Fetal Thyroid Function, Birth Weight, and in Utero Exposure to Fine Particle Air Pollution: A Birth Cohort Study

Abstract

Background: Thyroid hormones are critical for fetal development and growth. Whether prenatal exposure to fine particle air pollution (≤ 2.5 μm; PM_2.5) affects fetal thyroid function and what the impact is on birth weight in normal healthy pregnancies have not been studied yet.

Objectives: We studied the impact of third-trimester PM_2.5 exposure on fetal and maternal thyroid hormones and their mediating role on birth weight.

Methods: We measured the levels of free thyroid hormones (FT₃, FT₄) and thyroid-stimulating hormone (TSH) in cord blood (n = 499) and maternal blood (n = 431) collected after delivery from mother-child pairs enrolled between February 2010 and June 2014 in the ENVIRONAGE birth cohort with catchment area in the province of Limburg, Belgium.

Results: An interquartile range (IQR) increment (8.2 μg/m³) in third-trimester PM_2.5 exposure was inversely associated with cord blood TSH levels (-11.6%; 95% CI: -21.8, -0.1) and the FT₄/FT₃ ratio (-62.7%; 95% CI: -91.6, -33.8). A 10th-90th percentile decrease in cord blood FT₄ levels was associated with a 56 g decrease in mean birth weight (95% CI: -90, -23). Assuming causality, we estimated that cord blood FT₄ mediated 21% (-19 g; 95% CI: -37, -1) of the estimated effect of an IQR increment in third-trimester PM_2.5 exposure on birth weight. Third-trimester PM_2.5 exposure was inversely but not significantly associated with maternal blood FT₄ levels collected 1 day after delivery (-4.0%, 95% CI: -8.0, 0.2 for an IQR increment in third-trimester PM_2.5).

Conclusions: In our study population of normal healthy pregnancies, third-trimester exposure to PM_2.5 air pollution was associated with differences in fetal thyroid hormone levels that may contribute to reduced birth weight. Additional research is needed to confirm our findings in other populations and to evaluate potential consequences later in life.

Figure 1

Flow chart depicting the selection procedure of study participants from the ENVIRONAGE birth cohort, Limburg, Belgium.

Figure 2

Unadjusted correlation between third-trimester PM_2.5 exposure (μg/m³) and cord blood TSH (mU/L, log₁₀) levels (left) and the FT₄/FT₃ ratio (right).

Figure 3

Difference in cord and maternal blood thyroid hormones in association with third-trimester PM_2.5. The estimated relative difference in percentage (95% CI) is calculated for an IQR increment (8.2 μg/m³) in third-trimester PM_2.5 exposure. Panel A displays the difference in TSH (left) and the difference in FT₄/FT₃ ratio (right). Panel B displays the difference in FT₄ (left) and FT₃ (right). The cord blood models were adjusted for sex, gestational age, season of delivery, Apgar score, maternal age, prepregnancy BMI, smoking status, parity, ethnicity, maternal education, and third-trimester apparent temperature, whereas for maternal blood sex and Apgar score were excluded. *p < 0.05. **p < 0.01. ***p < 0.001.

Figure 4

Estimated proportion of the association between PM_2.5 exposure and birth weight (g) mediated by cord blood FT₄ levels. The figure displays cord blood FT₄ levels as mediator, the estimate of the indirect effect (IE), the estimate of the direct effect (DE), and the proportion of mediation (IE/DE + IE). The estimated effect is calculated for an IQR increment (8.2 μg/m³) in PM_2.5 exposure during the third trimester of pregnancy. The mediation model was adjusted for sex, gestational age, season of delivery, Apgar score, maternal age, prepregnancy BMI, smoking status, parity, ethnicity, maternal education, and third-trimester apparent temperature.