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.

Dentine biomarkers of prenatal and early childhood exposure to manganese, zinc and lead and childhood behavior.

BACKGROUND: Metal exposure alters neurodevelopmental outcomes; little is known about critical windows of susceptibility when exposure exerts the strongest effect. OBJECTIVE: To examine associations between dentine biomarkers of manganese (Mn), zinc (Zn) and lead (Pb) and later childhood behaviors. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Vegetables and lean proteins-based and processed meats and refined grains -based dietary patterns in early childhood are associated with pubertal timing in a sex-specific manner: a prospective study of children from Mexico City.

Childhood diet has been implicated in timing of sexual maturation. A key limitation of published studies is the focus on individual foods rather than patterns. We hypothesized that dietary patterns characterized by fruits and vegetables during early childhood (age 3 years) would be associated with delayed pubertal timing, whereas energy-dense and meat-based dietary patterns would relate to earlier puberty. The study population included 496 participants of a Mexico City birth cohort. The exposures of interest were dietary patterns derived from principal component analysis of dietary data collected via a semiquantitative food frequency questionnaire when the children were 3 years of age, and the outcomes were physician-assessed Tanner stages for pubic hair, breast (girls), genitalia, and testicular volume (boys) between 9 and 18 years, and initiation of menarche (girls). In regression analyses, we estimated adjusted hazard ratios and 95% confidence intervals for having reached Tanner stage ≥4 or initiation of menarche in girls and testicular volume ≥15 mL in boys. Among girls, those in the highest vs lowest tertile of vegetables and lean proteins pattern had a 35% (95% confidence interval 3%-67%) lower adjusted probability of having reached breast stage ≥4. Among boys, the processed meats and refined grain pattern score was associated with more advanced testicular development (adjusted hazard ratio = 3.58 [0.62-6.53]). Early childhood dietary patterns may play a role in the tempo of sexual maturation, which could ultimately carry implications for chronic disease susceptibility.

Prenatal exposure to PM2.5 and birth weight: A pooled analysis from three North American longitudinal pregnancy cohort studies.

A common practice when analyzing multi-site epidemiological data is to include a term for 'site' to account for unmeasured effects at each location. This practice should be carefully considered when site can have complex relationships with important demographic and exposure variables. We leverage data from three longitudinal North American pregnancy cohorts to demonstrate a novel method to assess study heterogeneity and potential combinability of studies for pooled analyses in order to better understand how to consider site in analyses. Results from linear regression and fixed effects meta-regression models run both prior to and following the proposed combinability analyses were compared. In order to exemplify this approach, we examined associations between prenatal exposure to particulate matter and birth weight. Analyses included mother-child dyads (N=1966) from the Asthma Coalition on Community Environment and Social Stress (ACCESS) Project and the PRogramming of Intergenerational Stress Mechanisms (PRISM) study in the northeastern United States, and the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study in Mexico City. Mothers' daily third trimester exposure to particulate matter≤2.5µm in diameter (PM2.5) was estimated using a validated satellite-based spatio-temporally resolved model in all studies. Fenton birth weight for gestational age z-scores were calculated. Linear regression analyses within each cohort separately did not find significant associations between PM2.5 averaged over the third trimester and Fenton z-scores. The initial meta-regression model also did not find significant associations between prenatal PM2.5 and birthweight. Next, propensity scores and log linear models were used to assess higher order interactions and determine if sites were comparable with regard to sociodemographics and other covariates; these analyses demonstrated that PROGRESS and ACCESS were combinable. Adjusted linear regression models including a 2-level site variable according to the pooling indicated by the log linear models (ACCESS and PROGRESS as one level and PRISM as another) revealed that a 5µg/m3 increase in PM2.5 was associated with a 0.075 decrease in Fenton z-score (p<0.0001); linear models including a 3-level site variable did not reveal significant associations. By assessing the combinability of heterogeneous populations prior to combining data using a method that more optimally accounts for underlying cohort differences, we were able to identify significant associations between prenatal PM2.5 exposure and birthweight that were not detected using standard methods.