Abstracts

Introduction

The rising prevalence of dyslipidemia in children emerges as a notable concern at childhood, evidenced by alterations in the levels of blood lipoproteins, including triglycerides (TG), cholesterol, and high- and low-density lipoproteins (HDL-c and LDL-c, respectively). The main causes of dyslipidemia in childhood are unhealthy lifestyle habits, including diets rich in saturated or trans fats, and physical inactivity. Dyslipidemias can be classified, according to the altered lipid fraction, into the following categories: isolated hypercholesterolemia (increased LDL-c), isolated hypertriglyceridemia (increased TG), mixed hyperlipidemia (increased LDL-c and TG), and low HDL-c (either isolated HDL-c reduction or in association with an increase in LDL-c or TG) ¹1. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol 2017; 109 (2 Suppl 1):1-76..

These changes in lipid fractions play a central role in the development of atherosclerotic cardiovascular diseases ²2. Burlutskaya AV, Tril VE, Polischuk LV, Pokrovskii VM. Dyslipidemia in pediatrician's practice. Rev Cardiovasc Med 2021; 22:817-34.. Clinical manifestations of the atherothrombotic events are more frequent in adulthood. However, early exposure to a hyperlipidemia environment can lead to lipid deposition in the artery walls as early as the first weeks after conception ³3. Napoli C, D'Armiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997; 100:2680-90.. Atherosclerosis can begin in childhood, and serum lipoproteins levels found at this stage tend to remain stable throughout life ⁴4. McMahan CA, Gidding SS, Malcom GT, Tracy RE, Strong JP, McGill Jr. HC. Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis. Pediatrics 2006; 118:1447-55.^,55. Pires A, Sena C, Seiça R. Dyslipidemia and cardiovascular changes in children. Curr Opin Cardiol 2016; 31:95-100.. Fatty streaks can be observed in the intimal layer of the aorta as early as the age of three, and they may progress during the third and fourth decades of life ⁶6. Daniels SR, Greer FR. Lipid screening and cardiovascular health in childhood. Pediatrics 2008; 122:198-208..

Brazilian population studies report prevalence of elevated LDL-c in children ranging from 10% to 47% ⁷7. Pereira AS, Peixoto NGA, Nogueira Neto JF, Lanzillotti HS, Soares EA. Estado nutricional de pré-escolares de creche pública: um estudo longitudinal. Cad Saúde Colet (Rio J.) 2013; 21:140-7.^,88. Calliari SS, Grando LG, Bertol CD, Siqueira LO. Dislipidemia em crianças e adolescentes do município de Marau-RS. Cad Saúde Colet (Rio J.) 2019; 27:368-73.^,99. Maia JAF, Pinto FJM, Silva FR, Dantas DSG, Sampaio RMM, Chaves EMC, et al. Prevalência de dislipidemias em crianças de 2 a 9 anos. Rev Bras Enferm 2020; 73 Suppl 4:e20190759.^,1010. Gomes EIL, Zago VHS, Faria EC. Avaliação de perfis lipídicos infanto-juvenis solicitados nas unidades básicas de saúde em Campinas/SP, Brasil: um estudo laboratorial transversal. Arq Bras Cardiol 2020; 114:47-56.^,1111. Souza NA, Vieira SA, Fonsêca PCA, Andreoli CS, Priore SE, Franceschini SCC. Dislipidemia familiar e fatores associados a alterações no perfil lipídico em crianças. Ciênc Saúde Colet 2019; 24:323-32.. These data highlight the need for timely diagnostic, as well as therapeutic and preventive measures, considering that childhood is a strategic phase in the prevention of atherosclerosis at the population level for the formation of lifestyle habits, which are important causes of cardiovascular risk modulation ¹²12. Faulhaber MCB, Fernandes MA, Roiseman MDML, Taam Filho W. Dislipidemias na infância e na adolescência: um caso de saúde pública? Revista de Pediatria SOPERJ 2009; 10:4-15..

The primary determinants of dyslipidemias are excess weight, diet, physical activity, and genetics. Socioeconomic vulnerability, particularly factors such as low maternal education, and early weaning, is also associated with elevated blood lipids ¹¹11. Souza NA, Vieira SA, Fonsêca PCA, Andreoli CS, Priore SE, Franceschini SCC. Dislipidemia familiar e fatores associados a alterações no perfil lipídico em crianças. Ciênc Saúde Colet 2019; 24:323-32.^,1313. Magalhães TCA, Vieira SA, Priore SE, Ribeiro AQ, Franceschini SCC, Sant'ana LFDR. Fatores associados à dislipidemia em crianças de 4 a 7 anos de idade. Rev Nutr 2015; 28:17-28.. Regarding diet, it is known that increases in total cholesterol (TC) and TG concentrations can be caused by increased intake of cholesterol, carbohydrates, saturated fats, and trans fatty acids. Additionally, increased energy is associated with these changes ¹⁴14. Dearborn JL, Urrutia VC, Kernan WN. The case for diet: a safe and efficacious strategy for secondary stroke prevention. Front Neurol 2015; 6:1.. Data from the Brazilian National Health Survey (PNS, acronym in Portuguese) show high prevalences of consumption of soft drinks, sweets, biscuits, porridge, and other ultra-processed foods, which are high in calories and rich in fats, among children under 2 years of age ¹⁵15. Flores TR, Neves RG, Wendt A, Costa CS, Bertoldi AD, Nunes BP. Padrões de consumo alimentar em crianças menores de dois anos no Brasil: Pesquisa Nacional de Saúde, 2013. Ciênc Saúde Colet 2021; 26:625-36..

