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.

Characteristics and risk factors for SARS-CoV-2 in children tested in the early phase of the pandemic: a cross-sectional study, Italy, 23 February to 24 May 2020.

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe included cases aged 0-18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19.ResultsAmong 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52-90.55; p < 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p < 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions.

Missed intracranial injuries are rare in emergency departments using the PECARN head injury decision rules.

PURPOSE: The PECARN head trauma (HT) prediction rules have been developed to guide computed tomography-related decision-making for children with minor HT (mHT). There are currently limited data on the rate of unscheduled revisits to emergency departments (EDs), and initially missed intracranial injuries, in children with mHT initially assessed using the PECARN rules. This study aimed to fill this gap in knowledge. METHODS: Clinical charts of children assessed for mHT over a 5-year period at two EDs that implemented the PECARN rules in Italy and France were reviewed retrospectively. Children who returned to EDs for mHT-related, or potentially related complaints, within 1 month of initial assessment were included. RESULTS: The total number of children with mHT presenting for the first time to the EDs of both sites was 11,749. Overall, 180 (1.5%) unscheduled revisits to the EDs occurred for mHT-related or potentially related complaints. Twenty-three of these 180 patients underwent neuroimaging, and seven had an intracranial injury (including one ischemic stroke). Of these, three were hospitalized and none needed neurosurgery or intensive care. CONCLUSION: Unscheduled revisits for mHT in EDs using the PECARN rules were very uncommon. Initially missed intracranial injuries were rare, and none needed neurosurgery or intensive care.

Association between functional gastrointestinal disorders and migraine in children and adolescents: a case-control study.

BACKGROUND: Functional gastrointestinal disorders and migraine are both common causes of medical attention. We have previously shown an association between migraine and infant colic. In this case-control study, we aimed to establish whether there is an association between migraine and other functional gastrointestinal disorders in children and adolescents. METHODS: We included children and adolescents aged 6-17 years presenting to the emergency department of four tertiary hospitals in France and Italy. Patients diagnosed with either migraine or tension-type headache by the hospital's paediatric neurologist were enrolled as cases. Patients presenting to the emergency department with minor trauma and no history of recurrent headache were enrolled as controls. Investigators masked to a patient's group allocation diagnosed functional gastrointestinal disorders using the Rome III diagnostic criteria. Univariable and multivariable analyses were done to identify specific disorders and baseline factors associated with migraines and tension-type headache. FINDINGS: Between Nov 1, 2014, and Jan 31, 2015, we enrolled 648 controls and 424 cases (257 patients with migraine and 167 with tension-type headache). 83 (32%) children and adolescents in the migraine group were diagnosed with functional gastrointestinal disorders compared with 118 (18%) in the control group (p<0·0001). Multivariable logistic regression showed a significant association between migraine and three gastrointestinal disorders: functional dyspepsia (odds ratio 10·76, 95% CI 3·52-32·85; p<0·0001), irritable bowel syndrome (3·47, 1·81-6·62; p=0·0002), and abdominal migraine (5·87, 1·95-17·69; p=0·002). By contrast, there was an inverse association between migraine and functional constipation (0·34, 0·14-0·84, p=0·02). 41 (25%) participants with tension-type headache had functional gastrointestinal disorders, which did not significantly differ from the prevalence of these disorders in the control group (p=0·07); no significant association was noted between any functional gastrointestinal disease and tension-type headaches. INTERPRETATION: Three abdominal-pain-related functional gastrointestinal disorders were associated with migraine in children and adolescents. These findings are of value to the diagnosis and management of these common diseases. Future studies should investigate whether antimigraine drugs are of benefit in functional gastrointestinal disorders. FUNDING: None.

The Pediatric Emergency Care Applied Research Network intermediate-risk predictors were not associated with scanning decisions for minor head injuries.

