Prenatal Iodine Intake and Maternal Pregnancy and Postpartum Depressive and Anhedonia Symptoms: Findings from a Multiethnic US Cohort.

Objective: Emerging evidence suggests that essential trace elements, including iodine, play a vital role in depressive disorders. This study investigated whether prenatal dietary iodine intake alone and in combination with supplemental iodine intake during pregnancy were associated with antepartum and postpartum depressive and anhedonia symptoms. Methods: The study population included 837 mothers in the PRogramming of Intergenerational Stress Mechanisms (PRISM) study. The modified BLOCK food frequency questionnaire was used to estimate prenatal dietary and supplemental iodine intake, while the 10-item Edinburg Postpartum Depression Scale (EPDS) ascertained depressive symptoms. Analyses considered the global EPDS score and the anhedonia and depressive symptom subscale scores using dichotomized cutoffs. Logistic regression estimating odds ratios and 95% confidence intervals (CIs) assessed associations of iodine intake in the second trimester of pregnancy and 6-month postpartum depressive and anhedonia symptoms considering dietary intake alone and combined dietary and supplementary intake in separate models. Results: Most women were Black/Hispanic Black (43%) and non-Black Hispanics (35%), with 39% reporting a high school education or less. The median (interquartile range, IQR) dietary and supplemental iodine intake among Black/Hispanic Black (198 (115, 337) µg/day) and non-Black Hispanic women (195 (126, 323) µg/day) was higher than the overall median intake level of 187 (116, 315) µg/day. Relative to the Institute of Medicine recommended iodine intake level of 160-220 µg/day, women with intake levels < 100 µg/day, 100-<160 µg/day, >220-<400 µg/day and ≥400 µg/day had increased adjusted odds of 6-month postpartum anhedonia symptoms (aOR = 1.74 (95% CI: 1.08, 2.79), 1.25 (95% CI: 0.80, 1.99), 1.31 (95% CI: 0.82, 2.10), and 1.47 (95% CI: 0.86, 2.51), respectively). The corresponding estimates for postpartum global depressive symptoms were similar but of smaller magnitude. Conclusions: Prenatal iodine intake, whether below or above the recommended levels for pregnant women, was most strongly associated with greater anhedonia symptoms, particularly in the 6-month postpartum period. Further studies are warranted to corroborate these findings, as dietary and supplemental iodine intake are amenable to intervention.

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.

Prenatal ambient air pollutant mixture exposure and neurodevelopment in urban children in the Northeastern United States.

BACKGROUND: Studies of prenatal air pollution (AP) exposure on child neurodevelopment have mostly focused on a single pollutant. We leveraged daily exposure data and implemented novel data-driven statistical approaches to assess effects of prenatal exposure to a mixture of seven air pollutants on cognitive functioning in school-age children from an urban pregnancy cohort. METHODS: Analyses included 236 children born at ≥37 weeks gestation. Maternal prenatal daily exposure levels for nitrogen dioxide (NO2), ozone (O3), and constituents of fine particles [elemental carbon (EC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+)] were estimated based on residential addresses using validated satellite-based hybrid models or global 3-D chemical-transport models. Children completed Wide Range Assessment of Memory and Learning (WRAML-2) and Conners' Continuous Performance Test (CPT-II) at 6.5 ± 0.9 years of age. Time-weighted levels for mixture pollutants were estimated using Bayesian Kernel Machine Regression Distributed Lag Models (BKMR-DLMs), with which we also explored the interactions in the exposure-response functions among pollutants. Resulting time-weighted exposure levels were used in Weighted Quantile Sum (WQS) regressions to examine AP mixture effects on outcomes, adjusted for maternal age, education, child sex, and prenatal temperature. RESULTS: Mothers were primarily ethnic minorities (81% Hispanic and/or black) reporting ≤12 years of education (68%). Prenatal AP mixture (per unit increase in WQS estimated AP index) was associated with decreased WRAML-2 general memory (GM; ß = -0.64, 95%CI = -1.40, 0.00) and memory-related attention/concentration (AC; ß = -1.03, 95%CI = -1.78, -0.27) indices, indicating poorer memory functioning, as well as increased CPT-II omission errors (OE; ß = 1.55, 95%CI = 0.34, 2.77), indicating increased attention problems. When stratified by sex, association with AC index was significant among girls, while association with OE was significant among boys. Traffic-related pollutants (NO2, OC, EC) and SO42- were major contributors to these associations. There was no significant evidence of interactions among mixture components. CONCLUSIONS: Prenatal exposure to an AP mixture was associated with child neurocognitive outcomes in a sex- and domain-specific manner.