Screening children’s lipid profiles is important to assist health promotion policies aimed at reducing cardiovascular risk factors in this population. Furthermore, identifying risk factors associated with dyslipidemia in childhood can contribute to the control of this pathology and reduction of cardiovascular mortality ¹⁶16. Beserra JB, Soares NIS, Marreiros CS, Carvalho CMRG, Martins MCC, Freitas BJSA, et al. Crianças e adolescentes que consomem alimentos ultraprocessados possuem pior perfil lipídico? Uma revisão sistemática. Ciênc Saúde Colet 2020; 25:4979-89.. This study was conducted due to the significance of this subject, the high prevalence of dyslipidemia in childhood, and the lack of research in this age group. Therefore, this study aimed to evaluate the prevalence and factors associated with lipid profile abnormalities in children aged 6 to 42 months in a Brazilian capital city.

Materials and methods

This is a cross-sectional study that used a baseline data from a parallel cluster-randomized clinical trial titled Effect of Fortification with Multiple Micronutrient Powder on the Prevention and Treatment of Iron Deficiency and Anaemia in Brazilian Children: A Randomized Clinical Trial, carried out by the Faculty of Nutrition at the Federal University of Goiás (UFG, acronym in Portuguese), Brazil. The matrix study was previously described in details by Machado et al. ¹⁷17. Machado MMA, Lopes MP, Schincaglia RM, da Costa PSS, Coelho ASG, Hadler MCCM. Effect of fortification with multiple micronutrient powder on the prevention and treatment of iron deficiency and anaemia in Brazilian children: a randomized clinical trial. Nutrients 2021; 13:2160..

The sample consisted of children aged between 6 and 42 months, from early childhood education centers (CMEIs, acronym in Portuguese) in the city of Goiânia (Goiás State), located in the Central-West region of Brazil. The age range of the NutriSUS Strategy - Brazilian Ministry of Health is from 6 to 48 months, therefore, the children were selected at baseline with the criteria of being from 6 to 42 months of age, for them to correspond the age range after the intervention. CMEIs are public institutions linked to the Goiânia Municipal Department of Education. Professionals trained in pedagogy take care of the children for up to eight hours a day, in this first stage of Brazilian primary education (from 6 months to 5 years and 11 months). The exclusion criteria was premature children, twins, those with low birth weight, as well as children being treated for anemia, malaria, HIV or haemoglobinopathies. Children allergic to any of the offered micronutrients were also excluded. Additionally, children without available results of the lipid profile test were excluded.

In the city, CMEIs that had already received fortification with multiple micronutrient powders, those lacking a nursery, or those not operating full-time were excluded from the study. Of the seven existing health districts in Goiânia, five were randomly selected and, subsequently, two CMEIs were randomly selected per health district. In a subsequent random draw, for each district one group was selected to receive ferrous sulfate heptahydrate plus folic acid, while the other received NutriSUS. The selection was performed using a random number list generated by Epi Info 6.04d (https://www.cdc.gov/epiinfo/index.html). By employing a simple random draw function in Excel 365 (https://products.office.com/), the randomization process was stratified by gender and age group ¹⁷17. Machado MMA, Lopes MP, Schincaglia RM, da Costa PSS, Coelho ASG, Hadler MCCM. Effect of fortification with multiple micronutrient powder on the prevention and treatment of iron deficiency and anaemia in Brazilian children: a randomized clinical trial. Nutrients 2021; 13:2160..

Collection took place between March 2018 and March 2019, in the city of Goiânia, after the parents or children’ guardians signed the Informed Consent Form. Interviews were conducted in CMEIs by trained undergraduate students of Nutrition, and supervised by a nutritionist, or master and doctoral students in Nutrition. The registered variables were: child age (months), sex (male/female), race or skin color (white vs. non-white), maternal age (years), maternal education (completed years), monthly income per capita (converted from BRL 3.60 to USD 1.00 at the exchange rate on May 9, 2018), breastfeeding maternal status (current practice - yes/no), duration of exclusive breastfeeding (days), body mass index for age (BMI-for-age z-score) and height for age (z-score) ¹⁸18. World Health Organization. Child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. Geneva: World Health Organization; 2006..

Weight and height measurements were taken in duplicate at the CMEIs. For the body weight measurement, a SECA 877 digital scale (https://www.seca.com) with a capacity of 200kg and an accuracy of 100g was used. For height measurement, the child was placed in an orthostatic position using a portable stadiometer (Alturexata; https://alturexata.com.br/) affixed to a baseboard-free wall. For children under 2 years of age, length was assessed in the supine position.

Blood collection was performed by a technician from the laboratory responsible for the analyses. Children who did not attend the CMEI on the date of the blood collection had their samples collected at home or at the laboratory. Venous blood was collected after a fasting period of three hours (for children under 12 months) to eight hours. TC, HDL-c, and TG were determined by the enzymatic colorimetric method, with automation by the Cobas 8000 c502 equipment (Roche Corporation; https://www.roche.com/), following the manufacturer’s recommendations. LDL-c concentrations were calculated using the Friedewald formula ¹⁹19. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chemistry 1972; 18:499-502..

