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Iodine supplementation during pregnancy in areas with mild-moderate deficiency is still a matter of debate. The present study aimed at systematically reviewing currently available evidences provided by meta-analyses with the aim to further clarify controversial aspects regarding the need of iodine supplementation in pregnancy as well as to provide guidance on clinical decision-making, even in areas with mild-moderate deficiency. Medline, Embase and Cochrane search from 1969 to 2022 were performed. For the purpose of this review, only studies containing meta-analytic data were selected. A total of 7 meta-analyses were retrieved. Four meta-analyses evaluated the relationship between iodine status during pregnancy and neonatal and maternal outcomes suggesting the existence of a U-shaped correlation between iodine status and several maternal and neonatal consequences, especially if iodine status is evaluated at the beginning of pregnancy. Three meta-analyses evaluating the results of intervention trials failed to provide straightforward conclusions on the benefits of iodine supplementation in pregnant women in areas with mild-moderate iodine deficiency. Although evidence coming from meta-analyses suggests a role of iodine status during pregnancy in determining maternal and child outcomes, results of meta-analyses of intervention trials are still controversial. Several factors including, degree of iodine deficiency, and pooling studies conducted in areas with different iodine intake, may account for the lack of benefits reported by meta-analyses of intervention trials. More high-quality, randomized, controlled trials including information on timing, dose and regimen of iodine supplementation are needed to further elucidate this issue.

La diffusione del modello etico-culturale del vegetarianismo nelle societa industrializzate, certamente utile a contribuire alla prevenzione di diabete e obesita e di alcuni tumori, puo essere gravata, nelle sue piu estreme declinazioni, da inappropriata assunzione di alcuni nutrienti. Nel caso dello iodio, una dieta vegetariana particolarmente restrittiva puo risultare in carenza o eccesso del nutriente con conseguenze sulla salute, specialmente in momenti della vita critici dal punto di vista nutrizionale quali la gravidanza e l’eta evolutiva.

Adequate iodine intake is necessary for normal thyroid function. Iodine deficiency is associated with serious complications, but also iodine excess can lead to thyroid dysfunction, and iodine supplementation aimed to prevent iodine deficiency disorders has been associated with development of thyroid autoimmunity. The epidemiology of thyroid diseases has undergone profound changes since the implementation of iodoprophylaxis, notably by means of iodine-enriched salt, specifically resulting in decreased prevalence of goiter and neonatal hypothyroidism, improved cognitive function development in infancy, and reduced incidence of more aggressive forms of thyroid cancer. The main question we address with this review is the clinical relevance of the possible effect on autoimmunity exerted by the use of iodine-enriched salt to correct iodine deficiency. In animal models, exogenous iodine is able to trigger or exacerbate thyroid autoimmunity, but it is still not clear whether the observed immunological changes are due to a direct effect of iodine on immune response, or whether they represent a secondary response to a toxic effect of iodine on thyroid tissue. Previous iodine status of a population seems to influence the functional thyroid response to increased iodine intake and possibly the development of thyroid autoimmunity. Moreover, the prevalence of thyroid antibodies, regarded as hallmark of autoimmune thyroid disease, varies between populations under the influence of genetic and environmental factors, and the presence of thyroid antibodies does not always coincide with the presence of thyroid disease or its future development. In addition, the incidence of autoimmune diseases shows a general increasing trend in the last decades. For all these reasons, available data are quite heterogeneous and difficult to analyze and compare. In conclusion, available data from long-term population surveys show that a higher than adequate population iodine intake due to a poorly controlled program of iodine prophylaxis could induce thyroid dysfunction, including thyroid autoimmunity mostly represented by euthyroid or subclinical hypothyroid autoimmune thyroiditis. Close monitoring iodine prophylaxis is therefore advised to ensure that effects of both iodine deficiency and iodine excess are avoided.

