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Introduction: Screening for congenital hypothyroidism (CH) was re-established in Iran in 1998 following elimination of iodine deficiency. Material and methods: The incidence of CH and its etiologic factors in addition to some demographic features of the screened neonates were assessed. From 21 February 1998 to 21 June 2001 cord blood spot samples from 8 hospitals and a rural birth center were collected and tested for TSH measurement using a two-site IRMA method. TSH values  20 mU/mL were recalled. The diagnosis of CH was confirmed using age adjusted reference values for serum TSH and T4 levels and replacement L-T4 therapy, 10-15 g/kg/d, started promptly. Results: Out of 20107 screened neonates 256 had cord TSH values  20 U/mL (recall rate: 1.3%) and 22 showed hypothyroidism (1: 914 live births). Median iodine excretion levels of 50 recalled neonates and 47 mothers were 37.5 and 21 g/dl, respectively. History of drugs and dietary goitrogens was negative. 15 out of 21 CH neonates had parental consanguinity. The odds ratio of CH occurrence in blood-related to non-related marriages was 6.9 (95% CI = 1.82-25.87) and the risk of CH in consanguineous marriages was 0.0036. Thyroid dysgenesis occurred in 10 neonates 1: 2011 births. Conclusion: There is a high incidence of CH and thyroid dysgenesis in Islamic Republic of Iran. Consanguineous marriages could be considered a probable causative factor for the increased incidence of CH in the study.

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Introduction: Awareness of the distribution of recall rate and CH incidence in different seasons could provide a better understanding of their etiologies and appropriate allocation of resources in a CH screening program. This report illustrates the distribution of recall rate and CH incidence in different seasons during the program of screening for CH in Tehran and Damavand. Material and Methods: From March 1998 to March 2002 (48 months), cord blood spot samples from 8 hospitals and a rural birth center in Tehran and Damavand were collected on filter papers. TSH values were measured using a two-site IRMA method. Cord TSH levels  20 mU/L were considered abnormal and recalled for serum confirmatory tests. CH was diagnosed by abnormal serum TSH and T4 levels using age adjusted reference values for the age. The odds ratios and 95% confidence intervals (CI) for the occurrence of cord TSH levels  20 mU/L and CH in winter and other seasons were assessed. Also, the effect of using iodine-containing antiseptics for the maternal preparation prior to delivery was assessed. Results: Out of 29908 cord blood samples, 314 had TSH levels of  20 mU/L (recall rate: 10.5‰). The recall rate was 13.1‰ and 9.5‰ of live births in winter and other seasons, respectively. The odds ratio of occurrence of cord TSH  20 mU/L in winter to other seasons was 1.39 with a 95% CI of 1.10-1.76 (P<0.01). The effect of iodine-containing antiseptics on the increased recall rate in winter as compared to other seasons was not significant. Sixteen (1: 502 live births) and 15 (1: 1458 live births) CH neonates were born in winter and other seasons, respectively (odds ratio: 2.91 95% CI: 1.44-5.89 [p<0.01]). Conclusion: The recall rate and CH occurrence are higher in winter than in other seasons.

