Sensitive development windows of prenatal air pollution and cognitive functioning in preschool age Mexican children.

Introduction: Neurotoxicity resulting from air pollution is of increasing concern. Considering exposure timing effects on neurodevelopmental impairments may be as important as the exposure dose. We used distributed lag regression to determine the sensitive windows of prenatal exposure to fine particulate matter (PM2.5) on children's cognition in a birth cohort in Mexico. Methods: Analysis included 553 full-term (≥37 weeks gestation) children. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatiotemporal model. McCarthy Scales of Children's Abilities (MSCA) were used to assess children's cognitive function at 4-5 years old (lower scores indicate poorer performance). To identify susceptibility windows, we used Bayesian distributed lag interaction models to examine associations between prenatal PM2.5 levels and MSCA. This allowed us to estimate vulnerable windows while testing for effect modification. Results: After adjusting for maternal age, socioeconomic status, child age, and sex, Bayesian distributed lag interaction models showed significant associations between increased PM2.5 levels and decreased general cognitive index scores at 31-35 gestation weeks, decreased quantitative scale scores at 30-36 weeks, decreased motor scale scores at 30-36 weeks, and decreased verbal scale scores at 37-38 weeks. Estimated cumulative effects (CE) of PM2.5 across pregnancy showed significant associations with general cognitive index (CE^ = -0.35, 95% confidence interval [CI] = -0.68, -0.01), quantitative scale (CE^ = -0.27, 95% CI = -0.74, -0.02), motor scale (CE^ = -0.25, 95% CI = -0.44, -0.05), and verbal scale (CE^ = -0.2, 95% CI = -0.43, -0.02). No significant sex interactions were observed. Conclusions: Prenatal exposure to PM2.5, particularly late pregnancy, was inversely associated with subscales of MSCA. Using data-driven methods to identify sensitive window may provide insight into the mechanisms of neurodevelopmental impairment due to pollution.

Association between prenatal and childhood PM2.5 exposure and preadolescent anxiety and depressive symptoms.

Background: Fine particulate matter (PM2.5) exposure has been linked to anxiety and depression in adults; however, there is limited research in the younger populations, in which symptoms often first arise. Methods: We examined the association between early-life PM2.5 exposure and symptoms of anxiety and depression in a cohort of 8-11-year-olds in Mexico City. Anxiety and depressive symptoms were assessed using the Spanish versions of the Revised Children's Manifest Anxiety Scale and Children's Depression Inventory. Daily PM2.5 was estimated using a satellite-based exposure model and averaged over several early and recent exposure windows. Linear and logistic regression models were used to estimate the change in symptoms with each 5-µg/m3 increase in PM2.5. Models were adjusted for child's age, child's sex, maternal age, maternal socioeconomic status, season of conception, and temperature. Results: Average anxiety and depressive symptom T-scores were 51.0 (range 33-73) and 53.4 (range 44-90), respectively. We observed consistent findings for exposures around the fourth year of life, as this was present for both continuous and dichotomized anxiety symptoms, in both independent exposure models and distributed lag modeling approaches. This window was also observed for elevated depressive symptoms. An additional consistent finding was for PM2.5 exposure during early pregnancy in relation to both clinically elevated anxiety and depressive symptoms, this was seen in both traditional and distributed lag modeling approaches. Conclusion: Both early life and recent PM2.5 exposure were associated with higher mental health symptoms in the child highlighting the role of PM2.5 in the etiology of these conditions.

Urban Stress and its Association with Symptoms of Depression, Fatigue, and Sleep Disruption in Women in Mexico City.

Women in urban neighborhoods often face disproportionately higher levels of environmental and social stressors; however, the health effects from urban stressors remains poorly understood. We aimed to evaluate the association between urban stress and symptoms of depression, fatigue, and sleep disruption in a cohort of 460 women in Mexico City. To assess urban stress, women were administered the Urban Annoyances (Nuisances Environnementales) scale. Six constructs were summarized to create an overall index. Depressive symptoms were assessed using the Edinburgh Depression Scale; the Patient-Reported Outcomes Information System scales were used to assess sleep disruption and fatigue. Linear regression models were used to estimate the association with continuous symptoms comparing women with high urban stress to those with lower levels. Models were adjusted for socioeconomic status, education, age, social support, and previous depressive symptoms. High urban stress was associated with greater depressive symptoms (ß: 1.77; 95%CI: 0.83, 2.71), fatigue (ß: 2.47; 95%CI: 0.87, 4.07), and sleep disruption (ß: 2.14; 95%CI: 0.54, 3.73). Urban stress plays an important role in women's psychological and physical health, highlighting the importance of including these measures in environmental health studies. Urban interventions, such as promoting alternative transport options, should additionally be addressed to improve health of urban populations.

