Exploring the impact of lifestyle and environmental exposures on appetite hormone levels in children and adolescents: An observational study.

BACKGROUND: Appetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. OBJECTIVES: In this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. METHODS: A total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 µM (PM2.5), nitrogen dioxide (NO2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. RESULTS: GLP-1 was associated with air pollution exposure (NO2 ß* = -0.13, BC ß* = -0.15, PM2.5 ß* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (ß* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin ß* = -0.16; p = 0.04, total ghrelin ß* = -0.23; p = 0.0051) and happiness (active ghrelin ß* = 0.25; p < 0.001, total ghrelin ß* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (ß* = -0.22; p = 0.036). DISCUSSION: Our findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations.

Assessing the influence of COVID-19 lockdown measures on cognition and behavior in school age children in Arba Minch Health and Demographic Surveillance site, Southern Ethiopia: A cross-sectional study.

Ethiopian schools were closed for nearly 40 weeks as a measure to control the COVID-19 pandemic. The objective of the study was to evaluate the role of COVID-19 pandemic's restrictive measures on cognition and behavioral difficulties of schoolchildren in Arba Minch Health and Demographic Surveillance Site. Two cross-sectional surveys were conducted in November 2019 (pre-COVID-19-lockdown) and November 2020 (post-COVID-19 lockdown). Data were collected both at the school and homes of the children. Cognitive development of the children was assessed using digit span, Raven's coloured progressive matrices (RCPM) and Visual search using cancellation task. Behavioral difficulties score of the children was assessed using Strengths and Difficulties Questionnaire. Analysis of covariance (ANCOVA) was used to compare between the cognition outcomes and behavioral difficulties score pre- and post-COVID-19-lockdown. In a sub-group of children who provided data in both surveys, the difference in cognitive and behavioral outcomes was tested using a mixed effect model. Compared to the pre-COVID-19-lockdown, schoolchildren post-COVID-19-lockdown scored lower in the standardized performance index for the visual search task, which measures attention (0.27 SD, 95% confidence intervals (95%CI): -0.40, -0.13). However, they scored higher by 0.26 SD (95%CI: 0.13, 0.40) and 0.36 SD (95%CI: 0.22, 0.49) in digit span and RCPM, respectively, measuring working memory and non-verbal intelligence. There was no significant difference in total difficulties score between pre- and post-COVID-19-lockdown (0.01 SD, 95%CI: -0.12, 0.15). The subgroup analysis showed a significant increase in digit span among children post-COVID-19-lockdown while the other domains did not show a significant change. Factors contributing to the improvement of children's cognitive domains while away from the school environment should be explored and utilized to enhance child development. This study was registered at clinicaltrials.gov as NCT04137354 on October 14, 2019.

Survey data linking coastal visit behaviours to socio-demographic and health profiles.

Coastal destinations are highly popular for leisure, yet the effects of spending time at the coast on mental and physical health have remained underexplored. To accelerate the research about the effects of the coast on health, we compiled a dataset from a survey on a sample (N = 1939) of the adult Flemish population about their visits to the Belgian coast. The survey queried the number of days spent at the coast in the previous year or before and the following characteristics of their visits: how often they performed specific activities, which of the 14 municipal seaside resorts they visited, who they were with, what they mentally and physically experienced, and what reasons they had for not visiting the coast more often. The respondents' geo-demographic (including residential proximity to the coast), socio-economic, and health profile was also collected. We anticipate that investigations on the data will increase our understanding about the social structuring of coastal visits and give context to the effects of the coast on human health.

A longitudinal causal graph analysis investigating modifiable risk factors and obesity in a European cohort of children and adolescents.