KERNEL MACHINE AND DISTRIBUTED LAG MODELS FOR ASSESSING WINDOWS OF SUSCEPTIBILITY TO ENVIRONMENTAL MIXTURES IN CHILDREN'S HEALTH STUDIES.

Exposures to environmental chemicals during gestation can alter health status later in life. Most studies of maternal exposure to chemicals during pregnancy have focused on a single chemical exposure observed at high temporal resolution. Recent research has turned to focus on exposure to mixtures of multiple chemicals, generally observed at a single time point. We consider statistical methods for analyzing data on chemical mixtures that are observed at a high temporal resolution. As motivation, we analyze the association between exposure to four ambient air pollutants observed weekly throughout gestation and birth weight in a Boston-area prospective birth cohort. To explore patterns in the data, we first apply methods for analyzing data on (1) a single chemical observed at high temporal resolution, and (2) a mixture measured at a single point in time. We highlight the shortcomings of these approaches for temporally-resolved data on exposure to chemical mixtures. Second, we propose a novel method, a Bayesian kernel machine regression distributed lag model (BKMR-DLM), that simultaneously accounts for nonlinear associations and interactions among time-varying measures of exposure to mixtures. BKMR-DLM uses a functional weight for each exposure that parameterizes the window of susceptibility corresponding to that exposure within a kernel machine framework that captures non-linear and interaction effects of the multivariate exposure on the outcome. In a simulation study, we show that the proposed method can better estimate the exposure-response function and, in high signal settings, can identify critical windows in time during which exposure has an increased association with the outcome. Applying the proposed method to the Boston birth cohort data, we find evidence of a negative association between organic carbon and birth weight and that nitrate modifies the organic carbon, elemental carbon, and sulfate exposure-response functions.

Relationships of Nutritional Factors and Agrochemical Exposure with Parkinson's Disease in the Province of Brescia, Italy.

Environmental exposures to agrochemicals and nutritional factors may be associated with Parkinson's Disease (PD). None of the studies to date has examined the combined effects of diet and agricultural chemical exposure together. To address these research gaps, we aimed to assess the association of nutritional factors and agrochemical exposure with the risk of PD. A hospital-based case-control study was conducted. Multivariable logistic regressions were used to estimate the association of nutritional and agrochemical exposures with PD, adjusting for gender, age, socio-economic status, head injury, family history, smoking, metals exposure, and α-synuclein gene polymorphism. Weighted Quantile Sum (WQS) regression was applied to examine the effect of dietary components as a mixture. We recruited 347 cases and 389 controls. Parent history of PD (OR = 4.15, 95%CI: 2.10, 8.20), metals exposure (OR = 2.50, 95%CI: 1.61-3.89), SNCA rs356219 polymorphism (OR = 1.39, 95%CI: 1.04-1.87 for TC vs. TT; OR = 2.17, 95%CI: 1.43-3.28 for CC vs. TT), agrochemical exposures (OR = 2.11, 95%CI: 1.41-3.16), and being born in the Brescia province (OR = 1.83, 95%CI: 1.17-2.90) were significantly associated with PD. Conversely, fish intake and coffee consumption had a protective effect. The study confirmed the role of environmental exposures in the genesis of PD. Fish intake and coffee consumption are protective factors even when agricultural chemical exposures exist. Genetic factors and metals exposure were confirmed as risk factors for PD.

Prenatal Fine Particulate Matter, Maternal Micronutrient Antioxidant Intake, and Early Childhood Repeated Wheeze: Effect Modification by Race/Ethnicity and Sex.

