IODINE STATUS IN ROMANIA AFTER 20 YEARS OF MANDATORY SALT IODIZATION: DISCORDANT RESULTS IN SCHOOLCHILDREN AND NEONATES

Abstract

Objective

To monitor the iodine status in Romanian schoolchildren and neonates after 20 years of mandatory salt iodization.

Subjects and methods

In a national representative sample of 1352 children (7-12 years) we measured median urinary iodine concentration (mUIC) and creatinine (UCC) in spot urine samples and investigated household use of iodized salt. From 18349 neonates registered in the MEDILOG program for TSH screening we calculated the percentage of neonatal TSH >5 mIU/L (<3% indicating adequate iodine intake).

Results

mUIC in schoolchildren was 141 µg/L (bootstrapped 95% CI 134, 146), showing adequate iodine intake in all but 1 county; mUIC was similar in historical endemic and non-endemic counties (140 µg/L and 143 ug/L, respectively) and in urban and rural areas (140 µg/L and 142 µg/L, respectively); mUIC/UCC = 118 ug/g. Iodized salt was used in 62% of households. In children using iodized salt (61.7%), mUIC was higher than in those using coarse (non-iodized) salt (24.6%): 150 vs. 121 µg/L (p<0.001). The percentage of nTSH >5 mIU/L was 14.7% (3.2%-27.3%), higher in non-endemic counties and urban areas.

Conclusion

The current salt iodization program for households and bakery industry ensures an adequate iodine intake in schoolchildren. Discordantly, nTSH levels indicate a mild-moderate ID in neonates, suggesting ID in pregnant women. The percentage of households using iodized salt is below the recommended >90% needed for an efficient ID prevention program. More efforts should be directed to increase the public awareness on the health risks of ID and the benefits of ID prevention, notably for the neurointellectual development in children.

INTRODUCTION

Iodine is a trace element necessary for the normal functioning of the thyroid gland. It is instrumental in the synthesis of thyroid hormones, which play a key role in cell metabolism, in the process of growth and differentiation of all organs and, above all, of the brain: both during intra-uterine life, but also after birth (1). Iodine deficiency (ID) causes irreversible alterations in fetal brain development and functioning, with varying degrees of mental retardation, out of which the most severe is thyroid endemic cretinism (2,3). Postnatally, ID affects the child’s physical and mental development. ID continues to remain the most common cause of preventable mental retardation (4). ID can lead to thyroid overgrowth with the appearance of goiter, thyroid nodules, and hypothyroidism. In adults, it can generate a higher percentage of more aggressive thyroid cancers (follicular or anaplastic cancer) (1,5). ID disorders (IDD) cover all the negative consequences of ID on growth and differentiation processes in the exposed population (1,4). The disorders can be prevented by providing the population with normal iodine intake (6-8).

The age-standardized ID prevalence rate for both sexes worldwide, according to the Global Burden of Diseases (GBD) data, was 2216 per 100,000 population in 2019, compared to 2834 per 100,000 population in 1990 (9). According to the same source, for Romania, this indicator was 455 per 100,000 population for 2019 vs. 507 per 100,000 population in 1990 (9).

The daily dietary intake of iodine recommended by the World Health Organization (WHO), by the United Nations Children’s Fund (UNICEF), and the European Food Safety Authority (EFSA) is 90 µg (15 µg/kg/day) for preschool children 0-59 months, 120 µg (6-4 µg/kg/day) for school children 6 - 12 years, 150 µg (2 µg/kg/day) for adolescents over 12 years and adults, and about 250 µg/day for pregnant and breastfeeding women (10, 11). Dietary iodine insufficiency affects around 2 billion people worldwide, of whom 50 million show clinical manifestations. The most vulnerable groups are children and breastfeeding women (7, 11). In 1999, WHO, UNICEF and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD, currently named Iodine Global Network, IGN) reported ID in 21 countries in Central and Western Europe and in 12 Eastern European countries, including Romania where there is a permanent and widespread geoclimatic deficiency in this microelement (7,12). More recent European surveys have reported ID in 1 out of 16 (6.3%) studies in schoolchildren, 54% in adults and 64-70% of pregnant women (13,14).