Iodine deficiency still represents a global health threat to individuals and societies. Although goiter is the most frequent consequence of an inadequate iodine intake, iodine deficiency has multiple adverse effects on growth and development in animals and humans. These are collectively termed iodine deficiency disorders (IDD) and result from inadequate thyroid hormone production due to insufficient iodine intake. Iodine deficiency during pregnancy and breast feeding adversely affects the neurodevelopment of the fetus and the infant. During childhood, it has been linked to reduced growth and intellectual and motor performance. Goiter in children is usually small and diffuse, but over time may evolve toward nodular goiter. Adults living in iodine-deficient regions show a high risk of goiter, thyroid nodules, and hyperthyroidism. To eradicate IDD, the WHO recommended universal salt iodization as the preferred strategy. Over the years, voluntary or mandatory programs of salt iodization have been implemented in many countries. The WHO recommends combining strategies of salt/sodium reduction with parallel salt iodization programs. To make both prevention programs effective, iodine prophylaxis programs should be adapted to the actual salt intake of the population by increasing iodine concentration of iodized salt, when necessary, and by promoting the use of iodized salt in processed food production.

Background: The frequency of overweight (OW) and obese (OB) children has increased worldwide, particularly in economically developed countries. No studies have been conducted to verify whether the ...

International audience; Objective. Maintaining upright posture is a complex task governed by the integration of afferent sensorimotor and visual information with compensatory neuromuscular reactions. The objective of the present work was to characterize the visual dependency and functional dynamics of cortical activation during postural control. Approach. Proprioceptic vibratory stimulation of calf muscles at 85 Hz was performed to evoke postural perturbation in open-eye (OE) and closed-eye (CE) experimental trials, with pseudorandom binary stimulation phases divided into four segments of 16 stimuli. 64-channel EEG was recorded at 512 Hz, with perturbation epochs defined using bipolar electrodes placed proximal to each vibrator. Power spectra variation and linearity analysis was performed via fast Fourier transformation into six frequency bands (Δ, 0.5-3.5 Hz; θ, 3.5-7.5 Hz; α, 7.5-12.5 Hz; β, 12.5-30 Hz; γ_low, 30-50 Hz; and γ_high, 50-80 Hz). Finally, functional connectivity assessment was explored via network segregation and integration analyses. Main Results. Spectra variation showed waveform and vision-dependent activation within cortical regions specific to both postural adaptation and habituation. Generalized spectral variation yielded significant shifts from low to high frequencies in CE adaptation trials, with overall activity suppressed in habituation; OE trials showed the opposite phenomenon, with both adaptation and habituation yielding increases in spectral power. Finally, our analysis of functional dynamics reveals novel cortical networks implicated in postural control using EEG source-space brain networks. In particular, our reported significant increase in local θ connectivity may signify the planning of corrective steps and/or the analysis of falling consequences, while α band network integration results reflect an inhibition of error detection within the cingulate cortex, likely due to habituation. Significance. Our findings principally suggest that specific cortical waveforms are dependent upon the availability of visual feedback, and we furthermore present the first evidence that local and global brain networks undergo characteristic modification during postural control.

When newborn screening (NBS) for congenital hypothyroidism (CH) using thyroid-stimulating hormone (TSH) as a primary screening test was introduced, typical TSH screening cutoffs were 20–50 U/L of whole blood. Over the years, lowering of TSH cutoffs has contributed to an increased prevalence of detected CH. However, a consensus on the benefit deriving from lowering TSH cutoffs at screening is lacking. The present paper outlines arguments both for and against the lowering of TSH cutoffs at NBS. It includes a review of recently published evidence from Australia, Belgium and Italy. A section focused on economic implications of lowering TSH cutoffs is also provided. One issue that bears further examination is the extent to which mild iodine deficiency at the population level might affect the association of neonatal TSH values with cognitive and developmental outcomes. A debate on TSH cutoffs provides the opportunity to reflect on how to make NBS for CH more effective and to guarantee optimum neurocognitive development and a good quality of life to babies with mild as well as with severe CH. All authors of this debate article agree on the need to establish optimal TSH cutoffs for screening programs in various settings and to ensure the benefits of screening and access to care for newborns worldwide.

