Review on Advances in Pediatric Endoscopy in the Management of Inflammatory Bowel Disease

Over the past decades, an increased importance has been given to gastrointestinal (GI) endoscopy in the management of children with inflammatory bowel diseases (IBD), considering that mucosal healing has been recognized as the optimal endpoint in the treat-to-target paradigm. The recent advances in technology and anesthesia have facilitated the comprehensive evaluation of the GI tract. In this review, we will discuss the role of ileocolonoscopy, upper GI endoscopy, and device-assisted enteroscopy in the work-up and management of pediatric Crohn's disease (CD) and ulcerative colitis, with particular attention on non-invasive endoscopic techniques, such as wireless capsule endoscopy. We will also analyze the most commonly used endoscopic scoring systems, including small bowel scoring systems and endoscopic recurrence grading of neo-terminal ileum CD. Moreover, we will focus on the endoscopic management of complications, such as strictures, that commonly require surgery. Lastly, we will discuss cancer surveillance in children with IBD, with particular consideration of the role of high-definition endoscopic equipment and chromoendoscopy in dysplasia detection rates.

Rectal Bleeding in Infants: Diagnostic Work-up and Management.

Lower gastrointestinal bleeding is an alarming symptom in pediatrics, especially in infancy. However, it is commonly secondary to benign and self-limiting conditions, such as anal fissures, infections, and allergies; more rarely it is caused by more serious disorders, such as necrotizing enterocolitis, very early onset inflammatory bowel diseases, and vascular malformations. The present review aims at summarizing the different clinical conditions presenting with rectal bleeding in infancy and provides an evidence-based diagnostic work-up for the clinical management of patients with this occurrence.

Diagnostic and therapeutic approach to children with chronic refractory constipation: Consensus report by the SIGENP motility working group.

Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation. Children with refractory constipation deserve specialist management and guidance. Over the last decades, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome.

Management of collagenous gastritis in children: Case series and literature review.

Collagenous gastritis (CG) is a rare histopathological finding on gastric biopsies in children. It is associated with abdominal pain and iron deficiency anemia, usually not respondent to oral iron supplements. The aim of this study was to describe our experience in the management of pediatric patients with CG. Moreover, we propose to review the literature on this topic. We retrospectively reviewed all pediatric patients diagnosed with CG at our centre from January 2014 to January 2019. Three pediatric patients (2 F, mean age 12.3) were diagnosed with CG during the study period. Two presented with moderate and one with severe anemia. Symptoms were abdominal pain, asthenia and headache in two and asthenia and abdominal pain in one. All underwent upper and lower gastrointestinal endoscopy. All were firstly started with oral iron supplements with no benefit, principally due to poor compliance secondary to the worsening of the epigastric pain and proton pump inhibitor resistance. Therefore, they underwent ferric carboxymaltose (FCM) infusion with good clinical and laboratory response. Patients received a mean of two infusions/year, with stable hemoglobin levels and no adverse outcomes. Our review failed to identify a consistent response to specific treatments. Considering the apparent benign nature of the disease, symptomatic and supportive treatments are advisable. Iron deficiency anemia is largely present and therapy with oral iron supplements is not always successful. In our study, FCM infusion was effective in increasing the key blood indices in patients who poorly tolerated oral supplements.

Role of inflammation in pediatric irritable bowel syndrome.

BACKGROUND: IBS affects a large number of children throughout the world and is thought to be the result of disturbed neuroimmune function along with the brain-gut axis. Although the underlying pathophysiologic mechanisms are not clear, the role of low-grade inflammation and mucosal immune activation in IBS symptom generation has become evident also in subsets of pediatric patients. Animal models provided meaningful insight in the causal relationship between abnormal mucosal immune activation and changes in gastrointestinal (GI) sensory-motor function. Likewise, the development of long-standing GI symptoms fulfilling the current criteria for functional GI disorders after infection gastroenteritis and in patients with IBD or celiac disease in remission further supports this hypothesis. Immune activation, its impact on gut sensory-motor function, and potential implications for symptom generation emerged in both children and adults with IBS. PURPOSE: The aim of this review is to summarize the main evidence on the presence of low-grade inflammation and immune activation in children with IBS, its possible role in symptom generation, and its potential implication for new therapeutic strategies.