Changes in depressive and anxiety symptoms during COVID-19 in children from the PROGRESS cohort.

BACKGROUND: We assessed associations between maternal stress, social support, and child resiliency during the COVID-19 pandemic in relation to changes in anxiety and depression symptoms in children in Mexico City. METHODS: Participants included 464 mother-child pairs from a longitudinal birth cohort in Mexico City. At ages 8-11 (pre-COVID, 2018-2019) and 9-12 (during COVID, May-Nov 2020) years, depressive symptoms were assessed using the child and parent-reported Children's Depressive Inventory. Anxiety symptoms were assessed using the child-reported Revised Manifest Anxiety Scale. Linear regression models were used to estimate associations between maternal stress, social support, and resiliency in relation to changes in depressive and anxiety symptoms. We additionally assessed outcomes using clinically relevant cut-points. Models were adjusted for child age and sex and maternal socioeconomic status and age. RESULTS: Higher continuous maternal stress levels during the COVID-19 pandemic were associated with increases in depressive symptoms (ß: 0.72; 95% CI: 0.12, 1.31), and higher odds of clinically relevant depressive and anxiety symptoms in the children. CONCLUSIONS: Maternal stress during the pandemic may increase mental health symptoms in pre-adolescent children. Additional studies are needed that examine the long-term pandemic-related impacts on mental health throughout the adolescent years. IMPACT: In this longitudinal cohort study of children in Mexico City, we observed that depressive symptoms were higher from before to during the pandemic. Maternal stress surrounding the pandemic may increase mental health symptoms in pre-adolescent children. Child resiliency may help to protect against pandemic-related stressors.

Early life exposure to lead and its association with parent-reported aggression and conduct problems during childhood and adolescence.

BACKGROUND AND AIM: An association between lead (Pb) exposure and antisocial behaviors has been documented, but findings have been inconclusive. We aimed to estimate the association between prenatal, early childhood, and preadolescent/adolescent (periadolescent) Pb exposure and aggression and conduct problems in periadolescent residents of Mexico City. METHODS: Using information from the ELEMENT cohort study, we assessed prenatal Pb exposure through maternal patella Pb (MPPb) measurement during the puerperium, early childhood (birth to 5 years of age) exposure through a cumulative blood lead index (CBLI), and periadolescent exposure through a blood Pb (BPb) measurement concurrent with the evaluation of the outcomes. Outcomes were assessed during periadolescence using the parent-reported scales of aggression and conduct problems of the Behavioral Assessment System for Children-2nd version (BASC-2). We modeled the association between Pb exposure at each stage and each outcome (defined as a T-score ≥60 in the corresponding behavioral scale) using logistic regression, adjusting for sex, maternal age at delivery, maternal education, and household socioeconomic status (SES). The differential effect by sex was assessed with an interaction term in the models. RESULTS: 743, 704, and 595 participants were respectively eligible for inclusion in final models of prenatal, early childhood, and periadolescent Pb exposure. Median Pb exposure at each stage was 9.9 µg/g for MPPb (prenatal), 5.19 µg/dl for CBLI (early childhood), and 2.62 µg/dl for concurrent BPb (periadolescence). 12 % of participants met the criterion for aggression, and 15 % for conduct problems. In adjusted models, a one interquartile range increase in MPPb increased the odds of conduct problems (OR:1.31; 95 % CI: 1.01, 1.70) and aggression (OR=1.24; 95 % CI: 0.93, 1.65) during periadolescence. Pb exposure during early childhood or periadolescence was not associated with either outcome. We found no evidence of interactions by sex. CONCLUSIONS: Exposure to Pb during the prenatal stage was associated with aggression and conduct problems during periadolescence.