Fine particulate matter (PM2.5) potentiates in utero oxidative stress influencing fetal development while antioxidants have potential protective effects. We examined associations among prenatal PM2.5, maternal antioxidant intake, and childhood wheeze in an urban pregnancy cohort (n = 530). Daily PM2.5 exposure over gestation was estimated using a satellite-based spatiotemporally resolved model. Mothers completed the modified Block98 food frequency questionnaire. Average energy-adjusted percentile intake of ß-carotene, vitamins (A, C, E), and trace minerals (zinc, magnesium, selenium) constituted an antioxidant index (AI). Maternal-reported child wheeze was ascertained up to 4.1 ± 2.8 years. Bayesian distributed lag interaction models (BDLIMs) were used to examine time-varying associations between prenatal PM2.5 and repeated wheeze (≥2 episodes) and effect modification by AI, race/ethnicity, and child sex. Covariates included maternal age, education, asthma, and temperature. Women were 39% Black and 33% Hispanic, 36% with ≤high school education; 21% of children had repeated wheeze. Higher AI was associated with decreased wheeze in Blacks (OR = 0.37 (0.19-0.73), per IQR increase). BDLIMs identified a sensitive window for PM2.5 effects on wheeze among boys born to Black mothers with low AI (at 33-40 weeks gestation; OR = 1.74 (1.19-2.54), per µg/m3 increase in PM2.5). Relationships among prenatal PM2.5, antioxidant intake, and child wheeze were modified by race/ethnicity and sex.

Joint associations among prenatal metal mixtures and nutritional factors on birth weight z-score: Evidence from an urban U.S. population.

The benefits of nutritional factors on birth outcomes have been recognized, however, limited studies have examined the role of nutritional factors in mitigating the detrimental effects of metals exposure during gestation. We used data collected from 526 mother-infant dyads enrolled in the Programming of Intergenerational Stress Mechanisms longitudinal pregnancy cohort to examine the joint effects of prenatal exposure to metals and maternal nutrition on birth weight for gestational age (BWGA) z-scores. We measured concentrations of twelve metals and trace elements in urine samples collected during pregnancy. Maternal nutritional intake was measured using the Block98 Food Frequency Questionnaire and converted into energy-adjusted consumption of individual nutrients. Using multivariable linear regression and Bayesian Kernel Machine Regression, we found that three metals [cobalt (Co), nickel (Ni), and lead (Pb)] and five metals [barium (Ba), caesium (Cs), copper (Cu), Ni, and zinc (Zn)] were associated with BWGA z-score in male and female infants, respectively. When examining the sex-specific interactions between these metals and nutrient groups [macro nutrients, minerals, A vitamins, B vitamins, anti-oxidant, methyl-donor nutrients, and inflammatory (pro- and anti-)] using a Cross-validated Kernel Ensemble model, we identified significant interactions between the macro nutrients and Co (p = 0.05), minerals and Pb (p = 0.04), and A vitamins and Ni (p = 0.001) in males. No significant interactions were found in females. Furthermore, three minerals (phosphorus, iron, potassium) and vitamin A were found to be more crucial than other nutrients in modifying the association between each respective metal and BWGA z-score in males. A better understanding of the sex-specific interactions between nutrients and metals on birth weight can guide pregnant women to protect their neonates from the adverse health impacts of metal exposures by optimizing nutrient intakes accordingly.

Prenatal PM2.5 exposure and infant temperament at age 6 months: Sensitive windows and sex-specific associations.

