Delivery room and early postnatal management of neonates with congenital heart disease.

Advancements in prenatal detection have improved postnatal outcomes for patients with congenital heart disease (CHD). Detailed diagnosis during pregnancy allows for preparation for the delivery and immediate postnatal care for the newborns with CHD. Most CHDs do not result in hemodynamic instability at the time of birth and can be stabilized following the guidelines of the neonatal resuscitation program (NRP). Critical CHD that requires intervention immediately after birth is recommended to be delivered in facilities where immediate neonatal and cardiology care can be provided. Postnatal stabilization and resuscitation for these defects warrant deviation from the standardized NRP. For neonatal providers, knowing the diagnosis of fetal CHD allows for preparation for the anticipated instability in the delivery room. Prenatal detection fosters collaboration between fetal cardiology, cardiology specialists, obstetrics, and neonatology, improving outcomes for neonates with critical CHD.

Identifying Gaps in Resuscitation Practices Across Level-IV Neonatal Intensive Care Units.

OBJECTIVE: This study aimed to describe resuscitation practices in level-IV neonatal intensive care units (NICUs) and identify possible areas of improvement. STUDY DESIGN: This study was a cross-sectional cohort survey and conducted at the Level-IV NICUs of Children's Hospital Neonatal Consortium (CHNC). The survey was developed with consensus from resuscitation and education experts in the CHNC and pilot tested. An electronic survey was sent to individual site sponsors to determine unit demographics, resuscitation team composition, and resuscitation-related clinical practices. RESULTS: Of the sites surveyed, 33 of 34 sites responded. Unit average daily census ranged from less than 30 to greater than 100, with the majority (72%) of the sites between 30 and 75 patients. A designated code response team was utilized in 18% of NICUs, only 30% assigned roles before or during codes. The Neonatal Resuscitation Program (NRP) was the exclusive algorithm used during codes in 61% of NICUs, and 34% used a combination of NRP and the Pediatric Advanced Life Support (PALS). Most (81%) of the sites required neonatal attendings to maintain NRP training. A third of sites (36%) lacked protocols for high-acuity events. A code review process existed in 76% of participating NICUs, but only 9% of centers enter code data into a national database. CONCLUSION: There is variability among units regarding designated code team presence and composition, resuscitation algorithm, protocols for high-acuity events, and event review. These inconsistencies in resuscitation teams and practices provide an opportunity for standardization and, ultimately, improved resuscitation performance. Resources, education, and efforts could be directed to these areas to potentially impact future neonatal outcomes of the complex patients cared for in level-IV NICUs. KEY POINTS: · Resuscitation practice is variable in level-IV NICUs.. · Resuscitation algorithm training is not uniform. · Standardized protocols for high-acuity low-occurrence (HALO) events are lacking.

Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a lethal neonatal lung disease characterised by severe pulmonary hypertension, abnormal vasculature and intractable hypoxaemia. Mechanisms linking abnormal lung vasculature with severe hypoxaemia in ACD/MPV are unknown. We investigated whether bronchopulmonary anastomoses form right-to-left shunt pathways in ACD/MVP. We studied 2 infants who died of ACD/MPV postmortem with direct injections of coloured ink into the pulmonary artery, bronchial artery and pulmonary veins. Extensive histological evaluations included serial sectioning, immunostaining and 3-dimensional reconstruction demonstrated striking intrapulmonary vascular pathways linking the systemic and pulmonary circulations that bypass the alveolar capillary bed. These data support the role of prominent right-to-left intrapulmonary vascular shunt pathways in the pathophysiology of ACD/MPV.

Histologic Evidence of Intrapulmonary Bronchopulmonary Anastomotic Pathways in Neonates with Meconium Aspiration Syndrome.

We examined lung histology from 8 infants who died with meconium aspiration syndrome in order to determine the presence of intrapulmonary bronchopulmonary anastomotic pathways. Each infant required mechanical ventilation to treat hypoxemic respiratory distress. Lung histology from each infant shows evidence of prominent bronchopulmonary vascular connections.

Multicentre study protocol comparing standard NRP to deveLoped Educational Modules for Resuscitation of Neonates in the Delivery Room with Congenital Heart Disease (LEARN-CHD).

