Prenatal exposure to air pollution and BWGA Z-score: Modifying effects of placenta leukocyte telomere length and infant sex.

BACKGROUND: Air pollutants, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), have been associated with adverse birth outcomes, including low birth weight, often exhibiting sex-specific effects. However, the modifying effect of placental telomere length (TL), reflecting cumulative lifetime oxidative stress in mothers, remains unexplored. METHOD: Using data from a Northeastern U.S. birth cohort (n = 306), we employed linear regression and weighted quantile sum models to assess trimester-average air pollution exposures and birth weight for gestational age (BWGA) z-scores. Placental TL, categorized by median split, was considered as an effect modifier. Interactions among air pollutants, placental TL, infant sex, and BWGA z-score were evaluated. RESULTS: Without placental TL as a modifier, only 1st trimester O3 was significantly associated with BWGA z-scores (coefficient: 0.33, 95% CI: 0.03, 0.63). In models considering TL interactions, a significant modifying effect was observed between 3rd trimester NO2 and BWGA z-scores (interaction p-value = 0.02). Specifically, a one interquartile range (1-IQR) increase in 3rd trimester NO2 was linked to a 0.28 (95% CI: 0.06, 0.52) change in BWGA z-score among shorter placental TL group, with no significant association among longer TL group. Among male infants, there were significant associations between 3rd trimester PM2.5 exposure and BWGA z-scores in the longer TL group (coefficient: -0.34, 95% CI: -0.61, -0.02), and between 1st trimester O3 exposure and BWGA z-scores among males in the shorter TL group (coefficient: 0.59, 95% CI: 0.06, 1.08). For females, only a negative association in 2nd trimester mixture model was observed within the longer TL group (coefficient: -0.10, 95% CI: -0.21, -0.01). CONCLUSION: These findings highlight the need to consider the complex interactions among prenatal air pollutant exposures, placental TL, and fetal sex to better elucidate those at greatest risk for adverse birth outcomes.

Impact of sedentary behavior and emotional support on prenatal psychological distress and birth outcomes during the COVID-19 pandemic.

Abstract. BACKGROUND: Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics. METHODS: Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report. RESULTS: After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed. CONCLUSIONS: There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.

Prenatal exposure to polybrominated diphenyl ethers and birth outcomes.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size. METHODS: The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity. RESULTS: Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (-0.25, 95% CI: -0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (-0.55, 95% CI: -0.98, -0.12). There was a negative association between the overall PBDE mixture and birth length z-score (-0.10, 95% CI: -0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity. CONCLUSIONS: These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns.

Ambient PM2.5 exposure and salivary cortisol output during pregnancy in a multi-ethnic urban sample.

OBJECTIVES: Evidence from murine research supports that fine particulate matter (PM2.5) may stimulate the hypothalamic-pituitary-adrenal axis, leading to elevated circulating glucocorticoid levels. Epidemiologic research examining parallel associations document similar associations. We examined these associations among a diverse sample of pregnant individuals exposed to lower levels of ambient PM2.5. MATERIALS AND METHODS: Participants included pregnant individuals enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pre-birth cohort. Daily residential PM2.5 exposure was estimated using a satellite-based spatial-temporal hybrid model. Maternal 3rd trimester salivary cortisol levels were used to calculate several features of the diurnal cortisol rhythm. We used multivariable linear regression to examine PM2.5 during the pre-conception period and during each trimester in relation to cortisol awakening rise (CAR), slope, and area under the curve relative to ground (AUCG). RESULTS AND DISCUSSION: The average PM2.5 exposure level across pregnancy was 8.13 µg/m3. PM2.5 in each exposure period was positively associated with AUCG, a measure of total cortisol output across the day. We also observed an inverse association between PM2.5 in the 3rd trimester and diurnal slope, indicating a steeper decline in cortisol throughout the day with increasing exposure. We did not detect strong associations between PM2.5 and slope for the other exposure periods or between PM2.5 and CAR for any exposure period. CONCLUSIONS: In this sample, PM2.5 exposure across the preconception and pregnancy periods was associated with increased cortisol output, even at levels below the U.S. National Ambient Air Quality Annual Standard for PM2.5 of 12.0 µg/m3.

A short form of the Crisis in Family Systems (CRISYS) in a racially diverse sample of pregnant women.