Additionally, the following lipid profile variables were determined for individuals older than 2 years: increased TC (≥ 170mg/dL), decreased HDL-c (≤ 45mg/dL), increased TG (≥ 75mg/dL), increased LDL-c (≥ 110mg/dL) ¹1. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol 2017; 109 (2 Suppl 1):1-76.^,2020. Slhessarenko N, Fontes CJ, Slhessarenko ME, Azevedo RS, Andriolo A. Proposition of decision limits for serum lipids in Brazilian children aged one to 13 years. J Pediatr (Rio J.) 2019; 95:173-9.^,2121. Sociedade Brasileira de Pediatria. Guia prático de atualização: dislipidemia na criança e no adolescente - orientações para o pediatra. Rio de Janeiro: Sociedade Brasileira de Pediatria; 2020., and alteration in at least one of the previously mentioned lipid profile parameters (at least one altered parameter). For children aged 6 to 23 months, reference values from the U.S. National Cholesterol Education Program (NCEP) - Expert Panel on Blood Cholesterol Levels in Children and Adolescents ²²22. National Cholesterol Education Program. Expert Panel of Blood Cholesterol Levels in Children and Adolescents: highlights of the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics 1992; 89:495-501. were used, due to the absence of specific recommendations for this age group within Brazilian guidelines ¹1. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol 2017; 109 (2 Suppl 1):1-76.. Lipoprotein concentrations thresholds for children aged 6 to 23 months are defined as follows: high TC (≥ 200mg/dL), high TG (≥ 100mg/dL), high LDL-c (≥ 130mg/dL), and low HDL-c (< 40mg/dL) ²²22. National Cholesterol Education Program. Expert Panel of Blood Cholesterol Levels in Children and Adolescents: highlights of the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics 1992; 89:495-501..

Dietary intake for one day was assessed, and for two days in 20% of the sample (one month interval), by direct food-weighing and 24-hour dietary recall (24hR). Weighing was carried for all meals served at the CMEI (breakfast, morning snack, lunch, afternoon snack, and dinner), using a BEL precision balance, model S6501 (https://www.belengineering.com), with an accuracy of 0.01g, according to the procedures by Cruz et al. ²³23. Cruz ATR, Sousa JMPS, Philippi ST. Avaliação da concordância dos métodos de pesagem direta de alimentos em creches, São Paulo - Brasil. Rev Bras Epidemiol 2003; 6:220-6.. The 24hR was applied to the parents or guardians of the child on the same day as the direct food-weighing, for nutrients consumption assessment outside of the CMEI, to obtain information about the child’s complete eating day, with the aid of utensils and photographic records of foods, following the multiple-pass method (MPM) ²⁴24. Steinfeldt L, Anand J, Murayi T. Food reporting patterns in the USDA automated multiple-pass method. Procedia Food Sci 2013; 2:145-56.. According to specific tables, all preparations mentioned in household measurements were converted into grams or milliliters ²⁵25. Instituto Brasileiro de Geografia e Estatística. Pesquisa de Orçamentos Familiares 2008-2009: tabela de composição nutricional dos alimentos consumidos no Brasil. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2011.^,2626. Sistema de Informação sobre a Biodiversidade Brasileira. Biodiversidade & nutrição. Composição nutricional e receitas. https://ferramentas.sibbr.gov.br/ficha/bin/view/FN/ (accessed on 14/Apr/2020).
https://ferramentas.sibbr.gov.br/ficha/b... ^,2727. Universidade Estadual de Campinas. Tabela brasileira de composição de alimentos - TACO. Campinas: Universidade Estadual de Campinas; 2011.. Nutrients intake was assessed by the sum of data from direct food: weighing + 24hR.

Total energy intake and the following nutrients were assessed: energy (kcal), carbohydrates (g), protein (g), total fat (g), saturated fat (g), trans fatty acids (g), monounsaturated fats (g), polyunsaturated fats (g), omega-6 (g), omega-3 (g), omega-6 to omega-3 ratio (ω-6/ω-3 ratio), cholesterol (mg), and dietary fiber (g). Dietary intake was analyzed using the dietWin Profissional Plus software (dbv3090; http://www.dietwin.com.br). Data were double-entered into Excel version 365 and validated in Epi-Info 6.04d. The statistical modeling software, Multiple Source Method (MSM; https://msm.dife.de/), was used to estimate usual macronutrients and energy intake, reducing intra-individual variance ²⁸28. Haubrock J, Nöthlings U, Volatier JL, Dekkers A, Ocké M, Harttig U, et al. Estimating usual food intake distributions by using the multiple source method in the EPIC-Potsdam Calibration Study. J Nutr 2011; 141:914-20..

The database was created using Excel for Windows (version 10), with double entry to check data consistency. Normality was assessed using the Shapiro-Wilk test (p > 0.05). The sample was characterized by absolute and relative frequencies for the categorical variables, mean and standard deviation for the parametric variables, and median and interquartile range (IQR) for the nonparametric variables. A boxplot was constructed for better visualization of nonparametric data. Pearson’s chi-square test or Fisher’s exact test were used to assess the association between the independent categorical variables and the outcome. The Mann-Whitney U-test and t-test were applied to compare the independent numeric variables with the outcome (lipid profile). Poisson regression with robust variance analysis was conducted, estimating the prevalence ratio (PR) with a 95% confidence interval (95%CI) ²⁹29. Barros AJ, Hirakata VN. Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio. BMC Med Res Methodol 2003; 3:21.. Variables with p < 0.20 were selected for the multiple regression model and adjusted pseudo R-squared (pseudo R²), estimated using the same regression statistical method. A significance level of 5% was adopted for all tests. Analyses were performed using Stata software, version 16.0 (https://www.stata.com).

