# Iodine Status in Pregnant Women Having Urinary Fluoride in Contaminated Areas: A Case Study of Phayao Province

Authors: Rattawan Somporn; Chaipat Lapinee; Chanin Umponstira; Robbie Weterings; Sanhawat Chaiwong
Journal: Journal of Environmental and Public Health
 (2023)

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## Abstract

Fluoride naturally occurs in the Earth’s crust and is widely dispersed in groundwater. The high consumption of fluoride can inhibit iodine metabolism in the human body, especially in the thyroid gland. This study assessed iodine knowledge, iodine consumption behavior, urinary iodine (UI), thyroid stimulating hormone (serum TSH), and free triiodothyronine3 (serum FT3) and examined the connection between fluoride exposure and UI and thyroid function as serum concentrations of TSH and FT3 in pregnant women dwelling in an area of endemic fluorosis. This was a cross-sectional study. The population included 152 pregnant women within the 1st trimester of pregnancy, during which they were provided antenatal care (ANC) in seven public community hospitals in Phayao province, Thailand. The study consisted of two components. First, the study consisted of a questionnaire in which we evaluated the iodine knowledge and iodine consumptive behaviors in subjects. Second, biochemical data were investigated to evaluate thyroid function in the subjects. The gestational age of most subjects was 8–12 weeks. The study population has lived in fluoride-contaminated areas since birth (76.97%). The iodine and iodine consumption levels were moderate (50.00%). Their food iodine consumption was 3–4 days/week, and the top five consumption ranks were iodized salt, cooked pork, eggs, sticky rice, and iodine fish sauce. In terms of biochemical parameters, 63.16% of respondents had UI levels below 150.00 g/L, which is below the normal reference range of 150.00–249.00 g/L. 89.47% of the risk of hypothyroidism was associated with serum TSH levels below 2.50 g/L. In 38.16% of the samples, normal levels of serum FT3 (2.00–4.40 pg/L) were identified in the subjects. In addition, 61.84% of the samples had FT3 concentrations greater than 4.40 pg/L (high intake of iodine). The approved association between positive serum FT3 data and serum TSH was positive (r = 260 and p < 0.05). These studies imply that these elevated levels of TSH and FT3 place pregnant women in their first trimester at risk for hypothyroidism.


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## Body

## 1. Introduction

Water fluoridation has been used to reduce the incidence of dental cavities for nearly six decades. In more than 30 countries, people consume fluoridated water according to the Center for Disease Control and Prevention [1–5]. The primary route of human exposure to fluoride is through food and water, which causes health implications in fluoride-contaminated areas. For example, Tewarangsri et al. [6] found that the risks to health in fluoride-contaminated areas are elevated. The HRA in fluoride-contaminated locations when bottled water was consumed was greater than 1 (hazard quotient: HQ > 1), corresponding with other areas where fluoride-containing streams were traversed. The fluoride (F) concentrations in 10 brands of bottled drinking water marketed in Bushehr, Iran, were measured and compared to the amounts listed on the bottles [7]. The mean F concentration of the samples ranged from 0.00 to 0.37 mg/L [8].Despite clear dental health benefits, uncontrolled fluoride absorption is also correlated with poorer tooth development. The U.S. National Research Council (NRC) has studied the impact of fluoridation on children and pregnant women. The perinatal impact of fluoride and its impact on the offspring are controversial [9, 10]. The two most frequent coexisting endemic problems occur in particular territories in specific areas of India: iodine deficiency disorders (IDD) and symptoms of fluorosis [11, 12, 13]. Fluoride is observed to affect the performance of the thyroid gland and to generate a variation of regression in the organization of the central nervous system, including disability of brain activities and malfunction in children [14, 15]. Fluoride is more electronegative than iodine-displacing in vivo, which affects the thyroid gland and thyroid hormone levels [16, 17]. Additionally, fluoride inhibits deiodinase activity [18, 19] and inhibits Na/K-ATPase [20, 21]. Thyroid function has two significant enzymes: Na/K-ATPase supports the symporter performance of sodium-iodine in the thyroid gland, which subsequently eases the absorption of iodide by the thyroid gland [11, 22]. T3 from the removal of iodine in T4 is catalyzed by iodothyronine deiodinase. In addition, T3 incorporation may be diminished, resulting in the production of prolactin TSH, which limits thyroid iodine absorption by fluorine. As a result, both the secretion of T4 and the stimulating impact of exogenous THS are diminished [23–25]. Studies in this area have revealed that enhanced consumption of fluoride in drinking water causes changes in hormones related to thyroid function (TSH, T3, FT3, T4, FT4, and rT3) and adjustments in the actions of deiodinase enzymes [5, 26–28]. The intensifying application of fluoride content to arrest cavities raises the question of whether fluoride could inhibit the success of iodine prophylaxis [18, 29]. Fluoride is used to prevent tooth decay through its addition to drinking water, but increased fluoride intake over prolonged periods of time might lead to dental and skeletal fluorosis. Furthermore, it may prevent iodine absorption in the body [4, 18, 21, 28, 30].Iodine is required for a variety of in vivo processes, including the production of thyroid hormones [31, 32]. Fluoride can interfere with critical iodine absorption. Fluoride can disturb iodine development between the thyroid and mammary glands [33–35]. Swelling of the thyroid glands (goiter) can be found in cases of iodine deficiency. Swelling is the body’s attempt to elevate the uptake of iodine from the blood [36–38].Phayao province is one of the eighth provinces in the northern region of Thailand and is located at latitude: 19° 11′ 31.31″ N and longitude: 99° 52′ 43.79″ E. Fluoride is found in the environment and other parts of the world including China, India, Iran, Sri Lanka, Pakistan, and Thailand, especially the upper north of Thailand, which covers Chiang Mai, Lamphun, and Mae Hong Son and Phayao provinces located in the Chiang Mai Basin. The geological sources of fluorine include fluorine-bearing minerals such as fluorite (CaF2), cryolite (Na3AlF6), apatite (Ca5(PO4)3(F, Cl, OH)), and micas (AB2–3(X,Si)4O10(O, F, OH)2) [39–43]. Humans are exposed to fluoride ingestion by both nature and human activities [44, 45]. The concentrations of fluoride presenting in various ranges depend on the location such as the authors in [46] reported that fluoride presented in the soils (150.0–400.0 mg/kg), rocks (100.0–2000.0 mg/kg), plants (0.01–42.0 mg/kg), and water (1.0–38.5 mg/L) (G. [46]. In addition to affecting health through dental and skeletal fluorosis, it can also inhibit iodine absorption into the body. Fluoride-thyroid-iodine antagonism can inhibit iodine absorption. Furthermore, by affecting thyroid gland performance, fluoride has been recognized to cause both gross and biochemical changes within the bodies of human beings, together with disordered thyroid hormone levels [47, 48]. The health impacts of high fluoride exposure from food and drinking water affected the functioning of the thyroid gland, especially in pregnant women.The purpose of this study is to evaluate the UI, as well as the levels of serum FT3 and serum TSH, in order to better understand the correlations between UI, FT3, and TSH concentrations in pregnant women from an area with endemic fluorosis in the first trimester of pregnancy.


## 2. Methodology

### 2.1. Study Area and Population

In all, there were 152 pregnant women in the community who were receiving prenatal care throughout the first trimester of their pregnancies (ANC). A descriptive research study was conducted by us at nine community public hospitals located throughout nine districts in Phayao province, Thailand. These districts are as follows: (1) Mae Chai, (2) Muang, (3) DoKhamam Tai, (4) Chun, (5) Poo Kam Yao, (6) Pong, (7) Chaing Muan, (8) Poo Sang, and (9) Chaing Kam (as shown in Figure1). After the pregnant woman has received medical attention, the panel will introduce themselves and describe the state of fluoride contamination in the area as well as its fluoride effects on iodine and the effect of iodine deficiency on the fetus through both lectures and videos, as well as the benefits of participating in the research by allowing blood transfusions and urine collection to be tested for UI, serum FT3, and serum TSH, which will benefit pregnant women and fetuses. After that, it was requested that the expecting mother sign the consent form.Figure 1
The investigated area in Phayao province covered 9 districts in the north of Thailand.We selected participants based on the following criteria:(1)
Having urinary fluoride levels higher than 0.7 ppm(2)
Registration of the 1st trimester of pregnancy in a community hospital in Phayao province(3)
Living in Phayao province for more than 5 years


#### 2.1.1. Excluded Criteria

(1)
Renal disorder(2)
Women with hypothyroidism and hyperthyroidism who are pregnant(3)
Pregnant women with gastrointestinal illnesses that impair food absorption, such as celiac disease, atrophic gastritis, ulcerative colitis, and Crohn’s disease, and those who have had their stomachs or intestines amputated


### 2.2. Data Collection and Tools

The quality control of the questionnaire was analyzed using three panels, including the content validity index (CVI) (0.86), reliability was then analyzed to determine Cronbach’s alpha coefficient of 0.78, and item objective congruence (IOC) was evaluated by three panels which were selected in the range of 0.60–0.80. Then, a questionnaire was tried out by conducting surveys of 30 similar samples for and proved before use.The study consisted of two main parts, namely, a questionnaire and laboratory analysis.