AIM: This study determined the predictors associated with the decision to perform a computed tomography (CT) scan in children with a minor head injury (MHI). We focused on those facing an intermediate risk of clinically important traumatic brain injury (ciTBI), according to the Pediatric Emergency Care Applied Research Network (PECARN) prediction rule. METHODS: A 1-year, cross-sectional study was performed in an Italian paediatric emergency department, focusing on children presenting within 24 h of an MHI and meeting the PECARN intermediate-risk criteria. RESULTS: We included 308 children, and 47% were younger than 2 years of age. CT scans were carried out on 13%, 1.3% had a ciTBI and one was initially missed but did not need neurosurgery following diagnosis. Single and multiple PECARN intermediate-risk predictors were not associated with whether a CT scan was carried out. The only clinical variable associated with the decision to perform a CT scan was if the child was <3 months of age (OR 18.1, 95% CI, 4.91-66.61). CONCLUSION: The PECARN intermediate-risk predictors did not play a major role in the decision to perform a CT scan. The only factor significantly associated with the decision to perform a CT scan was when the patient was younger than 3 months of age.

Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection.

INTRODUCTION: Much effort has been put in the past years to create and assess accurate tools for the management of febrile infants. However, no optimal strategy has been so far identified. A sequential approach evaluating, first, the appearance of the infant, second, the age and result of the urinanalysis and, finally, the results of the blood biomarkers, including procalcitonin, may better identify low risk febrile infants suitable for outpatient management. OBJECTIVE: To assess the value of a sequential approach ('step by step') to febrile young infants in order to identify patients at a low risk for invasive bacterial infections (IBI) who are suitable for outpatient management and compare it with other previously described strategies such as the Rochester criteria and the Lab-score. METHODS: A retrospective comparison of three different approaches (step by step, Lab-score and Rochester criteria) was carried out in 1123 febrile infants less than 3 months of age attended in seven European paediatric emergency departments. IBI was defined as isolation of a bacterial pathogen from the blood or cerebrospinal fluid. RESULTS: Of the 1123 infants (IBI 48; 4.2%), 488 (43.4%) were classified as low-risk criteria according to the step by step approach (vs 693 (61.7%) with the Lab-score and 458 (40.7%) with the Rochester criteria). The prevalence of IBI in the low-risk criteria patients was 0.2% (95% CI 0% to 0.6%) using the step by step approach; 0.7% (95% CI 0.1% to 1.3%) using the Lab-score; and 1.1% (95% CI 0.1% to 2%) using the Rochester criteria. Using the step by step approach, one patient with IBI was not correctly classified (2.0%, 95% CI 0% to 6.12%) versus five using the Lab-score or Rochester criteria (10.4%, 95% CI 1.76% to 19.04%). CONCLUSIONS: A sequential approach to young febrile infants based on clinical and laboratory parameters, including procalcitonin, identifies better patients more suitable for outpatient management.

Diagnostic value of procalcitonin in well-appearing young febrile infants.

BACKGROUND AND OBJECTIVE: Procalcitonin (PCT) has been introduced in many European protocols for the management of febrile children. Its value among young, well-appearing infants, however, is not completely defined. Our objective was to assess its performance in diagnosing serious bacterial infections and specifically invasive bacterial infections (IBIs) in well-appearing infants aged <3 months with fever without source (FWS). METHODS: Well-appearing infants aged <3 months with FWS admitted to 7 European pediatric emergency departments were retrospectively included. IBI was defined as the isolation of a bacterial pathogen in blood or cerebrospinal fluid culture. RESULTS: We included 1112 infants who had PCT measured and a blood culture performed. IBI was diagnosed in 23 cases (2.1%). In the multivariate analysis including clinical and laboratory data, PCT was the only independent risk factor for IBI (odds ratio 21.69; 95% confidence interval [CI] 7.93-59.28 for PCT ≥ 0.5 ng/mL). Positive likelihood ratios for PCT ≥ 2 ng/mL and C-reactive protein (CRP) >40 mg/L were 11.14 (95% CI 7.81-15.89) and 3.45 (95% CI 2.20-5.42), respectively. Negative likelihood ratios for PCT <0.5 ng/mL and CRP <20 mg/L were 0.25 (95% CI 0.12-0.55) and 0.41 (95% CI 0.22-0.76). Among patients with normal urine dipstick results and fever of recent onset, areas under the receiver operator characteristic curve for PCT and CRP were 0.819 and 0.563, respectively. CONCLUSIONS: Among well-appearing young infants with FWS, PCT performs better than CRP in identifying patients with IBIs and seems to be the best marker for ruling out IBIs. Among patients with normal urine dipstick results and fever of recent onset, PCT remains the most accurate blood test.

