|Year : 2013 | Volume
| Issue : 2 | Page : 127-130
New-born screening for congenital hypothyroidism in Manipur by measurement of umbilical cord thyroid stimulating hormone: A hospital based study
Rajkumar Arbind Singh, Kshetrimayum Gomti Devi, Kshetrimayum Laskhmikumari Devi, Uttam Banik
Department of Physiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||19-Nov-2013|
Rajkumar Arbind Singh
Department of Physiology, Regional Institute of Medical Sciences, Imphal, Manipur
Source of Support: Financial assistance provided partly by RIMS,
Imphal and partly by DBT Nodal Cell, Tezpur University, Assam, Conflict of Interest: None
Objective: The objective of this study was to determine the incidence of congenital hypothyroidism (CH) in neonates by measuring umbilical cord thyroid stimulating hormone (TSH), born in a Teaching Hospital in Manipur. Materials and Methods: The study was based on the findings from cord blood samples collected from 1,000 babies born to mothers having no systemic (especially thyroid disorders) and obstetrical complications in the last 2 years. Estimation of serum TSH level was carried out by enzyme-linked immunosorbent assay method using Eliscan TM (Diagnova) kit manufactured by Ranbaxy Fine Chemicals Ltd. (RFCL) India in the Department of Physiology, Regional Institute of Medical Sciences, Imphal. Results: The mean, median and standard deviation for the TSH values of the samples were 8.833 mIU/L, 6.824 mIU/L and 7.059 mIU/L respectively. Nearly, 29.3% of the babies had TSH greater than 10 mIU/L. One baby was found to be having CH out of the 1,000 screened. Conclusion: CH represents one of the most common preventable causes of mental retardation. The finding of 1 case of CH out of 1,000 new-borns screened indicates that incidence is high in this state. Screening of all new-borns in the future is highly recommended.
Keywords: Congenital hypothyroidism, Screening, Thyroid stimulating hormone, Umbillical cord blood
|How to cite this article:|
Singh RA, Devi KG, Devi KL, Banik U. New-born screening for congenital hypothyroidism in Manipur by measurement of umbilical cord thyroid stimulating hormone: A hospital based study. J Med Soc 2013;27:127-30
|How to cite this URL:|
Singh RA, Devi KG, Devi KL, Banik U. New-born screening for congenital hypothyroidism in Manipur by measurement of umbilical cord thyroid stimulating hormone: A hospital based study. J Med Soc [serial online] 2013 [cited 2020 May 25];27:127-30. Available from: http://www.jmedsoc.org/text.asp?2013/27/2/127/121587
| Introduction|| |
Congenital hypothyroidism (CH) is the term applied to the hypothyroidism that is present at birth. It is usually caused by defects in the development of the thyroid gland, which may be genetic, or genetic defects in the synthesis of and secretion of thyroxine (T 4 ), the main product of the thyroid. Other rarer causes include defects in the secretion of and action of thyrotropin (thyroid stimulating hormone [TSH]) and the action of thyrotropin releasing hormone and the action of triiodothyronine (T 3 ), the biologically active thyroid hormone. 
CH of any cause is difficult to recognize at birth or very soon thereafter, in part because it is mitigated to some extent in utero by maternal-foetal transfer of T4. If the therapy is not initiated very soon after birth, the result is irreversible damage to the developing brain. 
The clinical manifestations of CH are often subtle or not present at birth. Common symptoms include decreased activity and increased sleep, feeding difficulties, constipation, and prolonged jaundice. On examination, common signs include myxedematous facies, large fontanels, macroglossia, distended abdomen with umbilical hernias, and hypotonia. 
Early diagnosis and therapy of CH improves the intellectual outcome and growth of the baby. In a study carried out earlier for CH, the mean intelligence quotient (IQ) of children with CH was 76. Specific cognitive defects were found even in those children who had normal IQs. Studies have shown that if therapy for CH is started before 3 months of age, the mean IQ is 89. If it is delayed the IQ drops to 70 between 3 months and 6 months and is as low as 54 after 6 months of postnatal life. 
