Factors Associated With Severe Gastrointestinal Diagnoses in Children With SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome

Importance Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown. Objective To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome. Design, Setting, and Participants A multicenter retrospective cohort study (February 25, 2020, to January 20, 2021) enrolled inpatient and outpatient children (aged <18 years) with acute SARS-CoV-2 infection, confirmed by positive real-time reverse-transcriptase–polymerase chain reaction on nasopharyngeal swab or fulfilling the US Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children (MIS-C). The study was conducted by pediatricians working in primary care or hospitals in Italy participating in the COVID-19 Registry of the Italian Society of Pediatric Infectious Diseases. Main Outcomes and Measures The occurrence of severe GI manifestations, defined by a medical and/or radiological diagnosis of acute abdomen, appendicitis (complicated or not by perforation and/or peritonitis), intussusception, pancreatitis, abdominal fluid collection, and diffuse adenomesenteritis requiring surgical consultation, occurring during or within 4 to 6 weeks after infection with SARS-CoV-2 infection. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs of factors potentially associated with severe outcomes. Results Overall, 685 children (386 boys [56.4%]; median age, 7.3 [IQR, 1.6-12.4] years) were included. Of these children, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with MIS-C. The presence of GI symptoms was associated with a higher chance of hospitalization (OR, 2.64; 95% CI, 1.89-3.69) and intensive care unit admission (OR, 3.90; 95% CI, 1.98–7.68). Overall, 65 children (9.5%) showed severe GI involvement, including disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Twenty-seven of these 65 children (41.5%) underwent surgery. Severe GI manifestations were associated with the child’s age (5-10 years: OR, 8.33; 95% CI, 2.62-26.5; >10 years: OR, 6.37; 95% CI, 2.12-19.1, compared with preschool-age), abdominal pain (adjusted OR [aOR], 34.5; 95% CI, 10.1-118), lymphopenia (aOR, 8.93; 95% CI, 3.03-26.3), or MIS-C (aOR, 6.28; 95% CI, 1.92-20.5). Diarrhea was associated with a higher chance of adenomesenteritis (aOR, 3.13; 95% CI, 1.08-9.12) or abdominal fluid collection (aOR, 3.22; 95% CI, 1.03-10.0). Conclusions and Relevance In this multicenter cohort study of Italian children with SARS-CoV-2 infection or MIS-C, 9.5% of the children had severe GI involvement, frequently associated with MIS-C. These findings suggest that prompt identification may improve the management of serious complications

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature

Tall stature: a difficult diagnosis?

Abstract Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean for age. The majority of subjects with tall stature show a familial tall stature or a constitutional advance of growth (CAG), which is a diagnosis of exclusion. After a careful physical evaluation, tall subjects may be divided into two groups: tall subjects with normal appearance and tall subjects with abnormal appearance. In the case of normal appearance, the paediatric endocrinologist will have to evaluate the growth rate. If it is normal for age and sex, the subject may be classified as having familial tall stature, CAG or obese subject, while if the growth rate is increased it is essential to evaluate pubertal status and thyroid status. Tall subjects with abnormal appearance and dysmorphisms can be classified into those with proportionate and disproportionate syndromes. A careful physical examination and an evaluation of growth pattern are required before starting further investigations. Physicians should always search for a pathological cause of tall stature, although the majority of children are healthy and they generally do not need treatment to cease growth progression. The most accepted and effective treatment for an excessive height prediction is inducing puberty early and leading to a complete fusion of the epiphyses and achievement of final height, using testosterone in males and oestrogens in females. Alternatively, the most common surgical procedure for reducing growth is bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula. This review aims to provide up-to-date information and suggestions about the diagnosis and management of children with tall stature

Is the equimolar mixture of oxygen and nitrous oxide (EMONO) associated with audiovisuals effective in reducing pain and side effects during peripheral venous access placement in children? Protocol for a single-centre randomised controlled trial from Italy