Universal salt iodization is the most effective method of preventing chronic ID disorders (11). In 2021, 89% of the world’s population was using iodized salt (15). It was estimated a potential global economic benefit of nearly $33 billion due to the improved cognitive development as a result of the increased number of countries who achieved adequate iodine intake (from 67 countries in 2003, to 118 in 2020) (16,17).

In Romania, in 2002 Government Decision no. 568 was passed on universal iodization of salt for human consumption, animal feed and use in the food industry, with subsequent amendments and additions, which stipulates the following: “the retail sale of non-iodized salt is prohibited on the territory of Romania, both for personal use and for public use in the restaurant and catering industry” and “the use of iodized salt in animal feed and in the food industry is optional, except for bread and bakery products”. Salt is iodized with 25 - 40 mg iodine/kg salt, using potassium iodide (KI) or potassium iodate (KIO3), in the range recommended by WHO (15-40 mg/kg at household level) (18).

Four indicators are recommended by WHO, UNICEF and IGN for the assessment of iodine intake in a defined population: urinary iodine concentration (UIC) in children or adults, the proportion of newborns with neonatal thyroid stimulating hormone (nTSH) levels >5 mIU/L, serum thyroglobulin levels and thyroid volume (determined by palpation and/or ultrasonography) (11,19,20). The prevalence of goiter reflects more the history of the iodine nutritional intake, while the other 3 indicators better reflect the current iodine status of the population (11,20). UIC varies significantly from one day to another in a healthy individual, depending on diet (21). It is therefore not recommended as an indicator to determine the long-term average dietary iodine intake of an individual. It is used in epidemiological studies involving at least several hundreds of individuals, taking the median value of randomly collected urine iodide (11,20). Sufficient dietary iodine intake is reflected in a median UIC of 100 - 300 µg/L (usually measured in morning urine samples) in school children 6-12 years of age, and 150 - 250 µg/L (maximum 499 µg/L) in pregnant women (11). The amount of daily dietary iodine intake can also be evaluated (10). ID in newborns is indicated by the proportion of neonates with nTSH > 5 mU/L, optimally being under 3% (11). In Romania neonatal TSH is measured as part of the screening for congenital hypothyroidism (22).

The present study aimed to assess iodine status in the Romanian population by measuring median UIC in schoolchildren aged 6-12 years and the proportion of newborns with nTSH > 5 mIU/L, as well as the use of iodized salt in the schoolchildren’ households.

SUBJECTS AND METHODS

Study design

For the evaluation of urinary iodine concentration and use of iodized salt we conducted a cross-sectional study from November 2023 to March 2024. It was designed to obtain a sample of school children (6–12 years) representative for the country and its 8 development regions (North-East, South-East, South, South-West, West, North-West, Centre, Bucharest-Ilfov).

The children were selected from the lists of family doctors and school doctors in a two-stage process, as recommended by WHO and UNICEF (11,20). In the first stage the family- and school doctors were chosen, and in the second, children were randomly selected from the doctors’ lists. Children were allocated per doctor according to the size of the representative sample per region and to the number of doctors registered in the program in each region. The regional representation was ensured by calculating the number of children in the sample against the actual population of children aged 6-12 years in that development region and by including children from 4 urban and 6 rural localities from at least 2 different counties in each development region.

Data collection was carried out by a trained field team who administered a face-to-face questionnaire to the child’s caregivers and collected urine samples. The questionnaire included, among other dietary evaluations, data on the use of iodized salt and other types of salt. Urine samples were collected from children at home or at the school doctor’s office. All data were collected coded and registered by subject number, location, age and sex. Samples were transported within 2-3 days after collection to the laboratory of the National Institute for Mother and Child Health “Alessandrescu Rusescu” where they were refrigerated.

For the neonatal TSH evaluation, heel prick TSH samples from newborns were analyzed from the MEDILOG database. The MEDILOG database is managed within the national neonatal screening program for hypothyroidism in Romania (22). The samples included in the study were from the Bucharest regional screening center (National Institute for Mother and Child Health “Alessandrescu Rusescu”). They were collected from newborns in maternity wards in 26 counties during the period December 2023 - February 15, 2024. Samples collected from premature babies, newborns with birth weight under 2500 g and after 5 days from birth were excluded.