#### 2.2.1. Survey Study

The tool was a questionnaire designed in three parts as follows.After obtaining each woman’s signature on an informed permission declaration, a questionnaire was employed to gather sociodemographic data as well as obstetric history from the women in the study.(1) Part 1: demographic data include age, gestational age, weight, height, number of pregnancies, education, location, and family members with thyroid disease.(2) Part 2 (knowledge of food iodine): the subjects surveyed the knowledge of iodine, including iodine in nature, necessary for iodine in pregnant women, health impact of deficiency, and overload of iodine. The questionnaire consisted of 15 items of closed-ended questions combined with negative and positive knowledge using a Likert scale. The correct answer was 1, and the incorrect answer is given in Table1.Table 1
The answer score given in terms of positive and negative knowledge.
AnswersScores for positive knowledgeScores for negative knowledgeCorrect10Incorrect01The criteria for evaluation were divided into 3 groups as shown in the following:(i)
Excellent knowledge was or higher than 12 items(ii)
Moderate knowledge was between 9 and 11 items(iii)
Poor knowledge was or lower than 8 items(3) Part 3 (behavioral consumption of iodine food in pregnant women): The pregnant women were interviewed about their iodine consumption behavior within a week by health staff working in health-promoting departments in the hospital. The food lists were set to relate the iodine content to (1). Natural iodine is a local plant, poultry, and animal meat, which are plants and farms in areas, (2) supplements supported by health ministry such as iodine-added water and iodine tablets, (3) commercial-iodine foods such as iodine-added fish sauce, daily food including instant noodles, etc., and (4) sea food. The food lists were checked under the condition of their behaviors and evaluated by frequency of consumption. After the interview on consumption behavior, the researchers evaluated and interpreted the consumption behaviors based on the data obtained from interviews with pregnant women and the consumption behavior criteria shown in Table2.Table 2
Consumptive behavior/intake frequency, scoring, and description for pregnant women based on dietary frequency, iodine water, and dietary supplements.
Consumptive behavior/intake frequencyScoresDescriptionMost consumption5Consuming food/supplement/iodine-added water every dayHigh consumption4Consuming food/supplement/iodine-added water around 5-6 days/weekFairy consumption3Consuming food/supplement/iodine-added water around 3-4 days/weekLess consumption2Consuming food/supplement/iodine-added water around 1-2 days/weekNo consumption1Never consume food/supplement/iodine-added water food in a weekTable3 summarizes the ranges for naturally occurring iodine, supplements backed by the health ministry, commercially produced foods, daily foods, and seafood, and interprets the ranges of scores for a pregnant woman’s intake.Table 3
Pregnant women’s average iodine consumption patterns, intakes, and interpretation.
RangesInterpretation3.41–5.00Good behavior/intake2.61–3.40Moderate behavior/intake1.00–2.60Poor behavior/intake


## 2.1. Study Area and Population

In all, there were 152 pregnant women in the community who were receiving prenatal care throughout the first trimester of their pregnancies (ANC). A descriptive research study was conducted by us at nine community public hospitals located throughout nine districts in Phayao province, Thailand. These districts are as follows: (1) Mae Chai, (2) Muang, (3) DoKhamam Tai, (4) Chun, (5) Poo Kam Yao, (6) Pong, (7) Chaing Muan, (8) Poo Sang, and (9) Chaing Kam (as shown in Figure1). After the pregnant woman has received medical attention, the panel will introduce themselves and describe the state of fluoride contamination in the area as well as its fluoride effects on iodine and the effect of iodine deficiency on the fetus through both lectures and videos, as well as the benefits of participating in the research by allowing blood transfusions and urine collection to be tested for UI, serum FT3, and serum TSH, which will benefit pregnant women and fetuses. After that, it was requested that the expecting mother sign the consent form.Figure 1
The investigated area in Phayao province covered 9 districts in the north of Thailand.We selected participants based on the following criteria:(1)
Having urinary fluoride levels higher than 0.7 ppm(2)
Registration of the 1st trimester of pregnancy in a community hospital in Phayao province(3)
Living in Phayao province for more than 5 years


### 2.1.1. Excluded Criteria

(1)
Renal disorder(2)
Women with hypothyroidism and hyperthyroidism who are pregnant(3)
Pregnant women with gastrointestinal illnesses that impair food absorption, such as celiac disease, atrophic gastritis, ulcerative colitis, and Crohn’s disease, and those who have had their stomachs or intestines amputated


## 2.1.1. Excluded Criteria

(1)
Renal disorder(2)
Women with hypothyroidism and hyperthyroidism who are pregnant(3)
Pregnant women with gastrointestinal illnesses that impair food absorption, such as celiac disease, atrophic gastritis, ulcerative colitis, and Crohn’s disease, and those who have had their stomachs or intestines amputated


## 2.2. Data Collection and Tools

The quality control of the questionnaire was analyzed using three panels, including the content validity index (CVI) (0.86), reliability was then analyzed to determine Cronbach’s alpha coefficient of 0.78, and item objective congruence (IOC) was evaluated by three panels which were selected in the range of 0.60–0.80. Then, a questionnaire was tried out by conducting surveys of 30 similar samples for and proved before use.The study consisted of two main parts, namely, a questionnaire and laboratory analysis.


### 2.2.1. Survey Study

The tool was a questionnaire designed in three parts as follows.After obtaining each woman’s signature on an informed permission declaration, a questionnaire was employed to gather sociodemographic data as well as obstetric history from the women in the study.(1) Part 1: demographic data include age, gestational age, weight, height, number of pregnancies, education, location, and family members with thyroid disease.(2) Part 2 (knowledge of food iodine): the subjects surveyed the knowledge of iodine, including iodine in nature, necessary for iodine in pregnant women, health impact of deficiency, and overload of iodine. The questionnaire consisted of 15 items of closed-ended questions combined with negative and positive knowledge using a Likert scale. The correct answer was 1, and the incorrect answer is given in Table1.Table 1
The answer score given in terms of positive and negative knowledge.
AnswersScores for positive knowledgeScores for negative knowledgeCorrect10Incorrect01The criteria for evaluation were divided into 3 groups as shown in the following:(i)
Excellent knowledge was or higher than 12 items(ii)
Moderate knowledge was between 9 and 11 items(iii)
Poor knowledge was or lower than 8 items(3) Part 3 (behavioral consumption of iodine food in pregnant women): The pregnant women were interviewed about their iodine consumption behavior within a week by health staff working in health-promoting departments in the hospital. The food lists were set to relate the iodine content to (1). Natural iodine is a local plant, poultry, and animal meat, which are plants and farms in areas, (2) supplements supported by health ministry such as iodine-added water and iodine tablets, (3) commercial-iodine foods such as iodine-added fish sauce, daily food including instant noodles, etc., and (4) sea food. The food lists were checked under the condition of their behaviors and evaluated by frequency of consumption. After the interview on consumption behavior, the researchers evaluated and interpreted the consumption behaviors based on the data obtained from interviews with pregnant women and the consumption behavior criteria shown in Table2.Table 2
Consumptive behavior/intake frequency, scoring, and description for pregnant women based on dietary frequency, iodine water, and dietary supplements.
Consumptive behavior/intake frequencyScoresDescriptionMost consumption5Consuming food/supplement/iodine-added water every dayHigh consumption4Consuming food/supplement/iodine-added water around 5-6 days/weekFairy consumption3Consuming food/supplement/iodine-added water around 3-4 days/weekLess consumption2Consuming food/supplement/iodine-added water around 1-2 days/weekNo consumption1Never consume food/supplement/iodine-added water food in a weekTable3 summarizes the ranges for naturally occurring iodine, supplements backed by the health ministry, commercially produced foods, daily foods, and seafood, and interprets the ranges of scores for a pregnant woman’s intake.Table 3
Pregnant women’s average iodine consumption patterns, intakes, and interpretation.
RangesInterpretation3.41–5.00Good behavior/intake2.61–3.40Moderate behavior/intake1.00–2.60Poor behavior/intake


