Basophil activation test as predictor of severity and threshold of allergic reactions to egg.

BACKGROUND: Identifying patients at risk of severe allergic reactions and/or low threshold of reactivity is very important, particularly for staple foods like egg. METHODS: One hundred and fifty children underwent double-blind placebo-controlled food challenge (DBPCFC) to baked egg (BE), skin prick testing and blood collection for serology and basophil activation test (BAT). Patients who passed BE DBPCFC underwent loosely cooked egg (LCE) DBPCFC. Severity of allergic reactions was classified following Practall guidelines and threshold dose was determined during DBPCFC. RESULTS: Sixty out of 150 (40%) children reacted to BE and 16 out of 77 (21%) to LCE on DBPCFC. Considering DBPCFC to BE, 23 children (38%) had severe reactions and 33 (55%) reacted to 0.13 g or less of egg protein (low threshold group). Two children (2 out of 16 = 12%) had severe reactions to LCE. Demographic, clinical and most immunological features were not significantly different between severe/non-severe BE reactors or low/high threshold groups. Severe BE reactors had higher ovomucoid-sIgE (p = .009) and higher BAT to BE (p = .001). Patients with lower threshold to BE had higher IgE-specific activity (p = .027) and BAT to egg (p = .007) but lower severity score (p = .008). Optimal cut-offs for ovomucoid-sIgE had 100% sensitivity, 35% specificity and 60% accuracy and for BAT 76% sensitivity, 74% specificity and 75% accuracy to identify BE severe reactors. Optimal cut-offs for specific activity had 70% sensitivity, 68% specificity and 69% accuracy and for BAT 70% sensitivity, 72% specificity and 71% accuracy to identify low threshold patients. CONCLUSIONS: BAT was the best biomarker to predict severity and threshold of allergic reactions to BE and can be useful when making decisions about management of egg allergy.

Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy.

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.

Iron Absorption from an Iron-Fortified Follow-Up Formula with and without the Addition of a Synbiotic or a Human-Identical Milk Oligosaccharide: A Randomized Crossover Stable Isotope Study in Young Thai Children.

BACKGROUND: Previous studies showed that pre- and probiotics may enhance iron absorption. Probiotics combined with prebiotics (synbiotics), including human-identical milk oligosaccharides (HiMOs), are commonly added to infant and follow-up formula (FUF). Whether these additions enhance iron absorption from iron-fortified commercial milk formula is uncertain. OBJECTIVES: We determined the effect of adding 1) a synbiotic [galacto-oligosaccharide [GOS] + Limosilactobacillus reuteri (L. reuteri)] or 2) the HiMO 2'-fucosyllactose (2'FL) to iron-fortified FUF on iron absorption in young Thai children. METHODS: In a randomized, controlled, single-blinded (participants) crossover study, 82 Thai children aged 8-14 mo were enrolled to consume single servings (235 mL) of FUF with isotopically labeled ferrous sulfate (2.2 mg iron) with 1) the synbiotic (400 mg/100 mL GOS and L. reuteri DSM 17938), 2) the HiMO 2'FL (100 mg/100 mL), and 3) without synbiotic and 2'FL (control) in random order and a 3-d washout period between administrations. Fractional iron absorption [FIA (%)] was assessed by measuring erythrocyte incorporation of isotopic labels 14 d (n = 26) and 28 d (n = 76) after consumption of the last test FUF. RESULTS: Median (IQR) FIA from iron-fortified FUF with the synbiotic [8.2 (5.2, 12.9)%] and with 2'FL [8.4 (5.5, 14.1)%] did not differ from the control FUF [8.1 (4.8,14.7)%] (synbiotic compared with control, P = 0.24; 2'FL compared with control, P = 0.95). FIA from all FUF did not differ when measured after 14 and 28 d of erythrocyte incorporation (Time, P = 0.368; FUF, P = 0.435; Time × FUF, P = 0.937). Fecal pH and hemoglobin were negatively associated with FIA. CONCLUSIONS: In young Thai children, the addition of a synbiotic (GOS + L. reuteri) or 2'FL to iron-fortified FUF did not impact FIA from a single serving. The study was registered at clinicaltrials.gov as NCT04774016.

