IODINE AND ENDEMIC GOITER
THYROID Volume 22, Number 10, 2012 ª Mary Ann Liebert, Inc. DOI: 10.1089/thy.2012.0016
Fortification of Bread with Iodized Salt Corrected Iodine Deficiency in School-Aged Children, But Not in Their Mothers: A National Cross-Sectional Survey in Belgium Stefanie Vandevijvere,1 Ahmed Bensouda Mourri,2 Sihame Amsalkhir,2 Freddy Avni,3 Herman Van Oyen,1 and Rodrigo Moreno-Reyes 2
Background: In the years 1985–1998, it was noted that mild iodine deficiency (MID) was a public health problem in Belgium. Therefore, an agreement was signed in 2009 between the bakery sector and the Ministry of Health, to fortify bread with iodized salt. We tested the hypothesis that the iodine status of Belgian children improved after the introduction of bread fortified with iodized salt. Since the dietary habits of children and adults may differ, we also investigated whether the median urinary iodine concentration (UIC) among the children in this study reflected the iodine status of their mothers. Methods: The study was cross-sectional. In a van, equipped with an ultrasound device, the thyroid volumes (Tvol) of children were measured and household salt samples and urine samples were collected from the children and their mothers. From across Belgium, 60 schools were selected and 1541 children participated in the study. Results: The median UIC in children was 113.1 and 84.4 lg/L among their mothers. The median UIC among children was substantially greater compared to more than 10 years ago (80 lg/L; p < 0.001). The median UIC in school-aged children was lower in Wallonia than in Flanders ( p < 0.001) and was higher in boys than in girls ( p < 0.001). The percentage of children with goiter was 7.2%. Of the 904 salt samples received, 63.2% did not contain iodine. Conclusions: Fortification of bread with iodized salt corrected iodine deficiency in Belgian children, but not in their mothers. To provide these women with an adequate iodine intake, the use of both iodized salt in bread and iodized instead of noniodized household salt needs to increase. Our findings suggest that the median UIC in children may not be an adequate surrogate of adults’ iodine status. Therefore, monitoring iodine status should not be limited to children, but should be extended to women of child-bearing age.
Introduction
T
he main consequences of mild iodine deficiency (MID) in adults are a higher prevalence of multinodular goiter (MNG) and thyroid nodules (1,2). Some studies suggest that MID during pregnancy may impair neurodevelopment in the offspring (3) and prevent them from reaching their full intellectual potential (4). Correction of mild-to-moderate iodine deficiency in primary school children improves cognitive and motor function (5). Despite worldwide success in the implementation of iodine supplementation programs over the last decades, iodine deficiency still remains a public health problem in Europe and other regions of the world. In 2004, it was estimated that of the
2 billion people around the world at risk of iodine deficiency, 20% of who live in Europe (6). In 2003, only 9 out of 40 countries in Europe had iodized salt coverage of at least 90% in their households (1). Although the number of European countries in which iodine deficiency is a public health problem decreased from 23 in 2003 to 14 at the present time (7), it is a matter of concern that iodine deficiency reappeared in countries whose previous iodine intake was sufficient, such as the United Kingdom (8). Several surveys in the past among neonates and schoolaged children indicated that Belgium is affected by MID, and that this represented a substantial economic burden to the health care system (9–11). The previous most recent national survey performed in 1998 among school-aged children found
1 Department of Public Health and Surveillance, Scientific Institute of Public Health, Brussels, Belgium. Departments of 2Nuclear Medicine and 3Radiology, Erasme Hospital, Free University of Brussels, Brussels, Belgium.
