Intelligence quotient in children with congenital hypothyroidism on treatment: A cross-sectional study

Introduction : Congenital hypothyroidism (CH) is the most commonly identified endocrine disorder. Early intervention can prevent intellectual deficits. Objective: To determine the intelligence quotient (IQ) and aetiology in children diagnosed with CH undergoing treatment and the associations between the IQ and the age of diagnosis. Method : A cross-sectional study was conducted in a tertiary care hospital in Bangalore, which enrolled 52 children aged 6 months to 15 years diagnosed with CH. Using a pre-designed proforma, we collected demographic data and confirmed CH aetiology. For IQ assessment, children under 3 years underwent the Vineland Social Maturity Scale (VSMS) and developmental screening test (DST), while those over 3 years were evaluated with the VSMS and Binet Kamat test of intelligence (BKT). Results : Among the 52 children with CH, dyshormonogenesis was the predominant aetiology. In the under-3-year age group (n=17), all demonstrated average to above-average intelligence. Among those over 3 years (n=35), 10.9% (95% CI: 6.5% to 17.2%) exhibited low average and borderline intelligence with the VSMS, and 5.7% (95% CI: 2.3% to 12.5%) had extremely low IQ (IQ <70). The BKT scale showed 20% (95% CI: 12.8% to 29.7%) with low average and borderline intelligence, and 2.9% (95% CI: 0.7% to 8.3%) with extremely low IQ (IQ <70). Children diagnosed at a mean age of 4.2 and 4.4 years exhibited intellectual disability on the VSMS and BKT scales, respectively. Conversely, those diagnosed at a mean age of 1.2 and 1.8 years showed average and above-average intelligence on the VSMS (p-value 0.02) and BKT scale (p-value 0.001), respectively. Conclusions : Children diagnosed with CH at mean ages of 4.2 and 4.4 years exhibited intellectual disability on the VSMS and BKT scales, respectively. Conversely, those diagnosed with CH at mean ages of 1.2 and 1.8 years ____________


Introduction
Congenital hypothyroidism (CH) is one of the most commonly identified endocrine disorders 1 .It is characterised by a deficiency of thyroid hormone (TH) present at birth 2 .TH is essential for the maturation of the central nervous system from the earliest phases of fetal life until the child is two years old 3 .Globally, CH incidence varies from 1 in 2000 to 4000 live births 1 .Many Western nations have established universal screening programmes since 1970 1,4 .With early and optimal treatment, the IQ is now around 20 points higher than in children born before the screening 1,5 .In 2013, the Indian Council for Medical Research conducted a multicentric study including around 100,000 babies.The findings indicated a greater frequency of CH (1 in 1172) across the country 6 .Numerous studies have indicated a correlation between the onset of treatment and cognitive abilities in individuals suffering from CH 4 .Globally, around 70% of newborns are born outside of areas with recognised newborn screening 1 .As a result, mental retardation caused by CH continues to be a major public health concern 1 .Due to the lack of universal screening, there is a significant research gap in India about the neurodevelopmental outcomes of newborns with CH 7 .This study aims to provide information by examining the intelligence quotient (IQ) of children with CH undergoing treatment in the Indian context and exploring the impact of early diagnosis and intervention.With such measures, it is possible to detect any developmental disability requiring early intervention, ultimately leading to better outcomes for affected kids and preventing intellectual deficits 5 .These data can support the adoption of universal screening programmes.

Objectives
To determine the IQ, identify the common aetiology in children with CH receiving treatment between the ages of 6 months and 15 years, and assess the relationship between IQ and the age of diagnosis and the initiation of thyroid hormone treatment.

Method
This prospective cross-sectional study involved children aged 6 months to 15 years and was conducted at a tertiary care hospital in Bangalore, South India.The study period was from January to September 2020.

Sample size and sampling:
This was calculated using the sample size formula: n=Z 2 S 2 /d 2 .[Z= standard deviation of IQ among congenital hypothyroidism children (Z = 16.323 at 5% alpha error), expected precision (d) =4] 8 .The calculated sample size was 63.
Inclusion criteria: Children diagnosed with CH on treatment for at least 6 months, aged 6 months to 15 years, were included.
Exclusion criteria: Children with chromosomal abnormalities, neurological diseases that could impair IQ, inborn metabolic problems, psychiatric illnesses like ADHD, and sensory deficiencies were excluded.
Data collection: All children with diagnosed CH aged 6 months to 15 years were selected during their routine endocrinology follow-up at a tertiary care hospital in Bangalore, South India.Children included in the study were on treatment for hypothyroidism for at least 6 months and had normal thyroid function levels at the time of IQ testing.The demographic information was gathered using a pre-designed proforma and prior investigation reports of thyroid function tests, ultrasonography of the thyroid gland, and thyroid scintigraphy tests were reviewed.After a detailed assessment of the investigations, the cause of CH was confirmed.
The IQ assessment was done by a certified clinical psychologist.The assessors were blinded to the participant's characteristics.Prior to the actual assessments, a calibration exercise was conducted.This involves having the assessors independently assess a set of participants and then comparing their results.We used a two-tiered approach to assess IQ based on the child's age, with tools validated for the Indian population.Each child was evaluated separately in the presence of their caregiver.Every child's evaluation took between thirty and forty-five minutes.
   On the VSMS scale, children with below-average intelligence and intellectual impairment were diagnosed at mean ages of 3.7 and 4.2 years, respectively.In comparison, children with average to above-average IQ on the VSMS scale were identified at a mean age of 1.2 years (p-value of 0.02) (Table 3).On the BKT scale, children with below-average intelligence and intellectual disabilities were diagnosed at a mean age of 3.6 years and 4.4 years, respectively.In comparison, children with average to above average IQ on the BKT scale were diagnosed at a mean age of 1.8 years (p-value 0.001).(Table 3)