Childhood obesity is a complex disorder that appears to be influenced by an interacting system of many factors. Taking this complexity into account, we aim to investigate the causal structure underlying childhood obesity. Our focus is on identifying potential early, direct or indirect, causes of obesity which may be promising targets for prevention strategies. Using a causal discovery algorithm, we estimate a cohort causal graph (CCG) over the life course from childhood to adolescence. We adapt a popular method, the so-called PC-algorithm, to deal with missing values by multiple imputation, with mixed discrete and continuous variables, and that takes background knowledge such as the time-structure of cohort data into account. The algorithm is then applied to learn the causal structure among 51 variables including obesity, early life factors, diet, lifestyle, insulin resistance, puberty stage and cultural background of 5112 children from the European IDEFICS/I.Family cohort across three waves (2007-2014). The robustness of the learned causal structure is addressed in a series of alternative and sensitivity analyses; in particular, we use bootstrap resamples to assess the stability of aspects of the learned CCG. Our results suggest some but only indirect possible causal paths from early modifiable risk factors, such as audio-visual media consumption and physical activity, to obesity (measured by age- and sex-adjusted BMI z-scores) 6 years later.

Prenatal exposure to mixtures of per- and polyfluoroalkyl substances and organochlorines affects cognition in adolescence independent of postnatal exposure.

BACKGROUND: Studies on cognitive and neurodevelopmental outcomes have shown inconsistent results regarding the association with prenatal exposure to perfluoroalkyl substance (PFAS) and organochlorines. Assessment of mixture effects of correlated chemical exposures that persist in later life may contribute to the unbiased evaluation and understanding of dose-response associations in real-life exposures. METHODS: For a subset of the 4th Flemish Environment and Health Study (FLEHS), concentrations of four PFAS and six organochlorines were measured in respectively 99 and 153-160 cord plasma samples and 15 years later in adolescents' peripheral serum by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Sustained and selective attention were measured at 14-15 years with the Continuous Performance Test (CPT) and Stroop Test as indicators of potential neurodevelopmental deficits. Quantile g-computation was applied to assess the joint associations between prenatal exposure to separate and combined groups of PFAS and organochlorines and performance in the CPT and Stroop Test at adolescence. Subsequently, individual effects of each chemical compound were analyzed in mixed effects models with two sets of covariates. Analytical data at birth and at the time of cognitive assessment allowed for off-setting postnatal exposure. RESULTS: In mixtures analysis, a simultaneous one-quantile increase in the natural log-transformed values of PFAS and organochlorines combined was associated with a decrease in the mean reaction time (RT) and the reaction time variability (RTV) in the CPT (ß = -15.54, 95% CI:-29.64, -1.45, and ß = -7.82, 95% CI: -14.97, -0.67 respectively) and for the mixture of PFAS alone with RT (ß = -11.94, 95% CI: -23.29, -0.60). In the single pollutant models, these results were confirmed for the association between perfluorohexanesulfonate (PFHxS) with RT (ß = -17.95, 95% CI = -33.35, -2.69) and hexachlorobenzene with RTV in the CPT (ß = -5.78, 95% CI: -10.39, -0.76). Furthermore, the participants with prenatal exposure above the limit of quantification for perfluorononanoic acid (PFNA) had a significantly shorter RT and RTV in the CPT (ß = -23.38, 95% CI: -41.55, -5.94, and ß = -9.54, 95% CI: -19.75, -0.43, respectively). CONCLUSION: Higher prenatal exposure to a PFAS mixture and a mixture of PFAS and organochlorines combined was associated with better sustained and selective attention during adolescence. The associations seemed to be driven by PFHxS and were not linked to exposure levels at the time of assessment.

Safety of magnesium l-threonate as a novel food pursuant to regulation (EU) 2015/2283 and bioavailability of magnesium from this source in the context of Directive 2002/46/EC.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of magnesium l-threonate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of magnesium from this source in the context of Directive 2002/46/EC. The NF, produced by chemical synthesis, is intended to be used as new source for magnesium in food supplements at a maximum intake level of 3000 mg per day by adults, except for pregnant and lactating women. This dose corresponds to ~ 2730 mg l-threonate and 250 mg magnesium, which also corresponds to the UL for supplemental magnesium from readily dissociable magnesium salts. Based on results obtained from a dissociation study, two rat studies and one human trial, the Panel considers that magnesium is bioavailable from the NF. The NF may contain up to 1% oxalic acid. The Panel considers that an additional exposure to oxalic acid, that is up to 30 mg daily from the NF, is not to be of safety concern. The Panel concludes that the NF is not nutritionally disadvantageous. In 2008, the EFSA ANS Panel concluded that a human intake of l-threonate of 2700 mg per day is safe. This intake is similar to the maximum intake of l-threonate from the NF under the maximum proposed uses, and the NDA Panel concurs with the ANS Panel that this intake is safe. The Panel considers that there are no concerns regarding the genotoxicity of the NF. The Panel concludes that the NF, Mg l-threonate, is safe under the proposed conditions of use. The Panel concludes that the NF is a source from which magnesium is bioavailable.