The influence of maternal anxiety and cortisol during pregnancy on childhood anxiety symptoms.

BACKGROUND: The etiology of child and adolescent anxiety remains poorly understood. Although several previous studies have examined associations between prenatal maternal psychological functioning and infant and child health outcomes, less is known about the impact of maternal anxiety specific to pregnancy and cortisol during pregnancy on childhood anxiety outcomes. METHODS: Participants included 496 mother-child pairs from the PROGRESS longitudinal birth cohort in Mexico City. Anxiety symptoms were assessed at age 8-11 years during 2018-2019 using the Revised Children's Manifest Anxiety Scale. Pregnancy-specific anxiety was assessed using an expanded version of the Pregnancy Anxiety Scale. Maternal biological stress response during pregnancy was assessed using salivary cortisol measures (area under the curve, cortisol awakening response, and diurnal slope). Linear regression models were used to estimate associations between maternal anxiety and cortisol in relation to continuous child anxiety symptom T-scores. Models were adjusted for maternal age, socioeconomic status, child sex and age, and gestational age at saliva collection. RESULTS: We found that higher levels of pregnancy-specific anxiety in the mother were associated with higher anxiety symptoms in the child (ß: 1.30, 95% CI: 0.19, 2.41). We additionally observed an association between higher maternal total cortisol output during pregnancy and higher anxiety symptoms in the child (ß: 1.13, 95% CI: 0.25, 2.01). DISCUSSION: These findings highlight the importance of screening for maternal pregnancy-specific anxiety and the need to identify interventions and support for mothers during pregnancy in order to promote healthy outcomes for mothers and their children.

Dietary fluoride intake during pregnancy and neurodevelopment in toddlers: A prospective study in the progress cohort.

Foods and beverages provide a source of fluoride exposure in Mexico. While high fluoride concentrations are neurotoxic, recent research suggests that exposures within the optimal range may also pose a risk to the developing brain. This prospective study examined whether dietary fluoride intake during pregnancy is associated with toddlers' neurodevelopment in 103 mother-child pairs from the PROGRESS cohort in Mexico City. Food and beverage fluoride intake was assessed in trimesters 2 and 3 using a food frequency questionnaire and Mexican tables of fluoride content. We used the Bayley-III to evaluate cognitive, motor, and language outcomes at 12 and 24 months of age. Adjusted linear regression models were generated for each neurodevelopment assessment time point (12 and 24 months). Mixed-effects models were used to consider a repeated measurement approach. Interactions between maternal fluoride intake and child sex on neurodevelopmental outcomes were tested. Median (IQR) dietary fluoride intake during pregnancy was 1.01 mg/d (0.73, 1.32). Maternal fluoride intake was not associated with cognitive, language, or motor outcomes collapsing across boys and girls. However, child sex modified the association between maternal fluoride intake and cognitive outcome (p interaction term = 0.06). A 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.50-point lower cognitive outcome in 24-month old boys (95 % CI: -6.58, -0.42); there was no statistical association with girls (ß = 0.07, 95 % CI: -2.37, 2.51), nor on the cognitive outcome at 12-months of age. Averaging across the 12- and 24-month cognitive outcomes using mixed-effects models revealed a similar association: a 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.46-point lower cognitive outcome in boys (95 % CI: -6.23, -0.70). These findings suggest that the development of nonverbal abilities in males may be more vulnerable to prenatal fluoride exposure than language or motor abilities, even at levels within the recommended intake range.

Changes in Depressive Symptoms, Stress and Social Support in Mexican Women during the COVID-19 Pandemic.

The aim of this study was to examine changes in depression, stress and social support levels before and during the COVID-19 pandemic in women living in Mexico City. We studied 466 women enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study who completed the Edinburgh Depression Scale (EDS) questionnaire prior (2018-2019) and during the lockdown period of the pandemic (May-November 2020). Psychosocial stress and social support for both time periods were ascertained using the Crisis in Family Systems (CRISYS) questionnaire and the Social Support Network (SSN) Scale, respectively. Associations between stress, social support and change in EDS score/depression were analyzed using generalized linear models adjusting for covariates. Higher stress (>median) during the pandemic was associated with an increase in EDS score (ß: 2.13; 95% CI (1.06, 3.19), p < 0.001), and higher odds of depression (OR: 3.75; 95% CI (2.17, 6.50), p < 0.001), while social support was associated with lower odds of depression (OR: 0.56, 95% CI (0.32, 0.97), p = 0.037). Higher levels of stress during the pandemic were associated with depression. Social support may act as a buffer for the effects of psychosocial stress. Future studies should examine the long-term effects of stress associated with the pandemic on mental and overall health.

