Quantitative and qualitative comparison of neonatal screening plan for the identification of hypothyroid neonates between Nahavand and Kashmar cities in 2016–2017(respectively in the west and east of Iran)

Maryam Soori,Sedigheh Soleymani,Samira Tabaei,Manoochehr Solgi

1Department of Biochemistry,Islamic Azad University of Hamadan,Hamadan,Iran.2Department of Biology,Damghan Branch,Islamic Azad University,Damghan,Iran.3Diseases Research Center,Shiraz University of Medical Sciences,Shiraz,Iran.4Department of Epidemiology,School of Public Health,Hamadan University of Medical Sciences,Hamadan,Iran.

Abstract

Keywords:Neonatal hypothyroidism,Screening,Special filter paper,Mental retardation,Prevalence,Iran

Introduction

Congenital hypothyroidism (CH) is the result of a reduction in the production of thyroid hormone or a decrease in the activity of thyroid hormone receptors[1].In 85%of cases,CH caused by a change in thyroid evolution called thyroid dysgenesis that characterized by defect in thyroid gland development or thyroid ectopy [2].Most of the remaining cases (15%) of CH include mild gene mutations (i.e.,dual oxidase,thyroglobulin (TG),GLIS3,thyroid stimulating hormone (TSH) receptor,thyroid peroxidase (TPO),maternal TSH receptor blocking antibodies),prenatal or postnatal iodine deficiency or excess,and so on [3,4].In other cases uses of contraceptives such as anti-thyroid drugs [5],high levels of iodine [6] are the contributing factors in CH.

The hypothalamus-thyroid pituitary axis begins to grow in the mid-embryonic period and continues until birth.In the case of hypothyroidism in the fetus,abnormalities develop in the development of the central nervous system and the fetal skeletal system.Still,in newborn babies,because of the supply of thyroxin through the umbilical cord blood,the mother's blood does not appear to have apparent symptoms [7,8].Of course,it should be noted that new research has found a direct relationship between exacerbation and prolongation of jaundice as nonspecific symptoms in neonatal hypothyroidism [9-11].Also,in cases of severe thyroid hormone deficiency,symptoms usually occur in the first two second weeks of birth.Still,in cases where the hormone deficiency is mild,symptoms may not be seen until months after birth.Thyroid hormone deficiency in the infant causes mental retardation,defects in the body's blood supply,and deficits in the nervous system and skeletal system unless appropriate diagnosis and treatment begin in the baby's early life.Among the factors that cause hypothyroidism in newborns,there is a decrease or no response to TSH (TSH unresponsiveness),failure to concentrate iodide,defects in the peroxides system(defective organography),defect in the synthesis of TG,defect in the iodotyrosine deiodinase enzyme,a defect in the synthesis of T4 and radioactive iodine [12,13].Today,screening in many advanced countries of the world is routinely evaluated through the examination of TSH and T4 blood pressure in the baby's leg or umbilical cord blood or using a blood sample on individual filter papers [14].CH screening studies began in North America in 1972,and gradually and gradually,due to the urgent burden of screening,it is now possible in many countries of the world,including Iran [15].In Iran,for the first time,screening was carried out in 1987 by Azizi and his colleagues in several provinces.Over time,this plan is a comprehensive screening in all hospital-centered hospitals for infants at birth [1].In Nahavand and Kashmar cities,according to the Ministry of Health's notification,the screening plan for infants is done according to the national program.But so far,the results have not been reported to reveal the prevalence and dispersion of it.According to the same population of both cities (200,000 population) and differences in the geopolitical region,Nahavand city is located in the western part of Iran.It has a cold and mountainous climate,and Kashmar is a city in eastern Iran with an arid and desert climate.On the other hand,considering the existence of natural salt lake in Kashmar city,the indigenous population of Kashmar city consumes natural salt in their diet while Nahavand city uses industrial iodized salts.Due to the differences mentioned above,a comparative study of congenital hypothyroidism in Kashmar and Nahavand cities was conducted.