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CORRECTION OF IODINE DEFICIENCY IN BELGIUM a median urinary iodine concentration (UIC) of 80 lg/L and a goiter prevalence of 5.7% (9,12). Consequently, optimizing iodine intake was one of the priorities in the first national nutrition and health plan (2005–2010) of the Belgian Ministry of Health. An agreement was signed between the bakery sector and the Ministry of Health in April 2009, to encourage the fortification of bread with iodized salt (10–15 ppm) (13). The World Health Organization (WHO) recommends (14) that iodine nutrition surveys should be conducted in children (ages 6–12) because of their vulnerability to iodine deficiency and because of the accessibility to children in a school environment. The median UIC of children has been used as a surrogate of the iodine status in the adult population. However, recent studies suggest that this assumption may not be valid (15). The aim of the present study was to evaluate iodine status of Belgian school-aged children. Our hypothesis was that iodine status may have improved, since a program to fortify bread with iodized salt had been implemented. We also investigated whether the median UIC in school-aged children was an adequate surrogate of iodine status of their mothers. Methods Sampling The target population of the survey comprised all schoolaged children attending primary school in Belgium (6–12 years) during the year 2010–2011. Children were selected according to a multistage proportionate-to-size stratified sampling design. Because some population-based data suggest that the prevalence of iodine deficiency is higher in the south than in the north of the country (16), the schools were stratified by region (17,18). A 30-cluster survey was performed in both regions with at least 20 children per cluster, as re-
1047 commended (19,20). The proportion of children with iodine deficiency in Belgium was previously estimated to be 0.7 (9). Because a lower proportion of children with iodine deficiency was expected in this survey, the expected proportion of children with iodine deficiency was fixed at 0.5 to obtain the largest possible sample size. A sample size calculation based on an estimated 50% prevalence of UIC < 100 lg/L, a 95% confidence interval (CI) for the true prevalence of UIC < 100 lg/L, a design effect of two, and an absolute precision of 5% resulted in a sample size of 769 children per region. In each region, schools were ordered by size and 60 clusters of four schools were selected using systematic sampling, while accounting for school size to have enough replacement schools in case schools refused to participate. Out of these 60 clusters, 30 clusters were randomly selected, and within each cluster the first school was invited to participate. The schools on the final list for participation were randomly distributed over the three different grades to try to include an equal number of children per age group in the study. In general, two classes within the assigned grade (50 pupils) were selected in each school, anticipating a response rate of 50%. Data collection The study was approved by the medical ethics committee of the Erasme Hospital in Brussels. The field work took place between September and December 2010. A van, equipped with an ultrasound instrument, a computer, a stadiometer, and a scale (Thyromobil) visited the 60 schools selected. The same methods were used as in the 1998 study (9), and the study was performed during the same season. Upon informed consent from the selected schools and the parents of the selected children, a urine sample was collected from the children and the thyroid volume (Tvol) and weight and height of children was measured. A general questionnaire
FIG. 1. Geographical distribution of the 60 schools investigated in Belgium and the number of school-aged children (n = 1541) investigated by site (national survey on iodine status of school-aged children, Belgium, 2010).
1048 was completed by the parents; a sample of household salt was collected, and the mothers of the children were requested to provide a urine sample. Tvol was measured by one physician with real-time sonography (Sonoline SI400; Siemens), according to Brunn et al. (21), using a 7.4-MHz linear array transducer. The investigator who performed the ultrasound measurements during the previous survey (9), Dr. W. Shabana, participated during the first week of the field work to standardize the measurements of the Tvol as in 1998. Longitudinal and transverse scans were performed, allowing measurement of the depth (d), width (w), and length (l) of each lobe. Measurement of Tvol was performed on children in the supine position with hyper extended neck (22). The volume of each thyroid lobe was calculated by the formula V (mL) = 0.479 · d · w · l (22). Tvol was the sum of the volumes of both lobes. The volume of the isthmus was not included. Tvol measured were compared with the European reference values of iodine-replete schoolaged children (12) and with the international reference values of school-aged children from areas of long-standing iodine sufficiency (22). Children were identified as suffering from goiter if the sex-specific Tvol, expressed as a function of age or body surface area (BSA) was higher than the 97th percentile established in an iodine-sufficient population. BSA was calculated by the formula BSA = W0.425 · H0.725 · 71.84 · 10 - 4, where W is the body weight in kg and H the height in cm. Analysis of samples All urine samples were frozen and kept at - 80C until analysis. UIC were measured in duplicate at Erasme hospital by using a modification of the Sandelle-Kolthoff reaction with spectrophotometric detection (23). The sensitivity of the assay was 12 lg/L. The Erasme laboratory participated successfully in the Program to Ensure the Quality of Urinary Iodine Procedures of the US Centers for Disease Control and Prevention (24). The iodine content of iodized salt samples was measured using the MBI kit, produced by MBI chemicals (20).
