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ORIGINAL ARTICLE
Year : 2023 | Volume
: 67
| Issue : 1 | Page : 41-46
Iodine status of pregnant women in iodine-sufficient regions: A tertiary care unit experience
Cigdem Tura Bahadir
Assistant Professor, Department of Endocrinology and Metabolism, Faculty of Medicine, Amasya University, Amasya, Turkey
Correspondence Address:
Cigdem Tura Bahadir
Amasya University Sabuncuoglu Serefeddin Training and Research Hospital, Department of Endocrinology and Metabolism, 05200, Amasya
Turkey
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ijph.ijph_831_22
Abstract
Background: The recommended urinary iodine concentration (UIC) levels in the overall adult population is 100–199 μg/L whereas 150–249 μg/L in pregnant women. Objectives: The objective is to determine the prevalence and severity of iodine deficiency in pregnant women in Amasya, which is located in the Western Black Sea region in Turkey, where sufficient iodine levels were achieved in the normal population. Methods: In this single-center study, we retrospectively searched hospital patient records and identified pregnant women who were assessed for iodine levels between January 2019 and January 2021. A total of 408 pregnant women were found eligible for the study. Thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroid peroxidase antibodies, and antithyroglobulin antibodies in serum samples and UIC were evaluated and compared between the trimesters. Insufficient iodine intake in pregnancy was defined as UIC <150 μg/L. Results: Median UIC and median TSH levels were 129 (range 45–452) μg/L and 2.98 (range 0.01–71.2) μIU/ml, respectively. 81.1% of pregnant women had UIC <150 μg/L. Iodine intake was adequate in 17.4% of pregnant whereas excessive in 1.5%. Prevalence of iodine deficiency during 1st, 2nd, and 3rd trimesters were 82.1%, 82.4%, and 74.5%, respectively. There was no significant difference in UIC levels between trimesters (P = 0.399). 72.9% of pregnant womens had TSH >2.5 mIU/L in the 1st trimester. Conclusion: Iodine deficiency in pregnancy may exist in an iodine-sufficient population. Appropriate measures must be taken to ensure sufficient iodine levels in these individuals.
Keywords: Iodine deficiency, iodine, iodine status, pregnancy, thyroid
Introduction 
Iodine deficiency is a leading cause of preventable mental retardation in the children. Severe iodine deficiency is also associated with complications such as preeclampsia, gestational diabetes, gestational hypertension, and spontaneous abortion. Elevated thyroid hormone production, renal iodine clearance, and transplacental iodine transfer to fetus during the pregnancy result in increased iodine demand in the pregnant women.[1] For this reason, pregnant women require more iodine compared top prepregnancy state.[2] Recommended daily iodine intake with foods for pregnant women and breastfeeding women is 250 μg/day compared to 90 μg/day for children younger than 2 years old and 150 μg/day for the general population.[3] The American Thyroid Association recommends 150 μg/day of supplementary iodine besides iodized salt use during pregnancy and lactation.[4]
Sufficient iodine levels were accepted as urinary iodine concentration (UIC) of 100–199 μg/L in school children and adults, and 150–249 μg/L in pregnant women.[5] Studies demonstrated that iodine deficiency is observed starting from the initial periods of pregnancy.[6] The addition of supplementary iodine at 4th week of pregnancy is associated with significantly higher Intelligence Quotient levels in the children.[7]
In 1997, the general Turkey population was found to have moderate iodine deficiency (median UIC 25.5 μg/L).[8] Starting from July 1998, the iodinization of table salts became mandatory in Turkey, but not the industrial salts. Following this move, the status in Turkey improved to mild iodine deficiency in 2001 (median UIC 87 μg/L). Adequate iodine intake was achieved by 2004 (median UIC 117 μg/L) and was still at sufficient levels in 2007 (median UIC 107 μg/L).[8],[9]
The World Health Organization (WHO) recommends at least 90% consumption of iodized salt for a healthy population.[3] The targeted household iodized salt consumption rate by the Ministry of Health in the Republic of Turkey is 95%.[10] In 2008 report of Turkey Demographic and Health Survey study, it has been stated that iodized salt consumption remains at 85.3%.
Based on Erdoğan et al.'s study, the International Council for Control of Iodine Deficiency Disorders (ICCIDD) listed Turkey among countries with sufficient iodine levels in their 2020 report.[9],[11] Although iodine levels have reached sufficient levels in nonpregnant population, studies performed on pregnant women show that iodine insufficiency continues to exist in the pregnant population.[6],[10],[12],[13],[14],[15],[16] The rate of iodine deficiency in pregnant women ranged between 50% and 90.7%. These studies were scattered across regions and years which might be the cause of this wide range.
In the present study, we aimed to evaluate the nutritional iodine status of pregnant women by measuring their UIC in Amasya located in the noncoastal Western Black Sea region after 20 years from the onset of mandatory iodization of table salts.
