MRI (100% sensitivity, 91% specificity, 60% positive predictive value, and 100% negative predictive value) and maximal volume >34.0 cm(3) by US (100% sensitivity, 85% specificity, 54% positive predictive value, and 100% negative predictive value).Ultrasound and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value. © 2017 John Wiley & Sons, Ltd.
View details for DOI 10.1002/pd.5002
View details for PubMedID 28061000
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Near-infrared spectroscopy for detection of a significant patent ductus arteriosus.
Pediatric research
2016; 80 (5): 675-680
Abstract
Near-infrared spectroscopy (NIRS) may assist with characterization of a hemodynamically significant patent ductus arteriosus (hsPDA) by measuring cerebral and renal saturation (Csat and Rsat) levels. We hypothesized that Csat and Rsat in preterm infants with an hsPDA would be decreased compared to those with no PDA or nonsignificant PDA.This non a-priori designed study retrospectively investigated clinical and ECHO characteristics of preterm infants <29 wk gestation who underwent routine NIRS monitoring. Logistic regression assessed association between NIRS measures and an hsPDA by ECHO.Of 47 infants, 21 had a confirmed hsPDA by ECHO, 14 had a nonsignificant PDA, and 12 had no ECHO performed due to low clinical suspicion for PDA. Logistic regression adjusted for gestational age found that lower Rsat was associated with an hsPDA by ECHO (OR 0.9, 95% CI 0.83-0.98, P = 0.01). Using ROC curves, Rsat < 66% identified an hsPDA with a sensitivity of 81% and specificity of 77%, while Csat was not significant.Low Rsat < 66% was associated with the presence of an hsPDA in the preterm infant. Csat may be preserved if cerebral autoregulation is largely intact. Bedside NIRS monitoring may reasonably increase suspicion for a significant PDA in the preterm infant.
View details for DOI 10.1038/pr.2016.148
View details for PubMedID 27603562
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HDlive imaging of a giant omphalocele.
Ultrasound in obstetrics & gynecology
2016; 48 (3): 407-408
View details for DOI 10.1002/uog.15993
View details for PubMedID 27299988
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Management of the Preterm Infant with Congenital Heart Disease
CLINICS IN PERINATOLOGY
2016; 43 (1): 157-?
Abstract
The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD.
View details for DOI 10.1016/j.clp.2015.11.011
View details for Web of Science ID 000372765500014
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Management of the Preterm Infant with Congenital Heart Disease.
Clinics in perinatology
2016; 43 (1): 157-171
Abstract
The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD.
View details for DOI 10.1016/j.clp.2015.11.011
View details for PubMedID 26876128
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Failed endotracheal intubation and adverse outcomes among extremely low birth weight infants.
Journal of perinatology
2016; 36 (2): 112-115
Abstract
To quantify the importance of successful endotracheal intubation on the first attempt among extremely low birth weight (ELBW) infants who require resuscitation after delivery.A retrospective chart review was conducted for all ELBW infants ⩽1000 g born between January 2007 and May 2014 at a level IV neonatal intensive care unit. Infants were included if intubation was attempted during the first 5 min of life or if intubation was attempted during the first 10 min of life with heart rate <100. The primary outcome was death or neurodevelopmental impairment. The association between successful intubation on the first attempt and the primary outcome was assessed using multivariable logistic regression with adjustment for birth weight, gestational age, gender and antenatal steroids.The study sample included 88 ELBW infants. Forty percent were intubated on the first attempt and 60% required multiple intubation attempts. Death or neurodevelopmental impairment occurred in 29% of infants intubated on the first attempt, compared with 53% of infants that required multiple attempts, adjusted odds ratio 0.4 (95% confidence interval 0.1 to 1.0), P<0.05.Successful intubation on the first attempt is associated with improved neurodevelopmental outcomes among ELBW infants. This study confirms the importance of rapid establishment of a stable airway in ELBW infants requiring resuscitation after birth and has implications for personnel selection and role assignment in the delivery room.Journal of Perinatology advance online publication, 5 November 2015; doi:10.1038/jp.2015.158.