Ethylenethiourea (ETU) is the common metabolite of the widely used ethylenebisdithiocarbamate fungicides. It is identified as Endocrine Disruptor given its ability to interfere with thyroid hormone biosynthesis by inhibiting thyroid peroxidase activity. As far as we know, no studies have been performed to assess potential effects of ETU exposure at low dose levels, i.e. below the established LOAEL and NOAEL, during critical phases of development. Therefore, the aim of the present study was to verify the short- and long-term effects on thyroid function, reproduction and development of oral exposure to ETU levels comparable to and lower than LOAEL/NOAEL in rats. Sixty dams were treated daily by gavage during pregnancy and lactation with 0, 0.1, 0.3, 1.0 mg/kg bw per day of ETU. F1 generation was similarly treated from weaning to sexual maturity. Thyroid biomarkers were analyzed in dams and in offspring. Reproductive biomarkers were analyzed in F1 rats. For the first time this study has demonstrated reproductive toxicity and hypothyroidism at a lower than LOAEL dose exposure in pregnant dams and F1 generation. Our data suggest that even low doses of ETU can interfere with thyroid homeostasis and reproductive hormone profile if exposure starts in critical stages of development.

Introduction Italy is still characterized by a mild iodine deficiency and is among the most intensive users of chemical products for agriculture in Europe. The aim of this study was i) to evaluate thyroid effects of exposure to mancozeb, a fungicide widely used in agriculture, in a sample of Italian grapevine workers, and ii) to verify whether the iodine intake may modulate the risk of thyroid disruption due to the mancozeb metabolite ethylenthiourea (ETU). Methods One hundred seventy-seven occupationally exposed male workers (29 from Chianti, a mild iodine deficient area, and 148 from Bolzano an iodine sufficient province) and 74 non-occupationally exposed male controls (34 from Chianti and 40 from Bolzano) were enrolled in the study. Serum biomarkers of thyroid function, as well as urinary iodine and ETU concentrations were assessed. Moreover all the recruited subjects underwent clinical examination and thyroid ultrasound. Results Multivariate comparisons showed lower mean serum levels of FT4 in Chianti-workers as compared to Bolzano-workers. Moreover, an increased urinary iodine excretion (>250 µg/L) was more frequently found among more exposed workers (ETU>20 µg/L) than among less exposed ones and this effect was more pronounced in Chianti- than in Bolzano-workers. Chianti-workers also showed a significantly higher frequency of very low thyroid volume (≤6.0 ml) as compared to controls. Conclusions These findings showed a mild thyroid disrupting effect due to occupational exposure to mancozeb, more pronounced in workers residing in an area characterized by a mild to moderate iodine deficiency as compared to workers residing in an area covered by a long-lasting iodine prophylaxis program.

Summary Recent data show that regulatory cells with transforming growth factor (TGF)-β1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-β1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-β1 (aTGF-β1) serum levels. In mice, aTGF-β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-β1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D.

Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against household pests; these compounds receive an increasing consideration as potential endocrine disrupters. The aim of the present study was to examine the potential short- and long-term effects of CPF on thyroid and adrenal glands in CD1 mice following exposure at dose levels not inducing brain acetyl cholinesterase (AchE) inhibition, during gestational and/or postnatal vulnerable phases. Pregnant dams were treated with 0, 3, 6 mg/kg bw/day of CPF on gestational days 15-18. After delivery, pups were treated subcutaneously on postnatal days (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum thyroxin (T4), thyroid and adrenals histology and histomorphometry were evaluated in dams and in F1 mice. In dams at 6 mg/kg, decreased T4 levels and increased cell height in thyroid were observed, and adrenal histology showed a slightly increased vacuolization in the X-zone. In the F1, short-term morphological modifications (reduced follicular size at PND 2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND 150 with an apparent higher vulnerability of males. For the first time these results indicate that CPF exposure at dose levels not inducing brain AchE inhibition causes thyroid alterations in dams and in F1 CD1 mice. Thyroid may be a sensitive target to CPF developmental exposure possibly leading to long-term effects on thyroid function. Because thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.

