General movement assessment efficacy for assessment of nervous system integrity in children after hypoxic-ischemic encephalopathy in middle income countries.

BACKGROUND: Many infants who survive hypoxic-ischemic encephalopathy (HIE) face long-term complications like epilepsy, cerebral palsy, and developmental delays. Detecting and forecasting developmental issues in high-risk infants is critical. AIM: This study aims to assess the effectiveness of standardized General Movements Assessment (GMA) and Hammersmith Infant Neurological Examinations (HINE) in identifying nervous system damage and predicting neurological outcomes in infants with HIE. DESIGN: Prospective. SUBJECTS AND MEASURES: We examined full-term newborns with perinatal asphyxia, classifying them as Grade 2 HIE according to Sarnat and Sarnat. The study included 31 infants, with 14 (45.2 %) receiving therapeutic hypothermia (Group 1) and 17 (54.8 %) not (Group 2). We evaluated general movements during writhing and fidgety phases and conducted neurological assessments using the HINE. RESULTS: All infants exhibited cramped-synchronized - like movements, leading to cerebral palsy (CP) diagnosis. Three children in Group 1 and four in Group 2 lacked fidgety movements. During active movements, HINE and GMA showed high sensitivity and specificity, reaching 96 % and 100 % for all children. The ROC curve's area under the curve (AUC) was 0.978. CONCLUSION: Our study affirms HINE and GMA as effective tools for predicting CP in HIE-affected children. GMA exhibits higher sensitivity and specificity during fidgety movements. However, study limitations include a small sample size and data from a single medical institution, necessitating further research.

Tackling equitable coverage and quality of care for neonates in hospitals: a pre-post assessment on asphyxia interventions in Mesoamerica.

BACKGROUND: Intrapartum-related hypoxic events, or birth asphyxia, causes one-fourth of neonatal deaths globally and in Mesoamerica. Multidimensional care for asphyxia must be implemented to ensure timely and effective care of newborns. Salud Mesoamérica Initiative (SMI) is a performance-based program seeking to improve maternal and child health for low-income areas of Central America. Our objective was to assess the impact of SMI on neonatal asphyxia care in health centers and hospitals in the region. METHODS: A pre-post design. Two hundred forty-eight cases of asphyxia were randomly selected from medical records at baseline (2011-2013) and at second-phase follow-up (2017-2018) in Mexico (state of Chiapas), Honduras, Nicaragua, and Guatemala as part of the SMI Initiative evaluation. A facility survey was conducted to assess quality of health care and the management of asphyxia. The primary outcome was coverage of multidimensional care for the management of asphyxia, consisting of a skilled provider presence at birth, immediate assessment, initial stabilization, and appropriate resuscitation measures of the newborn. Data were analyzed using multivariable logistic regression. RESULTS: Management of asphyxia improved significantly after SMI. Proper care of asphyxia in intervention areas was better (OR = 2.4; 95% CI = 1.3-4.6) compared to baseline. Additionally, multidimensional care was significantly higher in Honduras (OR = 4.0; 95% CI = 1.4-12.0) than in Mexico. Of the four multidimensional care components, resuscitation showed the greatest progress by follow-up (65.7%) compared to baseline (38.7%). CONCLUSION: SMI improved the care for neonatal asphyxia management across all levels of health care in all countries. Our findings show that proper training and adequate supplies can improve health outcomes in low-income communities. SMI provides a model for improving health care in other settings.

Eficacia y seguridad de hipotermia terapéutica de cuerpo completo con mantas térmicas en recien nacidos de 35 semanas o más con asfixia perinatal y encefalopatía hipóxico-isquémica moderada o severa / Efficacy and safety of whole body therapeutic hypothermia with heating blankets in newborns 35 weeks or older with perinatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy

INTRODUCCIÓN: El presente documento de evaluación de tecnología sanitaria (ETS) expone la evaluación de la eficacia y seguridad del equipo de hipotermia terapéutica de cuerpo completo (HTCC) con mantas térmicas en comparación al tratamiento de soporte estándar en la unidad de cuidados intensivos neonatales (UCIN) en recién nacidos de 35 semanas o más con asfixia perinatal (AP) y encefalopatía hipóxico-isquémica (EHI) moderada o severa sin malformaciones congénitas mayores, cromosomopatías incompatibles con la vida, retardo en crecimiento intrauterino severo (<1,8 kg), patologías quirúrgicas severas, o con criterios de severidad (bradicardia mantenida, midriasis paralítica, ausencia de reflejo corneal). La encefalopatía neonatal es un estado de alteración de la función neurológica del recién nacido. Esta patología se asocia a convulsiones y dificultad para iniciar o mantener la respiración; acarreando una alta morbilidad y mortalidad neonatal. La encefalopatía hipóxico-isquémica (EHI), producida por un cuadro de asfixia perinatal (AP), es uno de los principales subtipos de encefalopatía neonatal. En el Perú, un informe de la Dirección de Epidemiología del Ministerio de Salud reportó que la AP fue la tercera causa de muerte neonatal entre los años 2011 y 2012. Además, reportes del servicio de neonatología del Hospital Nacional Edgardo Rebagliati Martins (HNERM) del periodo 2015 - 2016 estimaron la incidencia de EHI en 2.5 casos por cada 1000 nacidos vivos. Diversos estudios han reportado que la neuroprotección mediante la hipotermia terapéutica (HT) disminuye la morbilidad y mortalidad en neonatos con EHI moderada o severa. Para la inducción de HT se utilizan, principalmente, dos tecnologías: 1) la HT de cuerpo completo (HTCC) y 2) la HT selectiva de cabeza (HTSC). Las unidades de cuidados intensivos neonatales (UCIN) de EsSalud brindan terapia de soporte a los recién nacidos con EHI consistente en monitoreo de signos vitales y atención oportuna frente a disfunciones orgánicas, además de reducción de la temperatura mediante el apagado de calefactor en la incubadora, pero no cuentan con equipos específicos que aseguren que el neonato alcance temperaturas de enfriamiento óptimas. Por ello, los especialistas en neonatología del HNERM solicitan la incorporación de la tecnología de HTCC con mantas térmicas con la finalidad de disminuir la mortalidad y discapacidad severa de los neonatos con EHI moderada o severa. En este sentido, el objetivo del presente dictamen preliminar fue evaluar la eficacia y seguridad de la hipotermia terapéutica de cuerpo completo con mantas térmicas en recién nacidos de 35 semanas o más con asfixia perinatal y encefalopatía hipóxico-isquémica moderada o severa. METODOLOGÍA: Se realizó una búsqueda sistemática para identificar la evidencia disponible a abril de 2021 sobre la eficacia y seguridad del procedimiento de hipotermia terapéutica de cuerpo completo en recién nacidos de 35 semanas o más con asfixia neonatal y encefalopatía hipóxico-isquémica moderada o severa. Se indagó en las bases de datos PubMed, Cochrane Library y LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud) y se creó una alerta semanas en PubMed que informara si surgiera nueva evidencia sobre el tema. Adicionalmente, se realizó una búsqueda manual de literatura gris mediante el motor de búsqueda Google. Se buscaron GPC y ETS que pudieran haber sido omitidas en la revisión sistemática por no encontrarse indixadas en las bases de datos consultadas. De igual forma, se consultaron las páginas oficiales de grupos conocidos por realizar ETS y GPC que incluyó el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institut für Qualitát und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) y la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), además de sociedades especializadas en manejo de pacientes pediátricos con patologías perinatales (sociedad británica de medicina perinatal (BAPM), la asociación americana del corazón, y la sociedad canadiense de pediatría). RESULTADOS: La presente sinopsis describe la evidencia disponible sobre la eficacia y seguridad de la HTCC con mantas térmicas en recién nacidos de 35 semanas o más con AP y EHI moderada o severa, según el tipo de publicación. CONCLUSIONES: El objetivo del presente dictamen preliminar es evaluar la eficacia y seguridad de la hipotermia terapéutica de cuerpo completo con mantas térmicas en recién nacidos de 35 semanas o más de gestación, con asfixia perinatal y encefalopatía hipóxico-isquémica moderada o severa. Se identificaron seis GPC American Heart Association (AHA), 2020; Ministerio de Salud Pública del Ecuador (MSP), 2019; Canadian Paediatric Society (CPS), 2018; Instituto Mexicano del Seguro Social (IMSS), 2017; Ministerio de Sanidad, Servicio Social e Igualdad de España (MSSSI), 2015; y Ministerio de Salud y Protección Social de Colombia (MinSalud), 2013) y siete publicaciones de cuatro ensayos clínicos aleatorizados (ECA) (HELIX: Thayyil et al., 2021; TOBY: Azzopardi et al., 2014, 2009; NICHD: Shankaran et al., 2012, 2008, 2005; y neo.nEURO.network: Simbruner et al., 2010). No existe evidencia de una mayor eficacia en el uso de HTCC frente a la HTSC. Pese a ello, en centros asistenciales que no han implementado aún un método de HT, las recomendaciones de las GPC indican que debería implementarse equipos de HTCC debido a su facilidad de uso, menor costo y facilidad de acceso para la utilización de otros equipos como el electroencefalograma. Entre las GPC, existe un consenso en que la aplicación de HTCC debe realizarse bajo protocolos similares a los utilizados en los principales ECA. La eficacia de la HTCC con mantas térmicas en infantes de 36 semanas o más de gestación con EIH moderada a severa es consistente en cuanto a la reducción de morbilidad, pero no en mortalidad. Los ECA más grandes en el tema han reportado beneficios clínicos, tanto en indicadores de desarrollo mental y psicomotor, como en ocurrencia de parálisis cerebral a los 18 - 22 meses y 6 - 7 años de vida. Pese a que uno de los ECA evaluados (HELIX) reporta mayor riesgo de muerte y ocurrencia de eventos adversos en los pacientes intervenidos con HTCC, esto se puede explicar debido a factores poblacionales que modificaron el efecto de la intervención. Por lo expuesto, el IETSI aprueba el uso de equipos de HTCC con mantas térmicas en recién nacidos de 36 semanas o más de edad gestacional, con AP y EHI moderada o severa, según lo establecido en el Anexo N°1. Debido a la falta de evidencia, no se aprueba su uso en recién nacidos con menos de 36 semanas de edad gestacional. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación.