View details for DOI 10.1038/jp.2015.158
View details for PubMedID 26540244
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Perinatal Neuroprotection for Extremely Preterm Infants
AMERICAN JOURNAL OF PERINATOLOGY
2016; 33 (3): 290-296
Abstract
The preterm brain is vulnerable to injury through multiple mechanisms, from direct cerebral injury through ischemia and hemorrhage, indirect injury through inflammatory processes, and aberrations in growth and development. While prevention of preterm birth is the best neuroprotective strategy, this is not always possible. This article will review various obstetric and neonatal practices that have been shown to confer a neuroprotective effect on the developing brain.
View details for DOI 10.1055/s-0035-1571148
View details for Web of Science ID 000370589700010
View details for PubMedID 26799965
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Prenatal hydrops foetalis associated with infantile free sialic acid storage disease.
Journal of obstetrics and gynaecology
2015; 35 (8): 850-852
View details for DOI 10.3109/01443615.2015.1017558
View details for PubMedID 26076308
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Red Blood Cell Transfusion Is Not Associated with Necrotizing Enterocolitis: A Review of Consecutive Transfusions in a Tertiary Neonatal Intensive Care Unit
JOURNAL OF PEDIATRICS
2014; 165 (4): 678-682
Abstract
To explore the association between red blood cell transfusion and necrotizing enterocolitis (NEC) in a neonatal intensive care unit with liberal transfusion practices.A retrospective cohort study was conducted for all infants weighing <1500 g who received at least 1 packed red blood cell transfusion between January 2008 and June 2013 in a tertiary neonatal intensive care unit. The primary outcome was NEC, defined as Bell stage II or greater. The temporal association of NEC and transfusion was assessed using multivariate Poisson regression.The study sample included 414 very low birth weight infants who received 2889 consecutive red blood cell transfusions. Twenty-four infants (5.8%) developed NEC. Four cases of NEC occurred within 48 hours of a previous transfusion event. Using multivariate Poisson regression, we did not find evidence of a temporal association between NEC and transfusion (P = .32).There was no association between NEC and red blood cell transfusion. Our results differ from previous studies and suggest that the association between NEC and transfusion may be contextual.
View details for DOI 10.1016/j.jpeds.2014.06.012
View details for Web of Science ID 000342694200009
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Red blood cell transfusion is not associated with necrotizing enterocolitis: a review of consecutive transfusions in a tertiary neonatal intensive care unit.
journal of pediatrics
2014; 165 (4): 678-682
Abstract
To explore the association between red blood cell transfusion and necrotizing enterocolitis (NEC) in a neonatal intensive care unit with liberal transfusion practices.A retrospective cohort study was conducted for all infants weighing <1500 g who received at least 1 packed red blood cell transfusion between January 2008 and June 2013 in a tertiary neonatal intensive care unit. The primary outcome was NEC, defined as Bell stage II or greater. The temporal association of NEC and transfusion was assessed using multivariate Poisson regression.The study sample included 414 very low birth weight infants who received 2889 consecutive red blood cell transfusions. Twenty-four infants (5.8%) developed NEC. Four cases of NEC occurred within 48 hours of a previous transfusion event. Using multivariate Poisson regression, we did not find evidence of a temporal association between NEC and transfusion (P = .32).There was no association between NEC and red blood cell transfusion. Our results differ from previous studies and suggest that the association between NEC and transfusion may be contextual.
View details for DOI 10.1016/j.jpeds.2014.06.012
View details for PubMedID 25039042
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Fetal centers and the role of the neonatologist in complex fetal care.
American journal of perinatology
2014; 31 (7): 549-556
Abstract
As prenatal imaging and genetic diagnostic techniques developed, clinicians knew earlier and with greater accuracy of the extent and severity of fetal anomalies. This, coupled with an acute awareness of high rates of death or devastating neonatal morbidities in some cases, drove efforts to create innovative fetal interventions. However, with advances in neonatal quaternary care, infants with even the most complex congenital anomalies now have a substantially greater chance of survival. But many still require highly coordinated intensive care from the moment of delivery, have lengthy and complicated hospitalizations, and need ongoing complex care and services. Therefore, a new vision of complex fetal medicine must evolve, actively integrating robust multidisciplinary involvement in collaborative counseling, planning, and management. The clinical arc visualized for complex fetal patients should shift toward a comprehensive continuum of care concept-extending from fetal life, through neonatal intensive care, to childhood. The neonatologist plays a critical role in bridging this trajectory, coordinating complex processes to a smooth delivery and neonatal plan, counseling and preparing expectant mothers, and integrating many components of subspecialty input for families and other fetal team members. Neonatologists' engagement and perspective can substantively inform the clinical and strategic direction for fetal centers.