Comparing parental distress and children's difficulties between parents of children with rheumatic diseases and parents of healthy children in families facing the COVID-19 pandemic.

The COVID-19 pandemic could be a threat for the health status of children with a chronic condition. The present study aimed to explore parents' and children's psychological adjustment during the current pandemic, pursuing a triple objective: to compare the psychological adjustment of parents of children with pediatric rheumatic diseases (PRDs) and parents of healthy children; to analyze children's psychological symptoms (emotional problems and hyperactivity) before and during the COVID-19 pandemic, and with or without a PRDs diagnosis; to explore the associations of children's emotional problems and hyperactivity with parents' psychological adjustment, parent-child interactions and belonging or not to families with PRDs. This cross-sectional study involved 56 parents of children with PRDs and 53 parents of healthy children. Self-report questionnaires about parents' depression, anxiety, parenting stress, and children's emotional symptoms and hyperactivity-inattention were administered. No differences were detected on psychological adjustment between parents of children with PRDs and parents of healthy children. Parents of children with PRDs reported statistically significant higher levels of children's emotional problems and hyperactivity before the pandemic, compared to parents of healthy children; during COVID-19 pandemic, emotional symptoms increased for both groups, while hyperactivity-inattention symptoms increased only in the group of healthy children. Children's emotional difficulties were associated with higher levels of parental anxiety, worse parent-child interaction and having PRDs; children's hyperactivity symptoms were related to parent-child difficult interaction and higher levels of parental depression. Findings suggest the importance to target the children in relation to their parents, when approaching the psychological aspects of PRDs.

Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP).

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment. METHODS: Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP). RESULTS: A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians. CONCLUSION: In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice.

Assessment of Cardio-Respiratory Function in Overweight and Obese Children Wearing Face Masks during the COVID-19 Pandemic.

OBJECTIVE: To evaluate whether the use of a surgical and N95 mask for overweight and obese children was associated with respiratory distress. METHODS: We enrolled 15 healthy and 14 overweight or obese children. We performed two sessions: one wearing a surgical, the other an N95 mask. We tracked changes in partial pressure of end-tidal carbon dioxide (PETCO2), oxygen saturation (SaO2), pulse rate (PR), and respiratory rate (RR) during a 72 min test: 30 min without a mask, 30 min wearing a mask, and then during a 12 min walking test. RESULTS: In healthy children, there was no significant change in SaO2 and PETCO2 during the study; there was a significant increase in PR and RR after the walking test with both the masks. In overweight or obese children, there was no significant change in SaO2 during the study period; there was a significant increase in PETCO2 as fast as wearing the mask and an increase in PETCO2, PR, and RR after walking test. After the walking test, we showed a significant correlation between PETCO2 and body mass index. CONCLUSION: Overweight or Obese children who wear a mask are more prone to developing respiratory distress, which causes them to remove it frequently. In a crowded environment, they are at greater risk of infection. For this reason, it is desirable that they attend environments where everyone uses a mask.

Clinical picture and long-term symptoms of SARS-CoV-2 infection in an Italian pediatric population.

