Agency (IAEA) and The American Academy of Paediatrics (AAP) have published material ...... There is no routine neonatal screening programme in Sri Lanka. ...... in Lebanon- An example of newborn screening in absence of Mandatory law.
1
Chapter 1
Detection of Congenital Hypothyroidism
1.1. Congenital hypothyroidism Congenital hypothyroidism (CH) is a significant health problem in children throughout the world (Fisher 1983, Therrell & Padilla 2005). It occurs in approximately 1:3000 to1:4000 newborns in the world. It is one of the most common and preventable causes of mental retardation.
Thyroxine
(3‟,5‟,3,5-tetraiodo-L-thyronine)
an
iodine
containing
hormone
produced and secreted by the thyroid gland is an important regulator of metabolic rate in the body and plays a critical role in brain and bone growth during infancy and early childhood. A deficiency in circulating Thyroxine (T4) is the biochemical defect that causes the CH. Hypothyroidism that is present from birth is referred to as congenital hypothyroidism.
At birth, the clinical picture may not be obvious and typical signs will appear several weeks after birth. During pregnancy, both maternal and foetal thyroid hormones contribute to the growth and development of the foetus. This explains why some of the athyreotic newborns usually do not show any signs of hypothyroidism at birth (Vulsma et al., 1989).However, delay in diagnosis has severe consequences consisting mainly of delayed physical and mental development.
2
Since early diagnosis by clinical methods is difficult, and the consequences of late diagnosis can irreversibly affect the growth and mental development of the infant, it is important to make the diagnosis through a biochemical screening method, which provides an early diagnosis. Prompt diagnosis and appropriate treatment of infants with CH allows normal growth and intellectual development. Thus detection of CH through routine biochemical neonatal screening is practised worldwide.
1.2. Neonatal screening for CH
1.2.1.
Definition of neonatal screening Neonatal screening is the term used to describe various types of tests that are done
during the first few days of life to detect those who are likely to have unapparent medical problems. The screening test separates those who might have disease from those who probably do not have the disease with a reasonable rate of false positive results and no false negative results. In contrast, diagnostic tests are performed to establish the presence of a disease condition. Positive results in screening indicate who needs confirmatory tests and follow up. A properly planned and timely performed neonatal screening programme with appropriate intervention will prevent devastating effects on the growth and development of infants (Therrell 2001). A screening test is justified when early treatment of a severe disorder promises a good prognosis with treatment. However, there are factors like prevalence of the disease, its geographical distribution, type of tests available for diagnosis, treatment available and the economic feasibility, which needs to be considered (Therrell & Padilla 2005).
3
1.2.2.
Guidelines for newborn screening With the emergence of newborn screening for inborn errors of metabolism in the
1960s, public health policies were developed regarding, which conditions were to be included in screening and the basis on which they should be chosen. International organisations like the World Health Organization (WHO), the International Atomic Energy Agency (IAEA) and The American Academy of Paediatrics (AAP) have published material on neonatal screening over the years in cooperation with numerous other interested governmental and nongovernmental organizations. All these publications provide useful guidelines for newborn screening programmes in general. Table 1.1, 1.2 and 1.3 show some commonly used recommendations for newborn screening by different agencies (WHO1991, Therrell & Padilla 2005).
