INTRODUCTION

1. Cord serum concentrations of iron are associated with decreased likelihoodof respiratory symptoms in the first year of life in at-risk childrenEW Triche1, K Belanger1, L Lundsberg1, BP Leaderer11Yale University School of Medicine, New Haven, CT ABSTRACT RESULTS Table 1. Associations between subject characteristics and respiratory outcomes Rationale: Increases in asthma prevalence in recent decades suggest that environmental exposures are important causal factors in this trend. Recent research implicates fetal exposures, including levels of trace elements, in the development of asthma symptoms and allergies. We investigated associations between cord concentrations of iron and zinc and early respiratory symptoms and allergies in a cohort of children at-risk for asthma. Methods: 1002 women delivering babies and who had at least one additional child with diagnosed asthma were enrolled in a birth cohort study. Asthma symptoms in the first year of life (wheeze, persistent cough, shortness of breath, and chest tightness) were obtained from quarterly telephone interviews. Cord blood samples were available for 101 of the children who also had symptom information available for the first year of life. Results: Mean (s.d.) iron and zinc concentrations in cord blood were 1.62 (0.58) and 1.13 (0.25), respectively. Cord blood concentrations of iron, but not zinc, were significantly lower in early-onset wheezers than in non-wheezers or late-onset wheezers (t=2.51, p=0.01). For each μg/ml increase in iron, there was a significant 63% decreased likelihood of early wheezing in analyses adjusted for zinc, race/ethnicity, number of children in household, and maternal asthma. No associations were found between either iron or zinc levels and IgE levels in early childhood. Conclusion: Fetal exposure to higher levels of iron appears to decrease risk of early wheeze and persistent cough in a cohort of children at risk for asthma. Figure 1. Serum concentrations of iron and zinc in cord blood Figure 2. Cord serum iron and zinc concentrations by respiratory symptom outcomes INTRODUCTION • Micronutrients including iron and zinc are necessary for many biological processes, including adequate fetal development and immune system function. Both iron and zinc cross the placental barrier by active transport. • Associations have been documented between diminished cord serum ferritin and negative neurodevelopmental outcomes as well as teratogenic effects resulting from zinc deficiencies. Cord ferrous levels can also predict iron status in early childhood. • There have been conflicting findings in the literature of associations between iron and zinc with respiratory health. Some studies have shown an increased risk of asthma while others have failed to demonstrate an elevated risk. Other research indicates that iron deficiency may increase risk of respiratory symptoms. Chronic cough due to extrathoracic airway hyperresponsiveness has been associated with iron deficiency. Previous research has also demonstrated the role of specific micronutrients as they relate to the development of wheezing, showing a protective effect of increased iron but no significant association with zinc. • Lack of consistent findings in previous studies warrants research to determine the role of both iron and zinc in the risk of respiratory disease. The current study investigates the role of both iron and zinc as measured in cord blood with asthma symptoms, wheezing, and persistent cough during the first year of life in a cohort of children at risk for developing asthma. • This study examines whether cord serum concentrations of zinc and iron are associated with asthma symptoms in the first year of life in a cohort of children at risk for asthma. SUMMARY • Cord serum concentrations of iron ranged from 0.24 – 3.69 μg/ml with a mean (s.d.) of 1.62 (0.58) μg/ml. Zinc concentrations ranged from 0.68 – 2.09 with a mean of 1.13 (0.25) μg/ml. • Mean concentrations of iron were significantly higher in children who had asthma symptoms, wheezing, and persistent cough in the first year of life. • Male gender was marginally associated with an increased in wheeze in the 1st year of life. Babies who were admitted to NICU had increased asthma symptoms / persistent cough in the 1st year of life. • In logistic regression models adjusted for a number of potential confounders, higher mean iron concentrations were associated with a strong, significant decrease in likelihood of asthma symptoms, wheeze and persistent cough in the first year of life. For each μg/ml increase in iron, there was a 58% - 70% decrease in respiratory symptoms. METHODS • Study population • Women delivering an infant in participating hospitals in Connecticut or south-central Massachusetts 1997-1999 were approached for eligibility • Infants with an older sibling with physician diagnosed asthma were invited to participate; a total of 1,002 index children were enrolled • Data collection • Mothers were interviewed quarterly to obtain symptom and exposure information for the first year of life • Symptoms, including wheeze, persistent cough, chest tightness, and shortness of breath and use of asthma medication were collected. • Exposure assessment • Cord blood samples were collected at birth, spun down to separate out the serum, and stored at -70oC. • Cord serum samples were analyzed for zinc and iron concentrations by the Children’s Hospital Oakland Research Institute using ICP-OES. • Samples were available for 101 index children with symptom information available. • Health outcomes • Three respiratory outcomes were analyzed: 1) any asthma symptom in the first year of life; 2) any wheeze in the first year of life; and 3) any persistent cough in the first year of life Table 2. Unadjusted and adjusted associations between cord serum concentrations of iron and zinc with respiratory symptoms for the first year of life CONCLUSIONS • Cord serum concentrations of iron, but not zinc, are associated with a strong decrease in likelihood of asthma symptoms in the first year of life in children at-risk of developing asthma • Possible mechanisms involved in the relationship of iron and respiratory disease may include disruptions in the inflammatory response following altered iron concentrations; alterations in cytokine function and airway inflammation; and disruption in ferroportin-1 (FPN-1) and transferring receptor-1(TfR-1) which facilitate iron transport across the placental barrier, directly affecting the fetal iron stores. ACKNOWLEDGEMENT This study was funded by NIEHS ES 07456 and ES 11013.