Hypothermic treatment for neonatal asphyxia in low-resource settings using phase-changing material-An easy to use and low-cost method.

AIM: To evaluate whether phase-changing material can be used for therapeutic hypothermia of asphyxiated newborns in low-resource settings. METHODS: Prospective interventional study of asphyxiated term infants fulfilling criteria for hypothermia treatment at Vietnam National Children's Hospital from September 2014 to September 2016. Hypothermia was induced within 6 hours after birth and maintained for 72 hours by a phase-changing material mattress with melting point of 32°C. Rectal temperature was continuously measured, and deviations from target temperature range 33.5-34.5°C were recorded. RESULTS: In total 52 infants (mean gestational age 39.3 ± 1.1 weeks) included and cooled, the median temperature at initiation of cooling was 35.3 (IQR 34.5-35.9)°C. The median time to reach target temperature was 2.5 (IQR 2-3) hours. The mean temperature during the cooling phase was 33.95 ± 0.2°C. Throughout the cooling phase, the target temperature range (33.5-34.5°C) was maintained more than 80% of the time. Rate of rewarming was 0.5 ± 0.14°C/hour. CONCLUSION: Phase-changing material can be used as an effective cooling method. Though not a servo-controlled system, it is easy to induce hypothermia, maintain target temperature and rewarm infants in a slow and controlled manner without need for frequent changes and minimum risk of skin injury.

Hemodynamic Instability in Hypoxic Ischemic Encephalopathy: More Than Just Brain Injury-Understanding Physiology, Assessment, and Management.

Hypoxic-ischemic encephalopathy (HIE) can have both transient and long-lasting effects on the neonate, including neurologic, renal, cardiac, hepatic, and hematologic. Both the disease process and the treatment option of therapeutic hypothermia can result in hemodynamic instability. Understanding the effects of HIE on the neonatal myocardium, pulmonary vascular bed, and the cardiac dysfunction that can occur is key to managing infants with HIE. This article focuses on causes of hemodynamic instability in neonates following perinatal asphyxia and how to recognize hemodynamic compromise. It reviews the underlying pathophysiology and associated management strategies to improve hemodynamics and potentially improve outcomes.

Impact of a mobile application for heart rate assessment in simulated neonatal resuscitation: a randomised controlled cross-over study.

