Laryngeal Penetration and Risk of Aspiration Pneumonia in Children with Dysphagia-A Systematic Review.

This study was a systematic review and meta-analysis that assessed the risk of aspiration pneumonia in children with laryngeal penetration or tracheal aspiration via a video-fluoroscopic study (VFSS) and compared the results to those for children with neither condition. Systematic searches were conducted using databases, including PubMed, Cochrane Library, and Web of Science. Meta-analysis was used to obtain summary odds ratios (OR) and 95% confidence intervals (CI). The overall quality of evidence was assessed using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. In total, 13 studies were conducted with 3159 participants. Combined results from six studies showed that laryngeal penetration on VFSS may be associated with aspiration pneumonia compared to no laryngeal penetration; however, the summary estimate was imprecise and included the possibility of no association (OR 1.44, 95% CI 0.94, 2.19, evidence certainty: low). Data from seven studies showed that tracheal aspiration might be associated with aspiration pneumonia compared to no tracheal aspiration (OR 2.72, 95% CI 1.86, 3.98, evidence certainty: moderate). The association between aspiration pneumonia and laryngeal penetration through VFSS seems to be weaker than that for tracheal aspiration. Prospective cohort studies with clear definitions of laryngeal penetration and that measure clinical and patient reported outcomes are needed to further define the association between laryngeal penetration and aspiration pneumonia.

Routine antibiotics for infants less than 6 months of age with growth failure/faltering: a systematic review.

OBJECTIVE: This systematic review commissioned by WHO aimed to synthesise evidence from current literature on the effects of systematically given, routine use of antibiotics for infants under 6 months of age with growth failure/faltering. SETTINGS: Low-income and middle-income countries. PARTICIPANTS: The study population was infants less than 6 months of age with growth failure/faltering. INTERVENTION: The intervention group was infants who received no antibiotics or antibiotics other than those recommended in 2013 guidelines by WHO to treat childhood severe acute malnutrition. The comparison group was infants who received antibiotics according to the aforementioned guidelines. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was all-cause mortality, and secondary outcomes: clinical deterioration, antimicrobial resistance, recovery from comorbidity, adverse events, markers of intestinal inflammation, markers of systemic inflammation, hospital-acquired infections and non-response. The Grading of Recommendations Assessment, Development and Evaluation approach was considered to report the overall evidence quality for an outcome. RESULTS: We screened 5137 titles and abstracts and reviewed the full text of 157 studies. None of the studies from the literature search qualified to answer the question for this systematic review. CONCLUSIONS: There is a paucity of evidence on the routine use of antibiotics for the treatment of malnutrition in infants less than 6 months of age. Future studies with adequate sample sizes are needed to assess the potential risks and benefits of antibiotics in malnourished infants under 6 months of age. PROSPERO REGISTRATION NUMBER: CRD42021277073.

Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years.

BACKGROUND: Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed. OBJECTIVES: To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years. SEARCH METHODS: A previous version of this review was published in 2014. In this update, we searched CENTRAL, MEDLINE, Embase, five other databases, and one trials register up to February 2022, together with reference checking and contact with study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) of preventive zinc supplementation in children aged 6 months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalized children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions. DATA COLLECTION AND ANALYSIS: Two review authors screened studies, extracted data, and assessed the risk of bias. We contacted study authors for missing information and used GRADE to assess the certainty of evidence. The primary outcomes of this review were all-cause mortality; and cause-specific mortality, due to all-cause diarrhea, lower respiratory tract infection (LRTI, including pneumonia), and malaria. We also collected information on a number of secondary outcomes, such as those related to diarrhea and LRTI morbidity, growth outcomes and serum levels of micronutrients, and adverse events. MAIN RESULTS: We included 16 new studies in this review, resulting in a total of 96 RCTs with 219,584 eligible participants. The included studies were conducted in 34 countries; 87 of them in low- or middle-income countries. Most of the children included in this review were under five years of age. The intervention was delivered most commonly in the form of syrup as zinc sulfate, and the most common dose was between 10 mg and 15 mg daily. The median duration of follow-up was 26 weeks. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes was affected by risk of bias. High-certainty evidence showed little to no difference in all-cause mortality with preventive zinc supplementation compared to no zinc (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.84 to 1.03; 16 studies, 17 comparisons, 143,474 participants). Moderate-certainty evidence showed that preventive zinc supplementation compared to no zinc likely results in little to no difference in mortality due to all-cause diarrhea (RR 0.95, 95% CI 0.69 to 1.31; 4 studies, 132,321 participants); but probably reduces mortality due to LRTI (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, 132,063 participants) and mortality due to malaria (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 42,818 participants); however, the confidence intervals around the summary estimates for these outcomes were wide, and we could not rule out a possibility of increased risk of mortality. Preventive zinc supplementation likely reduces the incidence of all-cause diarrhea (RR 0.91, 95% CI 0.90 to 0.93; 39 studies, 19,468 participants; moderate-certainty evidence) but results in little to no difference in morbidity due to LRTI (RR 1.01, 95% CI 0.95 to 1.08; 19 studies, 10,555 participants; high-certainty evidence) compared to no zinc. There was moderate-certainty evidence that preventive zinc supplementation likely leads to a slight increase in height (standardized mean difference (SMD) 0.12, 95% CI 0.09 to 0.14; 74 studies, 20,720 participants). Zinc supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 studies, 35,192 participants; high-certainty evidence). We report a number of other outcomes, including the effect of zinc supplementation on weight and serum markers such as zinc, hemoglobin, iron, copper, etc. We also performed a number of subgroup analyses and there was a consistent finding for a number of outcomes that co-supplementation of zinc with iron decreased the beneficial effect of zinc. AUTHORS' CONCLUSIONS: Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.