The study received approval from the Research Ethics Committee of the UFG (protocol n. 3,692,768). It was also registered with the Brazilian Registry of Clinical Trials (REBEC, acronym in Portuguese; protocol RBR-4hm7mz). The research strictly adhered to the criteria set by Resolution n. 466/2012 of the Brazilian National Health Council concerning research standards involving human subjects.

Results

Out of the initial 205 children who began the study, 169 were included in the present analysis, with the remaining participants being filtered based on inclusion and exclusion criteria [excluded (n = 36): not meeting inclusion criteria (n = 16), declined to participate (n = 4), without lipid profile test (n = 15), and other reasons (n = 1)]. The sample characteristics are detailed in Table 1. Slightly over 50% were girls and identified as belonging to a non-white racial or ethnic group (50% mixed race and 5% black). Breastfeeding is still practiced to feed approximately one-third of the children, with the median duration of exclusive breastfeeding being 4 months. Details on children’s nutrient intake are provided in Table 1.

In examining the associations between dyslipidemia diagnoses and sociodemographic, maternal, breastfeeding-related, anthropometric, and nutritional consumption variables, it was noted that children with increased triglycerides exhibited higher BMI-for-age z-score, and individuals with increased LDL-c levels were older (Table 1). The PRs of associations between socioeconomic, demographic, anthropometric, and nutritional consumption factors with dyslipidemia were presented using simple Poisson regression with robust variance adjustment model in Table 2, and with a multiple Poisson regression model as outlined in Table 3.

Older age was associated with a higher prevalence of children having increased TC and LDL-c. On the other hand, older age was associated with a decreased prevalence of reduced HDL-c (Table 3). Additionally, an increased intake of dietary cholesterol and energy was associated with a higher prevalence of reduced HDL-c levels in children. A higher prevalence of increased LDL-c was also associated with higher dietary cholesterol intake (Table 3). Finally, a higher BMI z-score was associated with a higher prevalence of elevated TG (Table 2).

The median TC was 146mg/dL (IQR: 131-169), HDL-c was 38mg/dL (IQR: 32-45), LDL-c was 88mg/dL (IQR: 74-107), and TG was 81mg/dL (IQR: 68-105) (Figure 1). It was determined that 48% of the sample population had at least two altered lipid parameters. In descending order of frequency, these were: low HDL-c, high TG, high LDL-c, and elevated TC (Figure 2). Regarding children older than 2 years, the prevalences of low HDL-c, high TG, high LDL-c, and elevated TC were 72%, 54%, 27%, and 24%, respectively.

Discussion

This study highlighted a significant finding: high prevalence of dyslipidemia in the sample, primarily characterized by reduced HDL-c and elevated TG. Data analysis showed that changes in the lipid profile were associated with age (older age linked to increased TC and LDL-c, and younger age linked to lower HDL-c), higher BMI-for-age (z-score), and increased dietary intake of calories and cholesterol. Notably, serum lipid levels did not display significant differences across genders, races, maternal age and education levels, income, breastfeeding practices, height, and certain dietary variables (such as carbohydrates, protein, total fat, saturated fat, trans fatty acids, monounsaturated fat, polyunsaturated fat, omega-6, omega-3, ω-6/ω-3 ratio, and fiber).

The proportion of children with low HDL-c found in this research exceeds some studies, which reported frequencies of 54% ⁹9. Maia JAF, Pinto FJM, Silva FR, Dantas DSG, Sampaio RMM, Chaves EMC, et al. Prevalência de dislipidemias em crianças de 2 a 9 anos. Rev Bras Enferm 2020; 73 Suppl 4:e20190759. and 57% ⁸8. Calliari SS, Grando LG, Bertol CD, Siqueira LO. Dislipidemia em crianças e adolescentes do município de Marau-RS. Cad Saúde Colet (Rio J.) 2019; 27:368-73. in the Brazilian states Ceará and Rio Grande do Sul, respectively. The observed frequency of high TC in our study is lower than that reported in other national studies, which have documented rates between 33% and 45% ⁸8. Calliari SS, Grando LG, Bertol CD, Siqueira LO. Dislipidemia em crianças e adolescentes do município de Marau-RS. Cad Saúde Colet (Rio J.) 2019; 27:368-73.^,99. Maia JAF, Pinto FJM, Silva FR, Dantas DSG, Sampaio RMM, Chaves EMC, et al. Prevalência de dislipidemias em crianças de 2 a 9 anos. Rev Bras Enferm 2020; 73 Suppl 4:e20190759.^,1010. Gomes EIL, Zago VHS, Faria EC. Avaliação de perfis lipídicos infanto-juvenis solicitados nas unidades básicas de saúde em Campinas/SP, Brasil: um estudo laboratorial transversal. Arq Bras Cardiol 2020; 114:47-56.^,1111. Souza NA, Vieira SA, Fonsêca PCA, Andreoli CS, Priore SE, Franceschini SCC. Dislipidemia familiar e fatores associados a alterações no perfil lipídico em crianças. Ciênc Saúde Colet 2019; 24:323-32.. For instance, one study conducted with 700 children aged 2 to 9 years in a Northeastern region also identified a high prevalence of elevated TC (45%) and dyslipidemia (68%) ⁹9. Maia JAF, Pinto FJM, Silva FR, Dantas DSG, Sampaio RMM, Chaves EMC, et al. Prevalência de dislipidemias em crianças de 2 a 9 anos. Rev Bras Enferm 2020; 73 Suppl 4:e20190759.. In another study by Gomes et al. ¹⁰10. Gomes EIL, Zago VHS, Faria EC. Avaliação de perfis lipídicos infanto-juvenis solicitados nas unidades básicas de saúde em Campinas/SP, Brasil: um estudo laboratorial transversal. Arq Bras Cardiol 2020; 114:47-56., 67% of the lipid profiles indicated the presence of at least one type of dyslipidemia.