Biological samples collected in biobanks are a resource with significant research potential. The Italian Joint Group CNB - CNBBSV (National Committee of Bioethics - National Committee for Biosecurity, Biotechnologies and Life Sciences) published a document reporting recommendations on storage and use of dried blood spot (DBS) and on the development of a National Network of Regional Newborn Screening Repositories for collection of residual DBS. Several ethical questions (about consent, possible use of genetic information, unanticipated possible usages for research purposes) rise from residual newborn screening specimens collections. Moreover, legal and ethical controversies are accentuated by the conflicts between the interests of sample donors, biobank holders, researchers and the public. To overcome these difficulties the identification of a few criteria for storage and research usage of DBS is crucial.

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder and one of the most common preventable causes of mental retardation. Over the years, a rise in the incidence has been described worldwide with a rate ranging currently between 1:1,660 and 1:2,828 live births. Epidemiological studies have shown that more than one cause is responsible for the rise in CH incidence worldwide. Both lowering of the screening TSH cutoff and improvements in neonatal medicine, which have increased the survival rate of a growing number of preterm babies, have played an important role. Moreover, the adoption of special screening procedures for at-risk newborns, a changing demography due to migration flows, and environmental factors such as iodine deficiency contribute to explain the large variability of the CH incidence in different countries. In this chapter, the most important issues regarding epidemiology of CH will be reviewed and discussed.

Salt iodization is one of the preferred strategies to eradicate iodine-deficiency disorders worldwide. The aim of this study was (i) to estimate the daily iodine intake in the Italian population, (ii) to verify whether the recently recommended salt intake of 5 g/day in adults and less in children may be sufficient to achieve the adequate daily iodine intake, (iii) to estimate the contribution of iodine-enriched vegetables to the total daily iodine intake.The content of iodine has been evaluated in 288 food samples highly representative of Italian eating habits. The contribution of foods and iodized salt to the total daily iodine intake was estimated in adults, adolescents, and children on the basis of available nationwide data of food consumption.The total daily iodine intake owing to food and uniodized salt consumption resulted lower than the daily requirement in all age groups. With a daily consumption of 5 g of salt iodized at 30 mg/kg, the estimated daily iodine intake resulted within the range of optimal iodine intake in all age groups. In children the recommended iodine intake is achieved with a daily consumption of 3 g of iodized salt. Moreover, the daily iodine intake significantly increased in all age groups if the consumption of iodine-enriched vegetables was considered in substitution of non iodine-enriched ones.Our study suggests that the recommended quantities of salt, if iodized at 30 mg/kg, are sufficient to achieve the adequate daily iodine intake both in adults and children.

A high incidence of autoimmune Type 1 diabetes mellitus (DM) has been clearly established in Sardinia. Although systematic epidemiological studies are still not available, an increased prevalence of thyroid autoantibodies (ATA) has been documented in the Sardinian adult population as compared to other Italian regions, suggesting that thyroid autoimmune disease may also have increased. We carried out a preliminary study with the aim of determining the prevalence of serological markers of thyroid (anti-thyroperoxydase antibodies, TPOAb) and islet cell (ICA) autoimmunity in a large number (no.=2249) of sera obtained from cord-blood of Sardinian pregnant women at delivery. The prevalence of TPOAb was 11.9%, while ICA were detected in 59 cases (2.6%). A higher prevalence of TPOAb (6/17=35.3%) was found in sera with high ICA titers (or = 20 JDF-U), as compared to sera with low ICA titers (5-19 JDF-U) and to ICA-negative sera (3/42=7,1%; chi2=5.4, p=0.02 and 258/2190=11,8%; chi2=6.8, p=0.009 respectively). Fourteen women (all ICA-negative) were diabetic: 4 had Type 1 and 10 had gestational DM; due to the low number, no correlation could be established between DM type and TPOAb prevalence and/or titer. These preliminary data indicate that ATA are frequently observed in the general population of Sardinian pregnant women at term. As a consequence, even the frequency of postpartum thyroiditis is expected to be high. Although ATA were not increased in women with clinical overt diabetes, a higher prevalence of ATA was found in women with high titers of circulating ICA. Our results also confirm that Sardinia represents, perhaps for its peculiar genetic characteristics, an ideal place to study organ-specific autoimmunity.