Diagnostic performance of the lab-score in predicting severe and invasive bacterial infections in well-appearing young febrile infants.

BACKGROUND AND OBJECTIVES: The "Lab-score" combining C-reactive protein, procalcitonin and urine dipstick results has recently been derived and validated as an accurate tool for predicting severe bacterial infections (SBIs) in children with fever without source. We aimed to assess the Lab-score usefulness in predicting SBI, especially invasive bacterial infections (IBIs), in well-appearing infants <3 months with fever without source. METHODS: A multicenter retrospective study was conducted in 7 pediatric emergency departments in Spain and Italy. An SBI was defined as isolation of a bacterial pathogen from urine, blood, cerebrospinal fluid or stools, an IBI as isolation of a bacterial pathogen from blood or cerebrospinal fluid. The diagnostic characteristics of the Lab-score for detection of SBI and IBI were calculated. RESULTS: An SBI was diagnosed in 287 (28.3%) of 1012 patients and an IBI in 23 (2.1%) of 1098. The positive and negative likelihood ratios of a score ≥3 for SBI prediction were 10.2 (95% confidence interval [CI]: 9.5-10.9) and 0.5 (95% CI: 0.5-0.5), respectively. The area under the receiver operating characteristic curve was 0.83 (95% CI: 0.80-0.86). The same diagnostic accuracy measures for identification of IBI were 4.3 (95% CI: 4-4.6), 0.4 (95% CI: 0.3-0.5) and 0.85 (95% CI: 0.76-0.94), respectively. Use of Lab-score would have resulted in misdiagnosis of 7 (30%) infants with IBI. CONCLUSIONS: In well-appearing infants with fever without source, the Lab-score seems a more useful tool for ruling in, rather than ruling out, SBI. Its accuracy for IBI prediction was unsatisfactory.

Bacteremia in feverish children presenting to the emergency department: a retrospective study and literature review.

AIM: To evaluate the incidence of bacteremia, and the isolated pathogens, in well-appearing children with fever without source (FWS) presenting to the pediatric emergency department (PED), after pneumococcal conjucate vaccine - 7 valent (PCV-7) widespread introduction in the Veneto region of north-eastern Italy, and to review the main literature contributions on the subject. METHODS: Blood cultures performed at the PED of Padova from 1 June 2006 to 31 January 2009 in febrile children aged 1-36 months were retrospectively retrieved. Medical records of previously healthy well-appearing children with FWS were identified and reviewed. RESULTS: The study finally included 392 patients. Bacteremia rate was 0.34% (95% CI 0-1) in the age group 3-36 months and 2% (95% CI 0-4.7) in infants 1-3 months. No Streptococcus pneumoniae was isolated. The literature review identified 10 relevant studies carried out in the USA and Spain showing an overall bacteremia rate <1% for feverish children aged 3-36 months, with values <0.5% in settings with high PCV-7 coverage. CONCLUSION: Overall bacteremia rate is currently <0.5% in well-appearing children aged 3-36 months with FWS attending the PED in areas with PCV-7 widespread vaccination and is sufficiently low to preclude laboratory testing in favour of close follow-up. Further research is needed to evaluate a more conservative approach in infants 2-3 months of age.