236089 1547.1552

Public Health Nutrition: 10(12A), 1547–1552 Evaluating iodine deficiency in pregnant women and younginfants—complex physiology with a risk of misinterpretation P Laurberg1,*, S Andersen1, RI Bjarnado´ttir2, A Carle´1, AB Hreidarsson2, N Knudsen3,L Ovesen4, IB Pedersen1 and LB Rasmussen41Department of Endocrinology, Aalborg Hospital, Aalborg, Denmark: 2Landspitali University Hospital, Reykjavik,Iceland: 3Medical Clinic I, Bispebjerg Hospital, Copenhagen, Denmark: 4Danish Institute for Food and VeterinaryResearch, Copenhagen, Denmark AbstractObjective: To review methods for evaluating iodine deficiency in pregnant womenand young infants and to discuss factors to be considered in the interpretation of theirresults.
Design: Review of the literature regarding the various methods available for assessingiodine status.
Setting: Population surveys and research studies.
Subjects: Pregnant women and young infants.
Results: Several factors to consider when assessing iodine status in pregnant womenand young infants include: 1) the urinary iodine (UI) concentration (mg l-1) is notinterchangeable with 24 h UI excretion (mg per 24 h); 2) the concentration of iodine ina spot or casual urine sample cannot be used to diagnose iodine deficiency in anindividual; 3) a moderate fall in the concentration of serum free T4 during pregnancyis not a sign of maternal iodine deficiency; 4) an increase in the concentration of serum thyroglobulin (Tg) during pregnancy is not a sign of maternal iodine deficiency; 5) a higher concentration of TSH and Tg in cord blood than in maternal blood is not a sign of iodine deficiency in the mother or neonate; and 6) thyroid function in a full-term foetus, a neonate or a small child is not more sensitive to a mild iodine deficiency than in the mother.
Conclusions: If the iodine status of pregnant women and small children is not to be misjudged, the above six factors need to be taken into account.
1. The urinary iodine (UI) concentration (mg l21) is not 4. An increase in the concentration of serum thyroglo- interchangeable with 24 h UI excretion (mg per 24 h).
bulin (Tg) during pregnancy is not a sign of a The two values are interchangeable only if the volume maternal iodine deficiency. Even in iodine-replete of urine passed in 24 h is one litre. The average volume women, the serum Tg concentration may increase of urine passed by an adult is approximately 1.5 l per during pregnancy. This is probably caused by the 24 h. Therefore, the median UI excretion given as mg greater thyroid secretory activity of pregnant women.
per 24 h will be 50% higher than the median iodine 5. A higher concentration of thyroid-stimulating hormone (TSH) and Tg in cord blood than in maternal 2. The concentration of iodine in a spot or casual urine blood is not a sign of iodine deficiency in the mother or sample cannot be used to diagnose iodine deficiency in neonate. This is a normal phenomenon, not related to an individual. The UI concentration may vary up to threefold in an individual during a day. This means that 6. Thyroid function in a full-term foetus, a neonate or a it is necessary to collect repeated urine samples from small child is not more sensitive to a mild iodine an individual over a period of time and estimate the deficiency than in the mother. Prospective intervention median or average, in order to evaluate their iodine studies and cross-sectional studies show no evidence 3. A moderate fall in the concentration of serum free T4 during pregnancy is not a sign of maternal iodine An adequate intake of iodine is essential for thyroid deficiency. Even in iodine-replete women, a 10 – 20% hormone synthesis and consequently for normal devel- fall in serum free T4 is observed in late pregnancy.
opment and metabolism. The major determinants of the *Corresponding author: Email laurberg@aas.nja.dk iodine intake of a population are: the natural iodine infood and water1; the iodine content of mineral mixturesand food given to domestic animals that provide food forhumans2; the use of iodine-containing chemicals by thefood industry3 and iodine supplements taken byindividuals or given to populations4. In large parts of theworld, the natural iodine content of food or water is lowand people living in such areas are at risk of iodinedeficiency disorders5.
Iodine deficiency in a population has a number of harmful consequences for health and economic develop-ment; this is reviewed elsewhere6. The most severeconsequence of iodine deficiency is brain damage7.
