Does Iodine Intake Modify the Effect of Maternal Dysglycemia on Birth Weight in Mild-to-Moderate Iodine-Deficient Populations? A Mother-Newborn Prospective Cohort Study.

It is unclear how maternal glycemic status and maternal iodine status influence birth weight among individuals with mild-to-moderate iodine deficiency (ID). We studied the association between birth weight and both maternal glucose levels and iodine intake among pregnant women with mild-to-moderate ID. Glucose values were assessed using a glucose challenge test (GCT) and non-fasting glucose levels that were determined before delivery; individuals' iodine statuses were assessed using an iodine food frequency questionnaire; and serum thyroglobulin (Tg) and urinary iodine concentrations (UIC) were used to assess each group's iodine status. Thyroid antibodies and free thyroxine (FT4) levels were measured. Obstetric and anthropometric data were also collected. Large-for-gestational age (LGA) status was predicted using a Cox proportional hazards model with multiple confounders. Tg > 13 g/L was independently associated with LGA (adjusted hazard ratio = 3.4, 95% CI: 1.4-10.2, p = 0.001). Estimated iodine intake correlated with FT4 among participants who reported consuming iodine-containing supplements (ICS) after adjusting for confounders (ß = 0.4, 95% CI: 0.0002-0.0008, p = 0.001). Newborn weight percentiles were inversely correlated with maternal FT4 values (ß = -0.2 95% CI:-0.08--56.49, p = 0.049). We conclude that in mild-to-moderate ID regions, insufficient maternal iodine status may increase LGA risk. Iodine status and ICS intake may modify the effect that maternal dysglycemia has on offspring weight.

Can Mild-to-Moderate Iodine Deficiency during Pregnancy Alter Thyroid Function? Lessons from a Mother-Newborn Cohort.

Severe iodine deficiency during pregnancy has substantial hormonal consequences, such as fetal brain damage. Data on the potential effects of mild-to-moderate iodine deficiency on the thyroid function of pregnant women and their newborns are scarce and divergent. We investigated the association between iodine intake in pregnancy and maternal and neonatal thyroid function in a region with mild-to-moderate iodine deficiency. Pregnant women's iodine status was evaluated using an iodine food frequency questionnaire, serum thyroglobulin (Tg), and urinary iodine concentration (UIC). Neonatal thyrotropin (nTSH) values were measured after birth. Obstetrics and anthropometric data were also collected. Among the 178 women (median age 31 years) included in the study, median (interquartile range) estimated dietary iodine intake, Tg and UIC were 179 (94−268) µg/day, 18 (11−33) µg/L, and 60 (41−95) µg/L, respectively. There was a significant inverse association of iodine intake with Tg values among the study population (ß = −0.2, F = 7.5, p < 0.01). Women with high free triiodothyronine (FT3) values were more likely to exhibit an estimated iodine intake below the estimated average requirement (160 µg/day, odds ratio [OR] = 2.6; 95% confidence interval [CI], 1.1−6.4; p = 0.04) and less likely to consume iodine-containing supplements (OR = 0.3, 95% CI, 0.1−0.8; p = 0.01). It is possible that thyroid function may be affected by iodine insufficiency during pregnancy in regions with mild-to-moderate iodine deficiency. The relatively small sample size of the studied population warrants further investigation.

Maternal iodine deficiency: a newborns' overweight risk factor? A prospective study.

OBJECTIVES: Childhood obesity and iodine deficiency are global public health concerns. Whether maternal iodine status mediates overweight in infancy has yet to be explored. We aimed to assess the relationship between maternal iodine status and infant birth weight, including small and large for gestational age (SGA and LGA, respectively). METHODS: A prospective study was carried out among 134 mother-infant pairs from Israel. Maternal iodine intake and status were estimated via questionnaire and serum thyroglobulin (Tg), respectively. Estimated iodine intake below the Recommended Daily Allowance for iodine sufficiency in pregnancy (220 µg/d) considered Inadequate. Maternal and neonatal thyroid function and anthropometric measurements, as well as maternal thyroid antibodies were also tested. RESULTS: After screening, 118 participants met the inclusion criteria (distributed trimesters I, II and III: n = 3, n = 21, and n = 94, respectively). There was a negative association of iodine intake with Tg values among the study population. Maternal median Tg value was higher than the sufficiency cutoff (16.5 vs 13 µg/L), indicating insufficient iodine status. No SGA cases were found. Inadequate iodine intake was associated with maternal isolated hypothyroxinemia (OR = 3.4; 95% CI 1.2, 9.9) and higher birthweight (including macrosomia and LGA) rates. A suggestive association of elevated Tg with a greater risk of LGA was observed. Offsprings' birth weight percentiles were associated with Tg values in pregnant women with suggestive sufficient iodine status (n = 62, R2 = 0.11, p < 0.05). CONCLUSIONS: Iodine status during pregnancy can be associated with newborn anthropometric index. Maternal inadequate iodine intake may alter fetal growth and might increase the risk of LGA among newborns. These initial findings support the need to further study the impact of iodine deficiency on newborns overweight in Israel and elsewhere.