## 2.2.1. Survey Study

The tool was a questionnaire designed in three parts as follows.After obtaining each woman’s signature on an informed permission declaration, a questionnaire was employed to gather sociodemographic data as well as obstetric history from the women in the study.(1) Part 1: demographic data include age, gestational age, weight, height, number of pregnancies, education, location, and family members with thyroid disease.(2) Part 2 (knowledge of food iodine): the subjects surveyed the knowledge of iodine, including iodine in nature, necessary for iodine in pregnant women, health impact of deficiency, and overload of iodine. The questionnaire consisted of 15 items of closed-ended questions combined with negative and positive knowledge using a Likert scale. The correct answer was 1, and the incorrect answer is given in Table1.Table 1
The answer score given in terms of positive and negative knowledge.
AnswersScores for positive knowledgeScores for negative knowledgeCorrect10Incorrect01The criteria for evaluation were divided into 3 groups as shown in the following:(i)
Excellent knowledge was or higher than 12 items(ii)
Moderate knowledge was between 9 and 11 items(iii)
Poor knowledge was or lower than 8 items(3) Part 3 (behavioral consumption of iodine food in pregnant women): The pregnant women were interviewed about their iodine consumption behavior within a week by health staff working in health-promoting departments in the hospital. The food lists were set to relate the iodine content to (1). Natural iodine is a local plant, poultry, and animal meat, which are plants and farms in areas, (2) supplements supported by health ministry such as iodine-added water and iodine tablets, (3) commercial-iodine foods such as iodine-added fish sauce, daily food including instant noodles, etc., and (4) sea food. The food lists were checked under the condition of their behaviors and evaluated by frequency of consumption. After the interview on consumption behavior, the researchers evaluated and interpreted the consumption behaviors based on the data obtained from interviews with pregnant women and the consumption behavior criteria shown in Table2.Table 2
Consumptive behavior/intake frequency, scoring, and description for pregnant women based on dietary frequency, iodine water, and dietary supplements.
Consumptive behavior/intake frequencyScoresDescriptionMost consumption5Consuming food/supplement/iodine-added water every dayHigh consumption4Consuming food/supplement/iodine-added water around 5-6 days/weekFairy consumption3Consuming food/supplement/iodine-added water around 3-4 days/weekLess consumption2Consuming food/supplement/iodine-added water around 1-2 days/weekNo consumption1Never consume food/supplement/iodine-added water food in a weekTable3 summarizes the ranges for naturally occurring iodine, supplements backed by the health ministry, commercially produced foods, daily foods, and seafood, and interprets the ranges of scores for a pregnant woman’s intake.Table 3
Pregnant women’s average iodine consumption patterns, intakes, and interpretation.
RangesInterpretation3.41–5.00Good behavior/intake2.61–3.40Moderate behavior/intake1.00–2.60Poor behavior/intake


## 3. Laboratory Investigation

### 3.1. Urinary Iodine Determination

Urine specimens were collected from expectant women who were patients at a community governor hospital in Phayao province, Thailand. To process urine samples, a 96-well polypropylene microplate was used to carry out the sample preparation process by thermal digestion using an oven with a high standard (ST-450 drying oven, Shibata Scientific Technology Japan). During later steps of the digestion process, corresponding polystyrene 96-well microplates were utilized for urine transference. The mixing solution for the reaction mixture was incubated for 30 min at 250°C, and the absorbance signal was measured at a wavelength of 405 nm using a microplate reader.


### 3.2. FT3 and TSH Analysis

Serum samples were harvested from all cases by centrifugation (at 3000 rpm for 10 minutes at room temperature) of specimens accumulated after storage during overnight fasting and kept at −4°C until examination. FT3 and TSH levels were assessed using an electrochemiluminescence immunoassay (ECLIA) using an Elecsys 2010 analyzer (Hitachi Ltd., Tokyo, Japan). The typical range was 2.00–4.40 pg/ml for FT3 and 0.27–4.20μIU/ml for TSH. The dissimilarity coefficients of intraassay and interassay were found to be 3.3 and 5.1% for FT3 and 8.6 and 8.7% for TSH. The sensitivity of the lower limit has been found at 0.26 pg/ml for FT3 and 0.005 μIU/ml for TSH.


#### 3.2.1. Analysis of the Test Results

We employed descriptive statistics for analysis, including frequency, percentage, and mean. The reference intervals for the tested hormones were determined to be between the 2.5% and 97.5% empirical percentiles. We assessed any associations between TSH, FT3, and UI using the Pearson product-moment correlation coefficient (r) at the 0.05 confident level (p < 0.05) for the laboratory data. A computer program analyzed the data automatically.


## 3.1. Urinary Iodine Determination

Urine specimens were collected from expectant women who were patients at a community governor hospital in Phayao province, Thailand. To process urine samples, a 96-well polypropylene microplate was used to carry out the sample preparation process by thermal digestion using an oven with a high standard (ST-450 drying oven, Shibata Scientific Technology Japan). During later steps of the digestion process, corresponding polystyrene 96-well microplates were utilized for urine transference. The mixing solution for the reaction mixture was incubated for 30 min at 250°C, and the absorbance signal was measured at a wavelength of 405 nm using a microplate reader.


## 3.2. FT3 and TSH Analysis

Serum samples were harvested from all cases by centrifugation (at 3000 rpm for 10 minutes at room temperature) of specimens accumulated after storage during overnight fasting and kept at −4°C until examination. FT3 and TSH levels were assessed using an electrochemiluminescence immunoassay (ECLIA) using an Elecsys 2010 analyzer (Hitachi Ltd., Tokyo, Japan). The typical range was 2.00–4.40 pg/ml for FT3 and 0.27–4.20μIU/ml for TSH. The dissimilarity coefficients of intraassay and interassay were found to be 3.3 and 5.1% for FT3 and 8.6 and 8.7% for TSH. The sensitivity of the lower limit has been found at 0.26 pg/ml for FT3 and 0.005 μIU/ml for TSH.


### 3.2.1. Analysis of the Test Results

We employed descriptive statistics for analysis, including frequency, percentage, and mean. The reference intervals for the tested hormones were determined to be between the 2.5% and 97.5% empirical percentiles. We assessed any associations between TSH, FT3, and UI using the Pearson product-moment correlation coefficient (r) at the 0.05 confident level (p < 0.05) for the laboratory data. A computer program analyzed the data automatically.


## 3.2.1. Analysis of the Test Results

We employed descriptive statistics for analysis, including frequency, percentage, and mean. The reference intervals for the tested hormones were determined to be between the 2.5% and 97.5% empirical percentiles. We assessed any associations between TSH, FT3, and UI using the Pearson product-moment correlation coefficient (r) at the 0.05 confident level (p < 0.05) for the laboratory data. A computer program analyzed the data automatically.


## 4. Results

### 4.1. Demographic Characteristics

In Table4, the median age ranged between 26.01 and 35.11 years (46.05%), the most common gestational status was 8.10 to 12.00 weeks (64.47%), the median weight ranged between 45.01 and 56.00 kilograms (42.11%), and the median height ranged between 151.00 and 160.00 cm (60.52%). BMI indicates a healthy weight range (18.5–24.9) (59.21%). Most women were pregnant for the first time (40.13%), subjects had a secondary school education on average (63.82%), respondents resided in fluoride-contaminated areas (76.97%), and nine of the subjects had a family history of thyroid disease (5.92%).Table 4
Demographic characteristics and according to thyroid disease family and pregnancy (N = 152).
VariablesN(%)(a) Age(1) <16.00 years old63.95(2) 16.01–26.00 years old6442.11(3) 26.01–35.11 years old7046.05(4) >35.01 years old127.89(b) Gestational age (weeks)(1) 0.10–4.00 weeks21.32(2) 4.10–8.00 weeks5234.21(3) 8.10–12.00 weeks9864.47(c) Weight (kilograms)(1) <45.00 kilograms3623.68(2) 45.01–56.00 kilograms6442.11(3) 57.01–68.00 kilograms3925.66(4) 69.01–80.00 kilograms95.92(5) >80.00 kilograms42.63(d) Height (centimeters)(1) 141.00–150.00 centimeters3019.74(2) 151.00–160.00 centimeters9260.52(3) 161.00–170.00 centimeters3019.74(e) Body mass index: BMIUnderweight (less than 18.5)2919.08Healthy weight (18.5–24.9)9059.21Over weight (25.0–29.9)2818.42Obese (30.0 or higher)53.29(f) Number of pregnancies(1) The 1st pregnancy6140.13(2) The 2nd pregnancy5938.82(3) The 3rd pregnancy2214.47(4) The 4th pregnancy74.61(5) The 5th pregnancy31.97(g) Education(1) No formal education74.61(2) Primary school1811.84(3) Secondary school9763.82(5) High school diploma85.26(6) Bachelor’s degree1912.50(7) Higher than bachelor’s31.97(h) Location(1) Same since birth11776.97(2) Subjects having migrated3523.03<1.00 year ago38.571.01–3.00 years ago1131.433.01–5.00 years ago1028.57>5.01 years ago1131.43(i) Thyroid disease in subjects’ family history(1) None14394.08(2) Some family history95.92(1) Only 1 person666.67(2) >1 person333.33


