Evolution of an influenza pandemic in 13 countries from 5 continents monitored by protein microarray from neonatal screening bloodspots.

BACKGROUND: Because of lack of worldwide standardization of influenza virus surveillance, comparison between countries of impact of a pandemic is challenging. For that, other approaches to allow internationally comparative serosurveys are welcome. OBJECTIVES: Here we explore the use of neonatal screening dried blood spots to monitor the trends of the 2009 influenza A (H1N1) pdm virus by the use of a protein microarray. STUDY DESIGN: We contacted colleagues from neonatal screening laboratories and asked for their willingness to participate in a study by testing anonymized neonatal screening bloodspots collected during the course of the pandemic. In total, 7749 dried blood spots from 13 countries in 5 continents where analyzed by using a protein microarray containing HA1 recombinant proteins derived from pandemic influenza A (H1N1) 2009 as well as seasonal influenza viruses. RESULTS: Results confirm the early start of the pandemic with extensive circulation in the US and Canada, when circulation of the new virus was limited in other parts of the world. The data collected from sites in Mexico suggested limited circulation of the virus during the early pandemic phase in this country. In contrast and to our surprise, an increase in seroprevalence early in 2009 was noted in the dataset from Argentina, suggestive of much more widespread circulation of the novel virus in this country than in Mexico. CONCLUSIONS: We conclude that this uniform serological testing of samples from a highly standardized screening system offers an interesting opportunity for monitoring population level attack rates of widespread diseases outbreaks and pandemics.

European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism

"OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy."

European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism

"OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy."

Positive effect of a simplified diet on blood phenylalanine control in different phenylketonuria variants, characterized by newborn BH4 loading test and PAH analysis.

Until today, the mainstay of phenylketonuria (PKU) treatment is a phenylalanine (Phe)-restricted diet. Strict dietary treatment decreases flexibility and autonomy and still has a major impact on patients and their families. Compliance is often poor, particularly in adolescence. The aim of this study was to investigate the effect of the intake of fruits and vegetables containing Phe less than 100 mg/100g ('simplified diet'), as recommended by WHO for all individuals, instead of classical totally restricted diet on the course and treatment control of the disease in a well-characterized PKU cohort (n=80). All individual blood Phe measurements of each patient (1992-2009) were statistically analyzed before and after diet switch. Epidemiological data, age at diagnosis, PAH mutations, BH(4) responsiveness, as well as Phe control measurements and detailed diet information were tabulated in a local database. 62.5% had BH4 loading test and 40% had PAH analysis; 50/80 switched from classical to simplified diet, including 26 classical PKU, 13 moderate PKU, 7 mild PKU and 4 mild hyperphenylalaninemia (HPA). Median Phe levels on a simplified diet did not differ significantly to the median Phe levels on classical diet in all disease groups. Our results indicate that a simplified diet has no negative effect on blood Phe control in patients with hyperphenylalaninemia, independent of severity of the phenotype or the age at diet switch, over the period of 3 years. Thus, a simpler approach to dietary treatment of PKU available to all HPA patients is more likely to be accepted and adhered by patients and might also increase quality of life.

Congenital adrenal hyperplasia: diagnostic advances.

Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90% of cases. Much has been learned about the genetics of the various clinical forms of 21-hydroxylase deficiency, and correlations between the genotype and the phenotype have been studied extensively. Gene-specific diagnosis is now feasible and neonatal screening and prenatal treatment have been widely implemented. This discussion will be limited to the most common form of congenital adrenal hyperplasia, with focus on the diagnostic advances in this disease.

First ISNS Reference Preparation for Neonatal Screening for thyrotropin, phenylalanine and 17alpha-hydroxyprogesterone in blood spots.