Low intake of iodized salt and iodine containing supplements among pregnant women with apparently insufficient iodine status - time to change policy?

BACKGROUND: Iodine is an essential nutrient for human health throughout the life cycle, especially during early stages of intrauterine life and infancy, to ensure adequate neurocognitive development. The growing global reliance on desalinated iodine-diluted water raises the specter of increased iodine deficiency in several regions. The case of Israel may be instructive for exploring the link between iodine status and habitual iodine intake in the setting of extensive national reliance on desalinated water. The aim of this study was to explore the relationship between iodine intake, including iodized salt and iodine-containing supplements intake, and iodine status among pregnant women residing in a sub-district of Israel that is highly reliant on desalinated iodine-diluted water. METHODS: A total of 134 consecutive pregnant women were recruited on a voluntary basis from the obstetrics department of the Barzilai University Medical Center during 2018. Blood was drawn from participants to determine levels of serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroglobulin (Tg). An iodine food frequency questionnaire (sIFFQ) was used to assess iodine intake from food, IS and ICS. A questionnaire was used to collect data on demographic and health characteristics. RESULTS: A total of 105 pregnant women without known or reported thyroid disease were included in the study. Elevated Tg values (≥ 13 µg/L), were found among 67% of participants, indicating insufficient iodine status. The estimated iodine intake (median, mean ± SD 189, 187 ± 106 µg/d by sIFFQ) was lower than the levels recommended by the World Health Organization and the Institute of Medicine (250 vs. 220 µg/day respectively). The prevalence of iodized salt intake and iodine containing supplement intake were 4 and 52% (respectively). Values of Tg > 13 µg/L were inversely associated with compliance with World Health Organization and Institute of Medicine recommendations. CONCLUSIONS: While the Israeli Ministry of Health has recommended the intake of iodized salt and iodine containing supplements, this is apparently insufficient for achieving optimal iodine status among Israeli pregnant women. The evidence of highly prevalent probable iodine deficiency in a sample of pregnant women suggests an urgent need for a national policy of iodized salt regulation, as well as guidelines to promote iodine containing supplements and adherence to them by caregivers. In addition, studies similar to this one should be undertaken in additional countries reliant on desalinated iodine-diluted water to further assess the impact of desalinization on maternal iodine status.

High-resolution inference of genetic relationships among Jewish populations.

Recent studies have used genome-wide single-nucleotide polymorphisms (SNPs) to investigate relationships among various Jewish populations and their non-Jewish historical neighbors, often focusing on small subsets of populations from a limited geographic range or relatively small samples within populations. Here, building on the significant progress that has emerged from genomic SNP studies in the placement of Jewish populations in relation to non-Jewish populations, we focus on population structure among Jewish populations. In particular, we examine Jewish population-genetic structure in samples that span much of the historical range of Jewish populations in Europe, the Middle East, North Africa, and South Asia. Combining 429 newly genotyped samples from 29 Jewish and 3 non-Jewish populations with previously reported genotypes on Jewish and non-Jewish populations, we investigate variation in 2789 individuals from 114 populations at 486,592 genome-wide autosomal SNPs. Using multidimensional scaling analysis, unsupervised model-based clustering, and population trees, we find that, genetically, most Jewish samples fall into four major clusters that largely represent four culturally defined groupings, namely the Ashkenazi, Mizrahi, North African, and Sephardi subdivisions of the Jewish population. We detect high-resolution population structure, including separation of the Ashkenazi and Sephardi groups and distinctions among populations within the Mizrahi and North African groups. Our results refine knowledge of Jewish population-genetic structure and contribute to a growing understanding of the distinctive genetic ancestry evident in closely related but historically separate Jewish communities.