### 4.2. Iodine Knowledge

Table5 shows that the highest iodine-knowledge levels of all pregnant women were moderate (51.31%), followed by good (38.16%), and finally poor (10.53%).Table 5
Pregnant women’s iodine-knowledge levels, proportions, and interpretation (N = 152).
Scores of the iodine-knowledge levelN (%)Interpretation16–2058 (38.16)Good iodine-knowledge12–1578 (51.31)Moderate iodine-knowledge<1216 (10.53)Poor iodine-knowledge


### 4.3. Consumptive Iodine Behaviour

Table6 displays the iodine consumption behavior of pregnant women. The most common frequency of food iodine consumption was 3-4 days/week (50%), followed by 5–7 days/week (28.95%), and at least 1-2 days/week (21.05%), respectively.Table 6
Behavior, proportion, and interpretation of iodine intake/consumption in pregnant women (N = 152).
Iodine intake/consumptionN (%)Interpretation5–7 days/week of intake/consumption44 (28.95)Good behavior3-4 days/week of intake/consumption76 (50.00)Moderate behavior1-2 days/week of intake/consumption32 (21.05)Poor behavior


### 4.4. Types of Iodine Consumption

The sources of iodine consumed by pregnant women are listed in Table7. Iodized salt (mean = 2.59), cooked pork (mean = 2.53), eggs (mean = 2.50), sticky rice (mean = 2.47), and iodine fish sauce (mean = 2.45) were the five most popular iodine sources. Mullet (mean = 0.95), canned salmon (mean = 0.86), hand-baked rice (mean = 0.82), oysters (mean = 0.81), and sushi wrapped in seaweed (mean = 0.74) were the sources of iodine least consumed by pregnant women.Table 7
Consumption of iodine sources, mean and standard deviation (SD), by pregnant women.
No.Types of iodine sourcesMeanSD1Iodized salt2.590.642Cooked pork2.530.603Egg2.500.594Sticky rice2.470.845Iodine fish sauce2.450.736Freshwater fish2.330.707Cooked chicken2.300.738Glutinous rice2.220.649Fruits2.180.6810Sea fish2.120.7111UHT milk2.040.7612Vegetables2.030.7513Broccoli1.990.7614Banana1.960.7215Pasteurize milk1.860.9216Strawberry1.830.6917Bread1.680.7218Iodized chicken/duck eggs1.670.9819Carrot1.640.7520Iodine instant noodle1.610.7321Ice cream1.600.6622Raw cabbage1.560.7323Cooked beef1.531.0724Cooked buffalo1.411.1325Chocolate milk1.390.8126Chinese radish1.370.7727Cauliflower1.360.7228Iodized tablets1.301.3429Corn1.220.7330Cooked duck1.181.0531Seaweed1.080.8132Canned tuna0.990.8033Drinking water with iodine0.980.9034Mullet0.950.9136Canned salmon0.860.8437Hand-baked rice0.820.7838Oyster0.810.7539Seaweed wrapped sushi0.740.86


### 4.5. Analysis of UI Results

In 96 cases included in Table8, iodine concentrations in urine were low (less than 150.00 g/L) (63.16%). In 29 cases (19.08%), iodine levels were within the normal range (150–249 g/L). Only 27 individuals (17.76%) had iodine concentrations above 500 g/L.Table 8
The range, prevalence, and interpretation of UIC in pregnant women (N = 152).
Ranges of UICN (%)Interpretation<150.00μg/L96 (63.16)Iodine deficiency150.00–249.00μg/L∗29 (19.08)Adequate iodine250.00–499.00μg/L27 (17.76)Excessive iodineMean = 138.66μg/L, geometric mean = 108.38 μg/L, median = 112.25, from minimum to maximum = 18.40–429.50 μg/L, subject UI levels, and 2.5th to 97.5th percentiles = 26.90–409.60 μg/L. ∗, the range of UI based on [23]; the range of UI than 150.00 μg/L in pregnant women may be insufficient. The range of UI in pregnant women between 150.00 and 249.00 μg/L is adequate. The iodine intake between 250.00 and 499.00 μg/L = iodine intake in pregnant women is more than adequate.


### 4.6. Analysis of TSH Results

The concentrations of serum TSH were, in 136 cases (89.47%), less than 2.50μg/L which is considered the normal range for blood TSH (Table 9). In 14 cases (9.21%), serum TSH was between 2.50–4.50 μg/L, the upper borderline for the risk of hypothyroidism. Two cases (1.32%) had serum TSH levels above 4.50 μg/L.Table 9
The range, frequency, and interpretation of pregnant women’s serum TSH (N = 152).
Range of serum TSHN (%)InterpretationSerum TSH less than 2.50μg/L136 (89.47)Hazard of hypothyroidismSerum TSH between 2.50 to 4.50μg/L∗14 (9.21)NormalSerum TSH higher than 4.50μg/L2 (1.32)Hazard to hyperthyroidismMean = 1.37μg/L, geometric mean = 0.89 μg/L, median = 1.12, and minimum to maximum = 0.01–5.54 μg/L. Subject serum TSH levels from 2.5th–97.5th percentile: 0.03–4.24 μg/L. ∗, the range of serum TSH based on [24]; the range of serum TSH is less than 2.50 μg/L = and iodine consumption in pregnant women should be increased. The range of serum TSH is between 2.50 and 4.50 μg/L = and iodine consumption in pregnant women is regular. The range of serum TSH is higher than 4.50 μg/L = and the iodine consumption in pregnant women should be reduced.


### 4.7. Analysis of FT3 Results

In Table10, serum FT3 concentrations in 58 cases ranged between 2.0 and 4.4 pg/mL (38.16%), indicating normal intake, and in 94 cases (61.84%), high intake of iodine is there. The median serum FT3 concentration was 4.72 g/L, while the 2.5th and 97.25th percentile concentrations were 3.82 and 13.82 g/L, respectively.Table 10
The range, frequency, and interpretation of pregnant women’s serum FT3 (N = 152).
Ranges of serum FT3N (%)InterpretationSerum FT3 between 2.00 and 4.40 pg/ml∗58 (38.16)NormalSerum FT3 > 44094 (61.84)High intake of iodineMean = 5.10μg/L, geometric mean = 4.88 μg/L, median 4.72, and minimum to maximum: 3.56–21.17 μg/L. Subject FT3 levels from 2.5th to 97.5th percentiles: 3.82–13.82 μg/L. ∗, the range of serum FT3 based on [23]. The range of serum FT3 between 2.00 and 4.40 pg/L is normal. The range of serum FT3 more than 4.40 pg/L may be a sign of an overactive thyroid gland (hyperthyroidism).


### 4.8. Correlation among UI, Serum FT3, and Serum TSH

In Table11, correlations between UI and thyroid parameters were demonstrated. UI and serum FT3 obviously lack a significant negative correlation (r = −0.178 and p > 0.05), while UI and serum TSH lack a significant positive correlation (r = 0.209 and p > 0.05). There was a significant negative correlation (r = −0.260∗ and p < 0.05) between serum FT3 and serum TSH.Table 11
Correlations of UI, serum FT3, and serum TSH in pregnant women (N = 152).
CorrelationCorrelations between UI and thyroid parametersUISerum FT3Serum TSHUI1−0.1780.209Serum FT3−0.17810.260∗Serum TSH0.2090.260∗1∗p < .05.


