Metal exposure alters neurodevelopmental outcomes; little is known about critical windows of susceptibility when exposure exerts the strongest effect.
To examine associations between dentine ...biomarkers of manganese (Mn), zinc (Zn) and lead (Pb) and later childhood behaviors.
Subjects enrolled in a longitudinal birth cohort study in Mexico City provided naturally shed deciduous teeth. We estimated weekly prenatal and postnatal dentine Mn, Zn and Pb concentrations in teeth using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and measured behavior at ages 8–11 years of age using the Behavior Assessment System for Children, 2nd edition (BASC-2). We used distributed lag models and lagged weighted quantile sum regression to identify the role of individual and combined dentine biomarkers of Mn, Zn and Pb on behavioral outcomes controlling for maternal education and gestational age.
Among the 133 subjects included in this study, prenatal and early postnatal dentine Mn appeared protective against childhood behavioral problems, specifically hyperactivity and attention. Postnatal dentine Mn was associated with increased reporting of internalizing problems, specifically anxiety. At 6 months, a 1-unit increase (unit = 1 SD of log concentration) in Mn was associated with a 0.18-unit (unit = 1 SD of BASC-2 score) increase in internalizing symptoms score and a 0.25-unit increase in anxiety. Postnatal Pb was associated with increasing anxiety symptoms; at 12 months, a 1-unit increase in Pb was associated with a 0.4 unit increase in anxiety symptoms. When examined as a metal mixture, we observed two potential windows of susceptibility to increased anxiety symptoms: the first window (0–8 months) appeared driven by Mn, the second window (8–12 months) was driven by the metal mixture and dominated by Pb. A 1-unit increase in the mixture index was associated with a 0.7-unit increase in SD of anxiety symptoms.
Childhood behaviors may demonstrate postnatal windows of susceptibility to individual and mixed metal concentrations measured in deciduous teeth. Prenatal dentine Mn may be protective, while excessive early postnatal Mn may increase risk for adverse behaviors. In combination, higher concentrations of Mn, Zn and Pb may have an adverse impact on behavior.
•Tooth-matrix biomarkers were used to identify windows of susceptibility to Mn, Zn, and Pb.•Prenatal and early postnatal Mn appears protective against externalizing behavior.•Postnatal Mn is associated with higher internalizing behaviors, especially anxiety.•Co-exposure to Mn, Zn and Pb at 12 months is associated with anxiety.
Epidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, ...no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention.
We aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD).
213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6–12. We measured urinary fluoride levels adjusted for creatinine (MUFcr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children.
Mean MUFcr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUFcr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity.
Higher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring.
•We measured urinary fluoride in 213 pregnant women living in Mexico City who were part of the ELEMENT pregnancy cohort study.•Higher concentration of maternal urinary fluoride was associated with more ADHD-like symptoms in school-age children.•Prenatal exposure to fluoride was most strongly associated with behavioral ratings of inattention, but not hyperactivity and impulse control.•Findings are consistent with the growing body of evidence suggesting neurotoxicity of early-life exposure to fluoride.
Controversy remains surrounding vitamin D routine supplementation in healthy pregnancy, and the doses are unclear. The aim of this study was to describe maternal vitamin D status throughout pregnancy ...in a group of Mexican women and evaluate the effect of frequently prescribed doses of vitamin D3 on longitudinal 25-OH-D concentrations, adjusting for obesity, season, and other factors. We conducted a cohort study (Instituto Nacional de Perinatología-INPer) (2017-2020)) of healthy pregnant women without complications. Pregestational overweight/obesity (body mass index ≥ 25), vitamin D3 supplementation (prescribed by physician; 0-250, 250-400, and >400 IU/day), and serum 25-OH-D concentrations (ELISA) were evaluated in each trimester of pregnancy. Vitamin D deficiency or insufficiency was computed (<20 and <30 ng/mL, respectively). We studied 141 adult women; 58.5% had pregestational obesity or overweight. In the first trimester, 45.8% of the women were supplemented with vitamin D3; 51.4% had vitamin D insufficiency and 37.3%, deficiency. In the third trimester, 75.4% of the women were supplemented, and 20% of them still had deficiency. The final general mixed linear model showed that 25-OH-D significantly increased throughout pregnancy (
< 0.001); the highest increase was observed in the third trimester in women with doses >400 IU/day of vitamin D3 (+4 ng/mL, 95% CI: 1.72-8.11 ng/mL). In winter/autumn, 25-OH-D concentrations were also lower (
≤ 0.05). In this group of pregnant Mexican women, the prevalence of vitamin D deficiency and insufficiency was high. A higher increase in 25-OH-D concentrations during pregnancy was observed when the women were supplemented with >400 IU/day. Common supplementation doses of 250-400 IU/day were insufficient for achieving an adequate maternal vitamin D status.
