Breakfast Skipping, Weight, Cardiometabolic Risk, and Nutrition Quality in Children and Adolescents: A Systematic Review of Randomized Controlled and Intervention Longitudinal Trials

Breakfast skipping increases with age, and an association with a high risk of being overweight (OW) and of obesity (OB), cardiometabolic risk, and unhealthy diet regimen has been demonstrated in observational studies with children and adults. Short-term intervention trials in adults reported conflicting results. The purpose of this systematic review was to summarize the association of breakfast skipping with body weight, metabolic features, and nutrition quality in the groups of young people that underwent randomized controlled (RCT) or intervention longitudinal trials lasting more than two months. We searched relevant databases (2000–2021) and identified 584 articles, of which 16 were suitable for inclusion. Overall, 50,066 children and adolescents were included. No studies analyzed cardiometabolic features. Interventions were efficacious in reducing breakfast skipping prevalence when multi-level approaches were used. Two longitudinal studies reported a high prevalence of OW/OB in breakfast skippers, whereas RCTs had negligible effects. Ten studies reported a lower-quality dietary intake in breakfast skippers. This review provides insight into the fact that breakfast skipping is a modifiable marker of the risk of OW/OB and unhealthy nutritional habits in children and adolescents. Further long-term multi-level intervention studies are needed to investigate the relationship between breakfast, nutrition quality, chronotypes, and cardiometabolic risk in youths.


Introduction
Childhood overweight (OW) and obesity (OB) are major public health issues in both developed and developing countries across the world. The prevalence of obesity has increased worldwide in children and adolescents from 1975 to 2016. By 2000, the trend in children's and adolescents' Body Mass Index (BMI) had reached a high-level-plateau in many high-income countries, but it is continuing to increase in East, South, and South-East Asia [1]. Several factors are involved in the obesity trend, such as genetic implications, birth weight, breastfeeding, parental obesity, physical activity, socioeconomic status, age, and gender [2]. However, dietary habits are among the main actors [3]; in particular, breakfast, the first meal of the day, has a critical role in energy balance and dietary regulation [4]. Weight imbalances during the first periods of life and across adolescence are associated with adverse health consequences over the course of life, particularly non-communicable

Outcome Measures
The primary outcome measures were: (1) body weight, BMI; (2) MetS, arterial hypertension, lipid profile, glucose levels, insulin resistance; and (3) nutrition quality. Included studies had to report at least one of these primary outcomes.

Inclusion and Exclusion Criteria
For inclusion, studies were required to (i) include children and/or adolescents aged 2-18 years (or a mean within these ranges) as subjects of study; (ii) have a defined measure of the child's or adolescent's breakfast consumption and/or breakfast skipping; (iii) be published in peer-reviewed journals in the English language; (vii) be published in the period 2000-2021; (viii) have a follow-up time of at least 2 months. We excluded studies if intervention was not described or if breakfast skipping was not defined.

Identification of Relevant Studies
Potentially relevant papers were selected by reading the titles and abstracts. If abstracts were not available or did not provide enough results, the entire article was retrieved and screened to determine whether it met the inclusion criteria.

Data Extraction and Synthesis
A form was generated to register whether individual studies met eligibility criteria and to collect data regarding the study design and methodological quality. Two authors (RR and AM) independently reviewed the titles and the abstracts in order to identify studies to be included in the review. Any disagreement was discussed with another reviewer (FP). Finally, the full texts of articles that passed the screening and eligibility steps were retrieved and read by the same reviewers. Any difference in opinion about the studies was resolved by discussion between all the investigators. The following data were extracted: author, publication year, study design, characteristics of the participants, description of the intervention, breakfast skipping definition, assessment methodology and reliability and validity of dietary measures, length of follow-up, methods of evaluation of body weight clinical outcomes and changes in cardiometabolic parameters, and nutrition quality.

