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Time Trend and Geographic Distribution of Treated Patients with

Congenital Hypothyroidism Relative to the Number of Available
Endocrinologists in Japan
Yan-Hong Gu, MD, PhD, Tadaaki Kato, MD, PhD, Shohei Harada, MD, PhD, Hiroaki Inomata, MD, and Kikumaro Aoki, MD
Objective To investigate the time trend and geographic distribution of treated patients with congenital hypothyroidism (CH) and explore their possible relationship to the availability of endocrinologists in Japan.

Study design The 2-source capture-recapture method was used to estimate the total number of patients. The
ratio of the total estimated number of patients with CH to the number of endocrinologists and Spearman correlation
coefficients were calculated. Curve fitting for changes in incidence or prevalence was estimated.
Results The incidence and prevalence of CH exhibited upward trends, with linear slopes of increase during the
period 1994-2002. A statistically significant positive correlation was observed between the prevalence of CH and
the ratio of the number of patients with CH to the number of endocrinologists in the 10 regions studied. The prevalence of CH was significantly higher in the regions with a higher ratio of patients with CH to endocrinologists, and
also in younger patients.
Conclusions A shortage of endocrinologists may be one reason for the upward trend in the incidence and prevalence of treated patients with CH. (J Pediatr 2010;157:153-7).

A

nationwide neonatal screening program for congenital hypothyroidism (CH) was implemented in Japan in 1979. Since
1984, nearly 100% of all neonates in Japan have been screened.1 In 1989, a highly sensitive method for detecting CH was
introduced, and by 1992, enzyme-linked immunosorbent assay had completely replaced older methods such as radioimmunoassay and enzyme immunoassay. Nationwide follow-up surveys to evaluate the status of neonatal screening were conducted every year during the periods 1979-1987 and 1994-2003.1,2 The 1994-2003 follow-up survey was conducted by the Aiiku
Maternal and Child Health Center, Tokyo (Aiiku), and had a response rate of 54.2%-91.5%.1,2
In Japan, treatment of patients with CH is supported by 3 categories of medical subsidies provided by the national and/or
local government: medical expenses for infants, the Medical Aid Program for Chronic Pediatric Diseases of Specified Categories
(MAPChD), and Medical Aid for Immature and Premature infants.3 Only 1 of these 3 subsidies may be used. MAPChD was
implemented in 1968. The number of diseases eligible under this program has expanded annually, and currently stands at 514. A
national registry of MAPChD beneficiaries was started in 1998. In 2005, the MAPChD was legalized and was included under the
Child Welfare Law in Japan.3 Beneficiaries of the MAPChD should be registered every year, and beneficiaries who sign a document of informed consent may be enrolled as subjects for MAPChD study projects. The registered data used for the study
projects do not include any personal data, such as names, home addresses or phone numbers. Thus, the list of patients with
CH is incomplete in both the follow-up survey at the Aiiku center and the registered data in the MAPChD.
The 2-source capture-recapture method (CRM) is widely used to estimate the total number of patients with CH. With CRM,
an estimated whole number of patients can be calculated using information from overlapping lists of patients from 2 distinct,
independent, incomplete sources. This statistical method, originally developed to estimate the size of a closed animal population, is used increasingly in epidemiologic studies to assess the completeness of cancer registries, to evaluate the incidence of
many diseases and health problems (including diabetes), and in governmental disease surveillance.4-9
Obtaining an accurate estimate of the number of treated patients with CH in
Japan is important. The present study was performed to estimate the total number of patients treated for CH and further explore the time trend and geographic
From the Department of Health Policy, National
distribution of CH by CRM, using lists from the Aiiku follow-up survey and the
Research Institute for Child Health and Development,
Tokyo, Japan (Y.-H.G., T.K., S.H.); Inomata Children’s
registered data in the MAPChD.
Clinic, Chiba, Japan (H.I.); and Department of Research
and Development, Aiiku Maternal and Child Health
Center, Tokyo, Japan (K.A.)