## 4.1. Demographic Characteristics

In Table4, the median age ranged between 26.01 and 35.11 years (46.05%), the most common gestational status was 8.10 to 12.00 weeks (64.47%), the median weight ranged between 45.01 and 56.00 kilograms (42.11%), and the median height ranged between 151.00 and 160.00 cm (60.52%). BMI indicates a healthy weight range (18.5–24.9) (59.21%). Most women were pregnant for the first time (40.13%), subjects had a secondary school education on average (63.82%), respondents resided in fluoride-contaminated areas (76.97%), and nine of the subjects had a family history of thyroid disease (5.92%).Table 4
Demographic characteristics and according to thyroid disease family and pregnancy (N = 152).
VariablesN(%)(a) Age(1) <16.00 years old63.95(2) 16.01–26.00 years old6442.11(3) 26.01–35.11 years old7046.05(4) >35.01 years old127.89(b) Gestational age (weeks)(1) 0.10–4.00 weeks21.32(2) 4.10–8.00 weeks5234.21(3) 8.10–12.00 weeks9864.47(c) Weight (kilograms)(1) <45.00 kilograms3623.68(2) 45.01–56.00 kilograms6442.11(3) 57.01–68.00 kilograms3925.66(4) 69.01–80.00 kilograms95.92(5) >80.00 kilograms42.63(d) Height (centimeters)(1) 141.00–150.00 centimeters3019.74(2) 151.00–160.00 centimeters9260.52(3) 161.00–170.00 centimeters3019.74(e) Body mass index: BMIUnderweight (less than 18.5)2919.08Healthy weight (18.5–24.9)9059.21Over weight (25.0–29.9)2818.42Obese (30.0 or higher)53.29(f) Number of pregnancies(1) The 1st pregnancy6140.13(2) The 2nd pregnancy5938.82(3) The 3rd pregnancy2214.47(4) The 4th pregnancy74.61(5) The 5th pregnancy31.97(g) Education(1) No formal education74.61(2) Primary school1811.84(3) Secondary school9763.82(5) High school diploma85.26(6) Bachelor’s degree1912.50(7) Higher than bachelor’s31.97(h) Location(1) Same since birth11776.97(2) Subjects having migrated3523.03<1.00 year ago38.571.01–3.00 years ago1131.433.01–5.00 years ago1028.57>5.01 years ago1131.43(i) Thyroid disease in subjects’ family history(1) None14394.08(2) Some family history95.92(1) Only 1 person666.67(2) >1 person333.33


## 4.2. Iodine Knowledge

Table5 shows that the highest iodine-knowledge levels of all pregnant women were moderate (51.31%), followed by good (38.16%), and finally poor (10.53%).Table 5
Pregnant women’s iodine-knowledge levels, proportions, and interpretation (N = 152).
Scores of the iodine-knowledge levelN (%)Interpretation16–2058 (38.16)Good iodine-knowledge12–1578 (51.31)Moderate iodine-knowledge<1216 (10.53)Poor iodine-knowledge


## 4.3. Consumptive Iodine Behaviour

Table6 displays the iodine consumption behavior of pregnant women. The most common frequency of food iodine consumption was 3-4 days/week (50%), followed by 5–7 days/week (28.95%), and at least 1-2 days/week (21.05%), respectively.Table 6
Behavior, proportion, and interpretation of iodine intake/consumption in pregnant women (N = 152).
Iodine intake/consumptionN (%)Interpretation5–7 days/week of intake/consumption44 (28.95)Good behavior3-4 days/week of intake/consumption76 (50.00)Moderate behavior1-2 days/week of intake/consumption32 (21.05)Poor behavior


## 4.4. Types of Iodine Consumption

The sources of iodine consumed by pregnant women are listed in Table7. Iodized salt (mean = 2.59), cooked pork (mean = 2.53), eggs (mean = 2.50), sticky rice (mean = 2.47), and iodine fish sauce (mean = 2.45) were the five most popular iodine sources. Mullet (mean = 0.95), canned salmon (mean = 0.86), hand-baked rice (mean = 0.82), oysters (mean = 0.81), and sushi wrapped in seaweed (mean = 0.74) were the sources of iodine least consumed by pregnant women.Table 7
Consumption of iodine sources, mean and standard deviation (SD), by pregnant women.
No.Types of iodine sourcesMeanSD1Iodized salt2.590.642Cooked pork2.530.603Egg2.500.594Sticky rice2.470.845Iodine fish sauce2.450.736Freshwater fish2.330.707Cooked chicken2.300.738Glutinous rice2.220.649Fruits2.180.6810Sea fish2.120.7111UHT milk2.040.7612Vegetables2.030.7513Broccoli1.990.7614Banana1.960.7215Pasteurize milk1.860.9216Strawberry1.830.6917Bread1.680.7218Iodized chicken/duck eggs1.670.9819Carrot1.640.7520Iodine instant noodle1.610.7321Ice cream1.600.6622Raw cabbage1.560.7323Cooked beef1.531.0724Cooked buffalo1.411.1325Chocolate milk1.390.8126Chinese radish1.370.7727Cauliflower1.360.7228Iodized tablets1.301.3429Corn1.220.7330Cooked duck1.181.0531Seaweed1.080.8132Canned tuna0.990.8033Drinking water with iodine0.980.9034Mullet0.950.9136Canned salmon0.860.8437Hand-baked rice0.820.7838Oyster0.810.7539Seaweed wrapped sushi0.740.86


## 4.5. Analysis of UI Results

In 96 cases included in Table8, iodine concentrations in urine were low (less than 150.00 g/L) (63.16%). In 29 cases (19.08%), iodine levels were within the normal range (150–249 g/L). Only 27 individuals (17.76%) had iodine concentrations above 500 g/L.Table 8
The range, prevalence, and interpretation of UIC in pregnant women (N = 152).
Ranges of UICN (%)Interpretation<150.00μg/L96 (63.16)Iodine deficiency150.00–249.00μg/L∗29 (19.08)Adequate iodine250.00–499.00μg/L27 (17.76)Excessive iodineMean = 138.66μg/L, geometric mean = 108.38 μg/L, median = 112.25, from minimum to maximum = 18.40–429.50 μg/L, subject UI levels, and 2.5th to 97.5th percentiles = 26.90–409.60 μg/L. ∗, the range of UI based on [23]; the range of UI than 150.00 μg/L in pregnant women may be insufficient. The range of UI in pregnant women between 150.00 and 249.00 μg/L is adequate. The iodine intake between 250.00 and 499.00 μg/L = iodine intake in pregnant women is more than adequate.


## 4.6. Analysis of TSH Results

The concentrations of serum TSH were, in 136 cases (89.47%), less than 2.50μg/L which is considered the normal range for blood TSH (Table 9). In 14 cases (9.21%), serum TSH was between 2.50–4.50 μg/L, the upper borderline for the risk of hypothyroidism. Two cases (1.32%) had serum TSH levels above 4.50 μg/L.Table 9
The range, frequency, and interpretation of pregnant women’s serum TSH (N = 152).
Range of serum TSHN (%)InterpretationSerum TSH less than 2.50μg/L136 (89.47)Hazard of hypothyroidismSerum TSH between 2.50 to 4.50μg/L∗14 (9.21)NormalSerum TSH higher than 4.50μg/L2 (1.32)Hazard to hyperthyroidismMean = 1.37μg/L, geometric mean = 0.89 μg/L, median = 1.12, and minimum to maximum = 0.01–5.54 μg/L. Subject serum TSH levels from 2.5th–97.5th percentile: 0.03–4.24 μg/L. ∗, the range of serum TSH based on [24]; the range of serum TSH is less than 2.50 μg/L = and iodine consumption in pregnant women should be increased. The range of serum TSH is between 2.50 and 4.50 μg/L = and iodine consumption in pregnant women is regular. The range of serum TSH is higher than 4.50 μg/L = and the iodine consumption in pregnant women should be reduced.


## 4.7. Analysis of FT3 Results

In Table10, serum FT3 concentrations in 58 cases ranged between 2.0 and 4.4 pg/mL (38.16%), indicating normal intake, and in 94 cases (61.84%), high intake of iodine is there. The median serum FT3 concentration was 4.72 g/L, while the 2.5th and 97.25th percentile concentrations were 3.82 and 13.82 g/L, respectively.Table 10
The range, frequency, and interpretation of pregnant women’s serum FT3 (N = 152).
Ranges of serum FT3N (%)InterpretationSerum FT3 between 2.00 and 4.40 pg/ml∗58 (38.16)NormalSerum FT3 > 44094 (61.84)High intake of iodineMean = 5.10μg/L, geometric mean = 4.88 μg/L, median 4.72, and minimum to maximum: 3.56–21.17 μg/L. Subject FT3 levels from 2.5th to 97.5th percentiles: 3.82–13.82 μg/L. ∗, the range of serum FT3 based on [23]. The range of serum FT3 between 2.00 and 4.40 pg/L is normal. The range of serum FT3 more than 4.40 pg/L may be a sign of an overactive thyroid gland (hyperthyroidism).


## 4.8. Correlation among UI, Serum FT3, and Serum TSH

In Table11, correlations between UI and thyroid parameters were demonstrated. UI and serum FT3 obviously lack a significant negative correlation (r = −0.178 and p > 0.05), while UI and serum TSH lack a significant positive correlation (r = 0.209 and p > 0.05). There was a significant negative correlation (r = −0.260∗ and p < 0.05) between serum FT3 and serum TSH.Table 11
Correlations of UI, serum FT3, and serum TSH in pregnant women (N = 152).
CorrelationCorrelations between UI and thyroid parametersUISerum FT3Serum TSHUI1−0.1780.209Serum FT3−0.17810.260∗Serum TSH0.2090.260∗1∗p < .05.


