Noninvasive human metabolome analysis for differential diagnosis of inborn errors of metabolism

Early diagnosis and treatment are critical for patients with inborn errors of metabolism (IEMs). For most IEMs, the clinical presentations are variable and nonspecific, and routine laboratory tests do not indicate the etiology of the disease. A diagnostic procedure using highly sensitive gas chromatography-mass spectrometric urine metabolome analysis is useful for screening and chemical diagnosis of IEM. Metabolite analysis can comprehensively detect enzyme dysfunction caused by a variety of abnormalities. The mutations may be uncommon or unknown. The lack of coenzymes or activators and the presence of post-translational modification defects and subcellular localization abnormalities are also reflected in the metabolome. This noninvasive and feasible urine metabolome analysis, which uses urease-pretreatment, partial adoption of stable isotope dilution, and GC/MS, can be used to detect more than 130 metabolic disorders. It can also detect an acquired abnormal metabolic profile. The metabolic profiles for two cases of non-inherited phenylketonuria are shown. In this review, chemical diagnoses of hyperphenylalaninemia, phenylketonuria, hyperprolinemia, and lactic acidemia, and the differential diagnosis of beta-ureidopropionase deficiency and primary hyperammonemias including ornithine transcarbamylase deficiency and carbamoylphosphate synthetase deficiency are described.     

The diffusion of new genetic tests for predicting disease.

This paper examines the pathways by which new genetic tests will become available to the public. In view of the scarcity of genetic specialists, the pathway is likely to involve primary care physicians. Other pathways entail state-mandated testing, community-based programs, or testing by laboratories without much involvement of primary care physicians. When testing does become available the "destination" will be either family-centered testing or population-oriented screening. The deterrent to screening will not be the inability to detect disease-causing mutations but the costs and attitudes of providers and the public. When tests are provided primarily to provide information about risks to future children, some people will oppose screening on religious or moral grounds. When there are no inexpensive treatments, some will fear that insurance companies and employers will use tests to deny them health care coverage. Some may not want to know their risks for disorders about which little can be done. For common, multifactorial disorders, genetic tests will have low predictive value. Because of these problems, the decision to be tested, regardless of the destination, requires that "testees" be fully informed and consent to testing. When acceptance rates are low, screening is less likely to be cost-effective; family-centered testing becomes the default destination.     

DIAGNOSIS OF DEAFNESS IN PRESCHOOL CHILDREN

Hearing and speech disorders in children are often not due to actual defects in the ear or speech organs. Supposed loss of hearing and speech can occur in children who hear well but who cannot identify the words, understand their meaning or express them because of damage to certain brain centers and nerve pathways in conditions called aphasia, psychic disorders and mental deficiency.The child uses his special senses (hearing, sight, touch, feel and smell) to establish contact with his environment and of these senses, hearing is most important because it helps to build the best avenue of communication with his immediate world.As the deafened child can usually be helped by treatment, it is necessary to make a correct diagnosis early in order that the proper measures may be instituted in the first five years of life.     

Diagnosis of inborn errors of metabolism using filter paper urine,urease treatment,isotope dilution and gas chromatography–mass spectrometry

This review will be concerned primarily with a practical yet comprehensive diagnostic procedure for the diagnosis or even mass screening of a variety of metabolic disorders. This rapid, highly sensitive procedure offers possibilities for clinical chemistry laboratories to extend their diagnostic capacity to new areas of metabolic disorders. The diagnostic procedure consists of the use of urine or filter paper urine, preincubation of urine with urease, stable isotope dilution, and gas chromatography–mass spectrometry. Sample preparation from urine or filter paper urine, creatinine determination, stable isotope-labeled compounds used, and GC–MS measurement conditions are described. Not only organic acids or polar ones but also amino acids, sugars, polyols, purines, pyrimidines and other compounds are simultaneously analyzed and quantified. In this review, a pilot study for screening of 22 target diseases in newborns we are conducting in Japan is described. A neonate with presymptomatic propionic acidemia was detected among 10,000 neonates in the pilot study. The metabolic profiles of patients with ornithine carbamoyl transferase deficiency, fructose-1,6-bisphosphatase deficiency or succinic semialdehyde dehydrogenase deficiency obtained by this method are presented as examples. They were compared to those obtained by the conventional solvent extraction methods or by the tandem mass spectrometric method currently done with dried filter blood spots. The highly sensitive, specific and comprehensive features of our procedure are also demonstrated by its use in establishing the chemical diagnosis of pyrimidine degradation defects in order to prevent side effects of pyrimidine analogs such as 5-flurouracil, and the differential diagnosis of three types of homocystinuria, orotic aciduria, uraciluria and other urea cycle disorders. Evaluation of the effects of liver transplantation or nutritional conditions such as folate deficiency in patients with inborn errors of metabolism is also described.     