View details for DOI 10.1055/s-0034-1371709
View details for PubMedID 24705973
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Fetal Centers and the Role of the Neonatologist in Complex Fetal Care
AMERICAN JOURNAL OF PERINATOLOGY
2014; 31 (7): 549-555
View details for DOI 10.1055/s-0034-1371709
View details for Web of Science ID 000337933200002
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Predictors of bronchopulmonary dysplasia or death in premature infants with a patent ductus arteriosus.
Pediatric research
2014; 75 (4): 570-575
Abstract
Background:Preterm infants with a PDA are at risk for death or development of BPD. However, PDA treatment remains controversial. We investigated if PDA treatment and other clinical or echocardiographic (ECHO) factors were associated with the development of death or BPD.Methods:We retrospectively studied clinical and ECHO characteristics of preterm infants with birth weight <1500 g and ECHO diagnosis of a PDA. Logistic regression and classification and regression tree (CART) analyses were performed to assess variables associated with the combined outcome of death or BPD.Results:Of 187 preterm infants with a PDA, 75% were treated with indomethacin or surgery and 25% were managed conservatively. Death or BPD occurred in 80 (43%). Logistic regression found lower gestational age (OR 0.5), earlier year of birth during the study period (OR 0.9), and larger ductal diameter (OR 4.3) were associated with the decision to treat the PDA, while gestational age was the only variable associated with death or BPD (OR 0.6, 95% CI 0.5-0.8).Conclusion:Only lower gestational age and not PDA treatment or ECHO score was associated with the adverse outcome of death or BPD. Further investigation of PDA management strategies and effects on adverse outcomes of prematurity is needed.Pediatric Research (2013); doi:10.1038/pr.2013.253.
View details for DOI 10.1038/pr.2013.253
View details for PubMedID 24378897
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NIPT in a Clinical Setting: An analysis of Uptake in the First Months of Clinical Availability.
Journal of genetic counseling
2014; 23 (1): 72-78
Abstract
The objective of our study was to describe the clinical experience in offering noninvasive prenatal testing (NIPT) for aneuploidy to pregnant patients, highlighting the clinical utility, barriers to acceptance and limitations of this novel test. Data were collected from 961 patients offered NIPT from 3/1/12 to 9/30/12. Univariate and multivariate logistic regression analysis was performed. Twenty-eight percent of patients elected NIPT and 72 % declined. Women continue to elect less sensitive and less specific screening through biochemical markers and nuchal translucency. Women considering all options at average risk for aneuploidy were less likely to accept NIPT testing than women who had a risk adjustment from an ultrasound marker or routine screening test. In our multi-ethnic population, Filipina women were significantly less likely to elect NIPT compared to other ethnicities. Five percent of NIPT ordered failed analysis. Several chromosome abnormalities were detected through CVS or amniocentesis that would not have been detected by NIPT. Even though NIPT offers a non-invasive, highly sensitive and specific analysis for aneuploidy, the majority of women in our study declined this option. NIPT should be offered in the context of genetic counseling so that women understand the limitations of the testing and make an educated decision about the testing option best suited to their situation.
View details for DOI 10.1007/s10897-013-9609-z
View details for PubMedID 23723049
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Variables Influencing Pregnancy Termination Following Prenatal Diagnosis of Fetal Chromosome Abnormalities
JOURNAL OF GENETIC COUNSELING
2013; 22 (2): 238-248
Abstract
The objective of this study was to identify variables that may influence the decision to terminate or continue a pregnancy affected by a chromosome abnormality. We performed a retrospective cohort analysis of 286 pregnancies diagnosed with a chromosome abnormality following genetic counseling and prenatal diagnosis. Data obtained included procedure type, chromosome results, ethnicity, maternal age, use of fertility treatments, and uptake of genetic counseling after results, among other factors. Wilcoxon rank sum test, Fisher's exact test, and univariate and multivariate logistic regression models were used for data analysis. The overall termination rate in this study was 82.9 %. A lower likelihood to terminate was found in pregnancies with a diagnosis of a sex chromosome abnormality (OR 0.05, p < .0001), Filipina race (OR 0.10, p = .03), and uptake of second genetic counseling session (OR 0.05, p < .0001). Prior history of termination was associated with increased likelihood to terminate (OR 8.6, p = .02). Factors revealing no statistically significant association with termination included maternal age, gestational age, clinic site, fetal gender, ultrasound anomalies, reason for referral and who informed the patient. Our data affirm the complexity of the decision making process and reinforce that providers should refrain from making assumptions regarding a patient's likelihood to terminate based on factors such as maternal age, gestational age, type of procedure, or ultrasound.