Assessing stressful life events in large-scale epidemiologic studies is challenged by the need to measure potential stressful events in a reasonably comprehensible manner balanced with burden on participants and research staff. The aim of this paper was to create a short form of the Crisis in Family Systems-Revised (CRISYS-R) plus 17 acculturation items, a measure that captures contemporary life stressors across 11 domains. Latent class analysis (LCA) was used to segment the sample of 884 women from the PRogramming of Intergenerational Stress Mechanisms (PRISM) study experiencing different patterns of exposure to stressful events and identify items from each domain that best discriminate between individuals with different patterns of stressful-event exposures (high vs. low stress exposure). The results from the LCA, in conjunction with the expert opinions provided by the original developers of the CRISYS, yielded a 24-item item short form (CRISYS-SF) with at least one question from each of the original domains. Scores on the 24-item CRISYS-SF had high correlations with scores on the 80-item CRISYS. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-021-02335-w.

Metal mixtures are associated with increased anxiety during pregnancy.

BACKGROUND: Exposure to low-dose toxic metals in the environment is ubiquitous. Several murine studies have shown metals induce anxiety-like behaviors, and mechanistic research supports that metals disrupt neurotransmitter signaling systems implicated in the pathophysiology of anxiety. In this study, we extend prior research by examining joint exposure to six metals in relation to maternal anxiety symptoms during pregnancy. METHODS: The sample includes 380 participants enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. Spot urine was collected during pregnancy (mean ± standard deviation: 31.1 ± 6.1 weeks), and concentrations of six metals (barium [Ba], cadmium [Cd], chromium [Cr], cesium [Cs], lead [Pb], antimony [Sb]) were measured by Inductively Coupled Plasma - Mass Spectrometry. Trait anxiety symptoms were measured during pregnancy using a short version of the Spielberger State Trait Anxiety Inventory (STAI-T) and information on covariates was collected by questionnaire. We used weighted quantile sum (WQS) regression as the primary modeling approach to examine metals, treated as a mixture, in relation to higher (≥20) vs. lower anxiety symptoms while adjusting for urinary creatinine and key sociodemographic variables. RESULTS: The sample is socioeconomically and racially/ethnically diverse. Urinary metal concentrations were log-normally distributed and 25% of the sample had an STAI-T score ≥20. Joint exposure to metals was associated with elevated anxiety symptoms (ORWQS = 1.56, 95% CI: 1.24, 1.96); Cd (61.8%), Cr (14.7%), and Cs (12.7%) contributed the greatest weight to the mixture effect. CONCLUSION: Exposure to metals in the environment may be associated with anxiety symptoms during pregnancy. This is a public health concern, as anxiety disorders are highly prevalent and associated with significant co-morbidities, especially during pregnancy when both the mother and developing fetus are susceptible to adverse health outcomes.

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 exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations. METHODS: Data were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, - 99, - 100, and - 153 were measured in cord plasma (ng/µL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)2 were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides. RESULTS: The prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures. CONCLUSIONS: Prenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.

Using the Personality Assessment Inventory-Adolescent in Legal Settings.

The Personality Assessment Inventory-Adolescent (PAI-A; Morey et al., 2007) is a self-report measure of personality and psychopathology appropriate for use with individuals aged 12-18. It is modeled after the Personality Assessment Inventory (PAI; Morey, 1991), a measure widely used with adults in clinical and legal settings. The PAI-A assesses a variety of features that have utility in legal settings, including validity scales that assess approach to testing, clinical scales measuring common types of psychopathology, and treatment consideration scales that provide indicators of treatment motivation and other factors that may be important for predicting outcomes. The PAI-A has been included in a limited number of research studies and few of those have focused on justice-involved youths. Additionally, because juvenile court records are not typically publicly available, there is limited information about the PAI-A available in case law. This manuscript reviews the properties, strengths, and weaknesses of the PAI-A and its existing literature. Factors for mental health and legal professionals to consider in relation to the admissibility of this measure, questioning and cross-examination, and how the PAI-A may be received in court are also discussed.

Adverse childhood experiences and asthma: trajectories in a national cohort.