Sufficient amounts of thyroid hormone are needed for Fig. 1 The average urinary iodine (UI) excretion (mg day21) and the proper development of the central nervous system8, the prevalence of goitre by clinical examination in people in 186 and a woman’s requirements for iodine in order to achieve localities in Central America between 1965 and 196714. In each physiological thyroid hormone production are increased locality, members of approximately 20 randomly selected familieswere investigated. A total of 21 611 people from 3712 families during pregnancy9. Prophylaxis against brain damage were investigated for goitre, and the concentrations of iodine and caused by iodine deficiency has been the major force creatinine were measured in a late morning spot urine sample in behind the tremendous movement in recent decades 3181 randomly chosen participants. The daily iodine excretionwas estimated from iodine and creatinine concentrations using an towards the eradication of iodine deficiency10. About 70% equation correcting for body weight, and age- and sex-dependent of the population of the world are now covered to some differences in 24 h urinary creatinine excretion39. The boxes degree by a public iodine supplementation programme, represent the range in UI excretion that corresponds to a severe,moderate or mild iodine deficiency. The dotted line was added in typically by the fortification of salt. Since the foetus and the the original publication to indicate the definition of endemic goitre young infant are most vulnerable, and since iodine (goitre prevalence of more than 10%) at the time of investigation.
requirements are greater than normal in pregnant and Redrawn from Ascoli and Arroyave14 with permission.
breast-feeding women, there are special concerns aboutensuring an adequate iodine intake during these periods.
(25 – 49 mg day21) by endemic goitre in many areas and In pregnancy and also in foetal and neonatal life, thyroid severe iodine deficiency (, 25 mg day21) by endemic function undergoes a series of interacting physiological changes that complicate the evaluation of iodine status11.
Since collecting all urine passed for 24 h is cumbersome Some of these changes are occasionally taken for signs of to do and may be incomplete, the iodine concentration in iodine deficiency, even if they are not associated with the spot sample of urine expressed as microgram of iodine per iodine intake. When evaluating iodine requirements, gram of creatinine is often used15. If on average, the 24 h physiological alterations should be separated from non- urinary creatinine excreted by an individual in the physiological disturbances. This is important because population under study is close to 1 g, this would give a epidemiological studies suggest that a high iodine intake value nearly identical to 24 h UI excretion. However, may be associated with more hypothyroidism in a general creatinine excretion may deviate substantially from 1 g per population12 and also in women of reproductive age13. The 24 h in some population groups16,17. In particular, it may optimal iodine intake should be sufficient to prevent iodine be lower than 1 g in protein-deficient populations and in deficiency disorders, but not greater.
children and may be higher in young men.
There are several circumstances in which data on For these reasons, the iodine/creatinine ratio came into indicators of iodine status and thyroid hormones may be discredit and was replaced by the simple concentration of misinterpreted when studying pregnant women and small iodine in urine18. This corresponds to 24 h UI excretion if the volume of urine produced by the group under study is1 l day21, as it may be in schoolchildren. However, in The UI concentration (mg l21) is not interchangeable with adolescents and adults, the average urine volume is more likely 1.5 l per 24 h, and therefore, an iodine concentration The original recommendations for iodine intake were of 100 mg l21 corresponds to an iodine excretion of mainly developed from data on the association between the prevalence of goitre in groups of people and their The discrepancy between the UI concentration and 24 h average UI excretion. The results from a large survey iodine excretion has been shown in a number of studies.
conducted in Central America in the late 1960s shown in Figure 2 illustrates this point and shows that the Fig. 1 reveal how a mild iodine deficiency (average UI concentration of iodine in a casual sample was, on an excretion of 50 – 99 mg day21) was characterised by average, 60 – 65% of the amount excreted in 24 h19. In the endemic goitre in some areas, moderate iodine deficiency study illustrated in Fig. 2, reliable estimates of the 24 h 150 mg, which corresponds to the recommended dailyiodine intake using the old system.
The concentration of iodine in a spot sample of urine is rarely identical to 24 h UI excretion. The UI excretion ofgroups of healthy adolescents and adults measured as mgper 24 h is often equal to UI measured as mg l21 £ 1.5.
When UI excretion is used to evaluate iodine intake, acorrection should also be made for the amount of iodineexcreted through other routes, mostly in faeces, which isapproximately 10% of intake.