We examined effects on child development of a group-based parenting support program (Educación Inicial - EI) when combined with Mexico's conditional cash transfer (CCT) program (Prospera, originally ...Oportunidades and Progresa). This cluster-randomized trial included 204 communities (n = 1,113 children in final sample), stratified by community indigenous status, and assigned to receive either: (T0) CCT only; (T1) CCT plus availability of EI in the community; or (T2) T1 plus promotion of the EI program by the CCT program. Interviews were conducted with the mother or primary caregiver of each child at baseline (2008, children 0-18 months old), and at follow-up (2012, children 3-5 years old); the intervention began after baseline and continued for all eligible households. Cognitive development was assessed with the Extended Ages and Stages Questionnaire (baseline) and the McCarthy Scales of Children's Development (follow-up); assessors were blinded to treatment. All analyses were intention to treat. There were significant effects on child development when EI received support and promotion from the CCT program (T2 vs. T0: General Cognitive Index, β = 3.90; 95% CI 0.51, 7.30, Verbal Score, β = 4.28; 95% CI 0.51, 8.05, and Memory Score, β = 4.14; 95% CI 0.62, 7.66), effects equivalent to 0.26-0.29 SD. There were no significant benefits when the programs operated independently (T1 vs. T0). In stratified analyses, EI showed significant effects in indigenous communities only. We found consistent results in regressions controlling for covariates, with some reductions in magnitude of differences. Our findings suggest that group-based, parenting support programs can improve child outcomes within the context of a CCT, but only when the 2 programs are integrated and mutually supportive.
•Evidence suggests air pollution exposure may influence mental health.•We studied PM2.5 exposure in pregnancy and postpartum depression (PPD) risk.•In Mexico City, PM2.5 in pregnancy was associated ...with higher PPD risk at 6 months.•PM2.5 in pregnancy was also linked with 6-month anhedonia and depression scores.•Air pollution in pregnancy may influence maternal postpartum psychological function.
Postpartum depression (PPD), which affects up to 1 in 5 mothers globally, negatively impacts the health of both mothers and children. Exposure to ambient air pollution has been linked to depressive symptoms in animal models and human studies, but the relationship between air pollution and PPD has not been widely studied.
In a birth cohort in Mexico City (509 mothers with available data), we examined the association between exposure to particulate matter ≤2.5 μm in diameter (PM2.5) with symptoms of psychological dysfunction at 1 and 6 months postpartum. Daily PM2.5 estimates were derived from a hybrid satellite-based spatio-temporally resolved model and averaged over pregnancy and the first year postpartum. Edinburgh Postnatal Depression Scale (EPDS) scores at 1 and 6 months were used to assess the relationship between PM2.5 exposure and probable PPD (EPDS score ≥13) using relative risk regression and symptoms of anhedonia, depression, and anxiety (derived from EPDS subscales) using negative binomial regression.
A 5-μg/m3 increase in average PM2.5 exposure during pregnancy was associated with an increased risk of PPD at 6 months (RR = 1.59; 95% CI: 1.11 to 2.28) and of late-onset PPD (no PPD at 1 month, PPD at 6 months) (RR = 2.58; 95% CI: 1.40 to 4.73) in covariate-adjusted models. No association was observed between PM2.5 exposure in the first year postpartum and PPD. Average PM2.5 exposure during pregnancy was also associated with increased 6-month EPDS subscale symptom scores for anhedonia (p = 0.03) and depression (p = 0.04).
