Using Digital Tools to Study the Health of Adults Born Preterm at a Large Scale: e-Cohort Pilot Study.

BACKGROUND: Preterm birth is a global health concern. Its adverse consequences may persist throughout the life course, exerting a potentially heavy burden on families, health systems, and societies. In high-income countries, the first children who benefited from improved care are now adults entering middle age. However, there is a clear gap in the knowledge regarding the long-term outcomes of individuals born preterm. OBJECTIVE: This study aimed to assess the feasibility of recruiting and following up an e-cohort of adults born preterm worldwide and provide estimations of participation, characteristics of participants, the acceptability of questions, and the quality of data collected. METHODS: We implemented a prospective, open, observational, and international e-cohort pilot study (Health of Adult People Born Preterm-an e-Cohort Pilot Study [HAPP-e]). Inclusion criteria were being an adult (aged ≥18 years), born preterm (<37 weeks of gestation), having internet access and an email address, and understanding at least 1 of the available languages. A large, multifaceted, and multilingual communication strategy was established. Between December 2019 and June 2021, inclusion and repeated data collection were performed using a secured web platform. We provided descriptive statistics regarding participation in the e-cohort, namely, the number of persons who registered on the platform, signed the consent form, initiated and completed the baseline questionnaire, and initiated and completed the follow-up questionnaire. We also described the main characteristics of the HAPP-e participants and provided an assessment of the quality of the data and the acceptability of sensitive questions. RESULTS: As of December 31, 2020, a total of 1004 persons had registered on the platform, leading to 527 accounts with a confirmed email and 333 signed consent forms. A total of 333 participants initiated the baseline questionnaire. All participants were invited to follow-up, and 35.7% (119/333) consented to participate, of whom 97.5% (116/119) initiated the follow-up questionnaire. Completion rates were very high both at baseline (296/333, 88.9%) and at follow-up (112/116, 96.6%). This sample of adults born preterm in 34 countries covered a wide range of sociodemographic and health characteristics. The gestational age at birth ranged from 23+6 to 36+6 weeks (median 32, IQR 29-35 weeks). Only 2.1% (7/333) of the participants had previously participated in a cohort of individuals born preterm. Women (252/333, 75.7%) and highly educated participants (235/327, 71.9%) were also overrepresented. Good quality data were collected thanks to validation controls implemented on the web platform. The acceptability of potentially sensitive questions was excellent, as very few participants chose the "I prefer not to say" option when available. CONCLUSIONS: Although we identified room for improvement in specific procedures, this pilot study confirmed the great potential for recruiting a large and diverse sample of adults born preterm worldwide, thereby advancing research on adults born preterm.

Correlates of bitter, sweet, salty and umami taste sensitivity in European children: Role of sex, age and weight status - The IDEFICS study.

We aimed to describe differences in taste sensitivity in children according to age across 7- to 11-year-old children from eight European countries. We further compared taste sensitivity between boys vs. girls and under-/normal weight vs. overweight/obese children. Within the European multicentre IDEFICS (Identification and prevention of dietary and lifestyle-induced health effects in children and infants) study, 1938 school children participated in sweet, bitter, salty and umami detection threshold tests between 2007 and 2010, using the paired comparison staircase method. The lowest concentration at which the child was able to detect a difference to water was determined as taste detection threshold as a proxy of taste sensitivity. Mean taste thresholds were calculated stratified for sex, age groups, weight groups and country. BMI was calculated using measured height and weight; socio-demographic information was collected using questionnaires. Ordinal logistic regressions were conducted to investigate the association between sex, weight status (as categorical exposure variable) and age (as continuous exposure variable) and the taste sensitivity for the four taste modalities (as outcome), separately. Older children were more taste sensitive for sweet and salty and less taste sensitive for umami and bitter than younger children. Girls were more sensitive to sweet taste than boys. Overweight or obese children were less sensitive to sweet and salty taste compared to normal weight children This was the first study comparing taste sensitivity by measuring taste thresholds in children across different European countries. We conclude that taste thresholds are associated with weight status, children become more sensitive to sweet and salty tastes with increasing age, and girls might be more sensitive to sweet than boys.