## 5. Discussion

We found that the most population was the 1st pregnancy who had both moderate of food-iodine intake/consumption and knowledge. Furthermore, in the biochemical investigation of subjects, they had UI (<150 μg/L) which interpreted the iodine deficiency and serum TSH (<2.50 μg/L) which indicated that risk to hypothyroidism. In contrast with FT3, they had >4.40 pg/ml, showing a high iodine intake. The health impacts of high fluoride exposure from food and drinking water are affected by the functioning of the thyroid gland, especially in pregnant women, as follows:


### 5.1. Effect of Iodine on Pregnant Women

Fluoride is a halogen element (IIV halogen group) which has the highest electronegativity (EN = 4.0). Iodine in the body can be displaced by fluorine anions, as it is much lighter and consequently more active [1]. The activity of any one of the halogens is inversely proportional to its atomic weight. One halogen can consequently displace another with a higher atomic weight, although it cannot displace one of the lower weights. Fluoride discharge may therefore be a favorable indicator of human fluoride absorption [49]. Fluoride exposure has the potential to disrupt thyroid functioning, though adequate iodine intake may mitigate this effect. An investigation by [50] indicated that the median iodine levels in the urine of pregnant women decreased from 183.6 to 104.2 μg/L [50]. The result was satisfied because it is in range (150–249 μg/L) of adequate the iodine intake based on the World Health Organization (WHO)/United Nations International Children’s Emergency Fund (UNICEF)/International Council for Control of Iodine Deficiency Disorders (ICCIDD) recommended the following epidemiological criteria [51]. In contrast with our study, most participants (63.16%) with elevated fluoride levels (>0.7 ppm) had UI concentrations of less than 150.00 μg/L (Table 8). Lindorfer et al. [52], however, found a much lower median urinary iodine (UI) level of 87 μg/L in pregnant women in Vienna. Only 13.8% of this population was within the suggested range of 150–249 μg/L while 21.5% had UI concentrations of 0–49 μg/L, 40.2% had UI of 50–99 μg/L, and 19.5% had UI of 100–149 μg/L [52], whereas 4.9% of the studied population had an average UI over 250 μg/L. In a Japan study, Fuse et al. [53] showed a median concentration of iodine in the urine of pregnant women of 219.0 μg/L [53]. Symbiotic impacts of high levels of fluoride and inadequate iodine were detected in both animals [54, 55] and humans [18, 56, 57]. Fluoride is known to inhibit both deiodinase activity and Na/K-ATPase [36, 58]. Thyroid function is substantially supported by two enzymes. Na/K-ATPase supports the performance of the sodium iodide symporter, which helps in thyroidal iodide absorbency [22].


### 5.2. Effect of TSH

Fluoride prevents iodine acceptors in the thyroid and disposes of the feedback mechanism that controls the thyroid-pituitary axis and, consequently, results in enhanced levels of thyroid-stimulating hormone [59]. Overactivation of the TSH acceptor by fluoride may result in insensitivity to TSH acceptors [60]. TSH receptor inactivation can result in decreased thyroid hormone production in the thyroid gland. These effects can be the reasons for the thyroid hormone feedback loop to attain new equivalence, resulting in increased TSH levels [18, 60, 61]. Fluoride additionally inhibits pathways that are indirectly a part of this TSH feedback loop, as described in the following. Urinary fluoride levels were negatively correlated with the THS. The mechanism is associated with G-proteins, adenylyl cyclase, cAMP, and protein kinases. After TSH binds to its receptors, G-proteins are activated, which increases the activity of adenylyl cyclase [62, 63]. TSH is a polypeptide hormone that is commonly believed to exert its cellular effects by stimulating adenylyl cyclase. cAMP then binds to protein kinases, leading to the expression of genes involved in T3–T4 production [46]. Fluoride is a universal G-protein stimulator, and stimulation of particular G-proteins occurs because of the detrimental effect of fluoride, which deactivates the cell’s intake of the active thyroid hormone. Consequently, the thyroid control mechanism will be impaired. Fluoride interferes with TSH discharge from the pituitary gland to the lower thyroid gland output. [64] assessed TSH levels in the blood at 7 to 12 gestational weeks, and median concentrations of serum TSH were found at 1.5 μg/L (0.10–4.34) [36]. The frequency of subclinical hypothyroidism in pregnant women was 27.8% on the symptomatic criterion (TSH > 2.5 μg/L). This is greater than in our study, where 16% of the population showed levels above the 2.5 μg/L TSH reference range. Veltri et al. [65] compared thyroid autoimmunity among different groups and found that thyroid autoimmunity was significantly lower in the sub-Saharan group than in the North African and Caucasian groups (3.3, 8.6, and 11.1%; p < 0.001) [65]. The median value of TSH was significantly lower in the sub-Saharan and North African groups than in the Caucasian group (1.3, 1.4, and 1.5 μg/L; p > 0.006 and 0.014, respectively). Diéguez et al. [65] identified 416 women with positive TD screening (16.6%, 95% CI = 15.1% to 18.0%). Of these, 47 had overt hypothyroidism (1.9%), 90 had subclinical hypothyroidism (3.6%), 23 had overt hyperthyroidism (0.8%), 20 had subclinical hyperthyroidism (0.8%), and 236 had isolated hypothyroxinemia (9.4%). Applying a logistic regression model, age ≥30 years was not associated with a higher risk of TD (odds ratio: OR = 0.85 and 95% CI = 0.67–1.08) or hypothyroidism (OR = 0.72 and 95% CI = 0.50–1.06) [66].


### 5.3. Effect of Serum FT3

Elhaj et al. [67] compared the trend of median (5th–95th percentile) values of TSH in the 1st, 2nd, and 3rd trimester which was 1.164 IU/ml (0.08–2.18 IU/ml), 1.36 IU/ml (0.54–2.52 IU/ml), and 1.45 IU/ml (0.59–2.46 IU/ml), respectively, and median (5th–95th centile) values of FT3 4.64 nmol/l (3.84–6.56 nmol/l), 4.35 nmol/l (3.43–5.45 nmol/l), and 4.13 nmol/l (3.18–5.16 nmol/l) in the 1st, 2nd, and 3rd trimester of pregnant women, respectively [67]. But Ren et al. [68] gave the mean FT3 at gestational weeks 8–14 as 2.93 ± 0.40 ng/L (reference intervals in normal pregnant women = 2.90 (2.33–3.65 ng/L) and 1.28 (0.17–4.59 ng/L based on the 2.5–97.5 percentile range for the control group [68]. Ashoor et al. [69] showed that serum TSH levels in this group were reinforced, while their FT3 and FT4 levels decreased with gestational age and TSH and FT3 levels were reinforced [69].Saxena et al. [70] results: the mean age of the study subjects was found to be 23.76 ± 3.80, 24.05 ± 3.18, and 23.80 ± 3.25 years in the first, second, and third trimester, respectively. A total of 35% prevalence of thyroid dysfunction was found among pregnant women. Out of this, 24% had hypothyroidism, 1% had hyperthyroidism, and 10% had euthyroid hyperthyroxinemia. A significant negative correlation was found between BMI and T4 levels in the underweight category, and a significant positive correlation between BMI and total T3 in the third trimester was observed [70].Iodothyronine deiodinase catalyzes T3 from deiodination of T4 [71]. The resulting disruption from fluoride could lower T3 production and subsequently enhance TSH [72]. Fluoride also interferes with the process of thyroid iodine intake, lowers T4 secretion, and hinders the stimulation of exogenous TSH [28, 66, 73]. Increased ingestion in endemic fluoride areas can depress thyroid function hormones (TSH, T3, FT3, T4, FT4, and rT3) and the activities of deiodinase enzymes [74]. Among the three deiodinases, D1 is expressed in the thyroid gland along with the liver and kidney, D2 is located in the brain, pituitary gland, and skeletal muscle, and D3 is expressed in the brain, placenta, and fetal tissue. D1 activity in the liver and kidney is stimulated in hyperthyroidism and decreased in hypothyroidism as a result of the positive feedback of T3 on D1 production [66, 72]. As shown in Table 10, high iodine intake in pregnant women is present when serum FT3 is higher than 4.40 pg/mL). In fluoride-contaminated areas, women with high FT3 levels showed low D1 activity, indicating thyroid hypofunction [75].


