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Have the prevalence of eczema symptoms increased in the Mexican pediatric population? Prevalence and associated factors according to Global Asthma Network Phase I

Open AccessPublished:October 16, 2022DOI:https://doi.org/10.1016/j.waojou.2022.100710

      Abstract

      Background

      In children, atopic dermatitis or eczema is the most common inflammatory disease of the skin. According to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase IIIB in Mexico, 5.8% of children and 4.9% of adolescents had eczema symptoms. In 2012, Global Asthma Network (GAN) was established to update the prevalence of eczema and estimate potential factors contributing to its development.

      Objective

      To estimate the prevalence and associated factors for atopic eczema symptoms and diagnosis in children and adolescents according to GAN Phase I and compare the results with ISAAC Phase IIIB in Mexico.

      Methods

      A cross-sectional, multicenter survey was conducted in 15 Mexican centers during the period of 2015–2017 using the GAN Phase I questionnaires in children (6–7-year-olds) and adolescents (13–14-year-olds). The prevalences obtained from the GAN Phase I study, were compared with ISAAC Phase IIIB results; a Spearman's correlation analysis was conducted between temperature, relative humidity, and altitude and eczema symptoms, and a logistic regression was performed to predict current eczema symptoms by age group.

      Results

      A total of 35 777 children and 41 399 adolescents were included. Since ISAAC Phase IIIB, the prevalence of itchy rash in the past 12 months significantly increased in the children's group [6.6% (95% CI 5.7–7.4) vs 7.8 (95% CI 7.5–8.1), p = 0.000] and adolescents' group [5.8% (95% CI 5.0–6.7) vs 6.7% (95% CI 6.5–7.0), p = 0.000].
      In the adolescents' group, the prevalence of nocturnal awakenings caused by rash symptoms on more than one night per week had a negative correlation between altitude (Spearman's Rho = −0.558, p value = 0.031), and a positive correlation with the average annual temperature (Spearman's Rho = 0.604, p value = 0.017) and annual relative humidity (Spearman's Rho = 0.742, p value = 0.002). The most significant associations in children were the presence of sneezing or runny or blocked nose in the past 12 months [(OR 3.13, 95% CI 2.60–3.77), p = 0.000], the use of paracetamol in the first year of life ([OR 1.52, 95% CI 1.15–2.01), p = 0.003] and the use of antibiotics in the first year of life [(OR 1.30, 95% CI 1.08–1.55) p = 0.004]. Moreover, altitude at 100–1000 m above sea level was associated with current eczema symptoms in adolescents (p = 0.001).

      Conclusions

      There has been a significant increase in eczema symptoms in both age groups since ISAAC Phase IIIB study. Additionally, eczema symptoms were associated with temperature, relative humidity, asthma, hay fever symptoms, the use of paracetamol and antibiotics.

      Keywords

      Atopic dermatitis (AD), or atopic eczema, is the most common inflammatory disease of the skin.
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      ISAAC Phase Three Study Group
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      At both ages, the highest prevalence was found in urban Africa, the Baltics, Australia, as well as Northern and Western Europe.
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      As part of ISAAC Phase I, Mexico participated with a center (Cuernavaca). The prevalence of eczema symptoms in children and adolescents was 4.9% and 4.4%, respectively.
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      Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys.
      According to ISAAC Phase IIIB, there has been a significant change in the prevalence of atopic eczema, with an increase in low-income countries such as Africa and East Asia. There has also been a large variation in the prevalence of current symptoms of eczema among groups aged 6–7 years (from 0.9% to 22.5%) and 13–14 years (from 0.2% to 24.6%).
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      • Robertson C.F.
      • Asher M.I.
      ISAAC Phase Three Study Group
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      Solé et al reported a prevalence of 10% of eczema symptoms among Latin American children (n = 93,851) and 8.3% among adolescents (n = 165,917). Mexico participated in this phase with 8 centers from 7 cities in the group for children (n = 23 391) and 10 centers from 8 cities in the group for adolescents (n = 29 723). There was a 5.8% (95% CI 5.0–6.7) prevalence of eczema symptoms among children and a 4.9% (95% CI 4.1–5.7) prevalence among adolescents and no associations observed between mean temperatures, altitudes, or air pollution levels in 35 Latin American countries and the current prevalence of eczema symptoms.
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      Prevalence of symptoms of eczema in Latin america: results of the international study of asthma and allergies in childhood (ISAAC) phase 3.
      Based on the valuable data regarding the variability of eczema symptoms among pediatric populations around the world and the contrast of factors associated with this disease, the Global Asthma Network (GAN) was established in 2012 in order to update the prevalence and associated factors of various allergic diseases, including atopic eczema.
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      The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors.
      In accordance with the results of GAN Phase I, this study aimed to estimate the prevalence and associated factors of eczema symptoms and diagnoses in children and adolescents, as well as compare the results with the findings of ISAAC Phase IIIB in Mexico.

      Methods

      Study design

      A comparative cross-sectional study was carried out in school-age populations of 6–7-year-olds (children) and 13–14-year-olds (adolescents) in 15 centers of 14 cities in Mexico including Puerto Vallarta, Matamoros, Mexicali, Tijuana, Ciudad Victoria, Córdoba, Ciudad Juárez, Chihuahua City, Xalapa, San Luis Potosí, Aguascalientes, Michoacán, Mexico City north area, Toluca urban area, and Toluca rural area.
      According to the methodology established by GAN, the sample unit was the entire population of children or adolescents within each school. Each center's public and private schools were randomly selected.
      • Ellwood P.
      • Asher M.I.
      • Billo N.E.
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      The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors.
      Children's questionnaires were completed by their parents, and adolescents' questionnaires were completed at school by themselves. Legal guardians of children and adolescents signed informed consent forms. In addition to the standardized written core questionnaires developed for ISAAC Phases I and III, GAN questionnaires also included a question regarding a doctor-confirmed diagnosis of eczema. In Mexico, the questionnaires were translated and back-translated into Spanish by 3 independent linguistic professionals according to the ISAAC English language questionnaire translation guidelines.
      • Ellwood P.
      • Williams H.
      • Aït-Khaled N.
      • Björkstén B.
      • Robertson C.
      Translation of questions: the international study of asthma and allergies in childhood (ISAAC) experience.
      After the Spanish version of each questionnaire was completed, a pilot test was conducted in Mexico City with children and adolescents. Each of the centers involved in this study used the same version of the questionnaire according to the age group. Written questionnaires collected information regarding demographics such as age, date of birth, gender, school, and date of interview, as well as questions regarding eczema prevalence and severity, and associated factors such as paracetamol use and antibiotic use in the first year of life, physical activity, place of residence, food consumption, and daycare attendance. To ensure confidentiality, the questionnaires were coded using a unique number for each center, school, and participant. Additionally, fieldworkers took height and weight measurements in schools using a standardized approach. Details on the GAN methodology can be found at the Global Asthma Network Manual.
      • Ellwood P.
      • Asher M.I.
      • Billo N.E.
      • et al.
      The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors.