Biochemical analysis

Urinary iodine concentration (UIC) was spectrophotometrically measured by the Sandell - Kolthoff reaction, i.e. a color reaction obtained by reduction of cerium ions in the +4 oxidation state (ceric) in the presence of iodine ion catalyst (23). All samples, the calibration curve and the controls were measured in duplicates. Samples were repeated for difference values higher than 50 µg/L. Samples with iodine above 600 µg/L, i.e. suspected of iodine contamination, were excluded.

Urinary creatinine concentration (UCC), assessed by the Jaffe method, was used as a reporting parameter for iodine concentration, in order to correct for the urine dilution (24). The reference values for urinary creatinine spontaneous emission in pediatric population are 0.20-3 g/L (25). The samples with urinary creatinine < 0.2 g/L or > 4 g/L (i.e., suspicion of incorrect collection or kidney disease) were excluded.

Neonatal TSH level was measured by the FEIA method (Fluorescent-Enzyme Immuno-Assay), based on direct sandwich technique. Fluorescence signals are directly proportional to analyte concentrations in the samples. Kit includes all reagents required for sample processing including Dry Blood Spot calibrators and controls (Producer Kit).

A proportion of newborns with TSH > 5 mIU/L under 3% reflects normal iodine intake, 3-19.9% mild iodine deficiency, 20 – 39.9% moderate iodine deficiency, > 40% severe iodine deficiency (11).

All the data collected from Bucharest (the capital city) and the surrounding area (Ilfov county) were analyzed together as from a single center.

The laboratory works closely with the Ensuring the Quality of Urinary Iodine Program (EQUIP) and the Newborn Screening Quality Assurance Program (NSQAP) run by the Centers for Disease Control and Prevention in Atlanta, USA. The laboratory was also included in a project aiming to standardize the measurement of urinary iodine across Europe (14).

This study was approved by the Institutional Ethics Committee of Institute for Mother and Child Protection “Alessandrescu Rusescu” (no 329/7.01.2022). Written informed consent was obtained from the parents of the school-age children. An oral consent was also obtained from the children.

Statistical analysis

We used SPPS version 25 (IBM, Armonk, NY, USA) for data processing and analysis. Normally distributed continuous data are presented as mean ± SD. Nonparametric data are presented as median, IQR and the 95% CI around the median was obtained using the bootstrap technique (n = 1000). Differences were assessed using Mann-Whitney U test for two categories of nonparametric data. Group differences for more than two categories were tested using the Kruskal-Wallis ANOVA test followed by Mann-Whitney post hoc tests. Chi-square tests were used to evaluate differences for categorical data. Statistical significance was set at p < 0.05.

RESULTS

Schoolchildren

We enrolled 1352 children with a median age of 9 years (range 7 – 12 years), 701 girls (51.8%) and 651 boys (48.2%); 49% were from urban areas, 51% from rural areas; 1096 children (81%) reside in 16 counties formerly known with mild to moderate iodine deficiency (“endemic” counties), 256 children (19%) reside in 4 counties with iodine sufficiency (“non-endemic” counties) (Fig. 1 and Table 1). The percentage of urban population was lower in endemic vs. non-endemic counties, 44.5 versus 68.3%, p<0.001.

Figure 1.

Study population source (Romanian counties, in yellow) for urinary iodine concentration in schoolchildren (left) and for neonatal TSH (right).

Table 1.

Urinary iodine concentration (µg/L, median) in schoolchildren and neonatal TSH > 5 mIU/L (percentage) in newborns, as indicators of populational iodine status