BACKGROUND: SARS-CoV-2 infection in the pediatric age group has a milder course than in adults, but in some cases even children may present with severe forms or develop long-term consequences. The aim of this study was to analyze the clinical features, long-term effects, lifestyle changes and psychological effects of SARS-CoV-2 infection in a pediatric sample of the Italian population. METHODS: We conducted a telephone survey among 3075 children infected with SARS-CoV-2 in the Latina Local Health Authority. Outcomes included: clinical features of infection, long-term symptoms, lifestyle changes and emotional symptoms during the illness. The information obtained was automatically linked to a spreadsheet and analyzed. RESULTS: One thousand four hundred thirteen children agreed to participate in the study; the mean age was 112.8 ± 21.9 months. Children were infected mainly inside familial clusters (59.6%; n = 842); 99% (n = 1399) of children were asymptomatic or exhibited mild symptoms. 20% (n = 259) of children experienced long-term symptoms; risk factors were: older age, higher body mass index and longer duration of infection. Throughout the period of infection, children spent most of the time on devices like tv-video, social media and mobile phone for non-educational activities. 58.8% (n = 620) of parents expressed a negative opinion about distance learning. Finally, we observed that 49,6% (n = 532) of children experienced psychological symptoms during quarantine period. CONCLUSION: Despite a lower susceptibility to COVID-19 in children, it is important to keep the focus high in children, both because of the possible long symptoms after infection and the impact on a children's mental and physical health due to pandemic. We believe that the return to school or other extracurricular activities are important to correct some of the risk factors for the long COVID syndrome, as obesity, and to limit the cultural damage generated by distance learning and psychological effects related to restrictive measures.

Evaluation of Risk for Thromboembolic Events in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: The occurrence of thrombotic events in adult patients with inflammatory bowel disease (IBD) is linked to multiple interactions between hereditary and acquired risk factors. There are few published data concerning children with iBD. The aim of this study was to investigate the presence of thromboembolic risk factors also in children with iBD. METHODS: We enrolled three groups of children: one with Crohn disease (cD), one with ulcerative colitis (Uc), and a control group of healthy subjects. For all the participants the potential thromboembolic risk was evaluated clinically and with laboratory tests. RESULTS: We studied: 30 children (25.6%) with CD, 28 (23.9%) with UC, and 59 (50.4%) healthy control subjects. Regarding Pediatric Crohn Disease Activity Index, no significant differences between thromboembolic risk factors and disease activity were detected. Instead, in the patients with UC, stratified with the Pediatric Ulcerative Colitis Activity Index, there was a statistically significant difference in serum fibrinogen levels between patients with mild and moderate/severe disease [3.8 (3.2-4.5) g/L vs 5.7 (4.8-6.2) g/L, P  < 0.0032]. serum homocysteine levels were lower in healthy controls than in CD (P = 0.176) and UC (P = 0.026). An increased level ofhomocysteine in UC with a homozygous mutation in the methylene tetrahydrofolate reductase C677T gene was also observed. CONCLUSIONS: Our study showed that children with IBD have clinical features, acquired and congenital factors that can increase thrombotic risk, similarly to adults.

Change in Pediatric Health Care Spending and Drug Utilization during the COVID-19 Pandemic.

OBJECTIVE: To evaluate how the restrictive measures implemented during the SARS-CoV-2 pandemic have influenced the incidence of the most common children's diseases and the consumption of medications in 2020 compared to 2019. METHODS: We involved all family pediatricians of the local health authority of Latina, from which we requested data of monthly visits in 2019 and 2020 for six common diseases disseminated through droplets and contact, and the territorial and integrative pharmaceutical unit of the area, from which we requested data of the net expenditure regarding the most commonly used drugs at pediatric age. RESULTS: There was significant reduction in the incidence of the evaluated diseases and in the consumption of investigated drugs between 2019 and 2020 in the months when the restrictive measures were in place, with an attenuation of this effect during the months of the gradual loosening of those measures. CONCLUSION: Nonpharmaceutical intervention measures have caused changes in the diffusion of common pediatric diseases. We believe that the implementation of a reasonable containment strategy, even outside of the pandemic, could positively influence the epidemiology of infectious and allergic diseases in children, and healthcare system spending.

Assessment of respiratory function in children wearing a N95 mask with or without an exhalation valve: Data compared.