OBJECTIVE: Research has linked early adverse childhood experiences (ACEs) with asthma development; however, existing studies have generally relied on parent report of exposure and outcome. We aimed to examine the association of early life ACEs with empirically determined trajectories of childhood asthma risk, using independent register information on both exposures and outcome. METHODS: Based on nationwide registries, we established a study cohort of 466 556 children born in Denmark (1997-2004). We obtained information on ACEs during the first 2 years of life (bereavement, parental chronic somatic and/or mental illness) and childhood asthma diagnosis or medication use from birth through age 10 years from the Danish National Patient and Prescription Registries, respectively. We identified asthma phenotypes using group-based trajectory modelling. We then used multinomial logistic regression to examine the association between early ACEs and asthma phenotypes. RESULTS: We identified four asthma phenotypes: non-asthmatic, early-onset transient, early-onset persistent and late-onset asthma. Girls with early-onset transient asthma (OR 1.13, 95% CI 1.04 to 1.24), early-onset persistent asthma (1.27, 95% CI 1.08 to 1.48) or late-onset asthma (OR 1.28, 95% CI 1.11 to 1.48) vs no asthma were more likely to have early life ACE exposure compared with girls without ACE exposure. Results were similar for boys who also had experienced early life ACEs with ORs of 1.16 (95% CI 1.08 to 1.25), 1.34 (95% CI 1.20 to 1.51) and 1.11 (95% CI 0.98 to 1.25), respectively. CONCLUSION: In a nationwide-population study, we identified three childhood onset asthma phenotypes and found that ACEs early in life were associated with increased odds for each of these asthma phenotypes among both girls and boys.

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.

Associations of Maternal Trait Anger Expression and Lifetime Traumatic and Non-traumatic Experiences with Preterm Birth.

OBJECTIVES: Most studies examining psychosocial factors contributing to preterm birth (PTB) have focused on negative life events. Studies examining the influence of negative emotion, in particular maternal anger, remain sparse. We examined associations of maternal trait anger expression and lifetime traumatic and non-traumatic experiences with the risk of PTB. METHODS: Mother-newborn pairs were enrolled in the PRogramming of Intergenerational Stress Mechanisms pregnancy cohort based in Boston and New York City. Women completed the State-Trait Anger Expression Inventory-2 (STAXI-2), Life Stressor Checklist-Revised (LSC-R), and Childhood Trauma Questionnaire (CTQ) in pregnancy. We used modified Poisson regression to estimate the relative risk (RR) of PTB (1) in relation to continuous STAXI-2 Anger Expression-In (AX-I) and Anger Expression-Out (AX-O) subscales, (2) in relation to continuous LSC-R scores, and (3) between women who did versus did not experience childhood sexual, emotional, and/or physical abuse in six separate models. We also examined interactions between maternal anger expression and lifetime stress/childhood trauma. RESULTS: Younger, single, minority women had higher outward anger expression and inward anger suppression. AX-I and AX-O scores were higher among women who experienced abuse in childhood and who had higher lifetime stress. Maternal lifetime stress, outward anger expression, and inward anger suppression were associated with an increased risk of PTB in separate models; however, stress, trauma and anger did not interact to further increase the risk of PTB. CONCLUSIONS FOR PRACTICE: Higher anger expression and higher lifetime stress experiences were associated with an increased risk of PTB among a racially and ethnically diverse sample of pregnant women.

Integrated and diurnal indices of maternal pregnancy cortisol in relation to sex-specific parasympathetic responsivity to stress in infants.

Maternal hypothalamic-pituitary-adrenal axis activity may prenatally program sex-specific stress-response pathways. We investigated associations between maternal cortisol during pregnancy and infant parasympathetic responsivity to stress among 204 mother-infant pairs. Cortisol indices included 3rd trimester hair cortisol, as well as diurnal slope and area under the curve, derived from saliva samples collected during pregnancy. Mother-infant dyads participated in the Repeated Still-Face Paradigm (SFP-R) at age 6 months. We calculated respiration-adjusted respiratory sinus arrhythmia (RSAc ), an indicator of parasympathetic activation, from infant respiration and cardiac activity measured during the SFP-R. We used multivariable linear mixed models to examine each cortisol index in relation to infant RSAc and investigated sex differences using cross-product terms. Diurnal cortisol indices were not associated with RSAc . There was no association between hair cortisol and baseline RSAc . However, hair cortisol was associated with sex-specific changes in RSAc over the SFP-R such that, among girls, parasympathetic withdrawal was reduced with increasing prenatal exposure to cortisol. Consistently higher levels of prenatal cortisol exposure may lead to dampened parasympathetic responsivity to stress during infancy, particularly among girls. Maternal hair cortisol may be particularly valuable for studying the effects of prenatal cortisol exposure on infant autonomic reactivity.

