Susceptible windows of exposure to fine particulate matter and fetal growth trajectories in the Spanish INMA (INfancia y Medio Ambiente) birth cohort

Abstract

While prior studies report associations between fine particulate matter (PM_2.5) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure. We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid- (12-20 weeks), and late (20-34 weeks) pregnancy were calculated. A spatio-temporal random forest model with back-extrapolation provided weekly PM_2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [β_cum, 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM_2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 μg/m³ in PM_2.5, adjusted for covariates. Weeks 1-6 [β_cum = -0.77%, 95%CrI (-1.07%, -0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [β_cum = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM_2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM_2.5 and EFW or AC trajectories in late pregnancy were not observed. PM_2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such associations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth.

Keywords: Air pollution; Fetal growth; PM(2.5); Susceptible windows.

Figure 1.. Associations between weekly prenatal PM_2.5 exposure (per 5 μg/m³ increase) and percentage change in estimated fetal weight, abdominal circumference, femur length, and biparietal diameter during (A) early (first 12 weeks of gestation), (B) mid- (12–20 weeks of gestation), and (C) late (20–34 weeks of gestation) pregnancy.

Models were adjusted for maternal age, maternal and paternal education, social class, cohabitation, pre-pregnancy BMI, parity, smoking and alcohol use during pregnancy, child’s birth season, fetal sex, and account for heterogeneity between regions. The x-axes represent gestational weeks, and the y-axes represent the percentage change in fetal growth. The solid lines represent the estimated values from the fitted distributed lag non-linear models, and the shaded areas represent 95% CrI around the estimate for each gestational week. The gestational weeks where the 95% CrI excludes null value (dotted horizontal line) were identified as susceptible windows of exposure.

Figure 2.. Associations between prenatal PM_2.5 exposure (per 5 μg/m³ increase) averaged across multi-week pregnancy periods and percentage change in (A) estimated fetal weight, (B) abdominal circumference, (C) femur length, and (D) biparietal diameter during early (first 12 weeks of gestation), mid- (12–20 weeks of gestation), and late (20–34 weeks of gestation) pregnancy, mutually adjusted for exposure during each period.

Models were adjusted for maternal age, maternal and paternal education, social class, cohabitation, pre-pregnancy BMI, parity, smoking and alcohol use during pregnancy, child’s birth season, fetal sex, and account for heterogeneity between regions. The y-axes represent the percentage change in fetal growth. The dotted horizontal lines represent the null value.