Urban Moveability and physical activity in children: longitudinal results from the IDEFICS and I.Family cohort.

BACKGROUND: Physical activity (PA) is one of the major protective behaviours to prevent non-communicable diseases. Positive effects of the built environment on PA are well investigated, although evidence of this association is mostly based on cross-sectional studies. The present study aims to investigate the longitudinal effects of built environment characteristics in terms of a moveability index on PA of children in their transition phase to adolescence using data of the IDEFICS/I.Family cohort. METHODS: We used data on 3394 accelerometer measurements of 2488 children and adolescents aged 3 to 15 years old from survey centres of three countries, Germany, Italy, and Sweden, who participated in up to three surveys over 6 years. In network-dependent home neighbourhoods, a moveability index was calculated based on residential density, land use mix, street connectivity, availability of public transport and public open spaces such as green spaces and public playgrounds in order to quantify opportunities for PA of children and adolescents. Linear trajectories of light PA (LPA) and moderate-to-vigorous PA (MVPA) were estimated using linear mixed models accounting for repeated measurements nested within individuals. Least squares means were estimated to quantify differences in trajectories over age. RESULTS: LPA and MVPA declined annually with age by approximately 20 min/day and 2 min/day respectively. In girls, the moveability index showed a consistent significantly positive effect on MVPA ([Formula: see text] = 2.14, 95% CI: (0.11; 4.16)) for all ages, while in boys the index significantly lessened the decline in LPA with age for each year. ([Formula: see text] = 2.68, 95% CI: (0.46; 4.90)). Availability of public open spaces was more relevant for MVPA in girls and LPA in boys during childhood, whereas in adolescence, residential density and intersection density became more important. CONCLUSION: Built environment characteristics are important determinants of PA and were found to have a supportive effect that ameliorates the decline in PA during the transition phase from childhood to adolescence. In childhood environmental support for leisure time PA through public open spaces was found to be the most protective factor whereas in adolescence the positive influence of street connectivity and residential density was most supportive of physical activity.

Determinants of the urinary and serum metabolome in children from six European populations.

BACKGROUND: Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment-health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project ( http://www.projecthelix.eu ). METHODS: Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6-11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit). RESULTS: We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythreonic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum. CONCLUSIONS: We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children.

Further evidence for the role of pregnancy-induced hypertension and other early life influences in the development of ADHD: results from the IDEFICS study.

The aim of this study is to investigate whether in addition to established early risk factors other, less studied pre-, peri-, and postnatal influences, like gestational hypertension or neonatal respiratory disorders and infections, may increase a child's risk of developing attention-deficit/hyperactivity disorders (ADHD). In the IDEFICS study more than 18,000 children, aged 2-11.9 years, underwent extensive medical examinations supplemented by parental questionnaires on pregnancy and early childhood. The present analyses are restricted to children whose parents also completed a supplementary medical questionnaire (n = 15,577), including the question whether or not the child was ever diagnosed with ADHD. Multilevel multivariable logistic regression was used to assess the association between early life influences and the risk of ADHD. Our study confirms the well-known association between maternal smoking during pregnancy and a child's risk of ADHD. In addition, our study showed that children born to mothers younger than 20 years old were 3-4 times more likely to develop ADHD as compared to children born to mothers aged 25 years and older. Moreover, we found that children whose mothers suffered from pregnancy-induced hypertension had an approximately twofold risk of ADHD (OR 1.95; 95% CI 1.09-3.48). This also holds true for infections during the first 4 weeks after birth (OR 2.06; 95% CI 1.05-4.04). In addition, although not statistically significant, we observed a noticeable elevated risk estimate for neonatal respiratory disorders (OR 1.76; 95% CI 0.91-3.41). Hence, we recommend that these less often studied pre-, peri, and postnatal influences should get more attention when considering early indicators or predictors for ADHD in children. However, special study designs such as genetically sensitive designs may be needed to derive causal conclusions.

Longitudinal associations between food parenting practices and dietary intake in preschool children: The ToyBox Study.