Aiiku
CH
CI
CRM
MAPChD

Aiiku Maternal and Child Health Center, Tokyo
Congenital hypothyroidism
Confidence interval
Capture-recapture method
Medical Aid Program for Chronic Pediatric Diseases of Specified Categories

Supported by a Health Labor Sciences Research Grant
(Research on Child and Families) from the Japanese
Ministry of Health, Labor and Welfare (‘‘A Study of Information Offer, Assessment, Management, and Registration on Medical Aid Program for Chronic Pediatric
Diseases of Specified Categories After Legislation’’ and
‘‘A Study on the Construction of Comprehensive Database About Chronic Diseases in Children’’). The authors
declare no conflict of interest.
0022-3476/$ - see front matter. Copyright Ó 2010 Mosby Inc.
All rights reserved. 10.1016/j.jpeds.2009.12.051

153

the annual incidence from April 1994 to March 2003.6 41. age as of October 2002.4) 6. either detected by neonatal screening or diagnosed later after false-negative results on neonatal screening. N/P Age.8 (4. 95% CI of estimated total number of patients = N  1.8 (8.9 40.2) 5.5 43. The formulas are as follows: Total number = (eligible number of patients in source 1 [N1])  (eligible number of patients in source 2 [N2])/ number of patients in sources 1 and 2 [N12]).6% 357. Ltd. 32.9 (8.4-7. Stratified analysis was performed by birth year.9 40. The number of patients missed by both sources was estimated based on the assumption of an equal probability of ascertainment from both sources. 21. sex.6 41. 17. 24.1% 373.6% 1579.0-9.9% 179 203 150 211 193 195 171 124 153 1579 179. Data Matching In accordance with the Japan Personal Information Protection Act.1) 9. %) (April.9% 348. prefecture of birth.1% 171. 42.10 personal information about patients.4 (7.1 36.5) 6.2-8.1 (8.9 1 233 072 1 187 067 1 206 551 1 194 510 1 199 183 1 184 302 1 190 547 1 170 662 1 153 855 10 719 749 4. 30.4 (5.com 250 250 255 297 375 363 395 461 377 3023 Total number Birth year Total (April-March) number  1994 1995 1996 1997 1998 1999 2000 2001 2002 Total Population (P) (JanuaryDecember) Prevalence of CH in each age group per 10 000 children. such as names.2% 193.6 44. independent sources.0% 237. 20.4-9. rate of registration with the MAPChD.3) 8. comparable Patients with patients with of patients with CH CH from both CH calculated by with the MAPChD Live births per 10 000 live rate in CRM (N1/N.4% 124.8-5.2) 6. They were first identified as having CH by neonatal screening and then referred for further examination to a hospital or clinic in any of the various study regions.154 230.N12)  N1  N2} / {N12  N12  N12}. (Tokyo.9-8. location of hospital or clinic.7-5.1 (8.96 {Ovar (N)}.5-5.4-7.jpeds. date of diagnosis. 157. 34.3% 195.6) 8.4-5. and prefecture of current residence.7 (7.4% 150. and the prevalence of CH by age group as of October 1. except the Hokkaido region1. 38.6) 8. excluding the Hokkaido region (Tables I-III). This database comprised 1579 patients with primary CH born between April 1994 and March 2003 who were started on treatment with L-thyroxine.2 (4.1 (4.5-5.March) births (95% CI) (N12/N2  100%) sources (N12) CRM. 37.8% 2847.0-5. Estimated total number of patients with CH.9) 9.2) 5.8 (4. 1 Methods Data Sources Data source 1 included data from the electronic registry of MAPChD beneficiaries born between April 1994 and March 2003.6-9. Other Statistical Analyses The number of nationwide live births and the mortality of children were obtained from Japan’s Ministry of Health. 39.3) 5.7 (7. and location of hospital or clinic. Data source 2 was lists from the Aiiku nationwide followup survey for the neonatal screening.7 45.8) 7. and an equal probability of individual cases being captured within any source.7% 211.6% 354. 25.5) 4.2) 6. Two-Source CRM Analysis A 2-source CRM model (Lincoln method) was used to estimate the total number and 95% confidence interval (CI) of patients with primary and central CH. and Welfare.8. was not available from the MAPChD electronic registry. 43. 41.6) 4. N (95% CI) Eligible number (N1).9 (4. 38.4 (5.9) 1 209 000 1 205 000 1 186 000 1 192 000 1 198 000 1 170 000 1 168 000 1 171 000 1 168 000 10 667 000 4. var (N) = {(N1 .5 (8.4) 8.9) 8 7 6 5 4 3 2 1 0 www.3) 5.2-8.8 (6.N12)  (N2 .3-9.6-6.5% 203. 38.5% 69 78 61 89 74 84 64 51 53 623 597 (504-689) 617 (529-705) 583 (486-680) 647 (563-731) 923 (776-1070) 808 (694-921) 997 (821-1172) 1065 (854-1276) 1031 (824-1238) 7216 (6826-7605) 41. A matching software for 2-source CRM developed by our department and Mitsubishi Electric Business Systems Co.2 (Tables I and II). Japan) was used.9 39.9% 237.8 (6. Labor. No.9 There are 3 fundamental assumptions in 2-source CRM: a closed population.11 The nationwide number of children under age 9 years in each prefecture as of October 2002 was obtained from the Ministry of Internal Affairs and Gu et al .0-5. 14. This database comprised patients with both primary and central CH.. 40.1% 153. 32.8) 7. The number of patients captured by both sources was determined by data matching. (95% CI) years Estimated total number of Registration rate Incidence of CH Eligible number in infants (N2). 11.8 (6.2% 438. comparable rate in CRM (N12/N1  100%) By age group as of October 1. The identifying variables were date of birth.6-6. 2002 CH registered with the MAPChD (source 1) CH patients in Aiiku (source 2) Table I.5-5.9 (4. 2002 THE JOURNAL OF PEDIATRICS Vol.9 (6.7% 273.5-9.