      Definitions

      Regarding the symptoms and diagnosis of eczema, we considered the following 8 questions (Supplementary material 1). According to the ISAAC Phase IIIB study and GAN study, “current eczema symptoms” prevalence was estimated based on affirmative responses to the questions: “Have you (has this child) had this itchy rash at any time in the past 12 months?” and, “Has this itchy rash at any time affected any of the following places: the folds of the elbows; behind the knees; in front of the ankles; under the buttocks; or around the neck, ears, or eyes”. “Severe eczema symptoms” prevalence was defined as current symptoms being the cause of awakening 1 or more times per week, with a positive answer to: “In the past 12 months, how often, on average, have you (has this child) been kept awake at night by this itchy rash? (one or more nights per week).
      • Solé D.
      • Mallol J.
      • Wandalsen G.F.
      • Aguirre V.
      Prevalence of symptoms of eczema in Latin america: results of the international study of asthma and allergies in childhood (ISAAC) phase 3.
      ,
      • García-Marcos L.
      • Innes Asher M.
      • Pearce N.
      • et al.
      The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study.

      Sample size

      A sample size of 3000 was sought in each age group (with a minimum of 1000 deemed acceptable), which would have sufficient power (>90%) to detect 5% differences in eczema prevalence (at a significance level of 0.01) and allow for testing multiple hypotheses.
      • Ellwood P.
      • Asher M.I.
      • Billo N.E.
      • et al.
      The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors.
      All Mexican centers reached the average level of participation (at least 80% for adolescents and 70% for children).
      • Ellwood P.
      • Ellwood E.
      • Rutter C.
      • et al.
      Global asthma Network phase I surveillance: geographical coverage and response rates.

      Data collection and analysis

      Data entry was carried out by the medical personnel at the study center for the electronic GAN database. To minimize the possibility of errors, 10% of questionnaires were double entered.
      • Ellwood P.
      • Asher M.I.
      • Billo N.E.
      • et al.
      The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors.
      As part of the quality control process for Spanish and Portuguese-speaking centers in Spain, the GAN databases were checked and approved in 2019 by the Murcia data center.
      In accordance with the years in which the field work was conducted at each center, climatic data such as precipitation, temperature, relative humidity, the percentage of urban populations, and the type of climate according to Köppen-Geiger climate classification was obtained from the national databases of the Instituto Nacional de Estadística y Geografía (https://www.inegi.org.mx/) and Comisión Nacional del Agua (https://smn.conagua.gob.mx/es/).
      A descriptive data analysis was conducted using central tendency measurements (mean, standard deviation [SD], and 95% confidence intervals [95% CI ]), in addition to percentages and frequencies corresponding to each of the questions described in the Supplementary Material 1 on eczema prevalence. The prevalences obtained from the GAN Phase I study (including 15 centers) were compared with the prevalences obtained from the ISAAC Phase IIIB study (including 8 centers for children and 10 centers for adolescents) by chi-square test with a statistically significant p-value <0.05 for both age groups. We performed a Spearman's correlation analysis between climatic variables and the prevalences of eczema symptoms by center, (previously described in Supplementary Material 2), with a statistically significant p-value <0.05. Furthermore, an association analysis was performed between the current and cumulative eczema prevalence by sex and variables related to asthma symptoms, hay fever symptoms, history of breastfeeding, contact with domestic animals (dog, cat), frequency of consumption of antibiotics and paracetamol, frequency of hours of television, hours of exercise, food consumption by category and body mass index. Chi-square tests was used to identify all variables that might be influencing the prevalence of current symptoms (p < 0.05). These factors were further analyzed using backward conditional logistic regression to develop models to predict current eczema symptoms by age group.
      In order to organize the data, Microsoft Excel 2016 v16.0.6568.2036 (Microsoft Corporation) was used, along with IBM SPSS Statistics v25.0 (SPSS Inc., IBM) and Stata Statistical Software (Stata Corporation, LLC, College Station, TX, 2017) for statistical analysis.

      Results

      A total of 35 777 children and 41 399 adolescents were included from 790 schools; 51.7% of the population were female. The mean weight and height of children were 24.60 ± 5.48 kg and 1.21 ± 0.06 m, respectively. Among adolescents, the mean weight and height were 54.28 ± 11.53 kg and 1.59 ± 0.81 m, respectively.
      The national response rate of the delivered questionnaires was 88.55% for children and 91.19% for adolescents. A description of the climatic characteristics and percentage response by center can be found in Supplementary Material 2.

      Comparison of the results of the ISAAC Phase IIIB and GAN Phase I study

      Since ISAAC Phase IIIB, the national prevalence of itchy rash in the past 12 months significantly increased in the children's group [6.6% (95% CI 5.7–7.4) vs 7.8 (95% CI 7.5–8.1), p = 0.000] and adolescents' group [5.8% (95% CI 5.0–6.7) vs 6.7% (95% CI 6.5–7.0), p = 0.000]. The prevalence of eczema ever in the children's group also increased by 2.4% points [3.3% (95% CI 2.6–3.9) vs 5.7% (95% CI 5.5–6.0), p = 0.000] (see Table 1).
      Table 1Prevalence and severity of eczema symptoms in children and adolescents of Mexico according to ISAAC Phase IIIB (2002) and GAN Phase I (2015–2017).
      VariableChildren 6–7 years oldAdolescents 13–14 years old
      ISAAC Phase 3B (n = 23,391)GAN Phase I (n = 35,777)P valueISAAC Phase 3B (n = 29,723)GAN Phase I (n = 41,399)P value
      Itchy rash ever (%,95% CI)9.5 (8.5–10.6)9.4 (9.1–9.7)0.4258.3 (7.3–9.3)8.8 (8.5–9.0)0.300
      Itchy rash in the past 12 months (%,95% CI)6.6 (5.7–7.4)7.8 (7.5–8.1)0.000∗5.8 (5.0–6.7)6.7 (6.5–7.0)0.000∗
      Rash in flexures (%,95% CI)7.1 (6.2–8.0)5.9 (5.6–6.1)0.000∗5.8 (5.0–6.7)4.7 (4.5–4.9)0.000∗
      First occurrence:

      <2 years old (%,95% CI)
      3.3 (2.7–3.8)2.9 (2.7–3.1)0.056NININI
      2–4 years old (%,95% CI)2.6 (2.0–3.1)2.5 (2.4–2.7)0.878NININI
      >4 years old (%, 95% CI)3.5 (2.8–4.1)2.7 (2.5–2.9)0.000∗NININI
      Clearance of rash in the past 12 months (%,95% CI)15.9 (15.1–16.7)5.1 (4.9–5.4)0.000∗12.2 (11.5–12.9)5.9 (5.7–6.1)0.000∗
      One or more nighttime awakenings due to itchy rash in the past 12 months (%,95% CI)0.9 (0.6–1.3)0.8 (0.7–0.8)0.1560.8 (0.5–1.2)0.9 (0.8–1.0)0.548
      Eczema ever (%,95% CI)3.3 (2.6–3.9)5.7 (5.5–6.0)0.000∗2.7 (2.1–3.3)3.1 (2.9–3.2)0.000∗
      Eczema confirmed by a doctor (%,95% CI)NI5.4 (5.2–5.7)NINI2.1 (2.0–2.2)NI
      Current symptoms of eczema (%,95% CI)5.8 (5.0–6.7)5.7 (4.9–5.4)0.8544.9 (4.1–5.7)4.6 (4.4–4.8)0.000∗
      Current symptoms of severe eczema (%,95% CI)0.7 (0.4–1.0)0.6 (0.6–0.7)0.8470.6 (0.4–0.9)0.8 (0.7–0.8)0.111
      NI, No information.
      ∗p < 0.05-Statistically significant difference
      In both age groups, the prevalence of flexure rash decreased by 1.1–1.2 percentual points, and the prevalence of clearance of rash in the past 12 months decreased significantly [7.1% (95% CI 6.2–8.0) vs 5.9% (95% CI 5.6–6.1), p = 0.000] in the children's group and in the adolescents' group [12.2% (95% CI 11.5–12.9) vs 5.9% (95% CI 5.7–6.1), p = 0.000]. The prevalence of current symptoms of eczema decreased in the adolescents' group [4.9% [95% CI 4.1–5.7) vs 4.6% (95% CI 4.4–4.8), p = 0.000], and the current prevalence of severe eczema symptoms ranged from 0.6 to 0.8 in both age groups, without a significant difference (Table 1).
      In the 4 centers that participated in ISAAC Phase IIIB and GAN Phase I (Mexico City north area, Mexicali, Toluca urban area, and Ciudad Victoria), the prevalence of itchy rash in the past 12 months increased significantly, as did the prevalence of eczema symptoms in the first 2 years of life and eczema ever in at least 3 of the 4 centers in both age groups (p < 0.05). Please refer to Table 2.
      Table 2Prevalence and severity of eczema symptoms in children and adolescents of Mexico according to ISAAC Phase IIIB (2002) and GAN Phase I (2015–2017) in four centers.
      VariableCenterChildren 6–7 years oldAdolescents 13–14 years old
      ISAAC Phase 3B (n = 11,611)GAN Phase I (n = 9672)P valueISAAC Phase 3B (n = 13,022)GAN Phase I (n = 10,972)P value
      Itchy rash ever (%,95% CI)Mexico City north area12.4 (11.2–13.5)11.5 (10.2–12.7)0.30111.3 (10.3–12.3)8.0 (7.1–8.9)0.000∗
      Toluca urban area7.8 (6.9–8.7)9.9 (8.8–11.0)0.004∗7.4 (6.4–8.3)8.5 (7.4–9.6)0.122
      Mexicali12.5 (11.2–13.8)11.4 (10.0–12.8)0.2545.4 (4.6–6.2)7.9 (6.8–9.0)0.000∗
      Ciudad Victoria4.6 (3.8–5.4)10.2 (9.0–11.4)0.000∗8.9 (7.9–9.9)11.6 (10.4–12.9)0.001∗
      Itchy rash in the past 12 months (%,95% CI)Mexico City north area9.5 (8.5–10.5)9.9 (8.7–11.0)0.6338.9 (8.0–9.8)6.4 (5.5–7.2)0.001∗
      Toluca urban area5.9 (5.1–6.7)8.9 (7.8–10.0)0.000∗4.1 (3.4–4.8)6.9 (6.0–7.9)0.000∗
      Mexicali6.2 (5.3–7.1)9.6 (8.4–10.9)0.000∗3.3 (2.6–3.9)5.8 (4.9–6.8)0.000∗
      Ciudad Victoria3.3 (2.6–4.0)8.0 (6.9–9.1)0.000∗5.8 (5.0–6.6)9.6 (8.5–10.8)0.000∗
      Rash in flexures (%,95% CI)Mexico City north area10.9 (9.8.-12.0)7.8 (6.7–8.8)0.000∗10.1 (9.1–11.0)4.0 (3.4–4.7)0.000∗
      Toluca urban area5.4 (4.6–6.2)6.3 (5.4–7.2)0.1423.6 (2.9–3.7)4.9 (4.1–5.8)0.013
      Mexicali7.6 (6.6–8.6)7.8 (6.6–9.0)0.7993.7 (3.0–4.4)4.1 (3.3–4.9)0.409
      Ciudad Victoria3.2 (2.5–3.9)6.1 (5.2–7.1)0.000∗7.0 (6.1–7.9)6.5 (5.5–7.5)0.441
      First occurrence:

      <2 years old (%,95% CI)
      Mexico City north area14.4 (13.2–15.6)4.1 (3.4–4.9)0.000∗NININI
      Toluca urban area1.2 (0.8–1.6)3.2 (2.5–3.9)0.000∗NININI
      Mexicali1.7 (1.2–2.2)3.9 (3.1–4.8)0.000∗NININI
      Ciudad Victoria0.9 (0.5–1.2)1.7 (1.2–2.2)0.009∗NININI
      2–4 years old (%,95% CI)Mexico City north area3.6 (2.9–4.2)3.4 (2.7–4.1)0.670NININI
      Toluca urban area2.1 (1.6–2.6)2.9 (2.3–3.6)0.037∗NININI
      Mexicali2.5 (1.9–3.1)3.6 (2.8–4.4)0.029∗NININI
      Ciudad Victoria1.7 (1.2–2.2)2.1 (1.6–2.7)0.256NININI
      >4 years old (%,95% CI)Mexico City north area5.1 (4.3–5.8)3.3 (2.6–4.0)0.001∗NININI
      Toluca urban area2.4 (1.9–2.9)3.8 (3.0–4.5)0.002∗NININI
      Mexicali3.7 (3.0–4.4)3.2 (2.3–3.9)0.269NININI
      Ciudad Victoria2.3 (1.7–2.9)4.1 (3.3–4.9)0.000∗NININI
      One or more nighttime awakenings due to itchy rash in the past 12 months (%,95% CI)Mexico City north area1.0 (0.7–1.3)0.8 (0.5–1.2)0.5221.0 (0.7–1.3)0.8 (0.5–1.1)0.365
      Toluca urban area0.4 (0.2–0.6)0.5 (0.2–0.8)0.5130.9 (0.6–1.2)0.6 (0.3–0.9)0.151
      Mexicali1.1 (0.7–1.5)0.8 (0.4–1.3)0.4140.3 (0.1–0.5)0.7 (0.4–1.1)0.026∗
      Ciudad Victoria0.5 (0.2–0.8)1.4 (0.9–1.9)0.001∗1.5 (1.1–1.9)1.3 (0.9–1.7)0.511
      Eczema ever (%,95% CI)Mexico City north area4.1 (3.4–4.8)11.4 (10.2–12.7)0.000∗2.3 (1.8–2.8)5.7 (4.9–6.5)0.000∗
      Toluca urban area3.4 (2.8–4.0)7.7 (6.7–8.7)0.000∗4.1 (3.4–4.8)4.9 (4.0–5.7)0.146
      Mexicali3.6 (2.9–4.3)11.4 (10.0–12.8)0.000∗1.3 (0.9–1.7)2.2 (1.6–2.8)0.010∗
      Ciudad Victoria2.0 (1.5–2.5)3.7 (3.0–4.5)0.000∗0.8 (0.5–1.1)1.9 (1.4–2.4)0.000∗
      Current symptoms of eczema (%,95% CI)Mexico City north area8.7 (7.7–9.7)7.1 (6.1–8.1)0.024∗8.5 (7.6–9.4)3.9 (3.2–4.5)0.000∗
      Toluca urban area5.4 (4.6–6.2)6.0 (5.1–6.9)0.3193.1 (2.5–3.7)4.5 (3.7–5.3)0.004∗
      Mexicali5.4 (4.5–6.3)7.2 (6.1–8.3)0.013∗2.8 (2.2–3.4)4.0 (3.2–4.8)0.016∗
      Ciudad Victoria2.3 (1.7–2.9)6.1 (5.1–7.0)0.000∗5.1 (4.4–5.9)6.5 (5.5–7.5)0.030∗
      Current symptoms of severe eczema (%,95% CI)Mexico City north area0.7 (0.4–1.0)0.6 (0.3–0.9)0.8160.9 (0.6–1.2)0.7 (0.4–0.9)0.233
      Toluca urban area0.3 (0.1–0.5)0.4 (0.2–0.7)0.5270.5 (0.2–0.7)0.5 (0.2–0.7)0.811
      Mexicali0.8 (0.4–1.1)0.6 (0.3–1.0)0.6890.1 (0.0–0.2)0.6 (0.3–0.9)0.002∗
      Ciudad Victoria0.3 (0.1–0.5)1.1 (0.7–1.5)0.001∗1.1 (0.7–1.5)1.1 (0.7–1.5)0.916
      Eczema confirmed by a doctor (%,95% CI)Mexico City north areaNI11.0 (9.8–12.2)NINI4.7 (4.0–5.4)NI
      Toluca urban areaNI7.3 (6.4–8.3)NINI3.9 (3.2–4.6)NI
      MexicaliNI11.1 (9.7–12.5)NINI1.4 (0.9–1.8)NI
      Ciudad VictoriaNI3.4 (2.7–4.2)NINI1.3 (0.9–1.7)NI
      NI, No information; ∗p < 0.05-Statistically significant difference
      Children in the north area of Mexico City reported a decrease in current eczema symptoms by 1.6% points and adolescents by 4.6% points. In adolescents, a significant decrease of over 3% points was also observed in the prevalence of itchy rash ever [11.3% (95% CI 10.3–12.3) vs 8.0% (95% CI 7.1–8.9), p = 0.000] and rash in flexures [10.1% (95% CI 9.1–11.0) vs 4.0% (95% CI 3.4–4.7), p = 0.000].
      On the other hand, Ciudad Victoria reported the highest increase in current eczema symptoms in children and adolescents (3.8% points, p = 0.000 and 1.4% points, p = 0.030, respectively) and in symptoms of severe eczema in children (0.8% points, p = 0.001). However, both groups reported the lowest prevalence of eczema medical diagnoses (3.4% in children and 1.3% in adolescents).
      According to Mexicali, in adolescents, nighttime awakenings due to rash in the past 12 months increased by 0.4% points (p = 0.026), as did current symptoms of severe eczema by 0.5% points (p = 0.002). In the children group, the prevalence of eczema ever increased significantly by 7.8% points (p = 0.000) and reported the highest prevalence of eczema medical diagnoses [11.1% (95% CI 9.7–12.5)].
      The Toluca urban area reported a significant increase of at least 2% points in the prevalence of itchy rash ever [7.8% (95% CI 6.9–8.7) vs 9.9% (95% CI 8.8–11.0), p = 0.004]), itchy rash in the last 12 months [5.9% (95% CI 5.1–6.7) vs 8.9% (95% CI 7.8–10.0), p = 0.000]), and eczema ever among children [3.4% (95% CI 2.8–4.0) vs 7.7% (95% CI 7.8–10.0), p = 0.000]).