4
Table 1.1General Newborn Screening Recommendations (Therrell & Padilla 2005) (WHO Scientific Group, 1968) 1. Appropriate techniques and methods should be developed for screening the general population as well as high risk groups for certain diseases 2. Automatic procedures should be developed for the analysis of samples and handling data. Long term storage of biological specimens should be studied 3. Large scale pilot studies should be made to evaluate and compare screening methods. Selected populations should be investigated to obtain data on the frequency of these diseases 4. Multidisciplinary groups should be set up to study the short term and long term social and biological consequences of screening programmes 5. For each proposed screening programme estimated cost should be done 6. Central laboratories specialized in screening procedures should be created on a regional basis and those that already exist should be assisted 7. Specialized regional centres should be set up for the study and the management of patients or if they exist expanded 8. Collaborative studies should be undertaken to evaluate the investigation and management of patients. International co-operation should be enlisted for the exchange and training of personnel, the exchange of information and materials, and the comparison of methods and results
5
Table 1.2
Traditional Criteria for Newborn Screening (Therrell & Padilla 2005) (Wilson and Jungner, 1968) 1. The Conditions address should be an important health problem 2. There should be accepted treatment for the patient 3. Facilities for diagnosis and treatment should be available 4. There should be a latent or an early symptomatic stage 5. There should be a suitable screening test 6. The test should be acceptable to the public 7. The natural history of the disease should be adequately understood 8. There should be agreed policies on whom to treat 9. The cost of the screening , case finding including diagnosis and treatment should be economically balanced in relation to the expenditures of medical care as a whole 10. Case finding should be a continuing process
6
Table 1.3 AAP Task Force on Newborn Screening -basic recommendations (Therrell & Padilla 2005) (American Academy of Paediatrics 2000) 1. Infants should benefit from and be protected by newborn screening system. 2. Using previously defined (WHO) criteria for inclusion of a screening test not all conditions are good candidates for newborn screening. 3. Newborn screening is a system and every newborn should receive appropriate and timely services. 4. Newborn screening is an essential public health prevention activity requiring service integration for affected newborns. 5. State public health agencies have responsibility for assessment, assurance and policy development. 6. The newborn screening system must be clinically, socially and ethically acceptable to the public and health professionals. 7. Every newborn should have a medical home. 8. All newborns should have access to screening according to nationally accepted criteria regardless of their location. 9. Parents have a right to get information about newborn screening, the right to refuse testing and the right to privacy protection. 10. Increased newborn screening programme co-ordination and uniformity will benefit families, health care providers and public health agencies.
7
1.2.3.
History & Background of Neonatal Screening Programme Newborn screening for metabolic diseases began in the US in the year 1962
(Therrell 2006, El Ezzi et al., 2004). Professor Robert Guthrie (1916-1995) is considered as the „father‟ of neonatal screening. He pioneered the use of filter paper for collecting blood specimens and developed an inexpensive newborn screening test for phenylketonuria (PKU) and CH (Guthrie & Susi 1963). When he knew that radioimmunoassay technique could be applied to the Guthrie specimen, he worked hard to introduce this method for measurements of Thyroxine to identify infants with congenital hypothyroidism and to include this in the detection of CH in neonatal screening (Dussault 1985). At the beginning of neonatal screening most of the programmes were carried out as part of medical research. Because of economic constraints, these were highly criticized as not being practical. With the development of the radioimmunoassay technique and the introduction of the filter paper blood spot method, development of large scale screening programmes have become feasible. Neonatal screening for CH has become a good example of basic research providing the basis for an important practical application. It also has demonstrated the direct cost benefit of medical research (Dussault 1985).
8
1.2.4.
Incidence of Congenital Hypothyroidism The incidence of CH varies in different population groups. As newborn screening
programmes developed, the incidence of CH has also slowly increased due to better methods of case detection and increased disease awareness in screened populations. The global incidence of CH is about 1:3000 but it is significantly high in iodine deficient areas, sometimes in excess of 1: 600 (Therrell & Padilla 2005). Table1.4 shows prevalence of CH at birth in selected populations. Racial and ethnic differences in incidence of CH vary in different populations. For example, the incidence of CH in the Japanese population is around 1:7600 & none in Singapore (Joseph 2003) whereas, in Israel it is 1: 2473 nearly 3 times higher than among the Japanese. Variations in prevalence of CH have also been reported within populations. The prevalence of CH in Latino/Hispanic infants was the highest at 1:1750 and in non Latino/Hispanic infants; it was 1:4648 (Scheon et al., 2004). Studies in England (Rosenthal et al., 1988) found that CH appears to be several times more prevalent in children of Asians than in the Caucasians. Some studies have shown that prevalence of CH is high among female infants than in the male infants (2:1) (LaFranchi 1999, Scheon et al., 2004). Screening for CH in Asia has been progressively expanding. The International Atomic Energy Agency (IAEA) has been actively involved in regional development of congenital hypothyroidism screening since 1999. Table 1.5 shows the data on prevalence of CH in some of the countries in East Asia (Therrell & Padilla 2005). This data shows that the incidence of CH in Asia varies from 1:1000 to 1:6467. The reported number of babies born with CH in this region is high.
