Prenatal particulate air pollution and neurodevelopment in urban children: Examining sensitive windows and sex-specific associations

Abstract

Background: Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex.

Objectives: We implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter ≤ 2.5 μm (PM2.5) and children's neurodevelopment.

Methods: 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±0.98 years. 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.

Results: Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12 years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31-38 weeks with lower IQ, at 20-26 weeks gestation with increased OEs, at 32-36 weeks with slower HRT, and at 22-40 weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18-26 weeks with reduced VIM, at 12-20 weeks with reduced GM).

Conclusions: 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.

Keywords: Air pollution; Neurodevelopment; Particulate matter; Prenatal exposure; Sensitive windows; Sex-specific associations.

Figure 1. Sex-specific associations between weekly prenatal PM_2.5 levels over gestation and full-scale IQ

This figure demonstrates PM_2.5 exposure over pregnancy and full-scale IQ scores (WISC-IV) using distributed lag models assuming week-specific effects. Models were adjusted for maternal age, race, education, prenatal/postnatal maternal smoking, parity, and blood lead level at neurodevelopmental testing; child’s sex was adjusted in the model not stratified by sex. The y-axis represents the change in full-scale IQ percentile associated with a 10 μg/m³ increase in PM_2.5; the x- axis is gestational age in weeks. Lower IQ scores indicate less favorable functioning. Solid lines show the predicted change in the IQ percentile. Gray areas indicate 95% CIs. A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero.

Figure 2. Sex-specific associations between weekly prenatal PM_2.5 levels over gestation and attention domains

This figure demonstrates PM_2.5 exposure over pregnancy and attention domains (CPT-II) using distributed lag models assuming week-specific effects. Models were adjusted for maternal age, race, education, prenatal/postnatal maternal smoking, parity, and blood lead level at neurodevelopmental testing; child’s sex was adjusted in models not stratified by sex. The y-axis represents the change in attention domain score percentile associated with a 10 μg/m³ increase in PM_2.5; the x-axis is gestational age in weeks. Higher percentiles in attention domains indicate less favorable performance. Solid lines show the predicted change in each test score percentile. Gray areas indicate 95% CIs. A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero.

Figure 3. Sex-specific associations between weekly prenatal PM2.5 levels over gestation and memory domains

This figure demonstrates PM_2.5 exposure over pregnancy and memory domains (WRAML-2) using distributed lag models assuming week-specific effects. Models were adjusted for maternal age, race, education, prenatal/postnatal maternal smoking, parity, and blood lead level at neurodevelopmental testing; child’s sex was adjusted in models not stratified by sex. The y-axis represents the change in memory domain score percentile associated with a 10 μg/m³ increase in PM_2.5; the x-axis is gestational age in weeks. Lower percentiles in memory domains indicate less favorable performance. Solid lines show the predicted change in each test score percentile. Gray areas indicate 95% CIs. A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero.

Figure 4. Sex-specific associations between PM_2.5 exposure over gestation and attention domains and IQ: Comparing models based on levels averaged over pregnancy vs. identified sensitive windows

This figure demonstrates estimated sex-specific associations and 95% CIs between prenatal PM_2.5 levels and each attention related domain (CPT-II) and full-scale IQ (WISC-IV) percentiles, obtained from multivariate regression models in which the prenatal PM_2.5 levels were (A) averaged across the sensitive windows identified by DLMs as in Figures 1 and 2, and (B) averaged over gestation. Higher CPT-II measures (in percentiles) indicate more omission errors, slower HRT, and more variability in response time throughout the test (HRT-SE), whereas lower full-scale IQ (standardized IQ score) indicates poorer composite intellectual performance. Models were adjusted for maternal age, race, education, prenatal/postnatal maternal smoking, parity, and blood lead level at neurodevelopmental testing.

Figure 5. Sex-specific associations between PM_2.5 exposure over gestation and memory domains: Comparing models based on levels averaged over pregnancy vs. identified sensitive windows

This figure demonstrates estimated sex-specific associations and 95% CIs between prenatal PM_2.5 levels and each memory-related domain (WRAML-2) percentiles, obtained from multivariate regression models in which the prenatal PM_2.5 levels were (A) averaged across the sensitive windows identified by DLMs as in Figure 3, and (B) averaged over gestation. Lower percentiles of WRAML-2 measures indicate less favorable memory related performance. Models were adjusted for maternal age, race, education, prenatal/postnatal maternal smoking, parity, and blood lead level at neurodevelopmental testing.