Low Iodine Intake from Dairy Foods Despite High Milk Iodine Content in Israel.

BACKGROUND: Milk is a major source of iodine in human nutrition. Because both iodine content and the consumption of milk and dairy vary widely over time and populations, their contribution to iodine intake must be evaluated regularly. A recent national iodine survey found Israel's population to be mildly iodine deficient, possibly due to unmonitored changes in the food content of dietary iodine. Accounting for dairy iodine content can help guide efforts to prevent iodine deficiency. OBJECTIVES: This study aimed to determine the iodine concentration of dairy products typically consumed in the Israeli diet, and to estimate iodine intake from dairy products among Israeli adults. METHODS: Iodine was analyzed in 33 selected dairy products that account for 89% of the total population's dairy intake according to the "MABAT" Israeli National Health and Nutrition survey. Based on these data, the distribution of iodine intake from milk, dairy, and dairy-based foods in the adult population was calculated. RESULTS: Israeli milk is rich in iodine, with a mean concentration of 22 µg/100 g. However, due to low dairy consumption, the mean iodine intake from milk and dairy was only 34 µg/day (median 23 µg/day; range: 0-337 µg/day) or 22% of the recommended daily allowance. Self-reported intake among poor, male, and Arab subgroups was even lower. CONCLUSIONS: Because Israeli milk and dairy products are iodine rich, their contribution to the population's iodine intake would increase if they were consumed in greater amounts, particularly by high-risk groups. Dairy's potential contribution to iodine nutrition should be considered in recommendations for dairy consumption and iodine prophylaxis.

First Israeli National Iodine Survey Demonstrates Iodine Deficiency Among School-Aged Children and Pregnant Women.

BACKGROUND: National data on iodine status in Israel are lacking. Reliance on iodine-depleted desalinated water, the absence of a salt iodization program, and reports of increased use of thyroid medication in Israel suggest that the population's iodine intake is likely inadequate. The aims of this study were therefore to determine the iodine status of Israeli school-age children (SAC) and pregnant women (PW) in a nationally representative sample obtained by a novel approach of using pre-discard urinalysis samples collected from a centralized national laboratory. METHODS: Spot urine samples from 1023 SAC and 1074 PW, representing all regions and major sectors in Israel, were collected during 2016 at the Maccabi Healthcare Services central laboratory. Urinary iodine concentration (UIC) was measured, and the results were analyzed by trimester, sex, region, and sector. RESULTS: SAC were iodine deficient, with a median (interquartile range [IQR]) UIC of 83 µg/L (52-127 µg/L); 62% of SAC UICs were below the World Health Organization adequacy range for SAC (100-199 µg/L). PW were also iodine deficient, with a median (IQR) UIC of 61 µg/L (36-97 µg/L); 85% of PW UICs were below the adequacy range for PW (150-249 µg/L). For both SAC and PW, the median UIC was below the World Health Organization's adequacy range across all sectors, sexes, and districts. Among SAC, the median (IQR) UIC was lower among females (75 µg/L; 48-119 µg/L) than males (92 µg/L; 59-133 µg/L; p < 0.05). Median UIC values of PW correlated significantly with the median UIC for SAC by sub-district (R2 = 0.3, p < 0.05). CONCLUSIONS: Urine sampling via a centralized national laboratory was efficient and cost-saving. Iodine deficiency in Israeli SAC and PW is a serious public-health concern. A national program of salt iodization and iodine supplementation of PW should be urgently considered.

Can desalinated seawater contribute to iodine-deficiency disorders? An observation and hypothesis.