Discussion
Screening for CH at birth is now routine practice in many nations across the world.However, in developing countries where there is no regular neonatal screening, delayed treatment of CH is a common cause of severe neurodevelopmental sequelae.Numerous studies have demonstrated the effectiveness of early newborn screening in normalising the cognitive function of children with CH.This study highlights the significance of early CH detection and treatment, particularly in India.In the present study, 52 children with CH were enrolled, out of whom 17 were below 3 years of age.They had average and above-average IQs, and none of them had a low IQ.Thirty-five children were above 3 years of age, and 9 (17.3%)children had below-average intelligence or an intellectual disability.Out of those 5 (9.6%) children on both scales, only 1 (1.9%) and 3 (5.7%)children had low IQ (IQ <70) on the VSMS and BKT scales, respectively (Table 2).
In our study, the evaluation revealed 40% of children were diagnosed with dyshormonogenesis, 23% with agenesis, 17% with an ectopic thyroid gland, and 19.2% could not be diagnosed due to financial constraints or refusal of tests.Some children were diagnosed elsewhere and were already on treatment; hence, they were not evaluated.Similarly, Kim S, et al 9 study results revealed that 40% had dyshormonogenesis, 17.8% and 6.7% had ectopic and aplasia, respectively.In a study by Hashemipur M, et al 10 , 58.8% had dyshormonogenesis and 42.2% had dysgenesis (agenesis and ectopic) (p<0.05 for dyshormonogenesis vs. dysgenesis).Karamizadah Z, et al 11 found that dyshormonogenesis was the commonest aetiology (57%), followed by dysgenesis (43%).However, a study by Karki S, et al 12 found that thyroid agenesis (42.1%) was the commonest, followed by dyshormonogenesis (31.6%) and ectopic thyroid (26.4%).In the current study, if those 19.2% were diagnosed, then our percentage would have been different.
The age of diagnosis and the start of treatment had a substantial impact on intellectual outcome, as shown by the data in our study.On the VSMS and BKT scales, we discovered that children with a mean diagnostic age of 4.2 and 4.4 years had intellectual impairment (IQ <70) whereas the mean age of diagnosis was 3.7 and 3.6 years, below average intelligence (IQ = 70-89), not amounting to ID on the VSMS and BKT scales, respectively.Yet when diagnosed at a mean age of 1.2 and 1.8 years, average and above-average intelligence (IQ >90) were noted on evaluation with the VSMS and BKT scales, respectively.This was similar to the study done by Kumar MV, et al 13 where the mean IQ was 92.3 and 81.09 in those who were diagnosed after 1 month but before 6 months of age and after 6 months of age, respectively.In a study by Klien AH, et al 14 children treated before three months of age had a significantly higher mean IQ of 89 (range 64-107) than those treated after three months; the mean IQ was 71 (range 35 to 96).LaFranchi SH, et al 15 conducted a meta-analysis of 11 trials, revealing that children who received treatment before the age of one month had a higher IQ.
The study had some limitations.This was a cross-sectional study, where scores on assessments are indicative of current functioning.A small study population was included.There was no control group of normal children.Socioeconomic factors and the education status of caregivers were not considered.The assessment of VSMS and DST is carried out based on parental reports and clinical observation.This could not be supplemented by an objective assessment of BKT for all children.

Conclusions
Children diagnosed with CH at mean ages of 4.2 and 4.4 years exhibited intellectual disability on the VSMS and BKT scales, respectively.Conversely, those diagnosed with CH at mean ages of 1.2 and 1.8 years showed average and above-average intelligence on the VSMS (p = 0.02) and BKT scale (p = 0.001), respectively.

Table 1
Data were entered into a Microsoft Excel data sheet and analysed using Statistical Package for the Social Sciences version 20 software.The statistical analysis was done using the Chi square test and Fisher's exact test for categorical variables.An independent t-test was used for the continuous variables.A p-value <0.05 was considered statistically significant.
For children less than 3 years of age, the Vineland Social Maturity Scale (VSMS) was used to assess adaptive functioning.This assessment yielded a Social Quotient (SQ).In addition, we utilised developmental screening test (DST) to assess developmental functioning, providing a 'Developmental Quotient (DQ).Both the VSMS and DST assessments relied on parental reports and clinical observation of the child.