|Year : 2014 | Volume
| Issue : 2 | Page : 503-506
Incidence of congenital hypothyroidism in Jordan
Queen Rania Al Abdullah Hospital for Children, King Hussein Medical Center, Amman, Jordan
|Date of Submission||18-Dec-2013|
|Date of Acceptance||03-Mar-2014|
|Date of Web Publication||26-Sep-2014|
MD, Queen Rania Al Abdullah Hospital for Children, King Hussein Medical Center, Royal Medical Services, Amman
Source of Support: None, Conflict of Interest: None
The aim of the study was to compare the incidence of congenital hypothyroidism (CH) in Jordan with its incidence worldwide.
CH is a preventable disease of mental retardation. Its incidence worldwide is almost 1 : 4000. Early screening, diagnosis, and treatment are mandatory to prevent later sequelae.
Materials and methods
This is a descriptive retrospective analysis of 13 452 newborns screened for CH. Data were collected from records during the period from February 2010 to November 2013 in the pediatric endocrine clinic in Queen Rania Al Abdullah Hospital for Children at King Hussein Medical Center, Amman, Jordan. There were 5978 male and 7474 female participants. Their age ranged between 3 and 10 days. Heel-prick whole blood was collected on a filter paper and sent everyday to the Princess Eman Laboratory Center for analysis. The thyroid-stimulating hormone (TSH) level using the enzyme-linked immunosorbent assay was considered as normal if the TSH value was less than 10 mU/ml, equivocal at values between 10 and 20 mU/ml, and positive for CH if TSH values were greater than 20 mU/ml. Parents of newborns with positive and equivocal results were called to return for further assessment. Central blood samples for free T4 and TSH were sent for patients with equivocal results and for those with TSH screen greater than 20 mU/ml. These two groups were reassessed for symptoms and signs of CH. Newborns screened for CH younger than the age of 3 days and older than the age of 10 days were excluded from the study. Newborns with clinical sepsis and premature babies were also excluded. Descriptive analysis using frequencies was applied to describe the study variables.
Out of the 13 452 newborns tested, 5978 (44%) were male and 7474 (56%) were female. Newborns were categorized into three groups according to the TSH screening result. Group 1 included 13 231 newborns [5903 male (45%) and 7328 female (55%)] with normal TSH screen less than 10 mU/ml. Group 2 included 173 newborns [52 male (30%) and 121 female (70%)] with TSH 10-20 mU/ml. Group 3 included 48 newborns [23 male (48%) and 25 female (52%)] with TSH level greater than 20 mU/ml. Central samples for T4 and TSH were sent for group 2 and group 3. In group 2, one female newborn was confirmed to have primary hypothyroidism, whereas in group 3, five newborns were diagnosed to have CH, one male and four female.
The incidence of CH in Jordan is higher than the incidence worldwide; this could be due to the higher rate of consanguineous marriages in Jordan, which can increase the incidence of primary hypothyroidism due to dyshormonogenesis, although other contributing factors should be considered.
Keywords: Congenital hypothyroidism, incidence, Jordan, neonatal screening
|How to cite this article:|
Alawneh H. Incidence of congenital hypothyroidism in Jordan. Menoufia Med J 2014;27:503-6
| Introduction|| |
Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates as well as the most common preventable cause of mental retardation in children ,,,,,,,,,,,,,,. The majority of the neonates with CH are asymptomatic at birth, and this will result in severe neurodevelopmental impairment if treatment is delayed ,,. Therefore, it is mandatory to screen neonates for CH for early diagnosis and treatment.
CH has a worldwide incidence of 1/4000-1/3000 [4-6]; the incidence may be higher or lower depending on the race, the ethnicity, and the screening method . The female-to-male ratio of CH is nearly 2 : 1 .
CH is caused by thyroid dysgenesis in 85% of the cases, which is sporadic, whereas 15% are due to defects in thyroid hormone biosynthesis (dyshormonogenesis), which is an autosomal recessive disorder ,.
Approximately 10% of the infants with CH have associated congenital anomalies with cardiac defects being the most common, but other anomalies of the nervous system and eyes have been reported ,,.
CH screening was introduced in 1974 and has become a common practice . In Jordan, it has been performed since 2004; this is not very late in that region if we compare it with Turkey, which started performing neonatal thyroid screening in 2006 .
Screening for CH in Jordan is performed in three sectors: the Ministry of Health, Royal Medical Services, and the Private Sector.
| Materials and methods|| |
This is a descriptive retrospective study approved by the ethical committee of Royal Medical Services of Jordan and was conducted during the period from February 2010 to November 2013 in the Queen Rania Al Abdullah Hospital for Children at King Hussein Medical Center, Royal Medical Services, Amman, Jordan. Data were collected from records for 13 452 newborns who were screened for CH at the age of 3-10 days, and the mean average age was 5.3 days.