In response to the current COVID-19 pandemic, universal face masking represents one of the most important strategies to limit the spread of infection. However, their use in children is still highly debated (Esposito and Principi, 2020; Esposito et al., 2020) and there are few data (Lubrano et al., 2021a, 2021b) describing their possible effects on respiratory function in children. A dataset in this paper presents a comparison of the data related to the effects on respiratory function of children wearing a filtering facepiece 2 (N95 mask) with or without exhalation valve. 22 healthy children were randomly assigned to two groups, both groups wearing an N95 mask: one without an exhalation valve (group A), another with an exhalation valve (group B). Children were subjected to a 72 min test: the first 30 min without mask, then 30 min wearing face mask while practiced their usual play activity; finally, 12 min, with face mask in place, while they walked as in a walking test. They were monitored through to microstream capnography system (Rad-97TM with Nomo-Line Capnography, Masimo, Irvine, CA, USA) to log oxygen saturation (SpO2) and respiratory rate (RR). We use the Wilcoxon test to analyzed the differences between the parameters recorded during the study in group A and B. Data analysis was performed using JMP14.3.0 program for Mac by SAS Institute inc.

Physical and Neurological Development of a Girl Born to a Mother with Methylmalonic Acidemia and Kidney Transplantation and Review of the Literature.

BACKGROUND: actual literature suggests that children of methylmalonic acidemia patients are mostly healthy, but data are only partial, especially regarding long-term outcome. Therefore, our aim was to evaluate the possible long-term neurological effects of fetal exposure to high levels of methylmalonic acid in a child of a renal transplant recipient. METHODS: we retrospectively evaluated the clinical and neurological records of a girl whose mother is a kidney transplant recipient affected by methylmalonic acidemia. Subsequently, we compared our results with the ones already published. RESULTS: the girl's weight and stature were within the normal range in the first years of life but, starting from 4 years of age, she became progressively overweight. Regarding the neurodevelopment aspects, for the first time we performed a complete and seriated neuropsychological evaluation, highlighting a mild but significant weakness in the verbal domain, with a worsening trend at three-year revaluation. CONCLUSIONS: since children of MMA patients are exposed to methylmalonic acid, the efforts of the physicians caring for these children should be directed on careful evaluation of growth, prevention of obesity and regular neurological examination together with structured neuropsychological tests to achieve a better insight in possible complications of pregnancy in patients suffering from this condition.

Serum IgG levels in children 6 months after SARS-CoV-2 infection and comparison with adults.

Since the outbreak of SARS-CoV-2 among the population has occurred quite recently, there is a lack of evidence on the long-term duration of antibody response, especially in children. It is therefore crucial to clarify this aspect, considering its implications in the development of successful surveillance strategies, therapies, and vaccinations. The aim of this study was to assess the antibody response in a children group after SARS-CoV-2 infection, and to compare it with that of their parents affected by SARS-CoV-2 infection. We enrolled 12 children and their parents, both groups being affected by COVID-19 in April 2020. In the children's group, we collected real-time RT-PCR cycle threshold (Ct) values and gene characterization of first nasal-throat swab at the time of diagnosis (T0); 30 days after the diagnosis (T30), we performed blood tests to detect anti-SARS-CoV-2 IgM and IgG. Finally, 180 days after the diagnosis (T180), we measured anti-SARS-CoV-2 IgG in both children and parents. In children, antibody levels declined significantly at 180 days (T180) after first measurement (T30). There were no significant differences in IgG level related to age, sex, and clinical manifestations. We found a significant correlation between IgG titers at T30 and Ct value of gene N. Children showed a lower level of antibodies against SARS-CoV-2 at T180 compared to their parents.Conclusion: Antibody responses in children waned 180 days after SARS-CoV-2 infection, and at the same time, their parents showed a different antibody response to the virus. These results highlight that serological tests should be used with caution in surveillance strategies among the general population. What is known: • Currently is not known how long antibody response will be maintained or if it protects from reinfection. • Recent reports in adults suggest that antibodies to SARS-CoV-2 declined several months after infection, but data are missing in pediatric age. What is new: • We showed that antibody responses to SARS-CoV-2 wane several months after infection also in children with quantitative differences in antibody levels between children and adults. • In this context, serological tests should be used with caution in surveillance strategies.