The concentration of iodine in a spot or casual urinesample cannot be used to diagnose iodine deficiency in anindividual Fig. 2 Comparison of various methods used to estimate 24 hurinary iodine (UI) excretion using a single urine sample collected Such misinterpretation may be illustrated by a recent study from healthy adults (n ¼ 21). The columns show the median of iodine deficiency in Spanish schoolchildren22. A cross- estimated 24 h UI excretion, obtained from a single urine sample sectional study of 987 four-year-old children gave a mean by measurements and calculations as indicated, expressed as apercentage of the median amount of iodine directly measured in UI concentration of 214 mg l21 (median 189 mg l21), which the 24 h urine collected on the same day. The estimates in the is not low. Nevertheless, it was concluded that 7.8% of the columns A – C were obtained using the equation: 24 h iodine children had iodine deficiency, because 7.8% of urinary excretion (mg per 24 h) ¼ (iodine concentration (mg l21)/creatinineconcentration (g l21)) £ (24 h creatinine excretion for group (g per samples had an iodine concentration of , 100 mg per l22.
24 h)), whereas the estimates in columns D – F (shaded) were The concentration of iodine in casual samples of urine obtained from the simple assumption that: 24 h iodine excretion may vary up to threefold in an individual during a single (mg per 24 h) ¼ iodine concentrations in the sample of urine(mg l21). The UI excretion (mg per 24 h) was considerably day19, and in a group of people, the distribution of average underestimated from the iodine concentration in a casual sample iodine concentrations in several samples from the same at all times of the day (D – F) (*P ¼ 0.006, **P ¼ 0.001). When the subjects is much narrower than the distribution of values creatinine concentration was used to correct the iodine content,only the iodine excretion estimated from a fasting morning urine from single spot samples from the same people23. Only the sample (A) was significantly different from the actual iodine median or average can be used to classify iodine intake. If content of the 24 h collection. The normal 24 h creatinine excretion iodine deficiency is to be diagnosed in an individual, a for people of the same sex and age used for calculation (‘24 h Crnorm’) were the average values taken from a population study.
series of samples taken over a period of time should be collected and analysed. Alternatively, a group ofindividuals may be studied and median values from single iodine excretion were obtained from the iodine and sampling used for evaluation of the entire group.
creatinine concentrations measured in a non-fasting urinesample collected in the morning and adjusted using data A moderate fall in the serum concentration of free T4 on the average 24 h urinary creatinine excretion in a during pregnancy is not a sign of maternal iodine similar cohort of people, as suggested by Knudsen et al.20 The values of UI excretion in microgram per day depicted When a reliable method such as equilibrium dialysis is used in Fig. 1 are derived from the iodine and creatinine to make measurements, the serum concentration of free T4 concentrations measured in a spot sample of urine using a is 10 – 20% lower than normal in late pregnancy24. This decrease is not ameliorated by giving iodine supplements In practical terms, the shift from using a UI excretion to mothers25, but iodine-deficient women may show an of 100 mg per 24 h to a UI concentration of 100 mg l21, as even greater fall in their free T4 concentration9. Thus, a low the low threshold indicating a sufficient iodine intake, free T4 concentration in late pregnancy may be a sign of a resulted in an increase in the recommended iodine low iodine intake, but not necessarily so.
intake for many groups of people without any realevidence that this was necessary to avoid iodinedeficiency disorders. The impact of this was consider- An increase in the serum concentration of Tg during able. For example, Fonzo et al.21 studied UI excretion in pregnancy is not a sign of a maternal iodine deficiency over 3800 young men in Piedmonte and the Aosta Valley, In population studies, the serum Tg concentration is a a formerly severely iodine-deficient area in Italy. The good marker of iodine deficiency26, but a high serum median UI concentration was 101.8 mg l21 and the concentration of Tg is not a specific sign of iodine conclusion was that iodine intake may still be of deficiency. The release of Tg from the thyroid may be borderline sufficiency. But the median 24 h UI excretion altered in a number of thyroid disease states, and even if in these young men would probably be approximately the iodine intake is sufficient, stimulation of thyroid hormone secretion will lead to an increase in the serum concluded: ‘The study suggests that in areas with mild concentration of Tg27. During a normal pregnancy, there iodine deficiency, neonates may be at the limit of is a considerable increase in requirements for thyroid decompensation as evidenced by their enhanced TSH hormone and therefore also in thyroid secretory and Tg levels’. It is however normal to find a considerably higher concentration of TSH and Tg in cord blood than in In Denmark, we found a higher serum Tg concentration in maternal blood8 – 11. Moreover, this difference is not pregnant women than in controls29. To evaluate if this ameliorated by iodine supplementation25.