Clinical and laboratory assessment of zinc deficiency in Dutch children

The clinical spectrum of acrodermatitis enteropathica (n=226) is compared with symptoms reported in other Zn deficiencies: total parenteral nutrition without Zn (n=21), protein energy malnutrition (n=24), gastrointestinal disease (n=79), geophagia (n=227), and dietary, low intake (n=23). Common features of deficiency are diarrhea, recurrent infection, and growth retardation. Dermatitis is less common in other types of deficiency than in acrodermatitis enteropathica (9 vs 88% of cases). Anorexia and/or hypogeusia is reported more frequently in the other types of deficiency (30 vs 16%). The main symptoms in acrodermatitis enteropathica vary with age. These differences in the clinical picture of Zn deficiency are discussed in relation to the degree of the deficiency (acute, subacute, or chronic; severe, mild, or subclinical). The results of the conventional laboratory tests to diagnose Zn deficiency (Zn levels in serum, urine or hair) are reviewed. In healthy Dutch infants and children, the mean values of these levels vary by a factor of 1.6–3.0. Also, the clinical interpretation of their results is prone to errors. Therefore, we advocate the erythrocytic⁶⁵Zn uptake test. Its mean varies by 1.3. However, its reference values for different age intervals need to be established. From the comparison of the results of three conventional tests of samples taken concurrently (serum, urine, and hair) in groups of Dutch children with symptoms common in Zn deficiency (diarrhea, recurrent infection, or growth retardation) it is estimated that ±1% of Dutch children with minor complaints suffer from either acute or subacute Zn deficiency. Other deficiencies occur occasionally. In order to detect the individual patient with deficiency, the erythrocytic⁶⁵Zn uptake test is promising and needs to be evaluated. Therefore, we review a set of reference laboratory tests with results that alter during sequential stages of overload and deficiency. Such a scheme is advocated as a guidance for future clinical research on deficiency, and solves the problem of differentiating those conditions that identify the individual patients who need treatment by supplementation.     

Phenylketonuria—Experience at One Center in the First Year of Screening in California

One year''s experience with phenylketonuria during the calendar year 1966, the first year for compulsory newborn screening in California, was reviewed. The over-all prevalence rate from reported cases in California during this period was one case per 19,500 persons tested. Fifty-seven persons suspected of having pku were evaluated, and 25 of them were determined to be phenylketonuric. Eleven of the 25 were infants in whom the abnormality was detected through the newborn screening program or because it was detected in a sibling through a screening program. All the newborn phenylketonuric patients were developing normally at the time of last report (although the follow-up periods were short).In nine of the other children, pku was detected because they were retarded. Five retarded children who were diagnosed as phenylketonuric at another clinic were given dietary assistance.Five additional infants had elevated serum phenylalanines but did not have the classic biochemical findings of pku and are being evaluated further. Nine infants with positive screening tests exhibited biochemical and clinical findings consistent with transient tyrosinemia. Eighteen other children were evaluated and found to have no metabolic abnormality.The newborn screening program for pku is of decided benefit in early identification of a group of infants who have a high rate of potentially serious metabolic disease. Early identification permits treatment soon enough to prevent mental retardation. Newly identified patients should be evaluated in a medical setting capable of careful pediatric, biochemical and nutritional surveillance.     

Molecular and functional characterisation of mild MCAD deficiency

We report a novel mild variant of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) diagnosed in four infants who, in neonatal screening, showed abnormal acylcarnitine profiles indicative of MCADD. Three patients showed completely normal urinary organic acids and phenylpropionic acid loading tests were normal in all four patients. Enzyme studies showed residual MCAD activities between "classical" MCADD and heterozygotes. ACADM gene analysis revealed compound heterozygosity for the common mutation K329E and a novel mutation, Y67H, in two cases, and homozygosity for mutation G267R and the novel mutation S245L, respectively, in two children of consanguineous parents. As in other metabolic disorders, the distinction between "normal" and "disease" in MCAD deficiency is blurring into a spectrum of enzyme deficiency states caused by different mutations in the ACADM gene potentially influenced by factors affecting intracellular protein processing.     