Fish consumption, cognitive impairment and dementia: an updated dose-response meta-analysis of observational studies.

BACKGROUND: Cognitive impairment is projected to affect a preponderant proportion of the aging population. Lifelong dietary habits have been hypothesized to play a role in preventing cognitive decline. Among the most studied dietary components, fish consumptionhas been extensively studied for its potential effects on the human brain. AIMS: To perform a meta-analysis of observational studies exploring the association between fish intake and cognitive impairment/decline and all types of dementia. METHODS: A systematic search of electronic databases was performed to identify observational studies providing quantitative data on fish consumption and outcomes of interest. Random effects models for meta-analyses using only extreme exposure categories, subgroup analyses, and dose-response analyses were performed to estimate cumulative risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: The meta-analysis comprised 35 studies. Individuals reporting the highest vs. the lowest fish consumption were associated with a lower likelihood of cognitive impairment/decline (RR = 0.82, 95% CI: 0.75, 0.90, I2 = 61.1%), dementia (RR = 0.82, 95% CI: 0.73, 0.93, I2 = 38.7%), and Alzheimer's disease (RR = 0.80, 95% CI: 0.67, 0.96, I2 = 20.3%). The dose-response relation revealed a significantly decreased risk of cognitive impairment/decline and all cognitive outcomes across higher levels of fish intake up to 30% for 150 g/d (RR = 0.70, 95% CI: 0.52, 0.95). The results of this relation based on APOE ε4 allele status was mixed based on the outcome investigated. CONCLUSIONS: Current findings suggest fish consumption is associated with a lower risk of cognitive impairment/decline in a dose-response manner, while for dementia and Alzheimer's disease there is a need for further studies to improve the strength of evidence.

Diagnostic utility of allergy tests to predict baked egg and lightly cooked egg allergies compared to double-blind placebo-controlled food challenges.

BACKGROUND: Double-blind placebo-controlled food challenges (DBPCFC) are the gold-standard to diagnose food allergy. However, they can cause allergic reactions of unpredictable severity. We assessed accuracy of current and new diagnostic tests compared to DBPCFC to baked egg (BE) and to lightly cooked egg (LCE). METHODS: Children aged 6 months to 15 years were assessed for possible egg allergy as part of the BAT2 study (NCT03309488). They underwent clinical assessment, skin prick test (SPT), specific IgE (sIgE) and basophil activation test (BAT). The results of the tests were compared with DBPCFC outcomes to both BE and LCE. RESULTS: A total of 150 children underwent DBPCFC to BE, 60 (40%) reacted to and 85 (57%) tolerated BE and 5 (3%) had inconclusive oral food challenges (OFC). Seventy-seven children tolerant to BE had DBPCFC to LCE and 16 reacted. The test within each modality with the best diagnostic performance for BE allergy was as follows: SPT to egg white (EW) (AUC = 0.726), sIgE to EW (AUC = 0.776) and BAT to egg (AUC = 0.783). BAT (AUC = 0.867) was the best test in the younger than 2 years age group. Applying 100% sensitivity and 100% specificity cut-offs, followed by OFC, resulted in 100% diagnostic accuracy. BAT enabled the greatest reduction in OFC (41%). Using sIgE followed by BAT allowed to reduce the number of BATs performed by about 30% without significantly increasing the number of OFC. CONCLUSIONS: The best diagnostic test was BAT to egg in terms of diagnostic accuracy and reduction in number of OFC. Using sIgE to EW followed by BAT required fewer BATs with sustained OFC reduction and diagnostic accuracy.