INTRODUCTION: Food Parenting Practices (FPPs) include the practices parents use in the act of feeding their children, which may further influence their health. OBJECTIVES: To assess associations between changes in FPPs (permissiveness, food availability, guided choices, water encouragement, rules and limits and the use of food as reward) over 1 year and dietary intake (water, energy-dense/nutrient-poor and nutrient-dense foods) at follow-up in 4- to 6-year-old preschool-aged children. METHODS: Longitudinal data from the control group of the ToyBox study, a cluster-randomized controlled intervention study, was used (NCT02116296). Multilevel ordinal logistic regression analyses including FPP as the independent variables and dietary intake as outcome. RESULTS: Nine hundred sixty-four parent-child dyads (50.5% boys and 95.0% mothers) were included. Limited changes on the use of FPPs were observed over time. Nevertheless, in boys, often having F&V at home was associated with higher F&V consumption (OR = 6.92 [1.58; 30.38]), and increasing home availability of F&V was directly associated with higher water consumption (OR = 7.62 [1.63; 35.62]). Also, not having sweets or salty snacks available at home was associated with lower consumption of desserts (OR = 4.34 [1.75; 10.75]). In girls, having F&V availability was associated with higher F&V consumption (OR = 6.72 [1.52; 29.70]) and lower salty snack consumption (OR = 3.26 [1.50; 7.10]) and never having soft drinks at home was associated with lower consumption of sweets (OR = 7.89 [6.32; 9.86]). Also, never being permissive about soft drink consumption was associated with lower soft drink consumption (OR = 4.09 [2.44; 6.85]). CONCLUSION: Using favorable FPPs and avoiding the negative ones is prospectively associated with healthier dietary intake, especially of F&V, and less intake of soft drinks, desserts, and salty snacks.

Eating a rainbow. Introducing vegetables in the first years of life in 3 European countries.

Low vegetable consumption in children is a concern in many EU countries, fewer than one fifth of children in Europe consume the WHO recommended amounts. Systematic studies demonstrate that experience with a variety of vegetables early in childhood can promote later consumption as early dietary habits often track into adulthood. This study examined pre-school children's experience with vegetables across three European countries in order to assess cultural differences, effects of age and culinary practices. Mothers of pre-school children (N=234) in the UK (N=71), Denmark (N=93) and France (N=70) completed a survey assessing parental and infant familiarity, frequency of offering and liking for 56 vegetables as well as preparation techniques for these vegetables. Analyses revealed that although children aged 25-36 months had been introduced to the greatest number of vegetables, children aged 6-12 months were offered vegetables more frequently and had a higher reported liking for these vegetables. UK children's liking was related to frequency of maternal intake and frequency of offering. Denmark had introduced the greatest number of vegetables and offered vegetables more frequently than both the UK and France. Choice of preparation methods differed between countries while choice of seasonings was similar. Results suggest increasing variety and frequency of vegetable offering between 6 and 12 months, when children are most receptive, may promote vegetable consumption in children.

Clinical Evaluation of MyoCare in Europe (CEME): study protocol for a prospective, multicenter, randomized, double-blinded, and controlled clinical trial.