VANDEVIJVERE ET AL. Table 1. Number of School-Aged Children by Region, Sex, and Age Brussels
Flanders
Wallonia
Age (years)
Boys
Girls
Boys
Girls
Boys
Girls
5 6 7 8 9 10 11 12 13 Total
1 25 16 10 25 16 19 1 0 113
4 22 15 12 12 25 13 1 0 104
7 35 56 80 68 69 62 13 0 390
1 37 43 64 61 68 64 4 0 342
5 39 33 49 50 54 40 17 1 288
4 39 36 57 46 64 38 17 1 302
National survey on iodine status among school-aged children Belgium, 2010. Two missing data for age in Flemish boys.
collected from the children, and the number of urine samples collected from their mothers, can be found in Figure. 2. The median UIC in Belgian school-aged children was 113.1 lg/L (interquartile range 79.8–161.5 lg/L [CI 110.4– 116.6 lg/L]), which is within the optimal level of 100–199 lg/ L (14). The median UIC in boys was significantly higher than in girls. The median UIC in Flanders was significantly higher than in Wallonia (Table 2). In a pair of 624 children and mothers, the median UIC was 114.6 lg/L in school-aged children, and 84.4 lg/L in their
Statistical analyses The statistical analyses were carried out using STATA 10.1 (StataCorp). As UIC is not normally distributed, nonparametric methods were used. The median UIC was used as the measure of central tendency. Differences between regions, sex, and age groups were explored using the two-sample Wilcoxon rank-sum test or the Kruskal-Wallis equality-ofpopulations rank test. Differences in Tvol by region were explored using the two-sample t-test after logarithmic transformation. Results Among the 1541 children participating in the survey, 1515 were between 6 and 12 years old, of which 217 from Brussels, 734 from Flanders, and 590 from Wallonia (Fig. 1 and Table 1). The overall response rate at the level of the children was 51.4%. The mean age was similar in Flanders and Wallonia, while there was a higher percentage of boys in Flanders, compared to Wallonia, but this difference was not significant ( p = 0.097). An overview of the number of children invited, the number of children included in the study, the number of urine samples, household salt samples, and thyroid echographies
FIG. 2. Overview of the number of children invited, the number of children included in the study, the number children who provided a urine sample, a household salt sample and underwent thyroid echography, and the number of mothers who provided a urine sample.
CORRECTION OF IODINE DEFICIENCY IN BELGIUM
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Table 2. Urinary Iodine Concentrations in Belgian School-Aged Children UIC (lg/L)
All population
n
Median [95% CI]
P25
P75
P95
Percent < 100 lg/L
Percent < 50 lg/L
1507
113.1 [110.4–116.6]
79.8
161.5
249.5
39.4%
8.8%
a
Boys Girls
785 722
120.3 [113.9–126.9] 108.4 [104.9–112.8]
84.7 75.8
170.6 148.5
254.8 234.4
35.9% 43.1%
6.8% 11.1%
Age 6–8 years Age 9–10 years Age 11–12 years
650 547 284
114.5 [111.0–121.0] 113.0 [107.5–119.2] 110.7 [105.5–119.2]
81.9 78.6 78.5
164.3 162.6 153.6
253.3 248.3 235.1
38.3% 40.4% 39.8%
9.1% 9.1% 8.1%
Walloniab Flandersb
572 723
107.4c [101.5–112.3] 118.5 [113.1–124.8]
76.6 82.9
150.9 169.8
237.0 255.3
44.1% 36.4%
9.3% 8.2%
National survey on iodine status among school-aged children Belgium, 2010. a p < 0.001 for boys compared to girls. b Excluding Brussels. c p < 0.001 for Wallonia compared to Flanders. UIC, urinary iodine concentration; CI, confidence interval of the median.