9
Table 1.4 Prevalence of Congenital Hypothyroidism at Birth in Selected Populations (Therrell & Padilla 2005)
Country
Study period
Australia
1977-85
Number screened 1,812,683
Austria
1985-88
Belgium
CH cases
Prevalence
436
1:4151
346,185
63
1:5495
1985-88
360,264
109
1:3305
Canada
1973-83
874,000
209
1:4182
Denmark
1981-82
224,189
76
1:2950
Finland
1985-88
246189
58
1:4254
France
1985-88
3,216.596
750
1:4289
Germany
1985-88
1,148,415
279
1:4116
Hungary
1985-88
306265
56
1:5469
Hong Kong
1984-95
451391
145
1:3113
Israel
1985-88
393304
1647
1:2473
Italy
1977-91
5,018,241
1151
1:3047
Japan
1979-85
8,846,279
1151
1:7686
Korea
1991-92
147,098
34
1:4326
Kuwait
1981-87
86910
25
1:7686
Singapore
1981-99
>500,000
0
-
Sweden
1985-88
413,616
131
1:3157
UK
1985-88
2,784,603
840
1:3315
US
1991-00
40,214,946
13,213
1:3044
10
Table 1.5
Birth Prevalence of Congenital Hypothyroidism in Developing Nations in East Asia (Therrell & Padilla 2005)
Country
Study
Number
period
screened
CH cases
Prevalence
Reference
Bangladesh
2000-02
12341
6
1:2042
China
1982-01
543,192
84
1:6467
Indonesia
2000-02
360,264
109
1:3305
IAEA
Korea
1991-99
1431791
330
1:4339
2005
Malaysia
2000-02
319807
36
1:3029
Mongolia
2000-02
3785
3
1:3057
Pakistan
1996-03
2500
3
1:1000
Philippines
1996-03
272547
83
1:3284
Thailand
1996-01
1425025
430
1:3314
Vietnam
2000-02
9451
4
1:2500
SRI LANKA
?
?
11
1.3. Thyroid Gland - Functions and Dysfunctions
1.3.1.
Embryology, Anatomy and Physiology Development of the thyroid gland, its function and the regulation of Thyroxine
synthesis in the foetus follows a well-characterised process (Fisher 1980a & Fisher 1997). This process involves following steps; 1. Embryogenesis 2. Hypothalamic maturation 3. Development of thyroid gland regulatory system 4. Maturation of iodothyronine deiodination system 5. Feed back mechanism of T4 on the Pituitary hypothalamic axis Early in embryonic life i.e., during the first trimester of pregnancy, thyroid tissues are located at the base of the tongue. This gradually grows into a bi-lobed thyroid gland that resembles a butterfly in shape. By the end of first trimester, the thyroid gland starts to descend from the base of the tongue to its final destination just below the thyroid cartilage (i.e. Adam‟s apple) in the anterior neck. The foetal thyroid gland acquires the capacity to concentrate iodine and synthesize iodothyronine by 10-12 weeks of gestation to produce thyroid hormone. Hypothalamic maturation proceeds from the 4-5th weeks through 30-35th weeks of gestation. By 12 weeks, pituitary thyrotrophs are evident and the hypothalamus begins to stimulate the pituitary gland to release a trophic hormone known as thyroid stimulating hormone (TSH) into the foetal blood stream.