BACKGROUND: Neonatal screening for congenital disorders like phenylketonuria (PKU), congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH) is generally performed in dried blood spots on filter paper. The analytes of interest for testing for PKU, CH and CAH are phenylalanine, thyrotropin (TSH) and 17alpha-hydroxyprogesterone (17OHP), respectively. The International Society for Neonatal Screening (ISNS) decided to prepare a combined reference preparation for the three analytes on filter paper Schleicher & Schuell #903, Whatman BFC180 and Toyo Roshi 545. This 'First ISNS Reference Preparation for Neonatal Screening for TSH, phenylalanine and 17OHP in blood spots' (1st ISNS-RPNS) has been prepared by the RIVM (Bilthoven). METHOD: The number of filter paper cards prepared, each with two sets of six blood spot calibrators, was 480, 42 and 69 for Schleicher & Schuell #903, Whatman BFC180 and Toyo Roshi 545, respectively. The volume of blood dispensed was 50 microl. The range of concentrations for TSH was 1-121 mIU/L blood, for phenylalanine 65-865 micromol/L blood and for 17OHP 2.2-302 nmol/L blood. RESULTS: The linearity of the blood spot calibrators and the homogeneity of the batch (only tested for Schleicher & Schuell) were good. The differences between the three filter papers were small: i.e. the potency of the ISNS-RPNS on Whatman and Toyo Roshi in terms of Schleicher & Schuell was between 0.98 and 1.09 for the three analytes. CONCLUSION: The 1st ISNS-RPNS for TSH, phenylalanine and 17OHP can be said to be suitable as formal reference preparation and as a source for (re)calibrating kit calibrators.

Filter paper cards contaminated with EMLA cream produce artefacts on acylcarnitine analysis.

Electrospray ionization tandem mass spectrometry is a widely applied method for the analysis of acylcarnitines in blood samples spotted on filter paper cards (Guthrie cards). When the filter paper cards are contaminated by EMLA cream, highly intense signals at m/z 221 and 235 are detected under ESI-MS/MS conditions, monitoring for precursors of m/z 85. These signals correspond to the active ingredients prilocaine and lidocaine in EMLA and overlap with the signals from the isotopically labelled internal standards (2H3)propionyl carnitine and (2H3)butyrylcarnitine. This interference prevents the proper quantification of the two short-chain acylcarnitines when samples are analysed without derivatization.

Evaluation of neonatal screening for congenital adrenal hyperplasia.

Neonatal screening for congenital hypothyroidism has been effective in early detection and treatment of the condition. The position with respect to neonatal screening for congenital adrenal hyperplasia has been debated for many years. Some countries have performed congenital adrenal hyperplasia screening for many years, others have conducted pilot studies that were then not adopted. This article endeavours to summarize the complex issues behind decisions whether to screen or not and summarizes the findings of neonatal congenital adrenal hyperplasia screening programmes.

Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism.

OBJECTIVE: It is suggested that iodide organification defects account for 10% of all cases with congenital hypothyroidism (CH). One candidate gene for these defects is the thyroid peroxidase (TPO) gene. DESIGN: Exons 2, 8-10 and 14 of the TPO gene were examined in 30 patients with permanent CH without a family history of CH. This group was characterized by the presence of an orthotopic thyroid gland and elevated TSH levels. METHODS: The mutational screening was performed by single-strand conformational polymorphism followed by sequence analysis of fragments with abnormal migration patterns and by restriction enzyme analysis. RESULTS: In four patients we were able to identify mutations on both alleles which have not been described so far. One patient was a carrier of a new homozygous point mutation in exon 9 resulting in an exchange from Leu to Pro at codon 458. Another patient was found to be compound heterozygous for two mutations, a 20 bp duplication in exon 2 and a new mutation in exon 9 (Arg491His). Two brothers of consanguineous parents showed a homozygous T deletion in exon 14 at position 2512. CONCLUSIONS: Our findings confirm the genetic heterogeneity of TPO defects and support the suggested prevalence of organification defects.

Epidemiology of type I diabetes mellitus in Switzerland: steep rise in incidence in under 5 year old children in the past decade.

