Management of the Preterm Infant with Congenital Heart Disease CLINICS IN PERINATOLOGY 2016; 43 (1): 157-?
Management of the Preterm Infant with Congenital Heart Disease. Clinics in perinatology 2016; 43 (1): 157-171
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
Failed endotracheal intubation and adverse outcomes among extremely low birth weight infants. Journal of perinatology 2016; 36 (2): 112-115
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 1000g 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 5min of life or if intubation was attempted during the first 10min 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
Perinatal Neuroprotection for Extremely Preterm Infants AMERICAN JOURNAL OF PERINATOLOGY 2016; 33 (3): 290-296
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
Prenatal hydrops foetalis associated with infantile free sialic acid storage disease. Journal of obstetrics and gynaecology 2015; 35 (8): 850-852
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
Fetal centers and the role of the neonatologist in complex fetal care. American journal of perinatology 2014; 31 (7): 549-556
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
Fetal Centers and the Role of the Neonatologist in Complex Fetal Care AMERICAN JOURNAL OF PERINATOLOGY 2014; 31 (7): 549-555
Predictors of bronchopulmonary dysplasia or death in premature infants with a patent ductus arteriosus PEDIATRIC RESEARCH 2014; 75 (4): 570-575
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 <1500g 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 Web of Science ID 000333139400014
View details for PubMedID 24378897
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
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 Web of Science ID 000330956200010
Variables Influencing Pregnancy Termination Following Prenatal Diagnosis of Fetal Chromosome Abnormalities JOURNAL OF GENETIC COUNSELING 2013; 22 (2): 238-248
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
Short-term Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease: The Era of Newer Surgical Strategies CONGENITAL HEART DISEASE 2012; 7 (6): 544-550
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
Cerebral Autoregulation in Neonates with a Hemodynamically Significant Patent Ductus Arteriosus JOURNAL OF PEDIATRICS 2012; 160 (6)
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
Cerebral Oxygenation during Different Treatment Strategies for a Patent Ductus Arteriosus NEONATOLOGY 2011; 100 (3): 233-240
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
Inhaled Nitric Oxide for Preterm Premature Rupture of Membranes, Oligohydramnios, and Pulmonary Hypoplasia AMERICAN JOURNAL OF PERINATOLOGY 2009; 26 (4): 317-322
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 Web of Science ID 000264506400012
View details for PubMedID 19067285
Inflammation and NF kappa B activation is decreased by hypothermia following global cerebral ischemia NEUROBIOLOGY OF DISEASE 2009; 33 (2): 301-312
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
Neurologic events in neonates treated surgically for congenital heart disease JOURNAL OF PERINATOLOGY 2006; 26 (4): 237-242
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
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
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
Development of neonatal murine microglia in vitro: Changes in response to lipopolysaccharide and ischemia-like injury PEDIATRIC RESEARCH 2005; 57 (4): 475-480
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
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
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
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
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