      GAN Phase I study results

      There was a wide variety of the current prevalence of eczema between centers. According to the children group, Córdoba, Ciudad Victoria, and Ciudad Juárez had the highest prevalence (more than 6%). Among adolescents, Mexico City, Mexicali, Chihuahua, and Puerto Vallarta had the highest current prevalence of eczema (>7%), while Michoacán had the lowest prevalence in both age groups (<3.5%). (Supplementary materials 3a and 3b) The prevalence of eczema confirmed by a doctor ranged from 2.1% (95% CI 2.0–2.2) to 5.4% (95% CI 5.2–5.7) in adolescents and children, respectively (see Table 1). Additionally, over fifty percent of the children and adolescents with current eczema symptoms were also diagnosed as having asthma or hay fever by a doctor.
      In the adolescents' group, the prevalence of nocturnal awakenings caused by rash symptoms on more than one night per week had a negative correlation between altitude (Spearman's Rho = −0.558, p value = 0.031), and a positive correlation with the average annual temperature (Spearman's Rho = 0.604, p value = 0.017) and annual relative humidity (Spearman's Rho = 0.742, p value = 0.002) (Fig. 1, Fig. 2, Fig. 3). Children did not show any statistically significant correlations.
      Fig. 1
      Fig. 1Spearman's correlation between the prevalence of nighttime awakening due to itchy rash in the past 12 months and the altitude of the fifteen GAN Phase I centers in 13–14-year-old.
      Fig. 2
      Fig. 2Spearman's correlation between the prevalence of nighttime awakening due to itchy rash in the past 12 months and the average annual temperature of the fifteen GAN Phase I centers in 13–14-year-old.
      Fig. 3
      Fig. 3Spearman's correlation between the prevalence of nighttime awakening due to itchy rash in the past 12 months and the annual relative humidity of the fifteen GAN Phase I centers in 13–14-year-old.
      Table 3, Table 4 present factors associated with current symptoms of eczema in children and adolescents by sex, respectively. The most significant associations in children were the presence of sneezing or runny or blocked nose in the past 12 months [males (OR 3.13, 95% CI 2.60–3.77), p = 0.000] vs [females (OR 2.92, 95% CI 2.42–3.52), p = 0.000], the use of paracetamol during the pregnancy of the child more than once a month [males (OR 2.02, 95% CI 1.38–2.93), p = 0.000] vs [females (OR 1.50, 95% CI 1.01–2.21), p = 0.040], the use of paracetamol in the first year of life [males (OR 1.10, 95% CI 0.84–1.45), p = 0.471] vs [females (OR 1.52, 95% CI 1.15–2.01), p = 0.003] and the use of antibiotics in the first year of life [males (OR 1.19, 95% CI 0.98–1.45), p = 0.066] vs [females (OR 1.30, 95% CI 1.08–1.55) p = 0.004]. For the adolescents' group, the most significant associated factors were wheezing or whistling in the past 12 months [males (OR 2.45, 95% CI 1.97–3.03), p = 0.000] vs [females (OR 2.03, 95% CI 1.77–2.35) p = 0.000], sneezing or a runny or blocked nose without a cold or a flu in the past 12 months [males (OR 2.93, 95% CI 2.44–3.52), p = 0.000] vs [females (OR 3.01, 95% CI 2.64–3.42), p = 0.000], hay fever ever [males (OR 2.14, 95% CI 1.67–2.75), p = 0.000] vs [females (OR 1.84, 95% CI 1.55–2.18), p = 0.000] and the use of paracetamol at least once a month [males (OR 1.68, 95% CI 1.29–2.20), p = 0.000] vs (females [OR 1.71, 95% CI 1.39–2.10), p = 0.000].
      Table 3Associated factors for current eczema symptoms identified in the logistic regression in the 6–7-year age group according to the Global Asthma Network (GAN) study in Mexico 2015–2017
      Variables according to GAN study Phase IMales 6–7Females 6–7
      OR (95% CI)pOR (95% CI)p
      Wheezing or whistling in the chest in the past 12 months1.91 (1.54–2.39)0.0001.61 (1.27–2.03)0.000
      Asthma ever1.07 (0.82–1.40)0.5911.19 (0.88–1.60)0.239
      Sneezing or a runny or blocked nose without a cold or a flu In the past 12 months3.13 (2.60–3.77)0.0002.92 (2.42–3.52)0.000
      Hay fever ever1.70 (1.37–2.11)0.0001.39 (1.10–1.76)0.005
      Frequency of maternal paracetamol consumption during pregnancy:
      Once compared to never1.41 (1.18–1.69)0.0001.24 (1.04–1.48)0.014
      Once a month compared to never1.56 (1.18–2.08)0.0021.21 (0.91–1.61)0.186
      More than once a month compared to never2.02 (1.38–2.93)0.0001.50 (1.01–2.21)0.040
      More frequent compared to never2.05 (0.66–6.35)0.2111.80 (0.52–6.25)0.351
      Regular maternal contact (at least once a week) with farm animals during pregnancy1.73 (1.31–2.29)0.0001.48 (1.11–1.96)0.006
      Premature birth1.01 (0.80–1.27)0.9051.03 (0.81–1.30)0.805
      Breastfeeding duration:
      6–12 months compared to less than 6 months0.97 (0.80–1.16)0.7440.94 (0.78–1.12)0.508
      More than 12 months compared to less than 6 months1.14 (0.92–1.41)0.2090.96 (0.77–1.18)0.716
      Antibiotics during the first year of life1.19 (0.98–1.45)0.0661.30 (1.08–1.55)0.004
      Paracetamol for fever during the first year of life1.10 (0.84–1.45)0.4711.52 (1.15–2.01)0.003
      Contact with a dog during the first year of life1.29 (1.08–1.54)0.0051.28 (1.07–1.52)0.006
      Contact with a cat during the first year of life1.15 (0.86–1.54)0.3201.24 (0.95–1.63)0.109
      Frequency of paracetamol use for fever in the past 12 months:
      At least once a year compared to never1.19 (0.87–1.64)0.2621.02 (0.76–1.38)0.865
      At least once a month compared to never1.30 (0.92–1.84)0.1301.31 (0.95–1.82)0.097
      Contact with a dog during the past 12 months0.86 (0.72–1.02)0.0910.89 (0.75–1.05)0.179
      Contact with a cat during the past 12 months1.05 (0.82–1.34)0.6700.96 (0.76–1.21)0.766
      Altitude (mamsl) comparison <100 mts
      100–1000 m1.01 (0.77–1.33)0.9120.87 (0.67–1.15)0.348
      >1000–1500 m0.93 (0.72–1.20)0.6180.75 (0.58–0.96)0.022
      >1500–2000 m0.74 (0.56–0.96)0.0280.65 (0.50–0.84)0.001
      >2000–2500 m1.36 (0.97–1.19)0.0740.95 (0.68–1.33)0.792
      >2500 m1.26 (0.96–1.65)0.0951.17 (0.91–1.50)0.212
      Table 4Associated factors for current eczema symptoms identified in the logistic regression in the 13–14 year age group according to the Global Asthma Network (GAN) survey in Mexico 2015–2017
      Variables according to GAN study Phase IMales 13–14Females 13–14
      OR (95% CI)pOR (95% CI)p
      Wheezing or whistling in the chest in the past 12 months2.45 (1.97–3.03)0.0002.03 (1.77–2.35)0.000
      Asthma ever1.21 (0.95–1.55)0.1221.04 (0.86–1.24)0.665
      Sneezing or a runny or blocked nose without a cold or a flu In the past 12 months2.93 (2.44–3.52)0.0003.01 (2.64–3.42)0.000
      Hay fever ever2.14 (1.67–2.75)0.0001.84 (1.55–2.18)0.000
      Frequency of paracetamol use for fever in the past 12 months:
      At least once a year1.23 (0.97–1.58)0.0871.27 (1.04–1.55)0.019
      At least once a month1.68 (1.29–2.20)0.0001.71 (1.39–2.10)0.000
      Contact with a dog during the past 12 months0.99 (0.81–1.22)0.9601.23 (1.06–1.42)0.006
      Contact with a cat during the past 12 months1.18 (0.97–1.43)0.0891.13 (0.99–1.29)0.064
      Altitude (mamsl) comparison <100 mts
      100–1000 m1.50 (1.14–1.96)0.0031.34 (1.12–1.61)0.001
      >1000–1500 m1.13 (0.86–1.48)0.3781.05 (0.88–1.26)0.566
      >1500–2000 m0.90 (0.68–1.20)0.4950.94 (0.78–1.13)0.553
      >2000–2500 m0.88 (0.58–1.33)0.5661.09 (0.85–1.39)0.488
      >2500 m1.67 (1.28–2.19)0.0000.91 (0.72–1.13)0.404
      Among the children, living in centers located between 1500 and 2000 m above sea level was reported by both sexes as a protective factor for current eczema symptoms (males = OR 0.74, 95% CI 0.56–0.96, p < 0.028 ; females = OR 0.65, 95% CI 0.50–0.84, p < 0.001). In the adolescent group, living in centers with an altitude of 100–1000 m above sea level was reported as an associated factor for current eczema symptoms in both sexes (males = OR 1.50, 95% CI 1.14–1.96, p < 0.003 ; females = OR 1.34, 95% CI 1.12–1.61, p < 0.001).