BACKGROUND: Clinical assessment of newborn heart rate (HR) at birth has been reported to be inaccurate. NeoTapAdvancedSupport (NeoTapAS) is a free-of-charge mobile application that showed good accuracy in HR estimation. This study aimed to evaluate the impact of NeoTapAS on timing of HR communication and resuscitation interventions. METHODS: This was a randomised controlled cross-over (AB/BA) study evaluating HR assessment using auscultation plus NeoTapAS compared with auscultation plus mental computation in a high-fidelity simulated newborn resuscitation scenario. Twenty teams each including three paediatric residents were randomly assigned to AB or BA arms. The primary outcome was the timing of the first HR communication. Secondary outcomes included the timing of the following four HR communications and the timing of resuscitation interventions (positive pressure ventilation, chest compressions, intubation and administration of first dose of epinephrine). RESULTS: NeoTapAS reduced the time to the first HR communication (mean difference -13 s, 95% CI -23 to -4; p=0.009), and the time of initiation of chest compressions (mean difference -68 s, 95% CI -116 to -18; p=0.01) and administration of epinephrine (mean difference -76 s, 95% CI -115 to -37; p=0.0004) compared with mental computation. CONCLUSIONS: In a neonatal resuscitation simulated scenario, NeoTapAS reduced the time to the first HR communication and the time of initiation of chest compressions and administration of epinephrine compared with mental computation. This app can be especially useful in settings with limited availability of monitoring equipment, but further studies in clinical scenarios are warranted. TRIAL REGISTRATION NUMBER: NCT03730025.

Neonatal resuscitation using a supraglottic airway device for improved mortality and morbidity outcomes in a low-income country: study protocol for a randomized trial.

BACKGROUND: Intrapartum-related death is the third leading cause of under-5 mortality. Effective ventilation during neonatal resuscitation has the potential to reduce 40% of these deaths. Face-mask ventilation performed by midwives is globally the most common method of resuscitating neonates. It requires considerable operator skills and continuous training because of its complexity. The i-gel® is a cuffless supraglottic airway which is easy to insert and provides an efficient seal that prevents air leakage; it has the potential to enhance performance in neonatal resuscitation. A pilot study in Uganda demonstrated that midwives could safely resuscitate newborns with the i-gel® after a short training session. The aim of the present trial is to investigate whether the use of a cuffless supraglottic airway device compared with face-mask ventilation during neonatal resuscitation can reduce mortality and morbidity in asphyxiated neonates. METHODS: A randomized phase III open-label superiority controlled clinical trial will be conducted at Mulago Hospital, Kampala, Uganda, in asphyxiated neonates in the delivery units. Prior to the intervention, health staff performing resuscitation will receive training in accordance with the Helping Babies Breathe curriculum with a special module for training on supraglottic airway insertion. A total of 1150 to 1240 babies (depending on cluster size) that need positive pressure ventilation and that have an expected gestational age of more than 34 weeks and an expected birth weight of more than 2000 g will be ventilated by daily unmasked randomization with a supraglottic airway device (i-gel®) (intervention group) or with a face mask (control group). The primary outcome will be a composite outcome of 7-day mortality and admission to neonatal intensive care unit (NICU) with neonatal encephalopathy. DISCUSSION: Although indications for the beneficial effect of a supraglottic airway device in the context of neonatal resuscitation exist, so far no large studies powered to assess mortality and morbidity have been carried out. We hypothesize that effective ventilation will be easier to achieve with a supraglottic airway device than with a face mask, decreasing early neonatal mortality and brain injury from neonatal encephalopathy. The findings of this trial will be important for low and middle-resource settings where the majority of intrapartum-related events occur. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT03133572 . Registered April 28, 2017.

Hypothermia for perinatal asphyxia: trial-based resource use and costs at 6-7 years.

OBJECTIVE: To assess the impact of hypothermic neural rescue for perinatal asphyxia at birth on healthcare costs of survivors aged 6-7 years, and to quantify the relationship between costs and overall disability levels. DESIGN: 6-7 years follow-up of surviving children from the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial. SETTING: Community study including a single parental questionnaire to collect information on children's healthcare resource use. PATIENTS: 130 UK children (63 in the control group, 67 in the hypothermia group) whose parents consented and returned the questionnaire. INTERVENTIONS: Intensive care with cooling of the body to 33.5°C for 72 hours or intensive care alone. MAIN OUTCOME MEASURES: Healthcare resource usage and costs over the preceding 6 months. RESULTS: At 6-7 years, mean (SE) healthcare costs per child were £1543 (£361) in the hypothermia group and £2549 (£812) in the control group, giving a saving of -£1005 (95% CI -£2734 to £724). Greater levels of overall disability were associated with progressively higher costs, and more parents in the hypothermia group were employed (64% vs 47%). Results were sensitive to outlying observations. CONCLUSIONS: Cost results although not significant favoured moderate hypothermia and so complement the clinical results of the TOBY Children study. Estimates were however sensitive to the care requirements of two seriously ill children in the control group. A quantification of the relationship between costs and levels of disability experienced will be useful to healthcare professionals, policy makers and health economists contemplating the long-term economic consequences of perinatal asphyxia and hypothermic neural rescue. TRIAL REGISTRATION NUMBER: This study reports on the follow-up of the TOBY clinical trial: ClinicalTrials. gov number NCT01092637.

