In this study, the metabolic profiles of pregnant women in the first or second trimester with iodine deficiency significantly differed from those of pregnant women with adequate iodine nutrition. A total of 28 distinct metabolites were identified as potential markers for iodine deficiency in pregnant women. The impact of iodine deficiency on metabolic pathways and functions was discussed, providing valuable insights for the prevention and treatment strategies targeting iodine deficiency in pregnancy.
At the population level, iodine status is typically evaluated by the MUIC from spot urine samples [15]. However, at an individual level, spot urine iodine levels may not accurately reflect iodine status due to significant day-to-day and within-day variations in urine iodine concentrations [17–18]. Currently, 24-hour UIE is considered a quasi-reference standard for assessing individual-level iodine status because it reduces hydration-dependent variations in iodine excretion [16]. Nevertheless, collecting 24-hour urine samples can be challenging due to its elaborate procedure and potential lower compliance rates that could compromise data quality particularly in field studies. In this study, the excretion Angle was employed in this study to assess the dietary iodine intake of pregnant women, which provided a relatively scientific and accurate approach for individual iodine nutrition evaluation during pregnancy.
Studies investigating the impact of mild iodine deficiency during the first and second trimesters on offspring development have yielded inconsistent results, which can be attributed to numerous confounding factors or the relatively weak effect of mild iodine deficiency that might be overshadowed by other influential factors [19–21]. In our current study, no significant differences were observed in maternal thyroid function and birth outcomes between pregnant women with low UIE levels and those with normal UIE levels. Therefore, it can be concluded that the effects of mild iodine deficiency on both maternal thyroid function and offspring birth outcomes do not exhibit prominent manifestations in major phenotypes. However, a comprehensive analysis of small molecular metabolites present in pregnant women's blood samples revealed significant distinctions in metabolic profiles between individuals with iodine deficiency and sufficient nutrition, indicating underlying changes at a molecular level despite minimal discernible phenotypic differences.
In the current study, the expression of indoleacetaldehyde was significantly changed. Indoleacetaldehyde plays a pivotal role in the metabolic pathway of tryptophan. Empirical evidence suggests that tryptophan metabolism is implicated in the pathogenesis of depression and hyperactivity in pediatric populations [22–23]. During pregnancy, the metabolism of tryptophan also plays a pivotal role [24]. Zhao YJ’s study shown that tryptophan related metabolites were important in regulating endothelial function during pregnancy [25]. Lee’s study observed that higher plasma tryptophan concentrations were associated with a lower prevalence of poor sleep quality during pregnancy [26]. Ünüvar S’s study showed thyroid disorders may lead to changes in tryptophan degradation, neopterin production and catalase enzyme activities [27]. In our study, alterations in tryptophan metabolism were observed in pregnant women with iodine deficiency, suggesting a potential association between iodine deficiency and its impact on thyroid function, subsequently affecting tryptophan metabolism.
In addition, alterations were observed in the metabolism of arachidonic acid. Arachidonic acid plays a crucial role in fetal growth and development, particularly in the development and functioning of the fetal brain and retina [28]. Ghebremeskel’s study demonstrated reduced levels of arachidonic acid both in maternal serum and newborns born to diabetic mothers [29]. It is likely that lower level of arachidonic acid in the babies of diabetic mothers were reflection of the impair in placental transfer. In our study, arachidonic acid levels were also decreased in iodine deficient pregnant women, which was consistent with the trend of arachidonic acid changes in diabetic pregnant women.
The expression of many lipid-related substances changed in this study. Fatty acid metabolism have been found to affect on the proinflammatory properties and the aggregation of platelets [30–31]. A growing body of evidence suggests that essential fatty acids and their active metabolic byproducts play a crucial role in maintaining the structural and functional integrity of both the central nervous system. These metabolites may contribute to proper development of the nervous system while reducing the likelihood of preterm birth or low birth weight. Additionally, it is believed that several fatty acid could potentially enhance children's learning abilities and academic performance. The majority of brain growth occurs during fetal life, making this period particularly important for adequate nutrient intake [32–33]. The present study unveiled alterations in the fatty acid pathway among pregnant women in the iodine deficient group, indicating that iodine deficiency may potentially impact fetal neurointelligence development by disrupting fatty acid metabolism.
The findings in this study presented alterations in the tyrosine metabolism pathway. Iodine serves as an indispensable substrate for thyroid hormone synthesis, and thyroid hormone is intricately associated with tyrosine metabolism. The constituents required for synthesizing thyroid hormone encompass iodine and thyroglobulin, wherein thyroglobulin undergoes iodination at the tyrosine residue to produce thyroid hormone. Thus, iodine deficiency leads to changes in tyrosine metabolism.
Due to the limited availability of comprehensive epidemiological survey data, the precise impact of pentose and glucuronate interconversions during pregnancy remains uncertain. However, it is important to note that purine metabolism disorders often coexist with glucose and lipid metabolism disorders as integral components of metabolic syndrome [34–35].
There are certain limitations in this study. Firstly, due to the relatively short recruitment period and other factors, the sample size was comparatively small. Secondly, only a single measurement of 24-hour UIE was utilized instead of multiple collections over a 24-hour period. Thirdly, further validation on a larger external scale is required for the biomarkers used, and additional exploration is necessary to understand their biological roles.
In conclusion, although mild iodine deficiency during the first and second trimesters may not lead to overt adverse effects on pregnant women and their offspring, however, at the metabolic level, it could disrupt the metabolic profile of pregnant women and impact fetal development.