AIMS/HYPOTHESIS: In this nationwide prospective study we wanted to verify the trend of increasing diabetes incidence data from our earlier retrospective analysis of the military registry of Swiss men. SUBJECTS AND METHODS: The data collection of newly diagnosed children in Switzerland at an age younger than 15 years started in 1991. The countrywide survey used a small questionnaire which was sent back to the study centre. The questionnaire was anonymous and contained: hospital of diagnosis, initials, sex, birth date, date of diagnosis, residence, country of citizenship, and responsible physician. General data on the population were taken from publications of the Swiss Federal Statistical Office. RESULTS: A total of 941 children below the age of 15 years with newly diagnosed Type I (insulin-dependent) diabetes mellitus were collected (434 girls, 507 boys). The incidence in children aged 0 to 14 years rose significantly between 1991 and 1999 with a yearly average increase of 5.1%. In the age group 0 to 4 years a more than four-fold increase in incidence from 2.4/100,000 per year to 10.5/100,000 per year (p = 0.0002) was recorded, whereas the age-specific incidence in the 5 to 9-year-old and 10 to 14-year-old children did not change during the data collection period. The incidence was significantly higher in boys than in girls, whereas no difference was found between rural and urban populations. CONCLUSION/INTERPRETATION: The incidence of Type I diabetes is rising in children living in Switzerland but only the youngest age group of under 5 years of age is affected showing a large annual average increase of 23.8%.

Monitoring the adequacy of salt iodization in Switzerland: a national study of school children and pregnant women.

BACKGROUND: Several countries with long-standing salt iodization programs, including Switzerland, have recently reported declining and/or low urinary iodine (UI) levels in their populations. In Switzerland, in response to studies indicating low UI levels in children and pregnant women, the salt iodine level was increased in 1998 from 15 to 20 mg/kg. OBJECTIVE: Our objective was to evaluate iodine nutrition in a national sample of Swiss school children and pregnant women 8 16 months after the increase in the salt iodine level. DESIGN: A 3-stage probability proportionate to size cluster sampling method was used to obtain a representative national sample of 600 children aged 6-12 y and 600 pregnant women. We then measured UI in both groups, thyrotropin (TSH) in pregnant women and thyroid volume by ultrasound to determine goiter prevalence in school children. RESULTS: The median UI (range) of the children and pregnant women was 115 microg/l (5-413) and 138 microg/l (5-1881), respectively. The median blood TSH concentration (range) of pregnant women was 0.6 mU/l (0.2-2.1). Based on the current WHO/ICCIDD normative data for thyroid volume, none of the children were goitrous, using either age/sex-specific or BSA/sex-specific cutoffs. CONCLUSIONS: The iodine status of the Swiss population is once again adequate, illustrating the value of periodic monitoring and prudent adjustments to the iodine level in salt. This approach could serve as a model for countries struggling to maintain dietary iodine intake in the face of shifting dietary habits and changes in the food supply.

The release of antidiuretic hormone is appropriate in response to hypovolemia and/or sodium administration in children with severe head injury: a trial of lactated Ringer's solution versus hypertonic saline.