### 5.4. Practical Implications and Recommendations

Singh et al. [76] reported significantly inhibited FT3 and TSH hormone levels with elevated fluoride levels in children [76]. The higher urine fluoride levels in first-trimester women may be associated with the higher fluoride levels found in fluoride-contaminated areas. The present study (Table 9) found that when serum TSH is lower than 2.50 μg/L, additional iodine should be supplemented. The activity of D2 was high because it is related to the pituitary gland, which stimulates the production of TSH. In addition, TSH stimulates thyroid gland hormone production in cases of deficiency or overload. These results are significant for D1 and D2 [71]. Clinch [77] suggested that iodide transport is inhibited by fluoride, resulting in impairment of iodide pump binding sites, thereby conceivably removing iodide and increasing TSH in the thyroid gland [77]. Utilizing the reference gaps of nonpregnant women for TSH, 10.6% of women were misclassified. The present study shows that thyroid disturbances, such as iodine insufficiency, may be caused by fluoride [78]. FT3 and TSH levels in the blood were significantly negatively correlated (r = −0.260∗ and p < 0.05).Ashoor et al. [69] determined the standard ranges of maternal serum TSH and FT3 at 11–13 weeks of gestation [69]. Pregnancies were antibody-negative, and group serum TSH was enhanced, while FT3 diminished with gestation. [79] found enhanced TSH levels in occupants of an endemic fluorosis area with sufficient iodine absorption [57]. Zulfiqar et al. [80] compared the [80] mean concentration of water fluoride (WF) in the sample group and control group. The biochemical parameters including urine fluoride (UF), serum fluoride (SF), free tetra-iodothyronine (FT4), free tri-iodothyronine (FT3), and thyroid stimulating hormone (TSH) were significantly elevated (p = 0.001) [80]. Similar results were also observed by Lindorfer et al. [52], who reported that maternal UI concentration was associated with positive serum TSH levels during pregnancy [70]. A remarkable distinction was not found in UI between both cases of subjects with positive correlation for thyroid autoantibodies and negative correlation for antibodies. High levels of TSH (>2.5 μg/L) might indicate hypothyroidism in pregnant women [81, 82]. Hypothyroidism, a disorder of the thyroid gland, has been identified as the destruction of thyroid function. Subclinical hypothyroidism is misindicated by high serum concentrations of TSH of 4.5–9.0 μg/L with regular triiodothyronine (T3) and thyroxine (T4) status [83, 84]. Nevertheless, TSH levels higher than 2.5 μg/L can increase the subclinical risk and the severity of clinical hypothyroidism. Moreover, “high normal” TSH levels of 2.0–4.0 μg/L and 2.5–4.5 μg/L related to hypocholesterolemia can increase the risk in metabolic syndrome [60, 85]. High levels of fluoride in drinking water can cause an increase in TSH concentrations [59]. Higher levels of fluoride in urine and levels of TSH have also been observed in children and teenagers from areas with endemic fluorosis [86, 87]. Our findings are in line with those published by Kheradpisheh et al. [59]. They found a positive correlation between fluoride in drinking water and TSH hormone around R2 = 0.85. Inadequate iodine can lead to decreased creation of thyroid hormones, as well as fluoride [59]. Harmful goitrogenic effects can be neutralized by sufficient iodine levels [5]. For our results, maternal UI corresponded to positive serum TSH levels during pregnancy. There was no significant difference in UI concentration between subjects with positive data for thyroid autoantibodies and those with negative data for antibodies.It is evident from Table7 that the average source of iodine intake by pregnant women was iodized salt, which may have a concentration greater or less than the standard for the pregnant woman’s body. However, the average of the second rank is primarily derived from conventional diets and noniodine-rich freshwater animals, which may cause iodine deficiency in pregnant women. Therefore, the relevant departments of the Ministry of Public Health should review the factors of fluoride exposure from the consumption of food, vegetables, fruits, and meat grown in contaminated soils, and fluoride in toothpaste, and provide knowledge and guidelines to staff about public health concerns about exposure to fluoride in excess of the body’s needs, as these directly impact health and the thyroid gland’s function.


## 5.1. Effect of Iodine on Pregnant Women

Fluoride is a halogen element (IIV halogen group) which has the highest electronegativity (EN = 4.0). Iodine in the body can be displaced by fluorine anions, as it is much lighter and consequently more active [1]. The activity of any one of the halogens is inversely proportional to its atomic weight. One halogen can consequently displace another with a higher atomic weight, although it cannot displace one of the lower weights. Fluoride discharge may therefore be a favorable indicator of human fluoride absorption [49]. Fluoride exposure has the potential to disrupt thyroid functioning, though adequate iodine intake may mitigate this effect. An investigation by [50] indicated that the median iodine levels in the urine of pregnant women decreased from 183.6 to 104.2 μg/L [50]. The result was satisfied because it is in range (150–249 μg/L) of adequate the iodine intake based on the World Health Organization (WHO)/United Nations International Children’s Emergency Fund (UNICEF)/International Council for Control of Iodine Deficiency Disorders (ICCIDD) recommended the following epidemiological criteria [51]. In contrast with our study, most participants (63.16%) with elevated fluoride levels (>0.7 ppm) had UI concentrations of less than 150.00 μg/L (Table 8). Lindorfer et al. [52], however, found a much lower median urinary iodine (UI) level of 87 μg/L in pregnant women in Vienna. Only 13.8% of this population was within the suggested range of 150–249 μg/L while 21.5% had UI concentrations of 0–49 μg/L, 40.2% had UI of 50–99 μg/L, and 19.5% had UI of 100–149 μg/L [52], whereas 4.9% of the studied population had an average UI over 250 μg/L. In a Japan study, Fuse et al. [53] showed a median concentration of iodine in the urine of pregnant women of 219.0 μg/L [53]. Symbiotic impacts of high levels of fluoride and inadequate iodine were detected in both animals [54, 55] and humans [18, 56, 57]. Fluoride is known to inhibit both deiodinase activity and Na/K-ATPase [36, 58]. Thyroid function is substantially supported by two enzymes. Na/K-ATPase supports the performance of the sodium iodide symporter, which helps in thyroidal iodide absorbency [22].


## 5.2. Effect of TSH

Fluoride prevents iodine acceptors in the thyroid and disposes of the feedback mechanism that controls the thyroid-pituitary axis and, consequently, results in enhanced levels of thyroid-stimulating hormone [59]. Overactivation of the TSH acceptor by fluoride may result in insensitivity to TSH acceptors [60]. TSH receptor inactivation can result in decreased thyroid hormone production in the thyroid gland. These effects can be the reasons for the thyroid hormone feedback loop to attain new equivalence, resulting in increased TSH levels [18, 60, 61]. Fluoride additionally inhibits pathways that are indirectly a part of this TSH feedback loop, as described in the following. Urinary fluoride levels were negatively correlated with the THS. The mechanism is associated with G-proteins, adenylyl cyclase, cAMP, and protein kinases. After TSH binds to its receptors, G-proteins are activated, which increases the activity of adenylyl cyclase [62, 63]. TSH is a polypeptide hormone that is commonly believed to exert its cellular effects by stimulating adenylyl cyclase. cAMP then binds to protein kinases, leading to the expression of genes involved in T3–T4 production [46]. Fluoride is a universal G-protein stimulator, and stimulation of particular G-proteins occurs because of the detrimental effect of fluoride, which deactivates the cell’s intake of the active thyroid hormone. Consequently, the thyroid control mechanism will be impaired. Fluoride interferes with TSH discharge from the pituitary gland to the lower thyroid gland output. [64] assessed TSH levels in the blood at 7 to 12 gestational weeks, and median concentrations of serum TSH were found at 1.5 μg/L (0.10–4.34) [36]. The frequency of subclinical hypothyroidism in pregnant women was 27.8% on the symptomatic criterion (TSH > 2.5 μg/L). This is greater than in our study, where 16% of the population showed levels above the 2.5 μg/L TSH reference range. Veltri et al. [65] compared thyroid autoimmunity among different groups and found that thyroid autoimmunity was significantly lower in the sub-Saharan group than in the North African and Caucasian groups (3.3, 8.6, and 11.1%; p < 0.001) [65]. The median value of TSH was significantly lower in the sub-Saharan and North African groups than in the Caucasian group (1.3, 1.4, and 1.5 μg/L; p > 0.006 and 0.014, respectively). Diéguez et al. [65] identified 416 women with positive TD screening (16.6%, 95% CI = 15.1% to 18.0%). Of these, 47 had overt hypothyroidism (1.9%), 90 had subclinical hypothyroidism (3.6%), 23 had overt hyperthyroidism (0.8%), 20 had subclinical hyperthyroidism (0.8%), and 236 had isolated hypothyroxinemia (9.4%). Applying a logistic regression model, age ≥30 years was not associated with a higher risk of TD (odds ratio: OR = 0.85 and 95% CI = 0.67–1.08) or hypothyroidism (OR = 0.72 and 95% CI = 0.50–1.06) [66].