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Introduction: The production of neonatal TSH kits for the measurement of the analyte on filter papers has been considered a necessity for national screening program of congenital hypothyroidism (CH) in the I. R. Iran. This report aims at evaluating the afore mentioned kit, which has been produced for the first time in the I. R. Iran and used by Endocrine Research Center in the screening program for CH. Material and Methods: From February 1998 to June 2001, cord dried blood spot (DBS) samples applied onto filter papers were sent to Endocrine Research Center laboratory from 8 hospitals in Tehran and Damavand for TSH measurement using a two-site IRMA kit produced by Atomic Energy Organization of Iran according to the NETRIA company instructions. Validity of the method including precision (intra- and inter-assay tests), accuracy (recovery tests), sensitivity, and specificity were assessed. Also, absolute values in difference of TSH values of 41 randomly selected cord DBS samples measured by both the present and DRG (ELISA) neonatal TSH kits were calculated and their correlation was assessed using Pearson’s correlation coefficient. For statistical analyses, the SPSS version 9.05 software was employed. Results: Cord DBS TSH levels of 20107 samples were measured. Three CH cases with borderline cord TSH values (23-35 mIU/L) were detected. The sensitivity of the method was 1 mIU/L. The coefficients of variation (%) were 10.7, 8.7, 9.4, and 9.6 (intra-assay) and 12.2, 9.1, 10.2, and 11.1 (inter-assay) for TSH values of 3, 23, 45, and 82 mIU/L. Recovery tests showed a recovery of 108, 112, and 109% for the proportion of the measured (13, 36, 69 mIU/L) to the expected (12, 32, 63 mIU/L) TSH concentrations. Specificities of the method for TSH, LH, hCG, FSH, PRL, and GH were 100, <0.005, <0.005, <0.003, <0.01, and <0.02%, respectively. The differences of corresponding TSH values as measured by both kits were less than 1.5 mIU/L in 95% of comparisons. There was a significant correlation between TSH levels measured by both kits (r = 0.96, p < 0.001). Conclusion: The quality of TSH kits was considered acceptable for the detection of CH, especially in mildly abnormal cord DBS values, according to the findings of the screening program for CH and of the methodologic evaluation.

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Introduction: The recall of neonates with primary abnormal tests has almost always been considered the first step in the detection of congenital hypothyroidism (CH) in the CH screening programs. Considering recall rate as one of the indicators of cost-benefit and operational feasibility assessment of a program, forecasting of recall rate(s) could be beneficial to an optimized allocation of funds and resources. The trend of time-series of neonatal monthly recall rates was assessed in this report. Methods: From March 1998 to March 2002 (48 months), cord blood spot samples from 8 hospitals and a rural birth center in Tehran and Damavand District were collected on filter papers (Whatman BFC 180). TSH values were measured in the Endocrine Research Center laboratory using a two-site IRMA method. Primary TSH levels  20 mU/L were considered abnormal and recalled for serum confirmatory tests. Monthly recall rate (total number of primary TSH levels  20 mU/L to total live births per month  100) was recorded for 48 consecutive months. Monthly recall rates were analyzed using linear models of Box and Jenkins (ARIMA). The autoregressive model was fitted to forecast the next recall rates with a 95% confidence interval. Results: Out of 29908 cord blood spot samples, 314 showed TSH levels  20 mU/L (total recall rate of 1.05%) of whom 32 had CH (1: 935 live births). Total data showed normal distribution and were stationary. Fitting of particular type of AR(3) model showed that monthly recall rate is predictable according to the recall rate obtained three months ago. Therefore, the autoregressive model of zt = 0.67 + 0.45 zt-3 + et, with significant parameters (p  0.003), was obtained to forecast the next recall rates, ultimately. Conclusion: Forecasting of monthly recall rates is possible using the autoregressive model.

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Introduction: Following screening of newborns for congenital hypothyroidism (CH) in Tehran for 49 months and in Damavand for 21 months, a question was raised as to whether there are any differences between the recall rates and CH incidences in metropolitan and district populations. The present study was conducted to address the aforementioned issue. Material and Methods: From February 1998 to March 2002, cord blood spot samples from 8 hospitals and a rural birth center in Tehran (the capital) and Damavand (district) were collected and tested for TSH measurement using a two site IRMA method. TSH values  20 mU/L were recalled. The diagnosis of CH was confirmed using age-adjusted reference values for serum TSH and T4 levels. The frequency distribution of recalls and CH cases in Tehran and Damavand were compared using 2 and Fisher’s exact tests, respectively. Results: Of 30085 (Tehran: 28001 and Damavand: 2084) screened neonates, 319 (Tehran: 297 and Damavand: 22) had cord TSH values  20 mU/L. The recall rate was 1.06% (Tehran: 1.06% and Damavand: 1.06%). Thirtyـtwo (Tehran: 30 and Damavand: 2) neonates had CH. The CH incidence was 1 in every 940, 933, and 1042 live births in total, Tehran, and Damavand populations, respectively. A total of 5119 out of 18260 (28%) neonates had parental consanguinity. This was 4582 out of 16178 (28.3%) in Tehran and 537 out of 2082 (25.8%) in Damavand. The recall rates and CH incidences were not significantly different in Tehran and Damavand. conclusion: Preliminary findings of CH screening program showed that recall and CH occurrence do not have significantly different distributions in Tehran and Damavand and CH was prevalent in both regions. It could be concluded that CH might be prevalent in other parts of the country.