	Urinary Iodine Concentration					Neonatal TSH
	N	% Urban	UIC mIU/L	UIC/ UCC	UIC urban/ rural	N	% Urban	%TSH>5	%TSH>5 miu/l urban/ rural
Endemic counties
Arges	69	42.8	104	97	137/86	968	44.2	14.2	17.5/11.5
Dambovita	82	35.9	139	111	166/126	752	26.3	13.2	12.6/13.4
Dolj	24	100	117	93	117/-	981	48.7	3.2	3.8/2.6
Hunedoara	66	40.2	129	100	135/118	468	56.0	13.9	13.4/14.6
Mehedinti	70	44.0	165	147	165/166	270	46.3	4.4	4.8/4.1
Olt	73	36.0	142	130	170/124	556	44.4	10.3	12.6/8.4
Prahova	43	33.3	153	109	293/141	1167	44.3	13.3	13.9/12.8
Valcea	97	35.7	125	117	105/149	414	49.8	13.8	13.1/14.4
Vrancea	71	26.3	147	125	110/159	499	28.9	13.6	16.7/12.4
Botosani	71	21.0	86	66	81/86	N/A
Cluj	78	81.4	151	115	155/143	N/A
Harghita	102	31.4	169	158	182/166	N/A
Iasi	55	43.6	126	115	83/159	N/A
Mures	72	60.8	167	157	195/146	N/A
Neamt	68	35.7	133	107	113/160	N/A
Sibiu	55	57.9	176	148	210/151	N/A
Alba	N/A					411	39.6	5.6	4.9/6.0
Brasov	N/A					1245	57.0	27.3	29.6/24.3
Buzau	N/A					624	37.7	12.0	9.4/13.6
Covasna	N/A					378	31.5	22.8	26.1/21.2
Gorj	N/A					439	38.7	7.1	9.4/5.6
Non-endemic counties
Bucharest+Ilfov	83	100	117	120	117/-	4233	85.3	21.1	21.7/17.8
Braila	68	64.7	136	120	116/163	436	54.6	19.7	20.2/19.2
Teleorman	51	46.1	160	120	142/166	381	30.4	14.4	14.7/14.3
Bihor	54	46.3	171	113	175/163	N/A
Arad	N/A					587	42.2	10.9	10.5/11.2
Calarasi	N/A					516	29.1	16.7	14.0/17.8
Constanta	N/A					1152	58.4	8.8	8.2/9.6
Galati	N/A					679	44.2	7.7	8.7/6.9
Giurgiu	N/A					502	23.7	14.7	10.9/15.9
Ialomita	N/A					426	39.9	11.0	11.8/10.5
Tulcea	N.A					265	52.1	4.2	4.3/3.9

UIC spot urinary iodine concentration (µg/L), UCC spot urinary creatinine concentration (g/L), UIC/UCC=iodine/creatinine ratio (µg/g), TSH thyroid stimulating hormone. For neonatal TSH values, low-birth weight and premature neonates < 36 weeks were excluded.

Median UIC in schoolchildren (49% from urban areas) is 141 µg/L (bootstrapped 95% CI 134, 146), showing adequate iodine intake (i.e., > 100 µg/L) in both urban areas - 140 µg/L and rural areas - 142 µg/L, p = NS (Table 2).

Table 2.

Urinary iodine concentration in schoolchildren (µg/L, median) and neonatal TSH > 5 mIU/L (%) in counties with and without historical endemic iodine deficiency

	Urinary Iodine Concentration						Neonatal TSH
	N	% Urban	UIC	UCC	UIC/UCC	UIC Urban/Rural	N	% Urban	%TSH >5 mIU/L	%TSH >5 mIU/L Urban/Rural
Endemic counties	1096	44.5#	140 (134, 147) [IQR 92-209]	1.16 (1.14, 1.20) [IQR 0.84-1.59]	117 (112, 122) [IQR 78-180]	143/135	9172	43.6	13.5^	15.0**,&/12.3**
Non-endemic counties	256	68.3#	143 (125, 151) [IQR 95-151]	1.14 (1.05, 1.23) [IQR 0.79-1.58]	120 (113, 130) [IQR 87-171]	125*/164*	9177	62.8	16.0^	17.6**,&/13.3**
Total	1352	49.0	141 (134, 146) [IQR 93-207]	1.15 (1.13, 1.19) [IQR 0.83-1.60]	118 (114, 122) [IQR 79-177]	140/142	18349	53.2	14.7	16.5**/12.7**