Materials and Methods Local ethics committee approval (Amasya University Ethical Commitee of Non-Invasive Clinical Research, Date: 04.02.2021, No: 27) was obtained. The study was conducted in accordance with the Declaration of Helsinki.
We conducted an observational study in Amasya, which is at an elevation of 412 meters and located in noncoastal Western Black Sea Region of Turkey. We used the below formula to determine the required sample size before the study:[17]
Where Z = Confidence interval, P = Estimated prevalence, and d = Precision. We determined Z as 95%. Based on the previous studies, we determined P as 50%, lowest reported prevalence, to be safe. Moreover, we determined d as 0.05 to keep the sample size reliable, but not oversized. The required sample size was determined as 384.
In this single-center study conducted in the sole hospital in the city's central district, we retrospectively searched hospital patient records and identified women who were assessed for iodine levels between January 2019 and January 2021. Then, we identified the pregnant women and included in the study. From the institutional patient file database, we gathered demographic and laboratory data, including age, gestational week, serum Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, and antithyroid peroxidase antibody (anti-TPO) and antithyroglobulin antibody (TgAb) positivity, and UIC levels. Total triiodothyronine and total thyroxine levels were not collected since those tests were not available in our institution. The exclusion criteria were: Insufficient data to determine gestational age, absence of thyroid hormone-related studies described above, history of any diagnostic/therapeutic study or intervention involving iodized contrast materials, urinary system infection, chronic renal failure, iodine-containing drugs, vaginal shower, and antiseptic skin cleansing agents in the past 6 months before blood and urine sampling. A total of 408 pregnant women were found eligible for the study.
Pregnant women were categorized into one of the following groups: 1st trimester (1–13 weeks of gestation), 2nd trimester (14–27 weeks of gestation), and 3rd trimester (28–40 weeks of gestation).
In our institution, fasting blood samples for TSH, FT3, FT4, anti-TPO, and TgAb levels were taken in the morning. The levels were measured from serum on the same day. Roche Cobas-e 602 immunoassay analyzers were used to assess thyroid hormone levels. TSH reference intervals were 0.1–2.5 mIU/L for the 1st trimester, 0.2–3.0 mIU/L for the 2nd trimester, and 0.3–3.0 mIU/L for the 3rd trimester.[18] The reference range for FT3 was 2–4.4 pg/ml and for FT4 0.93–1.7 ng/dl. Anti-TPO and TgAb levels were studied by electrochemiluminescence immunoassay. Anti-TPO levels >60 IU/ml and TgAb levels >60 IU/ml were regarded as positive.
UIC levels were used as a measure of iodine intake in this study. Urine samples for UIC were taken between 09.00 and 12.00 in the morning in our hospital as a single-spot urine sample. Urine is collected in de-iodized tubes, stored at −40°C. Then UIC levels were measured using the spectrophotometric method described by Sandell and Kolthoff.[19] The UIC was expressed as micrograms per liter (μg/L).
The nutritional iodine status in pregnant women was determined according to the criteria recommended by WHO/UNICEF/ICCIDD:[3]
Insufficient iodine intake was defined as UIC <150 μg/LAdequate intake of iodine as UIC 150–249 μg/LIodine intake above the requirements as UIC 250–499 μg/LExcessive intake of iodine as UIC ≥500 μg/L.Iodine deficiency (UIC <150 μg/L) was classified as mild (100–149 μg/L), moderate (50–99 μg/L), and severe (<50 μg/L).
Trimesters were compared with each other regarding demographic and laboratory data.
Statistical analysis
Data analysis was conducted using PASW SPSS version 18.0 (SPSS Inc., Chicago, USA). The distribution of continuous parameters was evaluated by Kolmogorov–Smirnov and Shapiro–Wilk tests. Mann–Whitney U-Test was used for the comparison of nonnormally distributed continuous parameters. Nominal parameters were analyzed by the Chi-square test and Fisher's exact test. Statistical significance was accepted at P < 0.05.
Results The median age of the study population (n = 408) was 28 (range 18–44) years. Women in 1st trimester were younger than those in 2nd and 3rd trimesters. The median UIC was 129 (range 45–452) μg/L and 81.1% (n = 331) of the population had UIC <150 μg/L. 86.3% (n = 352) of the population consumed iodized salt. The demographic and laboratory data of the overall population are summarized in [Table 1].
Table 1: Evaluation of demographic and laboratory data of pregnant womenThe median UIC level was similar in all 3 trimesters (P = 0.399). Similarly, the prevalence of iodine deficiency was similar across all groups (P = 0.407).