Safety of ashitaba sap as a Novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on ashitaba sap as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Ashitaba sap is collected from harvested stems of Angelica keiskei plants. The principal constituents of the sap with regard to the safety assessment are chalcones (1%-2.25%) and furanocoumarins (< 0.01%). The applicant proposed to use the NF in food supplements at a maximum dose of 780 mg per day. The target population is adults excluding pregnant and lactating women. Taking into consideration the composition of the NF and the proposed uses, the composition of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study performed with the product as intended to be placed on the market (30% ashitaba sap powder and 70% cyclodextrins), the Panel establishes a safe dose of 0.5 mg/kg body weight (bw) per day for the product as it is intended to be placed on the market. For the target population, i.e. adults, this safe dose corresponds to 35 mg per day of the product as it is intended to be placed on the market and 137 mg per day of the NF, which is lower than the use level proposed by the applicant. The Panel concludes that the NF is safe for the target population at intake levels up to 137 mg per day.

Interplay of the Mediterranean diet and genetic hypertension risk on blood pressure in European adolescents: Findings from the HELENA study.

Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.   Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known: • Adherence to the Mediterranean diet may reduce BP levels. What is New: • It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure. • It is conducted within a multicenter cohort of European adolescents.

Extension of use of isomalto-oligosaccharide as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of isomalto-oligosaccharide (IMO) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of glucose oligomers with degrees of polymerisation of 3-9, along with various amounts of mono- and disaccharides. The NF comes in both syrup and powder form. The applicant intends to extend the current uses of the NF as an ingredient in several foods, and use the NF in food supplements aimed at the general population older than 10 years of age. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. Along with literature data, the applicant carried out a tolerability study in adult volunteers with the NF at doses up to 120 g/day. The Panel concludes that this study provides reassurance that the NF is tolerable at doses of 120 g/day. Conservative intake estimates resulting from the use of the NF as an ingredient according to the currently authorised uses and new proposed uses result in a highest intake estimate in adolescents of 112 g/day at the 95th percentile, and reach 142 g/day in adolescents when the use as a food supplement is included. The Panel notes this amount is higher than the dose of 120 g/day for which tolerability has been demonstrated. However, considering the source, compositional characterisation, production process and nature of the NF, as well as the available nutritional and toxicological data on the NF, the Panel considers that the NF does not present safety concerns under the proposed conditions of use.

Effects of community-based educational video interventions on nutrition, health, and use of health services in low- and middle-income countries: systematic review and meta-analysis.

CONTEXT: Health education using videos has been promoted for its potential to enhance community health by improving social and behavior change communication. OBJECTIVE: To provide stakeholders in maternal and child health with evidence that can inform policies and strategies integrating video education to improve maternal, newborn, and child health. DATA SOURCES: Five databases (MEDLINE, Embase, Scopus, Web of Science, and CENTRAL) were searched on January 28, 2022, and November 10, 2022 (updated search). Quantitative and qualitative studies conducted in low- and middle-income countries on the effects of video-based interventions on nutrition, health, and health service use were eligible. There was no restriction on time or language. Study selection was done in 2 stages and in duplicate. DATA EXTRACTION: A total of 13 710 records were imported to EndNote. Of these, 8226 records were screened by title and abstract using Rayyan, and 76 records were included for full-text evaluation. RESULTS: Twenty-nine articles (n = 12 084 participants) were included in this systematic review, and 7 were included in the meta-analysis. Video interventions improved knowledge about newborn care (n = 234; odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.40), colostrum feeding (n = 990; OR, 60.38; 95%CI, 18.25-199.78), continued breastfeeding (BF; n = 1914; OR, 3.79; 95%CI, 1.14-12.64), intention to use family planning (FP) (n = 814; OR, 1.57; 95%CI, 1.10-2.23), and use of FP (n = 864; OR, 6.55; 95%CI, 2.30-18.70). Video interventions did not result in reduced prelacteal feeding or improvement in early initiation of BF. The qualitative studies showed that video interventions were acceptable and feasible, with perceived impacts on communities. CONCLUSION: This systematic review and meta-analysis indicated that video interventions improved knowledge of newborn care, colostrum feeding, and continuing BF, and the intention to use FP. Given the high levels of heterogeneity and inconsistency in reporting, more research with stronger designs is recommended. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022292190.

