Lead exposure during childhood contributes to intellectual disability among children. Absorption of ingested lead is higher in children with nutritional deficiencies, and pica further enhances the absorption rate [1-3]. Children are more vulnerable to the toxic effects of lead even with low levels of exposure potentially causing serious and possible irreversible neurological damage. Lead exposure is also known to adversely affect the behavior and cognitive development among children [3-5]. Younger age and pre-existing iron deficiency pose increased risk of developing lead-induced anemia. The prevalence and severity of lead induced anemia is known to correlate well with blood lead levels (BLL) [6-8].

This study aimed to investigate the proportion of children with elevated BLLs and associated risk factors for elevated BLLs at 15 and 24 months among the Mal-ED cohort in Vellore, India. The effects of elevated blood lead levels on child cognition and anemia among pre-school children were also assessed.

Vellore is a large town in Southern India located 120 km from the Tamilnadu State capital Chennai. As part of a multi-country study on malnutrition, a birth cohort (called the Mal-ED) was recruited from an urban slum of 8 neighbourhoods with an approximate population of 12,000 to be followed up at home, and at a clinic in the study area by a team of trained field workers, nutritionists, psychologists and medical staff.

Pregnant women residing in an urban slum were identified through a house-to-house survey, and information on the expected date of delivery was obtained. Mothers were visited soon after birth and invited to participate in the study. Exclusion criteria were: multiple pregnancies, another sibling in the study or family planning to migrate outside study area.

Socio-economic status (SES) of the families was assessed at 6 monthly intervals after recruitment using the following components: access to improved water and sanitation, assets owned by the family, maternal education and income (the WAMI index). The households were further classified as belonging to low, middle or high SES based on tertiles of the total score.

The risk factors tested included sex of the child, low birth weight, duration of exclusive breastfeeding, maternal anthropometry two months after childbirth, maternal mental status, and (as collected by a SRQ-20 questionnaire), number of living children in the family, any previous child death in the family, socioeconomic status, and housing indicators, including the type of floor, walls and drinking water. The association between socio-demographics, associated risk factors and elevated BLLs was tested using a multivariate backward conditional logistic regression analysis to adjust for confounding factors; adjusted ORs were estimated.

Blood lead levels: A maximum of 5 mL of venous blood was collected from the children at 7, 15 and 24 months for various biochemical tests, of which around 1 mL of whole blood was preserved with Dipotassium Ethylenediamine-tetraacetic acid (K2 EDTA) for determination of lead levels. The samples were refrigerated immediately, and were transported to the laboratory within a few hours using cold packs. Lead levels in whole blood were estimated by Graphite Furnace Atomic Absorption Spectroscopy (GFAAS) method using an M Series Atomic Absorption Spectro-photometer. A value of 10 µg/dL was considered as the cut-off level to identify elevated BLLs.

Cognition, motor, language, social-emotional and adaptive behaviours were assessed using the Bayley Scales of Infant Development III (BSID III) [9,10] at 6, 15 and 24 months. BLLs at 15 months were correlated with cognition scores at 24 months, as recorded by the BSID-III.

A total of 301 mothers were visited soon after child birth and invited to participate in the study, thereby enrolling 251 children between March 2010 and February 2012. Ten mothers were unwilling to participate and 40 babies were excluded. Of the enrolled 251 children, 25 were lost to follow-up due to non-participation (8), migration (15), and death (2). The mean (SD) birth weight of the cohort was 2.82 (0.44) kg; 124 (56%) were girls.

An association between early childhood lead levels and cognitive impairment at a later age is well documented [18-20]. Evidence from a systematic review indicates that doubling of BLL is associated with a mean deficit in the full scale IQ by 1 to 2 points [21]. A study among urban children aged 3 to 7 years from Chennai, India, found that high BLLs were associated with reduced visual-motor abilities [15]. In our study, children with elevated BLLs at 15 months had excess risk of having poorer cognitive scores at 24 months although this finding was not statistically significant. Future prospective assessments of cognition and school performances are needed to better understand the effect of lead exposure on neurodevelopment of children. Younger age and pre-existing iron deficiency pose increased risk of developing lead induced clinical anemia. Anemia has been reported to be more common among children below 3 years of age with high BLLs (75.3 % vs. 67.4 %) [17]. In our study, more than half of the study children were anemic at 15 months of age but significant association between BLLs and hemoglobin levels at 15 months was found. Findings from this study could be limited in terms of not adjusting for other risk factors for anemia, including nutritional deficiencies.

Elevated BLLs are clearly a public health concern among preschool children living in urban slums of Vellore. Poorer conditions of the living environment seem to be associated with higher lead levels. More research focusing on the built environment and behavioral characteristics of children and parents is needed to understand the exposure pathways in greater detail, and to investigate causality.

Funding: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill and Melinda Gates Foundation, the Foundation for the NIH and the National Institutes of Health/Fogarty International Center. The authors thank the staff and participants of the MAL-ED Network Project for their important contributions; Competing Interest: None stated.