Reactive Gliosis in Neonatal Disorders: Friend or Foe for Neuroregeneration?

A developing nervous system is particularly vulnerable to the influence of pathophysiological clues and injuries in the perinatal period. Astrocytes are among the first cells that react to insults against the nervous tissue, the presence of pathogens, misbalance of local tissue homeostasis, and a lack of oxygen and trophic support. Under this background, it remains uncertain if induced astrocyte activation, recognized as astrogliosis, is a friend or foe for progressing neonatal neurodevelopment. Likewise, the state of astrocyte reactivity is considered one of the key factors discriminating between either the initiation of endogenous reparative mechanisms compensating for aberrations in the structures and functions of nervous tissue or the triggering of neurodegeneration. The responses of activated cells are modulated by neighboring neural cells, which exhibit broad immunomodulatory and pro-regenerative properties by secreting a plethora of active compounds (including interleukins and chemokines, neurotrophins, reactive oxygen species, nitric oxide synthase and complement components), which are engaged in cell crosstalk in a paracrine manner. As the developing nervous system is extremely sensitive to the influence of signaling molecules, even subtle changes in the composition or concentration of the cellular secretome can have significant effects on the developing neonatal brain. Thus, modulating the activity of other types of cells and their interactions with overreactive astrocytes might be a promising strategy for controlling neonatal astrogliosis.

Drug-induced fetal and offspring disorders, beyond birth defects.

Studies on drug utilization in western countries disclosed that about nine over ten women use at least one or more drugs during pregnancy. Determining whether a drug is safe or not in pregnant women is a challenge of all times. As a developing organism, the fetus is particularly vulnerable to effects of drugs used by the mother. Historically, research has predominantly focused on birth defects, which represent the most studied adverse pregnancy outcomes. However, drugs can also alter the ongoing process of pregnancy and impede the general growth of the fetus. Finally, adverse drug reactions can theoretically damage all developing systems, organs or tissues, such as the central nervous system or the immune system. This extensive review focuses on different aspects of drug-induced damages affecting the fetus or the newborn/infant, beyond birth defects, which are not addressed here.

Global, regional, and national burden of ambient and household PM2.5-related neonatal disorders, 1990-2019.

Previous studies have shown a relationship between fine particulate matter (PM2.5) exposure and an increased risk of neonatal disorders. Considering the huge burden of neonatal disorders, we assessed spatiotemporal trends of neonatal disorders burden caused by ambient and household PM2.5 at the global, regional, and national levels from 1990 to 2019. The number, rate, and population attributable fraction (PAF) of ambient and household PM2.5-related neonatal disorders disability-adjusted life years (DALYs) in 204 countries and territories from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 to measure the related neonatal disorders burden by age, sex, subtype, and region. Estimated annual percentage change (EAPC) was estimated to quantify temporal trends. In 2019, approximately a fifth of the global neonatal disorders burden was attributable to PM2.5 exposure, with 7.54% for ambient PM2.5 and 13.23% for household PM2.5. Although the global neonatal disorders burden attributable to household PM2.5 has decreased substantially in the past 30 years, that attributable to ambient PM2.5 has increased, especially in lower sociodemographic index (SDI) regions. The highest rate and PAF of ambient PM2.5-related neonatal disorders DALYs in 2019 were in South Asia and East Asia, respectively, and the fastest increases were in Eastern Sub-Saharan Africa (for rate: EAPC = 2.55, 95% CI: 2.37-2.73) and South Asia (for PAF: EAPC = 3.88, 95% CI: 3.68-4.08). In addition, we found an inverted V-shaped between rates and PAFs of ambient PM2.5-related neonatal disorders DALYs in 2019, as well as corresponding EAPCs, and SDI, while rates and PAFs of household PM2.5-related neonatal disorders DALYs in 2019 were highly negatively correlated with SDI. In the past three decades, the global ambient PM2.5-related neonatal disorders burden largely increased, especially in lower SDI regions. Comparatively, the household PM2.5-related neonatal disorders burden decreased but still accounted for about two-thirds of the PM2.5-related neonatal disease burden.

Disease burden and attributable risk factors of neonatal disorders and their specific causes in China from 1990 to 2019 and its prediction to 2024.