Quality Assessment
The methodological quality of the included studies was assessed by two reviewers independently (MC and SP). The risk of bias within the included longitudinal studies was assessed by applying the ROBINS-I ("Risk Of Bias In Non-randomized Studies of Interventions") tool [15], which covers seven domains: bias due to confounding; bias in selection of participants into the study; bias in classification of interventions; bias due to deviations from intended intervention; bias due to missing data; bias in measurement of outcomes; and bias in selection of the reported result. The categories for domain-level as well as for the overall risk of bias judgements were: low risk, moderate risk, serious risk, critical risk of bias, and no information. The study was classified as low risk if it was judged to be at low risk of bias for all domains, and as moderate risk if it was considered at low or moderate risk of bias for all domains. If the study was judged to be at serious or critical risk in any domain, it was classified as having a serious or critical risk of bias, respectively. "No information" was used only when there were insufficient data to permit judgement [15]. The risk of bias within the included RTCs was assessed using the Cochrane's revised risk of bias tool RoB 2 [16]. The following domains were evaluated: bias arising from the randomization process; bias due to deviations from intended interventions; bias due to missing outcome data; bias in measurement of the outcome; and bias in selection of the reported result. Each domain was judged as recommended: low risk, high risk, or some concerns [16]. The study was classified as low risk if a low risk of bias for all domains was demonstrated, and as having a high risk of bias if high risk of bias in at least one domain or concerns in multiple domains lowering confidence in the result were demonstrated. Otherwise, if the study was judged to have some concerns in at least one domain but was not at high risk of bias for any domain, it was considered as having some concerns [16]. Consequently, the web app robvis was used to generate figures to present the risk of bias assessments for the selected studies [17]. Disagreements were resolved by discussion between the reviewers. Agreement between reviewers was good: K for agreement was 75.8% (k Cohen: 0.758) after screening titles and abstracts, and 100% after screening full-text articles.

Results
Our search identified a total of 584 potentially eligible studies. Of these, 441 were excluded, having been judged irrelevant on the basis of their titles. The remaining 143 records were screened by reading abstracts and a further 115 studies were excluded as they were observational studies with no intervention described. Thus, 28 articles were retrieved and underwent full-text assessment. Among these, 12 were excluded because they were observational studies without intervention (n = 7) or for reasons related to their outcomes (n = 1) or because breakfast skipping was not defined (n = 4). The selection process is summarized in Figure 1.

Results
Our search identified a total of 584 potentially eligible studies. Of these, 441 were excluded, having been judged irrelevant on the basis of their titles. The remaining 143 records were screened by reading abstracts and a further 115 studies were excluded as they were observational studies with no intervention described. Thus, 28 articles were retrieved and underwent full-text assessment. Among these, 12 were excluded because they were observational studies without intervention (n = 7) or for reasons related to their outcomes (n = 1) or because breakfast skipping was not defined (n = 4). The selection process is summarized in Figure 1.

Risk of Bias within Longitudinal Studies
The risk of bias assessment for the included longitudinal studies is presented in Figure 2a,b. All studies [18][19][20][21][22] were judged to be at moderate risk both for bias due to confounding and for bias in measurement of the outcome, mainly due to some expected, but not serious, residual confounding and to self-reported measures, respectively. Two studies (40%) [18,20] were judged to be at moderate risk for bias due to deviation from intended intervention, particularly in terms of implementation or adherence. All studies [18][19][20][21][22] were considered at low risk for bias in classification of intervention and bias due to missing data. Thus, the overall risk of bias judgment for all the selected longitudinal studies was "Moderate risk".

Risk of Bias within Longitudinal Studies
The risk of bias assessment for the included longitudinal studies is presented in Figure 2a,b. All studies [18][19][20][21][22] were judged to be at moderate risk both for bias due to confounding and for bias in measurement of the outcome, mainly due to some expected, but not serious, residual confounding and to self-reported measures, respectively. Two studies (40%) [18,20] were judged to be at moderate risk for bias due to deviation from intended intervention, particularly in terms of implementation or adherence. All studies [18][19][20][21][22] were considered at low risk for bias in classification of intervention and bias due to missing data. Thus, the overall risk of bias judgment for all the selected longitudinal studies was "Moderate risk".