difference was caused by a low iodine intake alone or if itwas due to an increase in thyroid secretory activity Thyroid function in a full-term foetus, a neonate or in a associated with pregnancy, we compared the concentration small child is not more sensitive to a mild iodine deficiency of Tg in serum of pregnant and non-pregnant women in areas with different iodine intakes30. As illustrated in Fig. 3, As discussed above, the most severe consequences of a the concentration of Tg in serum was higher in the area of thyroid hormone deficiency caused by a low iodine intake low iodine intake, but pregnant woman had higher serum Tg are observed in the foetus and during the first years of life.
concentration than control women in all areas. The findings During this period, the iodine stores of the thyroid are suggest that the increase in serum Tg concentration during small relative to daily thyroid hormone production, and pregnancy is primarily caused by greater thyroid secretory undoubtedly, a sudden cessation of iodine supply would activity and that it is not a sign of iodine deficiency. This is lead to a much faster decrease in thyroid hormone supported by a recent longitudinal study of serum Tg secretion in the neonate than in the mother. However, concentration in pregnant women living in Sweden: the there is little evidence that thyroid hormone secretion is concentration was approximately 33% higher in late more impaired in the foetus or neonate than in the mother pregnancy than 1-year post-partum31.
in localities where there is a mild iodine deficiency.
In two randomised prospective studies of pregnant A higher concentration of TSH and Tg in cord blood than women with mild to moderate iodine deficiency, iodine in maternal blood is not a sign of iodine deficiency in the supplements led to a lower serum TSH concentration in the women in late pregnancy, but iodine had no In a recent study performed in the Sudan, the median significant effect on the concentration of TSH in cord concentrations of TSH and Tg in cord blood serum were blood25,33. In an observational study of women living in an 2 – 3 times higher than in the mother’s blood32. The authors area with mild to moderate iodine deficiency, we foundthat mothers supplemented with iodine had a lower TSHconcentration in serum at full term than non-sup-plemented control mothers. On the other hand, whenthe mother had been taking iodine supplements, the TSHconcentration in cord blood serum was higher than in cordblood serum of controls34. In a study performed in Sydney,Australia, McElduff et al. found a positive correlationbetween the maternal UI concentration during pregnancyand the neonatal serum TSH concentration35. The medianconcentration of iodine in the urine of mothers (n ¼ 84)was 109 mg l21. Similarly, the same researchers found apositive correlation between the concentrations of TSH inneonates and the concentration of iodine in breast-milk36.
Even a recent large Spanish study, in which the authorssuggested that iodine deficiency was the cause of lowintelligence, found a positive correlation between theconcentration of iodine in urine and serum TSH. Themedian UI concentration in the children was 90 mg per l37.
Iodine exerts profound regulatory effects on many Fig. 3 The serum thyroglobulin concentration (median with 95% processes in the thyroid gland, which includes inhibition confidence interval) of pregnant women (Prg) and non-pregnant of thyroid hormone secretion after excessive iodine controls (Ctr) in three places with different iodine intakes (East- intake. As indicated, some studies suggest that the foetal Jutland, Denmark; North Sweden; and Iceland)30. Serum wasobtained from 20 Prg admitted for delivery at full term and after and neonatal thyroid is more sensitive to the inhibitory an uncomplicated pregnancy; Ctr were 20 non-pregnant healthy effect of iodine than the maternal thyroid and that slight hospital employees of a similar age. None of the women took iod- inhibition may occur even at a relatively low iodine intake.
ine-containing supplements. The median urinary iodine concen-trations in spot urine samples from the Prg are shown in boxes However, the interaction between the pituitary and thyroid glands is complex at around the time of birth, and certainly there is no indication that a slightly high Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid serum TSH concentration in cord blood indicates a risk of function. New England Journal of Medicine 1994; 331:1072 – 8.
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