A Prospective Birth Cohort Study on Early Childhood Lead Levels and Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences

Ji, Yuelong; Hong, Xiumei; Wang, Guoying; Chatterjee, Nilanjan; Riley, Anne W.; Lee, Li Ching; Surkan, Pamela J.; Bartell, Tami R.; Zuckerman, Barry; Wang, Xiaobin

doi:10.1016/j.jpeds.2018.03.076

Cited by 52 publications

(24 citation statements)

References 49 publications

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“…Within the studies that used European populations, one used a German population [37], one a Spanish population [38] and one a Belgian population [39]. The other studies used an American population [35,46,48], a Chinese population [34,40], a Turkish population [49] and a Mexican population [33].…”

Section: Resultsmentioning

confidence: 99%

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The Association between Lead and Attention-Deficit/Hyperactivity Disorder: A Systematic Review

Donzelli

Carducci

Llópis-González

et al. 2019

IJERPH

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The etiology of Attention-Deficit/Hyperactivity Disorder (ADHD) is complex and multifactorial. Although the development of ADHD symptoms remains to be elucidated, in recent years, epigenetic processes have emerged as candidate mechanisms. Lead is one of the most dangerous environmental pollutants, and it is suspected to be associated with ADHD. The aim of the present study was to review the epidemiological literature currently available on the relation between lead exposure and the diagnosis of ADHD. The PubMed and EMBASE databases were searched from 1 July 2018 up to 31 July 2018. The authors included observational studies (cohort, case–control and cross-sectional studies) published in English carried out on children within the last 5 years, measuring lead exposure and health outcomes related to ADHD. Seventeen studies met the inclusion criteria: 5 of these studies found no association between lead exposure and ADHD whereas the remaining 12 studies showed positive associations, even though not all of them were homogeneous in terms of exposure periods considered or ADHD diagnosis. To conclude, the evidence from the studies allowed us to establish that there is an association between lead and ADHD and that even low levels of lead raise the risk. However, there is still a lack of longitudinal studies about the relationship between lead exposure and the development of ADHD. Given the potential importance for public health, further research that includes the entire potential risk factors for ADHD in children must be encouraged.

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Section: Resultsmentioning

confidence: 99%

“…Blood samples were obtained from each child via venipuncture in the arm. Two of these studies, References [35,39], also collected and analyzed the cord blood lead levels of the mothers. One each of the cohort [38] and case–control [41] studies collected urine samples and analyzed them by inductively coupled plasma mass spectrometry (ICP-MS).…”

Section: Resultsmentioning

confidence: 99%

The Association between Lead and Attention-Deficit/Hyperactivity Disorder: A Systematic Review

Donzelli

Carducci

Llópis-González

et al. 2019

IJERPH

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“…Based on previous literature [ 29 , 37 , 38 , 39 , 40 , 41 ], the following covariates were included as potential confounders: maternal age at delivery, maternal race/ethnicity, maternal education, smoking from six months before pregnancy to birth (never smoked, quit during this period, continued to smoke during this period), ever drank alcohol from six months before pregnancy to birth, maternal pre-pregnancy BMI, parity, maternal fever during pregnancy, intrauterine infection/inflammation, baby’s sex, delivery type, gestational age, birthweight, breastfeeding, early childhood lead levels, and maternal high-density lipoprotein (HDL) levels. Maternal demographic covariates were collected using a standard questionnaire interview.…”

Section: Methodsmentioning

confidence: 99%

“…The rapid rise of ADHD cannot be attributed to genetic mutations. Indeed, multiple social and environmental risk factors have been associated with the development of ADHD, including family-related factors [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], maternal obesity [ 16 , 17 ], maternal smoking [ 8 , 18 , 19 , 20 ], maternal drinking [ 8 , 21 ], low birthweight and preterm birth [ 22 ], exposure to organophosphates [ 23 ], polychlorinated biphenyls [ 24 , 25 ], and lead exposure [ 24 , 26 , 27 , 28 , 29 ]. These findings underscore the role of environmental factors in the etiology of ADHD, and the need to explore other important yet unknown risk factors for ADHD [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder

Riley

Lee

et al. 2018

Brain Sciences

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Previous studies have suggested a positive association between self-reported maternal acetaminophen use during pregnancy and risk of attention deficit hyperactivity disorder (ADHD) in offspring. We sought to examine the prospective association between maternal plasma biomarkers of acetaminophen intake and ADHD diagnosis in the offspring. This report analyzed 1180 children enrolled at birth and followed prospectively as part of the Boston Birth Cohort, including 188 with ADHD diagnosis based on electronic medical record review. Maternal biomarkers of acetaminophen intake were measured in plasma samples obtained within 1–3 days postpartum. Odds ratios for having ADHD diagnosis or other developmental disorders were estimated using multinomial logistic regression models, adjusting for pertinent covariables. Compared to neurotypical children, we observed significant positive dose-responsive associations with ADHD diagnosis for each maternal acetaminophen biomarker. These dose–responsive associations persisted after adjusting for indication of acetaminophen use and other pertinent covariates; and were specific to ADHD, rather than other neurodevelopmental disorders. In the stratified analyses, differential point estimates of the associations were observed across some strata of covariates. However, these differences were not statistically significant. Maternal acetaminophen biomarkers were specifically associated with increased risk of ADHD diagnosis in offspring. Additional clinical and mechanistic investigations are warranted.

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“…Developmental exposures to lead (Pb) and to prenatal stress (PS) remain significant risk factors for subsequent adverse behavioral outcomes in children (Bock et al 2015;Canfield et al 2003Canfield et al , 2004Jusko et al 2008;Nigg et al 2008;Pallarés and Antonelli 2017), including cognitive dysfunction, reduced IQ, and attention deficits (Canfield et al 2004;Geier et al 2018;Gutteling et al 2006;Ji et al 2018;Lamb et al 2014;Lanphear et al 2005;Zhu et al 2015). These consequences can even persist across the life span (Needleman et al 1990;Schwabe et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Lineage- and Sex-Dependent Behavioral and Biochemical Transgenerational Consequences of Developmental Exposure to Lead, Prenatal Stress, and Combined Lead and Prenatal Stress in Mice

Sobolewski

Abston

Conrad

et al. 2020

Environ Health Perspect

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BACKGROUND: Lead (Pb) exposure and prenatal stress (PS) during development are co-occurring risk factors with shared biological substrates. PS has been associated with transgenerational passage of altered behavioral phenotypes, whereas the transgenerational behavioral or biochemical consequences of Pb exposure, and modification of any such effects by PS, is unknown. OBJECTIVES: The present study sought to determine whether Pb, PS, or combined Pb and PS exposures produced adverse transgenerational consequences on brain and behavior. METHODS: Maternal Pb and PS exposures were carried out in F0 mice. Outside breeders were used at each subsequent breeding, producing four F1-F2 lineages: [F1 female-F2 female (FF), FM (male), MF, and MM]. F3 offspring were generated from each of these lineages and examined for outcomes previously found to be altered by Pb, PS, or combined Pb and PS in F1 offspring: behavioral performance [fixed-interval (FI) schedule of food reward, locomotor activity, and anxiety-like behavior], dopamine function [striatal expression of tyrosine hydroxylase (Th)], glucocorticoid receptor (GR) and plasma corticosterone, as well as brain-derived neurotrophic factor (BDNF) and total percent DNA methylation of Th and Bdnf genes in the frontal cortex and hippocampus. RESULTS: Maternal F0 Pb exposure produced runting in F3 offspring. Considered across lineages, F3 females exhibited Pb-related alterations in behavior, striatal BDNF levels, frontal cortical Th total percentage DNA methylation levels and serum corticosterone levels, whereas F3 males showed Pb-and PS-related alterations in behavior and total percent DNA methylation of hippocampal Bdnf. However, numerous lineage-specific effects were observed, most of greater magnitude than those observed across lineages, with outcomes differing by F3 sex. DISCUSSION: These findings support the possibility that exposures of previous generations to Pb or PS may influence the brain and behavior of future generations. Observed changes were sex-dependent, with F3 females showing multiple changes through Pb-exposed lineages. Lineage effects may occur through maternal responses to pregnancy, altered maternal behavior, epigenetic modifications, or a combination of mechanisms, but they have significant public health ramifications regardless of mechanism. https://doi.

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A Prospective Birth Cohort Study on Early Childhood Lead Levels and Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences

Cited by 52 publications

References 49 publications

The Association between Lead and Attention-Deficit/Hyperactivity Disorder: A Systematic Review

The Association between Lead and Attention-Deficit/Hyperactivity Disorder: A Systematic Review

Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder

Lineage- and Sex-Dependent Behavioral and Biochemical Transgenerational Consequences of Developmental Exposure to Lead, Prenatal Stress, and Combined Lead and Prenatal Stress in Mice

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