BACKGROUND: Prenatal exposure to fine particulate matter with a diameter of ≤2.5 µm (PM2.5) has been linked to adverse neurodevelopmental outcomes in later childhood, while research on early infant behavior remains sparse. OBJECTIVES: We examined associations between prenatal PM2.5 exposure and infant negative affectivity, a stable temperamental trait associated with longer-term behavioral and mental health outcomes. We also examined sex-specific effects. METHODS: Analyses included 559 mother-infant pairs enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort. Daily PM2.5 exposure based on geocoded residential address during pregnancy was estimated using a satellite-based spatiotemporal model. Domains of negative affectivity (Sadness, Distress to Limitations, Fear, Falling Reactivity) were assessed using the Infant Behavior Questionnaire-Revised (IBQ-R) when infants were 6 months old. Subscale scores were calculated as the mean of item-specific responses; the global Negative Affectivity (NA) score was derived by averaging the mean of the four subscale scores. Bayesian distributed lag interaction models (BDLIMs) were used to identify sensitive windows for prenatal PM2.5 exposure on global NA and its subscales, and to examine effect modification by sex. RESULTS: Mothers were primarily racial/ethnic minorities (38% Black, 37% Hispanic), 40% had ≤12 years of education; most did not smoke during pregnancy (87%). In the overall sample, BDLIMs revealed that increased PM2.5 at mid-pregnancy was associated with higher global NA, Sadness, and Fear scores, after adjusting for covariates (maternal age, education, race/ethnicity, sex). Among boys, increased PM2.5 at early pregnancy was associated with decreased Fear scores, while exposure during late pregnancy was associated with increased Fear scores (cumulative effect estimate = 0.57, 95% CI: 0.03-1.41). Among girls, increased PM2.5 during mid-pregnancy was associated with higher Fear scores (cumulative effect estimate = 0.82, 95% CI: 0.05-1.91). CONCLUSIONS: Prenatal PM2.5 exposure was associated with negative affectivity at age 6 months, and the sensitive windows may vary by subdomains and infant sex.

Maternal active asthma in pregnancy influences associations between polyunsaturated fatty acid intake and child asthma.

BACKGROUND: Studies evaluating effects of prenatal polyunsaturated fatty acid (PUFA) intake on childhood asthma reveal mixed results. Inconsistencies may result from not accounting for important modifying factors such as maternal asthma or child sex. OBJECTIVE: To evaluate whether associations between prenatal PUFA intake and childhood asthma are modified by prenatal active maternal asthma or child sex in 412 mother-child dyads. METHODS: Energy-adjusted prenatal dietary and supplement intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs were estimated using the Block98 Food Frequency Questionnaire, administered during pregnancy. Mothers reported asthma in children followed prospectively to 4.0 plus or minus 1.7 years. Generalized additive models with smooth terms for PUFA (n-3, n-6, n-6/n-3 ratio) effects were used to investigate associations between PUFAs and child asthma, without prespecifying the form of these relationships, including effect modification by active maternal asthma or child sex. RESULTS: Among mothers (40% Black, 31% Hispanic), 22% had active asthma in pregnancy; 17.5% of children developed asthma. Lower maternal n-3 PUFA intake was significantly associated with risk of childhood asthma (P = .03), in particular among children of mothers with active asthma and low n-3 PUFA intake (P = .01). This inverse association was more apparent in girls (P = .01) compared with boys (P = .30), regardless of maternal asthma status. For n-6 PUFA and the n-6/n-3 ratio, there was a lower risk of childhood asthma in the midrange of intake and increased risk at higher intake (n-6 PUFA P = .10, n-6/n-3 ratio P = .13). CONCLUSION: Consideration of factors that modify effects of prenatal PUFA intake on childhood asthma has implications for designing intervention strategies tailored to impact those at greatest risk.

Prenatal Ambient Ultrafine Particle Exposure and Childhood Asthma in the Northeastern United States.