## 5.3. Effect of Serum FT3

Elhaj et al. [67] compared the trend of median (5th–95th percentile) values of TSH in the 1st, 2nd, and 3rd trimester which was 1.164 IU/ml (0.08–2.18 IU/ml), 1.36 IU/ml (0.54–2.52 IU/ml), and 1.45 IU/ml (0.59–2.46 IU/ml), respectively, and median (5th–95th centile) values of FT3 4.64 nmol/l (3.84–6.56 nmol/l), 4.35 nmol/l (3.43–5.45 nmol/l), and 4.13 nmol/l (3.18–5.16 nmol/l) in the 1st, 2nd, and 3rd trimester of pregnant women, respectively [67]. But Ren et al. [68] gave the mean FT3 at gestational weeks 8–14 as 2.93 ± 0.40 ng/L (reference intervals in normal pregnant women = 2.90 (2.33–3.65 ng/L) and 1.28 (0.17–4.59 ng/L based on the 2.5–97.5 percentile range for the control group [68]. Ashoor et al. [69] showed that serum TSH levels in this group were reinforced, while their FT3 and FT4 levels decreased with gestational age and TSH and FT3 levels were reinforced [69].Saxena et al. [70] results: the mean age of the study subjects was found to be 23.76 ± 3.80, 24.05 ± 3.18, and 23.80 ± 3.25 years in the first, second, and third trimester, respectively. A total of 35% prevalence of thyroid dysfunction was found among pregnant women. Out of this, 24% had hypothyroidism, 1% had hyperthyroidism, and 10% had euthyroid hyperthyroxinemia. A significant negative correlation was found between BMI and T4 levels in the underweight category, and a significant positive correlation between BMI and total T3 in the third trimester was observed [70].Iodothyronine deiodinase catalyzes T3 from deiodination of T4 [71]. The resulting disruption from fluoride could lower T3 production and subsequently enhance TSH [72]. Fluoride also interferes with the process of thyroid iodine intake, lowers T4 secretion, and hinders the stimulation of exogenous TSH [28, 66, 73]. Increased ingestion in endemic fluoride areas can depress thyroid function hormones (TSH, T3, FT3, T4, FT4, and rT3) and the activities of deiodinase enzymes [74]. Among the three deiodinases, D1 is expressed in the thyroid gland along with the liver and kidney, D2 is located in the brain, pituitary gland, and skeletal muscle, and D3 is expressed in the brain, placenta, and fetal tissue. D1 activity in the liver and kidney is stimulated in hyperthyroidism and decreased in hypothyroidism as a result of the positive feedback of T3 on D1 production [66, 72]. As shown in Table 10, high iodine intake in pregnant women is present when serum FT3 is higher than 4.40 pg/mL). In fluoride-contaminated areas, women with high FT3 levels showed low D1 activity, indicating thyroid hypofunction [75].


## 5.4. Practical Implications and Recommendations

Singh et al. [76] reported significantly inhibited FT3 and TSH hormone levels with elevated fluoride levels in children [76]. The higher urine fluoride levels in first-trimester women may be associated with the higher fluoride levels found in fluoride-contaminated areas. The present study (Table 9) found that when serum TSH is lower than 2.50 μg/L, additional iodine should be supplemented. The activity of D2 was high because it is related to the pituitary gland, which stimulates the production of TSH. In addition, TSH stimulates thyroid gland hormone production in cases of deficiency or overload. These results are significant for D1 and D2 [71]. Clinch [77] suggested that iodide transport is inhibited by fluoride, resulting in impairment of iodide pump binding sites, thereby conceivably removing iodide and increasing TSH in the thyroid gland [77]. Utilizing the reference gaps of nonpregnant women for TSH, 10.6% of women were misclassified. The present study shows that thyroid disturbances, such as iodine insufficiency, may be caused by fluoride [78]. FT3 and TSH levels in the blood were significantly negatively correlated (r = −0.260∗ and p < 0.05).Ashoor et al. [69] determined the standard ranges of maternal serum TSH and FT3 at 11–13 weeks of gestation [69]. Pregnancies were antibody-negative, and group serum TSH was enhanced, while FT3 diminished with gestation. [79] found enhanced TSH levels in occupants of an endemic fluorosis area with sufficient iodine absorption [57]. Zulfiqar et al. [80] compared the [80] mean concentration of water fluoride (WF) in the sample group and control group. The biochemical parameters including urine fluoride (UF), serum fluoride (SF), free tetra-iodothyronine (FT4), free tri-iodothyronine (FT3), and thyroid stimulating hormone (TSH) were significantly elevated (p = 0.001) [80]. Similar results were also observed by Lindorfer et al. [52], who reported that maternal UI concentration was associated with positive serum TSH levels during pregnancy [70]. A remarkable distinction was not found in UI between both cases of subjects with positive correlation for thyroid autoantibodies and negative correlation for antibodies. High levels of TSH (>2.5 μg/L) might indicate hypothyroidism in pregnant women [81, 82]. Hypothyroidism, a disorder of the thyroid gland, has been identified as the destruction of thyroid function. Subclinical hypothyroidism is misindicated by high serum concentrations of TSH of 4.5–9.0 μg/L with regular triiodothyronine (T3) and thyroxine (T4) status [83, 84]. Nevertheless, TSH levels higher than 2.5 μg/L can increase the subclinical risk and the severity of clinical hypothyroidism. Moreover, “high normal” TSH levels of 2.0–4.0 μg/L and 2.5–4.5 μg/L related to hypocholesterolemia can increase the risk in metabolic syndrome [60, 85]. High levels of fluoride in drinking water can cause an increase in TSH concentrations [59]. Higher levels of fluoride in urine and levels of TSH have also been observed in children and teenagers from areas with endemic fluorosis [86, 87]. Our findings are in line with those published by Kheradpisheh et al. [59]. They found a positive correlation between fluoride in drinking water and TSH hormone around R2 = 0.85. Inadequate iodine can lead to decreased creation of thyroid hormones, as well as fluoride [59]. Harmful goitrogenic effects can be neutralized by sufficient iodine levels [5]. For our results, maternal UI corresponded to positive serum TSH levels during pregnancy. There was no significant difference in UI concentration between subjects with positive data for thyroid autoantibodies and those with negative data for antibodies.It is evident from Table7 that the average source of iodine intake by pregnant women was iodized salt, which may have a concentration greater or less than the standard for the pregnant woman’s body. However, the average of the second rank is primarily derived from conventional diets and noniodine-rich freshwater animals, which may cause iodine deficiency in pregnant women. Therefore, the relevant departments of the Ministry of Public Health should review the factors of fluoride exposure from the consumption of food, vegetables, fruits, and meat grown in contaminated soils, and fluoride in toothpaste, and provide knowledge and guidelines to staff about public health concerns about exposure to fluoride in excess of the body’s needs, as these directly impact health and the thyroid gland’s function.


## 6. Additional Points

The panel did not examine the health of pregnant women for preliminary information on sample screening, such as the history of radiation exposure, the history of various illnesses, drug exposure, and customer behavioral data that affects daily food and drinking water exposure, such as exposure to perchlorate, nitrate, and thiocyanate. In addition, pregnant women’s environmental fluoride exposure behaviors in experimental and control areas should be compared.


## 7. Conclusions

The article “iodine status in pregnant women having urinary fluoride in contaminated areas: A case study of Phayao province” investigated experimentally such as UI, serum TSH, and serum FT3, and the survey studied the knowledge of food iodine and behavioral consumption of iodine food in pregnant women living in excessive fluoride consumption from food and drink. These prediction analyses suggest that high fluoride exposure is associated with impaired thyroid function, which is indicated by elevated levels of serum TSH and lower levels of serum FT3 in the 1st trimester of pregnant women who are at risk of hypothyroidism.Based on the results, the following conclusions can be drawn:(i)
The major behavior consumption/intake of participants was consumed food iodine at least 3‐4 days/week which the most 5 ranks of consumption/intake were iodized salt, cooked pork, iodine fish salt, sticky rice, and fresh-water fish, respectively.(ii)
The major knowledge of participants (50.00%) was moderate iodine-knowledge(iii)
The UI was <150.00μg/L in which interpretation was iodine deficiency(iv)
The serum TSH of major subjects was less than 2.50μg/L which was at risk of hypothyroidism(v)
The serum FT3 of major subjects was more than 4.40 pg/ml which was high iodine intakeIn the further study, the cohort study should be investigated between infants born from mothers exposed to excessive fluoride and among thyroid parameter deficiency in pregnant women.



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*Source: 3677359-2023-01-30.xml*