BACKGROUND: Neonatal health is a cornerstone for the healthy development of the next generation and a driving force for the progress of population and society in the future. Updated information on the burden of neonatal disorders (NDs) are of great importance for evidence-based health care planning in China, whereas such an estimate has been lacking at national level. This study aims to estimate the temporal trends and the attributable burdens of selected risk factors of NDs and their specific causes in China from 1990 to 2019, and to predict the possible trends between 2020 and 2024. METHODS: Data was explored from the Global Burden of Disease study (GBD) 2019. Six measures were used: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute numbers and age-standardized rates (with 95% uncertainty intervals) were calculated. The specific causes of NDs mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). An autoregressive integrated moving average (ARIMA) model was used to forecast disease burden from 2020 to 2024. RESULTS: There were notable decreasing trends in the number of deaths (84.3%), incidence (30.3%), DALYs (73.5%) and YLLs (84.3%), while increasing trends in the number of prevalence (102.3%) and YLDs (172.7%) from 1990 to 2019, respectively. The corresponding age-standardized rates changed by -74.9%, 0.1%, -65.8%, -74.9%, 86.8% and 155.1%, respectively. Four specific causes of NDs followed some similar and different patterns. The prediction results of the ARIMA model shown that all measures still maintained the original trends in the next five years. Low birth weight, short gestation, ambient particulate matter pollution and household air pollution from solid fuels were the four leading risk factors. CONCLUSION: The health burden due to NDs is declining and is likely to continue to decline in the future in China. Delaying the increasing burden of disability may be the next target of concern. Targeted prevention and control strategies for specific causes of NDs are urgently needed to reduce the disease burden.

Stem cells in neonatal diseases: An overview.

Preterm birth and its common complications are major causes of infant mortality and long-term morbidity. Despite great advances in understanding the pathogenesis of neonatal diseases and improvements in neonatal intensive care, effective therapies for the prevention or treatment for these conditions are still lacking. Stem cell (SC) therapy is rapidly emerging as a novel therapeutic tool for several diseases of the newborn with encouraging pre-clinical results that hold promise for translation to the bedside. The utility of different types of SCs in neonatal diseases is being explored. SC therapeutic efficacy is closely associated with its secretome-conditioned media and SC-derived extracellular vesicles, and a subsequent paracrine action in response to tissue injuries. In the current review, we summarize the pre-clinical and clinical studies of SCs and its secretome in diverse preterm and term birth-related diseases, thereby providing new insights for future therapies in neonatal medicine.

Congenital diaphragmatic hernia: a single-centre experience at Kepler University Hospital Linz.

Congenital diaphragmatic hernia (CDH) is found in about 1 of 3000 live births and is often complicated by pulmonary hypoplasia and alteration of the pulmonary arterial wall with resulting pulmonary hypertension. Since 2005, with the fusion of the children's hospital and the maternity clinic of the Kepler University Hospital Linz, affected neonates have been treated according to a standard protocol at our perinatal centre. Some prenatally measured parameters have been used to predict mortality, e.g., observed-to-expected lung-to-head ratio or lung volume measurements by nuclear magnetic resonance imaging. We performed a retrospective chart review of 67 new-borns with CDH treated at our institution to detect any predictors of hospital mortality from parameters routinely collected within the first 24 h of life. The term "liver up" was identified as a predictor of hospital mortality; OR 9.2 (95% CI 1.9-51.1, p = 0.002, sensitivity 79%, specificity 71%). In addition, the need for application of high-frequency oscillatory ventilation during the first 24 h was associated with mortality; OR 44.4 (95% CI 6.3-412.1, p = 0.001, sensitivity 85.7%, specificity 88%).

Risk Factors and Outcomes of Pulmonary Hypertension in Infants With Bronchopulmonary Dysplasia: A Meta-Analysis.

Background: Pulmonary hypertension is one of the most common co-morbidities in infants with bronchopulmonary dysplasia (BPD), but its risk factors are unclear. The onset of pulmonary hypertension in BPD has been associated with poor morbidity- and mortality-related outcomes in infants. Two review and meta-analysis studies have evaluated the risk factors and outcomes associated with pulmonary hypertension in infants with BPD. However, the limitations in those studies and the publication of recent cohort studies warrant our up-to-date study. We designed a systematic review and meta-analysis to evaluate the risk factors and outcomes of pulmonary hypertension in infants with BPD. Objective: To systematically evaluate the risk factors and outcomes associated with pulmonary hypertension in infants with BPD. Methods: We systematically searched the academic literature according to the PRISMA guidelines across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE). We conducted random-effects meta-analyses to evaluate the pulmonary hypertension risk factors in infants with BPD. We also evaluated the overall morbidity- and mortality-related outcomes in infants with BPD and pulmonary hypertension. Results: We found 15 eligible studies (from the initial 963 of the search result) representing data from 2,156 infants with BPD (mean age, 25.8 ± 0.71 weeks). The overall methodological quality of the included studies was high. Our meta-analysis in infants with severe BPD revealed increased risks of pulmonary hypertension [Odds ratio (OR) 11.2], sepsis (OR, 2.05), pre-eclampsia (OR, 1.62), and oligohydramnios (OR, 1.38) of being small for gestational age (3.31). Moreover, a comparative analysis found medium-to-large effects of pulmonary hypertension on the total duration of hospital stay (Hedge's g, 0.50), the total duration of oxygen received (g, 0.93), the cognitive score (g, -1.5), and the overall mortality (g, 0.83) in infants with BPD. Conclusion: We identified several possible risk factors (i.e., severe BPD, sepsis, small for gestational age, pre-eclampsia) which promoted the onset of pulmonary hypertension in infants with BPD. Moreover, our review sheds light on the morbidity- and mortality-related outcomes associated with pulmonary hypertension in these infants. Our present findings are in line with the existing literature. The findings from this research will be useful in development of efficient risk-based screening system that determine the outcomes associated with pulmonary hypertension in infants with BPD.

