Introduction:
Ambient air pollution is a significant contributor to the global disease burden. During pregnancy, exposure to air pollutants like nitrogen dioxide (NO2), nitrogen oxides (NO), particulate matter (PM), and polycyclic aromatic hydrocarbons (PAHs) can lead to structural changes in the brain, impairs executive function, learning disabilities, and behavioral issues in offspring. These effects are influenced by oxidative stress, neuroinflammation, and disruption of the hypothalamus-pituitary-adrenal axis, with endocrine disruption possibly playing a role through PAH mechanisms affecting estrogen receptors. It may also disrupt thyroid signaling and function, affecting fetal thyroid development.
What Is the Thyroid Gland?
The thyroid gland is a butterfly-shaped organ in the neck responsible for secreting hormones that regulate metabolism, brain development, and overall growth. During pregnancy, the fetal thyroid gland begins to function during the first trimester but heavily relies on maternal thyroid hormones until it can produce its own. The thyroid gland produces two main hormones: thyroxine (T4) and triiodothyronine (T3), essential for average fetal growth and development. Any disruption to the thyroid's normal function during this delicate period can have far-reaching consequences for the developing fetus.
What Is the Importance of Thyroid Function in Pregnancy?
Thyroid function is crucial during pregnancy due to its essential role in fetal brain development. The fetal thyroid gland fully develops only from mid-gestation onwards. If thyroid insufficiency in pregnant women goes undetected or is not adequately controlled, it can negatively affect the growth and development of the fetus, even without causing neonatal hypothyroidism. Recent evidence proves that mild thyroid insufficiency, referred to as hypothyroxinemia, is characterized by low free thyroxine (T4) levels with normal thyrotropin (TSH) concentrations in pregnancy may contribute to impaired cognition and neurodevelopmental disorders in the offspring.
Thyroid imbalances during pregnancy can significantly affect both the mother and the baby. Hypothyroidism (low thyroid hormone levels) can lead to complications like preterm birth, preeclampsia, and developmental issues in the baby. On the other hand, hyperthyroidism (high thyroid hormone levels) can also cause complications such as premature birth and low birth weight.
What Is the Impact of Air Pollution on the Development of the Thyroid Gland in the Fetus?
Air Pollution and Its Components:
Air pollution comprises a mixture of harmful substances, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3), volatile organic compounds (VOCs), heavy metals, and polycyclic aromatic hydrocarbons (PAHs). Industrial processes, vehicular emissions, and burning fossil fuels mainly produce these pollutants.
When exposed to these pollutants, pregnant women can cross the placental barrier and reach the developing fetus.
The Impact of Air Pollution on Thyroid Development
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Disruption of Thyroid Hormone Synthesis: Certain air pollutants, such as PAHs and heavy metals, interfere with the synthesis of thyroid hormones, leading to imbalances in maternal and fetal thyroid hormone levels. These imbalances can potentially hinder fetal brain development and overall growth.
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Endocrine Disruption: Some air pollutants act as endocrine disruptors, which can interfere with the hormonal system. This disruption may affect the production and regulation of thyroid hormones, leading to adverse effects on fetal development.
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Inflammation and Oxidative Stress: Air pollutants trigger inflammation and oxidative stress in maternal and fetal tissues, including the placenta. These processes can further disrupt thyroid function and may have a cascading effect on fetal development.
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Epigenetic Changes: Prenatal exposure to air pollution can cause epigenetic changes in the fetus, altering the expression of genes involved in thyroid function. These changes may persist throughout life, potentially impacting the individual's thyroid health in the long term.
How Does Air Pollution Affect Thyroid Development in the Fetus?
Some studies investigated the link between airborne PM exposure and thyroid hormones in cord blood. Notably, they found an inverse association between PM2.5 exposure during the third trimester of pregnancy and TSH levels and the FT3 or FT4 ratio in cord blood. However, no such association was observed with thyroid hormones in maternal blood. The FT4/FT3 ratio in cord blood was identified as an indicator of T4 to T3 conversion efficiency. Moreover, mediation analysis suggested that cord blood FT4 partially mediated the link between PM2.5 exposure during the third trimester and birth weight. The results underscore the potential impact of early-life PM2.5 exposure on fetal thyroid function and growth.
During pregnancy, thyroid hormones are essential in regulating metabolism, promoting fetal growth and differentiation, and influencing neurocognitive development. Even though the fetus begins secreting small amounts of thyroid hormone starting mid-gestation, the mother supplies thyroid hormones to the fetal circulation right from the first trimester without compromising her levels. The increase in maternal thyroid hormones during the first trimester is crucial for ensuring normal neurological development. Both maternal T4 and T3 can cross the placenta, reaching concentrations in the fetus similar to those in adult tissues. Additionally, fetal T3 is produced locally from T4 by type 2 deiodinase, showing a strong affinity for nuclear binding sites in the placenta and stimulating factors that regulate trophoblast growth and development.
Thyroid hormones, specifically maternal T4 and T3, cross the placenta and reach fetal concentrations similar to those in adult tissues. Fetal T3 is locally produced from T4 by type 2 deiodinase, showing a strong affinity for nuclear binding sites in the placenta. This process stimulates factors that control trophoblast growth and development, indicating the vital role of thyroid hormones in normal development and fetal growth.
A study by Shields et al. on women with healthy pregnancies revealed a positive association between placental weight and cord blood Ft4 levels. They inferred that thyroid hormones might indirectly influence fetal growth by affecting placental development. In another study of pregnant women with no previous history of thyroid issues, researchers found that lower levels of FT4 in maternal blood were associated with increased placental growth. These findings indicate a potential difference in FT4 function between maternal and fetal blood, particularly concerning fetal growth.
The FT4 or FT3 ratio in cord blood, which indicates the body's ability to convert T4 into T3, was inversely associated with PM2.5 during pregnancy. This suggests that when T4 levels decrease, placental type 2 deiodinase activity increases as a homeostatic mechanism to maintain T3 production. Tobacco smoke constituents may stimulate the conversion of T4 to T3 by boosting type 2 deiodinase activity. Low TSH and FT4 levels may indicate central hypothyroidism, where the thyroid gland is normal but lacks sufficient stimulation by TSH for hormone synthesis.
What Precautions Should Be Taken to Protect Fetal Health?
Some precautions to protect fetal health include:
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Avoid exposure to Pollution Areas.
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Improve indoor air quality by using air purifiers and keeping windows closed during high pollution days.
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Opt for outdoor activities when pollution levels are lower, such as early or late evenings.
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Regular prenatal check-ups to monitor thyroid function and address any concerns promptly.
Conclusion:
Air pollution is an insidious threat that extends beyond respiratory health, potentially impacting fetal development during pregnancy. The thyroid gland's vital role in regulating fetal growth and metabolism makes it particularly susceptible to the effects of air pollution. Understanding the intricate relationship between air pollution and thyroid development is essential for safeguarding the health and well-being of future generations. As we strive to combat air pollution globally, it is crucial to prioritize measures that protect the most vulnerable members of society, including the developing fetus.