Background Thyroid autoantibodies (ThyAb) and subclinical hypothyroidism occur more frequently in pregnant women with insulin-dependent diabetes mellitus than in healthy pregnant women. Few studies have investigated the presence of ThyAb in women with gestational diabetes mellitus (GDM), and no significant association between diabetes in pregnancy and thyroid function has been reported. Objective To assess the thyroid biochemical profile and estimate the prevalence of ThyAb in a group of pregnant women at increased risk of GDM due to family and personal risk factors, and to investigate the relationship between a positive family history of diabetes or thyroid diseases and the eventual presence of ThyAb during pregnancy. Methods Oral glucose tolerance, serum ThyAb and thyroid function were evaluated in 181 pregnant women with increased risk for GDM (study group). Seventeen healthy pregnant women without risk factors for GDM and with a normal glucose tolerance were recruited as controls. Results The women who developed GDM showed a mean free thyroxine concentration significantly lower than that observed in the healthy pregnant women and in those with impaired gestational glucose tolerance and normal glucose tolerance. Twenty-nine of the 181 women in the study group (16%) were ThyAb positive. However, the risk of being ThyAb positive during pregnancy was three times greater in the women with positive family history of both diabetes mellitus and thyroid disease than in those with no family history of these conditions. Conclusions This study showed that women with increased risk of GDM, mostly those with family history of diabetes mellitus and thyroid disease, also have an increased risk of being ThyAb positive during pregnancy. It also highlighted the importance of evaluating thyroid function in pregnant women with impaired glucose tolerance, in view of their increased risk of subclinical hypothyroidism.

Mortality for thyroid cancer (TC) is low and has been decreasing worldwide; yet few population studies based on mortality have been conducted. Several nonradiation risk factors have been associated with TC, including residence in goiter-endemic areas (as an indicator of iodine deficiency). We used mortality data to perform a spatial-temporal analysis regarding TC in Italy and investigated the association between mortality and socioeconomic status and geographical features (residing in a mountainous area is a proxy for iodine deficiency).We analyzed data from Italy's National Mortality Database (1980-2009). To evaluate temporal trends in mortality the age-standardized death rate (ASR) was used; to identify geographic areas with excess deaths due to TC standardized mortality rates (SMR) were calculated. We also calculated the rate ratios (RR) of the ASR and the 95% CI by sex. We performed a cluster analysis to identify municipalities with major departures from expected mortality, both in the entire study period and in two separate periods to evaluate the spatial-temporal variability. Finally, we evaluated the association between mortality and index of deprivation and altitude.There were 16,473 deaths due to TC (10,690 females, 5783 males). The mean ASR was unsurprisingly low (0.58/100.000). There was a trend of decrease in mortality throughout Italy (-42% for 2007-2009 vs. 1980-1984), more pronounced among women. The decrease was greater in the north. Four geographic clusters were identified when considering the entire study period, two in the north and two in the south; however, the clusters in northern Italy refer to the earlier period (1980-1994) and those in southern Italy to the later period (1995-2009). Mortality was associated with residing in a mountainous area. A slight association with high socioeconomic status was found.This study reveals space-time differences in TC mortality in Italy. It shows an association between mortality and residing in mountainous areas, which is a proxy of iodine deficiency. The observed temporal north-south shift cannot be explained by socioeconomic differences, whereas the efficient prophylaxis program implemented in the 1980s in some areas of northern Italy can help to explain the disappearance of the clusters in those areas in the period 1995-2009.

The effect of hypothyroidism on the lipid composition of synaptosomes, density and affinity of muscarinic receptor sites, and acetylcholinesterase activity in the cerebral cortex of young and aged rats was investigated. The animals were made hypothyroid by adding 0.05% propyl-2-thiouracil to their drinking water for four weeks. This pathological state induced an increase in the relative percentage of sphingomyelin in young rats. In aged rats hypothyroidism induced a decrease of sphingomyelin and glycerophosphocholine and an increase of cholesterol. The effect of hypothyroid state on cerebral cortex resulted in an increase of acethylcholinesterase activity both in young and aged rats and was also reflected in an increase of density of M1-AChRs but only in the former.