Introduction: new technologies for genetic and newborn screening

Screening newborn infants for inherited disorders has been effective in preventing mental retardation, growth failure, and death from several metabolic disorders for more than two decades. Technical advances have provided more screening tools for both genetic and nongenetic conditions, and in the coming decades these techniques will be used not only to screen newborns but to assess genetic risks in entire populations. The financial, legal, and ethical issues which these activities raise must influence the development of public policies in order to reap the benefits promised. The conference published here was designed to address these issues for health care practitioners, health policy planners, and public health professionals.     

Cost-effectiveness evidence of mental health prevention and promotion interventions: A systematic review of economic evaluations

BackgroundThe prevention of mental disorders and promotion of mental health and well-being are growing fields. Whether mental health promotion and prevention interventions provide value for money in children, adolescents, adults, and older adults is unclear. The aim of the current study is to update 2 existing reviews of cost-effectiveness studies in this field in order to determine whether such interventions are cost-effective.Methods and findingsElectronic databases (including MEDLINE, PsycINFO, CINAHL, and EconLit through EBSCO and Embase) were searched for published cost-effectiveness studies of prevention of mental disorders and promotion of mental health and well-being from 2008 to 2020. The quality of studies was assessed using the Quality of Health Economic Studies Instrument (QHES). The protocol was registered with PROSPERO (# CRD42019127778). The primary outcomes were incremental cost-effectiveness ratio (ICER) or return on investment (ROI) ratio across all studies.A total of 65 studies met the inclusion criteria of a full economic evaluation, of which, 23 targeted children and adolescents, 35 targeted adults, while the remaining targeted older adults. A large number of studies focused on prevention of depression and/or anxiety disorders, followed by promotion of mental health and well-being and other mental disorders. Although there was high heterogeneity in terms of the design among included economic evaluations, most studies consistently found that interventions for mental health prevention and promotion were cost-effective or cost saving. The review found that targeted prevention was likely to be cost-effective compared to universal prevention. Screening plus psychological interventions (e.g., cognitive behavioural therapy [CBT]) at school were the most cost-effective interventions for prevention of mental disorders in children and adolescents, while parenting interventions and workplace interventions had good evidence in mental health promotion. There is inconclusive evidence for preventive interventions for mental disorders or mental health promotion in older adults. While studies were of general high quality, there was limited evidence available from low- and middle-income countries.The review was limited to studies where mental health was the primary outcome and may have missed general health promoting strategies that could also prevent mental disorder or promote mental health. Some ROI studies might not be included given that these studies are commonly published in grey literature rather than in the academic literature.ConclusionsOur review found a significant growth of economic evaluations in prevention of mental disorders or promotion of mental health and well-being over the last 10 years. Although several interventions for mental health prevention and promotion provide good value for money, the varied quality as well as methodologies used in economic evaluations limit the generalisability of conclusions about cost-effectiveness. However, the finding that the majority of studies especially in children, adolescents, and adults demonstrated good value for money is promising. Research on cost-effectiveness in low-middle income settings is required.Trial registrationPROSPERO registration number: CRD42019127778.

In a systematic review, Long Khanh-Dao Le and colleagues investigate the cost effectiveness of mental health interventions among children, adolescents, and adults.     

Screening Foster Children for Mental Disorders: Properties of the Strengths and Difficulties Questionnaire

Background

High prevalence of mental disorders among foster children highlight the need to examine the mental health of children placed out of home. We examined the properties of the Strengths and Difficulties Questionnaire (SDQ) in screening school-aged foster children for mental disorders.

Methods

Foster parents and teachers of 279 foster children completed the SDQ and the diagnostic interview Developmental and Well-Being Assessment (DAWBA). Using the diagnoses derived from the DAWBA as the standard, we examined the performance of the SDQ scales as dimensional measures of mental health problems using receiver operating characteristic (ROC) analyses. Recommended cut-off scores were derived from ROC coordinates. The SDQ predictive algorithms were also examined.