INTRODUCTION: Infants born with critical congenital heart defects (CCHDs) have unique transitional pathophysiology that often requires special resuscitation and management considerations in the delivery room (DR). While much is known about neonatal resuscitation of infants with CCHDs, current neonatal resuscitation guidelines such as the neonatal resuscitation programme (NRP) do not include algorithm modifications or education specific to CCHDs. The implementation of CCHD specific neonatal resuscitation education is further hampered by the large number of healthcare providers (HCPs) that need to be reached. Online learning modules (eLearning) may provide a solution but have not been designed or tested for this specific learning need. Our objective in this study is to design targeted eLearning modules for DR resuscitation of infants with specific CCHDs and compare HCP knowledge and team performance in simulated resuscitations among HCPs exposed to these modules compared with directed CCHD readings. METHODS AND ANALYSIS: In a prospective multicentre trial, HCP proficient in standard NRP education curriculum are randomised to either (a) directed CCHD readings or (b) CCHD eLearning modules developed by the study team. The efficacy of these modules will be evaluated using (a) individual preknowledge/postknowledge testing and (b) team-based resuscitation simulations. ETHICS AND DISSEMINATION: This study protocol is approved by nine participating sites: the Boston Children's Hospital Institutional Review Board (IRB-P00042003), University of Alberta Research Ethics Board (Pro00114424), the Children's Wisconsin IRB (1760009-1), Nationwide Children's Hospital IRB (STUDY00001518), Milwaukee Children's IRB (1760009-1) and University of Texas Southwestern IRB (STU-2021-0457) and is under review at following sites: University of Cincinnati, Children's Healthcare of Atlanta, Children's Hospital of Los Angeles and Children's Mercy-Kansas City. Study results will be disseminated to participating individuals in a lay format and presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals.

Hemoglobinopathies and stroke: strategies for prevention and treatment.

OPINION STATEMENT: Current treatment options for stroke in sickle cell disease (SCD) and thalassemia are limited. Hypercoagulation occurs in both diseases partly due to activated platelets and red blood cell dysmorphology and dysfunction, resulting in chronic anemia. This overlapping pathophysiology of the nervous system promotes the role of some common treatment modalities for these similar diseases. The current evidence suggests that chronic exchange transfusion and stem cell transplantation/bone marrow transplant (BMT) can be used in both diseases. Exchange transfusion is the mainstay of therapy of acute stroke in SCD whereas blood transfusions and hydroxyurea appear to be the most effective current treatments. However, evidence suggests that exchange transfusion should be initiated in acute ischemic stroke (AIS) and chronic transfusion continued in both diseases after AIS. Exchange transfusion can also be used acutely in AIS with thalassemia as this disorder is also associated with hypervolemia at baseline, occurring secondary to chronic anemia. The ideal length of chronic transfusions for both primary and secondary stroke prevention still needs to be better defined. Stem cell transplant or BMT is the only curative treatment for both diseases. However, timing needs to be further investigated. If transplantation is effective, it may need to be done before the child with SCD expresses disease, such as in infancy. However, in infancy, we cannot predict the severity of the phenotype in SCD with certainty, so an individual decision about transplantation is difficult to make. In thalassemia, transplantation may be effective later because vasculopathy is not the problem as in SCD. Furthermore, cerebrovascular disease occurs later in thalassemia than in SCD. Finally, aspirin is a treatment modality that also warrants further investigation. There are limited studies on the effectiveness of aspirin in SCD and thalassemias. Few studies have demonstrated clinical improvement of stroke in patients with hemoglobinopathies. Given the successful use of aspirin in the treatment and prevention of recurrent cardioembolic events in patients without hemoglobinopathies, diseases with hypercoagulability, such as SCD and thalassemia, may also benefit from the use of aspirin for treatment and prevention. However, the evidence available is based on case and retrospective studies, necessitating future larger and more valid studies to evaluate safety and effectiveness.

Special consideration in neonatal resuscitation.

Delivery room resuscitation of neonates is performed according to evidence-based neonatal resuscitation guidelines. Neonatal resuscitation guidelines focus on the resuscitation of newborns suffering from perinatal asphyxia. Special considerations are needed when resuscitating newborns in locations other than the delivery room and for newborns with congenital anomalies. In this review, we examine the resuscitation of newborns at home and in the emergency department and highlight special considerations for resuscitating newborns with specific congenital anomalies. In addition, we explore the resuscitation of neonates in the neonatal intensive care unit and discuss the potential use of pediatric advanced life support guidelines. Finally, we highlight the importance of simulation to prepare teams for neonatal resuscitations. This review aims to prepare healthcare professionals in all disciplines caring for neonates at risk for requiring resuscitation under special circumstances.