BACKGROUND: Myopia prevalence has been increasing in the last decades, and its pathological consequences, including myopic maculopathy and high myopia-associated optic neuropathy, are now one of the most common causes of visual impairment. It is estimated that by 2050, more than 50% of Europeans and Americans will be myopes, which is alarming due to the high morbidity of myopes over - 6.00D. Once myopia has appeared, there are different options with scientific evidence to try to slow the axial length growth. Ophthalmic lenses are the less invasive treatment to control myopia, and there is evidence about the efficacy of different designs, mainly in the Asiatic population. However, new designs have been launched, and it is not known if efficacy is the same between Asiatic and European subjects. Thus, we have set up a randomized, controlled, double-blind, and multicenter trial to investigate the efficacy of a new design of ophthalmic lenses for myopia control in European children. METHODS: A 2-year prospective, multicenter, randomized controlled, and double-blind clinical trial is used to investigate the efficacy of a new design of ophthalmic lenses to slow the progression of myopia. Three hundred children aged from 6 to 13 years old will be recruited and randomly assigned to a study or control group. The study group will be composed of 150 children wearing MyoCare while the control group will be composed of 150 children wearing Clearview. The inclusion criteria will be myopia with a spherical equivalent between - 0.75D and - 5.00D, astigmatism < 1.50D, and anisometropia < 1.00D and having a historical evolution of at least - 0.50 The primary outcome is to compare the mean annual progression of the spherical equivalent between both groups. The secondary outcomes are axial length, choroidal thickness, phorias, and accommodative status of both groups. DISCUSSION: This study will be the first randomized and controlled clinical trial in European children with spectacle lenses based on simultaneous competing defocus. The results will shed light on the clinical evidence of spectacle lenses relying on this new design for the management of myopia with results of efficacy in the non-Asiatic population. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2022-001696. Registered on 27 April 2022. CLINICALTRIALS: gov NCT05919654. Registered on 26 June 2023.

Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health.

Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used 1H NMR spectroscopy in a multicountry study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, N-methylnicotinic acid, urea, and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food consumption and also had higher capacity in discriminating children's diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.

Longitudinal Associations between Food Parenting Practices and Dietary Intake in Children: The Feel4Diabetes Study.

Food parenting practices (FPPs) have an important role in shaping children's dietary behaviors. This study aimed to investigate cross-sectional and longitudinal associations over a two-year follow-up between FPP and dietary intake and compliance with current recommendations in 6- to 11-year-old European children. A total of 2967 parent-child dyads from the Feel4Diabetes study, a randomized controlled trial of a school and community-based intervention, (50.4% girls and 93.5% mothers) were included. FPPs assessed were: (1) home food availability; (2) parental role modeling of fruit intake; (3) permissiveness; (4) using food as a reward. Children's dietary intake was assessed through a parent-reported food frequency questionnaire. In regression analyses, the strongest cross-sectional associations were observed between home availability of 100% fruit juice and corresponding intake (ß = 0.492 in girls and ß = 0.506 in boys, p < 0.001), and between parental role modeling of fruit intake and children's fruit intake (ß = 0.431 in girls and ß = 0.448 in boys, p < 0.001). In multilevel logistic regression models, results indicated that improvements in positive FPPs over time were mainly associated with higher odds of compliance with healthy food recommendations, whereas a decrease in negative FPP over time was associated with higher odds of complying with energy-dense/nutrient-poor food recommendations. Improving FPPs could be an effective way to improve children's dietary intake.

Relative Validity of a Food and Beverage Preference Questionnaire to Characterize Taste Phenotypes in Children Adolescents and Adults.

To assess the relative validity of our food and beverage preference questionnaire we investigated the association between sweet and fatty taste preference scores (assessed using a food and beverage preference questionnaire) and sweet and fatty food propensity scores (derived from a food frequency questionnaire). In I.Family, a large European multi-country cohort study, 12,207 participants from Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden, including 5291 adults, 3082 adolescents, and 3834 children, completed a food and beverage preference questionnaire with 63 items. Cumulative preference scores for sweet and fatty taste were calculated from the single item ranking ranging from 1 to 5. The relative consumption frequency of foods classified as sweet and fatty was used to calculate the corresponding consumption propensities, a continuous variable ranging from 0 to 100. We conducted regression analyses to investigate the association between sweet and fatty taste preference scores and sweet and fatty food propensity scores, respectively, separately for adults, adolescents ≥12 years, and for children <12 years. The overall sweet taste preference score was positively associated with the sweet food consumption propensity score (ß = 2.4, 95% CI: 2.1;2.7) and the fatty taste preference score was positively associated with the fatty food consumption propensity score (ß = 2.0, 95% CI: 1.8;2.2). After stratification for age (children <12 years, adolescents ≥12 years, and adults), the effect remained significant in all age groups and was strongest in adolescents and adults. We conclude that our food and beverage preference questionnaire is a useful instrument for epidemiological studies on sensory perception and health outcomes and for the characterization of sensory taste phenotypes.