Evaluating services for perinatal asphyxia and low birth weight at two hospitals in Ghana: a micro-costing analysis.

BACKGROUND: Neonatal mortality has been decreasing slowly in Ghana despite investments in maternal-newborn services. Although community-based interventions are effective in reducing newborn deaths, hospital-based services provide better health outcomes. OBJECTIVE: To examine the process and cost of hospital-based services for perinatal asphyxia and low birth weight/preterm at a district and a regional level referral hospital in Ghana. METHODS: A cross-sectional study was conducted at 2 hospitals in Greater Accra Region during May-July 2016. Term infants with perinatal asphyxia and low birth weight/preterm infants referred for special care within 24hours after birth were eligible. Time-driven activity-based costing (TDABC) approach was used to examine the process and cost of all activities in the full cycle of care from admission until discharge or death. Costs were analysed from health provider's perspective. RESULTS: Sixty-two newborns (perinatal asphyxia 27, low-birth-weight/preterm 35) were enrolled. Cost of care was proportionately related to length-of-stay. Personnel costs constituted over 95% of direct costs, and all resources including personnel, equipment and supplies were overstretched. CONCLUSION: TDABC analysis revealed gaps in the organization, process and financing of neonatal services that undermined the quality of care for hospitalized newborns. The study provides baseline cost data for future cost-effectiveness studies on neonatal services in Ghana. FUNDING: Authors received no external funding for the study.

Parental costs for in-patient neonatal services for perinatal asphyxia and low birth weight in Ghana.

The major causes of newborn deaths in sub-Saharan Africa are well-known and countries are gradually implementing evidence-based interventions and strategies to reduce these deaths. Facility-based care provides the best outcome for sick and or small babies; however, little is known about the cost and burden of hospital-based neonatal services on parents in West Africa, the sub-region with the highest global neonatal death burden. To estimate the actual costs borne by parents of newborns hospitalised with birth-associated brain injury (perinatal asphyxia) and preterm/low birth weight, this study examined economic costs using micro-costing bottom-up approach in two referral hospitals operating under the nationwide social health insurance scheme in an urban setting in Ghana. We prospectively assessed the process of care and parental economic costs for 25 out of 159 cases of perinatal asphyxia and 33 out of 337 cases of preterm/low birth weight admitted to hospital on the day of birth over a 3 month period. Results showed that medical-related costs accounted for 66.1% (IQR 49% - 81%) of out-of-pocket payments irrespective of health insurance status. On average, families spent 8.1% and 9.1% of their annual income on acute care for preterm/LBW and perinatal asphyxia respectively. The mean out-of-pocket expenditure for preterm/LBW was $147.6 (median $101.8) and for perinatal asphyxia was $132.3 (median $124). The study revealed important gaps in the financing and organization of health service delivery that may impact the quality of care for hospitalised newborns. It also provides information for reviewing complementary health financing options for newborn services and further economic evaluations.

Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.

OBJECTIVE: To test the non-inferiority of an alternative to the Apgar score. STUDY DESIGN: The Neonatal Resuscitation and Adaptation Score (NRAS) was recorded in parallel to the Apgar score by a resuscitation team at deliveries. Correlation between the systems was assessed, as well as the predictive ability of NRAS and Apgar scores for mortality or short-term morbidities. RESULTS: A total of 340 infants were in the study group. The two scores correlated strongly (r = 0.87 and 0.83 at 1 and 5 min, respectively). Those needing ventilation at 48 h of life had a 5-min NRAS < 7 in 23/26 vs Apgar < 7 (23/36, p = 0.001). A low (0-3) 1-min NRAS score was more predictive of death, 53% vs 17%, p = 0.0065. CONCLUSIONS: NRAS correlates with Apgar status assessment, and identifies newborns who die or may require further care better than the Apgar score.

