Anemia as a risk factor for infectious diseases in infants and toddlers: Results from a prospective study Amalia Levy, Drora Fraser, Shirley D. Rosen, Ron Dagan, Richard J. Deckelbaum, Christian Coles & Lechaim Naggan S. Daniel Abraham International Center for Health and Nutrition, and Department of Epidemiology, Ben-Gurion University of the Negev, Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer-Sheva, Israel and Presbyterian Hospital, Columbia University, New York, USA Accepted in revised form 22 November 2004 Abstract. Anemia due to iron deficiency is the most prevalent form of micronutrient malnutrition in the world, however, the causal relationship between anemia and infection remains unclear. We examined prospectively, the association between anemia and infection among Bedouin infants. We recruited 293 families and newborns from the Bedouin population, which is ongoing major lifestyle changes, during the periods of 1989–1992 and 1994–1997 and followed them to age 18 months. The number of diarrhea and respiratory disease episodes as well as total days of diarrhea were ascertained weekly. Hemoglobin levels were obtained at age 6 months. Additional data on feeding practices, environmental, household and demographic characteristics were obtained through- out the 18 months. Diarrhea before 6 months of age was found to be a risk factor for diarrhea after that age. After controlling for early morbidity < 6 months, anemia (Hb < 11 g/dl) at 6 months was an indepen- dent risk factor for diarrhea and respiratory illness from 7 to 18 months of age. This associations re- mained significant even after controlling, in addition, for environmental and socio-economic factors. In the multivariable models, anemia at age 6 months in- creased the risk for diarrhea after that age by 2.9-fold (95% confidence interval 1.6–5.3; p ¼ 0.001) and that of respiratory disease by 2-fold (1.1–3.7; p ¼ 0.03). Our findings suggest that anemia may increase the rates of infections in toddlers. The possibility that reducing anemia in infants may be a preventive measure to lower disease burden from infectious disease in this and other vulnerable populations should be tested in fur- ther studies. Key words: Children, Cohort study, Diarrhea, Negev Bedouins, Respiratory diseases Introduction Iron deficiency anemia (IDA) is the commonest form of malnutrition worldwide, affecting 43% of the world’s children. It is particularly common in Asia and Africa [1] but is prevalent in low socio-economic populations in developed countries as well [1–3]. In infants it has wide-ranging adverse consequences including impaired physical growth and compro- mised cognitive development. Anemia is also associ- ated with a short attention span and impaired learning capacity [4]. The prevalence and causes of anemia among Israeli children have been studied during the last three dec- ades [5–8]. In the 1970s, rates of anemia were high among Jewish children, and were shown to be asso- ciated with low socio-economic status [5]. In the 1980s, anemia rates among Arab infants ranged from 19 to 71% and among Jewish children the rate was about 60% [6, 7]. As a result, in the mid 1980s the Israeli Ministry of Health recommended giving iron supplements to all infants age 5–12 months. Studies published in the early 1990s showed that the rates of anemia had decreased in various intervention areas [8]. Recently the Israeli Ministry of Health concluded that anemia in Israeli infants is due largely to iron deficiency [9]. This is due to the facts that alternative causes for anemia are rare in Israeli children and anemia in general improved following supplementa- tion. A recent study examined nutritional status in 534 healthy Bedouin children aged 1–2 years of age attending Ministry of Health Well Infant and Mother Clinics, for routine vaccination [10]. While 27% of the children were anemic (hemoglobin levels 11 g/dl), only 11.5% had zinc deficiency (<60 lg/dl). When comparing the median value for American 2 year olds from the NHANES II study [11] we find that it is <85 lg/dl as compared with our data of 89 lg/dl. Furthermore the mean (± SE) values for serum zinc levels were 82.5 (± 0.3) and 94.1 (± 1.3) for US children and the Bedouin group, respectively. These data suggest that while zinc may contribute to anemia in the Bedouin population iron deficiency has a more decisive role than does zinc. We therefore consider hemoglobin levels under 11 g/dl in the cohort infants as anemia due to iron deficiency. European Journal of Epidemiology (2005) 20: 277–284 Ó Springer 2005 DOI 10.1007/s10654-004-6515-6