OBJECTIVE: Over 300 million people rely on desalinated seawater and the numbers are growing. Desalination removes iodine from water and could increase the risk of iodine-deficiency disorders (IDD). The present study assessed the relationship between iodine intake and thyroid function in an area reliant on desalination. DESIGN: A case-control study was performed between March 2012 and March 2014. Thyroid function was rigorously assessed by clinical examination, ultrasound and blood tests, including serum thyroglobulin (Tg) and autoimmune antibodies. Iodine intake and the contribution made by unfiltered tap water were estimated by FFQ. The contribution of drinking-water to iodine intake was modelled using three iodine concentrations: likely, worst-case and best-case scenario. SETTING: The setting for the study was a hospital located on the southern Israeli Mediterranean coast. SUBJECTS: Adult volunteers (n 102), 21-80 years old, prospectively recruited. RESULTS: After screening, seventy-four participants met the inclusion criteria. Thirty-seven were euthyroid controls. Among those with thyroid dysfunction, twenty-nine were classified with non-autoimmune thyroid disease (NATD) after excluding eight cases with autoimmunity. Seventy per cent of all participants had iodine intake below the Estimated Average Requirement (EAR) of 95 µg/d. Participants with NATD were significantly more likely to have probable IDD with intake below the EAR (OR=5·2; 95 % CI 1·8, 15·2) and abnormal serum Tg>40 ng/ml (OR=5·8; 95 % CI 1·6, 20·8). CONCLUSIONS: Evidence of prevalent probable IDD in a population reliant on desalinated seawater supports the urgent need to probe the impact of desalinated water on thyroid health in Israel and elsewhere.

[SERUM THYROGLOBULIN LEVELS AND ESTIMATED IODINE INTAKE IN ADULTS EXPOSED TO IODINE­DILUTED DESALINATED DRINKING WATER].

AIMS: The aim of this study was to describe thyroglobulin levels and iodine intake estimations in a convenience sample of Israeli adults without TD in the Ashkelon District, where SWRO desalination has become the major source of drinking water. BACKGROUND: Iodine deficiency (ID) is a significant risk factor for thyroid disease (TD). Recently, there were increases in both selfreported use of TD medication among Israeli adults and the national use of sea water reverse osmosis (SWRO) desalinated water. METHODS: Iodine concentrations in tap water (supplied by Mekorot Israel National Water Co.) were estimated before and after SWRO desalination was implemented in the Ashkelon District. Volunteers were recruited at the Barzilai Medical Center Ashkelon between January 2012 and October 2013. Data regarding residency, BMI and use of iodine-containing or steroidal drugs were obtained for all volunteers. Blood was drawn from matching participants for determination of serum thyrotropin, thyroid peroxidase antibodies, thyroglobulin (Tg) antibodies and Tg. A semi-quantitative iodine food frequency questionnaire (sIFFQ) was administered. RESULTS: Iodine concentration estimation in tap water declined from 52 µg/L to 27 µg/L after SWRO desalination was implemented in the Ashkelon District. A total of 50 participants without reported or known TD were included in the study after screening 92 volunteers. The median serum Tg was 21 ng/mL, and 76% (35 participants) had elevated values (Tg ≥ 10 ng/mL), indicating a high prevalence of apparent ID. Iodine intake estimation (median 99 µg/d by sIFFQ) was lower than the Recommended Dietary Allowance (150 µg/d). Unfiltered tap water was estimated to provide 16% of the mean daily iodine intake. CONCLUSIONS: The finding of apparent ID in this sample, underscores the need to obtain further data regarding many other regions across Israel. This is particularly urgent in the context of Israel's increased dependence on SWRO desalination.

Elevated Serum Thyroglobulin and Low Iodine Intake Are Associated with Nontoxic Nodular Goiter among Adults Living near the Eastern Mediterranean Coast.

Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequate iodine intake can lead to thyroid diseases, including nontoxic nodular goiter (NNG). Objective. To estimate iodine intake and explore its correlation with thyroid diseases among Israeli adults living near the Mediterranean coast, where iodine-depleted desalinated water has become a major source of drinking water. Methods. Cross-sectional study of patients attending Barzilai Medical Center Ashkelon. Participants, who were classified as either NNG (n = 17), hypothyroidism (n = 14), or control (n = 31), provided serum thyroglobulin (Tg) and completed a semiquantitative iodine food frequency questionnaire. Results. Elevated serum Tg values (Tg > 60 ng/mL) were significantly more prevalent in the NNG group than in the other groups (29% versus 7% and 0% for hypothyroidism and controls, resp., P < 0.05). Mean estimated iodine intake was significantly lower in the NNG group (65 ± 30 µg/d) than in controls (115 ± 60 µg/d) (P < 0.05) with intermediate intake in the hypothyroid group (73 ± 38 µg/d). Conclusions. Elevated serum Tg values and low dietary iodine intake are associated with NNG among adult patients in Ashkelon District, Israel. Larger studies are needed in order to expand on these important initial findings.