Effects of N95 Mask Use on Pulmonary Function in Children.

OBJECTIVE: To assess whether use of an N95 mask by children is associated with episodes of desaturation or respiratory distress. STUDY DESIGN: Twenty-two healthy children were assigned at random to 1 of 2 groups: one group wearing N95 masks without an exhalation valve and the other group wearing N95 masks with an exhalation valve. We tracked changes in partial pressure of end-tidal carbon dioxide (PETCO2), oxygen saturation, pulse rate, and respiratory rate over 72 minutes of mask use. All subjects were monitored every 15 minutes, the first 30 minutes while not wearing a mask and the next 30 minutes while wearing a mask. They then performed a 12-minute walking test. RESULTS: The children did not experience a statistically significant change in oxygen saturation or pulse rate during the study. There were significant increases in respiratory rate and PETCO2 in the children wearing an N95 mask without an exhalation valve, whereas these increases were seen in the children wearing a mask with an exhalation valve only after the walking test. CONCLUSIONS: The use of an N95 mask could potentially cause breathing difficulties in children if the mask does not have an exhalation valve, particularly during a physical activity. We believe that wearing a surgical mask may be more appropriate for children.

Projectile vomiting and Valsalva-like abdominal contractions as an uncommon presentation of supraventricular tachycardia in an infant.

Paroxysmal supraventricular tachycardia (PSVT) is a prevalent pediatric arrhythmia. Neonatal and infantile-onset presentation is unspecific, thus making differential diagnosis essential in not delaying crucial intervention. We here describe the case of an undetected PSVT in an infant performing repeated abdominal contractions, thus presenting with projectile vomiting. At an early stage of tachycardia, infants are probably able to unconsciously attempt and succeed to terminate acute episodes by strengthening vagal stimulation in the form of Valsalva-like abdominal contractions, but only up to a point. As PSVT progresses, heart failure may develop. Early recognition and treatment are therefore required to minimize negative outcomes.

Assessment of Respiratory Function in Infants and Young Children Wearing Face Masks During the COVID-19 Pandemic.