UNLABELLED: We conducted an open, randomized, and prospective study to determine the effect of hypertonic saline on the secretion of antidiuretic hormone (ADH) and aldosterone in children with severe head injury (Glasgow coma scale <8). Thirty-one consecutive patients at a level III pediatric intensive care unit at a children's hospital received either lactated Ringer's solution (Ringer's group, n = 16) or hypertonic saline (Hypertonic Saline group, n = 15) over a 3-day period. Serum ADH levels were significantly larger in the Hypertonic Saline group as compared with the Ringer's group (P = 0.001; analysis of variance) and were correlated to sodium intake (Ringer's group: r = 0.39, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.42, R(2) = 0.18, P = 0.02) and volume of fluids given IV (Ringer's group: r = 0.38, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.32, R(2) = 0.1, P = not significant). Correlation of ADH to plasma osmolality was significant if plasma osmolality was >280 mOsm/kg (r = 0.5, R(2) = 0.25, P = 0.06), indicating an osmotic threshold for ADH release. Serum aldosterone levels were larger on the first day than during Days 2 and 3 in both groups and inversely correlated to serum sodium levels only in the Ringer's group (r = -0.55, R(2) = 0.3, P < 0.001). This group received a significantly larger fluid volume on Day 1 (P = 0.05, Mann-Whitney U-test) than did patients in the Hypertonic Saline group, indicating hypovolemia during the first day. Head-injured children have appropriate levels of ADH. They may be hypovolemic during the first day of treatment, especially if they receive lactated Ringer's solution. IMPLICATIONS: In head-injured patients, we recommend fluid restriction to avoid inappropriate secretion of antidiuretic hormone. In a prospective, randomized, and controlled study in 31 children, we were able to show that the antidiuretic hormone levels are appropriate in response to hypovolemia, sodium load, or both.

Thyroid ultrasound compared with World Health Organization 1960 and 1994 palpation criteria for determination of goiter prevalence in regions of mild and severe iodine deficiency.

OBJECTIVES: In 1994, WHO/International Council for the Control of Iodine Deficiency Disorders recommended replacing the WHO 1960 four-grade goiter classification with a simplified two-grade system. The effect of this change in criteria on the estimation of goiter prevalence in field studies is unclear. In areas of mild iodine deficiency disorders (IDD) where goiters are small, ultrasound is preferable to palpation to estimate goiter prevalence. However, in areas of moderate to severe IDD, goiter screening by palpation may be an acceptable alternative to thyroid ultrasound. To address these two issues, we compared WHO 1960 and 1994 criteria with thyroid ultrasound for determination of goiter prevalence in areas of mild and severe IDD in Morocco. DESIGN: A cross-sectional study of 400 six- to 13-year-old children from two mountain villages (Ait M'hamed and Brikcha) in rural Morocco was carried out. METHODS: Urinary iodine concentration (UI), whole blood TSH and serum thyroxine were measured. Thyroid size was graded by inspection and palpation by two examiners using both WHO 1960 and 1994 criteria. Thyroid volume was determined by ultrasound. Variation between examiners and examination methods was assessed. Sensitivity and specificity of the two classification systems compared with ultrasound were calculated. RESULTS: Median UIs in Aït M'hamed and Brikcha were 183 and 24 microg/l respectively. In Ait M'hamed, using 1960 and 1994 criteria, goiter prevalence was 21 and 26% respectively, compared with 13% by ultrasound. In Brikcha, with 1960 and 1994 criteria, goiter prevalence was 64 and 67% respectively, compared with 64% by ultrasound. Agreement between observers was better with the 1994 criteria than with the 1960 criteria in Ait M'hamed (kappa=0.53 and 0.47 respectively), while in Brikcha observer agreement was similar with the two systems (kappa=0.67). Using either the 1994 or 1960 criteria, agreement with ultrasound was only moderate in Ait M'hamed (kappa=0.41-0.44), but good in Brikcha (kappa=0.55-0.64). Overall, compared with ultrasound, sensitivity increased 3-4% using 1994 criteria, while specificity decreased 4-5%. CONCLUSIONS: The WHO 1994 criteria are simpler to use than the 1960 criteria and provide increased sensitivity with only a small reduction in specificity. Agreement between observers is better with the 1994 criteria than with the 1960 criteria, particularly in areas of mild IDD. Like the 1960 criteria, the 1994 criteria overestimate goiter prevalence in areas of mild IDD, compared with ultrasound. However, the 1994 palpation criteria provide an accurate estimate of goiter prevalence in areas of severe IDD, and may be an acceptable and affordable alternative to thyroid ultrasound in these areas.

Low dose oral iodized oil for control of iodine deficiency in children.

