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Original Studies |
Centers for Disease Control (J.G.H., N.W.S., P.L.G.), National Center for Environmental Health, Division of Environmental Hazards and Health Effects, Atlanta, Georgia 30341; National Center for Environmental Health, Division of Environmental Health Laboratory Science, Centers for Disease Control (W.H.H., E.W.G., D.T.M.), Atlanta, Georgia 30341; Emory University School of Public Health (D.W.F., G.F.M.), Atlanta, Georgia 30322; and Brigham and Women’s Hospital (L.E.B., S.P.), Boston, Massachusetts 02115
Address all correspondence and requests for reprints to: Joseph G. Hollowell, M.D., M.P.H., Centers for Disease Control and Prevention, 4770 Buford Highway, MS F-28, Atlanta, Georgia 30341. E-mail address: jgh1{at}cdc.gov
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Abstract |
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Introduction |
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This study complements previous qualitative dietary intake studies (6, 7, 8) by analyzing the concentration of UI in the population of the United States from data collected by the National Health and Nutrition Examination Surveys (NHANES). We have now compared data from NHANES III (1988–1994) with those from NHANES I (1971–1974), paying particular attention to the groups excreting UI concentrations less than 5.0 µg/dL. This report identifies trends in iodine nutrition and provides a basis for ensuring, or planning for, iodine adequacy in the United States in the 21st century.
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Subjects and Methods |
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For both surveys information was collected on income levels, metropolitan/nonmetropolitan residency, and race, categorized as white, black, and remaining races. In NHANES III, ethnicity was added and included white non-Hispanic, black non-Hispanic, Mexican-American, and remaining ethnic groups. The regions identified in NHANES III were northeast, midwest, south (including Texas), and west. Because the regions identified in NHANES I contained different states than those in NHANES III, we did not analyze NHANES I data for regional differences or compare regional data between the surveys.
Laboratory methods
Iodine. In both NHANES I and NHANES III, UI concentrations were determined using the Sandell-Koltoff reaction as modified by Benotti et al. (13, 14). UI concentrations in NHANES I were determined by the NHANES Laboratory, Centers for Disease Control (CDC; Atlanta, GA), on samples from 18,617 people. (13) In NHANES III, UI concentrations were determined by the Iodine Research Laboratory, University of Massachusetts Medical Center (Worcester, MA), on samples from 22,070 people. The UI detection limit for the method used by both laboratories was 0.2 µg/dL. In NHANES I, iodine standards were prepared from analytical grade potassium iodide (KI), consisted of 10 levels of KI covering the range of 0.1–1.0 µg/mL, and were analyzed in duplicate with every 80–120 urine samples. In NHANES III, iodine standards were prepared from analytical grade potassium iodate (KIO3), consisted of 4 levels of KIO3 covering the range 0.0–0.3 µg/mL iodine, and were analyzed in duplicate with every 10 urine samples. Calibration procedures were similar for both laboratories. UI concentrations are calculated from the slope and y-intercept of the standard curve. A quality control sample was digested and analyzed with every 10 urine samples. Samples were repeated for values below 0.1 µg/mL by using a larger sample size and for those above the highest standard by diluting the sample. The coefficient of variance for UI determination ranged from 3.8–11.0% in NHANES I and from 2.7–7.0% for NHANES III.
Creatinine. Urinary creatinine in both surveys was measured by the Jaffé alkaline picrate method, so that iodine concentration adjusted for creatinine concentration (I/Cr) could be calculated. Concentrations of creatinine standards of 50, 100, 150, 200, 250, and 300 mg/dL were analyzed in duplicate with every 60 urine samples. Urinary creatinine concentrations were calculated from the slope and y-intercept of the standard curve. Quality control samples were analyzed with every 20 urine samples. Repeat limits were below 10 and above 300 mg/dL. The creatinine detection limit for this method was 1 mg/dL. The coefficient of variance for urinary creatinine determination ranged from 2.9–4.7% in NHANES I and from 1.5–7.7% for NHANES III (12, 13).
Statistical analyses
We analyzed data with SUDAAN to account for the complex sample survey design using sample weights. When we compared regions and race in NHANES III, we standardized for age and sex using the distribution of the entire population. When we studied changes between the surveys, we standardized for age and sex in accordance with the population of NHANES III. To study characteristics of subjects with UI concentrations below 5.0 µg/dL, we calculated prevalences, prevalence differences, and prevalence ratios. In accord with WHO recommendations, we compared medians and proportions excreting UI concentrations below 5 µg/dL or I/Cr concentrations below 50 µg/g because the data were severely skewed to high values, perhaps due to exposure to iodine-rich substances such as medications or x-ray contrast agents.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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, indicate a
larger overall sample and less extensive oversampling of females in
NHANES III compared to NHANES I. Non-Hispanic blacks,
Mexican-Americans, and children were over sampled in NHANES III. The
age distributions were otherwise similar.