Materials and methods

This is a cross-sectional descriptive study that was performed on neonates born between April 2016 and March 2018 in two cities of Nahavand and Kashmar.All infants born in both cities were included in this study with parental consent.The neonates in this study were born in private and public hospitals by natural vaginal delivery or cesarean delivery.Several drops of blood were collected from the heel of the infant's baby in 3-5 birthdays on a special filter paper with parental consent (S & S903).Became blood samples from the pelvic floor were filtered and dried,premature,low weight (less than 2,500 grams),overweight (4 kg),multiple births,or newborns requiring blood transfusions or any newborn needed to be hospitalized were re-tested after two weeks.

The evaluation of the samples was done by the enzyme linked immunosorbent assay method by evaluating the TSH hormone.Autobio kit,made in China,was used to evaluate the TSH.Infants with a TSH screening test of less than 5 mili units per liter(mlU/L) are healthy.They have no problems with hypothyroidism,but if the screening test is equal to or greater than 5 mlU/L in the first week of birth,re-tested for further investigation.Babies who have been tested for 5-9.9 mlU/L are suspected of being ill and refer to the selected laboratory for further testing for serum testing babies whose screening tests are equal to or greater than 10 mlU/L and T4 ＜6.5 μg/dL,they are referred to a pediatrician or endocrinologist for further investigation.If in a sample of TSH ≥20 mlU/L,simultaneously,in addition to the request for testing,the second treatment begins.If the results of the second experiment were reasonable,the case would be interrupted as transient hypothyroidism,and its treatment would be discontinued.Statistical analysis was performed on the data by SPSS 16.0 software.Descriptive statistics and chi-square test were used for statistical analysis.Values ofP≤0.05 were considered significant[1,16-18].

Results

In this study,a comparative study was performed in the neonatal thyroid screening between newborn infants in private and public hospitals in two cities of Nahavand (west of Iran) and Kashmar (east of Iran)with a population of 200,000 for each city from April 2016 to March 2018.The statistical population of this study consisted of 13,110 infants.During this period,5,700 newborns were born in Nahavand and 7,410 newborns in Kashmar.In the Nahavand city with 5,700 birth,were reported 2,806 (49.3%) girl infants and 2,891 (50.7%) boy infants.Also,in Kashmar city of 7,410 birth,3,486(47.1%)girl infants and 3,924(53%)boy infants.The average participation rate in the National Hypothyroid Screening Plan in the first 3-5 days of birth in Nahavand and Kashmar in two years was 78.7% and 94%,respectively,which indicates higher participation in Kashmar.In both cities,about 95% of newborns with TSH were under 5 mlU/L,so they were healthy in terms of thyroid function.Infants with TSH ＞5 mlU/L summoned for re-testing.Cases with TSH ＞20 mlU/L were summoned for re-sampling of the heel and intravenous sampling (Table1).The frequency of infants with demographic factors of the second summon is listed in Table2.According to Table2,preterm infants and hospitalizations were the most frequency for the second summon.In Table3,the time of the announcement of the suspicious results of the experiment is presented in the first stage in terms of the day.As you can see,the time interval between diagnoses is the most significant determinant factor in the treatment and reduction of the complications of this abnormality,which must be improved and accelerated.Final results of suspected hypothyroidism tests were presented in less than 13 days,with a ratio of 92% in Nahavand city and 85%in Kashmar city.

According to Table4,over 95% of infants in both cities were healthy in the second experiment.In Nahavand city in 2016,25 infants (5 infants with transient hypothyroidism and 20 permanent hypothyroid infants) were diagnosed,also in 2017,20 infants (4 transient hypothyroidism and 16 permanent hypothyroidism) were registered for treatment.The same proportion was reported in Kashmar in 2,195 in 21 cases and 16 cases in 1,396.Nahavand,the incidence of neonatal hypothyroidism in the years 2016 and 2017 was 6.7 and 9.09 per 1,000 live births.And for the city of Kashmar,this figure increased to 5.6 and 4.3 per 1,000 births in 2016 and 2017,respectively.In total,26.6% were in Nahavand and 11%in Kashmar,parents had familial marriages.There was a significant correlation between the amount of TSH level of the studied infants and family marriages in their parents (P＜ 0.001).Also,in 44.4% of Nahavand and 48.5%in Kashmar of the patients had a cesarean delivery that has a significant association with hypothyroidism (P≤0.024).In this study,in both cities,the proportion of male patients was higher than that of the girl.In Nahavand city,64.6% of boys had hypothyroidism,and in Kashmar,this proportion was 51.5%for boys.