Comparison of Two Low-cost Methods of Cooling Neonates with Hypoxic Ischemic Encephalopathy.

Background: Several low-cost methods are used in resource-limited settings to provide therapeutic hypothermia in asphyxiated neonates. There is inadequate data about their efficacy and safety. This is a retrospective study comparing two low-cost cooling methods-frozen gel packs (FGP) and phase changing material (PCM). Results: There were 23 babies in FGP and 45 babies in the PCM group. Induction time was significantly shorter with FGP than PCM (45 vs. 90 minutes; p -value < 0.001). Proportion of temperature readings outside the target range was significantly higher (9.8% vs. 3.8%; p -value < 0.001) and fluctuation of core body temperature was wider (standard deviation of target temperature 0.4 °C vs. 0.28 °C) in the FGP group, compared with PCM group. Conclusion: Both FGP and PCM are effective and safe, comparable with standard servo-controlled cooling equipment. PCM has the advantage of better maintenance of target temperature with less nursing input, when compared with FGP.

Cost analysis of large-scale implementation of the 'Helping Babies Breathe' newborn resuscitation-training program in Tanzania.

BACKGROUND: Helping Babies Breathe (HBB) has become the gold standard globally for training birth-attendants in neonatal resuscitation in low-resource settings in efforts to reduce early newborn asphyxia and mortality. The purpose of this study was to do a first-ever activity-based cost-analysis of at-scale HBB program implementation and initial follow-up in a large region of Tanzania and evaluate costs of national scale-up as one component of a multi-method external evaluation of the implementation of HBB at scale in Tanzania. METHODS: We used activity-based costing to examine budget expense data during the two-month implementation and follow-up of HBB in one of the target regions. Activity-cost centers included administrative, initial training (including resuscitation equipment), and follow-up training expenses. Sensitivity analysis was utilized to project cost scenarios incurred to achieve countrywide expansion of the program across all mainland regions of Tanzania and to model costs of program maintenance over one and five years following initiation. RESULTS: Total costs for the Mbeya Region were $202,240, with the highest proportion due to initial training and equipment (45.2%), followed by central program administration (37.2%), and follow-up visits (17.6%). Within Mbeya, 49 training sessions were undertaken, involving the training of 1,341 health providers from 336 health facilities in eight districts. To similarly expand the HBB program across the 25 regions of mainland Tanzania, the total economic cost is projected to be around $4,000,000 (around $600 per facility). Following sensitivity analyses, the estimated total for all Tanzania initial rollout lies between $2,934,793 to $4,309,595. In order to maintain the program nationally under the current model, it is estimated it would cost $2,019,115 for a further one year and $5,640,794 for a further five years of ongoing program support. CONCLUSION: HBB implementation is a relatively low-cost intervention with potential for high impact on perinatal mortality in resource-poor settings. It is shown here that nationwide expansion of this program across the range of health provision levels and regions of Tanzania would be feasible. This study provides policymakers and investors with the relevant cost-estimation for national rollout of this potentially neonatal life-saving intervention.

Inpatient care of small and sick newborns: a multi-country analysis of health system bottlenecks and potential solutions.

BACKGROUND: Preterm birth is the leading cause of child death worldwide. Small and sick newborns require timely, high-quality inpatient care to survive. This includes provision of warmth, feeding support, safe oxygen therapy and effective phototherapy with prevention and treatment of infections. Inpatient care for newborns requires dedicated ward space, staffed by health workers with specialist training and skills. Many of the estimated 2.8 million newborns that die every year do not have access to such specialised care. METHODS: The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks" (or factors that hinder the scale up) of maternal-newborn intervention packages. For this paper, we used quantitative and qualitative methods to analyse the bottleneck data, and combined these with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for inpatient care of small and sick newborns. RESULTS: Inpatient care of small and sick newborns is an intervention package highlighted by all country workshop participants as having critical health system challenges. Health system building blocks with the highest graded (significant or major) bottlenecks were health workforce (10 out of 12 countries) and health financing (10 out of 12 countries), followed by community ownership and partnership (9 out of 12 countries). Priority actions based on solution themes for these bottlenecks are discussed. CONCLUSIONS: Whilst major bottlenecks to the scale-up of quality inpatient newborn care are present, effective solutions exist. For all countries included, there is a critical need for a neonatal nursing cadre. Small and sick newborns require increased, sustained funding with specific insurance schemes to cover inpatient care and avoid catastrophic out-of-pocket payments. Core competencies, by level of care, should be defined for monitoring of newborn inpatient care, as with emergency obstetric care. Rather than fatalism that small and sick newborns will die, community interventions need to create demand for accessible, high-quality, family-centred inpatient care, including kangaroo mother care, so that every newborn can survive and thrive.