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Introduction: To assess the relationship between parental consanguinity and permanent congenital hypothyroidism (PCH). Materials And Methods: From February 1998 to August 2002, cord dried blood spot samples, viz. only live births, in eight hospitals and a rural birth center in Tehran and Damavand were collected on Whatman BFC 180 filter papers. Samples with cord TSH  20 mU/L (two-site IRMA) were recalled. Between 7-14 days of life or thereafter, congenital hypothyroidism (CH) was confirmed by serum TSH > 10 mU/L and T4 < 6.5 g/dL and L-T4 was immediately started. CH-affected newborns were followed-up until May 2003. Thyroid dysgenesis was determined using 99m technetium pertechnetate thyroid scanning and/or ultrasonography. In thyroid eutopic newborns, dyshormonogenesis was diagnosed by a 4-week discontinuation of L-T4 between 2-3 years of age followed by abnormal serum TSH and T4 values. Results: Of 35067 specimens, 373 (1.06%) were recalled, 25 had PCH (1:1403 births), 18 had thyroid dysgenesis (1:1948 births), and 7 had thyroid dyshormonogenesis (1:5010 births). Twenty-one PCH cases were detected from July 2000 onwards and 6648 (28.6%) of 23227 neonates had parental consanguinity. The odds ratio of parental consanguinity in PCH was 2.75 (95%CI: 1.17-6.47 P=0.02) and in dysgenesis was 3.74 (95%CI: 1.33-10.52 P=0.01) and the odds ratio of first-cousin parental consanguinity in PCH was 2.96 (95%CI: 1.23-7.15 P=0.02) and in dysgenesis was 3.21 (95%CI: 1.14-9.02 P=0.03) compared to non-PCH and non-dysgenetic cases, respectively. Conclusions: Parental consanguinity can be considered as the possible causative factor for the high prevalence of PCH and dysgenesis in Tehran.

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Introduction: The incidence of permanent and transient CH has not yet been determined in Iran. This report illustrates the incidence of permanent and transient CH in Tehran and Damavand. Materials and Methods: From February 1998 to August 2002, cord dried blood spot samples in Tehran and Damavand were collected and those with TSH 20 mU/L were recalled (two-site IRMA). Between 7-14 days of life or thereafter, CH was confirmed by serum TSH >10 mU/L and T4 <6.5 g/dL or TSH >30 mU/L alone and L-T4 was immediately started. CH-affected newborns were followed-up until May 2003. Dysgenesis was determined using 99mTC thyroid scanning and /or ultrasonography. In thyroid eutopic newborns, dyshormonogenesis was diagnosed by a 4-week discontinuation of L-T4 between 2-3 years of age and abnormal serum TSH and T4 values, while normal levels after discontinuation confirmed transient CH. Cases with incomplete early follow-ups without thyroid imaging, were known as unknown CH. Results: Of 35067 screened neonates 373 had cord TSH 20 mU/L and were recalled (recall rate: 1.06%). 35 had CH (incidence of 1:1002 births), 25 had permanent CH (incidence of 1:1403 births), and 6 had transient CH (incidence of 1:5845 births). The type of CH remained unknown in 4 cases. Thyroid dysgenesis and dyshormonogenesis were detected in 18 (incidence of 1:1948 births) and 7 cases (incidence of 1:5010 births), respectively. Conclusions: The high incidence of permanent CH underlines the necessity to implement a national CH screening program in Iran.