Importance: Face masks have been associated with effective prevention of diffusion of viruses via droplets. However, the use of face masks among children, especially those aged younger than 3 years, is debated, and the US Centers for Disease Control and American Academy of Physicians recommend the use of face mask only among individuals aged 3 years or older. Objective: To examine whether the use of surgical facial masks among children is associated with episodes of oxygen desaturation or respiratory distress. Design, Setting, and Participants: This cohort study was conducted from May through June 2020 in a secondary-level hospital pediatric unit in Italy. Included participants were 47 healthy children divided by age (ie, group A, aged ≤24 months, and group B, aged >24 months to ≤144 months). Data were analyzed from May through June 2020. Interventions: All participants were monitored every 15 minutes for changes in respiratory parameters for the first 30 minutes while not wearing a surgical face mask and for the next 30 minutes while wearing a face mask. Children aged 24 months and older then participated in a walking test for 12 minutes. Main Outcomes and Measures: Changes in respiratory parameters during the use of surgical masks were evaluated. Results: Among 47 children, 22 children (46.8%) were aged 24 months or younger (ie, group A), with 11 boys (50.0%) and median (interquartile range [IQR]) age 12.5 (10.0-17.5) months, and 25 children (53.2%) were aged older than 24 months to 144 months or younger, with 13 boys (52.0%) and median (IQR) age 100.0 (72.0-120.0) months. During the first 60 minutes of evaluation in the 2 groups, there was no significant change in group A in median (IQR) partial pressure of end-tidal carbon dioxide (Petco2; 33.0 [32.0-34.0] mm Hg; P for Kruskal Wallis = .59), oxygen saturation (Sao2; 98.0% [97.0%-99.0%]; P for Kruskal Wallis = .61), pulse rate (PR; 130.0 [115.0-140.0] pulsations/min; P for Kruskal Wallis = .99), or respiratory rate (RR; 30.0 [28.0-33.0] breaths/min; P for Kruskal Wallis = .69) or for group B in median (IQR) Petco2 (36.0 [34.0-38.0] mm Hg; P for Kruskal Wallis = .97), Sao2 (98.0% [97.0%-98.0%]; P for Kruskal Wallis = .52), PR (96.0 [84.0-104.5] pulsations/min; P for Kruskal Wallis test = .48), or RR (22.0 [20.0-25.0] breaths/min; P for Kruskal Wallis = .55). After the group B walking test, compared with before the walking test, there was a significant increase in median (IQR) PR (96.0 [84.0-104.5] pulsations/min vs 105.0 [100.0-115.0] pulsations/min; P < .02) and RR (22.0 [20.0-25.0] breaths/min vs 26.0 [24.0-29.0] breaths/min; P < .05). Conclusions and Relevance: This cohort study among infants and young children in Italy found that the use of facial masks was not associated with significant changes in Sao2 or Petco2, including among children aged 24 months and younger.

The comprehensive clinic, laboratory, and instrumental evaluation of children with COVID-19: A 6-months prospective study.

OBJECTIVES: To perform a comprehensive clinic, laboratory, and instrumental evaluation of children affected by coronavirus disease (COVID-19). METHODS: Children with a positive result of nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underwent laboratory tests, anal and conjunctival swab, electrocardiography, lung, abdomen, and cardiac ultrasound. Twenty-four-hour ambulatory blood pressure monitoring was performed if abnormal basal blood pressure. Patients were followed-up for 6 months. RESULTS: Three hundred and sixteen children were evaluated; 15 were finally included. Confirmed family member SARS-CoV-2 infection was present in all. Twenty-seven percent were asymptomatic. Anal and conjunctival swabs tests resulted negative in all. Patients with lower body mass index (BMI) presented significantly higher viral loads. Main laboratory abnormalities were: lactate dehydrogenase increasing (73%), low vitamin D levels (87%), hematuria (33%), proteinuria (26%), renal hyperfiltration (33%), and hypofiltration (13%). Two of the patients with hyperfiltration exhibited high blood pressure levels at diagnosis, and persistence of prehypertension at 6-month follow-up. No abnormalities were seen at ultrasound, excepting for one patient who exhibited B-lines at lung sonography. Immunoglobulin G seroconversion was observed in all at 1-month. CONCLUSIONS: Our study confirm that intra-family transmission is important. The significant higher viral loads recorded among patients with lower BMI, together with low vitamin D levels, support the impact of nutritional status on immune system. Renal involvement is frequent even among children with mild COVID-19, therefore prompt evaluation and identification of patients with reduced renal function reserve would allow a better stratification and management of patients. Seroconversion occurs also in asymptomatic children, with no differences in antibodies titer according to age, sex and clinical manifestations.

Scientific Evidence for the Treatment of Children with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is one of the most common functional gastro-intestinal disorders which significantly impacts the quality of life of affected children. Abdominal pain improved by defecation, associated with a change in stool form and frequency, represents its specific clinical marker. Even if a number of potential patho-physiological mechanisms have been described, the exact underlying etiology of IBS is so far unclear. Likewise, no optimal treatment has ever been found neither for adult nor for pediatric patients. Current therapeutic options include drugs, dietary interventions and biopsychosocial therapies. The present review aims at evaluating the scientific evidence supporting the efficacy of these treatments for children with IBS.