In areas where iodized salt is not available, oral iodized oil is often used to correct I deficiency despite a lack of consensus on the optimal dose or duration of effect, particularly in children, a main target group. Annual doses ranging from 400 to 1000 mg have been advocated for school-age children. Because lower doses of iodized oil have been shown to be effective in treating I deficiency in adults, the aim of this study was to evaluate the efficacy and safety of a low dose of oral iodized oil in goitrous I-deficient children. Goitrous children (n 104, mean age 8.4 years, range 6-12 years, 47% female) received 0.4 ml oral iodized poppyseed-oil containing 200 mg I. Baseline measurements included I in spot urines (UI), serum thyroxine (T4), whole blood thyroid-stimulating hormone (TSH), and thyroid-gland volume using ultrasound. At 1, 5, 10, 15, 30 and 50 weeks post-intervention, UI, TSH and T4 were measured. At 10, 15, 30 and 50 weeks, thyroid-gland volume was remeasured. At 30 and 50 weeks the mean percentage change in thyroid volume from baseline was -35% and -41% respectively. The goitre rate fell to 38% at 30 weeks and 17% at 50 weeks. No child showed signs of I-induced hypo- or hyperthyroidism. UI remained significantly increased above baseline for the entire year (P < 0.001); the median UI at 50 weeks was 97 micrograms/l, at the World Health Organization cut-off value (100 micrograms/l) for I-deficiency disorders risk. In this group of goitrous children, an oral dose of 200 mg I as Lipiodol (Guerbert, Roissy CdG Cedex, France) was safe and effective for treating goitre and maintaining normal I status for at least 1 year.

Evaluation of a clinical algorithm involving serum eosinophil cationic protein for guiding the anti-inflammatory treatment of bronchial asthma in childhood.

A pilot study was performed to investigate a clinical algorithm using serum-eosinophil cationic protein level (S-ECP) as an objective parameter for tapering the anti-inflammatory treatment in chronic childhood asthma. We studied 21 outpatient asthmatic children (6 girls and 15 boys, mean age 9 yr, range 3-12 yr, all with initial S-ECP > or = 15 microg/l) over a period of 12 months at monthly intervals. At each visit a short history, clinical examination, blood sample for S-ECP and eosinophil count, lung function tests and drug compliance were assessed. According to the initial S-ECP, patients were allocated to two anti-inflammatory treatment groups: patients with S-ECP between 15 microg/l and 30 microg/l were treated with Budesonide 200 microg twice daily, while patients with S-ECP of 30 microg/l and above received Budesonide 400 microg twice daily. After this induction treatment the anti-inflammatory medication was tapered at monthly intervals according to actually measured S-ECP: patients with S-ECP < 15 microg/l received sodium cromoglycate (SCG) 10 mg twice daily per inhalation via spacer, patients with S-ECP > or = 15 microg/l and < 30 microg/l received Budesonide 200 microg twice daily via spacer, and patients with S-ECP > or = 30 microg/l received Budesonide 400 microg twice daily. Prior to inhalation of topical steroids or SCG all patients had to inhale 500 microg Terbutaline twice daily for optimal bronchodilatation. The use of medication was assessed by weighing the metered dose inhaler containers each month. Our results showed a decrease in symptoms (p = 0.0001) and in S-ECP (p= 0.02) and MEF50% predicted (p= 0.02) after the initial month of Budesonide treatment. During a total of 246 months of investigation there was no need for emergency room treatment or hospital admission, and no need for oral steroids. During the whole study period there was a tendency for inhaled steroids to be more effective than SCG in reduction of markers of airway inflammation, improvement of symptoms and lung function. Inadequate use of medication was related to an increase in S-ECP in all treatment groups. From this open pilot study it is concluded that a clinical algorithm including S-ECP for tapering the anti-inflammatory treatment may be helpful in childhood asthma. These first observations should be confirmed by a controlled long-term study.

Effect of oral iodized oil on thyroid size and thyroid hormone metabolism in children with concurrent selenium and iodine deficiency.

