Autism Spectrum Disorder and Its Association with Urinary Lead And Essential Elements: A Case-Control Study Among Preschool Children In Kuala Lumpur

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a multifactorial pathogenesis. Lead (Pb), a heavy metal that is ubiquitous in the environment and has been linked to neurotoxicity in children even at low concentrations. Essential elements are required by humans for development of brain function. The primary goal of this study is to assess the role of urinary Pb and essential elements in the development of ASD among preschool children in Kuala Lumpur. The unmatched case-control study included 81 ASD children and 74 typically developed (TD) children aged 3 to 6 years. The assessment was done on parents and children. The parents completed the self-administered online questionnaires which consisted of demographic sections, validated parental Pb knowledge test, and section of risk factors for ASD. For children, their urine samples were collected by parents at home for laboratory analysis. By using inductively coupled plasma mass spectrometry (ICP-MS), the prepared samples were tested for Pb, calcium (Ca), magnesium (Mg), zinc (Zn), and iron (Fe). The result demonstrated the mean urinary Pb, Mg, Zn and Fe levels were lower in ASD children than TD children (p < 0.05). The urinary Pb level in both groups were below the “elevated level”. The cut-off point of urinary Pb level was 0.25 μg/dL (p < 0.05). There was no negative correlation between urinary Pb and essential elements observed to demonstrate inhibitory mechanism between these elements during excretion. Higher parental education level, children of non-Malay, male gender, first-born, those who lived outside Kuala Lumpur and those who had urinary Pb level equal or less than 0.25 μg/dL, and ex-smoker parents had higher odds of developing ASD (p < 0.05). The reduction of odds of having ASD increased from 5.0 % to 11.0 % after interaction of Zn with Pb (p < 0.05). In conclusion, the neurotoxic effect of Pb at low concentrations and the lack of essential elements contributed to the occurrence of ASD.