UIC spot urinary iodine concentration (µg/L), UCC spot urinary creatinine concentration (g/L), UIC/UCC=iodine/creatinine ratio (µg/g), TSH thyroid stimulating hormone. Values are median (bootstrapped 95% CI) [interquartile range], all such values. For neonatal TSH values, low-birth weight and premature neonates < 36 weeks were excluded. # percentage of urban population is lower in endemic vs nonendemic counties, p<0.001. * UIC is lower in urban vs. rural population in nonendemic counties, p<0.01 (of note, corresponding UCC were also lower in urban 1.06 g/L vs rural areas 1.26 g/L, p<0.05). ^ Proportion of TSH>5 mIU/L is higher in nonendemic vs. endemic counties, p < 0.001. ** Proportion of TSH>5 mIU/L is higher in urban vs. rural population, p<0.001 in endemic, non-endemic counties and in the total study population. & Proportion of TSH>5 mIU/L is higher in urban population of non-endemic vs. endemic counties, p < 0.001.

Median UIC was adequate in most counties (range 104 – 176), except in 1 endemic county (Botosani) in which it was 87 µg/L (indicating mild iodine deficiency) (Table 1, Fig. 2).

Figure 2.

Distribution of median urinary iodine concentration (UIC) in schoolchildren (A) and proportion of neonatal TSH > 5 mIU/L (B) in counties with geographical (endemic) iodine deficiency and counties with iodine sufficiency (non-endemic). The red lines mark the cutoffs for iodine sufficiency (median UIC ≥ 100 µg/L, neonatal TSH>5 mIU/L < 3%), the dotted line mark the cutoff between mild iodine deficiency (nTSH>5 mIU/l in 3-19.9% of the population) and moderate (20 – 39.9%).

Median UIC was 140 µg/L (bootstrapped 95% CI 134, 147) in endemic and 143 ug/L (bootstrapped 95% CI 125, 151) in non-endemic counties (p = NS) (Fig. 3);

Figure 3.

A. Urinary iodine concentration (UIC) in schoolchildren from counties formerly known with mild to moderate iodine deficiency (endemic) or with iodine sufficiency (non-endemic). B. UIC in schoolchildren from urban and rural areas, in endemic and non-endemic counties.

Median UIC/UCC ratio (118 µg/g for the studied population) was generally lower than median UIC alone (141 µg/L). Median UIC/UCC in studied counties ranged from 66 – 158 µg/g, 3 endemic counties having levels < 100 µg/g (Botosani, Arges, Dolj).

Comparing urban and rural areas, median UIC was similar in schoolchildren from endemic counties, while it was higher in rural areas from non-endemic counties (164 vs. 125 µg/L, p < 0.01) (Table 2, Fig. 3). However, median UCC was also significantly higher in those rural areas 1.26 vs. 1.06 g/L, p<0.05), and UIC/UCC ratios were statististically non-different in rural and urban non-endemic areas (123 vs. 117 µg/g, p = 0.084).

Median UIC distribution in the 8 regions of Romania is represented in Figure 4.

Figure 4.

Distribution of median urinary iodine concentration (UIC, µg/L) and % neonatal TSH > 5 mIU/L in the Romanian development regions (1 North-East, 2 South-East, 3 South, B+IF- Bucharest and Ilfov, 4 South-West, 5 West, 6 North-West, 7 Center. The horizontal lines indicate the cutoff between mild iodine deficiency and sufficiency.

The distribution of UIC levels in schoolchildren is presented in Table 3. Only 8% of the evaluated urines had low UIC values < 50 µg/L, while 7% had more than adequate levels (> 300 µg/L), with similar distribution in endemic and non-endemic counties.

Table 3.

Distribution of urinary iodine concentration in schoolchildren

UIC	Total N=1352	Endemic counties N = 1096	Non-endemic counties N = 256
UIC >300 µg/L	94 (7.0%)	80 (7.3%)	14 (5.4%)
UIC 100-299 µg/L	866 (64.0%)	694 (63.3%)	172 (67.2%)
UIC 50-99 µg/L	284 (21.0%)	230 (21.0%)	54 (21.1%)
UIC 20-49 µg/L	108 (8.0%)	92 (8.4%)	16 (6.3%)
UIC < 20 µg/L	0	0	0
Median populational UIC µg/L	141	140	143

Use of iodized salt

Data from the 1352 questionnaires showed that 61.7% of the families of enrolled schoolchildren use iodized salt, 10.8% sea salt (imported, with non-standardized iodine content, usually much lower than the reglemented concentration), 24.6% coarse salt (which is non-iodized), 2.7% other types of salt (which are also usually non- iodized, e.g., pink “Himalayan” salt), 0.2% unknown salt type.