A Working Group of the Joint Commission "Italian National Committee of Bioethics" and "Italian National Committee for Biosafety Biotechnologies and Life Sciences" has recommended a National Network of Regional Newborn Screening Repositories the for collection of residual dried blood samples, coordinated by the Italian National Institute of Health.

The effect of hypothyroidism on the lipid composition of myelin and synaptosomes isolated from adult rat brain was investigated. The animals were made hypothyroid by adding 0.05% propyl-2-thiouracil to their drinking water for four weeks. This pathological state resulted in a significant increase in the relative percentage of choline glycerophospholipids in synaptosomes with a concomitant decrease in ethanolamine glycerophospholipids as compared to controls. In myelin, hypothyroidism significantly influenced only the relative percentage of sulfatides. The effect of the hypothyroid state on mature brain was also reflected in changes in the membrane fatty acid composition. Myelin and synaptosomes showed an increase in arachidonic (20:4) and eicosatrienoic (20:3) acids and an increase in the fatty acid unsaturation index. Furthermore, the 20:4/20:3 and 20:3/18:2 ratios were lower and higher, respectively, in treated animals. The data indicate that hypothyroidism affects the lipid composition of synaptosomes and myelin even though the effects were less pronounced in myelin. The lipid changes observed in hypothyroidism may be of physiological significance, as it is well known that lipid composition modulates various membrane-bound enzymes, transporters and receptors.

Thyroid dysfunction is frequently observed among comorbidities associated with prematurity. The main factors reported to affect thyroid function in preterm infants are the immaturity of the hypothalamic-pituitary-thyroid axis, immature thyroid hormone synthesis and metabolism, and insufficient or excessive exposure to iodine [1, 2], as well as drugs used to treat critically ill premature babies, such as caffeine, dopamine, morphine and glucocorticoids [3]. We propose further factors that may contribute to explaining disturbances of the hypothalamus-pituitarythyroid axis observed in preterm babies, i.e., preand postnatal exposures to environmental chemical compounds with thyroid-disrupting activity, such as phthalates. Phthalates are a group of chemicals with many commercial uses such as solvents, additives and particularly plasticizers to impart flexibility to an otherwise rigid polyvinylchloride (PVC). In particular, di-(2-ethylhexyl)phthalate (DEHP) is the most commonly used plasticizer in PVC medical devices, such as infusion systems, tracheal tubes, and blood bags [4]. It is well known that the developing fetus and the neonate are the most vulnerable phases of life for exposure to these environmental contaminants. It has also been shown that prenatal exposure to DEHP is associated with shorter pregnancy duration [5, 6]. According to Food and Drug Administration (FDA), due to their small body size, physical condition, and particularly multiple medical device DEHP-related exposure, neonates in the Neonatal Intensive Care Unit (NICU) environment are a population especially at risk [7]. In addition, it has been shown that neonates in the NICU environment are exposed to higher concentrations of DEHP than the general population [8], and their daily exposure to DEHP may increase up to 20-fold the tolerable daily intake [9]. Phthalates have also been reported to interfere with the endocrine system, especially when exposure begins early in life [6]. Several lines of evidence, mainly based on in vivo and in vitro studies, indicate that thyroid function is a further target of these compounds and that these chemicals may act through a number of potential mechanisms [10, 11]. In this regard, a recent review of the most recently published epidemiological studies reported that exposure to phthalates negatively impacts thyroid function in children [12]. Moreover, a positive relationship between urinary DEHP metabolites and thyroid-stimulating hormone levels has been reported, in both adults and adolescents from the general population [13]. Therefore, it is conceivable that prenatal and postnatal exposure to phthalates may have a role in producing thyroid hazards in exposed preterm babies. In conclusion, although alternative materials have been developed [14], only few DEHP–free medical devices are available on the market and their high cost is still a major limit to their exploitation. Therefore, research into alternatives to DEHP-containing medical devices that may come in contact with human tissues should be urgently encouraged. In the meantime, further studies are needed to evaluate the real impact of preand postnatal DEHP exposure G. Latini Division of Neonatology, Ospedale Perrino, Brindisi, Italy

Objective: To identify risk factors for permanent and transient congenital hypothyroidism (CH). Design: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. Methods: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrolment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. Results: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) = 12.2, 95% confidence interval (CI): 2.4–62.3). A statistically significant association with additional birth defects, female gender and gestational age >40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR = 1.9, 95% CI: 0.7–5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR = 15.7, 95% CI: 0.9–523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. Conclusion: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease.