All 3 trimester groups were different in terms of age, TSH, FT3, and FT4 levels. Median TSH and FT4 levels in 1st trimester were significantly higher compared to those in 2nd and 3rd trimesters [Table 2]. 72.9% (n = 183) of the pregnant women had TSH >2.5 mIU/L and 37.8% (n = 95) had TSH >4 mIU/L in the 1st trimester. Nine patients had a TSH level above 10 mIU/L. 30.4% (n = 31) of the patients in the 2nd trimester and 30.9% (n = 17) of those in 3rd trimester had TSH >3 mIU/L and these were not statistically different (P = 0.947). FT3 levels significantly differed across all three groups, being highest in the 1st trimester and lowest in the 3rd trimester [Table 2].
TSH, FT4, and FT3 levels did not differ significantly between pregnant women with iodine deficiency (UIC <150 μg/L) and those without (UIC >150 μg/L) (P = 0.841, 0.791, and 0.691, respectively).
Neither anti-TPO positivity nor TgAb positivity did differ across three groups [Table 2]. Regarding anti-TPO positivity, there was no difference between patients with TSH over 4 mIU/L and those with below (P = 0.180).
Discussion The iodine levels of pregnant women in our study were within the normal range for the overall adult population. However, in the majority of the women, these levels were on the low side and corresponded to iodine deficiency in pregnancy. This study demonstrated that 23 years after the onset of mandatory salt iodization and achieving sufficient iodine levels in normal population, iodine deficiency in pregnancy still appears to exist in Amasya, a noncoastal region of Western Black Sea, Turkey. This is an important public health issue since many studies have reported that mild-to-moderate iodine insufficiency during pregnancy may affect intrauterine fetal health adversely, cause permanent damage to mental functions in the newborn, and have an adverse effect on the development of intelligence in the children.[20],[21]
Iodine deficiency in pregnant women has been reported in different regions of Turkey.[6],[12],[16],[22] Excluding two studies that included Mugla and Istanbul populations, median UIC among pregnant women was lower than 150 μg/L in studies which were conducted after the mandatory salt iodinization.[6],[10],[12],[13],[14],[15],[16],[22],[23],[24],[25] In the study of Çetinkaya et al., while median UIC was 137.3 μg/L in general population, 63.6% of pregnant women had iodine insufficiency and the median UIC in this population was 132.8 μg/L.[24] Oral et al. demonstrated that 90% of the pregnant women in Istanbul, which is an iodine-sufficient city, had iodine insufficiency.[12] In some studies, even UIC levels lower than 100 μg/L have been observed. The Black Sea region, which Amasya is part of, is also among the iodine-sufficient regions with a UIC level of 172 (range 26–291) μg/L.[9],[11] Despite this, iodine deficiency is observed in 81.1% of pregnant women in our study. Although the degree of iodine deficiency varies with geographical regions, these studies demonstrate that iodine deficiency still exists in pregnant women despite normal iodine levels were achieved in the normal population.
The reason behind this situation lies in the different levels of iodine requirement between normal population and the pregnant women. The UIC value between 100 and 199 μg/L corresponds to adequate iodine level in the general population. However, a UIC value between 100 and 149 μg/L, which is normal level for the general population, corresponds to mild iodine deficiency for a pregnant woman. When looked into the studies mentioned above, it can be seen that the iodine levels of study populations are at low normal levels. A woman with a normal iodine level below 149 μg/L and do not need iodine replacement can become iodine deficient once become pregnant since the iodine requirement in pregnancy is higher than a nonpregnant woman or man. Interestingly, this situation is not limited to Turkey. Wong et al. found that the median UIC of nonpregnant women was within normal limits whereas half of the pregnant women had insufficient iodine consumption in their study.[26] Iodized salt consumption rates and median UIC levels show geographical variations.[6],[12],[13] Iodized salt consumption rate is 84.7% in the Western Black Sea Region where Amasya is located.[27] We found this rate as 86.3% which is close to the WHO recommendation, but despite this, we observed iodine deficiency in the majority of the pregnant women. There may be several reasons behind low UIC in pregnant women despite a high rate of iodized salt consumption. First, edible salts may contain an insufficient amount of iodine. Second, the improper use of iodized salt, such as inappropriate storage conditions (i.e., lack of protection against moisture and light) might have diminished the iodine content of the consumed salt.[28] Third, the amount of daily consumed salt might fall short for the needs of a pregnant woman. The WHO recommends <5 g daily salt intake to decrease the cardiovascular risk.[29] The normal amount of salt consumption can establish 100–150 μg iodine intake daily which is adequate for normal population but insufficient for the pregnant. In order to achieve daily iodine intake recommended for pregnant women by WHO (250 μg/day), one must consume 6–15 g iodized salt each day.[3] UIC of newborns whose mothers consumed iodized salt were significantly higher than those whose mothers consumed rock salt.[15] And finally, daily salt intake might be further restricted due to gestational hypertension or hyperemesis. These factors might have caused the population having low normal iodine levels despite a high rate of iodized salt consumption, which eventually results in a high frequency of iodine deficiency in pregnant women. Of note, it must be said that some studies did not find any association between iodized salt consumption and UIC in the pregnant women.[15],[16],[30]