Increased vs. Standard Dose of Iron in Ready-to-Use Therapeutic Foods for the Treatment of Severe Acute Malnutrition in a Community Setting: A Systematic Review and Meta-Analysis.

The optimal dose of iron in ready-to-use therapeutic foods (RUTF) used to treat uncomplicated severe acute malnutrition (SAM) in community settings is not well established. The objective of this systematic review was to assess if an increased iron dose in RUTF, compared with the standard iron dose in the World Health Organization (WHO)-recommended peanut-based RUTF, improved outcomes in children aged six months or older. We searched multiple electronic databases and only included randomized controlled trials. We pooled the data in a meta-analysis to obtain relative risk (RR) and reported it with a 95% confidence interval (CI). Three studies, one each from Zambia, the Democratic Republic of Congo, and Malawi, were included. In all studies, the RUTF used in the intervention group was milk-free soya-maize-sorghum-based RUTF. The pooled results showed that, compared to the control group, a high iron content in RUTF may lead to increase in hemoglobin concentration (mean difference 0.33 g/dL, 95% CI: 0.02, 0.64, two studies, certainty of evidence: low) and a decrease in any anemia (RR 0.66, 95% CI: 0.48, 0.91, two studies, certainty of evidence: low), but also decrease recovery rates (RR 0.91, 95% CI: 0.84, 0.99, three studies, certainty of evidence: low) and increase mortality (RR 1.30, 95% CI: 0.87, 1.95, three studies, certainty of evidence: moderate). However, the CIs were imprecise for the latter outcome. Future studies with large sample sizes are needed to confirm the beneficial versus harmful effects of high iron content in RUTF in treating uncomplicated SAM in children aged 6-59 months in community settings.

Protocol for a systematic review on routine use of antibiotics for infants less than 6 months of age with growth failure/faltering.

INTRODUCTION: Antibiotics have been used as an adjunct in treating children with severe acute malnutrition 6-59 months of age; however, the data for infants less than 6 months are scarce. The WHO recently started guideline development for preventing and treating wasting, including growth failure/faltering in infants less than 6 months. This systematic review commissioned by WHO aims to synthesise evidence from current literature on the effectiveness of antibiotics for infants less than 6 months of age with growth failure/faltering. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis for studies that assessed the effect of antibiotics in the treatment of infants with growth faltering. We will search multiple electronic databases. We will include randomised control trials and non-randomised studies with a control arm. The study population is infants less than 6 months of age with growth failure. The intervention group will be infants who received no antibiotics or antibiotics other than recommended in 2013 guidelines by WHO to treat severe acute malnutrition in children. The comparison group will be infants who received antibiotics according to the 2013 guideline by WHO. We will consider the following outcomes: mortality, clinical deterioration, antimicrobial resistance, recovery from comorbidity, adverse events, markers of intestinal inflammation, markers of systemic inflammation, hospital-acquired infections, non-response. We will use the meta-analysis to pool the studies where applicable. We will use the Grading of Recommendations Assessment, Development, and Evaluation approach to reporting the overall evidence quality for an outcome. ETHICS AND DISSEMINATION: This is a systematic review and will not involve contact with a human subject. The findings of this review will be published in a peer-review journal and will guide the WHO's recommendation for the use of antibiotics in infants less than 6 months of age with growth failure. PROSPERO REGISTRATION NUMBER: CRD42021277073.

The Effect of Consumption of Animal Milk Compared to Infant Formula for Non-Breastfed/Mixed-Fed Infants 6-11 Months of Age: A Systematic Review and Meta-Analysis.

Many infants do not receive breastmilk for the recommended 2-year duration. Instead, alternative milk beverages are often used, including infant formula and raw animal milk products. The purpose of this systematic review was to summarize the effect of animal milk consumption, compared to infant formula, on health outcomes in non-breastfed or mixed-fed infants aged 6-11 months. We searched multiple databases and followed Cochrane guidelines for conducting the review. The primary outcomes were anemia, gastrointestinal blood loss, weight-for-age, length-for-age, and weight-for-length. Nine studies were included: four randomized controlled trials (RCT) and five cohort studies. All studies, except one, were conducted in high income countries. There was a low certainty of evidence that cow's milk increased the risk of anemia compared to formula milk (Cohort studies RR: 2.26, 95% CI: 1.15, 4.43, RCTs: RR: 4.03, 95% CI: 1.68, 9.65) and gastrointestinal blood loss (Cohort study RR: 1.52, 95% CI: 0.73, 3.16, RCTs: RR: 3.14, 95% CI: 0.98, 10.04). Additionally, there was low certainty evidence that animal milk consumption may not have a differential effect on weight and length-for-age compared to formula milk. Overall, the evidence was of low certainty and no solid conclusions can be drawn from this data. Further studies are needed from low- and middle-income countries to assess optimal milk type in non-breastfed infants aged 6-11 months.