%) 900 000 3 740 000 215 000 72 545 25 Ratio of patients with CH to endocrinologists Number of endocrinologists (pediatrics and internal medicine) as on February 28.3 45.939. 25. Table II shows the estimated total number of patients with CH.3 (5.6% 94.11 (2) the mortality rate of infants with CH was very low (1.1) 6.0 7. The probabilities of ascertainment of a case shown in Table I were 52. 19.4-10.6) 119 (106-133) 5848 (5452-6012) 40 671 Comparable Data and Probability of Ascertainment of a Case From Source 1 and Source 2 The comparable rates were 21.0-5.2% 237. Spearman correlation coefficients (2-tailed) were calculated to determine the association between the ratio of the number of patients with CH to the number of endocrinologists and the prevalence of CH in each region. 41.865.34%) during the period 1985-1987.4% 1044 (893-1195) 490 (391-589) 89 42 392.6 per 1000 live births.877. alternatively.3) 5.2% 110.2 7.2 45.8% 508. The prevalence of CH was calculated assuming that all of the neonates with CH were alive throughout the study period.001) during the study period was linear.5 44. 90.7% 158 (129-187) 440 (362-518) 33 50 62.9 (5.1) 37.0) Registration rate of patients with CH with the MAPChD (N’1/N’.5% 324 (232-415) 1188 (1061-1315) 25 137 87. the annual incidence (and 95% CI) for 1994-2002. 35. The comparable rates were 27.6% 67.7% from both sources {(N1 + N2 .6 5. Table III shows an upward trend of the Time Trend and Geographic Distribution of Treated Patients with Congenital Hypothyroidism Relative to the Number of Available Endocrinologists in Japan 155 .0% 102 140 13 202.8-8.7) 10. 39.9 2. 26.9%) from source 1 (N12/N1) and 39.1 8. in 2006).9%-75.5% from source 1 (N1/N).3 (4. 40.8-9. Moreover. 2002.6 6.5%) from source 2 (Table II). and 21. endocrinologists usually care for both pediatric and adult patients in clinics.1%) from source 2 (N12/N2) (Table I).6%-43.3 and 2.4 per 10 000) during the period 1994-2002.7 1 981 000 661 000 325 63 3. and 27.5% (range. 27. 42.1-3.2%-44.9 (3. respectively. A regional variation in the prevalence of CH is significant (P <.14 and (3) the mortality rate of children under age 19 years also was very low (3. P <. Illinois). The probabilities of ascertainment of a case shown in Table II were 57.5% 84.. 28.2) 3.4% 93.9% from source 2 (N2/N). 2007 Prevalence of patients with CH in each region.4% The number of patients with CH in both sources (N’12) Location of hospital or clinic that the CH patients visited Regions of Japan Japan is divided into 47 prefectures (‘‘todofuken’’) or.13 In Japan. adjusted R2 = 0. N’1). N’2). 53.9% 302. 50.3-4. and the ratio of the number of patients with CH to the number of endocrinologists in the 10 regions studied. 27.4 370 000 1 190 000 62 147 3.05).0 495 (443-547) 1441 (1277-1604) 149 (95-204) 5.5 296 000 1 271 000 48 172 6.936.7-8. 45.ORIGINAL ARTICLES 14.8 5. especially in rural areas. 19. because (1) the mortality rate of neonates less than 28 days old.N12)/N}. comparable rate (N’12/N’1  100%) Table II.2% from both sources. The slope of the increase in incidence (R = 0. the prevalence (with 95% CI) of patients with CH. and the prevalence of CH by age group as of October 1. rate of registration with the MAPChD.6) 7.6%-32. into 11 regions.8) 53.0 (9. An upward trend of incidence and a higher prevalence of younger patients with CH are evident.5% 1579.4 (5.5 (3. 44.5% 397. per 10 000 children (N’/P’) (95% CI) Population of children under 9 years of age in each region as on October 1. 37.3% 29. *No data available.5% (range. Chicago. 11. 44. P <.4% 2436.5% (range. 45.0 50.6) 3.7% from source 1.9 45.3-5. Results Eligible number of patients with CH in Aiiku (source 2. 26.3% 200. N’ (95% CI) Communications.2 8. 44. 34. 75. 25. 39. Estimated total number of patients with CH.0 (SSPS Inc. 2002 (P’) Estimated total number of patients with CH calculated by CRM. is extremely low in Japan (1.6) 26. as well as that of infants under 1 year old.5% 53.4%) from source 1 and 42. prevalence of CH and the ratio of the number of patients with CH to the number of endocrinologists in each region of Japan July 2010 Time Trend and Geographic Distribution of CH Table I shows the estimated total number of patients with CH.7 170 000 10 794 000 8 1467 5.8% Tohoku region Kanto region Shin’etsu region (not including Niigata Prefecture*) Hokuriku region Tokai region (not including Gifu Prefecture*) Kinki region Chugoku region (not including Tottori Prefecture*) Shikoku Kyushu (not including Saga Prefecture*) Okinawa Total 250.9% (range.0% from source 2.5-6.5 35.7% 219.3 2.9 4.4 (6.5 (4. 19.8 (7.0 (5.6-5. 75. 22.8-8.7% 539.12 The number of society-certified endocrinologists in each region as of February 2008 was obtained from the Japan Endocrine Society.11 Curve fitting for the changes of the incidence or prevalence was estimated using SSPS version 15. comparable rate (N’12/N’ 2  100%) Eligible number of patients with CH with the MAPChD (source 1.7-4. adjusted R2 = 0.001) and prevalence (R = 0.6 41.