Rationale: Ambient ultrafine particles (UFPs; with an aerodynamic diameter < 0.1 µm) may exert greater toxicity than other pollution components because of their enhanced oxidative capacity and ability to translocate systemically. Studies examining associations between prenatal UFP exposure and childhood asthma remain sparse. Objectives: We used daily UFP exposure estimates to identify windows of susceptibility of prenatal UFP exposure related to asthma in children, accounting for sex-specific effects. Methods: Analyses included 376 mother-child dyads followed since pregnancy. Daily UFP exposure during pregnancy was estimated by using a spatiotemporally resolved particle number concentration prediction model. Bayesian distributed lag interaction models were used to identify windows of susceptibility for UFP exposure and examine whether effect estimates varied by sex. Incident asthma was determined at the first report of asthma (3.6 ± 3.2 yr). Covariates included maternal age, education, race, and obesity; child sex; nitrogen dioxide (NO2) and temperature averaged over gestation; and postnatal UFP exposure. Measurements and Main Results: Women were 37.8% Black and 43.9% Hispanic, with 52.9% reporting having an education at the high school level or lower; 18.4% of children developed asthma. The cumulative odds ratio (95% confidence interval) for incident asthma per doubling of the UFP exposure concentration across pregnancy was 4.28 (1.41-15.7), impacting males and females similarly. Bayesian distributed lag interaction models indicated sex differences in the windows of susceptibility, with the highest risk of asthma seen in females exposed to higher UFP concentrations during late pregnancy. Conclusions: Prenatal UFP exposure was associated with asthma development in children, independent of correlated ambient NO2 and temperature. Findings will benefit future research and policy-makers who are considering appropriate regulations to reduce the adverse effects of UFPs on child respiratory health.

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.

Associations among maternal socioeconomic status in childhood and pregnancy and hair cortisol in pregnancy.

Dysregulation of the maternal-fetal hypothalamic-pituitary-adrenal axis (HPAA) has been hypothesized to negatively influence various offspring physical and mental health outcomes. Limited data suggest that low maternal socioeconomic status (SES) in pregnancy may disrupt maternal HPAA functioning. Research is needed that examines how maternal SES in childhood may influence maternal HPAA functioning in pregnancy, given evidence that early life adversity can have persistent effects on physiological stress reactivity. In a sample of 343 sociodemographically diverse women, we tested whether indices of life course SES were associated with HPAA functioning across pregnancy reflected in hair cortisol collected within one week after delivery. Mothers were asked whether their parent(s) owned their home across three developmental periods, from birth through adolescence, as an indicator of their childhood SES. Measures of maternal SES in pregnancy included maternal educational attainment, annual household income, and current homeownership. Analyses revealed that indicators of lower maternal SES in childhood and in pregnancy were associated with higher cortisol levels during each trimester. In analyses adjusted for maternal race/ethnicity, pre-pregnancy body mass index, smoking in pregnancy, use of inhaled and topical corticosteroids, and mode of delivery, each indicator of maternal SES in pregnancy fully mediated maternal childhood SES effects on maternal hair cortisol levels in pregnancy. This is the first study to show an association between maternal life course SES and hair cortisol in pregnancy. The results suggest that maternal SES, starting in childhood, may have intergenerational consequences via disruption to the maternal-fetal HPAA in pregnancy. These findings have implications for elucidating mechanisms contributing to health disparities among socioeconomically disadvantaged populations.

Free versus purchased mosquito net ownership and use in Budondo sub-county, Uganda.

BACKGROUND: While the distribution of mosquito bed nets is a widely adopted approach for malaria prevention, studies exploring how the usage of a net may be influenced by its source and other factors remain sparse. METHODS: A standardized questionnaire and home-visit observations were used to collect data from 9 villages in Budondo sub-county, Uganda in 2016. Household- and individual-level data were collected, such as bed net ownership (at least one net versus none), acquirement source (free versus purchased), demographics, as well as knowledge of malaria and preventative measures. Net-level data, including alternative uses, and bed net quantity and integrity, were also collected. Mixed effects logistic regression models were performed to identify the key determinants of bed net use. RESULTS: Overall, the proportion of households with at least one bed net was 40%, while bed net availability was only reported among 27% of all household members. Awareness of the benefits of bed net use was statistically significantly associated with ownership of at least one net (OR = 1.72, 95% CI 1.11-2.68, p = 0.02). Among those who own net(s), the odds of a bed net being correctly used (i.e., to sleep under) after adjusting for potential confounders were significantly lower for nets that were obtained free compared to nets that were purchased by the owners themselves (OR = 0.33, 95% CI 0.21-0.51, p < 0.01), resulting in an alternative use of the net. Other factors such as female gender, children ≤ 5 years old, and pregnancy status were also significantly associated with having a net to sleep under (all p < 0.01). CONCLUSION: Understanding inter- and intra-household net-use factors will help malaria control programmes more effectively direct their efforts to increase public health impact. Future studies may additionally consider socioeconomic status and track the lifetime of the net.

