The influence of particulate air pollution on respiratory health starts in utero. Fetal lung growth and structural development occurs in stages; thus, effects on postnatal respiratory disorders may ...differ based on timing of exposure.
We implemented an innovative method to identify sensitive windows for effects of prenatal exposure to particulate matter with a diameter less than or equal to 2.5 μm (PM2.5) on children's asthma development in an urban pregnancy cohort.
Analyses included 736 full-term (≥37 wk) children. Each mother's daily PM2.5 exposure was estimated over gestation using a validated satellite-based spatiotemporal resolved model. Using distributed lag models, we examined associations between weekly averaged PM2.5 levels over pregnancy and physician-diagnosed asthma in children by age 6 years. Effect modification by sex was also examined.
Most mothers were ethnic minorities (54% Hispanic, 30% black), had 12 or fewer years of education (66%), and did not smoke in pregnancy (80%). In the sample as a whole, distributed lag models adjusting for child age, sex, and maternal factors (education, race and ethnicity, smoking, stress, atopy, prepregnancy obesity) showed that increased PM2.5 exposure levels at 16-25 weeks gestation were significantly associated with early childhood asthma development. An interaction between PM2.5 and sex was significant (P = 0.01) with sex-stratified analyses showing that the association exists only for boys.
Higher prenatal PM2.5 exposure at midgestation was associated with asthma development by age 6 years in boys. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms.
The impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex, and exposure dose and timing.
We prospectively examined associations between coexposure to ...prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5) and maternal stress and childhood asthma (n = 736).
Daily PM2.5 exposure during pregnancy was estimated using a validated satellite-based spatiotemporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE ≥ 3; low: NLE < 3). We used Bayesian distributed lag interaction models to identify sensitive windows for prenatal PM2.5 exposure on children's asthma by age 6 years, and determine effect modification by maternal stress and child sex.
Bayesian distributed lag interaction models identified a critical window of exposure (19-23 weeks' gestation, cumulative odds ratio, 1.15; 95% CI, 1.03-1.26; per interquartile range 1.7 μg/m3 increase in prenatal PM2.5 level) during which children concomitantly exposed to prenatal PM2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19-21 weeks' gestation; cumulative odds ratio, 1.28; 95% CI, 1.15-1.41; per interquartile range increase in PM2.5).
Prenatal PM2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress.
Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex.
We implemented ...innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter≤2.5μm (PM2.5) and children's neurodevelopment.
We assessed 267 full-term urban children's prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors OEs, commission errors CEs, hit reaction time HRT, and HRT standard error HRT-SE on the Conners' CPT-II), and memory (general memory GM index and its components — verbal VEM and visual VIM memory, and attention-concentration AC indices on the WRAML-2) assessed at age 6.5±0.98years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined.
Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31–38weeks with lower IQ, at 20–26weeks gestation with increased OEs, at 32–36weeks with slower HRT, and at 22–40weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18–26weeks with reduced VIM, at 12–20weeks with reduced GM).
Increased PM2.5 exposure in specific prenatal windows may be associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups.
•We used data-driven methods to objectively examine sensitive windows of prenatal PM2.5 on childhood neurodevelopment.•Our findings suggested sex-specific, time-dependent associations that may vary dependent on different cognitive domains.•A more definitive understanding of such sex-specific temporal associations may provide insights into underlying mechanisms.
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.
Exposure to maternal stress in utero negatively impacts cognitive and behavioral outcomes of children born at term. The neonatal intensive care unit (NICU) can be stressful for preterm infants during ...a developmental period corresponding to the third trimester of gestation. It is unknown whether stress in the NICU contributes to adverse neurodevelopment among NICU graduates. The aim was to examine the association between salivary cortisol and early neurodevelopment in preterm infants.
We examined the association between cortisol levels during the NICU hospitalization and subsequent performance on the NICU Network Neurobehavioral Scales (NNNS), estimating time-specific associations and considering sex differences.