Newborns undergoing CH screening in the endocrine clinic were evaluated regarding the gestational age, preterm, term, or postdate, the date of delivery, and any acute illness.
The name, the insurance number, and two (mobile, phone) contact numbers for parents were recorded. Premature babies, septic neonates, and neonates below 3 days of age and above 10 days of age were excluded from the study. A trained nurse assigned for the CH screening drew a heel-prick whole-blood sample collected properly to fill a circle completely on a filter paper. Dry blood samples collected on a filter paper were sent daily to the Princess Eman Laboratory Center for analysis. The thyroid-stimulating hormone (TSH) level was evaluated using enzyme-linked immunosorbent assay. Cutoff levels for TSH remain controversial; in Turkey, the cutoff level for TSH was initially 20 mU/ml, but it was lowered to 15 mU/ml in recent years ,. In our laboratory center, we consider the cutoff value for TSH to be 10 mU/ml, which will decrease the possibility of false-negative results. Newborns who had TSH level less than 10 mU/ml were considered as normal, newborns with TSH 10-20 mU/ml were considered as equivocal, and those with TSH greater than 20 mU/ml were considered as positive for CH. Parents of newborns with equivocal and positive results were called back for reassessment. These two groups were reassessed clinically for symptoms and signs of CH; central venous blood samples were drawn for T4 and TSH level, and results were available within 24 h. Newborns with central blood samples that indicate CH were reassessed regarding parents' consanguinity, and they were also screened for cardiac and renal anomalies using echocardiography and renal ultrasound.
Descriptive analysis using frequencies was applied to describe the study variables.
| Results|| |
Out of the 13 452 newborns tested, 5978 (44%) were male and 7474 (56%) were female.
Newborns were categorized into three groups according to the TSH screening results.
Group 1 included 13 231 newborns [5903 male (45%) and 7328 female (55%)] with normal TSH screen less than 10 mU/ml. Group 2 included 173 newborns [52 male (30%) and 121 female (70%)] with TSH 10-20 mU/ml. Group 3 included 48 newborns [23 male (48%) and 25 female (52%)] with TSH level greater than 20 mU/ml.
Newborns in groups 2 and 3 were reassessed regarding the symptoms and signs of CH. None of them had symptoms of CH: one female newborn in group 3 was found to have prolonged jaundice and umbilical hernia. Central samples for T4 and TSH were sent for groups 2 and 3. In group 2, one female newborn was confirmed to have primary hypothyroidism, whereas in group 3, five newborns (four female and one male) were confirmed to have primary hypothyroidism. The male-to-female ratio of CH was 1 : 5: two newborns out of six (33%) diagnosed to have CH were products of a consanguineous marriage. None of them had associated cardiac or renal anomalies as proven by echocardiography and renal ultrasound. The overall incidence of CH in this study was 6/13 452 (i.e. 1 : 2242), which is higher than the incidence worldwide. Results of the study are summarized in [Table 1] and [Table 2].
|Table 2: True-positive samples among the equivocal and the positive screen groups|
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| Discussion|| |
Thyroid hormones play a vital role in the functions of various organs. Brain development, including neural growth, neurotransmission, neural migration, as well as lamination enzyme induction , are the most important.
Failure of recognition of CH in the neonatal period will lead to irreversible permanent central nervous system damage, which will end in physical and mental retardation ,,,,,,,,,,,,,. The thyroid gland is visible in the embryo by 3 weeks, and it is capable of trapping iodine by 8-10 weeks and of producing T4 by 12 weeks, whereas the hypothalamic-pituitary-thyroid axis with negative feedback is not well established till the second half of pregnancy. The fetus is totally dependent on maternal thyroid hormones in the first trimester, and approximately one-third of the maternal T4 crosses the placenta ,.
Only 5-10% of affected newborns have clinical signs or symptoms at or soon after birth; hence, most of the affected newborns will appear healthy. Infants with severe CH lasting more than 4-6 weeks may present with poor feeding, constipation, lethargy or excessive sleeping, and a hoarse cry, whereas signs of CH may reveal failure to thrive, large anterior fontanelles, dry skin, prolonged jaundice, mottling, umbilical hernia, macroglossia, and coarse facial features . In this study, one female newborn (17% of newborns diagnosed to have CH) had some features of CH manifested by prolonged jaundice and umbilical hernia, whereas the other five newborns (four female and one male) diagnosed to have CH did not show any signs or symptoms of CH.