Our results suggest that in women in Mexico City, particulate matter exposure during pregnancy is positively associated with PPD and symptoms of anhedonia and depression at 6 months postpartum. Future studies should examine mechanisms linking air pollution and other environmental exposures during pregnancy with postpartum psychological functioning.
The programming of sleep architecture begins in pregnancy and depends upon optimal in utero formation and maturation of the neural connectivity of the brain. Particulate air pollution exposure can ...disrupt fetal brain development but associations between fine particulate matter (PM2.5) exposure during pregnancy and child sleep outcomes have not been previously explored.
Analyses included 397 mother-child pairs enrolled in a pregnancy cohort in Mexico City. Daily ambient prenatal PM2.5 exposure was estimated using a validated satellite-based spatio-temporally resolved prediction model. Child sleep periods were estimated objectively using wrist-worn, continuous actigraphy over a 1-week period at age 4–5 years. Data-driven advanced statistical methods (distributed lag models (DLMs)) were employed to identify sensitive windows whereby PM2.5 exposure during gestation was significantly associated with changes in sleep duration or efficiency. Models were adjusted for maternal education, season, child's age, sex, and BMI z-score.
Mother's average age was 27.7 years, with 59% having at least a high school education. Children slept an average of 7.7 h at night, with mean 80.1% efficiency. The adjusted DLM identified windows of PM2.5 exposure between 31 and 35 weeks gestation that were significantly associated with decreased sleep duration in children. In addition, increased PM2.5 during weeks 1–8 was associated with decreased sleep efficiency. In other exposure windows (weeks 39–40), PM2.5 was associated with increased sleep duration.
Prenatal PM2.5 exposure is associated with altered sleep in preschool-aged children in Mexico City. Pollutant exposure during sensitive windows of pregnancy may have critical influence upon sleep programming.
•Prenatal PM2.5 exposure was associated with sleep disruption in preschoolers.•Higher PM2.5 was linked to decreased sleep efficiency and altered sleep duration.•Significant associations were identified during sensitive windows of gestation.
Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic ...individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV).
We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers.
Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (β = 0.04–0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (βhigh = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and βlow = −0.06; 95% CI = 0.03, −0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN.
Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia.
•Mn in 3rd trimester blood and in cord blood was positively associated with mtDNA CN.•The relationship between 2nd trimester Mn and mtDNA CN was modified by anemia.•Mn in maternal blood at birth was not associated with cord blood mtDNA content.•Maternal anemia, serum ferritin, and MCV were not associated with mtDNA CN.
Assessing the status and determinants of early child development (ECD) requires accurate and regularly updated measurements. Yet, little information has been published on the subject in low- and ...middle-income countries, particularly regarding the proximal determinants of childhood development in contexts of high social marginalization. This article analyzes the factors that favor or mitigate suboptimal ECD outcomes in Mexico. A cross-sectional study was conducted using recently collected data for 918 children aged 0-38 months from socially marginalized communities in 23 Mexican municipalities. The ECD outcomes of the children were estimated based on indicators of chronic undernutrition and neurodevelopment (normal, lagging and at risk of delay). The distribution of outcomes was described across the ECD proximal determinants analyzed, including the co-occurrence of chronic undernutrition and suboptimal neurodevelopment. Covariate-adjusted prevalence of the ECD outcomes and co-occurrences were calculated as post-estimations from a multiple multinomial logistic regression. The prevalence of chronic undernutrition was 23.5%; 45.9% of children were classified with neurodevelopmental lag, and 11% at risk of neurodevelopmental delay. The prevalence of stunting co-occurring with suboptimal neurodevelopment came to 15.4%. The results of the multinomial logistic regression model indicated that early gestational age, low birth weight, a low household socioeconomic level, being male and having numerous siblings were all associated with the co-occurrence of chronic undernutrition and suboptimal child neurodevelopment. This study identified important predictors of child development in the first three years of life, specifically in two of its principal indicators: nutritional and neurodevelopmental status. Most of the predictors observed can be improved by means of social programs and interventions. Trial registration: ClinicalTrials.gov ID: NCT04210362.
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