3) 4.0. The MAPChD beneficiaries were registered every year.0 (Table II). Time Trend and Geographic Distribution of CH Cases Relative to the Number of Endocrinologists A highly statistically significant positive correlation was observed between the patient with CH-to-endocrinologist ratio and the prevalence of CH in each region (Table II). A guideline for neonatal CH screening in Japan has recommended examinations for differential disease-type diagnoses.1 nonetheless. considering the timing of the clinical classification of the diagnosis. 2002 (birth year) Group 1: Kanto. into 2 groups: a group in which the ratio was <4. No. nearly 100% of Japanese neonates are screened.3-10.6 (12.6 (7.9% to 75.8. prevalence of CH in both groups 1 and 2 (P <. Shikoku.0 (3. neonatal screening for CH was instituted in 1979.0 and a group in which the ratio was >4. and Welfare data for 1994-2002. and 4.com Vol. 4.05).3. Hokuriku. Ratio of the Number of Patients with CH to the Number of Endocrinologists in Each Region Table II shows the ratio of the number of patients with CH to the number of endocrinologists in each region.4) 9.4-9 According to Ministry of Health. Obvious differences in the ratio among the regions can be seen. with regional variation between the 2 groups (P <.0. the total number of patients treated for CH in Japan remains unclear. 3. and the corresponding P value for the correlation was . after age 3 years in children with CH. especially the incidence data shown in Table I. Prevalence of patients with CH in regions where the ratio of patients with CH to endocrinologists was above or below the nationwide level (4. 1 Table III. 3.5-10. The prevalence of CH calculated by age showed a higher prevalence of CH in younger patients (Tables I and III).7-4. low-cost tool for accurately estimating the number of patients with CH. the probability of ascertainment of a case from both sources and from source 1 was approximately $40%. Because of the small number of patients with CH in some regions within a single year. 4. according to Tables I and II.0) 7-8 (April 1994 to March 1996) 5-6 (April 1996 to March 1998) 3-4 (April 1998 to March 2000) 1-2 (April 2000 to March 2002) Total *CH patient-to-endocrinologist ratio below the nationwide value of 4. ranging from 26. 4.9) 4. however.1-4. we investigated these 2 groups in 2-year time frames (Table III).05). This positive rate of CH demonstrates the validity of our results. Thus.jpeds. 3.8. the fiscal year positive rates of CH (number of suspected cases/total number of tested neonates  100%.1-4. With regard to the annual incidence of CH. At present.6 (9. †CH patient-to-endocrinologist ratio above the nationwide value of 4. as pointed out by Brenner.9) 7. requiring a high level of Gu et al . allowing for an accurate estimate of the current number of beneficiaries. Thus.7-14. including primary CH and a small percentage of central CH) were 3. and Saga Prefectures)† 3.5 (4.3) 10.6% (Table II). Discussion The MAPChD database includes treated patients with both primary and central CH. Labor. and the incidence and prevalence of CH could be estimated.5) 7.5.81.THE JOURNAL OF PEDIATRICS  www. the total number of treated patients with CH nationwide during the study period could be calculated. Consequently. resulting in a higher incidence in recent birth years or a higher prevalence in younger patients with treated CH in Japan.3 (6. and the data in the Aiiku survey comprise treated patients with primary CH only. patients with treated infantile transient hyperthyrotropinemia also may be counted. Thus. and Okinawa regions (not including Niigata.3. 156 Moreover. suggesting that our results are credible. Notifications in both sources may originate from the same doctor. Tokai.9) 13. Chougoku. excluding the Hokkaido region.0.0.7-7.3 (3.9 this underestimation is much less severe than that associated with the traditional registration method. and Kinki regions (not including Gifu Prefecture)* Group 2: Tohoku.004.8 per 10 000. There was a significant difference in the prevalence of CH between the 2 groups during the study period (P <.0-3. The nationwide patient with CH-to-endocrinologist ratio was 4.3. The rate of registration with the MAPChD for each year from 1994 to 2002 ranged from 36.6) 4. 157. respectively. Thus. such as scintigraphy and radioactive iodine uptake test. The Spearman correlation coefficient was 0. Shin’etsu. Thus.15 such examinations are usually performed at age 5-6 years in Japan.9% (Table I). correctly diagnosing CH is not an easy task in infants. we divided the 10 regions of Japan. In Japan. Kyushu.001). we also used the estimated number of patients with CH to calculate the prevalence of CH in each age group for the year 2002 (Table I).0) Prevalence of patients with CH (95% CI)  10 000 Age group as of October 1. These 2 conditions could result in underestimation. Using 2-source CRM.5 (5.1-5. 2-source CRM is an effective.3 (4.6.6% to 45.0-8. Tottori.2 (9. the comparable rate from source 1 (MAPChD) was lower than that from source 2 (Aiiku). 4. despite the lower patient with CH-to-endocrinologist ratio (Table III).8) 5. an upward trend in incidence was obvious (Tables I and III). The rate of MAPChD registration varied among regions.

