The 50 most-cited articles in Pediatric Research, 2020

Integrins are heterodimeric transmembrane cell adhesion molecules made up of alpha (α) and beta (β) subunits arranged in numerous dimeric pairings. These complexes have varying affinities to extracellular ligands. Integrins regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis. This review presents current evidence from human and animal studies on integrin structure and molecular signaling, with particular emphasis on signal transduction in infants. We have included evidence from our own laboratory studies and from an extensive literature search in databases PubMed, EMBASE, Scopus, and the electronic archives of abstracts presented at the annual meetings of the Pediatric Academic Societies. To avoid bias in identification of existing studies, key words were short-listed prior to the actual search both from anecdotal experience and from PubMed's Medical Subject…

Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental…

Anemia, defined as a low blood hemoglobin concentration, is a major global public health problem. Identification of anemia is crucial to public health interventions. It is estimated globally that 273 million children under 5 years of age were anemic in 2011, and about ~50% of those cases were attributable to iron deficiency (Lancet Global Health 1:e16-e25, 2013). Iron-deficiency anemia (IDA) in infants adversely impacts short-term hematological indices and long-term neuro-cognitive functions of learning and memory that result in both fatigue and low economic productivity. IDA contributes to death and disability and is an important risk factor for maternal and perinatal mortality, including the risks for stillbirths, prematurity, and low birth weight (Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors. Ch. 3 (World Health Organization, Geneva, 2004)). Reduction in early infantile anemia and newborn mortality rates is possible with easily implemented, low- to no-cost intervention such as delayed cord clamping…

Germinal matrix-intraventricular haemorrhage (GMH-IVH), periventricular haemorrhagic infarction (PHI) and its complication, post-haemorrhagic ventricular dilatation (PHVD), are still common neonatal morbidities in preterm infants that are highly associated with adverse neurodevelopmental outcome. Typical cranial ultrasound (CUS) findings of GMH-IVH, PHI and PHVD, their anatomical substrates and underlying mechanisms are discussed in this paper. Furthermore, we propose a detailed descriptive classification of GMH-IVH and PHI that may improve quality of CUS reporting and prediction of outcome in infants suffering from GMH-IVH/PHI.

White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective…

Zero to 19 year-old children in sub-Saharan Africa bear a disproportionate proportion of the global burden of communicable and non-communicable diseases. Significant public health gains have been made in the fight against these diseases, however, factors such as underequipped health systems, disease outbreaks, conflict, and political instability continue to challenge prevention and control. The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduces new challenges to public health programs in sub-Saharan Africa. Of particular concern are programs targeting major conditions among children, such as undernutrition, vaccine-preventable pneumonia and diarrhea, malaria, tuberculosis, HIV, and sickle cell disease. This article focuses on the impact of the COVID-19 pandemic on child health in sub-Saharan Africa. We review the epidemiology of major pediatric diseases and, referencing modeling projections, discuss the short- and long-term impact of the pandemic on major disease control. We deliberate on potential…

In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18 MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated…

BACKGROUND: The impact of early adversity increases the risk of poor outcomes across the life course. Identifying factors that protect against or contribute to deleterious life outcomes represents an important step in resilience promotion among children exposed to adversity. Informed by resilience science, we hypothesized that family resilience mediates the relationship between adverse childhood experiences (ACEs) and child flourishing, and these pathways vary by race/ethnicity and income. METHODS: We conducted a secondary data analysis using the 2016-17 National Survey of Children's Health data reported by parents/guardians for 44,686 children age 6-17 years. A moderated-mediation model estimated direct, indirect, and total effects using a probit link function and stacked group approach with weighted least square parameter estimates. RESULTS: The main variables were related in expected directions. Family resilience partially mediated the ACEs-flourishing association. Although White and socioeconomically advantaged families were more likely to maintain family resilience, their…

BACKGROUND: Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic co-morbidities are likely to develop critical illness. Recently, a multisystem inflammatory syndrome (MIS-C) has been described in children with some of these patients requiring care in the pediatric ICU. METHODS: An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. RESULTS: This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed anti-viral drugs, anti-inflammatory or anti-thrombotic therapies are…