Maternal Lifetime Trauma and Birthweight: Effect Modification by In Utero Cortisol and Child Sex.

OBJECTIVES: To evaluate associations between maternal lifetime traumatic stress and offspring birthweight and examine modifying effects of third trimester cortisol and fetal sex. STUDY DESIGN: Analyses included 314 mother-infant dyads from an ethnically mixed pregnancy cohort. Maternal lifetime trauma was reported via the Life Stressor Checklist-Revised. Fenton birthweight for gestational age z-scores (BWGA-z) were calculated. A 3-cm scalp-nearest maternal hair segment collected at birth was assayed to reflect cumulative third trimester cortisol secretion. Multivariable regression was used to investigate associations between maternal lifetime trauma and BWGA-z and examine 2- and 3-way interactions with cortisol and fetal sex. Because subjects with low or high cortisol levels could represent susceptible populations, varying coefficient models that relax the linearity assumption on cortisol level were used to assess the modification of maternal lifetime trauma associations with BWGA-z as a function of cortisol. RESULTS: Women were primarily minorities (41% Hispanic, 26% black) with ≤12 years education (63%); 63% reported ≥1 traumatic event. Prenatal cortisol modified the association between maternal lifetime trauma and birthweight. Women with higher lifetime trauma and increased cortisol had significantly lower birthweight infants in males; among males exposed to the 90th percentile of cortisol, a 1-unit increase in trauma score was associated with a 0.19-unit decrease in BWGA-z (95% CI, -0.34 to -0.04). Associations among females were nonsignificant, regardless of cortisol level. CONCLUSIONS: These findings underscore the need to consider complex interactions among maternal trauma, disrupted in utero cortisol production, and fetal sex to fully elucidate intergenerational effects of maternal lifetime trauma.

Subconstructs of the Edinburgh Postpartum Depression Scale in a postpartum sample in Mexico City.

BACKGROUND: Postpartum depression is an important cause of morbidity in mothers and children. The Edinburgh Postpartum Depression Scale (EPDS), the most widely used self-reported measure of postpartum depression, was conceived as a one-dimensional measure. However, evidence that depressive symptoms may be experienced differentially across cultural and racial groups highlights the need to examine structural equivalence using factor analysis across populations. Variation in factor structure for the EPDS remains understudied in middle/low income countries. METHODS: We examined the factor structure of the EPDS assessed 6 months postpartum in 628 Mexican women in a longitudinal Mexico City birth cohort. We performed exploratory factor analysis (EFA) to determine the optimal fit in our sample and confirmatory factor analysis (CFA) to examine the fit of two- and three-factor models previously reported in Hispanic populations. RESULTS: The majority of participants had no more than high school education (77%), maternal age was 28 ±â€¯5.4 years and the mean total EPDS score was 6.72 ±â€¯5.8. Using EFA, we identified that the three-factor model provided the optimal fit, with subscales for depression, anxiety, and anhedonia. CFA confirmed that the three-factor model provided the best fit. LIMITATIONS: The study population was lower SES, potentially limiting generalizability. The single administration of the EPDS measure in the postpartum period limited our ability to assess stability over time. CONCLUSIONS: Better delineation of the multi-factorial structure of the EPDS will allow a more comprehensive understanding of psychological functioning in postpartum women and better inform diagnosis, management and policy.

Association between particulate air pollution exposure during pregnancy and postpartum maternal psychological functioning.