Table1 Frequency of newborns based on the age of the sample and the amount of TSH first stage

Table2 Distribution of demographic factors in neonates screened in Nahavand and Kashmar in 2016-2017

Table3 Distribution of screened neonates based on the time of the announcement of the results of the initial test and by year

Table4 Frequency of newborns studied by age of sampling and TSH level of first stage

Discussion

In the city of Nahavand,the incidence of neonatal hypothyroidism in the years 2016 and 2017 was 7.2 and 5.4 per 1,000 live births.And for the city of Kashmar,this figure increased to 4.8 and 2.7 per 1,000 births in 2016 and 2018,respectively.Hypothyroidism in Nahavand is more than Kashmar,while both cities have a high incidence of national and global statistics.In Nahavand and Kashmar cities,the prevalence of hypothyroidism in infants and boys was higher than that of the daughters.In total,26.6% of cases of hypothyroidism were in Nahavand and 11% in Kashmar,their parents had familial marriages,and there was a significant relationship between the amount of TSH in their infants and their relative marriages (P＜0.001).Also,in 44.4% of Nahavand and 48.5% in Kashmar,48.5% of the patients had a cesarean delivery that has a significant association with hypothyroidism (P≤0.024).In this study,in both cities,the proportion of male patients was higher than that of the girl.64.4% of the cases of hypothyroidism were reported in boys and 65.5% of boys in Kashan and Nahavand.

The overall incidence of neonatal hypothyroidism varies from 1 in 3,000 live births to 1 in 4,000 live births.The prevalence of neonatal hypothyroidism is higher in Spanish and Asian populations.In India,the incidence of 2,640 cases in 40,000 live births[19].But in our country,Iran has reported about 1 patient per 1,000 births.In the screening program for neonatal hypothyroidism in Arak,in 2006,revealed a high level of hypothyroidism in the city of this city relative to national and global values.The statistics in the city of Arak in 2006 for hypothyroid babies ranged from 1 to 300,which had a significant difference even with the statistics of the country in the same year that the author increased the disorder to the geographical area and familial marriages and iodine deficiency and genetic status of the area related [20].The results of this study are consistent with our study.In the study of Mazandaran province between 2006 and 2010,congenital hypothyroidism was found to be 1,549 live births.The male was 6% more likely to have hypothyroidism [14].According to different studies,the incidence of this malformation is different in males and females,but in Iran,studies in Sanandaj and south Khorasan indicate more abnormalities in male infants[12].On average,in two years 2018 and 2016,the order in the city of Nahavand was 78.6%,and in the city of Kashmar,94.9% of the neonates participated in this screening period.According to the statistics,the city of Kashmar has had a better partnership in this regard.The results of screening tests showed that about 95% of neonates in both cities had TSH less than 5%.In Mazandaran province,96.6% of neonates with hormone replacement therapy were less than 5%.In another case,in the study of the prevalence of hypothyroidism in babies in Mazandaran province between 2006 and 2016 had a 25 to 75 percent ratio of non-familial family marriage [1].The results of other studies in Iran show that the disease is more pronounced in males.And the incidence varies from place to place [21-25].According to this study in Nahavand,this ratio is 26.6 to 73.4 percent,and in Kashmar,it is 11 to 89 percent.These ratios do not raise the impact of familial marriages of hypothyroidism.

Due to the higher hypothyroidism rate of infants in Nahavand city and considering the consumption of iodized salt in this city (compared to Kashmar city,which uses natural salt without iodine) and due to regional and cultural differences,it is suggested in addition to inspecting iodized salt factories.The next study will address a questionnaire to identify the scientific reasons for this hypothyroid neonatal increase in Nahavand.

Conclusion

Our study shows that the prevalence of hypothyroidism is high in both Kashmar in eastern Iran and Nahavand in western Iran.Especially in Nahavand city of western Iran,where the prevalence of hypothyroidism is higher than global and national statistics.Further studies are needed to clarify the role of iodine deficiency and familial marriages geopolitical region and in a wider context.