Before the onset of newborn-screening programs, the incidence of CH as diagnosed by its clinical manifestations was in the range of 1 : 7000-1 : 10 000 ,,. In Jordan, we do not have data about the incidence of CH before the establishment of neonatal thyroid-screening program.
The concept of neonatal screening started in 1963 for phenylketonuria (PKU) by Guthrie and Susi. Ten years later, this concept was extended to CH by Dussault and Laberge.
CH is seven-fold more frequent than PKU, and the early treatment of CH leads to a more drastic effect on the neuropsychological outcome than dietary restriction for PKU .
The cost of CH screening is not comparable to the cost of long-term care of patients with mental disability .
Thyroid screening was first developed in Quebec (Canada) and Pittsburgh (USA) in 1974 ,,. In Jordan, screening for CH started in 2004.
The heel-prick test for TSH or T4 or both may be used for CH screening. TSH screening has been shown to be more specific, whereas T4 screening is more sensitive, especially in detecting central hypothyroidism, but it is less specific than TSH screening and has a high frequency of false-positive results. TSH screening will not detect newborns with central CH, which contributes to less than 5% of cases of CH ,,. In Jordan, we use TSH screening for CH. In newborns who are suspected or are at risk to have central CH, such as newborns who have features of panhypopituitarism or those with midline defect (cleft palate, corpus callosum dysgenesis), T4 and TSH using a central blood sample are performed.
The incidence of CH in live births in different parts of the world is 1 : 3000-1 : 4000 [4-6,19]. This incidence may be higher in some places due to many factors such as environment, ethnicity, iodine deficiency, and the method of CH screening. All in all, the incidence of CH is increasing globally ,,,.
The incidence of CH during 1985-1990 in Europe was 1 : 3801, in Italy 1 : 2700 and 1 : 1446 in another study, in USA from 1 : 4098 to 1 : 2370, in Japan 1 : 3856, in China 1 : 2418-1 : 1678, in Croatia 1 : 4127, in Slovenia 1 : 300, in Serbia 1 : 3000, in Macedonia 1 : 2804, in Bosnia and Herzegovina 1 : 3957, in Greece 1 : 1800, in Iran 1 : 950-1 : 748, in Turkey 1 : 2736-1 : 2326, in the Netherlands 1 : 1300, and in Thailand and Lebanon 1 : 1800 ,,,. The incidence of CH in Jordan in this study was 1 : 2242, which is higher than the incidence reported in previous years in other localities.
In USA, the incidence rate of CH increased from 1 : 4100 in 1987 to 1 : 2350 live births in 2002. In New York, the incidence of CH increased over the last two decades from 1 : 3378 to 1 : 2370 . Defining the etiology of CH is essential in identifying as to why changes in incidence are occurring .
CH has been reported to be more common among Hispanics and Asians. Researchers attributed this higher incidence of CH among Asians to the increased rate of parental consanguinity ,. In this study, the consanguinity rate for parents of newborns who were found to have CH was 33%.
CH occurs more often in girls than in boys, generally with a ratio of 2 : 1, . In this study, there were six affected newborns with CH, one male and five female, with a female-to-male ratio of 5 : 1.
The high frequency of multiple congenital anomalies found in children with CH suggests an early impairment in embryonal development with a consequent involvement of different organs and structures . In this study, we did not recognize any associated congenital anomalies in newborns diagnosed to have CH. They were screened by cardiac echocardiography and renal ultrasound as it was reported that cardiac and urogenital anomalies are the most common associations . However, these data are not conclusive due to the small sample size.
Early treatment of infants diagnosed to have CH was associated with a normal mean IQ . Preferably, the diagnosis of CH must be confirmed within the first 14 days, and treatment should be started immediately. There are also some studies that stressed that treatment must be started before 3 months of age (ideally 1 month) . In this study, all newborns diagnosed to have CH were started on treatment before the age of 1 month, with an average age of starting treatment of 23 days.
The aim of management is to normalize T4 within 2 weeks and TSH within 4 weeks. The starting dose is 10-15 mg/kg/day of levothyroxine sodium. Frequent follow-up of T4 and TSH levels is mandatory for dose adjustment and to avoid undertreatment or overtreatment as hyperthyroxinemia has a potential to cause premature synostosis and developmental delay ,.
| Conclusion|| |
The incidence of CH in Jordan is higher than the incidence worldwide; this could be due to higher consanguineous marriages in Jordan, which can increase the incidence of primary hypothyroidism due to dyshormonogenesis. However, other etiological factors should be considered.
| Acknowledgements|| |
The author thanks the staff of the endocrine laboratory at the Princess Eman Laboratory Center for analyzing the samples as well as the nurses at the pediatric endocrine clinic for their cooperation and great support.
This study was funded by Royal Medical Services of Jordan.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]