Optimal iron content in ready-to-use therapeutic foods for the treatment of severe acute malnutrition in the community settings: a protocol for the systematic review and meta-analysis.

INTRODUCTION: The current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older. METHODS AND ANALYSIS: We will search multiple electronic databases. We will include randomised controlled trials and non-randomised studies with a control arm. The intervention group will be infants who received RUTF treatments other than the current recommended guidelines set forth by the WHO. The comparison group is children receiving RUTF containing iron at the current WHO-recommended level of 1.9 mg/100 kcal (10-14 mg/100 g). The primary outcomes of interest include blood haemoglobin concentration, any anaemia, severe anaemia, iron-deficiency anaemia, recovery from SAM and any adverse outcomes. We will use meta-analysis to pool findings if sufficient homogeneity exists among included studies. The risk of bias in studies will be evaluated using the Cochrane risk of bias-2. We will use the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach to examine the overall certainty of evidence. ETHICS AND DISSEMINATION: This is a systematic review and will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal and will guide the WHO's recommendation on the optimal iron content in RUTFs for the treatment of SAM in children aged 6-59 months.

Risk of aspiration pneumonia in paediatric patients with dysphagia who were found to have laryngeal penetration on the instrumental swallow evaluation: a systematic review protocol.

INTRODUCTION: Dysphagia affects several children in USA and around the globe. Videofluoroscopic Swallow Study (VFSS) and Fiberoptic Endoscopic Evaluation of Swallowing (FEES) are the most objective studies to define swallowing function. The presence of tracheal aspiration during VFSS or FEES in children with dysphagia is associated with an increased risk of aspiration pneumonia. However, the association of laryngeal penetration with aspiration pneumonia remains unclear. This systematic review aims to assess the risk of aspiration pneumonia in children with dysphagia with laryngeal penetration on VFSS/FEES and compare it with children with tracheal aspiration and children with neither tracheal aspiration nor laryngeal penetration. METHODS AND ANALYSIS: This study will be a systematic review and meta-analysis. Systematic electronic searches will be conducted on PubMed, EMBASE, Web of Science, CINHAL, Scopus, Cochrane CENTRAL, LILACS and WHO Global Index Medicus. We will include studies published through 6 October 2021. Primary outcome will be the incidence of aspiration pneumonia. Secondary outcomes will be incidence of hospitalisation, paediatric intensive care unit admission, enteral tube requirement, growth, symptoms improvement and mortality. The Cochrane Risk of Bias In Non-Randomised Studies of Interventions tool will be used to assess the risk of bias. Meta-analysis will be used to pool the studies. We will pool dichotomous outcomes to obtain an odd ratio (OR) and report with 95% CI. Continuous outcomes will be pooled to obtain mean difference and reported with 95% CI. Overall grade of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and findings will be presented in a summary of findings table. ETHICS AND DISSEMINATION: This study is a systematic review without contact with patients. Therefore, IRB approval is not required. Authors consent to publishing this review. Data will be kept for review by editors and peer reviewers. Data will be available to general public on request. PROSPERO REGISTRATION NUMBER: CRD42020222145.

Effect of consumption of animal milk compared to infant formula for non-breastfed/mixed-fed infants 6-11 months of age: a systematic review (protocol).

INTRODUCTION: Prevalence rates of breastfeeding remain low even though the World Health Organization (WHO) and the American Academy of Pediatrics recommend exclusive breast feeding for the first 6 months of life in combination with appropriate complementary feeding beyond six 6 months of age. There have been several studies that address the implication of drinking animal milk and/or infant formula on children's health and development when breast feeding is not offered during the first year of life. Vast improvements have been made in infant formula design, which may increase its benefits compared with animal's milk. The objective of this review is therefore to synthesise the most recent evidence on the effects of the consumption of animal milk compared with infant formula in non-breastfed or mixed breastfed infants aged 6-11 months. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of studies that assessed the effect of animal milk compared with formula or mixed-fed (breastmilk and formula) on infants aged 6-11 months. The primary outcomes of interest include anaemia, gastrointestinal blood loss, weight for age, height for age and weight for height. We will include randomised and non-randomised studies with a control group. We will use the Cochrane risk of bias tools to assess the risk of bias. We will use meta-analysis to pool findings if the identified studies are conceptually homogenous and data are available from more than one study. We will assess the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. ETHICS AND DISSEMINATION: This is a systematic review, so no patients will be directly involved in the design or development of this study. The findings from this systematic review will be disseminated to relevant patient populations and caregivers and will guide the WHO's recommendations on formula consumption versus animal milk in infants aged 6-11 months. TRIAL REGISTRATION NUMBER: CRD42020210925.