In North America, it is estimated that more than 5 million new-borns are screened with approximately 1400 infants with CH detected annually.  New-born screening is the most modern public health preventive population screening program in all the developed countries. With the advances in technology and knowledge in genetics, much attention has been focussed on screening for preventable causes of disability and death in the new-born babies. In India, such programs are yet to be undertaken as such no definite incidence of these disorders is known. 
As there are few published studies of CH in Manipur, this study is undertaken to make an attempt to study the prevalence of CH in this part of the country.
| Materials and Methods|| |
This was a cross-sectional study conducted in the Department of Physiology in collaboration with the Department of Obstetrics and Gynecology, Regional Institute of Medical Sciences, Imphal, Manipur, for a period of 1 year from June 2011 to June 2012, after getting approval from the Institutional Ethical Committee.
The study was based on the findings from cord blood samples collected from 1,000 babies born to mothers having no systemic (especially thyroid disorders) and obstetrical complications. Apgar score, baby's weight, and sex were recorded. Mother's weight, literacy, socio-economic status, mode of delivery, along with obstetrical history, and history of past illness (especially thyroid disorders) was properly noted.
After taking informed consent from the mother or the attendant, 3 ml of cord blood were collected within 1 h of delivery in plain vials. Serum analysis for TSH was carried out. The parameters was measured by microplate enzyme-linked immunosorbent assay kit, Eliscan™ T4 (Diagnova) manufactured by RFCL limited.
Descriptive statistical analysis, cross - tabulation were applied using the statistical software SPSS 16.0.A.
| Results|| |
Out of the 1,000 neonates screened, 51% (n = 514) were males although 48.6% (n = 486) were female new-borns. Male:Female ratio was 514:486 = 1.065:1. The birth weights ranged from 2.1 kg to 4.0 kg with an average of 3.012 kg [Table 1].
A total of 29.3% of the samples showed a TSH > 10.00 mIU/L. The mean value of TSH was 8.833 ± 7.059 mIU/L. The values ranged from 0.7570 mIU/L as the minimum and 101.78 mIU/L as the maximum value. TSH values corresponding to 95 th , 97 th and 99 th percentile were 20.055, 21.858 and 29.943 mIU/L respectively. [Table 2] depicts the TSH values of the entire samples. One baby was finally proved to be hypothyroid after repeat confirmation with a TSH value of 104.3 mIU/L and thyroxine value of 1.06 μg/dl.
| Discussion|| |
Screening for CH is widespread for the last two decades. Because of several factors like cost, lack of reliable laboratories on a large scale and non-availability of baseline data in our population, neonatal screening has not gained popularity in Manipur.
Our results showed that from the 1,000 new-borns screened 29.3% of the samples showed a TSH > 10.00 mIU/L. This was comparable to figures from Ethiopia in the study by Mekonnen et al.  Klein et al.  in North America showed that the TSH level in cord blood samples was lesser than 20 mIU/L in 85% and higher than 60 in 0.04% of the cases. The mean value from our study was 8.833 ± 7.059 mIU/L, which was comparable to that of Feleke et al.  who observed a value of 9.6 ± 7.8 mIU/L in 4206 new-borns. However, our TSH values were somewhat lower than found by Khadilkar et al.  who in a study of 203 neonates found a mean cord TSH value of 12.3 ± 4.9 mIU/L.
Our 95 th , 97 th and 99 th percentile were 20.055, 21.858 and 29.943 mIU/L respectively, whereas Manglik et al.  found a 97 th and 99 th percentile of 14.98 and 25.8 mIU/L respectively although Mekonnen et al.  found a 97.8 th percentile as 15.4 mIU/L and Kung et al.  have quoted a 95 th percentile of 16 mIU/L.