mothers; these medians were significantly different ( p < 0.001). Additionally, the frequency of school-aged children with UIC < 100 lg/L was only 38.6%, but 63.5% of the mothers had UIC < 100 lg/L (Fig. 3). UICs were not significantly different ( p = 0.8) between children whose mothers provided and children whose mothers did not provide a urine sample. Spearman rank correlation between UIC from children and mothers was 0.17 ( p < 0.001). There was no significant difference in median UIC of mothers among the regions. The percentage of school-aged children with goiter was 7.2% when using the European reference values by sex and age, while it was 4.3% as a function of sex and BSA (Table 3). There was a trend to a higher goiter prevalence in Wallonia than in Flanders as function of both sex and age and sex and BSA, but the difference was not significant ( p = 0.097 and p = 0.095, respectively) (data not shown). Tvol in school-aged children progressively increased with age in both sexes and was higher in girls than in boys (Fig. 4). The difference in Tvol between boys and girls was significant
( p = 0.002). There were no significant differences in the percentage of boys and girls included in every age group. Boys consumed significantly more milk than girls, and also consumed significantly more slices of bread per day. There were no significant differences in consumption frequency of any food group and in the percentage of use of iodized salt between boys and girls. Frequency of fish consumption was significantly higher in Flanders than in Wallonia, although the amount consumed was higher in Wallonia. There was no significant regional difference in frequency of milk and dairy drink consumption and in the utilization of iodized salt. The bread consumption was significantly higher in Flanders than in Wallonia (Table 4). Frequency of consumption of milk and dairy drinks was significantly higher among children than their mothers. The percentage of children consuming milk and dairy drinks at least once a day was 32.04%, while for mothers this was only 13.23%. Approximately, 44% of the children consumed more than one glass of milk per day, among the mothers only 25%. Among the 904 samples of household salt obtained, 63.2% did not contain iodine. Of the 333 iodine-containing samples, 43.5% was in the form of KI and 56.5% was in the form of KIO3. About 2.9% of the samples contained an iodine content of 7 ppm, 8.8% of the samples contained an iodine content of 15 ppm, and 25.1% of the samples contained an iodine content of 30 ppm. When comparing the children with and without a sample of household salt, there were no differences in sex, age group, and region. There were no differences in median UIC between children who provided a salt sample and children who did not provide a salt sample. There was no significant difference in percentage of households using iodized salt among the regions ( p = 0.70) (data not shown). There was no significant difference in UIC between children using iodized household salt and children not using iodized household salt. The same applied for their mothers. Discussion
FIG. 3. Frequency distribution of urinary iodine concentration in matched pairs of school-aged children and their mothers in Belgium (n = 624). The recommended range for the medurinary concentration is 100–199 lg/L (national survey on iodine status among school-aged children Belgium, 2010).
Compared to 12 years ago, iodine status in school-aged children in Belgium improved (9); median UIC increased from 80 to 113 lg/L. The current median UIC indicates iodine sufficiency in school-aged children, although the prevalence of goiter was similar to the previous national survey. Iodine
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VANDEVIJVERE ET AL. Table 3. Prevalence of Goiter Among Belgian School-Aged Children Reference values by sex and age (n = 1512)a
Age (years) 5 6 7 8 9 10 11 12 13 Total
Reference values by sex and body surface area (n = 1522)b
Boys (%)
Girls (%)
Total (%)
Boys (%)
Girls (%)
Total (%)
— 4.0 12.4 7.3 9.8 7.9 5.0 12.9 — 8.0
— 10.3 4.3 6.1 2.5 8.3 7.0 4.6 — 6.4
— 7.1 8.5 6.7 6.5 8.1 5.9 9.4 — 7.2
0.0 3.1 9.6 7.3 4.2 2.9 1.7 23.3 0.0 5.4
0.0 4.4 3.2 4.6 0.9 4.5 2.6 0.0 0.0 3.3
0.0 3.7 6.6 5.9 2.7 3.8 2.1 13.5 0.0 4.3
National survey on iodine status among school-aged children Belgium, 2010. a Children with a missing thyroid volume (n = 3), missing age (n = 2), children younger than 5.5 years (n = 22), and children older than 12.4 years (n = 2) were excluded from these analyses. b Children with a missing thyroid volume (n = 3), missing weight (n = 4), or height (n = 0), with a BSA value of 0.7 (n = 9) and with a BSA value higher than 1.7 (n = 3) were excluded from these analyses. BSA, body surface area.