Eight hundred and forty salivary cortisol levels were measured from 139 infants. Average cortisol levels were inversely associated with NNNS Regulation scores for both male and female infants (β = -0.19; 95% CI: -0.44, -0.02). Critical developmental windows based on postmenstrual age were identified, with cortisol measured <30 weeks PMA positively associated with Habituation and Lethargy scores (β = 0.63-1.04). Critical developmental windows based on chronological age were identified, with cortisol measured in the first week of life inversely associated with Attention score (β = -1.01 for females; -0.93 for males).
Stress in the NICU at specific developmental time points may impact early preterm infant neurodevelopment.
Stress in the neonatal intensive care unit can impact the neurodevelopmental trajectory of premature infants. The impact of stress is different at different points in development. The impact of stress is sexually dimorphic.
Air pollution is a well-known contributor to asthma. Air toxics are hazardous air pollutants that cause or may cause serious health effects. Although individual air toxics have been associated with ...asthma, only a limited number of studies have specifically examined combinations of air toxics associated with the disease. We geocoded air toxic levels from the US National Air Toxics Assessment (NATA) to residential locations for participants of our AiRway in Asthma (ARIA) study. We then applied Data-driven ExposurE Profile extraction (DEEP), a machine learning-based method, to discover combinations of early-life air toxics associated with current use of daily asthma controller medication, lifetime emergency department visit for asthma, and lifetime overnight hospitalization for asthma. We discovered 20 multi-air toxic combinations and 18 single air toxics associated with at least 1 outcome. The multi-air toxic combinations included those containing acrylic acid, ethylidene dichloride, and hydroquinone, and they were significantly associated with asthma outcomes. Several air toxic members of the combinations would not have been identified by single air toxic analyses, supporting the use of machine learning-based methods designed to detect combinatorial effects. Our findings provide knowledge about air toxic combinations associated with childhood asthma.
Background
Studies report associations between maternal mental health and adverse respiratory outcomes in children; however, the impact of timing and duration of maternal distress remains ...understudied. We sought to longitudinally examine associations between maternal depression and childhood asthma and wheeze, and explore sex differences.
Methods
Maternal depression (n = 601) was assessed using the Edinburgh Depression Scale questionnaire, dichotomized at a clinically relevant cutoff (>12) (a) during pregnancy, (b) postpartum, and (c) postpartum and subsequent time points postnatally (recurrent depression). Report of wheeze in the past 12 months (current wheeze) and asthma were obtained using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire at 48 and 72 months. Associations were analyzed using a modified Poisson regression adjusted for covariates, and in interaction models.
Results
Both postpartum and recurrent depression were associated with higher risk of current wheeze (relative risk RR: 1.87, 95% confidence interval CI: 1.21, 2.90; RR: 2.41, 95% CI: 1.53, 3.79) and asthma at 48 months (RR: 2.42, 95% CI: 1.01, 5.84; RR: 2.45, 95% CI: 1.02, 5.84). In interaction analyses, associations were stronger in females. Recurrent depression was associated with a higher risk of current wheeze at 48 months in females (RR: 4.34, 95% CI: 2.02, 9.32) when compared to males (RR: 1.89, 95% CI: 1.05, 3.39).
Conclusions
Postpartum and recurrent depression were associated with a higher risk of wheeze and asthma in children. Understanding the temporal‐ and sex‐specific effects of maternal depression may better inform prevention strategies.
In utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere ...biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM2.5 effects and explore sex differences.
Women who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers’ prenatal exposure to PM2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models.
In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM2.5 exposure during early pregnancy (4–9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14–19 and 34–36 weeks in which increased PM2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM2.5 and shortened LTL were stronger in girls when compared to boys.
Increased PM2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.
•Examined sensitive windows of prenatal PM2.5 exposure on LTL in cord blood.•Sensitive window identified at gestational weeks 4–9, 14–19 and 34–36.•Findings suggest sex-specific associations.•PM2.5 more strongly associated with shortened LTL in girls compared to boys.
To evaluate associations between maternal lifetime traumatic stress and offspring birthweight and examine modifying effects of third trimester cortisol and fetal sex.
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.
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.
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.
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