Normal cord TSH values show a wide range of 1-38.9 mIU/L,  and in our study the range was from 0.7570 mIU/L as the minimum and 101.78 mIU/L as the maximum value. For the screening purpose, we had used a cut-off value of 40.00 mIU/L as recommended by the American Academy of Pediatrics  new-born screening for CH guidelines, which states that any infant with low T4 level and TSH concentration greater than 40 mIU/L is considered to have primary hypothyroidism until proved otherwise. In an earlier study, Manglik et al.  used a cut-off of 20 mIU/L and In Ethiopia, in an earlier study, Feleke et al.  measured TSH from heel pricks in neonates from 6 h of life up to 7 days old infants and determined the cut-off point for TSH to be 29.4 mIU/L.
In the present study, there was one new-born diagnosed with CH out of the total of 1,000 giving incidence of 1 in 1,000, which is much higher than the world [Figure 1] in 4000  but other Indian data too have quoted higher incidences as 1 in 248 and 1 in 1700  the findings of the present study were comparable to that of Winkler et al.  in which the overall incidence of CH was 1:2759 live births with a female: Male ratio of 1.8:1. No seasonal variation was observed. Probably geographic and ethnic differences are responsible and of course this study of 1,000 samples is too small to assess the incidence.
|Figure 1: Histogram showing Thyroid stimulating hormone (TSH) level frequency|
Click here to view
The world-wide incidence of CH is 1:3500-4000 live births  and it is twice as common in girls. A study conducted in Mumbai suggested incidence of 1:2800 live births.  This may be the tip of the iceberg and further screening would reveal the extent of this problem in our country.
To clarify the disease characteristics and investigate this high CH incidence rate, researchers will need to conduct a study with 4-5 fold higher population coverage. Iodine deficiency, which is one of the risk factors for CH according to Kochupillai et al.,  which said that the incidence of neonatal hypothyroidism as reflected in cord blood thyroxine and thyrotrophin levels is significantly higher in regions with iodine deficiency and endemic goitre. Although we did not measure neonatal and maternal urinary iodine levels, a study by Chandra et al.  in selected areas of Imphal west district of Manipur showed that the total goitre rate was 34.96% showing that Iodine deficiency disorders is a severe public health problem. Iodine content in drinking water ranged from 1.8 μg/L to 2.6 μg/L showing that the studied region is environmentally deficient.
Manipur is located in the foothills of the Himalayas. Owing to its geographical location, the entire state is in the classical goitre belt of India.  Determination of the incidence of neonatal hypothyroidism by measuring the cord blood thyroxine levels at birth is the most useful and reliable method to assess the risk of brain damage to infants and children growing up in an iodine deficient environment.  Elevated serum TSH in the neonate indicates insufficient supply of thyroid hormones to the developing brain, and therefore constitutes the only indicator that allows the prediction of possible impairment of mental development at a population level, which is the main consequence of iodine deficiency. In the absence of iodine deficiency, the frequency of neonatal TSH above 5 mIU/L whole blood is lesser than 3%. 
| Conclusion|| |
The present study was based on the findings from 1,000 new-borns tested for thyroid hormones (TSH). From this study, it was found that 29.3% of the studied population had TSH values in the upper normal range. Furthermore, in the study there was one new-born diagnosed with CH out of the 1,000 giving incidence of 1 in 1,000 which is much higher than the world [Figure 1] in 4000. 
Manipur is located in the foothills of the Himalayas. Owing to its geographical location, the entire state is in the classical goitre belt of India,  this is extremely significant in view of the fact that Iodine deficiency is one of the risk factors for CH.
Determination of the incidence of neonatal hypothyroidism by measuring the cord blood TSH levels at birth is the most useful and reliable method to assess the risk of brain damage to infants and children growing up in an iodine deficient environment.  Elevated serum TSH in the neonate indicates insufficient supply of thyroid hormones to the developing brain, and therefore constitutes the only indicator that allows the prediction of possible impairment of mental development at a population level, which is the main consequence of iodine deficiency.
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[Table 1], [Table 2]