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Introduction: Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation in newborns. In this study, we investigated the incidence of CH in Rafsanjan. Materials and Methods: From all neonates born from 22 Dec 2001 to 22 Apr 2002, heel blood samples on filter paper were collected and TSH values were assayed using ELISA method and TSH  20 mIU/L was considered abnormal and recalled. Upon recall, the diagnosis of CH was confirmed according to abnormal serum TSH levels using age-adjusted reference values for thyrotropin. TSH < 3.98 mIU/L was considered normal according to the manufacturer's instructions. The association between heel-blood TSH values and of birth weight and height, sex, maternal age, gestational age, delivery mode, maternal occupational status, parental educational level, thyroid disorders in family, and iodized salt consumption were assessed. Results: Of 950 neonates (480 girls and 470 boys), 230 (24.2%) had TSH  20 mIU/L. TSH levels were between 20-49.9 and  50 mIU/L in 206 and 24 neonates, respectively. Of total recalled neonates, only 152 came for serum confirmatory tests between 1-4 months of age. Nine cases had serum TSH  3.98 mIU/L but none of them had enough elevated TSH values to confirm the diagnosis of CH. The only neonate with heel-blood TSH of 137 mIU/L was inaccessible and the CH diagnosis remained unclear. No association was found between heel-blood and serum TSH and of the variables mentioned above. Conclusion: The incidence of CH in Rafsanjan remains unclear however, the recall rate was extremely high. The latter is not only suggestive of a high prevalence of CH, but also of some etiologic factors affecting the rate of hyperthyrotropinemia in Rafsanjan.

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Introduction: The incidence of permanent and transient congenital hypothyroidism (CH) has been previously reported. This report illustrates the causes of transient CH. Material and methods: From February 1998 to August 2002, cord spot samples were collected on filter papers in Tehran and Damavand hospitals and TSH  20 mU/L (two-site IRMA) were recalled. Between 7-14 days of life or thereafter, serum values of TSH > 10 mU/L and T4 < 6.5 g/dL were considered as CH. After taking the history of maternal ingestion of thyroid affecting drugs and goitrogens during pregnancy and perinatal period, CH-affected newborns were underwent thyroid scanning (99mTC) and eutopic cases were followed up until May 2003. Discontinuation of L-T4 for four weeks and normal serum TSH and T4 values determined transient CH. Maternal and neonatal serum were assayed for thyrotropin receptor autoantibodies (TRAb) and their urine samples were assayed for iodine concentrations. Results: Of 35067 neonates, 373 were recalled (1.06%), 35 had CH (1:1002 births), and 6 had transient CH (1:5845 births). Median urinary iodine concentration in CH neonates (n=26) and their mothers (n=25) was 363 (range 70-500) and 200 (72-410) g/L, respectively. The history of maternal ingestion of thyroid affecting drugs was negative and of goitrogens was minimal. Serum TRAb levels were normal. All mothers were exposed to iodinated disinfectants during perinatal period. Iodine excess (410-500 g/L) was detected in three cases with transient CH. Conclusion: Undue usage of iodinated disinfectants during perinatal period can result in transient CH in the offspring and should be prevented.