Results

ROC analyses supported the screening properties of the SDQ Total difficulties and Impact scores (AUC = 0.80–0.83). Logistic regression analyses showed that the prevalence of mental disorders increased linearly with higher SDQ Total difficulties scores (X² = 121.47, df = 13, p<.001) and Impact scores (X² = 69.93, df = 6, p<.001). Our results indicated that there is an additive value of combining the scores from the Total difficulties and Impact scales, where scores above cut-off on any of the two scales predicted disorders with high sensitivity (89.1%), but moderate specificity (62.1%). Scores above cut-off on both scales yielded somewhat lower sensitivity (73.4%), but higher specificity (81.1%). The SDQ multi-informant algorithm showed low discriminative ability for the main diagnostic categories, with an exception being the SDQ Conduct subscale, which accurately predicted the absence of behavioural disorders (LHR− = 0.00).

Conclusions

The results support the use of the SDQ Total difficulties and Impact scales when screening foster children for mental health problems. Cut-off values for both scales are suggested. The SDQ multi-informant algorithms are not recommended for mental health screening of foster children in Norway.     

Vision screening at 8 and 18 months. Steering Committee of Oxford Region Child Development Project.

OBJECTIVE--To determine the effectiveness of an existing screening programme based in the community for ocular and vision defects in infants considered at increased risk of such defects. DESIGN--Children with ocular or vision defect by the age of 2 were ascertained by searching records. Those from populations at high risk were matched with their results from screening tests. The characteristics of the cases among this population were compared with those of the cases in the remainder of the population. Patterns of referral and age at referral were studied in both groups. SETTING--The study was conducted within Oxfordshire Health District. SUBJECTS--433 Children at high risk born in 1984 to mothers living in the health district at delivery and who either weighed less than 2000 g or weighed 2000 g and over and required admission to a special care nursery for longer than 24 hours. The low risk population (6254) were infants without these characteristics who were resident in the health district at the time of referral. INTERVENTIONS--Screening tests for vision or ocular defects already routinely used were applied by health visitors at 8 and 18 months to the children at high risk. MAIN OUTCOME MEASURE--Comparison of results of screening tests with vision and ocular defects detected by the age of 2. RESULTS--Screening tests in current use for vision loss and squint in this age group were insensitive and had a low positive predictive value when applied to a high risk population. Defects that were not apparent on direct inspection were unlikely to be detected by these tests. In the high risk group the relative risk of having a defect was 2.8 (95% confidence interval 1.8 to 4.5) but 85% of all cases detected by the age of 2 were in children at low risk. Referral patterns and age of referral differed in the two groups. CONCLUSIONS--Screening by health visitors of high risk populations contributes little to the detection of vision and ocular defects. This type of evaluation needs to be applied also to low risk populations, who have different referral patterns and contribute most of the cases.     

Correlation between breakfast tryptophan content and morning-evening in Japanese infants and students aged 0-15 yrs

Tryptophan can be metabolized via 5-hydroxytryptamine=serotonin to melatonin by a series of 4 enzymes in pineal body. Lack of serotonin in body fluid in the brain during daytime can lead to several psychiatric disorders, while shortage of plasma-melatonin at night can be related to sleep disorders. The Morning-Evening (M-E) questionnaire and the original questionnaire including questions on sleep habits, mental symptoms, and contents of meals were administered to 1055 infants aged 0-6 yrs, 751 students attending an elementary school, and 473 students attending junior high school in Kochi City (33 degrees N). The index of tryptophan taken at breakfast (Trp-Index) was calculated as tryptophan amount per one meal based on the tryptophan included in each 100 g of the foods and a standard amount of food per one meal. A significant positive-correlation between M-E scores and Trp-Index was not shown by relatively older students, aged 9-15 yrs (Pearson's test, r=0.044-0.123, p=0.071-0.505), whereas a significant positive correlation was shown by infants and young elementary school students aged 0-8 yrs (r=0.180, 0.258, p<0.001). The more frequently the infants had difficulty falling asleep at bedtime and waking up in the morning, the less the Trp-Indices taken at breakfast were (Kruskall-Wallis-test, p=0.027 for difficulty falling asleep; p=0.008 for difficulty waking up). The more frequently infants became angry even by a little trigger, or depressed, the lower (more evening-typed) the M-E scores were (Kruskal-Wallis test: p相似文献   