The Spectrum of Neonatal Disorders Managed at the University Hospital of the West Indies over the Past Two Decades / El Espectro de los Trastornos Neonatales Tratados en el Hospital Universitario de West Indies Durante las dos últimas Décadas

ABSTRACT Objective: To define the spectrum of medical disorders managed on the neonatal unit at the University Hospital of the West Indies (UHWI) over the past two decades. Method: A review of published data pertaining to neonatal medical disorders managed at the UHWI over the past 20 years was conducted. Pertinent findings, implications of these findings and recommendations based on these findings were collated and presented under themes. Results: Common medical disorders managed includes complications of prematurity and very low birthweight infants, neonatal sepsis, hypoxic ischaemic encephalopathy, meconium aspiration syndrome, neonatal jaundice, hypernatraemic dehydration, complications of macrosomia and complications resulting from neonatal transport. Conclusion: It is clear that a diverse spectrum of neonatal disorders is managed on the neonatal unit of the UHWI and that the fledgling neonatal unit providing basic care for neonates of the 1960s has matured into the level II Newborn Special Care Nursery and Level III NICU that it is today. The time is now opportune for Neonatology to gain independent status as a Division of Neonatology within the Department of Child and Adolescent Health at the UHWI.

RESUMEN Objetivo: Definir el espectro de trastornos médicos tratados en la Unidad Neonatal del Hospital Universitario de West Indies (UHWI) en las últimas dos décadas. Método: Se realizó una revisión de los datos publicados sobre los trastornos médicos neonatales tratados en UHWI durante los últimos 20 años. Los hallazgos pertinentes, las implicaciones de estos hallazgos y las recomendaciones basadas en estos hallazgos fueron recopiladas y presentadas en temas. Resultados: Los trastornos médicos comunes tratados incluyen complicaciones de la prematuridad y los neonatos de muy bajo peso al nacer, sepsis neonatal, encefalopatía isquémica, síndrome de aspiración de meconio, ictericia neonatal, deshidratación hipernatrémica, complicaciones de macrosomía y las complicaciones resultantes del transporte neonatal. Conclusión: Está claro que un espectro diverso de trastornos neonatales es tratado en la Unidad Neonatal de UHWI, y que la unidad neonatal incipiente que proporcionó atención básica a los neonatos de los años 60 ha madurado, llegando a ser hoy la Sala de Atención Especial a Neonatos de Nivel II y la Unidad de Cuidados Intensivos Neonatales (UCIN) de Nivel III. Es hora ya de que la Neonatología tenga estatus independiente como División de Neonatología dentro del Departamento de Salud de Niños y Adolescentes de UHWI.

Disability-Adjusted Life Years for Maternal, Neonatal, and Nutritional Disorders in Korea.

Maternal and child health is an important issue throughout the world. Given their impact on maternal and child health, nutritional issues need to be carefully addressed. Accordingly, the effect of maternal, child, and nutritional disorders on disability-adjusted life years (DALYs) should be calculated. The present study used DALYs to estimate the burden of disease of maternal, neonatal, and nutritional disorders in the Korean population in 2012. For this purpose, we used claim data of the Korean National Health Insurance Service, DisMod II, and death data of the Statistics Korea and adhered to incidence-based DALY estimation methodology. The total DALYs per 100,000 population were 376 in maternal disorders, 64 in neonatal disorders, and 58 in nutritional deficiencies. The leading causes of DALYs were abortion in maternal disorders, preterm birth complications in neonatal disorders, and iron-deficiency anemia in nutritional deficiencies. Our findings shed light on the considerable burden of maternal, neonatal, and nutritional conditions, emphasizing the need for health care policies that can reduce morbidity and mortality.

Disability-Adjusted Life Years for Maternal, Neonatal, and Nutritional Disorders in Korea

Maternal and child health is an important issue throughout the world. Given their impact on maternal and child health, nutritional issues need to be carefully addressed. Accordingly, the effect of maternal, child, and nutritional disorders on disability-adjusted life years (DALYs) should be calculated. The present study used DALYs to estimate the burden of disease of maternal, neonatal, and nutritional disorders in the Korean population in 2012. For this purpose, we used claim data of the Korean National Health Insurance Service, DisMod II, and death data of the Statistics Korea and adhered to incidence-based DALY estimation methodology. The total DALYs per 100,000 population were 376 in maternal disorders, 64 in neonatal disorders, and 58 in nutritional deficiencies. The leading causes of DALYs were abortion in maternal disorders, preterm birth complications in neonatal disorders, and iron-deficiency anemia in nutritional deficiencies. Our findings shed light on the considerable burden of maternal, neonatal, and nutritional conditions, emphasizing the need for health care policies that can reduce morbidity and mortality.