Pulseless electrical activity and asystolic cardiac arrest in infants: identifying factors that influence outcomes.

BACKGROUND: There is limited information on pulseless electrical activity (PEA)/asystolic cardiac arrest (CA) in the infant population. The aim is to describe the incidence and factors associated with outcomes in infants with PEA/asystolic CA. METHODS: Single-center retrospective chart review study of infants less than one year of age who suffer in-hospital PEA/asystolic CA from January 1 2011 to June 30 2019. The primary outcome was the return of spontaneous circulation. The secondary outcome was survival to discharge. RESULTS: CA occurred in 148 infants and PEA/asystolic was found in 38 (26%). Of those 29 (76%) achieved ROSC, and 12 (32%) survived to discharge. Infants on inotrope support or receiving longer duration of chest compressions and epinephrine had increase mortality. All infants with respiratory etiology of arrest survived to hospital discharge. CONCLUSION: PEA/asystolic CAs are uncommon. Poor prognostic indicators include the need for pre-arrest inotrope support and increased duration of chest compressions.

Training pathways and careers for neonatologists interested in cardiovascular care.

Neonatologists and neonatal-perinatal trainees continue to be invested in the cardiovascular care of the newborn, many focusing their careers in this area of expertise. Multiple formalized structured and non-structured training pathways have evolved for neonatologists caring for infants with congenital heart disease and other cardiovascular pathologies. Furthermore, the evolution of neonatal hemodynamic science over the past decade has also spawned a formal training pathway in hemodynamics consultation to enhance standard of care and guide the management of infants at risk for cardiovascular compromise. Neonatologists have also chosen to expand upon on their neonatology training with clinical and research exposure to enhance their roles in neonatal cardiovascular care, including fetal care consultation, delivery room management, and perioperative cardiac intensive care consultation. To provide insight and career guidance to interested neonatal trainees and early career physicians, this perspective article highlights several different pathways in the care of neonates with cardiovascular disease.

Predicting treatment of pulmonary hypertension at discharge in infants with congenital diaphragmatic hernia.

OBJECTIVE: To predict pulmonary hypertension (PH) therapy at discharge in a large multicenter cohort of infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: Six-year linked records from Children's Hospitals Neonatal Database and Pediatric Health Information System were used; patients whose diaphragmatic hernia was repaired before admission or referral, who were previously home before admission or referral, and non-survivors were excluded. The primary outcome was the use of PH medications at discharge and the secondary outcome was an inter-center variation of therapies during inpatient utilization. Clinical factors were used to develop a multivariable equation randomly applied to 80% cohort; validated in the remaining 20% infants. RESULTS: A total of 831 infants with CDH from 23 centers were analyzed. Overall, 11.6% of survivors were discharged on PH medication. Center, duration of mechanical ventilation, and duration of inhaled nitric oxide were associated with the use of PH medication at discharge. This model performed well in the validation cohort area under the receiver operating characteristic curve of 0.9, goodness-of-fit χ2, p = 0.17. CONCLUSIONS: Clinical variables can predict the need for long-term PH medication after NICU hospitalization in surviving infants with CDH. This information may be useful to educate families and guide the development of clinical guidelines.

Cerebral Blood Flow Monitoring in High-Risk Fetal and Neonatal Populations.

Cerebrovascular pressure autoregulation promotes stable cerebral blood flow (CBF) across a range of arterial blood pressures. Cerebral autoregulation (CA) is a developmental process that reaches maturity around term gestation and can be monitored prenatally with both Doppler ultrasound and magnetic resonance imaging (MRI) techniques. Postnatally, there are key advantages and limitations to assessing CA with Doppler ultrasound, MRI, and near-infrared spectroscopy. Here we review these CBF monitoring techniques as well as their application to both fetal and neonatal populations at risk of perturbations in CBF. Specifically, we discuss CBF monitoring in fetuses with intrauterine growth restriction, anemia, congenital heart disease, neonates born preterm and those with hypoxic-ischemic encephalopathy. We conclude the review with insights into the future directions in this field with an emphasis on collaborative science and precision medicine approaches.

Cardiopulmonary resuscitation in quaternary neonatal intensive care units: a multicenter study.