Findings
Regarding results after the interventions, eight studies described a positive effect with increased frequency in eating breakfast at follow-up [19,20,[22][23][24]26,28,33], while no changes were reported in four studies [25,27,29,32] and a negative final impact was reported in one study [18]. However, the study of Kobel et al. reported an increase in breakfast skipping only in the control group, with stable prevalence in the intervention group, although the results were not significant [29]. Interestingly, one study reported a decrease in breakfast skipping if the intervention was related to a delay of the starting time of the school [22]. Two longitudinal studies and three RCTs reported data about BMI and its correlation with breakfast skipping and/or health promotion intervention [19,21,23,30,33]. O'Dea et al. described a greater prevalence of combined OW/OB in 2006, after a national breakfast promotion campaign, than in 2000 (24.8% versus 21.6%). Therefore, among all participants, those with OW or OB were more likely than normal-weight students to miss

Findings
Regarding results after the interventions, eight studies described a positive effect with increased frequency in eating breakfast at follow-up [19,20,[22][23][24]26,28,33], while no changes were reported in four studies [25,27,29,32] and a negative final impact was reported in one study [18]. However, the study of Kobel et al. reported an increase in breakfast skipping only in the control group, with stable prevalence in the intervention group, although the results were not significant [29]. Interestingly, one study reported a decrease in breakfast skipping if the intervention was related to a delay of the starting time of the school [22]. Two longitudinal studies and three RCTs reported data about BMI and its correlation with breakfast skipping and/or health promotion intervention [19,21,23,30,33]. O'Dea et al. described a greater prevalence of combined OW/OB in 2006, after a national breakfast promotion campaign, than in 2000 (24.8% versus 21.6%). Therefore, among all participants, those with OW or OB were more likely than normal-weight students to miss breakfast either at baseline and at follow-up [19]. Similarly, Traub et al. reported that children who skipped breakfast at baseline were significantly more likely to show increases in waist-to-height ratio, weight, and BMI, in addition to being more highly associated with abdominal obesity at follow-up [21]. Three RCTs did not report significant effects on weight or BMI but these trials were relatively short, with a range of follow-up from three to eight months [23,30,33]. None of the studies investigated glucose metabolism and MetS after the intervention. Only Elseifi et al. measured blood pressure without describing specific results [28]. The nutritional impact was investigated in 11 studies [19,20,23,25,26,[28][29][30][31][32][33]. Two studies reported that the intervention group increased juice consumption and decreased consumption of sugar-sweetened beverages and foods high in saturated fat and added sugars, in comparison with those who did not participate in the school-breakfast program [24,29]. Therefore, the other authors [20,23,26,28,[30][31][32] described the highest proportion of healthy breakfasting after the intervention. All the interventions regarding schools in low economic development areas reported an improvement in nutrition quality [19,25,31,32].