Akuttraumatisierung bei Unfallopfern

Motor vehicle and work-related accidents are the most common civil traumata. Between 10 and 30 % of accident victims develop posttraumatic mental health disorders with severe impacts on the patients themselves, as well as the health and social security systems. Unfortunately, recognition and secondary prevention of mental health problems still lack adequate attention in most surgical departments. A stepped-care model developed in the Psychotrauma Outpatient Unit of the University clinic of Freiburg is presented. With some modifications it can be adapted to the consultation service. The integration of different tasks of the consultation service (diagnosis, prevention, and treatment) and the interface between inpatient case identification and outpatient treatment are presented. It is essential to identify as early as possible those patients who need professional support because of already manifest severe symptoms or because of the high risk of developing posttraumatic mental health disorders. The steps differ concerning their intensity and specificity and have to be adapted to the individual needs of the patient. Usually trauma-focussed psychotherapy is not applied in the inpatient setting.     

Consequences of early adverse rearing experience (EARE) on development: insights from non-human primate studies

Early rearing experiences are important in one's whole life,whereas early adverse rearing experience (EARE) is usually related to various physical and mental disorders in later life.Although there were many studies on human and animals,regarding the effect of EARE on brain development,neuroendocrine systems,as well as the consequential mental disorders and behavioral abnormalities,the underlying mechanisms remain unclear.Due to the close genetic relationship and similarity in social organizations with humans,non-human primate (NHP) studies were performed for over 60 years.Various EARE models were developed to disrupt the early normal interactions between infants and mothers or peers.Those studies provided important insights of EARE induced effects on the physiological and behavioral systems of NHPs across life span,such as social behaviors (including disturbance behavior,social deficiency,sexual behavior,etc),learning and memory ability,brain structural and functional developments (including influences on neurons and glia cells,neuroendocrine systems,e.g.,hypothalamic-pituitary-adrenal (HPA) axis,etc).In this review,the effects of EARE and the underlying epigenetic mechanisms were comprehensively summarized and the possibility of rehabilitation was discussed.     

Selective screening for fatty acid oxidation disorders by tandem mass spectrometry: difficulties in practical discrimination

In a selective screening for fatty acid oxidation disorders by tandem mass spectrometry, we tested the diagnostic ratios and acylcarnitine concentrations in sera or blood spots, which were reported to be specific to very long-chain acyl CoA dehydrogenase deficiency, carnitine palmitoyltransferase I deficiency, and carnitine palmitoyltransferase II deficiency. While the acylcarnitine profiles in the majority of these patients were typical in the respective disorders, some overlapping of the indices was observed between these patients and the infants, who showed symptoms mainly related to hypoglycemia but did not have the disorders mentioned above. Although the diagnostic ratio of tetradecenoylcarnitine to dodecanoylcarnitine for very long-chain acyl CoA dehydrogenase deficiency seemed to minimize the overlapping in this study, additional measures including careful assessment of clinical data and enzyme assays may be necessary for the diagnosis in atypical cases.     

Screening of newborn infants for galactosemia in British Columbia

With simple microbiologic and fluorescent tests, we detected two cases of classic galactosemia, confirmed by specific enzyme assays, in the first 25 000 newborn infants in British Columbia screened for this disorder. The results were equivocally abnormal for another 31 infants, and a second blood sample was requested from each, either for repeat screening or for enzyme assays. The two infants with galactosemia were in hospital with an undiagnosed acute illness and had only a trace of nonglucose reducing substances in the urine when the screening tests were done. Screening for galactosemia fits well with our established programs of screening for phenylketonuria and hypothyroidism and costs less than $1 per infant tested.     

Newborn screening for Pompe disease: an update, 2011

There is mounting evidence in support of universal newborn screening for Pompe disease. Early treatment of children with infantile Pompe disease, prior to clinical diagnosis, is clearly of benefit in prolonging survival and improving cardiac and motor function. Several testing methods applicable to newborn screening using dried blood spots have been described and several are currently being tested in pilot screening programs. Although challenges remain, particularly in identification of the best strategy for follow-up and management of later onset Pompe disease, these challenges can surely be overcome as they have been with other disorders added to the newborn screening panel. It is anticipated that the results of the several pilot programs currently ongoing or in the planning stages in the United States will provide the data necessary to recommend universal newborn screening for Pompe disease for all infants.     

