Environmental pollutant exposure and adverse neurodevelopmental outcomes: An umbrella review and evidence grading of meta-analyses.

The proliferation of chemicals resulting from human activities and the rapid industrialization has profoundly impacted the global environment. Hazardous and toxic substances are introduced into the environment at a rate that exceeds the ability of natural processes to diffuse, dilute, decompose, recycle, or store them harmlessly. This leads to significant environmental pollution and poses serious threats to human health and well-being [1], [2]. The World Health Organization estimates that direct chemical pollution of air, soil, water, and occupational settings accounts for approximately 2 million fatalities per year [3]. Therefore, a rigorous and comprehensive assessment of the health risks associated with these pollutants is essential for establishing effective regulations and implementing policies that promote safer alternatives.

Exposure to the vast array of modern chemicals and their mixtures can cause both acute and chronic toxicity [2]. Compared to adults, foetuses and children are more sensitive and susceptible to these pollutants due to their actively developing brains and immature detoxification systems [4], [5]. Environmental pollutant exposure may disrupt normal development processes from the embryonic stage through adolescence, resulting in various adverse neurodevelopmental outcomes, including attention deficit hyperactivity disorder (ADHD) [6], [7], [8], autism spectrum disorder (ASD) [9], [10], [11], dyslexia [12], dyscalculia [12], intellectual impairments [13], [14], [15], psychomotor impairments [16], [17], [18], etc. Developmental disabilities currently constitute a significant health challenge, affecting over 316.8 million children globally [19]. However, substantial gaps remain in our understanding of the etiology of these diseases, particularly regarding the identification of specific environmental chemicals that confer risk.

Early-life neurodevelopmental deficits exist along a continuum, ranging from inconsequential to mild, moderate, and severe, potentially progressing to neurodevelopmental disorders (NDDs) and other functional impairments [20], [21]. The effects of environmental pollutant exposure can vary significantly over time and across different stages of neurodevelopment [21], [22]. An increasing number of meta-analyses have explored the impact of prenatal and early childhood pollutant exposures on neurodevelopment, including air pollutants [7], [12], [23], [24], inorganic substances (particularly heavy metals) [10], [11], [25], [26], and synthetic organic compounds like persistent organic pollutants (POPs) [9], [27], [28], [29]. However, the assessment of various types of bias (e.g., publication bias, excess significance bias, reporting bias, and residual confounding bias) in these meta-analyses is often insufficient, potentially leading to overestimated efficacy or false significance [30], [31]. Furthermore, these meta-analyses remain fragmented and lack credibility assessments, with inconsistent evidence complicating the ability to form a comprehensive profile due to variations in exposure windows, pollutant types, adverse neurodevelopmental outcomes, and analysis strategies. As a result, this hinders the translation of evidence on environmental pollutant exposure and neurodevelopment into policy decisions (e.g., pollution control, enhanced pollutant monitoring) and health promotion strategies (e.g., neurodevelopmental assessments of highly exposed populations and their offspring), limiting researchers in this field from identifying new research priorities.

To address these gaps, we conducted an umbrella review to systematically collect and organize the existing evidence and provide a comprehensive profile [32]. This study aimed to assess potential biases in the meta-analyses on environmental pollutant exposure and adverse neurodevelopmental outcomes, grade the evidence using an established framework [33], [34], [35], elucidate variations in evidence across different analytical modalities, and consolidate the most robust evidence available on this topic.