Newborn Thyroid Screening: Influence of Pre-Analytic Variables on Dried Blood Spot Thyrotropin Measurement.

BACKGROUND: Measuring thyrotropin (TSH) eluted from a dried blood spot (DBS) is used to screen an estimated 30 million newborns annually for congenital hypothyroidism (CH). Newborn thyroid screening has eliminated cretinism from the industrialized world and decreased the adverse effects of unrecognized CH on neurocognitive development. Hematocrit, a pre-analytic variable that affects the measurement of TSH from a DBS, contributes to the imprecision of DBS TSH measurement and could account for false-negative and false-positive DBS newborn screening test results. To assess whether variations in hematocrit found in newborns have a clinical effect in DBS-based newborn thyroid screening, the effects of hematocrit variability on the measurement of DBS TSH were studied. METHODS: U.S. Centers for Disease Control and Prevention procedures for manufacturing DBS performance testing standards were used to generate DBSs from blood samples, with hematocrits of 35%, 40%, 45%, 50%, 55%, 60%, and 65% and serum TSH concentrations of 6.3 ± 0.4 and 26.6 ± 8.0 mIU/L. TSH was measured in the eluates of four replicate DBS 3 mm punches at each hematocrit using the Thailand Ministry of Public Health Newborn Screening Operation Center enzyme-linked immunosorbent assay. Data were analyzed using a linear mixed-effects model. RESULTS: Based on the mixed-effects model, hematocrit significantly affected DBS TSH measurement (p < 0.001). A 1% increase in hematocrit resulted in a 0.06 mIU/L decrease in eluate TSH when TSH was 6.3 + 0.4 mIU/L, and a 0.21 mIU/L decrease in eluate TSH when TSH was 26.6 + 8.0 mIU/L. CONCLUSIONS: DBS TSH is significantly affected by the blood sample hematocrit. The pre-analytic variability due to hematocrit is independent of TSH assay sensitivity, specificity, precision, repeatability, and reference intervals. The effect of hematocrit on DBS TSH measurement is clinically relevant, could account for geographic and ethnic variation in the incidence of CH, and may result in both false-positive and false-negative CH screening results. Individual newborn and population-specific hematocrit correction factors may improve the precision of DBS TSH measurement.

Consuming iodine enriched eggs to solve the iodine deficiency endemic for remote areas in Thailand.

BACKGROUND: Evidence showed that the occurrence of iodine deficiency endemic areas has been found in every provinces of Thailand. Thus, a new pilot programme for elimination of iodine deficiency endemic areas at the community level was designed in 2008 by integrating the concept of Sufficient Economic life style with the iodine biofortification of nutrients for community consumption. METHODS: A model of community hen egg farm was selected at an iodine deficiency endemic area in North Eastern part of Thailand. The process for the preparation of high content iodine enriched hen food was demonstrated to the farm owner with technical transfer in order to ensure the sustainability in the long term for the community. The iodine content of the produced iodine enriched hen eggs were determined and the iodine status of volunteers who consumed the iodine enriched hen eggs were monitored by using urine iodine excretion before and after the implement of iodine enrichment in the model farm. RESULTS: The content of iodine in eggs from the model farm were 93.57 µg per egg for the weight of 55 - 60 g egg and 97.76 µg for the weight of 60 - 65 g egg. The biological active iodo-organic compounds in eggs were tested by determination of the base-line urine iodine of the volunteer villagers before and after consuming a hard boiled iodine enriched egg per volunteer at breakfast for five days continuous period in 59 volunteers of Ban Kew village, and 65 volunteers of Ban Nong Nok Kean village. The median base-line urine iodine level of the volunteers in these two villages before consuming eggs were 7.00 and 7.04 µg/dL respectively. After consuming iodine enriched eggs, the median urine iodine were raised to the optimal level at 20.76 µg/dL for Ban Kew and 13.95 µg/dL for Ban Nong Nok Kean. CONCLUSIONS: The strategic programme for iodine enrichment in the food chain with biological iodo-organic compound from animal origins can be an alternative method to fortify iodine in the diet for Iodine Deficiency Endemic Areas at the community level in Thailand.

Application of geographic information system in TSH neonatal screening for monitoring of iodine deficiency areas in Thailand.

By applying the WHO/UNICEF/ICCIDD guidelines for the Assessment of Iodine Deficiency Monitoring using Thyroid Stimulating Hormone (TSH) with the use of a Geographic Information System technique, the degree of severity of iodine deficiency for various areas can be evaluated. In this study, TSH data for neonates born in all 76 provinces of Thailand during 2003-2006 were classified according to their spatial demographic information. The results show that all provinces in Thailand suffer from iodine deficiency at mild to moderate levels, and the degree of severity increases year by year. The number of provinces with iodine deficiency were 10, 12, 35 and 36 for the years 2003, 2004, 2005 and 2006, respectively. This trend shows that each province in Thailand is at risk for iodine deficiency. Public health decision makers need to be aware of this problem anddevelop a program to eliminate iodine deficiency.