Prevalence of Depression, Anxiety, and Perceived Stress in Postpartum Mexican Women during the COVID-19 Lockdown.

The COVID-19 lockdown represents a new challenge for mental health researchers and clinical practitioners. This cross-sectional study aimed to investigate the prevalence of depression, anxiety, and perceived stress in postpartum Mexican women. The study included 293, 4-12-week postpartum women over the age of 18. The Edinburgh Postpartum Depression Scale (EPDS), Trait-State Trait Anxiety Inventory (T-STAI), and Ten Perceived Stress Scale (PSS-10), which are all questionnaires validated for the Mexican population, were applied using a web-based online survey. Prevalence and 95% confidence intervals (CIs) were calculated. The mean ± standard deviation (SD) of the maternal age was 29.9 ± 6.3 years; the EPDS score: 11 ± 6, T-STAI score: 41.7 ± 12.3, and PSS-10 score: 17.1 ± 7. The prevalence (95% CI) of the postpartum depression symptoms was 39.2% (34-45%), trait anxiety symptoms were found among 46.1% (32-43%) of the participants, and moderate and high perceived stress were in 58% (52-64) and 10.9% (7.8-15) of the participants, respectively. The prevalence of depressive symptoms, generalized anxiety, and perceived stress was higher among postpartum Mexican women during the COVID-19 outbreak than before the lockdown. Our findings highlight the importance of monitoring perinatal mental health during pandemics and the need to design effective psychologic interventions for these patients.

Early Gestational Exposure to High-Molecular-Weight Phthalates and Its Association with 48-Month-Old Children's Motor and Cognitive Scores.

In utero phthalate exposure has been associated with neurodevelopmental disorders, nevertheless, trimester-specific susceptibility remains understudied. Our aim was to identify susceptible windows to the effects of gestational High-Molecular-Weight Phthalates (HMWP) exposure on 48 months' neurodevelopment. We measured six HMWP metabolites (MEHP, MEHHP, MEOHP, MECPP, MBzP and MCPP) in urine samples collected during each trimester from women in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 218). We assessed children's motor (MS), cognitive (GCI) and memory (MeS) abilities using McCarthy Scales of Children's Abilities (MSCA). We used linear regression models to examine associations between trimester-specific phthalate metabolites and MSCA scores, adjusted for sex, gestational age, breastfeeding, and maternal IQ. Although phthalate concentrations were similar across trimesters, first and second trimester phthalates were inversely associated with MS and GCI, with first trimester associations with MS being the strongest and statistically significant. Stronger associations were seen with MS and GCI among boys compared to girls, however interaction terms were not statistically significant. Our results suggest that early gestation is a sensitive window of exposure to HMWP for neurodevelopment, particularly in boys. Regulations on phthalate content in food as well as pregnancy consumption guidelines are necessary to protect future generations.

Prenatal PM2.5 exposure and behavioral development in children from Mexico City.