The use of iodized salt in the studied counties varied from 35% (Arges) to 83% (Dambovita). In Botosani, the county with low median UIC, iodized salt was used by 55.5% of families.

Median UIC was significantly higher in children using iodized salt - 150 µg/L (bootstrapped 95% CI 142, 155, p < 0.001) or sea salt - 136 µg/L (bootstrapped 95% CI 125, 162, p = 0.01) compared to those using coarse salt - 121 µg/L (bootstrapped 95% CI 112, 138); median UIC in those using other types of salt was also lower - 125 µg/L (bootstrapped 95% CI 98, 142), but their number is small (37 children) and the difference did not reach statistical significance (Fig. 5).

Figure 5.

Urinary iodine concentration (UIC) in schoolchildren using different types of salt. UIC is expressed as median (bootstrapped 95% CI) [interquartile range IQR]; * p< 0.001 compared to the group using iodized salt and p = 0.01 compared to the group using sea salt.

Newborns

We evaluated neonatal TSH levels in 18349 newborns, 8835 girls (48%), 9514 boys (52%); 9172 (50%) were from 14 counties with endemic mild to moderate iodine deficiency and 9177 from 10 counties with iodine sufficiency) (Fig. 1); 53% of the sample reside in urban areas (43.6% in endemic counties, 62.8% in non-endemic counties, p = NS).

The proportion of newborns with nTSH > 5 mIU/L is 14.7% (range 3.8 – 27.3%), indicating mild to moderate iodine deficiency in newborns (Fig. 2).

Interestingly, the % of nTSH > 5 mIU/L is higher in non-endemic vs. endemic counties, p < 0.001, mainly in urban areas. It is higher in urban vs. rural population (p<0.001) in both endemic and non-endemic counties, as well as in the total study population (Table 2).

The distribution of % of nTSH > 5 mIU/L in the regions of Romania is presented in Figure 4.

DISCUSSION

Before the introduction of prophylactic programs for iodine deficiency (in 1956), Romania had endemic goiter throughout 2/3 of the country, with several areas of severe iodine deficiency and endemic cretinism (26). Following the introduction of salt iodization (in 1962), used on a voluntary basis, and the distribution of KI tablets (1mg) for children and pregnant women in the counties with endemic goiter, the median UIC improved and the cases of endemic cretinism significantly declined. However there was still mild to moderate iodine deficiency in most of the counties, as appreciated based on studies of UIC and thyroid volume in schoolchildren and pregnant women (27).

The mandatory universal salt iodization legislation for households and bakery industry in 2002 was progressively followed by normalization of median UIC levels in most counties in schoolchildren (27, 28) and in some, but not all counties, for pregnant women (27, 29, 30).

A previous study of UIC in 624 Romanian schoolchildren 6-7 years from 15 counties in 2015-2016 showed a median UIC of 255 µg/L (31). According to WHO recommendations (2004), median UIC levels of 100-199 µg/L indicate adequate iodine intake in a population, between 200 – 299 µg/L more than adequate iodine intake (i.e. above requirements) and > 300 µg/L indicate iodine intake in excess of the amount required to prevent and control iodine deficiency (11), with potential health risks (iodine-induced hyperthyroidism, thyroid autoimmune disease) (32). A subsequent study has shown that UIC levels of 100 up to 300 µg/L in schoolchildren are safe and may be considered adequate (19), a recommendation endorsed by UNICEF and IGN (20).

In 2016-2017, Romanian studies on median UIC in 631 pregnant women showed persistence of predominantly mild ID: median UIC 116 µg/L (below the recommended level of 150 µg/L in pregnancy) (30). In more than 7800 samples of neonatal TSH, the % of nTSH > 5 mIU/l was 22.9%, indicating mild ID in non-endemic counties (18%) and moderate ID in endemic counties (27%) (33). Several international studies have demonstrated that even mild ID, notably in mothers during pregnancy, is associated with neurointellectual impairment in children, language delay and poorer school performance (2,3).