Regardless of the cutoff points used for the diagnosis or the techniques applied in biochemical analysis, it is significant to emphasize that the prevalence of increased TG, but not high TC, observed in our study is higher than what has been reported in other Brazilian studies ⁷7. Pereira AS, Peixoto NGA, Nogueira Neto JF, Lanzillotti HS, Soares EA. Estado nutricional de pré-escolares de creche pública: um estudo longitudinal. Cad Saúde Colet (Rio J.) 2013; 21:140-7.^,88. Calliari SS, Grando LG, Bertol CD, Siqueira LO. Dislipidemia em crianças e adolescentes do município de Marau-RS. Cad Saúde Colet (Rio J.) 2019; 27:368-73.^,99. Maia JAF, Pinto FJM, Silva FR, Dantas DSG, Sampaio RMM, Chaves EMC, et al. Prevalência de dislipidemias em crianças de 2 a 9 anos. Rev Bras Enferm 2020; 73 Suppl 4:e20190759.^,1010. Gomes EIL, Zago VHS, Faria EC. Avaliação de perfis lipídicos infanto-juvenis solicitados nas unidades básicas de saúde em Campinas/SP, Brasil: um estudo laboratorial transversal. Arq Bras Cardiol 2020; 114:47-56.^,1111. Souza NA, Vieira SA, Fonsêca PCA, Andreoli CS, Priore SE, Franceschini SCC. Dislipidemia familiar e fatores associados a alterações no perfil lipídico em crianças. Ciênc Saúde Colet 2019; 24:323-32.^,1313. Magalhães TCA, Vieira SA, Priore SE, Ribeiro AQ, Franceschini SCC, Sant'ana LFDR. Fatores associados à dislipidemia em crianças de 4 a 7 anos de idade. Rev Nutr 2015; 28:17-28.. Moreover, our findings for high LDL-c exceed those of some studies ⁷7. Pereira AS, Peixoto NGA, Nogueira Neto JF, Lanzillotti HS, Soares EA. Estado nutricional de pré-escolares de creche pública: um estudo longitudinal. Cad Saúde Colet (Rio J.) 2013; 21:140-7.^,88. Calliari SS, Grando LG, Bertol CD, Siqueira LO. Dislipidemia em crianças e adolescentes do município de Marau-RS. Cad Saúde Colet (Rio J.) 2019; 27:368-73.^,1313. Magalhães TCA, Vieira SA, Priore SE, Ribeiro AQ, Franceschini SCC, Sant'ana LFDR. Fatores associados à dislipidemia em crianças de 4 a 7 anos de idade. Rev Nutr 2015; 28:17-28., while falling below others ^9,10,11. This difference may be attributed to the inclusion of children older than 2 ⁷7. Pereira AS, Peixoto NGA, Nogueira Neto JF, Lanzillotti HS, Soares EA. Estado nutricional de pré-escolares de creche pública: um estudo longitudinal. Cad Saúde Colet (Rio J.) 2013; 21:140-7.^,99. Maia JAF, Pinto FJM, Silva FR, Dantas DSG, Sampaio RMM, Chaves EMC, et al. Prevalência de dislipidemias em crianças de 2 a 9 anos. Rev Bras Enferm 2020; 73 Suppl 4:e20190759. or 4 ¹¹11. Souza NA, Vieira SA, Fonsêca PCA, Andreoli CS, Priore SE, Franceschini SCC. Dislipidemia familiar e fatores associados a alterações no perfil lipídico em crianças. Ciênc Saúde Colet 2019; 24:323-32.^,1313. Magalhães TCA, Vieira SA, Priore SE, Ribeiro AQ, Franceschini SCC, Sant'ana LFDR. Fatores associados à dislipidemia em crianças de 4 a 7 anos de idade. Rev Nutr 2015; 28:17-28. years in their samples. Previous research has indicated that pediatric dyslipidemia is a predictor of dyslipidemia and increased intima-media thickness of the carotid arteries in adulthood ²2. Burlutskaya AV, Tril VE, Polischuk LV, Pokrovskii VM. Dyslipidemia in pediatrician's practice. Rev Cardiovasc Med 2021; 22:817-34.^,44. McMahan CA, Gidding SS, Malcom GT, Tracy RE, Strong JP, McGill Jr. HC. Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis. Pediatrics 2006; 118:1447-55.^,55. Pires A, Sena C, Seiça R. Dyslipidemia and cardiovascular changes in children. Curr Opin Cardiol 2016; 31:95-100.^,2121. Sociedade Brasileira de Pediatria. Guia prático de atualização: dislipidemia na criança e no adolescente - orientações para o pediatra. Rio de Janeiro: Sociedade Brasileira de Pediatria; 2020.. LDL-c is considered the most atherogenic lipid fraction in the blood, elevating the risk of cardiovascular morbidity in later life ⁸8. Calliari SS, Grando LG, Bertol CD, Siqueira LO. Dislipidemia em crianças e adolescentes do município de Marau-RS. Cad Saúde Colet (Rio J.) 2019; 27:368-73..

