Adjusting Iron Deficiency for Inflammation in Cuban Children Aged Under Five Years: New Approaches Using Quadratic and Quantile Regression
July–October 2022, Vol 24, No 3–4

INTRODUCTION Ferritin is the best biomarker for assessing iron deficiency, but ferritin concentrations increase with inflammation. Several adjustment methods have been proposed to account for inflammation’s effect on iron biomarker interpretation. The most recent and highly recommended method uses linear regression models, but more research is needed on other models that may better define iron status in children, particularly when distributions are heterogenous and in contexts where the effect of inflammation on ferritin is not linear.

OBJECTIVES Assess the utility and relevance of quadratic regression models and quantile quadratic regression models in adjusting ferritin concentration in the presence of inflammation.

METHODS We used data from children aged under five years, taken from Cuba’s national anemia and iron deficiency survey, which was carried out from 2015–2018 by the National Hygiene, Epidemiology and Microbiology Institute. We included data from 1375 children aged 6 to 59 months and collected ferritin concentrations and two biomarkers for inflammation: C-reactive protein and α-1 acid glycoprotein. Quadratic regression and quantile regression models were used to adjust for changes in ferritin concentration in the presence of inflammation.

RESULTS Unadjusted iron deficiency prevalence was 23% (316/1375). Inflammation-adjusted ferritin values increased iron-deficiency prevalence by 2.6–4.5 percentage points when quadratic regression correction model was used, and by 2.8–6.2 when quantile regression was used. The increase when using the quantile regression correction model was more pronounced and statistically significant when both inflammation biomarkers were considered, but adjusted prevalence was similar between the two correction methods when only one biomarker was analyzed.

CONCLUSIONS The use of quadratic regression and quantile quadratic regression models is a complementary strategy in adjusting ferritin for inflammation, and is preferable to standard regression analysis when the linear model’s basic assumptions are not met, or when it can be assumed that ferritin–inflammation relationships within a subpopulation may deviate from average trends.

KEYWORDS Alpha-1-acid glycoprotein, C-reactive protein, anemia, iron deficiency, ferritin, acute phase protein, Cuba

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Influence of Inflammation on Assessing Iron-Deficiency Anemia in Cuban Preschool Children
July–October 2021, Vol 23, No 3–4

INTRODUCTION Anemia is a public health problem worldwide and is most prevalent in preschool children, for whom it is the most frequent cause of nutritional deficits. In turn, iron deficiency is the main cause of anemia, affecting 43% of children globally. Previous studies in Cuba show rates of iron deficiency in preschool children between 38.6% and 57.6%, higher in infants (71.2% to 81.1%). WHO recommends using serum ferritin as an indicator of iron deficiency accompanied by acute (C-reactive protein) and chronic (α1-acid glycoprotein) inflammation biomarkers.

OBJECTIVE Assess how inflammation affects measuring and reporting of iron-deficiency anemia rates in Cuban preschool children.

METHODS Data were obtained from serum samples contained in the National Anemia and Iron Deficiency Survey, and included presumably healthy preschool Cuban children (aged 6–59 months). Serum samples were collected from 1375 children from randomly selected provinces in 4 regions of the country from 2014 through 2018. We examined the association between ferritin and two inflammatory biomarkers: C-reactive protein and α1-acid glycoprotein. Individual inflammation-adjusted ferritin concentrations were calculated using four approaches: 1) a higher ferritin cut-off point (<30 g/L); 2) exclusion of subjects showing inflammation (C-reactive protein >5 mg/L or α1-acid glycoprotein >1 g/L); 3) mathematical correction factor based on C-reactive protein or α1-acid glycoprotein; and 4) correction by regression with the method proposed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia Group. We estimated confidence intervals of differences between unadjusted prevalence and prevalence adjusted for inflammation by each method.

RESULTS The proportion of children with inflammation according to C-reactive protein concentrations >5 mg/L was lower (11.1%, 153/1375) than the proportion measured according to the concentrations of α1-acid glycoprotein, at >1 g/L (30.8%, 424/1375). The percentage of children with high concentrations of at least one of the aforementioned biomarkers was 32.7% (450/1375). Thus, each correction method increased the observed prevalence of iron deficiency compared to unadjusted estimates (23%, 316/1375). This increase was more pronounced when using the internal regression correction method (based only on C-reactive protein) or the method based on a higher cut-off point. Adjustment using all four methods changed estimated iron deficiency prevalence, increasing it from 0.1% to 8.8%, compared to unadjusted values.