Anthropometric nutritional status of children (0-18 years) in South Africa 1997-2022: a systematic review and meta-analysis.

OBJECTIVE: To conduct a comprehensive systematic review and meta-analysis of the available literature on the anthropometric nutritional status of South African infants and children, 0-18 years old and to report on trends of changes in nutritional status over the period 1997-2022. DESIGN: Systematic review and meta-analysis. SETTING: Review of the available literature on the anthropometric nutritional status of South African infants and children, 0-18 years old, over the period 1997-2022. PARTICIPANTS: South African infants and children, 0-18 years old. RESULTS: Only quantitative data from ninety-five publications that described the nutritional status in terms of anthropometry were included. Most recent studies applied the WHO 2006 and 2007 definitions for malnutrition among children 0-5 years old and 5-19 years old, respectively. Meta-analysis of all prevalence data shows the highest stunting prevalence of 25·1 % among infants and preschool children, compared to 11·3 % among primary school-age children and 9·6 % among adolescents. Furthermore, the overweight and obesity prevalence was similar among children younger than 6 years and adolescents (19 %), compared to 12·5 % among primary school-age children. In national surveys, adolescent overweight prevalence increased from 16·9 % in 2002 to 23·1 % in 2011. Meta-regression analysis shows a decrease in stunting among children 6-18 years old and an increase in combined overweight and obesity in the 10-19 years age group. CONCLUSION: The double burden of malnutrition remains evident in South Africa with stunting and overweight/obesity the most prevalent forms of malnutrition among children.

Effects of egg as an early complementary food on growth of 6- to 9-month-old infants: a randomised controlled trial.

OBJECTIVE: To assess the effect of daily egg consumption for six months on linear growth (primary outcome), weight-for-age, weight-for-length, mid-upper arm circumference-for-age, head circumference-for-age Z-scores, gross motor milestones development, anaemia and iron status (secondary outcomes) in a low socioeconomic community. PARTICIPANTS: Infants aged 6 to 9 months living in the peri-urban Jouberton area, in the Matlosana Municipality, South Africa. DESIGN: A randomised controlled trial with a parallel design was implemented. Eligible infants were randomly allocated to the intervention (n 250) receiving one egg/day and the control group (n 250) receiving no intervention. The participants were visited weekly to monitor morbidity and gross motor development, with information on adherence collected for the intervention group. Trained assessors took anthropometric measurements, and a blood sample was collected to assess anaemia and iron status. There was blinding of the anthropometric assessors to the groups during measurements and the statistician during the analysis. RESULTS: Baseline prevalence of stunting, underweight, wasting, overweight and anaemia was 23·8 %, 9·8 %, 1·2 %, 13·8 % and 29·2 %, respectively, and did not differ between groups. Overall, 230 and 216 participants in the intervention and control groups completed the study, respectively. There was no intervention effect on length-for-age, weight-for-age, weight-for-length Z-scores, gross motor milestone development, anaemia and iron status. CONCLUSIONS: Daily egg intake did not affect linear growth, underweight, wasting, motor milestones development, anaemia and iron status. Other interventions are necessary to understand the effect of animal-source food intake on children's growth and development. This trial was registered at https://clinicaltrials.gov/ (NCT05168085).

Method's corner: Allergist's guide to network meta-analysis.

Network meta-analyses (NMAs) simultaneously estimate the effects of multiple possible treatment options for a given clinical presentation. For allergists to benefit optimally from NMAs, they must understand the process and be able to interpret the results. Through a worked example published in Pediatric Allergy and Immunology, we summarize how to identify credible NMAs and interpret them with a focus on recent innovations in the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). NMAs build on traditional systematic reviews and meta-analyses that consider only direct paired comparisons by including indirect evidence, thus allowing the simultaneous assessment of the relative effect of all pairs of competing alternatives. Our framework informs clinicians of how to identify credible NMAs and address the certainty of the evidence. Trustworthy NMAs fill a critical gap in providing key inferences using direct and indirect evidence to inform clinical decision making when faced with more than two competing courses of treatment options. This document will help allergists to identify trustworthy NMAs to enhance patient care.