12
TSH acts on the thyroid gland to produce thyroid hormones in the thyroid follicular cells. The hormone interaction between the hypothalamus, pituitary and the thyroid gland gradually matures towards term and this relationship is known as Hypothalamo-PituitaryThyroid (HPT) axis (Fig 1.1). However, foetal thyroid function remains at basal levels until mid-gestation i.e. 16-18 weeks (Helge1981, Fisher1980a, Ingbar & Wobber, 1981). By the time the baby reaches full term, the thyroid is ready to provide the T4 requirements necessary for normal postnatal growth and development. Feedback to the hypothalamus and pituitary gland regulates TSH synthesis and the production of T4 (Therrell & Padilla 2005, Fisher 1980b & Fisher et al., 2002). If any part of this process fails to either form or function correctly, the baby will become hypothyroid. Embryogenesis and the regulation of the thyroid gland function is a complex process. This makes it vulnerable to many potential developmental and functional abnormalities that arise within the system and is responsible for different types of hypothyroidism. Hence, understanding of the thyroid gland function and the regulatory mechanism is essential for understanding the aetiology of CH and planning the long-term management of children with CH. A diagrammatic representation of hypothalamic pituitary thyroid axis is shown in Fig.1.1.
13
Fig1.1.
Diagrammatic Representation of Thyroid Function Regulation (hypothalamic pituitary thyroid axis) (Greenspan 1997)
TRH- thyrotropin releasing hormone, TSH- thyroid stimulating hormone T4- Thyroxine, T3- triiodiothyronine
14
1.3.2.
Aetiologies for Congenital Hypothyroidism The aetiology of CH plays an important role in determining the disease severity and
its outcome (Germak & Foley, 1990). Approximately 85% of cases are sporadic and the main cause is thyroid dysgenesis. The remaining 15% of cases are hereditary (LaFranchi 1999). The major aetiologies of CH with their prevalence are shown in table1.6. Studies have shown that CH has a female preponderance. However, the significance of this gender difference is not yet known (LaFranchi 1999, Therrell & Padilla 2005).
1.3.2.1.
Permanent Disorders of CH
1.3.2.1.1.
Thyroid dysgenesis
Abnormalities of formation, migration and growth of the thyroid gland are called thyroid dysgenesis, which is the commonest cause of CH. This could be either agenesis (absent or aplasia of the gland), hypoplasia (markedly under develop) or ectopia (abnormal location). Ectopic location of the thyroid gland accounts for two-thirds of thyroid dysgenesis in the world (Fisher 1983). Studies have found that some relationship exists between the ethnicity and the genetic predisposing factors (LaFranchi 1999). One study demonstrates mutations in the PAX-8 gene in infants with thyroid dysgenesis (Macchia et al., 1997) and one study failed to find any association with gene mutations (Lapi et al., 1997). However, the exact pathogenesis for thyroid dysgenesis is not known.
15
Table1.6
Causes and Incidence of Neonatal Thyroid Dysfunction (Fisher 1987, Fisher 1991, John 1987, Therrell & Padilla 2005) Cause of disorder
Incidence
Permanent 1. Thyroid dysgenesis
1: 4500
(agenesis, hemiagenesis & ectopic) 2. Dyshormonogenesis
1: 30,000
3. Secondary hypothyroidism
1:25,000 – 1:100,000
4. Generalised resistance to thyroid
Very rare
Hormone
Transient
1. Transient hypoThyroxinemia
1:25,000-1: 100,000
(maternal antibody mediated) 2. Transient hypothyroidism
1:200
(main cause is prematurity) 3. Transient primary hypothyroidism (common in areas of iodine deficiency)
Variable (1:700)
16
1.3.2.1.2.