Genetics and the history of the Samaritans: Y-chromosomal microsatellites and genetic affinity between Samaritans and Cohanim.

The Samaritans are a group of some 750 indigenous Middle Eastern people, about half of whom live in Holon, a suburb of Tel Aviv, and the other half near Nablus. The Samaritan population is believed to have numbered more than a million in late Roman times but less than 150 in 1917. The ancestry of the Samaritans has been subject to controversy from late Biblical times to the present. In this study, liquid chromatography/electrospray ionization/quadrupole ion trap mass spectrometry was used to allelotype 13 Y-chromosomal and 15 autosomal microsatellites in a sample of 12 Samaritans chosen to have as low a level of relationship as possible, and 461 Jews and non-Jews. Estimation of genetic distances between the Samaritans and seven Jewish and three non-Jewish populations from Israel, as well as populations from Africa, Pakistan, Turkey, and Europe, revealed that the Samaritans were closely related to Cohanim. This result supports the position of the Samaritans that they are descendants from the tribes of Israel dating to before the Assyrian exile in 722-720 BCE. In concordance with previously published single-nucleotide polymorphism haplotypes, each Samaritan family, with the exception of the Samaritan Cohen lineage, was observed to carry a distinctive Y-chromosome short tandem repeat haplotype that was not more than one mutation removed from the six-marker Cohen modal haplotype.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations.

BACKGROUND: Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. RESULTS: We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. CONCLUSION: These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.

[Application of single nucleotide polymorphisms (SNPs) for the detection of genes involved in the control of complex diseases].

The advances in the Human Genome Project (HGP), which have created a huge database, may contribute to our understanding of the etiopathology of complex diseases. These diseases are characterized by a high prevalence within families and by the influence of genetic factors as well as environmental conditions on its natural history (multifactorial diseases). Researchers nowadays focus on the genetic diversity between people by learning the biological significance of a certain DNA marker--the single nucleotide polymorphism (SNP). The universal technology of miniaturization of biological and electronic devices is producing an important infrastructure. Among these tools of infrastructure is the high--throughput genotyping system which enables researchers to perform whole genome screening for hundreds of thousands of SNPs in a relatively short period of time. The evolving data is accumulating rapidly and is pushing the field of bioinformatics into the forefront. The more association studies there are on block-like structure of haplotypes of SNPs in complex diseases the more our ability to identify persons in presymptomatic states will improve. The end product of the above-mentioned developments is expected to contribute to better ways of treatment (pharmacogenomics).

Reconstruction of patrilineages and matrilineages of Samaritans and other Israeli populations from Y-chromosome and mitochondrial DNA sequence variation.

The Samaritan community, which numbered more than a million in late Roman times and only 146 in 1917, numbers today about 640 people representing four large families. They are culturally different from both Jewish and non-Jewish populations in the Middle East and their origin remains a question of great interest. Genetic differences between the Samaritans and neighboring Jewish and non-Jewish populations are corroborated in the present study of 7,280 bp of nonrecombining Y-chromosome and 5,622 bp of coding and hypervariable segment I (HVS-I) mitochondrial DNA (mtDNA) sequences. Comparative sequence analysis was carried out on 12 Samaritan Y-chromosome, and mtDNA samples from nine male and seven female Samaritans separated by at least two generations. In addition, 18-20 male individuals were analyzed, each representing Ethiopian, Ashkenazi, Iraqi, Libyan, Moroccan, and Yemenite Jews, as well as Druze and Palestinians, all currently living in Israel. The four Samaritan families clustered to four distinct Y-chromosome haplogroups according to their patrilineal identity. Of the 16 Samaritan mtDNA samples, 14 carry either of two mitochondrial haplotypes that are rare or absent among other worldwide ethnic groups. Principal component analysis suggests a common ancestry of Samaritan and Jewish patrilineages. Most of the former may be traced back to a common ancestor in the paternally-inherited Jewish high priesthood (Cohanim) at the time of the Assyrian conquest of the kingdom of Israel.