View details for DOI 10.1007/s10897-012-9539-1
View details for Web of Science ID 000316291100008
View details for PubMedID 23001505
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Short-term Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease: The Era of Newer Surgical Strategies
CONGENITAL HEART DISEASE
2012; 7 (6): 544-550
Abstract
The objective of this study was to determine neurodevelopmental outcomes up to 30 months of age in a cohort of neonates requiring surgical intervention without circulatory arrest for congenital heart disease and to correlate these outcomes with characteristics detected prior to hospital discharge.An observational cohort of surviving neonates who underwent surgical intervention without circulatory arrest for congenital heart disease between 2002 and 2003 was studied at a single tertiary care institution.Thirty-five patients were followed from 4 to 6 months of age until 24-30 months of age.Neuromotor abnormalities, use of special services, and degree of developmental delay at set intervals between 4 and 30 months of age were retrospectively obtained from clinical reports. The relationship between these outcomes and clinical characteristics prior to hospital discharge was analyzed.Those with neuromotor abnormalities prior to discharge were likely to have persistent abnormalities in muscle strength, tone, and symmetry until 4-6 months of age, odds ratio 6 (1.3-29). By 24-30 months of age, motor abnormalities or developmental delay occurred in 10 of 20 infants (50%), but were no longer significantly associated with predischarge findings.Infants undergoing surgical intervention for congenital heart disease are at risk for neurodevelopmental abnormalities, which may not become apparent until months after hospital discharge. Early impairment may also resolve over time. Close developmental follow-up in this high-risk cohort of patients is warranted.
View details for DOI 10.1111/j.1747-0803.2012.00678.x
View details for Web of Science ID 000311611000011
View details for PubMedID 22676547
View details for PubMedCentralID PMC3443535
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Cerebral Autoregulation in Neonates with a Hemodynamically Significant Patent Ductus Arteriosus
JOURNAL OF PEDIATRICS
2012; 160 (6)
Abstract
Very low birth weight (VLBW) preterm infants are at risk for impaired cerebral autoregulation with pressure passive blood flow. Fluctuations in cerebral perfusion may occur in infants with a hemodynamically significant patent ductus arteriosus (hsPDA), especially during ductal closure. Our goal was to compare cerebral autoregulation using near-infrared spectroscopy in VLBW infants treated for an hsPDA.This prospective observational study enrolled 28 VLBW infants with an hsPDA diagnosed by echocardiography and 12 control VLBW infants without an hsPDA. Near-infrared spectroscopy cerebral monitoring was applied during conservative treatment, indomethacin treatment, or surgical ligation. A cerebral pressure passivity index (PPI) was calculated, and PPI differences were compared using a mixed-effects regression model. Cranial ultrasound and magnetic resonance imaging data were also assessed.Infants with surgically ligated hsPDAs were more likely to have had a greater PPI within 2 hours following ligation than were those treated with conservative management (P=.04) or indomethacin (P=.0007). These differences resolved by 6 hours after treatment.Cerebral autoregulation was better preserved after indomethacin treatment of an hsPDA compared with surgical ligation. Infants requiring surgical hsPDA ligation may be at increased risk for cerebral pressure passivity in the 6 hours following surgery.