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In 1988–1994, the median UI concentrations for the entire
population was 14.5 µg/dL. The average concentrations of UI and I/Cr
in younger people were greater than those in older people. As shown in
Table 2, males had higher median UI
concentrations than females (16.0 vs. 13.0 µg/dL;
<0.00001). UI concentrations also varied by race, poverty level, and
region of the country (Table 3). The
difference in iodine concentration between residents of metropolitan
areas and residents of nonmetropolitan areas was small and lacked
statistical significance (P = 0.32). Of the entire
population, 11.7% had UI concentrations less than 5.0 µg/dL (Fig. 1).
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Time trends
As shown in Fig. 1
, UI concentrations for the U.S. population
were, overall, substantially lower in 1988–1994 than in 1971–1974.
The median UI concentration fell from 32.0 µg/dL in 1971–1974 to
14.5 µg/dL in 1988–1994 (P < 0.0001). When
categorized by participants’ race, metropolitan/nonmetropolitan
residence, poverty status, or region of the country, the median UI
concentrations in 1988–1994 were about half those found in 1971–1974
(Table 3). The proportion of the population with UI concentrations
below 5.0 µg/dL was 4.5 times higher in 1988–1994 than in
1971–1974, (P < 0.0001). This increase in the
proportion of people with low levels was seen for all demographic
categories (Table 3) and for all age groups (Fig. 2). In 1988–1994, 8.1% of males and
15.1% of females had UI concentrations below 5 µg/dL. As shown in
Fig. 2, the highest prevalence of low concentrations was in the 40- to
49-yr-old age group (23.1% of women and 12.7% of men). Among white
non-Hispanics, the percentage with UI concentrations below 5.0 µg/dL
was even higher in women of this age group (25.5%).
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When adjusted for creatinine concentration, the median I/Cr ratio in
NHANES III (124.6 µg/g creatinine) was lower (P <
0.0001) than that in NHANES I (293.3 µg/g creatinine). The total
population with I/Cr concentrations below 50 µg/g had increased
10-fold. The number of women of child-bearing age with I/Cr
concentrations below 50 µg/g had increased 9-fold, and the percentage
of pregnant women with these low levels had also increased. When
comparing the I/Cr ratios, adult men, aged 20–64 yr, had lower values
than women of those ages. Male children excreted higher concentrations
of iodine in urine than female children for both I/Cr and UI
concentrations (Fig. 3).
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Discussion |
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The increased proportion of women of child-bearing age and pregnant women who are in the iodine deficiency range is particularly important because iodine deficiency in fetuses and infants can lead to irreversible intellectual deficits with great impact on populations (15). Although the overall median intake of iodine in the United States is within acceptable limits, particular groups, namely women aged 40–49 and 50–59 yr and other women of child-bearing age, may be at risk for iodine deficiency. In Belgium, Glinoer et al. reported that the addition of 100 µg iodine daily to the diet of pregnant women significantly decreased maternal TSH and thyroglobulin concentrations and thyroid volume. In the newborn, serum thyroglobulin concentrations and thyroid volume also decreased (16). Such findings emphasize the importance of adequate iodine nutrition.
Although the laboratory analyses for iodine were conducted in different
laboratories 14–20 yr apart, the methods used were identical. Analytic
grade potassium iodide in 1971–1974 and analytic grade potassium
iodate in 1988–1994 were used to prepare standard iodine
concentrations, and quality assurance and controls for both
laboratories and time periods were considered entirely satisfactory by
the NHANES study groups. Reassuringly, in another study, May et
al. (17) showed close agreement among six different methods used
in six laboratories for the iodine range studied, with no method
showing a bias or inconsistency serious enough to alter the public
health interpretation of their dataset, and showed a high correlation
(
0.9), indicating good intermethod comparison for individual samples.
Thus, we found no supportive data that the use of different
laboratories or the time between studies explains the differences in
observed UI concentrations.
Daily iodine intake is most closely estimated by the amount of iodine excreted in the urine in 24 h. To compensate for the lack of a 24-h urine collection, in populations with adequate nutrition, the creatinine concentration has been used to adjust for factors that may affect the concentrations of the substances being measured during the collection period. Although used widely, the I/Cr ratio adds little and may be misleading with regard to iodine excretion in developing countries where nutrition is poor, thereby affecting creatinine excretion (18). The usefulness of the I/Cr ratio in the United States for population iodine studies has been questioned. Thomson et al. compared UI results from spot samples with those from 24-h collections samples from 62 adults and determined that "... fasting urine samples, but not casual urines, may give a reasonable estimate of urinary output of iodine ... on a population basis... . " (19). In both NHANES studies, urine was collected after a period of fasting, and similar protocols were used; thus, the urine collection procedures used should not have contributed to the differences observed.