BACKGROUND: The reported incidence of cardiopulmonary resuscitation (CPR) in quaternary NICU is approximately 10-times higher than in the delivery room. However, the etiologies and outcomes of CPR in quaternary NICUs are poorly understood. We hypothesized that demographic characteristics, diagnoses, interventions, and arrest etiologies would be associated with survival to discharge after CPR. METHODS: Multicenter retrospective cohort study of four quaternary NICUs over six years (2011-2016). Demographics, resuscitation event data, and post-arrest outcomes were analyzed. The primary outcome was survival to discharge. RESULTS: Of 17,358 patients admitted to four NICUs, 200 (1.1%) experienced a CPR event, and 45.5% of those survived to discharge. Acute respiratory compromise leading to cardiopulmonary arrest occurred in 182 (91%) of the CPR events. Most neonates requiring CPR were on mechanical ventilation (79%) and had central venous access (90%) at the time of arrest. Treatments at the time of the arrest associated with decreased survival to discharge included mechanical ventilation, antibiotics, or vasopressor therapy (p < 0.01). Etiologies of arrest associated with decreased survival to discharge included multisystem organ failure, septic shock, and pneumothorax (p < 0.05). Longer duration of CPR was associated with decreased survival to discharge. The odds of surviving to discharge decreased for infants who had a primarily cardiac arrest and for infants who received epinephrine during the arrest. CONCLUSION: Approximately 1% of neonates admitted to quaternary NICUs require CPR. The most common etiology of arrest is acute respiratory compromise on a ventilator. CPR events with respiratory etiology have a favorable outcome as compared to non-respiratory causes.

Treatment of pulmonary hypertension during initial hospitalization in a multicenter cohort of infants with congenital diaphragmatic hernia (CDH).

OBJECTIVE: Describe inpatient pulmonary hypertension (PH) treatment and factors associated with therapy at discharge in a multicenter cohort of infants with CDH. METHODS: Six years linked records from Children's Hospitals Neonatal Database and Pediatric Health Information System were used to describe associations between prenatal/perinatal factors, clinical outcomes, echocardiographic findings and PH medications (PHM), during hospitalization and at discharge. RESULTS: Of 1106 CDH infants from 23 centers, 62.8% of infants received PHM, and 11.6% of survivors were discharged on PHM. Survivors discharged on PHM more frequently had intrathoracic liver, small for gestational age, and low 5 min APGARs compared with those discharged without PHM (p < 0.0001). Nearly one-third of infants discharged without PHM had PH on last inpatient echo. CONCLUSIONS: PH medication use is common in CDH. Identification of infants at risk for persistent PH may impact ongoing management. Post-discharge follow-up of all CDH infants with echocardiographic evidence of PH is warranted.

A single-nucleotide polymorphism (-670) of the maternal Fas gene is associated with intrauterine growth restriction.

OBJECTIVE: We sought to determine whether the Fas (-670) single-nucleotide polymorphism is associated with intrauterine growth restriction. STUDY DESIGN: Twenty-seven pregnant women with intrauterine growth restriction in the absence of preeclampsia and 50 pregnant women with uncomplicated pregnancies were studied. DNA was extracted from maternal and infant buccal smears and allelic discrimination was performed for Fas (-670). Student t test, chi2, and z tests were used. RESULTS: There were no differences in maternal age, race, or parity between the intrauterine growth restriction and control patients. Mothers of intrauterine growth restriction infants had a significantly different genotype distribution for this single nucleotide polymorphism, and for the ratio of GG genotype (GG, AA: 0.41, 0.18 maternal intrauterine growth restriction; 0.14, 0.32 controls; respectively, P=.03). These genotype differences were significantly different in white, but not black mothers with intrauterine growth restriction (P=.03, and .3; respectively). In contrast, no differences were found in infants' Fas (-670) single-nucleotide polymorphism genotypes. CONCLUSION: This study demonstrates an association between the maternal Fas (-670) single-nucleotide polymorphism and the development of intrauterine growth restriction.

Noninvasive Ventilation in the Delivery Room for the Preterm Infant.