Thyroid Dyshormonogenesis
Inborn errors of Thyroxine synthesis (dyshormonogenesis) are the second most common cause accounting for approximately 10% of cases of CH (LaFranchi 1999). This defect could be due to abnormalities in enzymatic reactions involved in thyroid hormone production or release. The major defects of this group are shown in table 1.7. The most common inborn error is a defect in thyroid peroxidase (TPO) activity leading to impaired oxidation and organification of iodide to iodine, which interferes with binding to thyroglobulin (Tg) (LaFranchi 1999).
Table 1.7
Common Causes of Inborn Errors of Thyroxine Synthesis (LaFranchi 1999)
1. Iodide trapping defects due to sodium/iodide symporter mutation 2. Oxidation and organification defect 3. Coupling defect 4. Thyroglobulin (Tg) gene mutations 5. Defective proteolysis and secretion of T4 6. Deiodinase gene mutations
17
1.3.2.1.3.
Secondary hypothyroidism (hypothalamic -pituitary hypothyroidism)
In secondary hypothyroidism, the thyroid gland formation is normal but the tropic hormone, TSH is either not produced or not released from the pituitary gland. As a result, the thyroid gland is unable to produce or release thyroid hormone. It was estimated that less than 5% of babies with CH belong to this category and the worldwide prevalence varies from 1:110,000 to 1: 29,000 (Asakura et al., 2002, David et al., 2005, Hanna et al., 1986). However, secondary hypothyroidism is often mild and T4 levels are not always low, as such these infants can be missed during the screening programmes in spite of using both TSH and T4 measurements. The low FT4 and normal TSH measurement also found in some neonates due to benign state of hypothalamic pituitary immaturity or associated with TBG deficiency (Asakura et al., 2002 & Mitchell et al., 1981). Prematurity, respiratory distress syndrome and severe birth asphyxia may temporarily depress the TSH response. In routine clinical practice, it is important to understand the thyroid functions and dysfunctions for better therapeutic outcome and long-term follow up. However, in spite of early detection the efficacy of early treatment or the long-term prognosis of these children with secondary hypothyroidism is still uncertain (Vulsma 2006, Asakura et al., 2002 AAP 1993).
1.3.2.1.4.
Generalized Resistance to Thyroid Hormone
This is a very rare condition and rarely diagnosed as a cause of CH and needs no further discussion.
18
1.3.2.2.
Transient Congenital Hypothyroidism
In transient hypothyroidism, there is biochemical and possibly, clinical features of hypothyroidism which disappear spontaneously after a short period. Trans-placental passage of maternal TSH receptor blocking antibodies, account for reasonable cases of transient CH (Gaudino et al., 2005). This condition is characterized by maternal autoimmune thyroid diseases and should be suspected where more than one affected infant is born with goitre to the same mother. Other causes like prematurity, maternal ingestion of excess iodides and some maternal medications like antithyroid drugs that are transferred from maternal blood stream across the placenta can also give rise to this problem (Gaudino et al., 2005). The duration and the severity of transient hypothyroidism vary and may persist from several days to several months after birth. Several studies found that moderately elevated TSH levels are associated with certain other pathological conditions such as hypometabolic states and iodine deficiency (Siklar et al., 2002). Neonates are more sensitive to the effect of iodine deficiency than adults are because; they have a very small intra-thyroidal iodine pool, which requires increased TSH stimulation to maintain normal thyroid hormone synthesis (Delange 2001). Studies have shown that marginally elevated TSH is associated with iodine deficiency hence, neonatal TSH can be used as an indicator to assess the iodine status of a given population (Delange 1998).It has been estimated that the frequency of neonatal TSH above 5mU/L in whole blood (or 10mU/L in serum) is less than 3% in the normal population. A frequency of 319.9%, 20-39.9% and above 40% respectively was discovered in population with mild, moderate and severe iodine deficiency (Delange 1998, Mikelsaar & Vikkmaa, 1999).
19
1.4. Detection of Congenital Hypothyroidism CH is detected using a combination of the following methods: 1.
Clinical detection using clinical symptoms and signs ± X ray bone maturation
1.4.1.
2.