View details for DOI 10.1016/j.jpeds.2011.11.054
View details for Web of Science ID 000304377300012
View details for PubMedID 22226574
View details for PubMedCentralID PMC3335982
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Cerebral Oxygenation during Different Treatment Strategies for a Patent Ductus Arteriosus
NEONATOLOGY
2011; 100 (3): 233-240
Abstract
Preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) are at risk for fluctuations in cerebral blood flow, but it is unclear how different hsPDA treatment strategies may affect cerebral oxygenation.To compare regional cerebral oxygen saturation (rSO(2)) as measured by near-infrared spectroscopy (NIRS) in very low birth weight (VLBW) infants with a hsPDA treated with conservative management, indomethacin, or surgical ligation.This prospective observational study enrolled 33 VLBW infants with a hsPDA diagnosed by echocardiogram and 12 control VLBW infants without a hsPDA. Infants had NIRS cerebral monitoring applied prior to conservative treatment, indomethacin, or surgical ligation. Cranial ultrasound and magnetic resonance imaging data were also collected.Infants undergoing surgical ligation had a greater time period with >20% change in rSO(2) from baseline (30%) compared to those receiving indomethacin (7.4%, p = 0.001) or control infants without a hsPDA (2.6%, p = 0.0004). NIRS measures were not associated with abnormal neuroimaging in this small cohort.These findings suggest that infants requiring surgical ligation for a hsPDA are at high risk for significant changes in cerebral oxygenation, whereas those receiving either indomethacin or conservative management maintain relatively stable cerebral oxygenation levels. Additional research is necessary to determine if NIRS monitoring identifies infants with a hsPDA at highest risk for brain injury.
View details for DOI 10.1159/000325149
View details for Web of Science ID 000295588200004
View details for PubMedID 21701212
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Inhaled Nitric Oxide for Preterm Premature Rupture of Membranes, Oligohydramnios, and Pulmonary Hypoplasia
AMERICAN JOURNAL OF PERINATOLOGY
2009; 26 (4): 317-322
Abstract
We sought to determine if inhaled nitric oxide (iNO) administered to preterm infants with premature rupture of membranes (PPROM), oligohydramnios, and pulmonary hypoplasia improved oxygenation, survival, or other clinical outcomes. Data were analyzed from infants with suspected pulmonary hypoplasia, oligohydramnios, and PPROM enrolled in the National Institute of Child Health and Development Neonatal Research Network Preemie Inhaled Nitric Oxide (PiNO) trial, where patients were randomized to receive placebo (oxygen) or iNO at 5 to 10 ppm. Outcome variables assessed were PaO (2) response, mortality, bronchopulmonary dysplasia (BPD), and severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Twelve of 449 infants in the PiNO trial met criteria. Six infants received iNO and six received placebo. The iNO group had a mean increase in PaO (2) of 39 +/- 50 mm Hg versus a mean decrease of 11 +/- 15 mm Hg in the control group. Mortality was 33% versus 67%, BPD (2/5) 40% versus (2/2) 100%, and severe IVH or PVL (1/5) 20% versus (1/2) 50% in the iNO and control groups, respectively. None of these changes were statistically significant. Review of a limited number of cases from a large multicenter trial suggests that iNO use in the setting of PPROM, oligohydramnios, and suspected pulmonary hypoplasia improves oxygenation and may decrease the rate of BPD and death without increasing severe IVH or PVL. However, the small sample size precludes definitive conclusions. Further studies are required to determine if iNO is of benefit in this specific patient population.
View details for DOI 10.1055/s-0028-1104743
View details for PubMedID 19067285
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Inflammation and NF kappa B activation is decreased by hypothermia following global cerebral ischemia
NEUROBIOLOGY OF DISEASE
2009; 33 (2): 301-312
Abstract
We previously showed that hypothermia attenuates inflammation in focal cerebral ischemia (FCI) by suppressing activating kinases of nuclear factor-kappa B (NFkappaB). Here we characterize the inflammatory response in global cerebral ischemia (GCI), and the influence of mild hypothermia. Rodents were subjected to GCI by bilateral carotid artery occlusion. The inflammatory response was accompanied by microglial activation, but not neutrophil infiltration, or blood brain barrier disruption. Mild hypothermia reduced CA1 damage, decreased microglial activation and decreased nuclear NFkappaB translocation and activation. Similar anti-inflammatory effects of hypothermia were observed in a model of pure brain inflammation that does not cause brain cell death. Primary microglial cultures subjected to oxygen glucose deprivation (OGD) or stimulated with LPS under hypothermic conditions also experienced less activation and less NFkappaB translocation. However, NFkappaB regulatory proteins were not affected by hypothermia. The inflammatory response following GCI and hypothermia's anti-inflammatory mechanism is different from that observed in FCI.