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Introduction: The incidence of permanent and transient congenital hypothyroidism (CH) has been previously reported. This report illustrates the causes of transient CH. Material and methods: From February 1998 to August 2002, cord spot samples were collected on filter papers in Tehran and Damavand hospitals and TSH  20 mU/L (two-site IRMA) were recalled. Between 7-14 days of life or thereafter, serum values of TSH > 10 mU/L and T4 < 6.5 g/dL were considered as CH. After taking the history of maternal ingestion of thyroid affecting drugs and goitrogens during pregnancy and perinatal period, CH-affected newborns were underwent thyroid scanning (99mTC) and eutopic cases were followed up until May 2003. Discontinuation of L-T4 for four weeks and normal serum TSH and T4 values determined transient CH. Maternal and neonatal serum were assayed for thyrotropin receptor autoantibodies (TRAb) and their urine samples were assayed for iodine concentrations. Results: Of 35067 neonates, 373 were recalled (1.06%), 35 had CH (1:1002 births), and 6 had transient CH (1:5845 births). Median urinary iodine concentration in CH neonates (n=26) and their mothers (n=25) was 363 (range 70-500) and 200 (72-410) g/L, respectively. The history of maternal ingestion of thyroid affecting drugs was negative and of goitrogens was minimal. Serum TRAb levels were normal. All mothers were exposed to iodinated disinfectants during perinatal period. Iodine excess (410-500 g/L) was detected in three cases with transient CH. Conclusion: Undue usage of iodinated disinfectants during perinatal period can result in transient CH in the offspring and should be prevented.

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Introduction: Significant changes in thyroid hormones occur during the first weeks after birth. We assessed the degree of changes in thyroid-stimulating hormone (TSH) and total thyroxin (T4) concentrations in neonates screened seven days after the first high serum TSH levels, just before starting treatment. Materials and Methods: This prospective study was carried out on newborns referred for their high TSH concentrations on heel blood spot in hypothyroidism screening tests (5-20 miu/ml), between December 2009 and December 2010. First, serum TSH and T4 were assessed by radioimmunoassay. One week later, in neonates with the first serum TSH≥10, serum TSH and T4 were rechecked before starting treatment. Any definite decision to continue treatment was based on the second test results. Results: The results showed a significant decrease in serum TSH level after one week (p<0.01). Serum T4 level increased significantly in neonates with the first serum TSH≥40 (p<0.05), while no significant difference was observed in other infants with the first serum TSH<40. Incidence rate of Congenital Hypothyroidism (CH) reduced from 1/329 to 1/851, during the study. Conclusions: It may be appropriate to repeat serum T4 and TSH concentrations after 2 and 4 weeks in neonates with normal serum T4 but elevated TSH. In the case of persistent TSH elevation, the infant should be treated as this can prevent unnecessary treatments, family stress and iatrogenic hyperthyroidism in these patients.

 

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Introduction: Recent studies show that exposure to heavy metals can affect thyroid function. This study aimed to assess heavy metals in breast milk during the first few days postpartum and their relationships with hyperthyrotropinemia in neonates. Materials and Methods: In this case-control study, 82 mother-infant pairs, consisting of 21 pairs (neonates with hyperthyrotropinemia) in the case group and 61 pairs (healthy neonates) in the control group, were assessed at 3-5 days postpartum. Thyrotropin concentrations >5 mIU/L in the heel blood sample were considered as hyperthyrotropinemia. In the case group, thyrotropin concentration was also measured in the venous blood sample for confirmation. At the same time, to assess mercury (Hg), lead (Pb), and cadmium (Cd) concentrations, a breast milk sample was collected from each mother. Results: The median (interquartile range, IQR) thyrotropin concentrations in the heel blood sample of healthy neonates and neonates with hyperthyrotropinemia were 0.90 (0.40-1.85) and 6.80 (5.70-8.80) mIU/L, respectively (P<0.001). This value was 5.50 (5.00-6.75) mIU/L in the venous sample of neonates with hyperthyrotropinemia. None of the heavy metals in breast milk showed a significant correlation with thyrotropin concentration in the heel blood sample. However, there was a significant correlation between the concentration of Pb in breast milk and thyrotropin level in the venous blood sample (r=0.478, P=0.029). No correlations were observed between breast milk Hg and Cd concentrations and venous thyrotropin level. Conclusion: The present findings indicate that the concentration of Pb in breast milk correlates with neonates' thyroid function. However, further studies with larger sample sizes are needed to confirm our results.