Proton Pump Inhibitors and Risk of COVID-19 Infection in Children.

OBJECTIVE: To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children. STUDY DESIGN: This retrospective, case-control study included all children < 21 years undergoing COVID-19 PCR testing at a tertiary children's hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes. RESULTS: 116,209 patients age 8.5±6.2 years underwent 234,867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI non-use [RR 0.85 (95% CI 0.76, 0.94), P = 0.002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P = 0.77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P = 0.26]. CONCLUSIONS: We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children.

The Real Relevance of Nonacid Reflux in Pediatric Patients.

Gastroesophageal reflux (GER) is one of the most common presenting complaints to pediatric gastroenterologists, and a wide variety of symptoms in children are potentially attributable to typical or atypical GER. While reflux diagnosis and treatment paradigms classically have focused on targeting acid, there is a growing recognition of the prevalence and significance of nonacid GER in both children and adults. This review explores the role of nonacid reflux in pediatric patients, including definitions, associations with symptoms, pathophysiologic mechanisms, and treatment implications.

Characterization of Eosinophilic Esophagitis in Infants and Toddlers.

OBJECTIVES: The objective of this study is to determine demographic and clinical characteristics of infants and toddlers <2 years with eosinophilic esophagitis (EoE) and to assess treatment response in this rarely studied pediatric age group. METHODS: Retrospective study of children <2 years diagnosed with EoE at a single center from 2016 to 2018. EoE was defined by ≥15 eosinophils per high power field (eos/hpf) on at least 1 esophageal biopsy. Demographics, symptoms, and endoscopic findings were collected via chart review. EoE treatment [proton pump inhibitor (PPI), swallowed steroids, dietary restriction, or a combination] and treatment responses on all follow-up endoscopies were reviewed, with remission defined as <15 eos/hpf. RESULTS: Forty-two children ages 1.3 ± 0.4 years underwent 3.8 ± 2.3 endoscopies over 3.6 ± 1.7 years of follow-up. Thirty-six children (86%) were male, and comorbidities included atopy (86%), reflux (74%), and a history of cow's milk protein allergy (40%). Common symptoms were feeding difficulties in 67% of patients (with gagging or coughing with feeding in 60% and difficulty with progression to pureed or solid foods in 43%), vomiting (57%), and coughing/wheezing (52%). Of the 37 patients with follow-up endoscopies, 25 (68%) had histologic remission. There was an effect of therapy type on histologic response ( P = 0.004) with the best responses seen on combinations of diet/steroids or diet/PPI and the worst response seen on PPIs alone. All patients showed improvement in ≥1 symptom at the time of first follow-up endoscopy. CONCLUSIONS: EoE should be considered in young children with feeding difficulties, vomiting, or respiratory symptoms. All patients improved clinically with standard medical or dietary interventions, however there is dissociation between clinical and histologic response with only 2 of 3 patients achieving histologic remission.

Effect of Added Free Water to Enteral Tube Feeds in Children Receiving Commercial Blends.

OBJECTIVES: To determine the impact of free water administration on clinical outcomes in medically complex patients, based on the hypothesis that patients receiving more thin liquids have worse outcomes related to increased risk of gastroesophageal reflux. METHODS: This was a retrospective chart review of children initiated on commercial blenderized tube feedings from 2010 to 2019. The percentage of gastrostomy intake that was a thin liquid was determined, with thin liquids including free water or thin formula based on the International Dysphagia Diet Standardization Initiative (IDDSI) framework. Patients were categorized into those receiving low volumes of thin liquids ("percent thin" ≤20%) and those receiving higher volumes ("percent thin" >20%). Emergency room visits, hospital admissions, and chest X-rays during the year after starting the blend were compared. RESULTS: Forty-five patients age 12 months to 18.7 years (median 3.7 years) were included. Twenty patients (44%) were receiving a blend with an IDDSI-categorized thin consistency and 25 patients (56%) were receiving a thicker blend. In addition to the blend, patients received a median of 320 mL per day of water (range 0-1000 mL). Patients receiving <20% thin liquids were less likely to undergo chest X-rays during follow-up than patients receiving larger amounts of thin liquids (10% in the minimal thin group versus 48% in the greater thin group, P = 0.03). In a multivariable logistic regression, this relationship remained significant after controlling for underlying pulmonary disease, aspiration, method of feed administration (bolus or continuous feeds), fundoplication status, and oral intake status. CONCLUSIONS: Our study demonstrates that patients on blenderized tube feeds receive widely variable amounts of added thin liquids, like water. The addition of water to tube feeds, while typically given for hydration, can modify feed viscosity and clinical outcomes, such as chest X-ray performance.