OBJECTIVES: To determine the efficacy of oral iodized oil in goitrous children who are both selenium (Se) and iodine deficient; to investigate if Se status modifies the response of iodine deficient, goitrous children to oral supplementation with iodized oil. DESIGN: A longitudinal intervention trial. SETTING: Two rural villages in the western Côte d'Ivoire. SUBJECTS: 51 goitrous non-anemic schoolchildren with both iodine and Se deficiency. INTERVENTION: Each child received an oral dose of 0.4 ml iodized poppyseed oil containing 200 mg of iodine. They were followed for 1 y with measurements of urinary iodine (UI), thyrotropin (TSH), thyroxine (T4), and thyroid volume by ultrasound. RESULTS: At baseline all children were goitrous and Se deficient; median UI was 29 microg/l and mean serum Se (s.d.) was 14.8 (10.7) microg/l. After receiving iodized oil, thyroid volume decreased significantly vs baseline at 10, 15, 30 and 50 weeks (P<0.001). At 50 weeks mean percentage change in thyroid volume from baseline was-46.6% and only five children remained goitrous. Median TSH values at 5, 10, 15, 30 and 50 weeks were reduced significantly (P<0.001) compared to baseline. Among individual children the severity of Se deficiency predicted the degree of response to iodized oil. Baseline serum Se and percentage change in thyroid volume from baseline at 50 weeks were strongly correlated (r2=0.554). Baseline Se and percentage decrease in TSH from baseline at 30 weeks were also well-correlated (r2=0.467). CONCLUSION: Although more severe Se deficiency partially blunts the thyroid response to iodine supplementation, oral iodized oil is an effective method for iodine repletion in goitrous children who are Se deficient. SPONSORSHIP: The Swiss Federal Institute of Technology, Zürich, the Foundation for Micronutrients in Medicine, Rapperswil, Switzerland, and the Thrasher Research Fund, Salt Lake City, USA.

Iron supplementation in goitrous, iron-deficient children improves their response to oral iodized oil.

OBJECTIVE: In developing countries, many children are at high risk for both goiter and iron-deficiency anemia. Because iron deficiency may impair thyroid metabolism, the aim of this study was to determine if iron supplementation improves the response to oral iodine in goitrous, iron-deficient anemic children. DESIGN: A trial of oral iodized oil followed by oral iron supplementation in an area of endemic goiter in the western Ivory Coast. METHODS: Goitrous, iodine-deficient children (aged 6-12 years; n=109) were divided into two groups: Group 1 consisted of goitrous children who were not anemic; Group 2 consisted of goitrous children who were iron-deficient anemic. Both groups were given 200mg oral iodine as iodized oil. Thyroid gland volume using ultrasound, urinary iodine concentration (UI), serum thyroxine (T(4)) and whole blood TSH were measured at baseline, and at 1, 5, 10, 15 and 30 weeks post intervention. Beginning at 30 weeks, the anemic group was given 60mg oral iron as ferrous sulfate four times/week for 12 weeks. At 50 and 65 weeks after oral iodine (8 and 23 weeks after completing iron supplementation), UI, TSH, T(4) and thyroid volume were remeasured. RESULTS: The prevalence of goiter at 30 weeks after oral iodine in Groups 1 and 2 was 12% and 64% respectively. Mean percent change in thyroid volume compared with baseline at 30 weeks in Groups 1 and 2 was -45.1% and -21.8% respectively (P<0.001 between groups). After iron supplementation in Group 2, there was a further decrease in mean thyroid volume from baseline in the anemic children (-34.8% and -38.4% at 50 and 65 weeks) and goiter prevalence fell to 31% and 20% at 50 and 65 weeks. CONCLUSION: Iron supplementation may improve the efficacy of oral iodized oil in goitrous children with iron-deficiency anemia.

Persistence of goiter despite oral iodine supplementation in goitrous children with iron deficiency anemia in Côte d'Ivoire.