Maple syrup urine disease in Thai infants.

Maple syrup urine disease (MSUD) is a rare inborn error of metabolism, caused by a deficiency in activity of the branched chain alpha-keto acid dehydrogenase impairing the degradation of the branched-chain amino acids (leucine, isoleucine and valine). Classic MSUD usually manifests in the neonatal period with poor feeding, vomiting, lethargy, muscular hypertonicity, seizure, coma and death. Thirteen cases of classic MSUD were diagnosed from 1997-2007 at the Queen Sirikit National Institute of Child Health. All cases presented in the neonatal period. The onset of symptoms ranged from 3 to 20 days (median 8 days). The time taken to make the diagnosis ranged from 18 to 356 days (median 55 days). The diagnosis was accomplished by clinical diagnosis and confirmed by detecting abnormal levels of amino acids in the blood and organic acids in the urine. Clinical manifestations were non-specific such as poor suck, weak cry, drowsiness and seizures. Majority of cases were initially diagnosed as sepsis and/or meningitis. All patients had neurological sequelae and psychomotor retardation. This results show the need for increase awareness of metabolic disorder such as MSUD and the requirement for early detection and treatment to ensure a better outcome.

Neonatal screening program in Thailand.

The Neonatal Screening Program for congenital hypothyroidism (CHT) and phenylketonuria (PKU) commenced in 1996 with the objective of bringing better quality of life to people throughout the country, especially in the remote areas. This involved the implementation of routine services to the public health infrastructure all over the country. The plan of action has been designed so that by the year 2000 all public health service units throughout the country may provide screening services which can cover 1.2 million babies/ annum. Implementation of the screening program has been performed through public health sectors all over the country. These involved: education of the health personnel and communities, implementation of routine specimens collection and delivery systems to the central laboratories, establishment of central laboratory screening services, routine follow up and case management. Local in-house reagents using ELISA and IRMA techniques have been developed and utilized as screening and confirmation tests for CHT. In addition, Guthrie's test has been used for PKU screening and the automated Fluorometry has been selected for PKU confirmation. All 724 community hospitals have provided newborn screening services as one of the basic requirements for newborns according to public health policy. Of 1,425,025 babies screened, 3,450 (0.24%) were above the first screening cut off for CHT (TSH > 25 mU/l) and 321 (0.02%) for PKU (PKU > 4mg/dl). With a 63.10% follow up rate, the incidences were 1:3,314 for CHT and 1:237,504 for PKU. Newborn screening has been implemented as routine practice for all public health sectors of the country for CHT and PKU. It is expected that by the year 2003, all Thai newborns will be provided with screening services resulting in a better quality of life for the next generation.

Congenital adrenal hyperplasia: should nationwide screening be implemented in Thailand?

A project to establish the Thailand National Neonatal Screening Program was started in 1996 with the objective of screening every newborn for congenital hypothyroidism and phenylketonuria. Over a million newborns were screened and over 430 abnormal cases were detected. A study was also conducted to determine the feasibility of including CAH screening in the program. The incidence of this disease has not yet been clearly determined. Since 1999, 58,563 newborns have been screened for CAH and 144 newborns with serum 17-OHP higher than 40 ng/mL were recalled for confirmatory tests. Of those, 68 were retested and 6 were found to have elevated 17-OHP levels. Two were confirmed with salt wasting CAH one month after birth, two others were diagnosed with another disease that caused electrolyte imbalance, one patient died, and the sixth required further clinical diagnosis. Five other babies were reported dead before the second specimens could be collected for confirmation. It appears that CAH may be one of the underlying causes of death among Thai newborns and the incidence may be higher than thus far shown due to incomplete confirmation of positive screens and deaths to some infants.

Phenylketonuria detected by the neonatal screening program in Thailand.

Neonatal screening for phenylketonuria (PKU) was introduced as a pilot project in Thailand from 1992--1995, and mass screening was started in 1996 by the Department of Medical Sciences, Ministry of Public Health. Blood samples were collected by heelprick on filter paper either at 48 hours of life or before discharge from the hospital. Elevated blood phenylalanine was identified by screening with the Guthrie method, then followed by the fluorometric method: All infants with a phenylalanine level equal to or greater than 4 mg/dl were recalled and retested using the fluorometric method and confirmed by plasma amino acid analysis and urinary pterins for tetrahydrobiopterin deficiency. A total of 1,062,676 newborns were screened from October 1992--March 2001, with 5 cases confirmed with PKU. The incidence was 1 in 212,535. All patients have been treated with low phenylalanine diet. The results of this study confirm the benefit of early detection and treatment of PKU through the screening program.