High levels of TC and LDL-c were found to be associated with older age. Few studies have reported the prevalence of dyslipidemia in children under 4 years of age, primarily because of the challenges of blood collection, the requirement for higher fat intake to support myelination ¹1. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol 2017; 109 (2 Suppl 1):1-76., and the metabolic instability observed during the rapid growth phase before 24 months of life ¹⁰10. Gomes EIL, Zago VHS, Faria EC. Avaliação de perfis lipídicos infanto-juvenis solicitados nas unidades básicas de saúde em Campinas/SP, Brasil: um estudo laboratorial transversal. Arq Bras Cardiol 2020; 114:47-56.. The concentrations of lipids and lipoproteins experience significant fluctuations throughout different stages of human growth. Typically, there are two periods marked by a pronounced increase in these levels: the first three years of life and the conclusion of puberty ⁸8. Calliari SS, Grando LG, Bertol CD, Siqueira LO. Dislipidemia em crianças e adolescentes do município de Marau-RS. Cad Saúde Colet (Rio J.) 2019; 27:368-73..

Based on this theoretical foundation, we considered different cutoff points for the classification of children under the age of 24 months. TC and LDL-C levels increase rapidly during the first weeks of life, followed by a more gradual rise until the age of 2 years ³⁰30. US Preventive Services Task Force. Screening for lipid disorders in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA 2023; 330:253-60.. This pattern underlies the high prevalence of dyslipidemia observed in the current study. Screening for lipid disorders is, therefore, generally recommended after two years of age (when lipid and lipoprotein levels become quite constant until adolescence), if the child exhibits clinical signs (such as xanthomas or corneal arcus), risk factors (including hypertension, diabetes, or obesity), or family history of hypercholesterolemia or cardiovascular disease ¹1. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol 2017; 109 (2 Suppl 1):1-76.^,3030. US Preventive Services Task Force. Screening for lipid disorders in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA 2023; 330:253-60.. Our lipid profile data offer new scientific insights to reevaluate this recommendation of initiating serum lipid profile screenings from the age of 2 years.

An increase in the BMI-for-age z-score was associated with a higher prevalence of hypertriglyceridemia in our study (PR = 1.22; 95%CI; 1.05-1.41). Comparable findings have been reported by other studies involving students aged 6 to 17 years from the Brazilian states of Minas Gerais ³¹31. Lima MCC, Romaldini JH. Frequência de obesidade e fatores de risco relacionados entre escolares e adolescentes em uma comunidade de baixa renda. Um estudo transversal. Rev Bras Epidemiol 2015; 133:125-30., Rio Grande do Sul ³²32. Tornquist L, Tornquist D, Schneiders LB, Franke SI, Renner JD, Reuter CP. Risco cardiometabólico em crianças e adolescentes: o paradoxo entre índice de massa corporal e aptidão cardiorrespiratória. Arq Bras Cardiol 2022; 119:236-43.^,3333. Reuter CP, Brand C, Silva PT, Reuter ÉM, Renner JDP, Franke SIR, et al. Relação entre dislipidemia, fatores culturais e aptidão cardiorrespiratória em escolares. Arq Bras Cardiol 2019; 112:729-36., and Rio de Janeiro ³⁴34. Penha JT, Gazolla FM, Carvalho CNM, Madeira IR, Rodrigues-Júnior F, Machado EA, et al. Aptidão física e atividade, perfil metabólico, adipocinas e função endotelial em crianças. J Pediatr (Rio J.) 2019; 95:531-7.. An elevated BMI-for-age z-score has been linked with increased LDL-c cholesterol levels and decreased HDL-c cholesterol levels in a cross-sectional study of 218 individuals between the ages of 2 and 18 years ³⁵35. Milyani AA, Al-Agha AE. The effect of body mass index and gender on lipid profile in children and adolescents in Saudi Arabia. Ann Afr Med 2019; 18:42-6.. Insulin resistance is recognized as the primary mechanism underlying the correlation between BMI-for-age z-score and lipid profiles ¹³13. Magalhães TCA, Vieira SA, Priore SE, Ribeiro AQ, Franceschini SCC, Sant'ana LFDR. Fatores associados à dislipidemia em crianças de 4 a 7 anos de idade. Rev Nutr 2015; 28:17-28..

The elevation of TG could be attributed to the accumulation of chylomicrons and/or very low-density lipoproteins (VLDL-c). This may be a result of decreased TG hydrolysis in these lipoproteins or an increase in the synthesis of VLDL-c. Changes in dietary habits, coupled with increased physical activity and reduced intake of fats and/or carbohydrates for weight control, are also recommended for the management of hypertriglyceridemia ³⁶36. Filgueiras MS, Vieira SA, Ribeiro AQ, Novaes JF. O histórico familiar está associado à presença de dislipidemia em crianças pré-escolares. Rev Paul Pediatr 2019; 37:41-8..

