Air Pollution at Key Stages of Pregnancy Affects Fetal Thyroid

Nancy A. Melville

September 18, 2018

Exposure to pollution at key stages of pregnancy may result in significant increases in newborn total thyroxine (T4) concentrations, with early and mid-pregnancy found to be windows of risk, according to a new study.

The findings suggest that "exposure to high levels of air pollution in pregnancy may have subtle influences on the developing fetal thyroid gland and its subsequent function," senior author Carrie V. Breton, ScD, associate professor and director of the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) Center and Division of Environmental Health, University of Southern California, Los Angeles (USCLA), told Medscape Medical News.

However, she and her colleagues stress that the exact clinical implications remain unknown and more work is needed to fully untangle the potential health consequences.

One of the Few Studies to Examine Multiple Air Pollutants at the Same Time

For the study, published online September 14 in JAMA Network Open, by Caitlin G. Howe, PhD, also of the Division of Environmental Health at USCLA, and colleagues analyzed data on 2050 newborns included in the Children's Health Study who were born in Southern California between 1994 and 1997, and had information available on prenatal exposures to ambient pollution, including particulate matter, nitrogen dioxide, and ozone, as well as traffic-related air pollution.

Most participants were Hispanic (1202, 58.6%) or non-Hispanic white (638, 31.1%), while 66 (3.2%) were black and 144 (7.0%) were from other racial/ethnic groups.

Data on corresponding newborn heel-stick blood spot total thyroxine (TT4) measures — which include both free and protein-bound fractions of T4 — acquired from the California Department of Health revealed that for each 2-point increase in standard deviations (SD) of prenatal exposure to particulate matter levels with a diameter of less than 2.5 (PM diameter < 2.5 μm [PM2.5]), there was a significant increase in infants' TT4 concentrations of 1.2 μg/dL (95% CI, 0.5 - 1.8 μg/dL; P < .001).

With larger particulate matter exposure — a diameter less than 10 μm (PM10) — the corresponding newborn TT4 increase was 1.5 μg/dL (95% CI, 0.9 - 2.1 μg/dL; P < .001) per 2-point SD increase in exposure.

Prenatal exposures to the other pollutants, including ambient nitrogen dioxide and ozone and traffic-related pollutants, meanwhile werenot associated with newborn TT4, which Breton said was notable but not entirely unexpected.

"Very few studies have evaluated multiple air pollutants at the same time," she said. "But the different pollutants have different chemical properties, so it's not surprising that we might see different results."

Risks Differ Depending on Pollutant and Window of Exposure

When looking at whether exposure during certain stages of pregnancy was linked to neonatal thyroid risk, the authors found that the link between PM2.5 exposure and increased TT4 levels was limited to exposures occurring during months 3 to 7 of pregnancy, while the risk with PM10 was broader, seen with exposures from months 1 through 8 (P < .05 for each).

The higher risk during mid-pregnancy may be related to a critical stage of fetal thyroid development, the authors speculate.

"Because the fetus begins producing its own supply of T4 in mid-pregnancy, this may be a particularly vulnerable period for the developing thyroid gland," they say in the article.

Furthermore, the maternal thyroid gland, which changes dramatically during pregnancy, may also be especially vulnerable to exposures in mid-pregnancy, they add.

"It is therefore possible that alterations in maternal thyroid function may partially or fully explain the associations observed between particulate matter exposure and higher TT4 concentrations in newborns."

Finally, particle size in particulate matter could also play a role in the differing risk in windows of exposure.

"Discrepancies in the vulnerable windows identified for PM10 vs PM2.5 may be driven by differences in particle size, which affects deposition patterns in the airways, as well as particle composition," the authors explain.

"For example, in Southern California, certain crustal materials and trace elements are more abundant in coarse particulate matter, whereas metals and other toxicants derived from vehicular emissions tend to be more abundant in PM2.5, which could affect distinct aspects of thyroid gland development and function."

Indoor particulate matter pollution — notably tobacco smoke — has been shown to be associated with abnormal newborn thyroid measures, as have outdoor environmental toxicants including dioxins, biphenyls, heavy metals, and some pesticides.

In terms of ambient outdoor particulate matter pollution and newborn thyroid function, a previous smaller study (Environ Health Perspect. 2017;125:699-705) conducted with the Environmental Influence on Early Aging (ENVIRONAGE) birth cohort (n = 499), showed significant associations between exposure to PM2.5 in the third trimester and cord blood thyroid hormone concentrations.

However, that study did not look at exposure during other stages of pregnancy or at other air pollutants.

Key limitations of the current study include the fact that only TT4 measures were available for most participants, limiting the ability to examine other indicators of thyroid function, such as thyroxin-binding globulin (TBG) concentrations.

In addition, information on maternal thyroid function was not available; therefore, those women with hypo- or hyperthyroidism, which can have important clinical implications, could not be excluded.

"While the clinical significance of the PM-associated differences in newborn TT4 concentrations observed in this study...is currently unknown, even small differences in maternal thyroid function during pregnancy have been associated with reduced fetal growth and adverse effects on neurodevelopment," the authors explain

The study benefitted, however, from a large sample size that allowed for the detection of "relatively small, but highly significant, PM-associated differences in newborn TT4 concentrations after accounting for a large number of potential confounders and precision variables."

"Additional studies will be needed to assess the potential health consequences of PM-associated differences in newborn blood spot TT4 concentrations," they conclude.

The study received support from the National Institutes of Health (NIH). Co-author Frederick W. Lurmann has reported receiving grants from the NIH to Sonoma Technology, of which he is an employee and stockholder, during the conduct of the study.

JAMA Network Open. Published September 14, 2018. Abstract

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