Email: martin.chalumeau@gmail.com

Team: Obstetrical, perinatal and pediatric epidemiology research (EPOPE)

Website: www.epopé-inserm.fr

Keywords: iron deficiency, iron deficiency anemia, CARMA studies

Iron deficiency (ID) is the most frequent micronutrient deficiency and ID anemia (IDA) the most frequent red blood cells disease in children in industrialized countries. ID prevalence before the age of 3 years is estimated around 5 to 20% (1, 2). ID is associated with important neurological lesions in juvenile animal models (3) and with neurological consequences (reduced cognitive, motor, and behavioral capacity) in the short, intermediate, and long-term in observational studies and randomized trials in children (1, 4). Its main risk factors are low perinatal iron stocks but mainly an imbalance between iron requirements and dietary intake, due, for example, to dietary diversification that is delayed or inappropriate because iron-poor. Its main risk marker is low parental socioeconomic status. In theory, ID and IDA in children are easily accessible to simple primary prevention activities via dietary modification.

Issues

Main issues about ID in children concern the population level: the efficiency of prevention and screening strategies of ID, its prevalence (especially in Europe), and the specific contribution of risk factors. The performances of classical vs more recently proposed biological diagnosis criteria of ID are also controversial.

Learned societies and public health authorities identified ID in children as a health issue long ago. Nonetheless, current prevention strategies vary widely. In France, the National Nutrition Health Plan and the Nutrition Committee of the French Pediatrics Society have chosen a strategy based on toddler milk formula (enriched in iron), which they firmly recommend to the age of 3 years, at the same time as they recognize the low level of evidence supporting this recommendation (5). Other European positions (those of the European Food Safety Authority -EFSA- (6) and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition -ESPGHAN- (7)) and the one of the American Academy of Pediatrics (AAP) are much more circumspect and insist on the multiple potential of dietary sources of iron (1).

American guidelines also suggest routine screening for children ‘‘at risk’’ and enumerate clinical criteria that should be used to evaluate risk: ‘‘low socio-economic status, an history of prematurity or low birth weight, exposure to lead, exclusive breastfeeding beyond 4 months of age without supplemental iron, weaning to whole milk or complementary foods that do not include iron-fortified cereals or foods naturally rich in iron, and poor growth’’(1). Unfortunately, the AAP recommendations fail to indicate the number of criteria that should entail screening, respective weights of these criteria, and/or how they can be combined in practice. No other validated tool for measuring the risk of ID in children is proposed. Thus primary care clinicians cannot rely on a simple tool helping daily decision to prescribe blood tests for toddlers suspected to be at risk of ID.

Furthermore, the prevalence of ID and IDA in European children is extrapolated from old studies, with small numbers of subjects, or strong recruitment biases, or both (8). Studies of the risk factors for ID have not been accompanied by food intake surveys and thus do not allow an analysis of the independent protective role of the various source of iron including toddler milk formula and non-dairy iron intake. At last, the determinants of parental and medical behavior have never been studied, especially in relation to the use and prescription of toddler milk formula.

The conclusion that our knowledge on ID and IDA in children is very limited in relation to the health issues have also been made by the ESPGHAN which has set as priority research: the performance of population-based studies of the prevalence of ID and IDA in children in Europe, the study of the relation between dietary sources of iron and health status, as well as studies of the role of new biomarkers (hepcidin…) for routine assessment of iron status (7). ESPGHAN has also stressed the need to understand the obstacles to implementation of the dietary guidelines among the most disadvantaged populations.

Objectives

The goal of this project is to study the prevalence and main determinants of ID and IDA in France in 2-year-old children and to improve knowledge and strategies for prevention and screening. The specific objectives are:

1. To estimate the prevalence of ID and IDA in 2-year-old children living in France.

2. To study the nutritional determinants of ID in these children. In particular, to analyze the relationship between ID and consumption of toddler milk formula and non-dairy iron intake.

3. To study the determinants of parental and medical behaviors inappropriate for the primary prevention of ID: determinants of the prescription of toddler milk formula by physicians, determinants of the use of toddler milk formula and other dietary sources of iron for the parents (especially those associated with their socio-cultural background and knowledge), and obstacles to their use.

4. To improve clinical screening strategies. In particular, to test the ability of primary-care physicians to define a child’s risk level for ID based on the simple collection of the risk factors proposed by the AAP. To

derive and to perform the internal validation of a new clinical prediction tool to assist in the decision about prescribing a laboratory screening test.

5. To study the usefulness of non-routine iron status markers (hepcidin, erythrocyte protoporphyrin and reticulocyte hemoglobin content) for the diagnosis of ID.