Regarding dietary variables, cholesterol intake was associated with increased LDL-c and decreased HDL-c levels. Similarly, a study examining the diets of 227 preschoolers revealed that frequent consumption of convenience bakery products, which do not require preparation before consumption, as well as foods high in lipids, displayed a pronounced association with disruptions in lipid profiles, particularly elevated LDL-c levels ³⁷37. Nobre LN, Lamounier JA, Franceschini SCC. Sociodemographic, anthropometric and dietary determinants of dyslipidemia in preschoolers. J Pediatr (Rio J.) 2013; 89:462-9.. From this standpoint, the Brazilian guidelines on dyslipidemia emphasize the advantages of eliminating trans fats, controlling intake of saturated fats and cholesterol, favoring polyunsaturated (especially omega-3) and monounsaturated fats, and limiting sugar consumption ¹1. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol 2017; 109 (2 Suppl 1):1-76.^,3838. Izar MCO, Lottenberg AM, Giraldez VZR, Santos Filho RD, Machado RM, Bertolami A, et al. Posicionamento sobre o consumo de gorduras e saúde cardiovascular - 2021. Arq Bras Cardiol 2021; 116:160-212..

Contemporary research points to an imbalance in the Western dietary pattern, wherein excessive omega-6 polyunsaturated fatty acids and a disproportionately high ω-6/ω-3 ratio may drive the onset of numerous health conditions, including dyslipidemia ³⁹39. Mukhametov A, Yerbulekova M, Aitkhozhayeva G, Tuyakova G, Dautkanova D. Effects of ?-3 fatty acids and ratio of ?-3/?-6 for health promotion and disease prevention. Food Sci Technol 2022; 42:e58321.. It is worth noting that vegetable oils are primary sources of omega-6 fatty acids, especially those from sunflower, corn, and soy, which are components of a large portion of ultra-processed foods ²⁷27. Universidade Estadual de Campinas. Tabela brasileira de composição de alimentos - TACO. Campinas: Universidade Estadual de Campinas; 2011.^,4040. Departamento de Atenção Básica, Secretaria de Atenção à Saúde, Ministério da Saúde. Guia alimentar para a população brasileira. 2ª Ed. Brasília: Ministério da Saúde; 2014.. However, the ω-6/ω-3 ratio was not associated with the lipid profile in this study.

Another noteworthy finding of this study is the association of energy intake and higher prevalence of low HDL-c. This observation is significant as it underscores the urgency to assess the quality of CMEIs menus as well as meals provided at home, especially during weekends, when caregivers tend to be more lenient regarding the energy content of children’s diets. Currently, the prevailing perspective suggests that the consumption of ultra-processed foods, dining out, and replacing traditional meals with snacks contribute to excessive calorie ⁷7. Pereira AS, Peixoto NGA, Nogueira Neto JF, Lanzillotti HS, Soares EA. Estado nutricional de pré-escolares de creche pública: um estudo longitudinal. Cad Saúde Colet (Rio J.) 2013; 21:140-7.^,4040. Departamento de Atenção Básica, Secretaria de Atenção à Saúde, Ministério da Saúde. Guia alimentar para a população brasileira. 2ª Ed. Brasília: Ministério da Saúde; 2014.. The latest Brazilian Household Budget Survey (POF 2017/2018) emphasized the increase of ultra-processed products in household diets, constituting approximately one-fifth of the calories acquired for home consumption. Notably, there is a 93% consumption prevalence of these products among Brazilian children aged 24 to 59 months ⁴¹41. Universidade Federal do Rio de Janeiro. Alimentação infantil I: prevalência de indicadores de alimentação de crianças menores de 5 anos: ENANI 2019. https://enani.nutricao.ufrj.br/index.php/relatorios/ (accessed on 31/Aug/2023).
https://enani.nutricao.ufrj.br/index.php... ^,4242. Instituto Brasileiro de Geografia e Estatística. Pesquisa de Orçamentos Familiares 2017-2018: avaliação nutricional da disponibilidade domiciliar de alimentos no Brasil. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2020..

HDL-c is known to prevent the oxidation and aggregation of LDL-c in the arteries, thus reducing the risk of cardiovascular disease ¹¹11. Souza NA, Vieira SA, Fonsêca PCA, Andreoli CS, Priore SE, Franceschini SCC. Dislipidemia familiar e fatores associados a alterações no perfil lipídico em crianças. Ciênc Saúde Colet 2019; 24:323-32.. The high prevalence of reduced HDL-c in children appears to be linked to lifestyle factors, particularly inappropriate eating habits ¹⁰10. Gomes EIL, Zago VHS, Faria EC. Avaliação de perfis lipídicos infanto-juvenis solicitados nas unidades básicas de saúde em Campinas/SP, Brasil: um estudo laboratorial transversal. Arq Bras Cardiol 2020; 114:47-56.. In our study, a decrease in HDL-c was associated with higher energy and cholesterol intake. A comparable detrimental effect was noted by Souza et al. ¹¹11. Souza NA, Vieira SA, Fonsêca PCA, Andreoli CS, Priore SE, Franceschini SCC. Dislipidemia familiar e fatores associados a alterações no perfil lipídico em crianças. Ciênc Saúde Colet 2019; 24:323-32., who identified a statistically significant association between candy consumption (equal to or greater than seven times a week) and reduced HDL-c levels in children. This finding underscores the issue of poor dietary choices, as children who consume excessive amounts of candy typically lack a nutritionally balanced diet.