We included I/Cr data in our analyses, primarily for comparison with the results from previous Canadian and US studies. The 1971–1974 (NHANES I) values were similar to the findings of the Canadian national study of 1969–1972 (20), which reported that less than 1% of the population had I/Cr concentrations below 50 µg/g. In the Canadian study, no pregnant women and less than 0.2% of women of child-bearing age had I/Cr concentrations below 50 µg/g. Metropolitan, urban, and rural populations did not differ in I/Cr concentration. Most individuals of both sexes had I/Cr concentrations between 100–550 µg/g. Slightly lower values were found in males 20–39 yr old and males over 60 yr of age (20). In the U.S., Trowbridge et al. in a 1972 study of 7,785 children aged 9 to 16 yr (21) and in the Ten-State Nutrition Survey from 1968–1970 of 16,799 subjects aged 2 yr and older (22) found I/Cr values to be in the range of those found during the same approximate time period in NHANES I.
In Switzerland (23), where iodine prophylaxis has been practiced for a number of years and iodine intake is thought to be adequate, studies showed evidence of iodine deficiency and prompted health officials to increase the iodine content of salt; to reestablish health education programs focusing on the use of sea products, milk, and iodized salt; and to improve the monitoring programs for iodized salt (24). Iodine deficiency was also found in other continental European countries (25). Iodine deficiency, which was severe in some locations, may have contributed to the increased incidence of thyroid cancer among children exposed to fallout of 131I from the Chernobyl, Ukraine nuclear disaster in 1986, as thyroid radioactive iodine uptake is increased in areas of iodine deficiency (26).
In the United States iodized salt was introduced to prevent goiters in the upper Midwest in 1922. As the voluntary use of iodized salt spread rapidly throughout the country (27, 28) and as iodine was added to processed foods and milk products (29), the prevalence of goiter declined (30). Within 50 yr the country had excessive iodine intake to the extent that other forms of thyroid problems, namely iodine-induced hypothyroidism, autoimmune thyroiditis, and hyperthyroidism, had become of more concern than deficiency disorders (31). The 1982–1991 surveys from Total Diet Study may explain the decrease in UI concentration. The authors of that study argue that the apparent decline in iodine intake from 1982–1991 did not represent a trend, but was probably due to higher iodine intake during 1982–1984 than during the remaining 7 yr (8). The decrease since 1984 was thought to be due to the dairy industry’s effort to reduce iodine in milk and to the replacement of iodine by bromine salts as the dough conditioner in commercial bread production (7).
We need to know whether the decrease in UI concentrations seen between 1971–1974 and 1988–1994 can be explained entirely by the 1982–1984 changes seen in food production or whether additional factors or trends not measured by the Total Diet Study are involved, such as the use of iodized table salt or prepared "fast foods." Although the total consumption of iodized salt remains at about 50–60% of all salt consumed (Hanneman, R. L., Salt Institute, Alexandria, VA; personal communication), the extent to which voluntary reduction in added salt use by segments of the population concerned about sodium intake and hypertension has contributed to lower UI concentrations is unknown.
In 1971–1974, 27.8% of the population had excessive UI concentrations (>50 µg/dL), and the decline of those with excessive UI to 5.3% in 1988–1994 may be seen as beneficial in possibly reducing diseases due to iodine excess such as Hashimoto’s thyroiditis and perhaps Graves’ disease (31). Should the intake of iodine continue to decrease in the United States, in addition to a further change in the pattern of thyroid diseases, a portion of the population could become iodine deficient, resulting in the following consequences: 1) a reduction in the intellectual capacity of children born to mothers receiving insufficient amounts of iodine while pregnant, and 2) a rise in the prevalence of simple iodine deficiency goiter and nodular goiter. Whether the reduced UI seen in 1988–1994 can be directly correlated to measurable changes in thyroid function in the population is not known at this time because the results of thyroid function tests and thyroid antibodies in the 1988–1994 study are not available as yet, and comparison with results in 1971–1974 is not possible because TSH and antibodies were not measured in NHANES I. We know of no population-based study in the United States, such as transient neonatal hypothyroidism or recent goiter surveys, that have shown changes that resulted from decreased iodine intake. It will be important to know what UI concentrations in a population will predict thyroid dysfunction.
Clearly, the iodine intake in the United States has decreased over the past 20 yr. Awareness of a possible continuing decline in iodine intake in this population can be achieved by monitoring the food supply, especially the intake of iodine in women of child-bearing age. This monitoring can be performed by continuing the measurement of iodine in the Total Diet Study and by including UI in the next NHANES survey, which is about to begin. Surveillance of thyroid diseases should be emphasized, but we should not wait for the prevalence of goiter to increase or for changes in thyroid disease patterns to occur due to decreased iodine intake. Should surveillance indicate a further decrease in iodine intake, measures may be required to increase the amount of iodine consumed by the U.S. population to prevent the possibility of the reemergence of iodine deficiency in the United States.
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Acknowledgments |
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Footnotes |
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Received March 23, 1998.
Revised June 23, 1998.
Accepted July 1, 1998.
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