Discussion
Breakfast is the first meal of the day that ends the night fasting period and is deserving of special attention in the field of chrono-nutrition. Several observational studies of all ages reported an increased prevalence of OW/OB in people who skip breakfast [10,[34][35][36][37][38], although these findings have been questioned in two recent meta-analyses on interventional studies in adults [11,39]. Our review demonstrates that breakfast skipping remains associated with a high prevalence of OW/OB and a worse nutritional profile in intervention RCTs and intervention longitudinal trials in children and adolescents.
Manipulation of caloric intake or meal timing in a healthy balanced diet can delay the onset and progression of non-communicable diseases in humans and increase longevity in several organisms [40][41][42]. Time-restricted feeding regimens suggest consuming daily foods in a limited interval of the day in the active phase without caloric restriction but promoting a longer fasting period. Such regimens show higher associations with improved cardiometabolic features and decreased weight than do control diets [43][44][45]. Breakfast skipping/eating is an important issue in this debate, particularly in pediatric nutritional education. In children, the morning chronotype is prevalent, with a shift toward eveningness during puberty and late adolescence for several quite unexplored physiological, social, and environmental reasons [46]. Because eating habits seem to be strictly connected with chronotype and progressively consolidate from childhood to adulthood, strategies to counteract circadian misalignment, unhealthy food regimens, and cardiometabolic disease risk are of importance for the general population.
We selected RCTs and dietary intervention longitudinal trials with the aim of understanding whether breakfast consumption, indirectly favoring late eating in the evening and a healthy food regimen, achieved the goal of lowering the prevalence of OW/OB and cardiometabolic risk, and curbing unhealthy nutrient patterns. Studies included a wide population of 50,066 children and adolescents living in eight countries (seven western countries and one African country), a quite good representation of food habits over a fairly large area of the world, but these numbers remain lower than those previously published in reviews on observational studies [10,34,35]. This aspect is linked to our restrictive inclusion criteria, but also to difficulties in performing trials with an impact on lifestyle. In fact, when children and adolescents are recruited, studies should involve a series of social determinants, such as parents, school, and peers [12,47]. In line with this point, certain of the studies considered involved parents/caregivers [24,27] or the school setting [18][19][20][21]25,27,28,31,32].
Four out of five longitudinal studies promoting breakfast eating reported the skipping habit outcome with conflicting results, with breakfast skipping decreasing in three of them [19,20,22] and increasing in the remaining one [18]. The difference between the studies could depend on several factors, including the time of observation and the local or national context of the study. In fact, the three studies that reported positive results were national or nation-wide campaigns [19,20,22], one of them involving the use of mass media, with additional nutrition advice given at school as part of a health-promoting program and six years of follow-up [19], whilst the study with negative results was a local, less structured program with only one year of follow-up [18]. Interestingly, one of the effective studies reported a decrease in breakfast skipping in schools that delayed their starting time by about 1 h, suggesting that more time in the morning could help maintain a morningness chronotype [22,46]. Similarly contrasting results were reported in the trials with five efficacious studies [23,24,26,28,33] and three others without changes in the percentage of breakfast skipping [25,27,32]. The studies reporting no increase in breakfast eating were all school breakfast policies with free or reduced-price meals at school, while the others were associated with an educational program on the role of breakfast on health. This division across all the studies suggests that well-rounded and prolonged efforts, involving educators, media, governments, policymakers, physicians, and peers, should be expected to have a significant impact on lifestyle habits. Economic discounts are useful but not enough, even where children from low-income families are concerned [48,49]. Furthermore, the wide variety of definitions of breakfast skipping could have affected the results of negative studies.
The two longitudinal studies aiming to evaluate weight reported that OW/OB prevalence after 1 or 6 years, in particular visceral adiposity, is higher in children and adolescents who skipped breakfast, and that this result is independent of age and socio-economic status [19,21]. Although relatively few, these findings confirm those reported in a number of observational studies in children and adolescents [10,34,35]. The authors suggested that this effect derives from circadian rhythms, eating more in the evening, length of night fasting, and lower physical activity levels. Interestingly, some short-term cross-over studies which we did not include in our review due to differences in aims reported that introducing a protein breakfast in adolescents who frequently skipped breakfast reduced food craving and brain activation in regions controlling food motivation and reward, and increased satiety through dopamine mechanisms. Thus, they postulated that strategies with palatable foods and dietary strategies, including breakfast and increased dietary proteins, could restore the blunted dopamine pathway associated with obesity [50][51][52]. Two recent metaanalyses on RCTs in adults reported that introducing breakfast or breakfast skipping has quite negligible effects on weight [11,39]. We found three RCTs with findings on weight in adolescents