The lack of extensive data regarding levels of physical activity and consumption of food groups, which are primary sources of fats (e.g., oilseeds, animal-derived fats, oils, margarines, fried foods, among others), might have hindered a thorough analysis of the children’s dietary habits. Additionally, the proportion of nutrients relative to the total energy value of the diet was not determined. There was no differentiation as to determine whether the carbohydrates originated from fruits, whole/refined cereals, sugars, or legumes, nor whether the proteins or lipids came from animal or plant origin. Further investigations are necessary to shed light on the relation between nutrient intake, from different food sources, and alterations in serum lipids in the pediatric demographic.

This study was focused on examining the lipid profile of a distinct group in a city located in Central-West Brazil, referencing the epidemiological characteristics and in alignment with the stipulations outlined in the update of the 2017 Brazilian Guideline on Dyslipidemia and Atherosclerosis Prevention¹1. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol 2017; 109 (2 Suppl 1):1-76.. As a limitation, it is essential to consider the possible influence of unmeasured variables, such as genetically derived dyslipidemia, biomarkers (like C-reactive protein, apolipoproteins B and AI, fibrinogen, TNF, and IL-6), levels of physical activity, and duration of sedentary time, given that cardiometabolic risk is influenced by a multitude of factors.

In addition, given the nature of this cross-sectional study, which uses baseline data from a randomized clinical trial, it was not feasible to gauge the incidence of dyslipidemia cases or deduce any causal relation based on the findings. For models in the Poisson regression analysis with robust variance adjustment, the outcome variance explained by the independent variables (pseudo R²) was low. This may account for a minimal portion of the outcome variability ²⁹29. Barros AJ, Hirakata VN. Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio. BMC Med Res Methodol 2003; 3:21.. Furthermore, the diet was assessed using 24hR (supplemented with direct food weighing in CMEIs), and despite the clear guidelines and comprehensive training provided to the data collection team, there might be instances of underestimation or overestimation regarding the quantity or types of food provided and consumed by the children. Additionally, challenges are posed by the potential memory biases of mothers and/or guardians about the food offered to the children (regarding 24hR), coupled with the absence of data on certain foods and nutrients (like cholesterol, omega-6, omega-3) in Brazilian food composition tables.

A notable strength of this study was its focus on analyzing the lipid profiles of children under 2 years of age. We observed that dyslipidemia research is sparse in the age group from 6 to 42 months. To our acknowledgment, this is the inaugural study conducted in Brazil that probes the association between dyslipidemia and nutrients consumption (encompassing energy, carbohydrates, proteins, fats, and fiber) in children under 24 months. Other commendable attributes of this research include a high participation rate and the direct weighing of food at CMEIs, which is considered the gold standard for evaluating food consumption. This study thoroughly investigated crucial variables in the realm of children’s health, offering estimates and delineating factors associated with lipid profiles. Due to the significant prevalence of dyslipidemia detected in this research, researchers took proactive steps to ensure that all parents or guardians were apprised of the test results. Additionally, they received nutritional advice, and if required, a recommendation for a pediatric consultation.

This study findings underscore the pressing need to devise public health policies aimed at preventing childhood dyslipidemia. These insights should steer further research endeavors, inclusive of extension projects by UFG, to encourage healthy lifestyle habits. These habits encompass weight management, regular physical activity, and nutritional intake tailored to age-specific, caloric, and nutrient requirements, all working in tandem to mitigate the risk of cardiovascular incidents in adulthood. The importance of the dietary guide for children under 2 years old and the protocol for using the dietary guide for children aged 2 to 10 years stands out in this context of health promotion ⁴³43. Departamento de Promoção à Saúde, Secretaria de Atenção Primária à Saúde, Ministério da Saúde. Guia alimentar para crianças brasileiras menores de 2 anos. Brasília: Ministério da Saúde; 2019.. CMEIs also hold pivotal importance in fostering nutritional literacy among children and ensuring the quality of meals served, be it in the school lunch or institutional canteen.

In conclusion, a high prevalence of children aged 6 to 42 months exhibited one or more abnormalities in their serum lipid profiles. Notably, the highest observed prevalence rate was for low HDL-c levels. Factors such as an elevated BMI-for-age z-score, older children’s age, and high intake of cholesterol and calories were associated with abnormalities in the lipid profile. Conversely, older age was identified as a protective factor against low HDL-c. Engaging families in offering a balanced, nutritious diet during childhood might very well chart the course toward preempting cardiovascular ailments in this population’s future.

Acknowledgments

We would like to thank the parents and guardians of the children who participated in this study, as well the teachers and coordinators of the CMEIs. To FORNUTRI (Fortification with NutriSUS) Working Group for their support in the fieldwork. To Brazilian Ministry of Health/Brazilian National Research Council (CNPq) [CNPq/MS/SCTIE/DECIT/SAS/DAB/CGAN n. 13/2017, grant 408786/2017-5]. To Goiás State Research Foundation (FAPEG) [SES GO/CNPq/MS DECIT/2017 PPSUS/GO, grant 201710267001247].

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