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Background: Behaviour-based physical intensity evaluation requires rigorous calibration before application in long-term recordings of children's sleep/activity patterns. This study aimed at (i) calibrating activity counts of motor behaviour measured simultaneously with MotionWatch 8 (MW8) and ActiGraph (GT3X) in 3-year-old children, (ii) documenting movement intensities in 30s-epochs at wrist/hip positions, and (iii) evaluating the accuracy of cut-off agreements between different behavioural activities.

Methods: Thirty 3-year-old children of the NorthPop cohort performed six directed behavioural activities individually, each for 8-10 minutes while wearing two pairs of devices at hip and wrist position. These naturally-occurring behaviours were aligned to movement intensities from 'motionless' (watching cartoons) and 'sedentary' (recumbent story listening, sit and handcraft) to 'light activity' (floor play with toys), 'moderate activity' (engaging in a brisk walk) and 'vigorous activity (a sprinting game). Time-keeping was ensured using direct observation by an observer. Receiver-Operating-Curve classification was applied to determine activity thresholds and to assign two composite movement classes.

Results: Activity counts of MW8 and GT3X pairs of wrist-worn (rho = 0.94) and hip-worn (rho = 0.90) devices correlated significantly (p < 0.001). Activity counts at hip position were significantly lower compared to those at the wrist position (p < 0.001), irrespective of device type. Sprinting, floorball/walk and floorplay assigned as 'physically mobile' classes achieved outstanding accuracy (AUC > 0.9) and two sedentary and a motionless activities assigned into 'physically stationary' classes achieved excellent accuracy (AUC > 0.8).

Conclusion: This calibration provides useful cut-offs for physical activity levels of preschool children. Contextual information of behaviour is advantageous over intensity classifications only, because interventions will focus on behaviour-allocated time to reduce a sedentary lifestyle. Our comparative calibration is one step forward to behaviour-based movement guidelines for 3-year-old children.

Introduction: Diet diversity (DD) in infancy may be protective for early food allergy (FA) but there is limited knowledge about how DD incorporating consumption frequency influences FA risk.

Methods: Three measures of DD were investigated in 2060 infants at 6 and/or at 9 months of age within the NorthPop Birth Cohort Study: a weighted DD score based on intake frequency, the number of introduced foods, and the number of introduced allergenic foods. In multivariable logistic regression models based on directed acyclic graphs, associations to parentally reported physician-diagnosed FA at age 9 and 18 months were estimated, including sensitivity and stratified analyses.

Results: High weighted DD scores (24-31p) at age 9 months were associated with 61% decreased odds of FA at age 18 months [OR (95% CI) = 0.39 0.18–0.88] compared with infants with the lowest DD scores (0-17p). The association remained significant after exclusion of early FA cases. Having introduced 13–14 foods at age 9 months, independent of consumption frequency, was associated with 45% decreased odds of FA [OR (95% CI) = 0.55 (0.31–0.98)] compared to having introduced 0–10 foods. When stratifying, significantly reduced odds for FA were seen for children with eczema and for children with no FA history in the family. No association was seen between DD at age 6 months and FA at age 18 months.

Conclusion: A diverse diet at age 9 months may prevent FA at age 18 months. Our results underscore the need for additional investigations on the impact of consumption frequency in infancy.

Background: Respiratory infections in early life are an identified risk factor for asthma. We hypothesized that infection-prevention measures during the coronavirus disease 2019 (COVID-19) pandemic influenced the risk of respiratory morbidity and aeroallergen sensitization in early childhood. Objective: We compared respiratory morbidity and aeroallergen sensitization in children born before and during the pandemic. Methods: We compared a COVID-19 category (exposed children; n = 1661) to a pre–COVID-19 category (nonexposed children; n = 1676) by using data from the prospective population-based NorthPop Birth Cohort study in Sweden. Data on respiratory morbidity and concomitant medication were retrieved from national registers. Prospectively collected data on respiratory morbidity using web-based questionnaires at 9 and 18 months of age were applied. At age 18 months, serum IgE levels to aeroallergens were determined (n = 1702). Results: The risk of developing any respiratory tract infection (adjusted odds ratio [aOR] = 0.33 [95% CI, 0.26-0.42]), bronchitis (aOR = 0.50 [95% CI, 0.27-0.95]) and croup (aOR = 0.59 [95% CI, 0.37-0.94]) were decreased in the COVID-19 category. The risk of wheeze in the first 9 months was lower in the COVID-19 category (aOR = 0.70 [95% CI, 0.55-0.89]). There were also fewer prescriptions of antibiotics in the COVID-19 category. The prevalence of aeroallergen sensitization was similar between categories. Conclusion: Children born during the COVID-19 pandemic demonstrated significantly decreased risks of respiratory infections and prescribed antibiotics until 18 months of age compared to children born before the COVID-19 pandemic. Whether this will affect the risk of developing asthma in childhood is being followed.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2–4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN’s concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8–24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN’s physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity. The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.