Cooling in a low-resource environment: lost in translation.

Although cooling therapy has been the standard of care for neonatal encephalopathy (NE) in high-income countries for more than half a decade, it is still not widely used in low- and middle-income countries (LMIC), which bear 99% of the encephalopathy burden; neither is it listed as a priority research area in global health. Here we explore the major roadblocks that prevent the use of cooling in LMIC, including differences in population comorbidities, suboptimal intensive care, and the lack of affordable servo-controlled cooling devices. The emerging data from LMIC suggest that the incidence of coexisting perinatal infections in NE is no different to that in high-income countries, and that cooling can be effectively provided without tertiary intensive care and ventilatory support; however, the data on safety and efficacy of cooling are limited. Without adequately powered clinical trials, the creeping and uncertain introduction of cooling therapy in LMIC will be plagued by residual safety concerns, and any therapeutic benefit will be even more difficult to translate into widespread clinical use.

Holistic approach for automated background EEG assessment in asphyxiated full-term infants.

OBJECTIVE: To develop an automated algorithm to quantify background EEG abnormalities in full-term neonates with hypoxic ischemic encephalopathy. APPROACH: The algorithm classifies 1 h of continuous neonatal EEG (cEEG) into a mild, moderate or severe background abnormality grade. These classes are well established in the literature and a clinical neurophysiologist labeled 272 1 h cEEG epochs selected from 34 neonates. The algorithm is based on adaptive EEG segmentation and mapping of the segments into the so-called segments' feature space. Three features are suggested and further processing is obtained using a discretized three-dimensional distribution of the segments' features represented as a 3-way data tensor. Further classification has been achieved using recently developed tensor decomposition/classification methods that reduce the size of the model and extract a significant and discriminative set of features. MAIN RESULTS: Effective parameterization of cEEG data has been achieved resulting in high classification accuracy (89%) to grade background EEG abnormalities. SIGNIFICANCE: For the first time, the algorithm for the background EEG assessment has been validated on an extensive dataset which contained major artifacts and epileptic seizures. The demonstrated high robustness, while processing real-case EEGs, suggests that the algorithm can be used as an assistive tool to monitor the severity of hypoxic insults in newborns.

High placental index and poor pregnancy outcomes: a retrospective study of 18,386 pregnancies.

INTRODUCTION: Our aim was to state the correlation between placental index and pregnancy outcomes or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies. MATERIALS AND METHODS: We included in this retrospective study all singleton births in a third level clinic during the period 2001-2011 (n = 18,386). We divided placental index into quartiles and analyzed the differences between the groups in term of pregnancy outcomes. Then, we estimated crude and adjusted odds ratios (ORs) for placental index over the third centile of the distribution to correlate with pregnancy outcomes. We also analyzed the correlation between IVF/ICSI conceived pregnancies and placental index. RESULTS: Poor pregnancy outcomes were overrepresented in the highest quartile of placental index distribution. Thus, placental index was higher in pregnancies characterized by pregnancy-related hypertensive disorders (PRHDs), small for gestational age infants, newborn needing cardiopulmonary resuscitation or hospitalization in neonatal intensive care unit. These findings were independent of maternal age, length of gestation at delivery, IVF/ICSI conception and ethnicity. For IVF/ICSI pregnancies, the OR for being over the third quartile of placental index distribution was 2.01 (CI.95 1.40-2.90) after adjustment for maternal age, length of gestation, ethnicity, birth weight, parity, fetal sex, alteration of glucose metabolism in pregnancy and PRHDs. CONCLUSIONS: We found a high placental index among pregnancies characterized by poor outcomes and conceived by IVF/ICSI.

Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach.