BACKGROUND: In developing countries, many children are at high risk of goiter and iron deficiency anemia. Because iron deficiency can have adverse effects on thyroid metabolism, iron deficiency may influence the response to supplemental iodine in areas of endemic goiter. OBJECTIVE: The aim of this study was to determine whether goitrous children with iron deficiency anemia would respond to oral iodine supplementation. DESIGN: A trial of oral iodine supplementation was carried out in an area of endemic goiter in western Côte d'Ivoire in goitrous children (n = 109) aged 6-12 y. Group 1 (n = 53) consisted of goitrous children who were not anemic. Group 2 (n = 56) consisted of goitrous children who had iron deficiency anemia. At baseline, thyroid gland volume and urinary iodine, thyrotropin, and thyroxine were measured by using ultrasound. Each child received 200 mg I orally and was observed for 30 wk, during which urinary iodine, thyrotropin, thyroxine, hemoglobin, and thyroid gland volume were measured. RESULTS: The prevalence of goiter at 30 wk was 12% in group 1 and 64% in group 2. The mean percentage change from baseline in thyroid volume 30 wk after administration of oral iodine was -45.1% in group 1 and -21.8% in group 2 (P < 0.001). Among the anemic children, there was a strong correlation between the percentage decrease in thyroid volume and hemoglobin concentration (r(2) = 0.65). CONCLUSION: The therapeutic response to oral iodine was impaired in goitrous children with iron deficiency anemia, suggesting that the presence of iron deficiency anemia in children limits the effectiveness of iodine intervention programs.

Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia.

We investigated the feasibility and diagnostic utility of genotyping 9 CYP21 mutations, linked chromosome 6p markers, and a dimorphic X-Y marker from neonatal screening samples. Blood-impregnated filter papers (Guthrie cards) from 603 randomly chosen New Zealand neonates were genotyped blind to 17-hydroxyprogesterone (17-OHP) levels. Another 50 samples from Swiss and North American infants with correlative hormonal data were also genotyped. DNA was extracted, and gene-specific PCR was performed. CYP21 PCR products were subjected to ligase detection reaction, simultaneously analyzing 9 CYP21 mutations; PCR products of other genes were subjected to direct gel analysis. CYP21 genotyping indicated a heterozygote rate of 2.8% for classic mutations (excluding CYP21 deletions), and 2.0% for nonclassic mutations in New Zealanders. Ten full-term affected neonates showed a wide range of 17-OHP levels (15-1400 nmol/L). Sick or preterm infants or infants screened on the first day of life with high 17-OHP proved genetically unaffected. Genetic linkage disequilibrium was found between two CYP21 mutations and chromosome 6p markers. Guthrie cards can be used to accurately genotype CYP21 and other relevant markers, potentially enhancing the specificity and sensitivity of congenital adrenal hyperplasia screening. CYP21 heterozygote frequency for classic mutations is higher than expected based on genotype compared with that predicted by hormonal newborn screening.

Quality assurance and standardization: summary of the satellite meeting, Turku, Finland, 11-12 June 1999.

The Quality Assurance (QA) and Standardization satellite meeting addressed five major issues in newborn screening: (i) Pre- and post-analytical phases are important in the overall quality of screening, and quality assurance programs should include these aspects. (ii) It is possible to run a single screening program using laboratories on more than one site, as is done in Europe, California and Cuba. Special quality assurance procedures are necessary for success. (iii) It is possible to achieve improved analytical quality and international comparison of results by use of common reference materials such as the amino acid materials developed in Europe and the US. It will be important to use tested paper with defined performance characteristics. (iv) It is appropriate for newborn screening programs to be accredited, but it will also be important to develop criteria for pre- and post-analytic phases of screening. (v) A new QA program is being developed for Latin America. The Australasian QA program now includes amino acids and acylcarnitines in a form suitable for tandem mass spectrometry blind QA. The European Society for Paediatric Endocrinology has developed guidelines for CAH screening.