BACKGROUND: Childhood exposure to air pollution has been linked with maladaptive cognitive development; however, less is known about the association between prenatal fine particulate matter (PM2.5) exposure and childhood behavior. OBJECTIVES: Our aim was to assess the association between prenatal PM2.5 exposure and behavioral development in 4-6 year old children residing in Mexico City. METHODS: We used data from 539 mother-child pairs enrolled in a prospective birth cohort in Mexico City. We estimated daily PM2.5 exposure using a 1 km2 satellite-based exposure model and averaged over each trimester of pregnancy. We assessed childhood behavior at 4-6 years of age using the parent-completed Behavioral Assessment Scale for Children (BASC-2) composite scores and subscales. We used linear regression models to estimate change in BASC-2 T-scores with trimester specific 5-µg/m3 increases in PM2.5. All models were mutually adjusted for PM2.5 exposures during the other trimesters, maternal factors including age, education, socioeconomic status, depression, and IQ, child's age at study visit, and season. We additionally assessed sex-specific effects by including an interaction term between PM2.5 and sex. RESULTS: Higher first trimester PM2.5 exposure was associated with reduced Adaptive Skills scores (ß: -1.45, 95% CI: -2.60, -0.30). Lower scores on the Adaptive Skills composite score and subscales indicate poorer functioning. For PM2.5 exposure during the first trimester, decrements were consistent across adaptive subscale scores including Adaptability (ß: -1.51, 95% CI: -2.72, -0.30), Social Skills (ß: -1.63, 95% CI: -2.90, -0.36), and Functional Communication (ß: -1.21, 95% CI: -2.21, -0.21). The association between 1st trimester PM2.5 and depression was stronger in males than females (ß for males: 1.52, 95% CI: -0.41, 3.45; ß for females: -0.13, 95% CI: -1.99, 1.72; p-int: 0.07). CONCLUSIONS: Exposure to PM2.5 during early pregnancy may be associated with impaired behavioral development in children, particularly for measures of adaptive skills. These results suggest that air pollution impacts behavioral domains as well as cognition, and that the timing of exposure may be critical.

Maternal Prenatal Psychosocial Stress and Prepregnancy BMI Associations with Fetal Iron Status.

BACKGROUND: Iron accrued in utero is critical for fetal and infant neurocognitive development. Psychosocial stress and obesity can each suppress fetal iron accrual. Their combined effects and differences by fetal sex are not known. In an observational pregnancy cohort study in Mexico City, we investigated associations of maternal prenatal life stressors, psychological dysfunction, and prepregnancy BMI with fetal iron status at delivery. OBJECTIVES: We hypothesized that greater maternal prenatal psychosocial stress and prepregnancy overweight and obesity are associated with lower cord blood ferritin and hemoglobin (Hb), with stronger associations in boys than girls. METHODS: Psychosocial stress in multiple domains of life stress (negative life events, perceived stress, exposure to violence) and psychological dysfunction symptoms (depression, generalized anxiety, and pregnancy-specific anxiety) were assessed with validated questionnaires during pregnancy. Prepregnancy BMI was predicted with a validated equation and categorized as normal/overweight/obese. Cord blood ferritin and Hb associations with prenatal psychosocial stress and BMI were modeled in multivariable linear regressions adjusted for maternal age, socioeconomic status, child sex, and prenatal iron supplementation. Interactions with child sex and 3-way stress-overweight/obesity-sex interactions were tested with product terms and likelihood ratio tests. RESULTS: In 493 dyads, median (IQR) cord blood ferritin and Hb concentrations were 185 µg/L (126-263 g/dL) and 16 g/dL (14.7-17.1 g/dL), respectively. Ferritin was lower in infants of mothers with higher prenatal perceived stress (-23%; 95% CI: -35%, -9%), violence exposure (-28%; 95% CI: -42%, -12%), anxiety symptoms (-16%; 95% CI: -27%, -4%), and obesity (-17%; 95% CI: -31%, 0.2%). Interaction models suggested sex differences and synergism between maternal stress and overweight/obesity. No associations were observed between stress or BMI and Hb. CONCLUSIONS: Multiple prenatal psychosocial stressors and excess prepregnancy BMI were each inversely associated with fetal iron status at birth. Pregnancies and infants at elevated risk of impaired fetal iron accrual may be identifiable according to observed synergism between maternal stress and obesity and differential associations with fetal iron status by infant sex.

Prenatal particulate air pollution exposure and sleep disruption in preschoolers: Windows of susceptibility.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Early motor development and cognitive abilities among Mexican preschoolers.