Association between urbanization and metabolic syndrome in low- and middle-income countries: A systematic review and meta-analysis.

AIMS: The prevalence of metabolic syndrome (MetS) is on the rise in an increasingly urbanized world. The study aimed to review the association between urbanization and MetS in low- and middle-income countries (LMICs). DATA SYNTHESIS: A comprehensive search of five databases (MEDLINE, Web of Science, Scopus, EMBASE, and CENTRAL) was performed in January 2022 and updated in October 2022. Peer-reviewed studies that met the eligibility selection criteria were included. Search terms were used for the main concepts which are MetS, dietary patterns, and urbanization in LMICs. Study selection was done in two stages and in duplicate. Random effects models were used to calculate the overall pooled prevalence and main study-level characteristics. Out of 9,773 identified studies, nineteen were included in the systematic review and meta-analysis. The studies were done on 313,644 participants (149,616 urban and 164,028 rural). The pooled risk ratio (RR, 95% confidence interval) of MetS between urban and rural dwellers was RR = 1.24; 95%CI [1.15, 1.34] (I2 = 96.0%, P < 0.0001). A relatively higher prevalence of MetS among urban than rural residents has been observed, especially with the International Diabetes Federation criteria (RR = 1.54; 95%CI [1.21, 1.96]; I2 = 65.0%), and in the population in India (RR = 2.19; 95%CI = 1.24, 3.88, I2 = 85%). Overall, the role of dietary patterns in the development of MetS was inconsistent, and few studies showed a lower risk of MetS with adherence to recommended healthy dietary patterns. CONCLUSIONS: There was an association between urbanization and the high prevalence of MetS. Interventions and policies to reduce the risk of MetS are needed.

Safety of isomaltulose syrup (dried) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on isomaltulose syrup (dried) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of a mixture of mono- and disaccharides in powder form, mainly composed of isomaltulose (≥ 75%) and trehalulose (< 13%). The applicant intends to use the NF as a replacement for sucrose already on the market. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. No absorption, distribution, metabolism and excretion (ADME) or toxicological data were provided for the NF. Instead, the safety of the NF was assessed based on literature data available on isomaltulose and mixtures of isomaltulose and trehalulose. In addition, considering the nature, compositional characterisation and production process of the NF, the Panel considered that such data were sufficient to conclude that the NF is as safe as sucrose.

The role of psychosocial well-being and emotion-driven impulsiveness in food choices of European adolescents.