Biochemical thyroid function tests
3.
Imaging of thyroid gland by ultrasound scan and scintigraphy
4.
Other investigations
Clinical Detection of CH Physical examination Clinical diagnosis of CH is difficult in a baby soon after birth as the clinical signs
and symptoms are subtle and tend to be missed during the early neonatal period. Only 5% of cases are diagnosed by clinical examination immediately after birth. Prolonged jaundice, umbilical hernia, protruding tongue, constipation, poor feeding, increased sleep, poor crying or activity and cold / mottled skin are known clinical features associated with CH (Klein 1980, El Ezzi et al., 2004). Furthermore, the signs and symptoms seen in hypothyroid infants are not specific and may be seen in many other conditions and even in normal infants. Studies have shown that detection of CH by clinical features is far from satisfactory because many infants with CH are not diagnosed until very late.
20
Epidemiogical studies have shown that when clinical methods are used for the detection of CH approximately 90% were missed at one month of age, 65% even at 3 months and 30% even after one year (Interactive Multimedia Teaching Software on Neonatal Screening for Congenital Hypothyroidism, IMTS system version 1.1. 4-10.2001 IAEA; ( IAEA - IMTS (2001) & Alm et al., 1978). Hypothyroidism can be acquired after newborn screening. Hence, clinicians should continue clinical evaluation, judgment and experience in the face of normal newborn thyroid function (Rose & Brown et al., 2006, Klein, et al., 1974). It has been reported that infants born with normal thyroid gland functions whose gland then atrophies and develop clinical and biochemical hypothyroidism later (Klein 1980). Furthermore, cases have been reported that infants with lingual thyroid, who had adequate function for some time, had become hypothyroid later in life (Klein 1980). Hence, all these findings support the value of being aware of clinical features in the diagnosis of CH. However, in the absence of a biochemical screening method it becomes necessary to rely on clinical indices and therefore, some recommend biochemical thyroid function tests based upon an established the clinical index for the diagnosis of CH (Dussault 1997). Fig 1.2, Fig 1.3 and Fig 1.4 show a few examples of cases that were missed due to lack of biochemical hypothyroid screening. They presented with clinical features later in infancy or in childhood. In one child, the diagnosis had been delayed up to 6 years of age! These figures illustrate the problem of delayed diagnosis of CH by clinical methods probably a reflection of the lack of clinical features early in life and the lack of clinical skills of the attending health professionals later on.
21
It has been shown that there is an inverse relationship between the age at which timely Thyroxine treatment is started and satisfactory neurological outcome of children affected by CH. Therefore, early diagnosis and thyroxine replacement are the utmost important factors to prevent mental retardation (Klein et al., 1972, Raiti & Newns, 1971).
X- ray bone age Assessment of skeletal maturation by X - ray will support the clinical diagnosis of CH. Bone age x- ray films should be obtained during the neonatal period and compared with reference standards of foetal and neonatal epiphyseal ossification. For this purpose x ray of the knee is useful for comparison with standards for bone age. Skeletal maturation reflects the severity of in-utero hypothyroidism. Hypothyroid infants with low FT4 (28200
45
1.2%). 2. transport the samples in good order to the regional laboratories using the state ambulance services or hand delivery by a hospital worker 3. use blood spot TSH effectively with a cut off at 20 within acceptable recall rates (1.2%) 4. contact presumptive positive cases directly by the screening laboratory via the state postal services. In fact, in this study it was possible for all 54 presumed positive cases to be reconfirmed early using this method. 5. commence treatment early (4-5weeks) using communication of positive cases by phone to the relevant Paediatrician and informing the parents by post. (5/6 patients proved positive were commenced on treatment within 4 weeks and the other within 5 weeks)
146
Congenital hypothyroidism is a treatable deficiency of thyroid hormone that causes severe mental retardation and growth deficiency if it is not detected and treated early. The aim of a hypothyroid screening programme is to cover the total newborn population to identify babies at risk, treat and provide long-term follow up as effectively as possible. It is essential to have both national and international support to establish such a programme. This study was aimed at contributing to the initiative of setting up a CH screening programme in Sri Lanka. It is my fervent wish that I have succeeded in this mission.