Psychomotricity plays a very important role in children's development, especially for learning involving reading-writing and mathematical calculations. Evaluate motor development in children 3 years old and its relationship with their cognitive abilities at the age of 5 years. Based on a cohort study, we analyzed the information about motor performance evaluated at 3 years old by Peabody Motor Scale and cognitive abilities at 5 years old. The association was estimated using linear regression models adjusted by mother's intelligence quotient, sex, Bayley mental development index at 18 months, and quality of the environment at home (HOME scale). 148 children whose motor performance was determined at age 3 and was evaluated later at age 5 to determine their cognitive abilities. Cognitive abilities (verbal, quantitative, and memory) measured by McCarthy Scales. Significant positive associations were observed between stationary balance at age 3 with verbal abilities (ß = 0.67, p = .04) and memory (ß = 0.81, p = .02) at 5 years. Grasping and visual-motor integration were significant and positively associated with quantitative abilities (ß = 0.74, p = .005; ß = 0.61, p = .01) and memory (ß = 2.11, p = .001; ß = 1.74, p = .004). The results suggest that early motor performance contributes to the establishment of cognitive abilities at 5 years. Evaluation and early motor stimulation before the child is faced with formal learning likely helps to create neuronal networks that facilitate the acquisition of academic knowledge.

Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment.

BACKGROUND: Lead and psychosocial stress disrupt similar but not completely overlapping mechanisms. Exposure during the prenatal period to each of these insults singularly has been found to alter normal neurodevelopment; however, longitudinal associations with stress modifying the effect of lead have not been sufficiently analyzed in epidemiologic studies. OBJECTIVE: To evaluate prenatal stress as an effect modifier of gestational lead neurotoxicity. METHODS: We used a structural equations modeling approach with a trivariate response to evaluate cognitive, language and motor scores of the Bayley Scales of Infant Development-III in 24month-old children (n=360). Maternal blood lead levels were measured at the 2nd and 3rd trimester and psychosocial stress during pregnancy was assessed using a negative life events (NLE) scale derived from the CRYSIS questionnaire. RESULTS: 3rd trimester lead (mean 3.9±3.0 SDµg/dL) and stress (median=3 NLE) were negatively associated with Bayley III scores. Using the model's results we generated profiles for 0, 2, 4 and 6 NLE across lead levels (up to 10µg/dL) and observed a dose-response for the developmental scores when lead levels were below 2µg/dL. Each NLE curve had a different shape across increasing lead levels. Higher stress (NLE=6) resulted in lower cognitive scores for both sexes, in lower language scores in girls but not boys. In the absence of stress we saw a negative association with lead for all scores, however for language and motor scores, higher stress seemed to mask this association. CONCLUSIONS: Our work examined and confirmed prenatal stress exposure as a modifier of the well-known neurotoxic effects of prenatal lead. It adds to the existing evidence pointing at the importance of studying the co-exposure of chemical and non-chemical exposures, specifically of considering the emotional environment of children at early developmental stages of life.

Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: Distribution and relationships with child neurodevelopment.

BACKGROUND: In recent years, pyrethroid pesticide use has increased in Mexico, the United States, and elsewhere, resulting in extensive human exposure. There is growing concern that pregnant women may be a particularly vulnerable population, as in utero fetal exposure during critical periods of development could adversely affect long-term neurobehavioral function. METHODS: We measured maternal urinary 3-phenoxybenzoic acid (3-PBA) concentrations during the third trimester of pregnancy as a measure of in utero pyrethroid exposure to the fetus among participants in an established Mexico City birth cohort (n=187). In a subset of mothers, we measured 3-PBA during the first, second, and third trimester (n=21) to assess variability across pregnancy. We examined associations between third trimester 3-PBA concentrations and children's scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from the Bayley Scales for Infant Development (BSID-IIS) at 24 and 36 months of age. RESULTS: 3-PBA was detected in 46% of all urine samples, with similar detection rates and geometric mean concentrations across pregnancy among the 21 participants who provided repeat samples. Participants in the medium and high 3-PBA categories (≥LOD) had lower MDI scores at 24 months compared to those in the low 3-PBA category (

Prenatal p,p'-DDE exposure and establishment of lateralization and spatial orientation in Mexican preschooler.