BACKGROUND AND OBJECTIVES: Therapeutic hypothermia can influence the pharmacokinetics and pharmacodynamics of drugs, the discipline which is called thermopharmacology. We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effect of phenobarbital on the continuous amplitude-integrated electroencephalography (aEEG) in a prospective study. PATIENTS AND METHODS: Data were obtained from the prospective SHIVER study, performed in two of the ten Dutch level III neonatal intensive care units. Phenobarbital data were collected between 2008 and 2010. Newborns were eligible for inclusion if they had a gestational age of at least 36 weeks and presented with perinatal asphyxia and encephalopathy. According to protocol in both hospitals an intravenous (repeated) loading dose of phenobarbital 20 mg/kg divided in 1-2 doses was administered if seizures occurred or were suspected before or during the hypothermic phase. Phenobarbital plasma concentrations were measured in plasma using a fluorescence polarization immunoassay. aEEG was monitored continuously. RESULTS AND CONCLUSION: A one-compartmental population pharmacokinetic/pharmacodynamic model was developed using a multi-level Markov transition model. No (clinically relevant) effect of moderate therapeutic hypothermia on phenobarbital pharmacokinetics could be identified. The observed responsiveness was 66%. While we still advise an initial loading dose of 20 mg/kg, clinicians should not be reluctant to administer an additional dose of 10-20 mg/kg. An additional dose should be given before switching to a second-line anticonvulsant drug. Based on our pharmacokinetic/pharmacodynamic model, administration of phenobarbital under hypothermia seems to reduce the transition rate from a continuous normal voltage (CNV) to discontinuous normal voltage aEEG background level in hypothermic asphyxiated newborns, which may be attributed to the additional neuroprotection of phenobarbital in infants with a CNV pattern.

Assessment of knowledge on neonatal resuscitation amongst health care providers in Kenya.

INTRODUCTION: Competence in neonatal resuscitation, which represents the most urgent pediatric clinical situation, is critical in delivery rooms to ensure safety and health of newly born infants. The challenges experienced by health care providers during this procedure are unique due to different causes of cardio respiratory arrest. This study aimed at assessing the knowledge of health providers on neonatal resuscitation. METHODS: Data were gathered among 192 health providers drawn from all counties of Kenya. The clinicians were asked to complete questionnaires which were in two parts as; demographic information and assessment of their knowledge by different scenarios which were formatted in the multiple choice questions. Data were analyzed using SPSS version 15.0 for windows. The results are presented using tables. RESULTS: All the participants were aged 23 years and above with at least a certificate training. Most medical providers had heard of neonatal resuscitation (85.4%) with only 23 receiving formal training. The average duration of neonatal training was 3 hours with 50% having missed out on practical exposure. When asked on steps of resuscitation, only 68 (35.4%) of the participants scored above 85%. More than 70% of them considered their knowledge about neonatal resuscitation inadequate and blamed it on inadequate medical training programs. CONCLUSION: Health providers, as the key personnel in the management of neonatal resuscitation, in this survey seem to have inadequate training and knowledge on this subject. Increasing the duration and quality of formal training should be considered during the pre-service medical education to ensure acceptable neonatal outcome.

Neonatal resuscitation assessment: documentation and early paging must be improved!

OBJECTIVE: The authors had previously found flaws in resuscitation after severe neonatal asphyxia in cases selected on the grounds of suspected malpractice and financial compensation claims. The aim of the present study was to evaluate neonatal resuscitation in the general obstetric population in a setting with skilled attendance at birth. DESIGN: Observational study. SETTING AND PATIENTS: All infants born in the Stockholm County during 2004-2006 with a gestational age of ≥33 weeks, planned as vaginal delivery, with a normal cardiotocographic recording on admission to hospital and with an Apgar score of <7 at 5 min were included. MAIN OUTCOME MEASURES: Adherence to guidelines for neonatal resuscitation. RESULTS: Documentation was unsatisfactory in 142 (45%) infants. Other important shortcomings identified were delayed initiation of extensive resuscitation due to late paging or late arrival of attending paediatrician/neonatologist (n=48), and unsatisfactory ventilation related to late intubation and late securing of free airway (n=15). CONCLUSIONS: Substandard care in neonatal resuscitation is not limited to cases of severe asphyxia related to claims for medical malpractice. The overall documentation of neonatal resuscitation needs to be much better to enable accurate and reliable evaluation. Obvious actions to improve standards of care include the paging of skilled personnel at an earlier stage in cases of complicated deliveries and team and skills training in neonatal ventilation.