''Every child has a right to be endorsed free of preventable diseases like congenital hypothyroidism”
147
Research studies presented and published related to this study
1.
Nanayakkara, D., Wijekoon, A., Hemawardana, D., Weerasekara, G., Tammita, A.,
Silva, Perera, K., (2002). Retrospective analysis of clinical symptoms used for detection of congenital hypothyroidism. Proceedings of the University Research Sessions, Peradeniya, Sri Lanka.Vol.07. Abstract 100p
2.
Nanayakkara, D. & Wijekoon, A. (2003).Hypothalamo-Pituitary Hypothyroidism
detected by biochemical screening for congenital hypothyroidism. Proceedings of the The Kandy Society of Medicine 25th Silver Jubilee Annual academic sessions. Vol.25.Abstract 19p
3.
Nanayakkara, D. and Wijekoon, A. (2004). Laboratory Screening for Congenital
Hypothyroidism in early infancy: A hospital based study. Proceedings of the 9th University Research Sessions, Peradeniya, Sri Lanka, Vol.09. Abstract 103p
4.
Nanayakkara, D., Wijekoon, A. and Solanki, K. (2005a). The Role of Thyroid
Scans in Early Infancy. Eur. J Nucl Med & Mol. Imaging Vol.32.S 222
EANM‟05-Annual Congress of the European Association of Nuclear Medicine, 15-19 Oct 2005 in Istanbul, Turkey (Abstract P513 Paediatrics)
148
5.
Nanayakkara, D. and Wijekoon, A. (2005b). A report on the follow up of infants
with marginal hyperthyrotropinemia in early infancy. Proceedings of the10th University Research sessions, Peradeniya, Sri Lanka. Vol.10, Nov 10, abstract 49p
6.
Nanayakkara, D. (2005). Screening for Congenital Hypothyroidism: Filed
experience – Sri Lanka. Project coordination meeting to discuss Automation and Harmonization of Immunodiagnostics for strengthening and expansion of Newborn Screening Programme, 20-24 March in Hanoi, Vietnam.
7.
Nanayakkara,
D.
(2006).
Regional
screening
Network
for
Neonatal
hypothyroidism; Pilot project experience in Sri Lanka. The regional meeting on Technical and Clinical Audit for Strengthening and Expansion of Newborn Screening Programme. 27-31 March in Seoul, Republic of Korea.
8.
Wijekoon, A., Nanayakkara, D., Jiffry, N., Rasnayaka, M., Nilam, J., Liyanage, G.
and Solanki, K. (2006). Towards Neonatal screening for congenital hypothyroidism in Sri Lanka. The proceedings of the 6th meeting of the International Society for Neonatal Screening (Abstracts) WS 49, P108. ISSN, Sept 2006 Japan
9.
Nanayakkara, D., Perera, K., Herath, S., Jiffry, N., Nilam, J. and Solanki, K.
(2006). Neonatal Screening for congenital hypothyroidism. First Experience. Proceedings of the11th University Research sessions, Peradeniya, Sri Lanka. Vol.11, Nov 30, 2006 abstract 110p.
149
10.
Damayanthi Nanayakkara, Nawaz Jiffry, Nilam Jiffry, Liyanage, Guwani
Liyanage, Kishor Solanki, and Rasnayake Muduyanse (2007). Neonatal screening for congenital hypothyroidism – pilot project experience in Sri Lanka. Proceedings of the 12th Asia Pacific Congress of Paediatrics and 2nd Asia Pacific Congress of Paediatrics Nursing in Conjunction with 10th Annual Congress of Sri Lanka College of Paediatricians Vol 1, Issue 1 12-15th March 2007 Sri Lanka.