Background: The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein-specific CD-sens), the levels of milk- and casein-specific Immunoglobulin E antibodies (IgE-ab), and the severity of allergic reactions at milk challenges.

Methods: We enrolled 34 patients aged 5–15 (median 9) years who underwent a double-blind placebo-controlled milk-challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk- and casein-specific IgE-ab were analyzed. Following in vitro stimulation of basophils with casein, casein-specific CD-sens, was determined.

Results: Thirty-three patients completed the DBPCMC. There were strong correlations between casein-specific CD-sens and IgE-ab to milk (rs = 0.682, p <.001), and between casein-specific CD-sens and IgE-ab to casein (rs = 0.823, p <.001). There was a correlation between the severity of the allergic reaction and casein-specific CD-sens level (rs = 0.395, p =.041) and an inverse correlation between casein-specific CD-sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = −0.418, p =.027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein-specific CD-sens, 23% had negative casein-specific CD-sens, and 10% were declared non-responders.

Conclusion: Two thirds of those reacting at the DBPMC had positive casein-specific CD-sens, but reactions also occurred despite negative casein-specific CD-sens. The association between casein-specific CD-sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5–10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10−8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.

BACKGROUND: Polychlorinated alkanes (PCAs) constitute a large group of individual congeners originating from commercial chlorinated paraffin (CP) products with carbon chain lengths of PCAs-C_10-13, PCAs-C_14-17, and PCAs-C_18-32, occasionally containing PCAs-C_6-9 impurities. The extensive use of CPs has led to global environmental pollution of PCAs. This study aimed to quantify PCAs in paired serum and breast milk of lactating Swedish mothers, exploring their concentration relationship.

METHODS: Twenty-five paired samples of mothers' blood serum and breast milk were analysed and concentrations were determined for PCAs C_6-32 and compared to 4,4'-DDE, the PCB congener 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), and hexachlorobenzene (HCB).

RESULTS: The median concentrations of PCAs-C_6-9, PCAs-C_10-13, PCAs-C_14-17, PCAs-C_18-32 and ΣPCAs in serum were 14, 790, 520, 16 and 1350 ng/g lipid weight (lw), respectively, and in breast milk 0.84, 36, 63, 6.0 and 107 ng/g lw. Levels of 4,4'-DDE, CB-153 and HCB were comparable in the two matrices, serum and breast milk at 17, 12 and 4.9 ng/g lw. The results show significant differences of PCAs-C_10-13 and PCAs-C_14-17 in breast milk with 22- and 6.2-times lower lw-based concentrations than those measured in serum. On wet weight the differences serum/breast milk ratios of PCAs-C_6-9, PCAs-C_10-13, PCAs-C_14-17, PCAs-C_18-32 and ΣPCAs were 1.7, 3.2, 1.0, 0.4 and 1.6, respectively, while the ratio for 4,4'-DDE, CB-153 and HCB were each close to 0.1.

CONCLUSION: Swedish lactating mothers had high serum concentrations of PCAs-C_10-13 and PCAs-C_14-17, with the ΣPCAs median serum concentration of 1350 ng/g lw. The breast milk concentration, although considerably lower at 107 ng/g lw, still surpassed those of 4,4'-DDE, CB-153 and HCB, suggesting an exposure risk of infants to PCAs. The variation in blood and breast milk accumulation between PCAs and studied legacy POPs, is rarely discussed but warrants further studies on partitioning properties as well as associated toxicological implications.

Background: Randomized controlled trials have demonstrated that early introduction of allergenic foods, such as peanut and egg, can reduce food allergy in high-risk children. Many international guidelines recommend introduction of allergenic foods in the first year of life, and accordingly, the Swedish National Food agency released updated guidelines in June 2019.

Objective: Our aim was to examine whether the age at introduction and consumption frequency of allergenic foods have changed since release of the revised national guidelines on the introduction of solid foods in Sweden.

Methods: Children born between June 2016 and December 2018 (n = 1925) were compared with children born between June 2019 and April 2021 (n = 1761) by using data from the NorthPop Birth Cohort study. Data on food introduction, eczema, and food allergy were prospectively collected until age 18 months by using web-based questionnaires. IgE sensitization was assessed at 18 age months.

Results: The proportion of participants who had been introduced to egg, legume, soy products, peanut, almond, and cashew nut during the first year of life increased after implementation of the revised national guidelines. The most significant changes were seen for legume (from 55.2% to 69.8% [adjusted odds ratio = 1.90 (95% CI = 1.62-2.24)] and peanut (from 29.2% to 43.2% adjusted odds ratio = 1.87 (95% CI = 1.55-2.24)]); consumption frequency had also increased. No differences in the prevalence of eczema, food allergy, or sensitization to the foods of interest were found.

Conclusion: Since release of the revised guidelines, infants in the general population are introduced to and consume a variety of allergenic foods earlier and more frequently; however, early manifestations of allergic disease have remained unchanged.

Introduction: The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13).

Methods: These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared.

Results: Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence.

Discussion: Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.