Data-driven discovery of mid-pregnancy immune markers associated with maternal lifetime stress: results from an urban pre-birth cohort.

Changes to the maternal inflammatory milieu may be a mechanism through which maternal psychosocial stress is transmitted to the fetus. Research investigating a limited number of immune markers may miss important signals. We take a proteomics approach to investigate maternal lifetime stress and 92 biomarkers of immune system status. Participants were enrolled in an urban, dual-site (Boston, n = 301 and New York City, n = 110) pregnancy cohort. We measured maternal lifetime history of stress and trauma using the validated Life Stressor Checklist-Revised (LSC-R). We measured a panel of 92 immune-related proteins in mid-pregnancy serum using proximity extension assay technology. We leveraged the dual-site study design to perform variable selection and inference within the cohort. First, we used LASSO to select immune markers related to maternal stress among Boston mothers. Then, we performed OLS regression to examine associations between maternal stress and LASSO-selected proteins among New York City mothers. LASSO regression selected 19 immune proteins with non-null coefficients (CCL11, CCL23, CD244, CST5, CXCL1, CXCL5, CXCL10, CX3CL1, FGF-23, IL-5, IL-7, IL-10, IL-17C, MCP-2, MMP-1, SLAMF1, ST1A1, TNF-ß, and TWEAK). Of these, only the chemotactic cytokine CX3CL1 (i.e. fractalkine) was significantly associated with maternal stress among the validation sample (percent change in LSC-R score per 1% increase in relative fractalkine expression: 0.74, 95% confidence interval: 0.19, 1.28). Expanding research suggests fractalkine plays an important role in many aspects of pregnancy and fetal development and is stress-sensitive. We found that maternal lifetime history of stress and trauma was significantly associated with elevated serum fractalkine levels during pregnancy.

Prenatal toxic metal mixture exposure and newborn telomere length: Modification by maternal antioxidant intake.

BACKGROUND: Telomere length (TL) predicts the onset of cellular senescence and correlates with longevity and age-related disease risk. While telomeres erode throughout life, adults display fixed ranking and tracking of TL, supporting the importance of the early environment in determining inter-individual variability across the life course. Given their guanine-rich structure, telomeres are highly susceptible to oxidative stress (OS). We examined maternal metal exposure, which can induce OS, in relation to newborn TL. We also considered the modifying role of maternal antioxidant intake. METHODS: Analyses included 100 mother-newborn pairs enrolled in the Boston and New York City-based PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. We measured As, Ba, Cd, Ni, and Pb in maternal late-pregnancy urine by ICP-MS and quantified relative leukocyte TL (rLTL) in cord blood using qPCR. We used Weighted Quantile Sum (WQS) regression to estimate the metal mixture - rLTL association and conducted repeated holdout validation to improve the stability of estimates across data partitions. We examined models stratified by high (>median) versus low (≤median) maternal antioxidant intake, estimated from Block98 Food Frequency Questionnaires. We considered urinary creatinine, week of urine collection, maternal age, and race/ethnicity as covariates. RESULTS: In adjusted models, urinary metals were inversely associated with newborn rLTL (ßWQS = -0.50, 95% CI: -0.78, -0.21). The top metals contributing to the negative association included Ba (weight: 35.4%), Cd (24.5%) and Pb (26.9%). In models stratified by antioxidant intake, the significant inverse association between metals and rLTL remained only among mothers with low antioxidant intake (low: ßWQS = -0.92, 95% CI: -1.53, -0.30; high: ßWQS = -0.03, 95% CI: -0.58, 0.52). Results were similar in unadjusted models. CONCLUSIONS: Relative LTL was shorter among newborns of mothers with higher exposure to metals during pregnancy. Higher maternal antioxidant intake may mitigate the negative influence of metals on newborn rLTL.

Prenatal particulate air pollution and newborn telomere length: Effect modification by maternal antioxidant intakes and infant sex.