An interesting finding in our study was that the incidence of iodine deficiency did not decrease in 2nd and 3rd trimesters. Similar to our findings, neither Oral et al. (Istanbul) nor Cetinkaya et al. (Erzurum) found a change in the frequency of iodine deficiency as the pregnancy progresses.[12],[24] This might be due to inadequate or total absence of iodine replacement since iodine replacement is not in routine use before and during the pregnancy in our country; continued low consumption of iodized salt; or simply noncompliance of pregnant women to iodine replacement and dietary recommendations. However, Anaforoğlu et al. found that UIC, FT3, and FT4 decrease and TSH increases as the trimester progresses.[6] In our study, TSH levels in the 1st trimester were higher than 2nd and 3rd trimesters. Although iodine replacement is not in routine use before and during the pregnancy in our country, this might have resulted from the iodine-containing multivitamin supplements which can be prescribed by obstetricians in the 2nd and 3rd trimesters. In our population, we observed some quite high TSH levels, especially in the 1st trimester. These women turned out to have hypothyroidism before the pregnancy and interrupt their treatment for the fear of harming their baby until visiting the endocrinologist. FT4 and FT3 levels were higher in the 1st trimester compared to 2nd and 3rd trimesters in our study. This might have been resulted from the inclusion of patients with gestational thyrotoxicosis in the study.
As our findings and published literature show, iodine deficiency in pregnant women can still be observed in populations with normal iodine levels. Unlike any other disease, iodine deficiency in the pregnancy is a serious risk for the unborn that may have adverse outcomes that last lifelong. Furthermore, with low normal UIC levels of nonpregnancy, an unplanned pregnancy can leave the baby prone to devastating effects of iodine deficiency until the pregnancy is suspected and detected which may take more than 4 weeks.
Though the study is an observational study and did not focus on the prevention of iodine deficiency in pregnant women, we have some recommendations:
Awareness can be increased among primary health-care physicians and obstetricians regarding the possibility of iodine deficiency in pregnant women even in a population with normal iodine levelsIn regions where the normal population median UIC is <150 μg/L, women who are planning pregnancy can be checked for iodine status and given adequate iodine replacement if necessary to achieve a target UIC range of 150–199 μg/L before the pregnancyIn regions where unplanned pregnancies are quite high, decision-makers can establish policies that enable women at reproductive age to maintain a UIC level above 150 μg/L at all timesEducation regarding the importance and use of iodized salt can be given to pregnant women as part of pregnancy education programsIn regions where the normal population median UIC is <150 μg/L and individual iodine levels cannot be measured, ampirical iodine replacement can be given to women planning pregnancy since a UIC <250 μg/L will not be harmful during the pregnancy, but <150 μg/L probably will.However, it must be said that there are exceptions to iodine replacement before pregnancy. These are high titer anti-TPO positivity and Graves' Disease. Iodine replacement may increase the risk of postpartum thyroiditis in people with high anti-TPO levels and may aggravate hyperthyroidism in patients with Graves' Disease. 28.9% of patients in our study had anti-TPO positivity and iodine replacement was avoided in those with high titer of anti-TPO levels.
This study has some limitations. The study is retrospective in nature. Furhermore, the study results reflect the iodine status of pregnant women in noncoastal regions of the Western Black Sea region and would be improper to generalize the findings to other geographical regions. Furthermore, since the study used a hospital-based population in which the reasons why iodine status was investigated are unclear, there may be a selection bias. However, since the majority of the pregnancies are followed up in hospitals in Turkey, we do not think all these admissions were due to some kind of sickness. Further prospective studies can determine if these findings are valid for the overall population or only for a particular demographics. The UIC we used in this study was among the four methods that were recommended for evaluating and monitoring iodine intake in a population by WHO and ICCIDD, where the others were goiter prevalence, serum thyroglobulin, and neonatal TSH levels; and findings may be different in studies that use the other three criteria.[7]
In geographic regions, where the general population UIC is adequate but lower than 150 μg/L, health-care physicians must be aware of iodine deficiency and urge to maintain a target UIC range of 150–199 μg/L in women planning pregnancy to avoid 1st trimester iodine deficiency. If unplanned pregnancies are frequent in such a region, policies must be established to keep UIC levels in women at reproductive age above 150 μg/L regardless of pregnancy.
Conclusion Despite adequate iodized salt intake and normal population median UIC levels, iodine deficiency still appears to exist in the pregnant women in noncoastal Western Black Sea region after two decades of national compulsory iodine prophylaxis policy. Further prospective studies are needed to verify if these findings are valid for the overall population since neglecting this situation poses a risk to public health.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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