Introduction Nurses frequently place a peripheral venous catheter during children’s hospitalisation. Many studies suggest treatment of venipuncture-related pain. The administration of an equimolar mixture of oxygen and nitrous oxide (EMONO) is employed for pain control; however, no studies have analysed the association between EMONO and audiovisuals.The purpose of the study is to evaluate the effect of EMONO administration when combined with audiovisuals (EMONO+Audiovisual) versus EMONO alone on perceived pain, side effects and level of cooperation during peripheral venous access placement in children aged 2–5 years.Methods and analysis The first 120 eligible children admitted to the paediatric ward of the Lodi Hospital and presenting the indication for peripheral venous access will be enrolled. Sixty children will be randomly assigned to the experimental group (EMONO+Audiovisual) and 60 to the control group (EMONO alone).The Face, Legs, Activity, Cry, Consolability scale will be used to assess pain in the children aged 2-years old; pain in the children aged 3–5 years will be assessed using the Wong-Baker scale. The cooperation throughout the procedure will be measured using the Groningen Distress Rating Scale.Ethics and dissemination The Milan Area 1 Ethics Committee approved the study protocol (Experiment Registry No. 2020/ST/295). The trial results will be presented at conferences and published in peer-reviewed journals.Trial registration number NCT05435118

Sex-dependent association between variability in infants’ OXTR methylation at birth and negative affectivity at 3 months

Background: Sex-specific differences in DNA methylation of the oxytocin receptor gene (OXTR) have been shown in adults and are related to several mental disorders. Negative affectivity early in life is a trans-diagnostic risk marker of later psychopathology and is partly under genetic control. However, sex-specific variations in OXTR methylation (OXTRm) in infants and their associations with negative affectivity are still unknown. Aims: Here, we explored sex differences in the association between infant OXTRm at birth and negative affec- tivity at 3 months of age. Methods: Infants and their mothers (N = 224) were recruited at delivery. Infants’ methylation status was assessed in 13 CpG sites within the OXTR gene intron 1 region (chr3: 8810654–8810919) in buccal cells at birth while 3- month-old infants’ negative affectivity was assessed by mothers using a well-validated temperament questionnaire. Results: OXTRm at 12 CpG sites was higher in females than in males. Moreover, higher infants’ OXTRm at 6 specific CpG sites was associated with greater negative affectivity in males, but not in females. Conclusions: These results provide new insights into the role of sex-dependent epigenetic mechanisms linking OXTRm with early infants’ emotional development. Understanding the degree to which epigenetic processes relate to early temperamental variations may help inform the etiology of later childhood psychopathological outcomes

Epidemiology, Clinical Features and Prognostic Factors of Pediatric SARS-CoV-2 Infection: Results From an Italian Multicenter Study

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5-9 years and lymphopenia were statistically related to ICU admission (p < 0.05). Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission

Depression and Anxiety in Mothers Who Were Pregnant During the COVID-19 Outbreak in Northern Italy: The Role of Pandemic-Related Emotional Stress and Perceived Social Support

The COVID-19 pandemic is a collective trauma that is threatening citizens' mental health resulting in increased emotional stress, reduced social support, and heightened risk for affective symptoms. The present study aimed to investigate the effects of antenatal pandemic-related emotional stress and perceived social support on the symptoms of depression and anxiety of mothers who were pregnant during the initial COVID-19 outbreak in northern Italy. A sample of 281 mothers was enrolled at eight maternity units in the first hotspot region of the COVID-19 outbreak in northern Italy. Participants filled out online questionnaires assessing the direct or indirect exposure to the SARS-CoV-2 virus, pandemic-related stress, perceived social support, as well as symptoms of depression and anxiety. Depressive and anxious symptomatology was above clinical concern, respectively, in 26 and 32% of the respondents. Mothers who reported no exposure to SARS-CoV-2 during pregnancy and those who reported at least one direct or indirect exposure did not differ in terms of affective symptoms. Continuous scores and risk for severe depression and anxiety were positively associated with prenatal pandemic-related emotional stress and negatively linked with perceived social support during pregnancy. Women who become mothers during the COVID-19 emergency may be at high risk for affective problems. Dedicated preventive programs are needed to provide adequate preventive support and care for maternal mental health during and after the COVID-19 pandemic

Linear association between maternal pandemic-related stress (PRS) during pregnancy and infants’ over-arching socio-cognitive score (SCS) at 12-month-age.

Note. Infant SCS scores are standardized (mean = 0, sd = 1). Standardized estimate for PRS = -0.28, p = 0.01.</p

Linear association between maternal pandemic-related stress (PRS) during pregnancy and infants’ orienting (PC-ORI), pointing (PC-POI), communication (PC-COM) at 12-month-age.

Note. All outcome variables on the y-axis are standardized (mean = 0, sd = 1). In regression model predicting PC-ORI, standardized estimate for PRS = -0.09, p = 0.41; In regression model predicting PC-POI, standardized estimate for PRS = -0.16, p = 0.16; In regression model predicting PC-COM, standardized estimate for PRS = -0.26, p = 0.02.</p