CONCLUSION One-third of preschool children had biomarkers indicating elevated inflammation levels. Without adjusting for inflammation, iron deficiency prevalence was underestimated. The significant disparity between unadjusted and inflammation-adjusted ferritin when using some approaches highlights the importance of selecting the right approach for accurate, corrected measurement. The internal regression correction approach is appropriate for epidemiological studies because it takes into account inflammation severity. However, other models should be explored that account for inflammation and also provide better adjusted ferritin concentrations.

KEYWORDS Anemia, iron deficiency; child, preschool; inflammation; Cuba

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Anemia and Iron Deficiency Related to Inflammation, Helicobacter pylori Infection and Adiposity in Reproductive-age Cuban Women
April–July 2017, Vol 19, No 2–3

INTRODUCTION Iron deficiency is the main cause of anemia, but infections, inflammation and other factors also play a role. Anemia in women of childbearing age is a risk for pregnancy, childbirth and childhood development during the first two years of life. In Cuba, per WHO definition, anemia is a moderate public health problem in the third trimester of pregnancy and in preschoolers, with a prevalence of 21.6%, in both cases.

OBJECTIVE Estimate prevalence of anemia and iron deficiency in women of childbearing age and assess its relation to inflammation, overweight, central adiposity, H. pylori infection and ingestion of iron-rich foods and enhancers of iron absorption.

METHODS A cross-sectional, analytical study was performed in 391 women aged 18–40 years in four municipalities of Havana, Cuba, from February through June 2014. Variables (indicators in parentheses) were anemia (hemoglobin), iron deficiency (ferritin), nutritional status (body mass index and waist circumference), inflammation (C-reactive protein, acid alpha 1-glycoprotein and interleukin 6), H. pylori infection and ingestion of iron-rich foods. SPSS 20.0 and Epi Info 7.1.2.0 were used for statistical analysis.

RESULTS Anemia prevalence was 24.6% (96/391); iron deficiency, 68% (266/391); H. pylori infection, 47.1% (184/391); inflammation detected by C-reactive protein, 8.4 % (33/391) and by alpha-1-glycoprotein, 19.9% (78/391). Limited results are included for interleukin 6, which was determined in fewer cases (96). Excess body weight was found in 38.7% (150/388) and increased central adiposity in 26.7% (101/378). Iron deficiency was the main cause of anemia (OR 2.68). Central adiposity, excess body weight, and iron deficiency were positively associated with inflammation (OR of 1.77, 1.23 and 1.72, respectively), whereas H. pylori infection was negatively associated with iron deficiency and anemia (OR 0.75 and 0.94, respectively). Low consumption of meat (OR 1.17) and vegetables (OR 1.36) showed discrete limited positive associations with iron deficiency, as well as low consumption of eggs (OR 1.69) and vegetables (OR 1.56) with anemia.

CONCLUSIONS Anemia is a moderate public health problem in the studied group, but with iron deficiency present in two thirds of the population and associated with anemia. Risk factors for anemia and iron deficiency, such as menorrhagia and bacterial or viral infections, should be assessed in women of childbearing age, to support interventions needed to reduce risks in pregnancy and childbirth.

KEYWORDS Anemia, iron deficiency, women, women of childbearing age, inflammation, Helicobacter pylori, obesity, adiposity, Cuba

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La anemia en niños menores de cinco años en la región oriental de Cuba, 2005-2011
Selecciones 2014

INTRODUCCIÓN La anemia constituye el principal problema nutricional en los niños preescolares cubanos. Tal situación estimuló la realización de intervenciones de salud por parte de las autoridades sanitarias cubanas con el propósito de prevenir y controlar la enfermedad. En 2008 se estableció una estrategia nacional integral que proporcionó atención particular a las provincias orientales del país, por constituir la región con los más grandes desafíos en los determinantes sociales de salud.

OBJETIVO Determinar la prevalencia de anemia en los niños de 6 a 59 meses en las cinco provincias orientales de Cuba en tres años diferentes dentro de una década, así como estudiar la asociación de la anemia con los factores epidemiológicos y nutricionales, para evaluar el impacto del Plan Integral Cubano para la Prevención y el Control de la Anemia por Deficiencia de Hierro en Cuba.

MÉTODOS Se realizaron estudios de corte transversal en muestras representativas de la población de los niños con 6 a 59 meses, residentes en las provincias orientales del país, en los años 2005, 2008 y 2011. Se midió el nivel de hemoglobina para diagnosticar la anemia (hemoglobina menor de 110 g/L) y los resultados se relacionaron con variables independientes tales como la edad, el sexo, el área de residencia (urbana o rural), la asistencia a círculos infantiles [guarderías para niños entre 1 y 5 años de edad, pertenecientes al Sistema Nacional de Educación de Cuba —Eds.], el peso al nacer, la historia de lactancia materna, así como la anemia materna durante el embarazo. Se calcularon las frecuencias de distribución, las comparaciones se evaluaron mediante la prueba de χ2 y los Odds Ratio (OR) con intervalos de confianza (IC) del 95%.