View details for DOI 10.1016/j.nbd.2008.11.001
View details for Web of Science ID 000263120500018
View details for PubMedID 19063968
View details for PubMedCentralID PMC2737398
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Neurologic events in neonates treated surgically for congenital heart disease
JOURNAL OF PERINATOLOGY
2006; 26 (4): 237-242
Abstract
The incidence of acute neurologic events prior to discharge in neonates with congenital heart disease (CHD) was determined and peri-operative characteristics predictive of a neurologic event were identified.A retrospective chart review over 1 year was conducted of infants <1 month of age with a diagnosis of CHD. Outcomes were measured by the occurrence of an acute neurologic event defined as electroencephalogram (EEG)-proven seizure activity, significant hypertonia or hypotonia, or choreoathetosis prior to hospital discharge. Stepwise logistic regression identified variables most likely to be associated with an acute neurologic event.Surgical intervention occurred in 95 infants who were admitted with a diagnosis of CHD. The survival rate was 92%. Of the survivors, 16 (17%) had an acute neurologic event, with 19% of events occurring preoperatively. Factors associated with neurologic events included an elevated nucleated red blood cell (NRBC) count, an abnormal preoperative brain imaging study, and a 5-min Apgar score <7 (P<0.05).Neonates with CHD have a significant risk of neurologic events. Preoperative brain imaging, the 5-min Apgar score, and initial serum NRBC counts may identify infants at highest risk for central nervous system injury.
View details for DOI 10.1038/sj.jp.7211459
View details for Web of Science ID 000241843200006
View details for PubMedID 16496014
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Antegrade cerebral perfusion reduces apoptotic neuronal injury in a neonatal piglet model of cardiopulmonary bypass
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2006; 131 (3): 659-665
Abstract
Neonates with congenital heart disease might require surgical repair with deep hypothermic circulatory arrest, a technique associated with adverse neurodevelopmental outcomes. Antegrade cerebral perfusion is thought to minimize ischemic brain injury, although there are no supporting experimental data. We sought to evaluate and compare the extent of neurologic injury in a neonatal piglet model of deep hypothermic circulatory arrest and antegrade cerebral perfusion.Neonatal piglets undergoing cardiopulmonary bypass were randomized to deep hypothermic circulatory arrest or antegrade cerebral perfusion for 45 minutes. Animals were killed after 6 hours of recovery, and brain tissue was stained for evidence of cellular injury and for the apoptotic markers activated caspase 3 and cytochrome c translocation from mitochondria to cytosol.Piglets from the antegrade cerebral perfusion group exhibited less apoptotic or necrotic injury (4 +/- 3 vs 29 +/- 12 cells per field, P = .03). The piglets undergoing antegrade cerebral perfusion also had less evidence of apoptosis, with fewer cells staining for activated caspase 3 (57 +/- 8 vs 93 +/- 9 cells per field, P = .001) or showing cytochrome c translocation (6 +/- 2 vs 15 +/- 4 cells per field, P = .02).The use of antegrade cerebral perfusion in place of deep hypothermic circulatory arrest reduces evidence of apoptosis and histologic injury in neonatal piglets. Neonates with congenital heart disease might benefit from antegrade cerebral perfusion during complex cardiac surgery to improve their overall neurologic outcome.