FIG. 4. Thyroid volume as a function of age and sex (n = 1512) (national survey on iodine status among schoolaged children Belgium, 2010). Box plots show median values (the horizontal line in the center of each box), as well as the 25th and 75th percentile (bottom and top of error bar).
status was optimal, but the median UIC was significantly lower in Wallonia (107 lg/L) than in Flanders (119 lg/L). These findings corroborate the result of a previous national survey showing the same regional differences (16). The lower UIC in Wallonia may explain the higher prevalence of thyroid nodules, MNG, thyroidectomies, and more extensive use of antithyroid medication in the adult population in this region compared to Flanders as suggested in a previous study (16). Among the mothers, there was not found a regional difference in UIC, probably due to the smaller size of the sample. Interestingly, despite sharing a similar household food basket, the median UIC in the school-aged children was significantly higher than the median UIC of their mothers. According to the WHO criteria, the current median UIC in the Belgian school-aged children indicated optimal iodine status. By contrast, the median UIC in the mothers of the same children indicated MID. These data are in concordance with a survey performed in 2004 in adults residing in Brussels where the median UIC was only 68 lg/L (25). Additionally, other studies have shown that despite optimal median UIC in school-aged children, the median UIC in their mothers, in pregnant women, or weaning infants may indicate iodine deficiency (15,26). The most plausible explanation as to why Belgian school-aged children had a higher median UIC than their mothers is that it has been found previously that dairy products are the main source of iodine in Belgium (27), as in many other industrialized countries. Another Belgian study showed that the mean iodine concentration in milk from Belgian dairy cattle herds was 145 lg/L (28). Because the consumption of dairy products in Belgium is much higher in school-aged children than in adults, it is not surprising that the iodine intake of children is higher than in their mothers. The prevalence of goiter was found to be similar to 12 years ago (7.2% in 2010 compared to 5.7% in 1998) (9). Because the increase of iodine intake in Belgium is recent, it is not surprising that prevalence of goiter, which is the result of longterm iodine deficiency, has not yet changed after introduction of iodized salt as reported in other iodine deficient regions (29). The European reference values were used to allow for comparison with the results of the previous national school
CORRECTION OF IODINE DEFICIENCY IN BELGIUM
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Table 4. Food Consumption Habits by Sex and Region Sex
Mean number of slices of bread per day Use of iodized household salt (%) Frequency of fish consumption (%) Never Less than one day a week 1–3 days per month One day per week 2–4 days per week 5–6 days per week One time per day Two to three times a day Frequency of milk and dairy drink consumption (%) Never Less than one day a week 1–3 days per month One day per week 2–4 days per week 5–6 days per week One time per day Two to three times a day More than three times a day Quantity of fish consumption per day (%) Less than 100 g More or less 100 g More than 100 g Quantity of milk and dairy drink consumption per day (%) Less than one glass More or less one glass One to two glasses More than two glasses
Region
Boys (n = 531)
Girls (n = 519)
pValue
Flanders (n = 485)
Wallonia (n = 395)
pValue
3.6 – 1.8 25.0
3.4 – 1.6 23.3
0.040 0.525 0.542
4.2 – 1.8 22.3
2.9 – 1.4 23.6
< 0.001 0.659 0.005
6.4 13.2 31.3 37.3 7.5 0.2 0.0 0.2
5.6 15.4 31.4 35.1 8.7 0.0 0.4 0.0
5.4 11.5 35.3 38.1 7.6 0.2 0.0 0.0
8.6 18.0 31.1 34.7 4.1 0.0 0.0 0.0
5.8 2.1 2.4 3.6 8.1 7.5 33.3 28.8 4.0
3.5 2.7 1.9 4.8 10.0 8.1 34.7 27.6 2.9
5.2 2.3 3.3 4.1 9.1 7.6 31.3 31.1 3.5
4.1 1.8 1.5 4.1 7.6 6.6 39.2 27.8 4.1
16.9 36.9 23.9
19.7 40.7 20.8
21.0 40.0 19.8
14.7 35.7 27.6
10.0 37.9 32.6 11.5
14.1 37.8 33.7 7.3
11.1 40.8 35.3 9.5
11.9 38.2 32.4 10.4
0.515
0.314
0.251
0.003
0.036
0.860
National survey on iodine status among school-aged children Belgium, 2010.
children survey of 1998. However, it has been suggested that the European reference values overestimate Tvol and consequently underestimate the prevalence of goiter determined by ultrasound (22,30). In our study, only 37% of the households used iodized salt, which is below the WHO recommendation that at least 90% of the households should use iodized salt to eliminate iodine deficiency as a public health problem. There were no regional differences in the utilization of iodized salt. The differences in iodine status between the two main regions of Belgium may be explained by the higher consumption of sea food and bread in Flanders than in Wallonia. Similarly, the higher median UIC in boys than in girls could be explained by the higher consumption of bread and milk by boys. The implementation of bread fortification with iodized salt, since 2009, may have contributed to the substantial increase in iodine status and explain why Belgian school-aged children are currently iodine sufficient. According to data from ESCOSALT, one of the main suppliers of iodized salt to the bakers in Belgium, the utilization of iodized salt by the bakers increased over the years from 11% in 2001 to 41% in 2010, the year of the survey. According to ESCOSALT, the total volume of salt remained remarkably constant over these 10 years.
