In this study we aimed to perform a neurodevelopmental evaluation of children with CH, diagnosed by the national screening programme endocrinology, between the ages of 2 and 3 years using Bayley Scale of Infant Development – II (BSID-II).

The study was conducted after approval of the Local Research Ethics Committee of Dr. Behcet Uz Children’s Hospital, and written informed consent was taken from the parents of all study subject.

The study was conducted in the Pediatric Endocrinology Department of Dr. Behcet Uz Children’s Research and Teaching Hospital between May 2012 and May 2013. Children with congenital hypothyroidism, aged 24-36 months old, diagnosed on national screening program were included in the study as the patient group. Patients born preterm were excluded. The control group consisted of healthy children admitted to pediatric polyclinics in the same age-group, who do not have the history of any perinatal or postnatal disease affecting central nervous system. Demographic profile of the children, gestational age, birth weight, history of maternal hypothyroidism, antithyroid drug usage on pregnancy, the etiology of congenital hypothyroidism, level of TSH at the screening test, the severity of congenital hypothyroidism, age at the diagnosis, the initiation time of hormon replacement, the initial dosage of L-thyroxin, the length of the normalization period of TSH, the adherence to the treatment, socioeconomic status of the patients were recorded.

We used SPSS for Windows 19.0 for all calculations. The tests used were Pearson Chi-square test, Mann-Whitney U test, Student’s independent t-test and Kruskal-Wallis test. Probability value of P<0.05 were considered to be significant. Factors possibly affecting neurodevelopmental outcome were evaluated by univariate analysis.

Forty three patients (23 males) with congenital hypothyroidism and 40 healthy subjects were included in the study. There were no significant differences in the baseline characteristics of the two groups (Table I). Mothers of five patients had hypothyroidism and four of them had history of L-thyroxin replacement during pregnancy. Laboratory values and data about treatment of the patient group are given in Table II. Twenty nine of the patients (67.4%) had mild, 7 of the patients (16.3%) had moderate and 7 of the patients (16.3%) had severe congenital hypothyroidism. The mean MDI score of the patient group 92.6 (17.1) was lower than the control group 97.1 (9.7), but this difference was not statistically significant (P=0.14). The mean PDI scores were similar in the two groups 97.8 (15.6) vs 99.1 (10.6) (P=0.66). As per MDI scores, 4.7% and 20.9% of the patients were found to be moderately and mildly retarded, respectively. In terms of the PDI scores, 4.7% each had moderate and mild retardation. There was no patient with severe retardation according to the both MDI and PDI scores.

TABLE I Demographic Profile of the Study Population 

TABLE II	Details of Diagnosis and Treatment Among Congenital Hypothroidism Patients 

TABLE III Results of Univariate Risk Factor Analysis

MDI: mean developmental index; PDI: psychonotoe developmental index.

Using univariate risk factor analysis; the sex, birth weight, level of TSH at the screening test, socioeconomical status, the severity of congenital hypothyroidism, the initiation time of hormone replacement, the initial dosage of L-thyroxin, the length of the normalization peirod of TSH, and the adherence to the treatment were not found to be significantly associated with different MDI and PDI scores (Table III).

In this study of 43 infants diagnosed at birth with congenital hypothyroidism, 16.2% with CH were symptomatic, and the most common symptom was prolonged jaundice. Their neurodevelopmental status follow-up was not significantly different from normally developing peers.

The New England Congenital Hypothyroidism Collaborative reported no apparent specific impediments to learning in such children at 9-10 years of age [8]. In a meta-analysis [9], patients with CH detected by neonatal screening and treated from early age had been evaluated for neuropsychologic development. It showed a trend toward lower intelligence quotient (IQ) and poorer motor skills in CH patients compared with controls [9]. Pooling of the data demonstrated a significant deficit of the mean IQ of 6.3 (95% confidence interval 4.7-7.8) [9]. The most important factor for IQ deficit was found as the severity of the CH. Similar to these findings, some mildly and moderately retarded patients were detected in our study, despite the early diagnosis and treatment. These results suggest that at least part of brain damage in patients with CH is caused in utero and can not be prevented by early treatment.

The severity of CH has been reported to be associated with neurodevelopmental impairment in patients diagnosed by neonatal screening program [10,11]. Our study did not find a significant association with the severity of CH and neurodevelopment, but children in mild CH group had higher mean MDI scores than the moderate and severe CH group and had higher mean PDI scores than severe CH group. In the literature, early initiation of hormone replacement has been shown to positively affect the neurodevelopment [12]. In a review identifying 11 studies evaluating the age of onset of thyroid hormone treatment, infants started "early" (12 to 30 days of age) had been found to have higher IQ scores than infants started "later" (>30 days of age) [14]. In our study, mean (SD) treatment initiation time was not in the "later" category, 20.4 (13.4) days, and MDI and PDI scores did not change with the initiation time of hormone replacement. The effect of the initial dosage of L-thyroxin and the length of the normalization period of TSH on motor and mental development are controversial in the current literature [4,13], and we did not find any effect of the dose. The adherence to treatment is an important factor for neurodevelopmental prognosis [14]; however, we could not find significant association between the adherence to treatment and MDI or PDI scores. Socioeconomical status is also an important factor on neuromotor development [15]. In our study 91% of the patients had medium and high socioeconomical status so MDI and PDI scores were not significantly different.

Babies diagnosed with CH in a national screening program should be under regular follow up for neurodevelopmental status by a multidisciplinary team.

Contributors: BE, BTB, KD, EO, BO: involved in the management of patients; BT: planned the study, collected data, performed statistical analysis and drafted the manuscript; BE: involved in planning of the study and reviewed the script; BB: involved in statistical analysis; FG: involved in planning the study, critically reviewed the manuscript and would act as the guarantor of the study.

Funding: None; Competing interest: None stated.