that had results similar to those for adults [23,30,33]. However, the effects observed in the intervention longitudinal studies we selected are in contrast with the results of RCTs in both children and adults. These differences could be due to several factors, such as age, physical activity, socioeconomic status, ethnicity/country, breakfast and daily nutrient quality, and the use of drugs or other modifiers (tobacco, alcohol, substitute meals, etc.). Furthermore, all the studies with adults (mean duration between 7 and 8.6 weeks) and two out of the three studies with adolescents (lasting 12 to 16 weeks) are quite short [23,30], and therefore bias could have been introduced. Long-term dietary weight loss intervention studies have shown that the weight behavior observed has two phases, with the first one, usually after 6 months, characterized by weight loss, and the second one by weight maintenance or regain [53,54]. Indeed, results in short-term RCTs could not be expandable due to long-term effects. The third RCT study in adolescents had an observation time of 8 months, but the authors concluded that the lack of positive effects on weight could have resulted from poor participation and a failure to reach a moderate-to-high intensity level regarding the interventions [33].
Unfortunately, none of the studies investigated metabolic alterations, in contrast to several observational studies [10]. Only one study evaluated blood pressure values, though not with respect to the intervention [28]. A recent meta-analysis on case-control, crosssectional, longitudinal, or cohort studies in adulthood observed that breakfast skipping was associated with an increased risk of heart disease and with a pooled HR/OR of 1.24 [55]. Efforts are needed to provide further insight into the role of breakfast and its relation to cardiometabolic risk in children in order to help lifestyle prevention programs.
The most important result concerns the quality of diet. Eleven studies investigated nutrition quality and ten out of eleven reported that eating breakfast was associated with an improvement in dietary quality. A decreased intake of sugar-sweetened beverages, saturated fats, and added sugars, or generally unhealthy choices were reported [19,20,23,25,26,[28][29][30][31][32]. It is interesting to note that Ritchie et al. recorded a higher breakfast quality in those who consumed it in the classroom compared to those who ate it in the school cafeteria, and Ask et al. achieved the same results with respect to education on breakfast at home [32], suggesting that, in addition to the nutrient composition of foods, environment and peers have a role that ought to be investigated in further studies [20]. Our data confirm that interventions aimed at increasing breakfast consumption are effective strategies for improving nutrition education and quality, and that this also applies for economically deprived schools [19,25,31,32]. This supports the hypothesis that overall dietary quality, among other socioeconomic or health-related behaviors, may be responsible for the protective effects against weight gain and cardiometabolic risk associated with breakfast consumption recorded in the observational studies and intervention trials analyzed here [10,19,21,23,26,29,30,[34][35][36][37][38]55]. Health-promoting environments are further elements to consider in relation to protective effects concerning weight and metabolism [20,23].
This review has several limitations. In fact, we retrieved relatively few studies on the topics, and data on OW/OB are limited, whereas those on cardiometabolic features are absent. Furthermore, the heterogeneity in the design and the lack of information on daily food intake in most of the studies suggest that our findings ought to be interpreted with caution. However, restricting the analysis to RCTs and intervention longitudinal studies allowed for a causal interpretation of the results, reinforcing our previous findings on observational studies [10]. All the selected studies were at low (RCTs) or moderate risk (longitudinal studies) of bias, suggesting that a certain level of confidence can be placed in the main results. The primary risks are the result of self-reported data, very frequent in population studies, or a lack of detailed information on randomization or adherence. The latter point suggests putting more methodological effort into trials aiming to change lifestyle habits, considering that tailored adherence and empowerment approaches are critical [56].
With these limitations acknowledged, our systematic review on intervention studies suggests that breakfast skipping is associated with a high prevalence of OW/OB and a low nutrition quality-one of the potential players in weight gain and metabolic derangement ( Figure 4). Further high quality and long-term randomized controlled and longitudinal trials are needed to evaluate whether children and adolescents who eat breakfast are better protected against OW/OB and cardiometabolic risk than those who skip it, and whether strategies to introduce breakfast eating in young people is efficacious in the prevention of circadian rhythm misalignment. Our findings provide insights into the need for a multi-level approach to impact on lifestyle habits. Author Contributions: Conceptualization, F.P. and S.B.; methodology, R.R., M.C., A.M. and S.P.; software, S.P., V.A.; validation, M.C., V.A. and F.P.; formal analysis, R.R., M.C., A.M., S.P. and F.P.; investigation, R.R., M.C., A.M. and S.P.; data curation, S.P. and S.B.; writing-original draft preparation, R.R., M.C., A.M., S.P., V.A. and F.P.; writing-review and editing, F.P., M.C., S.P., V.A. and S.B.; supervision, S.B. and F.P.; funding acquisition, F.P. All authors have read and agreed to the published version of the manuscript.

Funding:
The study was supported by the Department of Health Sciences (Excellence Department grant), University of Piemonte Orientale. The funder had no role in the study design, data collection, and analysis.

Conflicts of Interest:
The authors declare no conflict of interest.