150
Appendices Appendix 1.1 Radiation Dosimetry in Children (5 years old); (ICRP 53)
Radio-
Half-life
pharmaceutical
Administered
Organ receiving the
Effective
activity
largest radiation dose
dose
MBq/kg
mGy/MBq
Per MBq
(mCi/kg)
(rad/mCi)
(per mCi) mSv (rem)
123
I
99m
Tc
pertechnetate
13h
6h
0.1-0.3 per oral
9.8 Thyroid
0.35
(0.003-0.01)
(36)
(1.23)
1-5 IV
0.21 large intestine
0.04
(0.015-0.07)
(0.78)
(0.15)
ICRP 53 , page 264 assuming 15% uptake and page 199 no blocking agent Appendix 1.2 The Recommended Radiation Doses for Children
Paediatric Task Group EANM (Eur Jour Nucl Med 1990;17:127-9 )
3kg = 0.1
Fraction of adult administered activity 22 kg = 0.53 42 kg
= 0.78
4 kg = 0.14
24 kg = 0.53
44 kg
= 0.80
6 kg = 0.19
26 kg = 0.56
46 kg
= 0.82
8 kg = 0.23
28 kg = 0.58
48 kg
= 0.85
10 kg = 0.27
30 kg = 0.62
50 kg
= 0.88
12 kg = 0.32
32 kg = 0.65
52-54 kg
= 0.90
14 kg = 0.36
34 kg = 0.68
56 -58 kg = 0.92
16 kg = 0.40
36 kg = 0.71
60 – 62 kg = 0.96
18 kg = 0.44
38 kg = 0.73
64- 66 kg = 0.98
20 kg = 0.46
40 kg = 0.76
68 kg
= 0.99
151
Appendix 5.1 DATA COLLECTION SHEET
S & S 903 Filter paper strip
Newborn Screening for Congenital Hypothyroidism Nuclear Medicine Unit, Faculty of Medicine, University of Peradeniya
(To avoid delays in processing complete this form accurately)
. Hospital
Mother BHT No
Mother‟s Name Mode of delivery
POG (Weeks) NVD
LFD
Date of birth Time of birth AM/PM
Normal Jaundice
Normal 1 Other
Sick
Premature
Constipation
sex of the baby
LSCS
Birth Wt (g) M
Date of collection Time of Collection
AM/PM
Maternal Thyroid status Baby‟s Status
V/E
DE
low BW
MNG Twins
Rx
carbimazole
on antibiotics
Congenital abnormalities
F
Downs‟
Thyroxine
date of blood transfusion B Asphyxia
Y
Address Contact No.
Consent of the Mother:
Date
TSH
T4
T4
N
152
Appendix 5.2 BLOOD SPOT TSH RESULT SHEET
NUCLEAR MEDICINE UNIT
Faculty of Medicine, University of Peradeniya Results of Neonatal blood spot TSH Screening
Patient‟s Name………………………………………
Age…………ex………….
Hospital……………………… BHT……… Our Ref No: Date of Collection /Received……………………………………….
TSH
mU/L
Whole blood
Reference range Normal
20mU/L (whole blood)
Hypothyroidism Possible, for serum confirmation
> 40mU/L (whole blood)
Probable primary Hypothyroidism
>100mU/L (whole blood)
Dr.D.K.K. Nanayakkara MBBS, M.Phil (UK) Senior Lecturer, Nuclear Medicine Unit,
URGENT sample for serum confirmation
University of Peradeniya Tel- 081-2388361
153
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Examined by
Bradford L. Therrell, Jr., PhD Professor, Department of Pediatrics, University of Texas Health Science Center at San Antonio, Texas, USA and Director, U.S. National Newborn Screening and Genetic Resource Center, Austin, Texas, USA
And
Chandrani Liyanage, PhD Professor, Department of Biochemistry, & Head, Nuclear Medicine Unit Faculty of Medicine, University of Ruhuna Galle, Sri Lanka