RESULTADOS La prevalencia de anemia en la región estudiada disminuyó de 31.8% en 2005 a 26% en 2011; en la mayoría de los casos era leve (hemoglobina = 100-109 g/L). La prevalencia fue superior en los niños de 6 a 23 meses comparado con los que tenían de 24 a 59 meses. No se encontró diferencia significativa en la prevalencia de anemia entre niños y niñas. La prevalencia fue superior en las áreas rurales comparadas con las áreas urbanas en 2005 (p = 0.026) y en 2011
(p = 0.012). La asistencia a círculos infantiles constituyó un factor protector en los tres años estudiados. El bajo peso al nacer solo estuvo asociado con la anemia en 2011 (OR 1.74, IC 1.04-2.92). La prevalencia de la lactancia materna de forma exclusiva durante los seis primeros meses de vida se incrementó durante el período de estudio y la anemia se asoció con la no utilización de lactancia materna exclusiva en 2005 (OR 1.57, IC 1.05-2.34). La anemia materna al inicio y durante el embarazo fue un factor de riesgo significativo tanto en 2005 (OR 1.98, IC 1.27-3.10) como en 2011 (OR 1.43, IC 1.05-1.94).

CONCLUSIONES Aunque la prevalencia de anemia disminuyó paulatinamente durante el período del estudio, la enfermedad continúa siendo un problema de salud pública en Cuba, por lo que se deben mantener y fortalecer las medidas para su prevención y su control, tales como realizar intervenciones de salud sobre las mujeres en edad reproductiva, la alimentación exclusiva por lactancia materna durante los primeros seis meses de edad, estimular el cumplimiento de las recomendaciones de las normas cubanas para la alimentación complementaria de los niños hasta los dos años de edad, así como continuar la evaluación y la investigación de las causas de la anemia en los niños en edad preescolar.

PALABRAS CLAVE Anemia, niños, preescolar, infantes, lactancia materna, círculos infantiles, guarderías, Cuba

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Anemia in Children under Five Years Old in Eastern Cuba, 2005–2011
January 2014, Vol 16, No 1

INTRODUCTION Anemia is the main nutritional problem in Cuban preschool children, prompting several interventions to prevent and control it. An enhanced national strategy was established in 2008, and particular attention paid to the eastern provinces, the region with greatest challenges in social determinants of health.

OBJECTIVE Determine anemia prevalence in children aged 6–59 months in Cuba’s five eastern provinces in three separate years within a decade, as well as association of anemia with epidemiological and nutritional factors, to assess impact of Cuba’s Comprehensive Plan for Prevention and Control of Iron-Deficiency Anemia in Cuba.

METHODS Cross-sectional studies of children aged 6–59 months (completed) were conducted in 2005, 2008 and 2011. Hemoglobin levels were measured to diagnose anemia (hemoglobin <110 g/L) and data were collected on independent variables such as age, sex, area of residence (urban or rural), daycare center enrollment, birth weight, breastfeeding history, and maternal anemia during pregnancy. Frequency distributions were created and comparisons tested with the chi square, and odds ratios calculated with 95% confidence intervals.

RESULTS Anemia prevalence in the region fell from 31.8% in 2005 to 26% in 2011; most of cases were mild (hemoglobin: 100–109 g/L). Prevalence was higher in children aged 6–23 months than in those aged 24–59 months throughout. No significant differences were found in anemia prevalence between boys and girls. Prevalence was higher in rural than in urban areas in 2005 (p = 0.026) and 2011 (p = 0.012). Daycare enrollment emerged as a protective factor in all three years. Low birth weight was associated with anemia only in 2011 (OR 1.74, CI 1.04–2.92). Prevalence of exclusive breastfeeding for six months increased over the study period; lack of breastfeeding was found to be associated with anemia in 2005 (OR 1.57, CI 1.05–2.34). Maternal anemia at onset of and during pregnancy was a significant risk factor in 2005 (OR 1.98, CI 1.27–3.10) and 2011 (OR 1.43, CI 1.05–1.94).

CONCLUSIONS Although anemia prevalence steadily decreased over the study period, it continues to be a public health problem in Cuba and anemia prevention and control measures should be maintained and strengthened: interventions for women of childbearing age, fostering exclusive breastfeeding of infants through their sixth month, and encouraging compliance with recommendations on complementary feeding per Cuba’s nutritional guidelines for children aged <2 years. Further evaluation is needed to identify the causes of anemia in the population of preschool children.

KEYWORDS Anemia, children, preschool, infants, breastfeeding, child daycare centers, Cuba

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