Animal-source foods as a suitable complementary food for improved physical growth in 6 to 24-month-old children in low- and middle-income countries: a systematic review and meta-analysis of randomised controlled trials.

Although animal-source foods are suitable complementary food for child growth in low- and middle-income countries (LMICs), their efficacy is still under discussion. This systematic review and meta-analysis was done to investigate the suitability of animal-source foods intake on child physical growth in LMICs. A systematic literature search was done using electronic databases and scanning the reference list of included studies, previous meta-analysis and systematic reviews. Paper selection was based on the PICO (ST) criteria. Papers were selected if based on 6 to 24-month-old children, if they were randomised controlled trials evaluating the effect of complementary animal-based food supplementation of any natural origin, if reporting at least a measure of body size and published after 2000. The PRISMA guidelines for reporting systematic review was followed in the paper selection. Fourteen papers were included in the systematic review and eight were considered for the meta-analysis. Animal-based food supplementation resulted in a higher length-for-age LAZ and weight-for-age (WAZ) Z-scores compared with the control group with random effect size of 0·15 (95 % CI 0·02, 0·27) and 0·20 (95 % CI 0·03, 0·36), respectively. Results were confirmed after influence analyses, and publication bias resulted as negligible. An increased effect on LAZ and WAZ was observed when the food supplementation was based on egg with effect size of 0·31 (95 % CI = -0·03, 0·64) and 0·36 (95 % CI = -0·03, 0·75), respectively. Animal-source foods are a suitable complementary food to improve growth in 6 to 24-month-old children in LMICs.

Maternal postpartum depression in relation to child undernutrition in low- and middle-income countries: a systematic review and meta-analysis.

Perinatal (antenatal and postpartum) depression is increasingly becoming a global public health problem. Studies have shown that the presence of depression during the perinatal period impact on a mother's ability to adequately provide nutritional care for herself and her infants and young children. This may thus negatively influence the nutritional status of these vulnerable children resulting in poor growth, such as stunting which is currently a public health problem in low- and middle-income countries (LMICs). The aim of this systematic review and meta-analysis was to determine the association between maternal postpartum depression and child growth in LMICs. Electronic databases were systematically reviewed by screening abstracts, titles, full text and additional data sources of eligible papers. Articles were eligible for inclusion if based on children aged 0 to 59 months, if reporting maternal postpartum depression as an exposure, if based on observational studies evaluating the relation between maternal postpartum depression and child growth, if reporting at least one physical growth indicator such as stunting as an outcome, and if published after 2000. Article selection was based on the PRISMA guidelines for reporting systematic reviews. Twelve articles were included in the quantitative synthesis (12 for stunting, 8 for underweight and 2 for wasting). Maternal postpartum depression was observed to be associated with an increased risk of child stunting (1.87 (95% CI: 1.52, 2.30; I2 = 41.6%, p = 0.064)) and underweight (1.81 (95% Cl: 1.25, 2.62; I2 = 70.7%, p = 0.001)). These results were confirmed after influence analyses, with publication bias being negligible.      Conclusion: Maternal depression is a risk factor for poor child growth in LMICs. This study contributes to the knowledge on this topic and calls on policymakers to improve on its understanding, screening and treatment to alleviate the potential negative impact on child growth. What is Known: • Maternal postpartum depression is currently a public health relevance in low- and middle-income countries (LMICs). • Maternal postpartum depression is a risk factor for poor nutritional status in children from LMICs. What is New: • Maternal postpartum depression is associated with an 80 to 90% increased risk of childhood stunting and underweight in LMICs. • The association between risk of childhood stunting and underweight with maternal postpartum depression is slightly influenced by geographical area, rural or urban location, by factors such as study design, study quality and sample size.