Fetal window of vulnerability to airborne polycyclic aromatic hydrocarbons on proportional intrauterine growth restriction

Abstract

Background: Although the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters.

Methods: In a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn.

Results: One natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (-3%, 95% Confidence Interval (CI), -5 to -0%), birthweight (-105 g, 95% CI, -188 to -22 g), and birth length (-0.78 cm, 95% CI, -1.30 to -0.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 μm/g, 95% CI, 1 to 5 μm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort.

Conclusion: PAH exposure appears to exert the greatest adverse effect on fetal growth during the first trimester. The present data support the need for the protection of pregnant women and the embryo/fetus, particularly during the earliest stage of pregnancy.

Figure 1. The observed and predicted individual gestational Σ8 c-PAH exposure using semi-parametric mixed effects model^a.

a. Black, open circle represents the observed concentration of Σ8 c-PAHs. Black line represents the pooled cohort mean during the entire monitoring period. Three persons were randomly selected to demonstrate estimated personal Σ8 c-PAHs exposure during her entire pregnancy period (in color). Based on the semi-parametric mixed effects model, Pearson's correlation coefficients between observed vs. predicted prenatal exposure were 0.91, 0.98 and 0.96 for the third, sixth and the eighth month.

Figure 2. Mixed Effects Model Estimated ln-unit Σ8 C-PAH Exposure and Their Effects on Fetal Growth Ratio.

The ln Σ8 c-PAHs effects on FGR was estimated as a mean effect per trimester-wise exposure and 95% confidence interval.

Figure 3. Semi-Parametric Mixed Model Estimated ln-Unit Σ8 C-PAH Exposure and Their Point-Wise Effects on Fetal Growth Ratio.

Exposure was estimated using semi-parametric mixed effects model. Figure shows continuous, point-wise effect throughout the trimester based on functional linear model. The bold line shows regression coefficient per natural-log (ln) unit exposure to airborne PAHs. The dotted lines show point-wise 95% confidence interval.

Figure 4. Mixed Effects Model Estimated ln-unit Σ8 C-PAH Exposure and Their Effects on Cephalization Index.

The ln Σ8 c-PAHs effects on the outcome was estimated as a mean effect per trimester-wise exposure and 95% confidence interval.

Figure 5. Semi-Parametric Mixed Model Estimated ln-Unit Σ8 C-PAH Exposure and Their Point-Wise Effects on Cephalization Index.

Exposure was estimated using semi-parametric mixed effects model. Figure shows continuous, point-wise effect throughout the trimester based on functional linear model. The bold line shows regression coefficient per natural-log (ln) unit exposure to airborne PAHs. The dotted lines show point-wise 95% confidence interval.

Figure 6. Mixed Effects Model Estimated ln-unit Σ8 C-PAH Exposure and Their Effects on Ponderal Index.

The ln Σ8 c-PAHs effects on the outcome was estimated as a mean effect per trimester-wise exposure and 95% confidence interval.