Association between Iron Deficiency and Prevalence of Thyroid Autoimmunity in Pregnant and Non-Pregnant Women of Childbearing Age: A Cross-Sectional Study
Thyroid autoimmunity (TAI) is a significant health concern among women of reproductive age, particularly due to its association with adverse pregnancy outcomes. The role of essential minerals such as selenium and iron in thyroid function has been extensively studied. Iron deficiency (ID) has been shown to impair thyroid metabolism by reducing the activity of thyroid peroxidase (TPO), an enzyme critical for thyroid hormone synthesis. This impairment can lead to decreased levels of circulating thyroid hormones and reduced efficacy of iodine prophylaxis. Conversely, iron overload (IO) can induce oxidative stress and inflammatory changes, potentially exacerbating autoimmune processes. Despite these findings, the relationship between iron status and TAI has not been thoroughly investigated. This study aims to explore the association between iron nutritional status and the prevalence of TAI in pregnant women during the first trimester and non-pregnant women of childbearing age.
The study was conducted in Liaoning province, China, between 2012 and 2015, involving 7463 pregnant women in their first trimester and 2185 non-pregnant women of childbearing age. Participants were recruited from 19 grade-A tertiary hospitals, ensuring a diverse and representative sample. Exclusion criteria included multiple pregnancies, a history of thyroid or other chronic diseases, and the use of medications that could affect thyroid function. Serum samples were collected to measure levels of thyrotropin (TSH), free thyroxine (FT4), thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin (SF), and urinary iodine (UI). ID was defined as SF 150 mg/L. TPOAb-positive was defined as >34 U/mL, and TgAb-positive was defined as >115 U/mL.
The study found that the prevalence of isolated TPOAb-positive was significantly higher in women with ID compared to those without ID, both in pregnant and non-pregnant women (6.28% vs. 3.23% and 6.25% vs. 3.70%, respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in both groups (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241–3.591 for pregnant women; OR: 1.822, 95% CI: 1.011–3.282 for non-pregnant women). However, ID was not associated with isolated TgAb-positive in either group. IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive.
The study also observed that pregnant women had lower TSH and TPOAb levels but higher SF and FT4 levels compared to non-pregnant women. The prevalence of ID was lower in pregnant women than in non-pregnant women (5.15% vs. 11.72%). The level of FT4 was lower in the ID group but higher in the IO group compared to the control group in both pregnant and non-pregnant women. The median TSH levels were similar between the ID and control groups but lower in the IO group than in the control group in pregnant women.
Further analysis revealed that the prevalence of isolated TPOAb-positive increased with the severity of ID in pregnant women. Specifically, the prevalence was 11.76% in the severe ID group and 5.75% in the mild ID group, both significantly higher than the control group (3.23%). In non-pregnant women, the prevalence of isolated TPOAb-positive was 7.48% in the mild ID group, significantly higher than the control group (3.70%). No such dose-dependent relationship was observed for isolated TgAb-positive.
Multivariable logistic regression analysis confirmed that ID remained associated with isolated TPOAb-positive after adjusting for confounding parameters in both pregnant and non-pregnant women. Multilevel regression analysis, which accounted for the cluster effect of hospitals, yielded similar results. ID was not associated with isolated TgAb-positive in either group.
The findings suggest that ID is a significant factor associated with an increased prevalence of isolated TPOAb-positive in both pregnant and non-pregnant women of childbearing age. This association may be due to the impairment of TPO activity by ID, leading to increased TAI. The study did not find a similar association between ID and isolated TgAb-positive, nor did it find any association between IO and TAI.
The study has several strengths, including its large sample size, the measurement of both TPOAbs and TgAbs, and the control for iodine status and other potential confounders. However, it also has limitations. The cross-sectional design precludes the establishment of causality, and the study was conducted in an iodine-adequate area, limiting the generalizability of the findings to iodine-deficient or excessive regions. Additionally, the study did not measure soluble transferrin receptor (sTfR), which could have provided a more accurate assessment of total body iron.
In conclusion, this study highlights the significant association between ID and the prevalence of isolated TPOAb-positive in both pregnant and non-pregnant women of childbearing age. These findings underscore the importance of monitoring iron status in women of reproductive age to mitigate the risk of TAI and its associated adverse outcomes. Further prospective studies are needed to confirm these findings and explore the underlying mechanisms.
doi.org/10.1097/CM9.0000000000000409
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