      Discussion

      According to the GAN Phase I methodology, this study represents one of the most comprehensive attempts to estimate the prevalence of atopic dermatitis symptoms in children and adolescents in Mexico. ISAAC Phase IIIB and GAN prevalence data were examined over time to determine patterns of change over more than a decade (2002–2017) and found that prevalence and severity of eczema vary by age group, center, and can be correlated with climatic characteristics. Additionally, in both age groups, GAN Phase I results indicated a national increase in eczema ever prevalence (from 0.4 to 2.4% points) and itchy rash in the past 12 months prevalence (from 0.9 to 1.2% points) compared to the ISAAC Study Phase IIIB. Nevertheless, it was determined that among the 4 centers involved in both phases, eczema prevalence increased by at least 1.5% points among children in the 4 centers and 1 percentage point among adolescents in Mexico City and Ciudad Victoria centers.
      We found a substantial burden of current eczema symptoms in Ciudad Victoria and Mexicali: 6 to 7 out of 100 children and 4 to 6 adolescents had eczema symptoms in their flexures areas or on their face within the last 12 months, and 1 out of 100 had nocturnal awakenings as a result. An estimated 46%–80% of children with AD suffer from sleep disturbances, manifesting as difficulty falling asleep, frequent awakenings during the night, and excessive sleepiness during the day.
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      An interesting finding in adolescents was the moderate positive correlation between nocturnal awakenings caused by eczema symptoms and the annual temperature of the centers at the time of recruitment, along with a high positive correlation with relative humidity. Even though relative humidity is influenced by temperature and air condition, it has been observed that high humidity could encourage the growth and reproduction of allergens such as mold,
      • Jaakkola J.J.
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      and high temperatures are associated with poorly controlled eczema.
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      Warm, humid, and high sun exposure climates are associated with poorly controlled eczema: PEER (Pediatric Eczema Elective Registry) cohort, 2004-2012.
      Sargen et al found that for every 5 °F increase in temperature, the odds (OR = 0.85, 95% CI 0.82–0.89, p < 0.001) for patients who describe their disease as poorly controlled increased by 15%. In addition, the association between temperature and disease control (OR = 0.90, 95% CI: 0.87–0.93, p = 0.001) was statistically significant after adjusting for potential confounders such as race, ethnicity, sex, annual household income, and use of topical medications (topical steroids, topical tacrolimus, topical pimecrolimus). With respect to humidity, this study initially reported a 10% increase in the odds of poorly controlled diseases (OR = 0.90, 95% CI 0.81–1.00, p = 0.04) for every 10% increase in humidity. Nevertheless, the statistical significance of this association was lost in the multivariate analysis (OR = 0.93, 95% CI 0.84–1.02, p = 0.14).
      • Sargen M.R.
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      • Margolis D.J.
      Warm, humid, and high sun exposure climates are associated with poorly controlled eczema: PEER (Pediatric Eczema Elective Registry) cohort, 2004-2012.
      In contrast, in the centers of Spain, Suárez-Varela et al reported a positive correlation between the prevalence of eczema symptoms and humidity and a negative correlation between annual temperature and eczema symptoms in children between 6 and 7 years of age.
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      Numerous studies have shown that eczema incidence increases in low temperatures and low humidity as a consequence of dehydration,
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       increased production of IL-α1
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      and mast cell granulation.
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      Dry environment increases mast cell number and histamine content in dermis in hairless mice.
      However, one explanation for our findings may be that high relative humidity and elevated temperatures may reduce evaporative heat loss during sweating and irritate the skin when central heating is increased, which may result in increased itching due to neuropeptide-induced vasodilation.
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      The external humidity was taken into account in this study and not the indoor humidity or the possibility of heating or air conditioning.
      For altitude, it was found that higher altitudes were associated with a lower prevalence of nocturnal awakenings at least once a week in adolescents, while lower altitudes were associated with an increased risk of eczema symptoms in centers below 1000 m. Furthermore, altitudes of 1500 to 2000 m were observed to protect against eczema symptoms in a group of schoolchildren. This is consistent with a systematic review that included 15 observational studies involving 40,148 patients with atopic dermatitis on therapy at high altitude centers (>1000 m). In this study, 96% of patients (n = 39,006) reported decreased disease activity during treatment, 64% reported improved symptoms in the last 12 months following treatment (n = 2670),
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       and 82% (n = 1178) reduced or stopped the use of local corticosteroid during treatment and at the 12-month follow-up (72% of the n = 3008).
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       Also, urinary eosinophilic protein X (EPX)
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      decreased and was significantly correlated with SCORAD.
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      However, the authors reported a very low quality of the information due to heterogeneity between the studies and the lack of description in some outcomes.
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      There have been high rates of eczema reported in pediatric populations near the equator, but altitude has not been associated with eczema in ISAAC studies.
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      However, other studies that have used questionnaires other than the ISAAC methodology, including the Prevalence and Risk Factors of Allergies in Turkey (PARFAIT), have assessed the prevalence and risk factors of asthma, hay fever, and eczema among children, as well as the geographical variables and weather conditions associated with them. Several factors were associated with atopic dermatitis prevalence in this study, including altitude <1000 m, annual temperature >15 °C, relative humidity >70%, and atmospheric pressure >1000 mbars.