BACKGROUND: It is unclear whether a hypothetical intervention targeting either psychosocial well-being or emotion-driven impulsiveness is more effective in reducing unhealthy food choices. Therefore, we aimed to compare the (separate) causal effects of psychosocial well-being and emotion-driven impulsiveness on European adolescents' sweet and fat propensity. METHODS: We included 2,065 participants of the IDEFICS/I.Family cohort (mean age: 13.4) providing self-reported data on sweet propensity (score range: 0 to 68.4), fat propensity (range: 0 to 72.6), emotion-driven impulsiveness using the UPPS-P negative urgency subscale, and psychosocial well-being using the KINDLR Questionnaire. We estimated, separately, the average causal effects of psychosocial well-being and emotion-driven impulsiveness on sweet and fat propensity applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). Further, we investigated a potential indirect effect of psychosocial well-being on sweet and fat propensity mediated via emotion-driven impulsiveness using a causal mediation analysis. RESULTS: If all adolescents, hypothetically, had high levels of psychosocial well-being, compared to low levels, we estimated a decrease in average sweet propensity by 1.43 [95%-confidence interval: 0.25 to 2.61]. A smaller effect was estimated for fat propensity. Similarly, if all adolescents had high levels of emotion-driven impulsiveness, compared to low levels, average sweet propensity would be decreased by 2.07 [0.87 to 3.26] and average fat propensity by 1.85 [0.81 to 2.88]. The indirect effect of psychosocial well-being via emotion-driven impulsiveness was 0.61 [0.24 to 1.09] for average sweet propensity and 0.55 [0.13 to 0.86] for average fat propensity. CONCLUSIONS: An intervention targeting emotion-driven impulsiveness, compared to psychosocial well-being, would be marginally more effective in reducing sweet and fat propensity in adolescents.

Safety of HelixComplex snail mucus (HSM) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on HelixComplex Snail Mucus (HSM) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of snail mucus collected from Helix aspersa maxima and is proposed to be used by adults as a food supplement. The data provided by the applicant about the composition and stability of the NF together with the report of the subchronic toxicity study were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the certificates of analysis and of the data on the subchronic toxicity provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

Cohort-Based Reference Values for Serum Ferritin and Transferrin and Longitudinal Determinants of Iron Status in European Children Aged 3-15 Years.

BACKGROUND: Reference values of ferritin and transferrin for European children do not exist. OBJECTIVE: We aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3-15-y-old children based on cohort data and to investigate determinants of iron status. METHODS: A total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using cross-sectional and longitudinal data. RESULTS: The age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 µg/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: ß = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: ß = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 µg/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin cross-sectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)]. CONCLUSIONS: Age-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3-15 y and may be used in clinical practice.

Effectiveness of intermittent iron and high-dose vitamin A supplementation on cognitive development of school children in southern Ethiopia: a randomized placebo-controlled trial.

BACKGROUND: Iron is an essential mineral whose deficiency results in cognitive alteration, impaired emotional behaviors, and altered myelination and neurotransmission. In animal models, it has been shown that vitamin A (VA) could affect cognition. OBJECTIVES: The study aimed to evaluate the effectiveness of intermittent iron and VA supplementation on cognitive development of schoolchildren, and to assess the interaction between these supplementations. METHODS: Considering a 2 × 2 factorial design, 504 children were randomly assigned to 1 of the 4 arms: placebo VA and placebo iron supplement; high-dose vitamin VA and placebo iron supplement; iron supplement and placebo VA; and iron and high-dose vitamin VA supplements. Cognitive development was assessed using Raven's Coloured Progressive Matrices, digit span, Tower of London, and visual search tasks. RESULTS: The mean [± standard deviation (SD)] age of the enrolled children was 9.6 (±1.6) y. One-fifth of the children had iron deficiency or anemia, whereas 2.9%, 3.9%, and 12.1% of children had low iron stores, iron deficiency anemia, and VA deficiency, respectively. Intermittent iron supplementation did not result in any significant improvement of children's cognitive development and had a negative effect on the performance index of the visual search task compared with placebo (-0.17 SD, 95% confidence interval: -0.32, -0.02). Effects were evident among children with stunting, thinness, or children coming from understimulating home environments. High-dose VA supplementation resulted in a significant improvement of digit span z-score with a mean difference of 0.30 SD (95% confidence interval: 0.14, 0.46) compared with placebo VA. VA had a more beneficial impact for girls, children infected with helminths, and those from food secure households. CONCLUSION: In a population where the prevalence of iron deficiency is low, intermittent iron supplementation did not have any or negative effect on the child's cognitive development outcomes. Conversely, VA supplementation improved the child's working memory. TRIAL REGISTRATION NUMBER: The study is registered at clinicaltrials.gov as NCT04137354 (https://clinicaltrials.gov/study/NCT04137354).

Population trajectories and age-dependent associations of obesity risk factors with body mass index from childhood to adolescence across European regions: A two-cohort study.

