Hypothyroidism is a relatively common condition among pregnant women [1,2]. During pregnancy, thyroid gland is subjected to stress and undergoes adaptation to maintain sufficient output of thyroid hormones for both the mother and the fetus [3]. In iodine-deficient areas like sub- Himalayan belt, predominant cause of hypothyroidism among pregnant women is iodine deficiency [5]. Studies have established the link between maternal hypothyroidism and adverse neurobehavioral outcome of the affected child [6]. Most of such studies were conducted in iodine sufficient areas where autoimmune thyroiditis is a predominant cause of hypothyroidism. We aimed to study the relation between maternal overt hypothyroidism and neurodevelopmental outcome of neonates in an iodine deficient region [7] of Northern India (Kashmir valley).

In each trimester, estimation of serum TSH and free thyroxine (FT4) levels were done by chemiluminescence method. Simultaneously, 3 mL of urine was also collected in each trimester and immediately stored at –700C for urinary iodine estimation. Urinary iodine estimation was done by Sandell-Kolthoff reaction principle and all the stored samples were processed together at the end of study period. All the enrolled neonates underwent thyroid screening anytime from 2nd day to 6th day of life by above mentioned method. Levels less than 10 mU/L were considered to be normal, 10-20 mU/L were considered borderline and >20 mU/L were labelled as abnormal. Borderline group was recalled for estimation of thyroid status after 2-4 weeks.

This hospital-based study comprised of 82 mothers with hypothyroidism and 51 control mothers. The mean (SD) age of cases and controls was 29.4 (3.5) and 29.9 (3.4) years, respectively. Table I compares anthropometric parameters in case and control neonates. Table II presents thyroid function tests in the mothers in 1st, 2nd and 3rd trimester. The mean TSH in group A was higher in 1st trimester than Group B and controls but the difference was statistically insignificant in 2nd and 3rd trimester. First trimester FT4 levels were lower in group A compared to group B pregnant women and controls. In all three groups, mean urinary iodine excretion in all trimesters was less than 150 µg/dL. Total T4 was significantly higher in group A and Group B Neonates than control neonates. The mean (SD) NABS score in group A [19.6 (2.15)] was significantly lower than group B [21.3 (3.72)] (P.0.037) and group C [24.0 (3.20)] (P <0.001). Moreover, the NABS scrore in group B was also significantly lower than controls (P<0.001).

TABLE I Anthropometric Parameters in  the Three Groups 

TABLE II  Comparison of Thyroid Function Parameters [Meadian (IQR)] in the Three Groups

Our study demonstrates that iodine deficiency is still prevalent in our population and iodine intake in our pregnant women is inadequate as median urinary iodine level was less than recommended median value of 150 µg/L [8] in all the 3 groups of patients. We also demonstrated that neurobehavior development of neonates born to hypothyroid mothers is lower in comparison to euthyroid mothers.

These results are in agreement with an earlier study [6] in which maternal hypothyroxinemia (low FT4, normal TSH) in the first trimester was associated with decreased NBAS (orientation) scores. However, this study was conducted in an iodine-sufficient area and included women with hypothyroxinemia of pregnancy with no overt hypothyroidism. Mothers in our study were overt hypothyroid with markedly elevated TSH and decreased FT4 in first trimester, and most of them were on thyroxine replacement.

The limitation of our study was that neurobehavioral assessment in our cohort was done between 3-4 weeks of postnatal age that may not be representative of future neurodevelopment of a child. Studies where assessment was done at a later age also support this observation [9,10]. Long term follow-up studies evaluating the causal link between maternal hypothyroidism and adverse neurodevelopmental outcome in the affected offsprings are required.

To conclude, our study suggests an important link between early maternal hypothyroidism and neurobehavioral outcome of affected offsprings. We recommend early identification of hypothyroidism in pregnant women, especially in endemic areas. and their optimal treatment to improve developmental outcome of their children.