BACKGROUND: Prenatal exposure to p,p'-DDE is associated with impairments in motor development during the first year of life, with no related repercussions on mental or motor development at 12-30 months and with impairments in cognitive areas, but not in perceptual and motor areas at preschool age. However, its association with particular psychomotor factors, such as establishment of lateralization and spatial orientation, essential elements to the overall learning and specifically reading, writing and spelling in preschoolers, has not been independently evaluated, since cognitive and motor areas have only been explored globally. OBJECTIVE: To determine the association between prenatal exposure to p,p'-DDE and the establishment of lateralization and spatial orientation in children 5 years of age. MATERIALS AND METHODS: Establishment of lateralization and spatial orientation was evaluated using the McCarthy Scale of Children's Abilities, with 167 children 5 years of age who participated in a birth cohort in the state of Morelos, Mexico. The information available for each child included: serum concentrations of p,p'-DDE of the mother during at least one trimester of pregnancy, mothers' intelligence quotients, stimulation at home and anthropometry. A logistic regression model was used to calculate the association between prenatal exposure to p,p'-DDE and lateralization and a multiple linear regression model was used for the association with spatial orientation. RESULTS: A two-fold increase in p,p'-DDE in lipid base during the second trimester of pregnancy was associated with a significant reduction, -0.18 points (95% CI -0.41; 0.04, in the spatial orientation index, with no impairment in the establishment of hemispheric dominance. Attending preschool and the maternal intelligence quotient were the main determinants of spatial orientation and the establishment of hemispheric dominance. CONCLUSIONS: Prenatal exposure to p,p'-DDE may affect the 5 year old's ability to identify spatial orientation of oneself and surrounding objects. Given the observed role of attending preschool in the functions studied, early attendance in formal education might serve as a stimulation strategy for preschoolers. These preliminary results should be verified and expanded in further prospective studies with DDE.

Prenatal p,p´-DDE exposure and neurodevelopment among children 3.5-5 years of age.

BACKGROUND: The results of previous studies suggest that prenatal exposure to bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and to its main metabolite, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), impairs psychomotor development during the first year of life. However, information about the persistence of this association at later ages is limited. OBJECTIVES: We assessed the association of prenatal DDE exposure with child neurodevelopment at 42-60 months of age. METHODS: Since 2001 we have been monitoring the neurodevelopment in children who were recruited at birth into a perinatal cohort exposed to DDT, in the state of Morelos, Mexico. We report McCarthy Scales of Children's Abilities for 203 children at 42, 48, 54, and 60 months of age. Maternal DDE serum levels were available for at least one trimester of pregnancy. The Home Observation for Measurement of the Environment scale and other covariables of interest were also available. RESULTS: After adjustment, a doubling of DDE during the third trimester of pregnancy was associated with statistically significant reductions of -1.37, -0.88, -0.84, and -0.80 points in the general cognitive index, quantitative, verbal, and memory components respectively. The association between prenatal DDE and the quantitative component was weaker at 42 months than at older ages. No significant statistical interactions with sex or breastfeeding were observed. CONCLUSIONS: These findings support the hypothesis that prenatal DDE impairs early child neurodevelopment; the potential for adverse effects on development should be considered when using DDT for malaria control.

Neonatal neurodevelopment and prenatal exposure to dichlorodiphenyldichloroethylene (DDE): a cohort study in Mexico.

Prenatal exposure to dichlorodiphenyldichloroethylene (DDE) is associated with decreased motor development during the first year of life, though the effects of DDE in the neonatal stage are not conclusive. The main aim of this study was to evaluate the association between prenatal DDE exposure and neonatal neurodevelopment in a cohort from four municipalities in the state of Morelos, Mexico. The children (265), born from pregnancies with no perinatal complications, were evaluated at 1 month of age (± 7 days) for the presence of abnormal reflexes with the Brazelton Scale (NBAS), neurological soft signs with the Graham-Rosenblith Scale, as well as mental and psychomotor development by the Bayley Scales of Infant Development. Maternal DDE concentrations during each trimester of the pregnancy were determined by gas chromatography. Multiple linear and ordinal logistic models assessed the association between DDE and the outcomes of interest. Prenatal exposure to DDE was associated with a non-significant increase in neurological soft signs (6-8%) and a decrease in psychomotor (ß(1T) = -0.02) and mental (ß(2T) = -0.03 and ß(3T) = -0.19) development. Our results are consistent with previous studies and suggest that prenatal DDE exposure is not associated with neurological functions present in the neonatal stage.