METHODS: We studied associations between prenatal exposure to particulate matter with diameter ≤ 2.5 µm (PM2.5) and postpartum psychological functioning in a lower income, ethnically mixed sample of urban US women enrolled in a pregnancy cohort study. Analyses included 557 mothers who delivered at ≥37 weeks gestation. Daily estimates of residential PM2.5 over gestation were derived using a satellite-based spatio-temporally resolved model. Outcomes included the Edinburgh Postnatal Depression Scale (EPDS) score from 6 or 12 months postpartum and subscale scores for anhedonia, depressive and anxiety symptoms. Associations were also examined within racial/ethnic groups. Distributed lag models (DLMs) were implemented to identify windows of vulnerability during pregnancy. RESULTS: Most mothers had less than a high school education (64%) and were primarily Hispanic (55%) and Black (29%). In the overall sample, a DLM adjusted for age, race, education, prenatal smoking, and season of delivery, we found significant associations between higher PM2.5 exposure in the second trimester and increased anhedonia subscale scores postpartum. In race stratified analyses, mid-pregnancy PM2.5 exposure was significantly associated with increased total EPDS scores as well as higher anhedonia and depressive symptom subscale scores among Black women. CONCLUSIONS: Increased PM2.5 exposure in mid-pregnancy was associated with increased depressive and anhedonia symptoms, particularly in Black women.

Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects.

BACKGROUND: In utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylation. METHODS: We prospectively examined associations among prenatal PM2.5 exposure and child lung function and GSTP1 methylation in an urban pregnancy cohort study. We employed a validated satellite-based spatiotemporally resolved prediction model to estimate daily prenatal PM2.5 exposure over gestation. We used Baysian distributed lag interaction models (BDLIMs) to identify sensitive windows for prenatal PM2.5 exposure on child lung function and nasal epithelia GSTP1 methylation at age 7 years, and to examine effect modification by child sex. RESULTS: BDLIMs identified a sensitive window for prenatal PM2.5 exposure at 35-40 weeks gestation [cumulative effect estimate (CEE) = - 0.10, 95%CI = - 0.19 to - 0.01, per µg/m3 increase in PM2.5] and at 36-40 weeks (CEE = - 0.12, 95%CI = - 0.20 to - 0.01) on FEV1 and FVC, respectively, in boys. BDLIMs also identified a sensitive window of exposure at 37-40 weeks gestation between higher prenatal PM2.5 exposure and increased GSTP1 percent methylation. The association between higher GSTP1 percent methylation and decreased FEV1 was borderline significant in the sample as a whole (ß = - 0.37, SE = 0.20, p = 0.06) and in boys in stratified analyses (ß = - 0.56, SE = 0.29, p = 0.05). CONCLUSIONS: Prenatal PM2.5 exposure in late pregnancy was associated with impaired early childhood lung function and hypermethylation of GSTPI in DNA isolated from nasal epithelial cells. There was a trend towards higher GSTP1 percent methylation being associated with reduced FEV1. All findings were most evident among boys.

Prenatal particulate matter exposure and mitochondrial dysfunction at the maternal-fetal interface: Effect modification by maternal lifetime trauma and child sex.

BACKGROUND: Prenatal ambient fine particulate matter (PM2.5) and maternal chronic psychosocial stress have independently been linked to changes in mithochondrial DNA copy number (mtDNAcn), a marker of mitochondrial response and dysfunction. Further, overlapping research shows sex-specific effects of PM2.5 and stress on developmental outcomes. Interactions among PM2.5, maternal stress, and child sex have not been examined in this context. METHODS: We examined associations among exposure to prenatal PM2.5, maternal lifetime traumatic stressors, and mtDNAcn at birth in a sociodemographically diverse pregnancy cohort (N=167). Mothers' daily exposure to PM2.5 over gestation was estimated using a satellite-based spatio-temporally resolved prediction model. Lifetime exposure to traumatic stressors was ascertained using the Life Stressor Checklist-Revised; exposure was categorized as high vs. low based on a median split. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNAcn in placenta and cord blood leukocytes. Bayesian Distributed Lag Interaction regression models (BDLIMs) were used to statistically model and visualize the PM2.5 timing-dependent pattern of associations with mtDNAcn and explore effect modification by maternal lifetime trauma and child sex. RESULTS: Increased PM2.5 exposure across pregnancy was associated with decreased mtDNAcn in cord blood (cumulative effect estimate=-0.78; 95%CI -1.41, -0.16). Higher maternal lifetime trauma was associated with reduced mtDNAcn in placenta (ß=-0.33; 95%CI -0.63, -0.02). Among women reporting low trauma, increased PM2.5 exposure late in pregnancy (30-38weeks gestation) was significantly associated with decreased mtDNAcn in placenta; no significant association was found in the high trauma group. BDLIMs identified a significant 3-way interaction between PM2.5, maternal trauma, and child sex. Specifically, PM2.5 exposure between 25 and 40weeks gestation was significantly associated with increased placental mtDNAcn among boys of mothers reporting high trauma. In contrast, PM2.5 exposure in this same window was significantly associated with decreased placental mtDNAcn among girls of mothers reporting low trauma. Similar 3-way interactive effects were observed in cord blood. CONCLUSIONS: These results indicate that joint exposure to PM2.5 in late pregnancy and maternal lifetime trauma influence mtDNAcn at the maternal-fetal interface in a sex-specific manner. Additional studies will assist in understanding if the sex-specific patterns reflect distinct pathophysiological processes in addition to mitochondrial dysfunction.