Kozinetz CA. Kato T. Moreover. 14. Working Group on Congenital Hypothyroidism of the Japanese Society for Pediatric Endocrinology and the Japanese Society for Mass Screening.go. http//www. consultation. Inomata H. Seasonality in the incidence of congenital hypothyroidism in Japan: gender-specific patterns and correlation with temperature.stat. Available from: http://www.jp/endocrine/senmon_i/ index. Anderson K.go. 2. Medical aid program for chronic pediatric diseases of specified categories in Japan: current status and future prospects. Available from: http://www. List of endocrinologists of the Japan Endocrine Society.91:445-50. Using the two-source capture-recapture method to estimate the incidence of acute flaccid paralysis in Victoria. treatment. especially in rural areas. Kelly H. In: Amstrup SC. Kakee N. 9. 2009. Nakajima H. Diabetes Care 1997. Handbook of Capture-Recapture Analysis. patients with CH preferred to register with the MAPChD than with other medical aid support systems (Table II).jp/data/ kokusei/2005/index. Thyroid 2007. Labor. MacNaughton N. 2009.do. Vital Statistics of Japan. and Welfare. Nationwide follow-up results of neonatal mass screening for congenital hypothyroidism in 1994-1999. 5. 16. Japan. n Submitted for publication May 25. 2009. Skender ML. Percy AK. 6. environmental conditions.13:27-32. Pediatrics 1993. 2009. that disease diagnosis. Epidemiology of Rett syndrome: a population-based registry. 1985-1993. Epidemiology 1995. Sato H. The 7th and 8th national studies of patients with congenital hypothyroidism and its related diseases found on neonatal screening.17 Such a situation demands urgent attention. Aoki K. Huggins R. One solution might be to train young doctors for the profession.jp/jp/it/privacy/houseika/hourituan/. Thus. kantei. Blanchard JF. 2009.July 2010 professional skill. Classical closed-population capture-recapture models.go.jp/shingi/2005/03/s0311-5a4. The prevalence of CH was significantly higher in the group with a higher patient with CH-toendocrinologist ratio in each region.2 suggesting that environmental factors also may be responsible for this upward trend in the incidence of CH. 17. Harris KB. J Jpn Pediatr Soc 1989. Sato Y. Pass KA. et al. Depew N. NJ: Princeton University Press. Gu YH.93:1152-8. Although neonatal screening for CH in Japan has been performed for 30 years and is well supported by medical aid systems. The variable rate of registration with the MAPChD in each region suggests variation in the medical aid support provided by local governments. Time Trend and Geographic Distribution of Treated Patients with Congenital Hypothyroidism Relative to the Number of Available Endocrinologists in Japan 157 . Almes MJ. Accessed February 3. including a shortage of specialists in endocrinology for the treatment and follow-up of patients with CH. The shortage of pediatricians and overworking of pediatricians in Japan are reaching crisis levels.jp/SG1/estat/GL02010101. suggesting that the uneven nationwide geographic distribution of endocrinologists may be one reason for the regional variations in the distribution of patients with CH (Table II). editors. 3. for example. Pediatr Int 2008. 