Relation between TSH and maternal and neonatal demographic factors has received less attention as compared to other factors. Identifying factors that influence TSH variability in infants may help understand abnormal thyroid level contributors at birth. As hypothesized, the newborn screening data were analyzed to study the effect of various maternal and infant factors on the nTSH of newborns. This study suggests that nTSH is influenced somewhat by various maternal and neonatal characteristics. It could be due to the interplay of different other factors for adequate thyroid functioning.
The nTSH value decreases with improvement in ANC check-ups (Fig. 1); this could be a proxy of improved antenatal care and nutrition. Deficiency of dietary iodine is a common cause of congenital and transient hypothyroidism in newborns. Maternal thyroid disease can also cause a suppression of thyroid function in the newborn. During ANC check-ups, thyroid disorders and iodine deficiency are diagnosed and treated, which improves the maternal condition and decreases the risk of thyroid disorders in newborns.
The present study evidenced an increase in nTSH with advanced maternal age (Fig. 2). A study from a rural center in South India demonstrated increased cord blood TSH with advancing maternal age . A prospective cohort study in China also reported similar findings . Another study by Lee et al. reported no significant association between maternal age and nTSH concentration .
A novel finding in our study was that for every 1% increase or decrease in hemoglobin levels, nTSH decreases or increases by 0.31% (Fig. 3), respectively. nTSH exhibited a significant inverse relationship with maternal hemoglobin (Table 2). The possible mechanism in this is impairment of heme-dependent thyroid peroxidase (TPO) enzyme in an iron-deficient state, limiting thyroid hormone synthesis .
It was seen that for every 1 unit increase in parity, nTSH gets elevated by 1% (Fig. 4). On the contrary, in
another study, inverse relation was observed between parity and TSH of newborns . Many studies have reported that first babies have higher nTSH levels than subsequent babies [8,9,10]. The difference may be due to the analysis of TSH in cord blood samples in their study. In contrast, some studies reported no differences in nTSH level according to birth order [11, 12].
For every 1% increase in gestational age, nTSH decreases by 0.23% (Fig. 5). Many previous studies have reported that nTSH levels increase with increasing gestational age [4, 11, 13, 14]. However, an inverse relationship has also been reported [15, 16], and several other studies have reported no difference in nTSH levels with gestational age [6, 12, 17, 18]. A likely explanation would be that the hypothalamic-pituitary response matures with the increase in gestational age. Impaired hypothalamic-pituitary responsiveness is seen in premature infants .
nTSH depicted a significant inverse correlation with every unit percent increase in length at birth. nTSH was found to be reduced by 0.03% (Fig. 6). Some studies showed no relation between birth length and nTSH levels .
The present study revealed a negative correlation with head circumference. With every unit percent change in head circumference, nTSH was expected to alter by 2.6% (Fig. 7). Lee SY found no association between head circumference and newborn TSH .
A significant negative correlation was observed between birth weight and nTSH level in this study. With every 1% increase in birth weight, nTSH was expected to decrease by 0.19% (Fig. 8). The findings agree with the results of Korada M et al., Rao PT et al., Lain SJ et al., and Sahoo et al. [12, 14, 15, 20]. Romagnoli C et al. and Lee SY et al. noted no significant influence of birth weight on nTSH [6, 21]. Birth weight, length, and head circumference are all associated with gestational age. As gestational age increases, growth parameters also increase. So, it is not surprising that hypothalamic-pituitary response is also positively correlated with the above factors.
During pregnancy, many physiological changes occur. Firstly, maternal total or bound thyroid hormone levels increase with serum concentration of thyroid-binding globulin. Second, the level of TSH decreases in early pregnancy because of weak stimulation of TSH receptors caused by human chorionic gonadotropin (hCG) during the first 12 weeks of gestation. Thyroid hormone secretion is thus stimulated, and the resulting increased serum free thyroxine (T4) levels suppress hypothalamic thyrotropin-releasing hormone, which in turn limits pituitary TSH secretion. In the later stage of pregnancy, TSH levels return to baseline values and progressively increase in the third trimester related to placental growth and production of placental deiodinase. These physiologic changes should be responsible for the decrease in TSH of the newborn with improvement in gestation and growth parameters .