Congenital heart disease (CHD) affects nearly 1% of births. As survival rates have dramatically improved, the majority of individuals with CHD now live into adulthood. As these patients age, they become prone to a large range of complications, such as chronic heart failure and acquired cardiovascular disease. Promotion of a healthy and active lifestyle from childhood onwards has been suggested as a sustainable and effective strategy to enhance cardiovascular health, improve quality of life and reduce immediate and long-term risk in people with CHD. Well-established physical activity consensus statements for youth with CHD have now been published. In this article, we review how increasing physical activity in youth with CHD may offer immediate and long-term cardiovascular benefits, what is known about physical activity in children with CHD, describe the unique factors that contribute to achieving sufficient and insufficient physical activity levels and summarize the evidence of trials on physical activity promotion in youth with CHD. Furthermore, we discuss some of the challenges…

At the time of writing, there are already millions of documented infections worldwide by the novel coronavirus 2019 (2019-nCoV or severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)), with hundreds of thousands of deaths. The great majority of fatal events have been recorded in adults older than 70 years; of them, a large proportion had comorbidities. Since data regarding the epidemiologic and clinical characteristics in neonates and children developing coronavirus disease 2019 (COVID-19) are scarce and originate mainly from one country (China), we reviewed all the current literature from 1 December 2019 to 7 May 2020 to provide useful information about SARS-CoV2 viral biology, epidemiology, diagnosis, clinical features, treatment, prevention, and hospital organization for clinicians dealing with this selected population. IMPACT: Children usually develop a mild form of COVID-19, rarely requiring high-intensity medical treatment in pediatric intensive care unit. Vertical transmission is unlikely, but not completely excluded. Children with confirmed or suspected COVID-19 must…

We review the history of antenatal corticosteroid therapy (ACS) and present recent experimental data to demonstrate that this, one of the pillars of perinatal care, has been inadequately evaluated to minimize fetal exposure to these powerful medications. There have been concerns since 1972 that fetal exposures to ACS convey risk. However, this developmental modulator, with its multiple widespread biologic effects, has not been evaluated for drug choice, dose, or duration of treatment, despite over 30 randomized trials. The treatment used in the United States is two intramuscular doses of a mixture of 6 mg betamethasone phosphate (Beta P) and 6 mg betamethasone acetate (Beta Ac). To optimize outcomes with ACS, the goal should be to minimize fetal drug exposure. We have determined that the minimum exposure needed for fetal lung maturation in sheep, monkeys, and humans (based on published cord blood corticosteroid concentrations) is about 1 ng/ml for a 48-h continuous exposure, far lower than the concentration reached by the current dosing. Because the slowly released Beta Ac results…

BACKGROUND: The quality of family-centered care and parental participation in care in neonatal units differ widely across the world. Appropriate education might be an effective way to support medical staff in neonatal units to collaborate with parents and implement family-centered care. The aim of this study was to evaluate the effects of the educational intervention on the quality of family-centered care in eight Finnish neonatal intensive care units from both the staff and parent perspectives. METHODS: A mixed-method pre-post intervention study was conducted in eight neonatal intensive care units in Finland. Data were collected from staff and parents using the Bliss Baby Charter audit tool and semi-structured interviews. RESULTS: The quality of family-centered care, as assessed by staff and parents, increased significantly after the intervention in all eight units. The intervention was able to help staff define and apply elements of family-centered care, such as shared decision making and collaboration between parents and staff. In interviews, staff described that they learned to…

INTRODUCTION: Very and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically. METHODS: A systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants. RESULTS: In total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and long-term neurodevelopmental outcome were inconsistent. DISCUSSION: There is no clear…

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality in neonates. When the gold standard MRI is not feasible, cerebral ultrasound (CUS) might offer an alternative. In this study, the association between a novel CUS scoring system and neurodevelopmental outcome in neonates with HIE was assessed. METHODS: (Near-)term infants with HIE and therapeutic hypothermia, a CUS on day 1 and day 3-7 after birth and available outcome data were retrospectively included in cohort I. CUS findings on day 1 and day 3-7 were related to adverse outcome in univariate and the CUS of day 3-7 also in multivariable logistic regression analyses. The resistance index, the sum of deep grey matter and of white matter involvement were included in multivariable logistic regression analyses. A comparable cohort from another hospital was used for validation (cohort II). RESULTS: Eighty-three infants were included in cohort I and 35 in cohort II. The final CUS scoring system contained the sum of white matter (OR = 2.6, 95% CI 1.5-4.7) and deep grey matter involvement (OR…