Implementation of CH screening program has been greatly facilitated its early detection and treatment which result in normal psychomotor development of the infants affected with CH. Though this program in our region was successful in achieving the mentioned goals, it seems that considering the high prevalence of CH, etiological studies are necessary for an appropriate screening program. So, in this study, the prevalence of positive TRAb in neonates with and without CH and their mothers was determined. The prevalence of positive TRAb in neonates with CH and their mothers was significantly higher than in the control group and there was significant correlation between TRAb and CH in our studied population.
Several studies have investigated the role of autoimmunity in the etiology of CH by focusing on different autoantibodies, of which TRAb seems to be more specific. So, we evaluated the role of TRAb in the etiology of CH.[16
Ordookhani and colleagues in their study regarding the etiologic factors of transient CH in Tehran have not reported any significant relation between TRAb antibody and transient CH. They concluded that iodine excess is considered as the most important factor in this field.[22
In a case report in the UK, Evans et al
. have reported a case of neonate with CH with positive TRAb. The cause of CH was maternal transplacental passage of TRAb. Though the level of TRAb was decreased in the neonate's serum to normal range within 3–4 months after birth, the thyroid function did not return to normal till 16 months of age. They concluded that maternal TRAb antibody during pre-and postnatal period could delay the development of thyroid gland and result in transient CH. Thyroid replacement therapy is necessary for these neonates and it should be continued until the normal thyroid function is resumed even when the autoantibody is not detectable in serum.[17
In another report from Greece, Mengreli and colleagues studied 173 neonates with CH (157 permanent and 16 transient forms of CH) out of 508,358 screened ones. The prevalence of positive TRAb among all the studied neonates with CH was 5.8% and it was 31.2% and 2.9% in transient and permanent forms, respectively. The prevalence of TRAb was significantly higher in the transient form of CH compared with the permanent form and control healthy neonates (1.9%). According to their findings, transient CH caused by maternal–fetal transfer of TRAb is considered a rare condition with a prevalence of 2.7% of all cases with CH. But its diagnosis, i.e. detection of transient CH cases due to maternal-fetal transfer of TRAb, is an important issue in CH screening. However, detecting these cases is useful for genetic counseling and preventing the occurrence of transient CH, especially in subsequent offspring, and consequently neurodevelopmental abnormality of the fetus.[16
In contrast, in the study of Ginsberg et al
. in 15 neonates with diagnosed CH, only one of their mothers had positive TRAb and they concluded that transplacental transfer of TRAb had no significant role in the development of CH.[23
In a recent study conducted in Wales, Evans et al
. have reported that from seven neonates with transient CH, TRAb was positive in the mothers of all patients. They indicated that identifying neonates with CH due to maternal TRAb is important for optimizing CH screening programs.[24
The reported prevalence of positive TRAb was different in different studies. In a study, during the screening of over 1 million babies, the prevalence of transient CH due to this autoantibody was reported to be 2% and it was detected in the serum of all mothers of transient CH cases.[25
] The prevalence of positive TRAb was 5.5% in neonates with CH and 7.1% in their mothers in a study conducted in Italy.[26
] It was positive in 8.2% of infants with CH and 6.5% in their mothers in a survey conducted in Germany.[13
In the current study, the prevalence of positive TRAb was 80% and 81.5% in neonates with CH and their mothers, respectively. It seems the prevalence of CH due to TRAb is significantly higher in our studied population in comparison with others. The results obtained could be explained as follows. Considering that TRAb which is found in infants’ circulation gradually clears by 3–4 months of age, we studied neonates who were primarily diagnosed with CH and it included both transient and permanent forms, whereas the permanency of CH would be determined in 3–4 years of age. But considering the high rate of transient CH in one study among this population (40.2%),[21
] the high rate of positive TRAb may be due to the high rate of cases with transient CH.
On the other hand, a recent study in Isfahan among this population indicated that iodine excess is considered as one of the possible factors for the high prevalence of CH in our community.[27
] Iodine excess has an important role in inducing thyroid autoimmunity,[28
] so it seems that it is one of the responsible factors for our findings. However, the different laboratory methods and ethnic variation should also be considered.
In this study, there was no significant relationship between TRAb and neonatal TSH level and maternal TSH level. Our results are similar to the results of Mengreli et al
] In a recent study conducted in mice, Postiglione et al
. showed that TSH or a functional TSH-R is not an essential factor for the development of a normal thyroid gland during prenatal period in utero
] However, further studies are needed in this field.
To conclude, the findings of this study indicate the role of TRAb in the etiology of CH in this population. It emphasizes the importance of screening of thyroid autoimmune disorders among mothers during pregnancy or CH screening program for preventing some autoimmune cases of CH. But for more conclusive results, it is recommended to evaluate the role of this autoantibody and also other autoantibodies in permanent and transient cases separately.