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      Considering the heterogeneity of the associations between altitude, temperature, and relative humidity, it is necessary to conduct multicenter studies in order to determine how these factors relate to eczema symptoms.
      It was found that the use of paracetamol and antibiotics was also associated with the presence of eczema symptoms in children and the frequency of paracetamol use among adolescents. It has been reported that in Latin American children, paracetamol use in the first year of life was associated with the presence of eczema with an OR of 1.49 (1.26–1.76)
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      and in Polish adolescents, paracetamol use at least once per month was associated with eczema with an OR of 1.5 (1.11–2.01), p < 0.05.
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      • et al.
      The association between paracetamol use and the risk of asthma, rhinitis and eczema in the Polish population.
      Even though the use of paracetamol and antibiotics in children are usually associated with respiratory infections, there are also other reasons for its use, such as otitis media, vaccination fever, infections in other organs, etc. Paracetamol, at recommended therapeutic doses, may deplete glutathione and glutathione-dependent enzymes, and reduce the body's ability to withstand oxidative stress.
      • Eneli I.
      • Sadri K.
      • Camargo Jr., C.
      • Barr R.G.
      Acetaminophen and the risk of asthma: the epidemiologic and pathophysiologic evidence.
      As a result, reactive oxygen species in response to allergic, viral, or other non-allergic stimuli, may lead to enhanced inflammation and the development or worsening of pre-existing asthma, rhinoconjunctivitis, or eczema, depending on the organ system affected.
      • Yamaura K.
      • Akiyama S.
      • Oda M.
      • Suwa E.
      • Ueno K.
      Acetaminophen enhances pruritus in a mouse model of contact dermatitis induced by suboptimal concentration of hapten.
      • Farquhar H.
      • Stewart A.
      • Mitchell E.
      • et al.
      The role of paracetamol in the pathogenesis of asthma.
      • Allmers H.
      Frequent acetaminophen use and allergic diseases: is the association clear?.
      In addition, long-term use of broad-spectrum antibiotics has been shown to cause dysbiosis of the intestinal tract, which negatively impacts extraintestinal organs such as the lungs, the brain, and the skin, leading to chronic AD progression and asthma.
      • Strzępa A.
      • Majewska-Szczepanik M.
      • Kowalczyk P.
      • Woźniak D.
      • Motyl S.
      • Szczepanik M.
      Oral treatment with enrofloxacin early in life promotes Th2-mediated immune response in mice.
      ,
      • Song H.
      • Yoo Y.
      • Hwang J.
      • Na Y.C.
      • Kim H.S.
      Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis.
      However, it is important to take into account the potential confounding effects of familial and genetic factors in this association.
      • Slob E.
      • Brew B.K.
      • Vijverberg S.
      • et al.
      Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study.
      Studies have found that having parents with a history of allergic disease and/or having a diagnosis of allergic disease are risk factors for developing another disease involving an allergic component in the future.
      • Shamssain M.
      Trends in the prevalence and severity of asthma, rhinitis and atopic eczema in 6- to 7- and 13- to 14-yr-old children from the north-east of England.
      In the ISAAC Phase III study, 0.8–1.2% of children and adolescents had asthma, rhinitis, and eczema symptoms, with significant associations between the three conditions.
      • Asher M.I.
      • Montefort S.
      • Björkstén B.
      • et al.
      Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys.
      ,
      • Shamssain M.
      Trends in the prevalence and severity of asthma, rhinitis and atopic eczema in 6- to 7- and 13- to 14-yr-old children from the north-east of England.
      As a result of our study, wheezing, nasal symptoms in the past 12 months, and hay fever are the most significant risk factors for eczema. Despite a similar association between asthma symptoms and hay fever with eczema among children of both sexes, wheezing in the past year and hay fever were more prevalent among adolescent males. According to research, asthma, allergic rhinitis, and atopic eczema are more common among children of both sexes during their school years;
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      • Cheng Y.W.
      • Lai C.S.
      • Chen W.
      Prevalence of childhood acne, ephelides, warts, atopic dermatitis, psoriasis, alopecia areata and keloid in Kaohsiung County, Taiwan: a community-based clinical survey.
      ,
      • Govaere E.
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      • Massa G.
      • Verhamme K.M.
      • Doli E.
      • De Baets F.
      The influence of age and gender on sensitization to aero-allergens.
      however, males are more sensitive to grass pollen, mites, and tree pollens
      • Osman M.
      • Hansell A.L.
      • Simpson C.R.
      • Hollowell J.
      • Helms P.J.
      Gender-specific presentations for asthma, allergic rhinitis and eczema in primary care.
      resulting in a greater likelihood of developing allergic disorders by the age of 14. Women, however, are more likely to develop eczema symptoms during their reproductive years (between 15 and 49 years old), when they are most likely to become sensitized to environmental allergens.
      • Ziyab A.H.
      Prevalence and risk factors of asthma, rhinitis, and eczema and their multimorbidity among young adults in Kuwait: a cross-sectional study.
      Finally, according to our study, more than 50% of children and adolescents with current eczema symptoms were also diagnosed as having asthma or hay fever by a doctor. Although eczema symptoms have increased since the ISAAC study in Mexico, less than 5.5% of patients in both groups received a diagnosis from a doctor. There are similar results in the literature, as only 6% of 17.1% of American patients with eczematous symptoms were diagnosed with atopic dermatitis
      • Hanifin J.M.
      • Reed M.L.
      Eczema Prevalence and Impact Working Group
      A population-based survey of eczema prevalence in the United States.
      and 93% of Puerto Rican children with symptoms of atopic dermatitis and sensitization to at least one allergen were not diagnosed with this disease.
      • Yang G.
      • Han Y.Y.
      • Forno E.
      • et al.
      Under-diagnosis of atopic dermatitis in Puerto Rican children.
      This suggests significant underdiagnosis and undertreatment of the condition in low-income settings, possibly related to limited access to healthcare specialists.

