This case-control study was performed to identify the risk factors for CH as a multifactorial disease in East Azerbaijan province. In this study, the incidence rate of CH from the beginning of 2011 to the end of 2013 was 1 in 545 live births. In comparison, similar studies around the world have reported an incidence of 1 in 2020 live births in Egypt , 1 in 2700 live births in Italy , and 1 in 3447 live births in Australia . Therefore, it seems that the incidence rate of CH in East Azerbaijan Province is higher than in other countries. In Iran, a systematic review and meta-analysis study across all provinces revealed that the incidence rate of CH is 2 per1000 (ranged 1 to 3 in 1000) live births .
It is possible that high rates of consanguineous marriage with an associated risk of hereditary thyroid hormone deficiency and ethnicity are important factors in increasing the incidence of CH in this province [14, 15]. The cut-off levels used in different screening programs may also influence the incidence rate [16, 17]. For example, the incidence of permanent CH in Greece  was reported at 1:1758 and 1:2441 with TSH cut-off levels of 10 and 20 mU/L, respectively.
Throughout Iran, a cut-off level of TSH = 10 mU/L is used for screening . Therefore, it seems that the higher incidence of CH in East Azerbaijan province is attributed to other genetic and environmental factors. In this study, we found that almost 60% neonates with CH had transient CH. These results suggest neonates with CH should be followed up for a longer period to rule out transient CH. However, most studies have only included permanent CH patients [10, 20].
This study showed that history of CH in first-degree relatives, consanguineous marriage, neonatal jaundice, and birth height is associated with an increased risk of CH. Moreover, in transient CH, in addition to the above-mentioned risk factors, the use of Betadine in the pregnancy and the gestational age are also associated with an increased CH risk.
One of the most important risk factors identified in this study and other national studies [6, 21] is the history of CH in first-degree relatives and consanguineous marriage. The frequency of history of CH in relatives was 11.5% in the case group and 1.5% in the control group. This risk factor had the highest OR for both transient and permanent CH, which is in line with the other studies from Iran [15, 22] as well as other countries . Previous studies have shown that the risk of CH is higher in Asian families than in other races , which may be related to a higher prevalence of consanguineous marriage. These results support the evidence for the strong effect of the genetic factors in the pathogenesis of transient and permanent CH. The genetic disorders causing hypothyroidism, such as dyshormonogenesis, show an autosomal recessive transmissions pattern . Therefore, a history of thyroid disease in other family members can be one of the main risk factors for CH, and it is important to pay attention to family history in pregnant mothers.
In the present study, 30.9% of the neonates with transient CH and 38.2% of the neonates with permanent CH (as compared to 11.3% healthy controls) suffered from neonatal jaundice. Other similar studies have also reported a similar association between neonatal jaundice and CH .
This study, consistent with the findings of a previous study , showed a significant association between the birth length and the incidence of transient and permanent CH. The incidence of permanent and transient CH was higher amongst neonates with short height as compared to neonates with normal height. Khammarnia and colleagues also showed similar results with a two-fold increased risk of CH among children with short height than those with normal height .
In the present study, 53.5% of neonates with transient CH were boys and 46.5% girls, with male to female ratio of 1.14. In permanent CH, male to female was 1.19 (54.5% boys and 45.5% girls). In our study, there was no significant difference between male and female sex among neonates with CH. Zainalzadeh et al. also found no gender difference in the incidence of CH in a study from East Azerbaijan province . In most case-control studies, the sex factor has been included as a matched variable . However, other studies indicate the role of the female gender as a risk factor for CH [29, 30].
In this study, there was no relationship between maternal age and transient or permanent CH, similar to previous studies showing a lack of relationship between mother’s age and CH . In contrast, Khammarnia and colleagues  showed that infants born to young mothers were at an increased risk of CH, Harris et al. found that infants born to mothers aged 40 years or older had an increased risk of CH .
This study showed no significant association between birth weight and transient or permanent CH, as shown by Khammarnia et al. previously .
In our study, Betadine usage in the pregnancy was a risk factor for transient CH. Other studies from Iran have shown similar results . Studies have shown that iodine (present in Betadine) has an inhibitory effect on thyroid hormone secretion . The use of iodine-containing substances during pregnancy can be absorbed into the mother’s blood and secreted in breast milk. Therefore, newborns are more exposed to iodine through the breast milk . Use of iodine-containing substances, such as vaginal Betadine, due to rapid absorption through the skin and mucosa, and immediately crossing through the placenta, can cause an increase in iodine level in mothers and, consequently, in newborns .
This study also showed an association between gestational age at birth and CH. Previous studies have examined the relationship between CH and gestational age at birth. Medda et al in a study from Italy showed that only a gestational age at birth above 41 weeks to be significantly associated with CH . In the study by Abedi et al , gestational age at birth, after controlling the effects of other variables in multiple regerssion analysis, was not significantly associated with permanent CH; however, gestational age at birth was found to be a risk factor for transient CH.