European Journal of Cardiovascular Medicine

Congenital hypothyroidism (CH) is a common endocrine disorder affecting approximately 1 in 2000 to 1 in 4000 live births worldwide (1). It is primarily caused by thyroid dysgenesis, dyshormonogenesis, or, in rare cases, central hypothyroidism. If left untreated, CH can result in irreversible intellectual disability and motor development delays due to the essential role of thyroid hormones in brain maturation, particularly during the first three years of life (2,3).

The implementation of universal newborn screening (NBS) programs has significantly improved early detection rates of CH, enabling prompt initiation of levothyroxine therapy within the critical window of neonatal neurodevelopment (4). Several studies have demonstrated that early treatment within the first two weeks of life can normalize intellectual and psychomotor outcomes in most children with CH (5,6). However, despite timely diagnosis and management, some children may still exhibit subtle deficits in cognitive, language, or motor domains, necessitating continued neurodevelopmental surveillance (7).

The variability in developmental outcomes can be influenced by several factors, including the timing of treatment initiation, initial severity of hypothyroidism, adequacy of hormone replacement, and adherence to follow-up protocols (8). Given the lifelong implications of delayed or suboptimal management, assessing the long-term neurodevelopmental trajectories of affected children is crucial.

This study aims to evaluate the neurodevelopmental outcomes of children with CH identified via newborn screening, with a focus on cognitive, motor, and language development during the first three years of life.

A total of 60 children diagnosed with congenital hypothyroidism (CH) through routine newborn screening were enrolled. Diagnosis was confirmed based on elevated thyroid-stimulating hormone (TSH) levels and low free thyroxine (fT4) levels in venous blood samples. Inclusion criteria were: infants with primary CH diagnosed before 30 days of life, initiated on levothyroxine within the first month, and regular follow-up up to at least 36 months of age. Children with genetic syndromes, neurological abnormalities unrelated to CH, or non-adherence to treatment were excluded.

Data Collection
Baseline data including birth weight, gestational age, age at diagnosis, TSH and fT4 values, and age at treatment initiation were recorded. Levothyroxine was administered orally, with dose adjustments based on follow-up thyroid function tests every 4–6 weeks during the first year, and every 2–3 months thereafter.

Neurodevelopmental Assessment
Neurodevelopment was evaluated at 6, 12, 24, and 36 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). This tool provides composite scores for three primary domains: cognitive, motor, and language development. Assessments were conducted by a pediatric psychologist who was blinded to the child’s treatment history to minimize bias.

Statistical Analysis
Data were analyzed using SPSS software version 26. Descriptive statistics were expressed as mean ± standard deviation for continuous variables and as percentages for categorical data. Independent t-tests and ANOVA were applied to assess differences in developmental outcomes based on treatment initiation timing and severity of hypothyroidism. A p-value <0.05 was considered statistically significant.

A total of 60 children diagnosed with congenital hypothyroidism (CH) were followed for 36 months. The mean age at diagnosis was 10.6 ± 4.2 days. Thirty-eight children (63.3%) began treatment within the first 14 days of life, while the remaining 22 (36.7%) started therapy between days 15 and 28. The baseline characteristics are detailed in Table 1.

Table 1. Baseline Characteristics of the Study Population

Neurodevelopmental outcomes at 36 months were assessed using the Bayley-III scales. Children who started treatment within 14 days demonstrated higher mean scores in all domains compared to those who initiated therapy after 14 days (Table 2). The differences in cognitive and language scores were statistically significant (p < 0.05).

Table 2. Neurodevelopmental Outcomes at 36 Months

At 36 months, 54 children (90%) scored within the normal developmental range in all domains, while 6 children (10%) exhibited mild delay in one or more areas, predominantly in language development. No cases of moderate or severe delay were recorded.

Overall, earlier initiation of therapy correlated positively with better cognitive and language performance, as shown in Table 2, suggesting the importance of prompt diagnosis and treatment in minimizing neurodevelopmental impairment.

The present study demonstrates that early diagnosis and timely initiation of levothyroxine therapy in infants with congenital hypothyroidism (CH) result in largely favorable neurodevelopmental outcomes by 36 months of age. Our findings align with existing evidence indicating that early thyroid hormone replacement can effectively support normal cognitive, language, and motor development in most children with CH (1–3).

Children who began treatment within the first 14 days of life exhibited significantly higher cognitive and language scores compared to those whose treatment was delayed beyond two weeks. These observations are in agreement with previous studies, which suggest that the timing of therapy initiation is a critical determinant of long-term neurological prognosis (4,5). Rovet and Walker reported that initiating treatment within the first two weeks could normalize IQ scores, while delays were associated with measurable cognitive deficits (6).

The use of the Bayley Scales of Infant and Toddler Development (Bayley-III) allowed comprehensive assessment across multiple domains of early development. In our cohort, 90% of children achieved scores within the normal range, reflecting the efficacy of newborn screening programs and adherence to treatment protocols. This outcome is comparable to studies from both high-income and resource-limited settings, which have demonstrated similar success when treatment is initiated promptly and monitored regularly (7–9).

However, a small proportion (10%) of our sample exhibited mild language delays despite early intervention. This trend has also been reported in other studies and may be attributed to factors such as suboptimal dosage adjustments, poor compliance, or underlying genetic susceptibility (10,11). Additionally, the severity of hypothyroidism at diagnosis has been linked to residual language or attention deficits, even with adequate treatment (12).

Although the mean motor scores did not significantly differ between early and late treatment groups, this may reflect the relatively less complex neurobiological basis of motor skills compared to cognitive or linguistic development (13). Continuous follow-up into school age is essential to determine whether these early advantages are maintained or if new challenges emerge later in childhood.

Our study is strengthened by its prospective design and standardized neurodevelopmental assessments; however, it is not without limitations. The relatively small sample size and short follow-up period limit the generalizability of results. Moreover, environmental factors such as parental education, socioeconomic status, and home stimulation were not controlled, though they are known to influence developmental outcomes (14,15).

In conclusion, our findings reinforce the vital role of newborn screening and early initiation of levothyroxine therapy in promoting optimal neurodevelopment in children with CH. These results underscore the need for timely detection, meticulous dosing, and long-term follow-up to ensure comprehensive developmental support.

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