Comparison of Aerodigestive and Nonaerodigestive Provider Responses to Clinical Case Vignettes.

OBJECTIVE: To evaluate differences in practice patterns between aerodigestive and nonaerodigestive providers in pediatric gastroenterology when diagnosing and treating common aerodigestive complaints. STUDY DESIGN: A questionnaire comprised of clinical vignettes with multiple-choice questions was distributed to both aerodigestive and nonaerodigestive pediatric gastroenterologists. Vignettes focused on management of commonly encountered general gastroenterology and aerodigestive issues, such as gastroesophageal (GE) reflux, aspiration, and feeding difficulties. Tests of equal proportions were used to compare rates of testing and empiric therapy within and across groups. Multivariate analysis was used to assess differences in response rates between aerodigestive and nonaerodigestive providers. RESULTS: A total of 88 pediatric gastroenterologists from 18 institutions completed the questionnaire. There were 35 aerodigestive gastroenterology providers and 53 nonaerodigestive gastroenterology providers. The nonaerodigestive group included 31 general gastroenterologists and 22 providers with self-identified subspecialty gastroenterology expertise. Aerodigestive specialists were more likely than nonaerodigestive gastroenterologists to pursue testing over empiric therapy in cases involving isolated respiratory symptoms (P < .05); aerodigestive providers were more likely to recommend pH-impedance testing, videofluoroscopic swallow studies, and upper gastrointestinal barium study (P < .05 for each test) depending on the referring physician. For vignettes involving infant GE reflux, both groups chose empiric treatments more frequently than testing (P < .001), although aerodigestive providers were more likely than nonaerodigestive providers to pursue testing like upper gastrointestinal barium studies (P < .05). CONCLUSIONS: Although some practice patterns were similar between groups, aerodigestive providers pursued more testing than nonaerodigestive providers in several clinical scenarios including infants with respiratory symptoms and GE reflux.

Botulinum Toxin as a Treatment for Feeding Difficulties in Young Children.

OBJECTIVE: To determine the effectiveness of intrapyloric botulinum toxin injection (IPBI) for treatment of feeding disorders and associated gastrointestinal symptoms in very young children. STUDY DESIGN: A single-center retrospective study of patients 2 months to 5 years old who received IPBI at Boston Children's Hospital from May 2007 to June 2019 was performed. Charts were reviewed for demographic data, comorbidities, symptoms leading to IPBI, oral and tube feeding data, symptom improvement after IPBI, and need for repeat injections. The primary outcome was symptom improvement at the first gastroenterology clinic visit following IPBI. Secondary outcomes included improvement in oral feeding, decreases in tube feeding, and need for repeat injections. The χ2 or Fisher exact tests and multivariate logistic regression were used to identify factors associated with symptomatic improvement. RESULTS: A total of 85 patients who received 118 injections were included in the final analysis; 57 patients (67%) had partial or complete improvement in symptoms after IPBI. Among the 55 patients with enteral tubes, there was an improvement in feeding, with more patients receiving at least some oral feeds after IPBI compared with before (26/55 vs 15/55; P = .004) and fewer patients receiving postpyloric feeds after IPBI compared with before (12/55 vs 21/55; P = .01). Twenty-six patients (31%) received repeat IPBI within 1 year, with only 6 patients receiving IPBI more than twice. CONCLUSIONS: IPBI is safe and effective in young children. Children with enteral tubes show improvement in oral feeding and reduction in need for postpyloric feeding after IPBI.

A prospective study of intrapyloric botulinum toxin and EndoFLIP in children with nausea and vomiting.