We previously showed that mice lacking galectin-3/AGE-receptor 3 develop accelerated diabetic glomerulopathy. To further investigate the role of galectin-3/AGE-receptor function in the pathogenesis of diabetic renal disease, galectin-3 knockout (KO) and coeval wild-type (WT) mice were injected for 3 months with 30 microg/day of N(epsilon)-carboxymethyllysine (CML)-modified or unmodified mouse serum albumin (MSA). Despite receiving equal doses of CML, KO had higher circulating and renal AGE levels and showed more marked renal functional and structural changes than WT mice, with significantly higher proteinuria, albuminuria, glomerular, and mesangial area and glomerular sclerosis index. Renal 4-hydroxy-2-nonenal content and NFkappaB activation were also more pronounced in KO-CML vs. WT-CML. Kidney mRNA levels of fibronectin, laminin, collagen IV, and TGF-beta were up-regulated, whereas those of matrix metalloproteinase-2 and -14 were down-regulated, again more markedly in KO-CML than WT-CML mice. Basal and CML-induced RAGE and 80K-H mRNA levels were higher in KO vs. WT mice. MSA injection did not produce any significant effect in both genotypes. The association of galectin-3 ablation with enhanced susceptibility to AGE-induced renal disease, increased AGE levels and signaling, and altered AGE-receptor pattern indicates that galectin-3 is operating in vivo as an AGE receptor to afford protection toward AGE-dependent tissue injury.

The Chernobyl fallout caused release of radioisotope contaminants in a very large area that includes Belarus, the Ukraine, and the Russian Federation. In this study, the authors monitored the health status and level of internal contamination in 422 children who resided in the aforementioned areas and who were < or = 10 y of age at the time of the accident. The children came to Italy for a 1-mo period between 1991 and 1992. During this time, the children underwent pediatric checkups and biochemical, immunological, and thyroid analyses. All children underwent whole-body counter measurements, and urine radiotoxicological analysis was performed for 224 of them. The 24 children evacuated from Pripiat, a village very close to the Chernobyl reactor site, were selected for cytogenetic analysis. All of these children continue to have a detectable internal contamination of caesium radioisotopes. This condition is likely the result of ground and foodstuff contamination in the various areas. The children did not evidence overt pathologies related to ionizing radiation. However, minor alterations in immunological and thyroid parameters were observed in the group of the evacuated children. Traditional cytogenetic dosimetry was not possible, but the occurrence of acentric fragments was observed-indicating a persistent effect of continuous exposure to low doses of radiation.

Introduction: Early diagnosis by neonatal thyroid screening is crucial for intellectual and neuropsychological outcome of children with congenital hypothyroidism (CH). Nevertheless, numerous reports have shown that some CH children, even if early treated, still have neuropsychological sequelae at a later age. In this study, we investigate whether the occurrence of a delayed onset of therapy, despite newborn screening, can be responsible for psychomotor abnormalities. Subject and methods: Intellectual and neuropsychological development was assessed in a group of 29 CH children diagnosed by screening in a defined Italian region, in 3 CH children detected on the basis of clinical symptoms and in 11 CH adults born before the screening program was introduced. Thyroid assessment and clinical examination were also performed in these patients. Results: The screened CH children with delayed therapy onset (range:40–70 days) had mostly ectopic and eutopic thyroids and showed significantly lower mean intelligence quotients (90.8 ± 16 vs 106.2 ± 13) and lower mean scores on neuropsychological tests than earlier treated CH children (range: 7–30 days). Discussion: Our study points out that children with ectopic thyroid and dyshormonogenesis, although showing a milder thyroid deficit at screening, may be at risk for delayed onset of therapy and consequent cognitive damage prompt, and adequate treatment should be given in all types of primary CH to prevent mental disturbances in CH children.