Potential for Bias When Estimating Critical Windows for Air Pollution in Children's Health.

Evidence supports an association between maternal exposure to air pollution during pregnancy and children's health outcomes. Recent interest has focused on identifying critical windows of vulnerability. An analysis based on a distributed lag model (DLM) can yield estimates of a critical window that are different from those from an analysis that regresses the outcome on each of the 3 trimester-average exposures (TAEs). Using a simulation study, we assessed bias in estimates of critical windows obtained using 3 regression approaches: 1) 3 separate models to estimate the association with each of the 3 TAEs; 2) a single model to jointly estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We used weekly fine-particulate-matter exposure data for 238 births in a birth cohort in and around Boston, Massachusetts, and a simulated outcome and time-varying exposure effect. Estimates using separate models for each TAE were biased and identified incorrect windows. This bias arose from seasonal trends in particulate matter that induced correlation between TAEs. Including all TAEs in a single model reduced bias. DLM produced unbiased estimates and added flexibility to identify windows. Analysis of body mass index z score and fat mass in the same cohort highlighted inconsistent estimates from the 3 methods.

Sex differences in sensitivity to prenatal and early childhood manganese exposure on neuromotor function in adolescents.

INTRODUCTION: While studies have suggested that exposure to manganese (Mn) may be associated with neurodevelopment in school-age children, there is limited information on prenatal and postnatal Mn exposures and tremor or motor function in children. METHODS: We measured Mn levels in dentine of shed teeth, representing prenatal, early postnatal, and cumulative childhood exposure windows, from 195 children (predominantly right-handed, 92%) in Italy. Pursuit Aiming, Luria Nebraska Motor Battery, as well as Tremor and Sway system from Computerized Adaptive Testing System (CATSYS) were administered at 11-14 years old. We examined the relationships of tooth Mn (ln-transformed) with motor function using multivariable linear regressions and generalized additive models, adjusting for age, sex, and socioeconomic status index. Effect modification by sex was also examined. RESULTS: We found that higher prenatal Mn was associated with better body stability in boys in a number of sway tests (including mean sway, transversal sway, sagittal sway, sway area, and sway intensity), while Mn was associated with poorer performance in girls on all of these metrics (all p for Mn × sex interaction < 0.05). Higher prenatal Mn was also modestly associated with better hand/finger and eye-hand coordination in boys compared to girls in sex-stratified analyses, although interaction models did not reach statistical significance. For tremor, on the other hand, higher early postnatal Mn was associated with increased right-hand center frequency in girls (p for interaction < 0.01), but increased Mn level at the later postnatal period was associated with increased center frequency in boys (p for interaction = 0.01). CONCLUSIONS: This study, which used a direct measure of prenatal and childhood Mn exposure, suggested sex-specific critical windows of early life Mn exposure in relation to neuromotor function in adolescents. The sex-specific associations might be strongest with measures of whole body stability, for which the critical exposure window was during the prenatal period.