BACKGROUND: Intrapyloric botulinum toxin injection (IPBI) is used to treat nausea and vomiting in children, but no prospective pediatric studies exist. The aims of the current study were to assess the efficacy of IPBI in children with refractory nausea or vomiting and to use EndoFLIP as a biomarker of IPBI response. METHODS: This was a prospective observational cohort study of pediatric patients undergoing IPBI for refractory nausea, vomiting, or feeding difficulties at a tertiary center. Patients completed validated questionnaires at baseline and 1, 2, and 3 months after IPBI. A subset of patients >10 years old underwent pyloric EndoFLIP at the time of IPBI. Symptoms were compared pre- and post-IPBI, and EndoFLIP measurements were assessed in relation to baseline characteristics and response to IPBI. KEY RESULTS: Forty-five patients (mean age 14.2 ± 6.0 years) received IPBI, and 23 of those patients underwent EndoFLIP. Twenty-nine patients (64%) had symptomatic improvement at 1-month follow-up, including improvements in overall GI symptoms (p = 0.003), nausea and vomiting (p = 0.009), and discomfort when eating (p = 0.006). Symptomatic improvements lasted up to 3 months. There was a trend towards lower pyloric distensibility in patients with delayed versus normal gastric emptying (4.5 ± 3.8 mm2 /mmHg in delayed vs. 8.9 ± 6.6 mm2 /mmHg in normal, p = 0.09), though there were no differences in EndoFLIP measurements between IPBI responders and non-responders (p > 0.05). CONCLUSIONS AND INFERENCES: The majority of patients responded to IPBI, with significant improvements seen in nausea, vomiting, and discomfort. Pyloric EndoFLIP tended to distinguish baseline delays in gastric emptying, but it did not predict IPBI response in this patient cohort.

Prucalopride for Treatment of Upper Gastrointestinal Symptoms in Children.

BACKGROUND: Upper gastrointestinal (GI) symptoms are common in pediatrics, and few prokinetics for children exist. The goal of this study was to determine the efficacy of prucalopride for treatment of upper GI symptoms and feeding difficulties in children. METHODS: This was a retrospective study of patients prescribed prucalopride for upper GI symptoms at a single tertiary care center from July 2019 to January 2021. Demographic data, the indication for prucalopride, comorbidities, and feeding data were recorded. The primary outcome was improvement in the primary upper GI symptom at first follow-up after prucalopride initiation. Univariable and multivariable analyses were used to assess for factors associated with improvement. RESULTS: The final study population included 71 patients who received prucalopride for treatment of upper GI symptoms. The most common indications were nausea (44%), feeding difficulties (20%), and reflux (11%). Patients had a median age of 16.7 years (range 1.9-21.8 years), and they had received 4 ± 4.8 years of care in our GI clinic and trialed 3.0 ± 2.0 other GI medications by the time of the prucalopride prescription. At follow-up 3.6 ± 2.9 months after the prucalopride was prescribed, 46 patients (65%) had symptomatic improvement of the upper GI symptom. Improvement was more likely in patients with enteral tubes (p = 0.04), pulmonary comorbidities (p = 0.006), and neurologic comorbidities (p = 0.02). Amongst patients with feeding difficulties, 79% of patients showed improvements in oral or tube feeding. CONCLUSIONS: In this sample of children treated for refractory upper GI symptoms at a single tertiary care center, patients showed improvements in symptoms like nausea, reflux, and feeding difficulties after starting prucalopride.

Eye-tracking, autonomic, and electrophysiological correlates of emotional face processing in adolescents with autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) often have difficulty with social-emotional cues. This study examined the neural, behavioral, and autonomic correlates of emotional face processing in adolescents with ASD and typical development (TD) using eye-tracking and event-related potentials (ERPs) across two different paradigms. Scanning of faces was similar across groups in the first task, but the second task found that face-sensitive ERPs varied with emotional expressions only in TD. Further, ASD showed enhanced neural responding to non-social stimuli. In TD only, attention to eyes during eye-tracking related to faster face-sensitive ERPs in a separate task; in ASD, a significant positive association was found between autonomic activity and attention to mouths. Overall, ASD showed an atypical pattern of emotional face processing, with reduced neural differentiation between emotions and a reduced relationship between gaze behavior and neural processing of faces.

Atypical face processing in children with tuberous sclerosis complex.

There is a high incidence of autism in tuberous sclerosis complex. Given the evidence of impaired face processing in autism, the authors sought to investigate electrophysiological markers of face processing in children with tuberous sclerosis complex. The authors studied 19 children with tuberous sclerosis complex under age 4, and 20 age-matched controls, using a familiar-unfamiliar faces paradigm. Of the children, 6 with tuberous sclerosis complex (32%) had autism. Children with tuberous sclerosis complex showed a longer N290 latency than controls (276 ms vs 259 ms, P = .05) and also failed to show the expected hemispheric differences in face processing. The longest N290 latency was seen in (1) children with autism and tuberous sclerosis complex and (2) children with temporal lobe tubers. This study is the first to quantify atypical face processing in children with tuberous sclerosis complex. This functional impairment may provide insight into a mechanism underlying a pathway to autism in tuberous sclerosis complex.