A decade ago, preterm infants were prophylactically intubated and mechanically ventilated starting in the delivery room; however, now the shift is toward maintaining even the smallest of neonates on noninvasive respiratory support. The resuscitation of very low gestational age neonates continues to push the boundaries of neonatal care, as the events that transpire during the golden minutes right after birth prove ever more important for determining long-term neurodevelopmental outcomes. Continuous positive airway pressure (CPAP) remains the most important mode of noninvasive respiratory support for the preterm infant to establish and maintain functional residual capacity and decrease ventilation/perfusion mismatch. However, the majority of extremely low gestational age infants require face mask positive pressure ventilation during initial stabilization before receiving CPAP. Effectiveness of face mask positive pressure ventilation depends on the ability to detect and overcome mask leak and airway obstruction. In this review, the current evidence on devices and techniques of noninvasive ventilation in the delivery room are discussed.

Brain imaging and electrophysiology biomarkers: is there a role in poverty and education outcome research?

BACKGROUND: Prekindergarten educational interventions represent a popular approach to improving educational outcomes, especially in children from poor households. Children from lower socioeconomic groups are at increased risk for delays in cognitive development that are important for school success. These delays, which may stem from stress associated with poverty, often develop before kindergarten. Early interventions have been proposed, but there is a need for more information on effectiveness. By assessing socioeconomic differences in brain structure and function, we may better be able to track the neurobiologic basis underlying children's cognitive improvement. METHODS: We conducted a review of the neuroimaging and electrophysiology literature to evaluate what is known about differences in brain structure and function as assessed by magnetic resonance imaging and electrophysiology and evoked response potentials among children from poor and nonpoor households. RESULTS: Differences in lower socioeconomic groups were found in functional magnetic resonance imaging, diffusion tensor imaging, and volumetric magnetic resonance imaging as well as electroencephalography and evoked response potentials compared with higher socioeconomic groups. CONCLUSIONS: The findings suggest a number of neurobiologic correlates for cognitive delays in children who are poor. Given this, we speculate that magnetic resonance imaging and electrophysiology parameters might be useful as biomarkers, after more research, for establishing the effectiveness of specific prekindergarten educational interventions. At the very least, we suggest that to level the playing field in educational outcomes, it may be helpful to foster communication and collaboration among all professionals involved in the care and education of children.

Young Patients With Diabetes Have Decreased Cerebrovascular Reactivity Under Hypercapneic Conditions.

OBJECTIVE: Adult diabetic patients have an abnormal cerebrovascular response to hypercapnia, but there are few studies focused on diabetes mellitus type 1 and cerebral blood flow in pediatric or adolescent patients. We hypothesize that young patients with diabetes exhibit a different response to hypercapnia than normal control counterparts. METHODS: Using transcranial Doppler techniques, we compared young diabetic patients with healthy controls by measuring cerebral blood velocity before and during carbon dioxide challenge. RESULTS: Subjects with diabetes had decreased cerebral blood velocity reactivity when compared with the control group (P = 0.005). CONCLUSION: Our results suggest cerebrovascular dysfunction in diabetic patients beginning at an early age. The possibility of long-term implications for cerebrovascular disease demonstrates the need for further studies in the pediatric and adolescent diabetic population to better understand this prevalent condition.

Late-developing rostral ventrolateral medullary surface responses to cardiovascular challenges during sleep.

Pressor and depressor manipulations are usually followed by compensatory autonomic, respiratory, somatomotor or arousal responses that limit the extent of blood pressure change. Of neural sites participating in blood pressure control, the rostral ventrolateral medullary surface (RVLMS) contributes significantly, and exhibits rapid-onset overall activity declines and increases to pressor and depressor challenges, respectively. In addition, longer-latency physiological responses develop that further compensate for the homeostatic challenge; some of these later influences are associated with arousal. Late-developing RVLMS activity changes accompanying physiologic responses that normalize a cardiovascular manipulation may provide insights into compensatory neural mechanisms during sleep following sustained or extreme blood pressure changes. We used intrinsic optical imaging procedures in seven unanesthetized adult cats to examine RVLMS and control site responses to pressor and depressor challenges during sleep that resulted in somatomotor, respiratory, heart rate or electroencephalographic indications of late-developing (post-baroreflex) compensatory responses. Although initial RVLMS responses differed in direction between pressor and depressor challenges, neural activity increased later in both manipulations, coincident with overt physiological manifestations indicative of compensatory responses, including arousal. Arousal occurred in 44% of blood pressure challenges. Comparable late-developing neural activity increases were not apparent in control sites. Latencies of late RVLMS responses during rapid eye movement sleep were significantly longer than in quiet sleep for pressor challenges. The pattern of the late RVLMS responses was not dependent on arousal, and suggests that the RVLMS participates in both the early baroreflex response and the late-developing compensatory actions.