OBJECTIVE: To investigate population trajectories of behavioural risk factors of obesity from childhood to adolescence and their associations with body mass index (BMI) in children across European regions. METHODS: Data were harmonised between the European multi-centre IDEFICS/I.Family and the Amsterdam Born Children and their Development Cohort. Participants were aged 2.0-9.9 and 5.0-7.5 years at baseline, respectively, and were followed until age 18 years. Behavioural risk factors of interest included diet, physical activity, media use and sleep. Mixed effects models were used for statistical analyses to account for repeated measurements taken from the same child. RESULTS: The study included a total of 14 328 individuals: 4114, 4582, 3220 and 2412 participants from Northern, Southern, Eastern Europe and Amsterdam, respectively. Risk factor means and prevalences changed with age, but the trajectories were mostly similar across regions. Almost no associations between behavioural factors and BMI were found at the age of 6 years. At 11 years, daily sugar-sweetened foods consumption, use of active transport, sports club membership and longer nocturnal sleep duration were negatively associated with BMI in most regions; positive associations were found with media use. Most associations at 11 years of age persisted to 15 years. CONCLUSIONS: Whilst population trajectories of media use and nocturnal sleep duration are similar across European regions, those of other behavioural risk factors like active transport and daily vegetable consumption differ. Also, associations between behavioural risk factors and BMI become stronger with age and show similar patterns across regions.

Safety of lacto-N-fucopentaose I/2'-fucosyllactose (LNFP-I/2'-FL) mixture as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-fucopentaose I (LNFP-I)/2'-fucosyllactose (2'-FL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharides (HiMO) LNFP-I and 2'-FL, but it also contains d-lactose, lacto-N-tetraose, difucosyllactose, 3-fucosyllactose, LNFP-I fructose isomer, 2'-fucosyl-d-lactulose, l-fucose and 2'-fucosyl-d-lactitol, and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli K-12 DH1 MDO MP2173b) of E. coli K-12 DH1 (DSM 4235). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant formula (IF) and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements (FS). The target population is the general population. The anticipated daily intake of LNFP-I from use in IF is similar to the estimated natural mean highest daily intake in breastfed infants. Overall, the anticipated daily intake of LNFP-I from the NF as a food ingredient at the maximum proposed use levels is unlikely to exceed the intake level of breastfed infants on a body weight basis. The intake in breastfed infants on a body weight basis is expected to be safe also for other population groups. The anticipated 2'-FL intake is generally rather low. The use of the NF in FS is not intended if other foods with added NF components or human milk (for infants and young children) are consumed on the same day. The Panel concludes that the NF, a mixture of LNFP-I and 2'-FL, is safe under the proposed conditions of use.

Safety of oil from Schizochytrium limacinum (strain TKD-1) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. (TKD-1) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain TKD-1, used by the applicant (ATK Biotech Co. Ltd.), belongs to the species Schizochytrium limacinum. The NF is a mixture of triglycerides in which docosahexaenoic acid (DHA) represents 53%-61% of fatty acids. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use levels proposed by the applicant were derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20-50 mg/100 kcal. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification 'for production purposes only'. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of marine biotoxins and viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

Scientific opinion on the tolerable upper intake level for manganese.

Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for manganese. Systematic reviews of the literature of human and animal data were conducted to assess evidence regarding excess manganese intake (including authorised manganese salts) and the priority adverse health effect, i.e. manganese-induced neurotoxicity. Available human and animal studies support neurotoxicity as a critical effect, however, data are not sufficient and suitable to characterise a dose-response relationship and identify a reference point for manganese-induced neurotoxicity. In the absence of adequate data to establish an UL, estimated background dietary intakes (i.e. manganese intakes from natural dietary sources only) observed among high consumers (95th percentile) were used to provide an indication of the highest level of intake where there is reasonable confidence on the absence of adverse effects. A safe level of intake of 8 mg/day was established for adults ≥ 18 years (including pregnant and lactating women) and ranged between 2 and 7 mg/day for other population groups. The application of the safe level of intake is more limited than an UL because the intake level at which the risk of adverse effects starts to increase is not defined.