Geographic Variations in the Incidence of Congenital Hypothyroidism in China: A Retrospective Study Based on 92 Million Newborns Screened in 2013–2018
Congenital hypothyroidism (CH) is a significant endocrine disorder that can lead to intellectual disability and developmental delays if not diagnosed and treated early. Despite its critical importance, the geographic variations in CH incidence across different administrative levels in China have remained largely unexplored. This study aimed to provide an updated incidence rate of CH in mainland China and reveal its spatial patterns, which could aid in the planning and implementation of preventative measures.
The data for this study were derived from the Chinese Newborn Screening Information System (CNBSIS), which included information from 245 newborn screening centers across 30 provinces. A total of 91,921,334 neonates were screened between 2013 and 2018, and 42,861 cases of primary CH were identified, yielding an overall incidence of 4.66 per 10,000 newborns screened (95% confidence interval [CI]: 4.62–4.71). The study employed various spatial analysis methods, including Global Moran I and Getis-Ord Gi statistics, Kriging interpolation, and Kulldorff space scanning, to examine the spatial distribution and clustering of CH cases at both provincial and city levels.
The findings revealed significant geographic variations in CH incidence across China. Neonates in the central (risk ratio [RR] = 0.84, 95% CI: 0.82–0.85) and western districts (RR = 0.71, 95% CI: 0.69–0.73) had a lower probability of CH cases compared to those in the eastern region. The CH incidence exhibited a moderate positive global spatial autocorrelation (Global Moran I value = 0.394, P < 0.05), indicating that CH cases were significantly clustered in spatial distribution. A most likely city-cluster (log-likelihood ratio [LLR] = 588.82, RR = 2.36, P < 0.01) and 25 secondary city-clusters of high incidence were identified. The most affected province and city were Zhejiang Province and Hangzhou city, respectively.
The study also highlighted the importance of environmental factors in the occurrence of CH. The higher incidence in the eastern region, particularly in coastal areas, could be attributed to factors such as air pollution and iodine intake. For instance, maternal exposure to fine particulate matter (PM2.5) during gestation has been associated with an increased risk of CH. The Yangtze River Delta region, known for its high levels of urban expansion and air pollution, was identified as a high-risk area. Additionally, the consumption of iodized salt in coastal areas, where seafood is abundant, could lead to excessive iodine intake, which has been linked to transient CH.
The spatial distribution of CH incidence at the city level revealed a clear gradient from the northwest to the southeast of China. The incidence in Hangzhou, Zhejiang (18.72 per 10,000 newborns screened) was 17 times higher than that in Aksu Prefecture, Xinjiang (1.10 per 10,000 newborns screened). The study also found significant variations in CH incidence within the same provinces. For example, the northern part of Zhejiang had a higher incidence than the southern part.
The spatial clustering analysis identified one most likely cluster and 25 secondary clusters encompassing 38 cities. The most likely cluster was centered on Jiaxing, Zhejiang (30.84 N, 120.93 E, with a radius of 75.38 km) and included five cities (Shanghai, Hangzhou, Suzhou, Huzhou, and Jiaxing). This cluster had 2181 total CH cases and 966 expected cases under the null hypothesis of no clusters (RR = 2.36, LLR = 588.82, P < 0.01). The secondary clusters were mainly located in Shandong (7/25 clusters) and Zhejiang (3/25 clusters). One cluster crossed the provincial border, involving the cities of Xuzhou and Linyi in Shandong and Jiangsu provinces.
The study also discussed the potential impact of differences in screening methods and recall rates on the observed variations in CH incidence. For example, the eastern region, which had more sensitive testing methods and lower thyroid-stimulating hormone (TSH) cut-off values, detected more cases of transient CH, leading to a higher reported incidence. Additionally, the recall and follow-up rates were higher in the east due to better socioeconomic conditions and more advanced healthcare infrastructure.
The findings of this study have important implications for public health policy and resource allocation. The identification of high-risk areas for CH can help target preventive measures and ensure that affected neonates receive timely diagnosis and treatment. The study also underscores the need for further research into the environmental and genetic factors contributing to CH, particularly in high-incidence regions.
In conclusion, this study provides a comprehensive overview of the geographic variations in CH incidence in mainland China. The results highlight the importance of spatial analysis in understanding the distribution of CH and identifying high-risk areas. The findings can inform public health strategies and contribute to the prevention and control of CH in China. Future research should focus on the environmental and genetic factors associated with CH to further elucidate its etiology and improve prevention efforts.
doi.org/10.1097/CM9.0000000000001613
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