Because of this, it can be derived that there was indeed a substitution of noniodized salt with iodized salt over the last 10 years. Presently, there is no need to increase the concentration of iodine in salt used for bread fortification (10–15 ppm), but there is a need to increase the number of bakers using iodized salt, as according to ESCOSALT data, still less than 50% of the bakers use iodized salt. Furthermore, the use of iodized instead of noniodized table salt by households needs also to be increased to correct iodine deficiency in Belgian adults and particularly in women of child-bearing age. At the moment, however, we do not recommend adding iodized salt to other foods than bread. The main drawback of the current situation in Belgium is the absence of a legal framework. This situation may lead to inefficiencies in the implementation of the strategy to optimize iodine intake. The utilization of iodized salt in bread— on voluntary basis—was endorsed by the bakery industry and the Ministry of Health in 2009. Other sectors in the food industry have also expressed their willingness to use iodized salt for food fortification. Therefore, to maintain an optimal iodine intake, a regulatory framework would be preferable where the concentration of iodine in salt for the production of
1052 bread and in household salt is determined by law. The recent report suggesting the reappearance of iodine deficiency in the United Kingdom (8) highlights the need for a regulatory legal framework of the market of iodized salt to sustain the control of iodine deficiency also in industrialized countries. For many years, the United Kingdom was considered to be an iodine sufficient country (31). The main source of iodine in the United Kingdom, as in Belgium, is milk. However, the lower consumption of milk by adolescents and adults compared to school-aged children may to some extent explain iodine deficiency among the United Kingdom adolescents. The results of the United Kingdom survey need to be confirmed in a representative national study, which also includes schoolaged children to truly grasp the public health extent of iodine deficiency in the United Kingdom. In Belgium, a national survey among women of child-bearing age and pregnant women should be organized. In conclusion, the fortification of bread with iodized salt corrected iodine deficiency in Belgian school-aged children, but not in their mothers. Our findings suggest that the median UIC in school-aged children may not be an accurate surrogate of adults’ iodine status. Therefore, monitoring iodine status should not be limited to school-aged children as currently recommended, but should be extended to women of child-bearing age and pregnant women. To provide an adequate iodine intake to women of child-bearing age, the current Belgian program needs to increase the use of iodized salt in bread and the consumption of iodized instead of noniodized household salt. These two objectives could be better achieved if a legal framework were put in place to regulate the market of iodized salt. Acknowledgments The authors acknowledge the financial support from the Federal Public Service of Health, Food Chain Safety and Environment. We would like also to acknowledge MERCK KgaA, Darmstad, Germany for their logistical support. We thank the schools who agreed to participate and all participating children and their parents. S.V. and R.M.R. designed and coordinated the research and wrote the paper. A.B.M., S.A., F.A. conducted the research. S.V. performed the statistical analyses and had primary responsibility for the final content. All authors read and approved the final article. The authors acknowledge B. Howovier and D. Martin for the laboratory analyses. Disclosure Statement All authors declare not having any conflict of interest with regard to this study. References 1. Andersson M, De Benoist B, Darnton-Hill I, Delange F (eds) 2007 Iodine deficiency in Europe: a continuing public health problem. World Health Organization/UNICEF, Geneva, Switzerland. 2. Laurberg P, Nohr SB, Pedersen KM, Hreidarsson AB, Andersen S, Bulow PI, Knudsen N, Perrild H, Jorgensen T, Ovesen L 2000 Thyroid disorders in mild iodine deficiency. Thyroid 10:951–963. 3. Zimmermann MB 2007 The adverse effects of mild-tomoderate iodine deficiency during pregnancy and childhood: a review. Thyroid 17:829–835.
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Address correspondence to: Stefanie Vandevijvere, M.Sc. Department of Public Health and Surveillance Scientific Institute of Public Health J. Wytsmanstraat 14 Brussels 1050 Belgium E-mail:
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