Evaluation of Iodine deficiency hypothyroidism in relation to neurodevelopmental outcome of children 5-9 years of age in the estates of Rathnapura district

Abstract

INTRODUCTION: The objective of this project was the assessment of Iodine deficiency hypothyroidism in relation to neurodevelopmental outcome of children 5-9 years of age in the estates of the Ratnapura district. This study consisted of development and validation of a tool to assess neuro-developmental outcome of children 5-9 years of age, a cross sectional study at baseline to determine iodine levels in household salt samples, a descriptive cross sectional study to determine the prevalence of poor neuro-developmental outcome and hypothyroidism, a case control study to identify risk factors of poor neuro-developmental outcome in children 5-9 years of age and a cross sectional study to determine iodine levels in water samples in selected estates in the Ratnapura district. METHODS: The development and validation of neuro developmental assessment tool was conducted in two stages. In stage one modifications were made to Griffiths'Mental Development Scale (GMDS) to adapt it to the Sri Lankan setting. The ROC curve analysis was used to determine the cutoff Genera! Quotient value to identify normal and poor neuro- developmental outcom.es. In stage two, 100 primary school children selected from the Ragama MOH area were tested using the new tool and the identified GQ cutoff value. The characteristics of salt usage and potable water sources in 1683 households in 20 randomly selected estates of the Ratnapura district were assessed in the selected estates, using a pre-tested interviewer administered questionnaire.. During the baseline survey, salt samples (n~1683) were tested for adequate iodine concentration (>30ppm of Iodine) by using a standard rapid iodine test kit. Using the validated neuro-developmental outcome assessment tool based on Griffiths Mental development scale, 1683 children were assessed for poor neuro-developmental outcome. Blood samples (2ml each) and a history relevant to hypothyroidism of 519 randomly selected 5-9 year old children from the same estates were obtained after obtaining informed written consent from the parents and/or guardians. TSH levels were assayed using the Immulite 3rd generation TSH Chemilu mines cent Immunometric assay. Water samples from 23 identified sources (wells, rivers and springs) were obtained and analyzed for iodine (I) levels by the catalytic reduction method. Based on neuro-developmental assessment screen, 64 children were randomly selected from the poor neuro developmental outcome group and 256 children (all in the 5-9 year age group) were selected from the normal neuro developmental outcome group to determine risk factors of poor neuro developmental outcome using a case control design. Data were analyzed using Statistical Package for Social Sciences 13 (SPSS) (SPSS 13.0, Chicago, Illinois, USA). Significance was considered when the p-value <0.05. Ethical clearance was obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya. RESULTS: In the validation study a cut-off GQ value of 00 (p<0.05) best differentiated children with poor and normal neuro-developmental outcome (sensitivity 100% and specificity 100%). The commonest source of household salt products was the retail shop (36.4%). Salt powder (54.5%) was preferred more than salt crystals (44.5%), 80% of households did not wash salt crystals before use. In 9.6% of households salt was kept near the fire place. Salt was commonly stored in in glass bottles (19.3% in brown coloured bottles and 38.8% in clear bottles). 88.7% of household salt samples had adequate iodine levels (Iodine>30ppm). When salt crystals were washed or salt was kept near a fire place, the salt iodine concentration was significantly lower as compared to when salt was kept away from a fire place or when salt crystals were not washed before use (p<0.01). There was a significant difference in the mean TSH levels between poor and normal neuro-developmental outcome children in each age category (pO.OOl). 9.4 % (n=159) of children had a GQ< 100. 3.7% (n-19) of children had a TSH level >5.4u.IU/ml and 1.2% of children TSH level < 0.6[iIU/ml. 2.1% of children had both poor neuro developmental outcome and a TSH level >5.4nIU/ml. 15.8% of children had clinical symptoms of hypothyroidism. Goiter was visible or palpable in 15.7% of children who had TSH levels >5.41uIU/ml. Poor neuro developmental outcome (57.8%) and a history of consuming inadequately iodized salt (63.1%) were prominent feature among children who had TSH levels above normal limits. The prevalences of subclinical hypothyroidism and subclinical hyperthyroidism in 5-9 year old children were 3.08% and 0.76% respectively. The prevalences of hypothyroidism and hyperthyroidism in these children were 0.578% and 0.385%, respectively. The main source of potable water was water springs (83.7%). Low altitude spring water had a significantly higher Iodine concentration than those located at higher altitudes (p=0.002). The mean iodine levels of spring water was significantly lower than that of other sources (p=0.0001). A serum TSH concentration >5.41 uTU/ml (OR=5.325; 95% CI 1.425-19.898), consumption of adequately iodized salt products (OR=0.021; 95% CI 0.011-0.041), meconium aspiration (OR=5.094; 95% CI 1.633-15.889) and introduction of formula milk before completion of 6 months of age (OR-6.330; 95% CI 1.862-21.518) were significant predictors of poor neuro-developmental outcome of 5-9 year old children in the estates of the Ratnapura district. CONCLUSION: The developed neuro developmental outcome assessment tool is a valid and reliable instrument to screen neuro developmental outcome of Sri Lankan children aged 5-9 years of age. The majority of the estate population in the Ratnapura district had access to adequately iodized salt. Storing salt near the fire place and washing salt crystals before use reduced the iodine concentration of salt. Children with poor neuro- developmental outcome had significantly higher serum TSH levels than normal children. The majority of children with high TSH levels had features of subclinical hypothyroidism; poor neuro-development outcome was a common feature among them. The iodine concentration of spring water was significantly lower than in other sources and the Iodine levels of spring water were higher at lower altitudes as compared to those at higher altitudes. Sub clinical hypothyroidism is a major risk factor for poor neuro-developmental outcome of children. Consumption of adequately iodized salt will reduce the risk ofpoorneuro-developmental outcome among children 5-9 years of age.