      Limitations

      As an observational study, this multicenter cross-sectional study has certain limitations, such as memory bias. Furthermore, this study did not include representative centers from southern Mexico due to a lack of information, preventing analysis by region (Pacific, Northeast, Bajío, Central, and Southeast).
      While the GAN study has demonstrated an adequate method for estimating the prevalence of allergic disease symptoms, we did not obtain biological samples to determine genetic differences or levels of IgE or confirm the presence of atopic eczema lesions.

      Conclusion

      This is Mexico's most extensive epidemiological study to estimate eczema symptoms in children and adolescents. There has been an increase in eczema symptoms in both age groups since the ISAAC Phase IIIB study and a low prevalence of diagnosis of eczema. Several interesting and potentially associated factors were also described, including temperature, relative humidity, asthma and hay fever symptoms, paracetamol use, and antibiotic use, so further investigation is required.

      Abbreviations

      GAN, Global Asthma Network; ISAAC, International Study of Asthma and Allergies in Childhood; OR, Odds ratio; 95% CI, 95% Confidence interval

      Funding

      No financial support for this work could have influenced its outcome.

      Authors' contributions

      NREM: Made substantial contributions to conception and drafting the manuscript.
      DRNBE: Made substantial contributions to conception, design, acquisition of data and drafting the manuscript.
      RNN: Made substantial contributions to design, acquisition of data and drafting the manuscript.
      BA: Made substantial contributions to the analysis, interpretation of data and drafting the manuscript.
      MPV: Made substantial contributions to design and acquisition of data.
      GAR: Made substantial contributions to design and acquisition of data.
      EP: Made substantial contributions to the analysis and drafting the manuscript.
      RGBDC: As centre coordinator, made substantial contributions on the acquisition of data.
      EDAJ: As centre coordinator, made substantial contributions on the acquisition of data.
      LZF: As centre coordinator, made substantial contributions on the acquisition of data.
      GML: As centre coordinator, made substantial contributions on the acquisition of data.
      OLGG: As centre coordinator, made substantial contributions on the acquisition of data.
      HMLO: As centre coordinator, made substantial contributions on the acquisition of data.
      LSJS: As centre coordinator, made substantial contributions on the acquisition of data.
      SHJA: As centre coordinator, made substantial contributions on the acquisition of data.
      JPMA: As centre coordinator, made substantial contributions on the acquisition of data.
      SCMG: As centre coordinator, made substantial contributions on the acquisition of data.
      RPN: As centre coordinator, made substantial contributions on the acquisition of data.
      AMMDJ: As centre coordinator, made substantial contributions on the acquisition of data.
      DRNBE: Involved in revising it critically for important intellectual content.
      SROJ: Involved in revising it critically for important intellectual content.

      Ethics approval and consent to participate

      The authors declare that all procedures were carried out in accordance with the ethical standards of the institutional committee on human investigation, the World Medical Association, and the Helsinki Declaration.
      The authors obtained informed consent from the parents or guardians of participants in the present study. The corresponding author accepts responsibility for this manuscript.
      The present study was approved by the Ethics, Research, and Biosafety committees of the Hospital Infantil de México Federico Gómez (HIMFG, protocol HIM/2016/065) in accordance with the guidelines of the institution.

      Consent for publication

      All authors consent this article for publication.

      Availability of data and materials

      The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

      Declaration of competing interest

      The authors declare that they have no conflict of interest in relation to the methods or materials employed in this study.

      Acknowledgments

      In the GAN study, we would like to thank all the children, adolescents, and parents who participated in obtaining information and updating the prevalence of eczema. This work was designed, elaborated, written, and analyzed by all of the authors involved. In order to complete this important project, we would like to acknowledge the financial support provided by the Mexican College of Pediatricians Specializing in Allergy and Clinical Immunology (COMPEDIA). In addition, we would like to thank Dr. Luis Garca-Marcos Álvarez and Dr. Virginia Pérez for their support.

      Appendix A. Supplementary data

      The following are the Supplementary data to this article:

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