BACKGROUND: Evidence links gestational exposure to particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) with changes in leukocyte telomere length in cord blood with some studies showing sex-specific effects. PM2.5 exposure in utero increases oxidative stress, which can impact telomere biology. Thus, maternal antioxidant intakes may also modify the particulate air pollution effects. METHODS: We examined associations among prenatal PM2.5 exposure and newborn relative leukocyte telomere length (rLTL), and the modifying effects of maternal antioxidant intake and infant sex. We estimated daily PM2.5 exposures over gestation using a validated spatiotemporally resolved satellite-based model. Maternal dietary and supplemental antioxidant intakes over the prior three months were ascertained during the second trimester using the modified Block98 food frequency questionnaire; high and low antioxidant intakes were categorized based on a median split. We employed Bayesian distributed lag interaction models (BDLIMs) to identify both sensitive windows of exposure and cumulative effect estimates for prenatal PM2.5 exposure on newborn rLTL, and to examine effect modification by maternal antioxidant intakes. A 3-way interaction between PM2.5, maternal antioxidant intake and infant sex was also explored. RESULTS: For the main effect of PM2.5, BDLIMs identified a sensitive window at 12-20 weeks gestation for the association between increased prenatal PM2.5 exposure and shorter newborn rLTL and a cumulative effect of PM2.5 over gestation on newborn telomere length [cumulative effect estimate (CEE) = -0.29 (95% CI -0.49 to -0.10) per 1µg/m3 increase in PM2.5]. In models examining maternal antioxidant intake effects, BDLIMs found that children born to mothers reporting low antioxidant intakes were most vulnerable [CEE of low maternal antioxidant intake = -0.31 (95% CI -0.55 to -0.06) vs high maternal antioxidant intake = -0.07 (95% CI -0.34 to 0.17) per 1µg/m3 increase in PM2.5]. In exploratory models examining effect modification by both maternal antioxidant intakes and infant sex, the cumulative effect remained significant only in boys whose mothers reported low antioxidant intakes [CEE = -0.38 (95% CI -0.80 to -0.004)]; no sensitive windows were identified in any group. CONCLUSIONS: Prenatal PM2.5 exposure in mid-gestation was associated with reduced infant telomere length. Higher maternal antioxidant intakes mitigated these effects.

Antenatal active maternal asthma and other atopic disorders is associated with ADHD behaviors among school-aged children.

BACKGROUND: Identifying modifiable risk factors for neuropsychological correlates of attention deficit hyperactivity disorder (ADHD) in early childhood can inform prevention strategies. Prenatal inflammatory states, such as maternal asthma and other atopic disorders, have been increasingly linked to enhanced risk for neurobehavioral disorders in children, with some studies suggesting sex-specific effects. OBJECTIVES: To assess the association between maternal active asthma and/or atopy in the antenatal period and child symptoms of ADHD during mid-childhood and, given the male-bias in ADHD prevalence, to examine modifying effects of child sex. STUDY DESIGN: The study sample includes 250 maternal-child pairs enrolled in the Boston-based Asthma Coalition on Community, Environment and Social Stress (ACCESS) pregnancy cohort. We defined antenatal active atopy based on maternal report of current asthma, allergic rhinitis or atopic dermatitis during and/or in the year before pregnancy. When children were approximately 6 years old, mothers completed a battery of standardized child behavior rating scales designed for evaluating symptoms of ADHD. We used multivariable quantile regression to assess the relations between maternal antenatal atopy and symptoms of ADHD among children. RESULTS: In adjusted models, maternal atopy was significantly associated with greater risk for ADHD behaviors, as indicated by scores on the Conners' Parent Rating Scale-Revised ADHD index (ß = 3.32, 95% CI: 0.33, 6.32). In sex-stratified models this association was stronger among girls (5.96, 95% CI = 0.95, 10.96) compared to boys (-2.14, 95% CI = -5.75, 1.45, p-interaction = 0.01). Among girls, we observed a similar finding for the Behavior Assessment System for Children 2nd Edition Parent Rating Scale Attention Problems subscale (ß = 7.77, 95% CI = 1.57, 13.97). Results from other outcome subscales were similar in magnitude and direction, however, associations did not reach statistical significance at the p = 0.05 level. CONCLUSIONS: Maternal antenatal active atopy may be a risk factor for the development of ADHD-like symptoms, especially among girls.

Prenatal cortisol modifies the association between maternal trauma history and child cognitive development in a sex-specific manner in an urban pregnancy cohort.

