Prevalence of congenital hypothyroidism in North Macedonia: data from a newborn screening program conducted for twenty years.

BACKGROUND: Congenital hypothyroidism (CH) is a common endocrine disorder that can be treated if timely detected by newborn screening, optimizing the developmental outcome in affected children. In the present study, we analyze the data of the national newborn thyroid screening program in North Macedonia collected over twenty years, including the CH prevalence as well as its geographical and ethnic variations. METHODS: The thyroid-stimulating hormone (TSH) was measured on a filter paper blood spot sample using the DELFIA fluoroimmunometric assay. A TSH value of 15 mIU/L whole blood was used as the cutoff point until 2010 and 10 mIU/L thereafter. RESULTS: Out of 377,508 screened live births, a total of 226 newborns with primary CH were detected, providing an overall prevalence of 6.0 per 10,000. Lowering the TSH cutoff led to an apparently increased prevalence of the transient CH, from 0.2 to 2.4 per 10,000 live births (p < 0.0001) with an impact on the overall prevalence of primary CH (from 4.0 to 7.1 per 10,000, p=0.0001). Taking ethnicity into account, the significantly highest primary CH prevalence of 11.3 per 10,000 live births was observed among the Roma neonates, with a predominance of permanent CH (75.5%). There were also regional differences in the prevalence of primary CH. The highest primary CH prevalence of 11.7 per 10,000 live births was observed in the Vardar region, together with the highest regional prevalence of the transient CH (3.2 per 10,000). The highest prevalence of permanent CH was observed in the Pelagonia region (6.6 per 10,000) where the largest percentage of the Roma population lives. CONCLUSIONS: The overall CH prevalence is high in North Macedonia, with substantial ethnic and geographical variations. Further analysis to elucidate the causes for the significant variations in the CH prevalence including environmental factors is warranted.

Regional Variation in the Incidence of Congenital Hypothyroidism in Macedonia.

The incidence of congenital hypothyroidism (CH) is increasing in different areas around the world. Potential causes include changes in population ethnic composition, environmental factors, changing screening program methodology and lowering of TSH cutoff levels. The incidence of CH in different regions of Macedonia has not been evaluated before. A total of 251,008 newborns from all eight regions in the country have been screened between 2002 and 2015, by measurement of the thyroid-stimulating hormone (TSH) from blood spots, sampled 48-72 h after birth, using the DELFIA assay. Overall CH incidence confirmed at birth was 1/1976. The highest CH incidence was observed in the Vardar region (1/970), while the Eastern region had the lowest incidence (1/4202; p=0.021). In the other regions, the following CH incidence was detected: Northeastern 1/1459, Pelagonia 1/1627, Polog 1/1444, Skopje 1/2430, Southwestern 1/3226, and Southeastern 1/1843. Interestingly, in the Vardar region, 4.44% of the screened newborns had a TSH concentration > 5 mIU/L, as an indicator of regional iodine deficiency, compared to the Eastern region where 1.66% of newborns had a TSH > 5 mIU/L. The higher CH incidence in some of the regions may be due to increasing exposure to environmental toxic agents and/or deficient iodine intake. Further research into the potential environmental determinants of increased CH risk is warranted.