Preventive psychiatry: a blueprint for improving the mental health of young people

Preventive approaches have latterly gained traction for improving mental health in young people. In this paper, we first appraise the conceptual foundations of preventive psychiatry, encompassing the public health, Gordon''s, US Institute of Medicine, World Health Organization, and good mental health frameworks, and neurodevelopmentally‐sensitive clinical staging models. We then review the evidence supporting primary prevention of psychotic, bipolar and common mental disorders and promotion of good mental health as potential transformative strategies to reduce the incidence of these disorders in young people. Within indicated approaches, the clinical high‐risk for psychosis paradigm has received the most empirical validation, while clinical high‐risk states for bipolar and common mental disorders are increasingly becoming a focus of attention. Selective approaches have mostly targeted familial vulnerability and non‐genetic risk exposures. Selective screening and psychological/psychoeducational interventions in vulnerable subgroups may improve anxiety/depressive symptoms, but their efficacy in reducing the incidence of psychotic/bipolar/common mental disorders is unproven. Selective physical exercise may reduce the incidence of anxiety disorders. Universal psychological/psychoeducational interventions may improve anxiety symptoms but not prevent depressive/anxiety disorders, while universal physical exercise may reduce the incidence of anxiety disorders. Universal public health approaches targeting school climate or social determinants (demographic, economic, neighbourhood, environmental, social/cultural) of mental disorders hold the greatest potential for reducing the risk profile of the population as a whole. The approach to promotion of good mental health is currently fragmented. We leverage the knowledge gained from the review to develop a blueprint for future research and practice of preventive psychiatry in young people: integrating universal and targeted frameworks; advancing multivariable, transdiagnostic, multi‐endpoint epidemiological knowledge; synergically preventing common and infrequent mental disorders; preventing physical and mental health burden together; implementing stratified/personalized prognosis; establishing evidence‐based preventive interventions; developing an ethical framework, improving prevention through education/training; consolidating the cost‐effectiveness of preventive psychiatry; and decreasing inequalities. These goals can only be achieved through an urgent individual, societal, and global level response, which promotes a vigorous collaboration across scientific, health care, societal and governmental sectors for implementing preventive psychiatry, as much is at stake for young people with or at risk for emerging mental disorders.     

Effects of an insect‐mediated mental healthcare program for mentally disordered children

Insects are the most diverse groups of animals on the planet, representing more than one‐half of all known living organisms, and are found in nearly every environment. Recently, the importance of insects as food sources or as pets has increased in many countries, including Korea. In addition, several insects have been shown to exert a strong influence on people's emotions. Our insect‐mediated mental healthcare program is designed to help meet the physical, behavioral and developmental needs of people with mental disorders. Children with mental disorders, the experimental group, were provided with an insect‐mediated mental healthcare program for a total of eight sessions, one session per week, at 1–2 h per session, accompanied by a pre‐test and post‐test. The overall, gender, education level, and mental disease profiles of the participants in this study were balanced. Our results indicated that children who participated in the insect‐mediated healthcare program group once showed significant improvement in their emotional health and insect awareness. Additionally, paired education level's t‐tests showed that the outcomes of the participants in treatment group were significantly improved (α < 0.05). However, participants' satisfaction with their school life (middle school) was not influenced. These results suggest that insects positively influence children's emotional health through an insect‐mediated healthcare program. Further research on the basis of this study is expected to help children with emotional therapy in other areas.     

Neonatal thyroid-stimulating hormone screening as an indirect method for the assessment of iodine deficiency in Estonia

According to neonatal thyroid screening the incidence of congenital hypothyroidism in Estonia is 1:2,860. Transient hyperthyrotropinemia with a raised thyroid-stimulating hormone level of 5 microU/ml occurred in 17.7% of infants and was not associated with low birth weight, small birth length, low gestational age or congenital anomalies. Based on WHO criteria (WHO/UNICEF, 1994) it corresponds to mild iodine deficiency in Estonia (3% or less is in iodine-sufficient areas). This is in agreement with the previously reported median urinary iodine content of 65 microg/l in children. The frequency of infants with TSH >5 microU/ml was 16.4, 21 and 17. 2% in three regions (north, central and south) of Estonia, respectively, indicating mild to moderate iodine deficiency. These findings show the possibility of using the results of newborn screening for congenital hypothyroidism to assess the severity of iodine deficiency in Estonia. The introduction of universal iodine prophylaxis is recommended.