Women's experience of trauma may cause lifelong alterations in physiological stress regulation, which can be transmitted to offspring in utero. We investigated, in a prospective pregnancy cohort, associations among maternal lifetime interpersonal trauma (IPT) history, prenatal cortisol dysregulation, and children's memory domains. Sex-specific effects were also explored. Pregnant women were enrolled from Brigham & Women's Hospital and affiliated clinics near Boston, MA, in 2002-2007. IPT was assessed with the Revised Conflict Tactics Scale, short form. Salivary cortisol was measured at five time points on each of three days in one week at 29.0 ± 5.1 weeks gestation, and morning rise and diurnal slope were calculated. The Wide Range Assessment of Memory & Learning, 2nd Edition was administered at 6.5 ± 1.0 years and scores were generated for general memory and three sub-domains: verbal, visual, and attention/concentration. In total, 258 maternal-child dyads provided memory and IPT and/or cortisol data. IPT was positively associated with verbal memory in boys (ß ± SE: 4.6 ± 2.6) and inversely associated with visual memory score in girls (-6.5 ± 3.2). IPT did not predict prenatal cortisol, but prenatal cortisol modified the association between IPT history and child memory in varying coefficient models allowing for non-linear effect modification. The strongest evidence of interaction was for visual memory in boys: IPT history was associated with poorer visual memory only in those with flatter prenatal diurnal slope (interaction p = .005). Maternal lifetime IPT that leads to prenatal HPA dysregulation may have consequences for child memory, more so than either trauma or elevated cortisol alone. Boys may be more vulnerable to effects. Sex- and timing-specific effects require further investigation.

Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems.

IMPORTANCE: Polycyclic aromatic hydrocarbons (PAH) are carcinogenic and neurotoxic combustion by-products commonly found in urban air. Exposure to PAH is disproportionately high in low income communities of color who also experience chronic economic stress. OBJECTIVE: In a prospective cohort study in New York City (NYC) we previously found a significant association between prenatal PAH exposure and Attention Deficit Hyperactivity Disorder (ADHD) behavior problems at age 9. Here, we have evaluated the joint effects of prenatal exposure to PAH and prenatal/childhood material hardship on ADHD behavior problems. MATERIALS AND METHODS: We enrolled nonsmoking African-American and Dominican pregnant women in New York City between 1998 and 2006 and followed their children through 9 years of age. As a biomarker of prenatal PAH exposure, PAH-DNA adducts were measured in maternal blood at delivery and were dichotomized at the limit of detection (to indicate high vs. low exposure). Maternal material hardship (lack of adequate food, housing, utilities, and clothing) was self-reported prenatally and at multiple time points through child age 9. Latent variable analysis identified four distinct patterns of hardship. ADHD behavior problems were assessed using the Conners Parent Rating Scale- Revised. Analyses adjusted for relevant covariates. RESULTS: Among 351 children in our sample, across all hardship groups, children with high prenatal PAH exposure (high adducts) generally had more symptoms of ADHD (higher scores) compared to those with low PAH exposure. The greatest difference was seen among the children with hardship persisting from pregnancy through childhood. Although the interactions between high PAH exposure and hardship experienced at either period ("persistent" hardship or "any" hardship) were not significant, we observed significant differences in the number of ADHD symptoms between children with high prenatal PAH exposure and either persistent hardship or any hardship compared to the others. These differences were most significant for combined high PAH and persistent hardship: ADHD Index (p < 0.008), DSM-IV Inattentive (p = 0.006), DSM-IV Hyperactive Impulsive problems (p = 0.033), and DSM-IV Index Total (p = 0.009). CONCLUSION: The present findings add to existing evidence that co-exposure to socioeconomic disadvantage and air pollution in early life significantly increases the risk of adverse neurodevelopmental outcomes. They suggest the need for multifaceted interventions to protect pregnant mothers and their children.

Ambient temperature, heat stress and fetal growth: A review of placenta-mediated mechanisms.

Pregnancy is increasingly considered a period of vulnerability for extreme heat exposure. Multiple lines of evidence support that heat stress is associated with placental insufficiency, poor fetal growth and decreased birth weight. In this narrative review, we first summarize evidence linking ambient temperature or experimentally-induced heat stress with fetal and placental growth outcomes in humans, ruminants and murine species. We then synthesize the literature on putative underlying biological pathways with a focus on the placenta. Reviewed mechanisms include: reduced uterine-placental blood flow, impaired supply of metabolic substrates to the fetus, activation of the maternal stress-response system, and disruption of other endocrine and immune system endpoints. Taken together, this body of evidence supports that exposure to extreme ambient heat likely has adverse consequences for placental development and function. However, research investigating placenta-mediated pathophysiological mechanisms in humans remains extremely limited.