It is reassuring that the present study, which included a national representative sample of schoolchildren 6 – 12 years, revealed a median UIC of 141 µg/L, with less than 10% of values being under 50 µg/L, indicating adequate iodine intake in children, both in previously endemic and non-endemic counties and in rural and urban areas. The proportion of values > 300 µg/L is similarly low, in both areas.

However, the proportion of neonatal TSH values over 5 mIU/L is above 3% in all the studied counties, indicating persistent ID in newborns and, indirectly, in pregnant women. A potential explanation for this discrepancy between schoolchildren and newborns, seen in most countries (13) is a lower intake of salt and bread, main sources of dietary iodine, during pregnancy (34,35). A trend towards a more plant-based (vegetarian and vegan) diet, which contains negligible quantities of iodine and may predispose to iodine deficiency, have been shown in several industrialized countries in the last decades (13,34-36). Moreover, in Romania there is an increased tendency towards what is percived as more “natural” products and several non-expert influencers campain against the use of iodized salt in the internet media. This may explain the high proportion of families who declared use of coarse salt and other non-iodized types of salt in the household (27%) or sea-salt (11%) which contains lower iodine concentration than the standardized iodized salt. Since these types of salt are more expensive than iodized salt, as are the plant-based drinks as an alternative to milk, it may be one of the reasons for the significantly higher proportion of nTSH > 5 mIU/L observed in urban areas compared to rural ones in our study, both in endemic and non-endemic counties. The development region with the lowest UIC is Bucharest-Ilfov, a highly urbanized area.

Salt iodization is a cheap and easy to implement method to prevent iodine deficiency-induced disorders in a population. Global Fortification Data Exchange (GFDx) centralizes data received via IGN and other sources on the global micronutrient fortification (vitamins and minerals) stemming from 5 most frequently consumed foods, i.e. maize flour, oil, rice, salt, and wheat flour (37). According to 2023 data, there is mandatory salt iodization in 18 European countries, out of which 11 are EU members: Austria, Bulgaria, Croatia, Denmark, Hungary, Italy, Lithuania, Poland, Romania, Slovakia, Slovenia, the other 7 countries, non EU, being Albania, Belarus, Bosnia and Herzegovina, Macedonia, Republic of Moldova, Serbia, Republic of Kosovo. Worldwide, 126 countries have mandatory salt iodization. In countries where iodine deficiency is no longer a public health problem, optional salt iodization was chosen (37). However, both the Romanian experience prior to 2002 (27) and the international experience have shown that voluntary (optional) use of iodized salt is less effective in ensuring adequate iodine status than mandatory salt iodization (13).

One measure of success in implementing universal salt iodization program is the use of iodized salt in more than 90% of the households, as recommended by WHO (18). In Romania, the percentage is only 62% in the current study. However, the mandatory use of iodized salt in the Romanian bakery industry is likely the reason for maintaining a normal iodine intake in most schoolchildren, but it appears to be not enough for women during pregnancy, who require individual iodine supplementation, as seen in other studies (13, 17, 38).

In conclusion, the current salt iodization program for households and bakery industry ensures an adequate iodine intake in Romanian schoolchildren. Discordantly, neonatal TSH levels indicate a mild-to-moderate ID in newborns, suggesting insufficient iodine intake in pregnant women. The percentage of households using iodized salt is below the recommended >90% needed for an efficient ID prevention program. More efforts should be directed to increase the public awareness of the health risks of iodine deficiency. Continuous monitoring of the iodine status in children and women of reproductive age is recommended in order to ensure adequate prevention of iodine deficiency disorders, notably prevention of neurodevelopmental delay in children.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding Statement

This research was financed in the frame of the project PDP1 (Consolidarea rețelei naționale de furnizori de îngrijiri primare de sănătate pentru îmbunătățirea stării de sănătate a populației, copii și adulți (inclusiv populație vulnerabilă)). Norway grants contract nr NT 2311/13.05.2020. National Institute for Public Health (INSP)/ INSMC partnership contract 14246/20.09 2019. Ministry of Health Romania.