10. Ozawa H. Guideline for neonatal mass screening for congenital hypothyroidism. Chao A. suggesting that higher prevalence of CH in regions with fewer endocrinologists may reflect a higher rate of incorrect diagnosis (Table III).jp.ac. Bull World Health Organ 2002. Canada. Unfortunately. Some of the nonspecialists may have. The pediatrician-to-patient ratio in Japan is reportedly about half that in the United States.6: 42-8.80:846-51. Available from: http://www.umin. Aoki K. 4. last revision received Nov 23. National Research Institute for Child Health and Development. Okinawa). Tokyo.17:869-74. Department of Health Policy. 2009. Japan Endocrine Society. Kato T. 8. especially younger patients.20:512-5. The use of 2-source CRM also helped clarify the rate of MAPChD registration by birth year or region.50:376-87. e-Stat Portal Site of Official Statistics of Japan. 2009. an increased number of pediatricians and other specialists is needed in some regions of Japan. Manly BFJ. Schultz RJ.go.e-stat. Reprint requests: Yan-Hong Gu.22:84-7. Inomata H. 157-8535. Ministry of Health. Japan Personal Information Protection Act. only 81. Gu YH. 15.go.1 The prevalence of CH varied among the 10 regions of Japan and showed a positive correlation with the patient with CH-to-endocrinologist ratio in the regions. there are some serious pediatric medical care problems in Japan. accepted the positive screening test as a definitive diagnostic study instead of viewing the screening result as an indication for a repeat assessment of thyroid function. we found that an upward trend in the incidence of CH was significantly associated with environmental temperature. 2005 Population Survey. Accessed February 3. Jpn J Inhert Metab Dis 2006. Dean H. Australia. 22-35.16 In our previous survey based on a list of positive cases of CH from Japanese screening centers. A previous study from the United States found similar results. It is clear that prenatal exposure to high levels of iodine or other substrates can lead to persistent or transient CH in neonates. 2-10-1 Okura.8:51-5. Re-estimation of incidence of Menke’s disease in Japan using the two-source capture-recapture method. 2005. Ministry of Internal Affairs and Communications of Japan. J Jpn Soc Mass Screen 2003. Accessed February 3. Wajda A. Available from: http://square. Setagayaku. mhlw. Whitfield K. McDonald TL.html. Saito T. accepted Dec 29.91:268-77. References 1. A comparison of the numbers of medical doctor between Japan and USA. This study ORIGINAL ARTICLES provides evidence supporting the need for improvement of local medical care. Kato T.html. 2009. Incidence and prevalence of diabetes in children aged 0-14 years in Manitoba. Clin Pediatr Endocrinol 1999. p.7% of CH cases detected by neonatal screening were diagnosed as CH by clinical examination in a clinic or a hospital. Brenner H. 13. and management of patients with CH. In some regions (eg. Ludwig S. Harada S. Increase in congenital hypothyroidism in New York State and in the United States. Princeton. E-mail: gyh@nch. 12. Accessed February 3. no maternal data are available to allow evaluation of this possibility in the present study. Gu YH. Harada S. Basically.html. Kodama H. Harada S. Mol Genet Metab 2007. Japan. in a previous study. 7. Use and limitations of the capture-recapture method in disease monitoring with two dependent sources. Accessed February 3. and prenatal exposure might contribute to the estimated incidence of CH. the endocrinologists may play an important role in the diagnosis. 11.