View details for DOI 10.1016/j.jtcvs.2005.09.005
View details for Web of Science ID 000235940600024
View details for PubMedID 16515920
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Development of neonatal murine microglia in vitro: Changes in response to lipopolysaccharide and ischemia-like injury
PEDIATRIC RESEARCH
2005; 57 (4): 475-480
Abstract
Hypoxic/ischemic brain injury in the neonate can activate an inflammatory cascade, which potentiates cellular injury. The role of microglia in this inflammatory response has not been studied extensively. We used an in vitro model of murine microglia to investigate changes in microglial cytokine release and injury during early development. Isolated microglia were subjected to lipopolysaccharide (LPS) activation or injury by glucose deprivation (GD), serum deprivation (SD), or combined oxygen-glucose deprivation (OGD) for varying durations. The extent and the type of cell death were determined by trypan blue, terminal deoxynucleotidyl end-nick labeling, and annexin staining. Early-culture microglia (2-3 d in purified culture) showed significantly more apoptotic cell death after SD, GD, and OGD compared with microglia maintained in culture for 14-17 d. Measurements of tumor necrosis factor-alpha (TNF-alpha) and IL-1beta in culture media demonstrated that OGD induced greater release of both TNF-alpha and IL-1beta than LPS activation, with early-culture microglia producing more TNF-alpha compared with late-culture microglia. Microglia that are cultured for a short time are more sensitive to ischemia-like injury in vitro than those that are cultured for longer durations and may contribute to worsening brain injury by increased release of inflammatory cytokines. Inhibition of microglial activation and decreasing proinflammatory cytokine release may be targets for reduction of neonatal hypoxic/ischemic brain injury.
View details for DOI 10.1203/01.PDR.0000155758.79523.44
View details for Web of Science ID 000227746600003
View details for PubMedID 15718374
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Developing microglia are sensitive to injury in an in vitro model of neonatal ischemia
KARGER. 2005: 270
View details for Web of Science ID 000230679400062
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Susceptibility to apoptosis varies with time in culture for murine neurons and astrocytes: changes in gene expression and activity
NEUROLOGICAL RESEARCH
2004; 26 (6): 632-643
Abstract
Apoptotic pathways in the brain may differ depending on cell type and developmental stage. To understand these differences, we studied several apoptotic proteins in the murine cortex and primary cultures of neurons and astrocytes of various ages in culture. We then induced apoptosis in our cultures using serum deprivation (SD) and observed changes in these apoptotic proteins. When analyzed by nuclear morphology and TUNEL staining, early cultures showed greater apoptotic injury compared with late cultures, and neuronal cultures showed greater apoptosis than astrocyte cultures. The decrease in apoptosis with development correlated best with a down-regulation of procaspase-3 and bax and decreasing caspase activation. Early culture astrocytes had higher caspase-11 levels compared with neurons. Mitogen-activated protein (MAP) kinases were also differentially expressed with activation of extracellular signal-regulated kinase (ERK) and p38 higher in early culture astrocytes and stress-activated protein kinase/C-jun N-terminal kinase (SAPK/JNK) greater in early culture neurons. However, caspase inhibitors, but not MAP kinase inhibitors reduced cell death. Our findings demonstrate that apoptosis regulatory proteins display cell type and developmentally specific expression and activation.
View details for DOI 10.1179/016164104225017587
View details for Web of Science ID 000223832200005
View details for PubMedID 15327753
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Neuroloeic events in neonates with congenital heart disease
INT PEDIATRIC RESEARCH FOUNDATION, INC. 2004: 39A
View details for Web of Science ID 000220591100238
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REMOVAL OF SIALIC-ACID FROM A GLYCOPROTEIN IN CHO CELL-CULTURE SUPERNATANT BY ACTION OF AN EXTRACELLULAR CHO CELL SIALIDASE
BIO-TECHNOLOGY
1995; 13 (7): 692-698
Abstract
We have directly tested the hypothesis that Chinese hamster ovary (CHO) cell-produced glycoproteins are subject to extracellular degradation by a sialidase endogenous to the CHO cell line. Factors important to understanding the potential for extracellular degradation are addressed including the glycoprotein specificity, subcellular source, mechanism of release, and stability of the sialidase activity. The extracellular CHO cell sialidase apparently originates from the cytosol of the cells, and is released to the cell culture supernatant as a result of damage to the cellular membrane. The extracellular sialidase is active toward a variety of CHO cell-produced glycoproteins, and can hydrolyze sialic acid from the recombinant glycoprotein gp120 in the culture supernatant. While measuring the actual degradation of a glycoprotein by extracellular CHO cell sialidase can be difficult, data presented here suggest that the level of degradation can be estimated indirectly by using a more convenient fluorescent substrate, 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid, to quantify sialidase activity. Degradation by sialidase is minimized through addition of the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid to the culture supernatant. The results in this study suggest additional potential approaches for minimizing degradation by sialidase, including isolation of a sialidase-deficient CHO cell line.
View details for Web of Science ID A1995RG36000023
View details for PubMedID 9634806