Increased incidence of congenital hypothyroidism in China: An analysis of 119 million screened newborns.

Despite the lack of nationwide epidemiological studies, congenital hypothyroidism (CH) incidence in China has increased. We aimed to evaluate the trends of CH and the possible reasons behind them. Data from screened newborns from the Chinese Newborn Screening Information System from 2012 to 2019 was collected. We applied the Bayesian hierarchical Poisson regression model and meta-analysis to estimate incidence or proportion over the years. The estimated CH incidence increased from 4.01 per 10,000 births in 2012 to 5.77 per 10,000 births in 2019. The average annual growth rate (ARG) of CH incidence for all provinces varied from 0.59 to 20.96%. The most rapid rise in incidence was observed in cases with an initial thyroid stimulating hormone (TSH) concentration of < 10 mIU/L. The meta-analysis results showed that the proportion of permanent CH increased by 0.024% (95%CI: 0.011%, 0.037%) annually. Each 1 mIU/L decrease in TSH cutoff value was associated with a 2.96% increase in CH incidence. In the same period, the proportion of premature CH cases increased from 6.60 to 9.10%, which was much higher than the increase in preterm births. A significant relationship was not found between provincial growth rates in screening coverage and provincial baseline incidences of CH.  Conclusion: CH incidence has substantially increased in China. The slight adjustment of the TSH cutoff value and increasing preterm birth rate contribute to such a trend; however, the contribution is limited. What is Known: • An uptrend in congenital hypothyroidism (CH) incidence has been reported in many European and American countries in the last two decades; however, no studies have been conducted in China to explain the increased CH incidence. • We provide a detailed epidemiological report on the trends of CH during 2012-2019 in China, with an attempt to explore the reasons behind it. What is New: • This first-ever national-wide epidemiological report in China showed an uptrend in CH incidence with variations over regions and CH subtypes. The mild lowering of TSH cutoff values and the increasing preterm birth rate contributed to this uptrend.

Global prevalence of congenital hypothyroidism among neonates from 1969 to 2020: a systematic review and meta-analysis.

Little is known about the global prevalence of congenital hypothyroidism (CH), though it is known to vary across countries and time periods. This meta-analysis aims to estimate the global and regional prevalence of CH among births between 1969 and 2020. PubMed, Web of Sciences, and Embase databases were searched for relevant studies between January 1, 1975, and March 2, 2020. Pooled prevalence was calculated using a generalized linear mixed model, and expressed as a rate per 10,000 neonates. The meta-analysis involved 116 studies, which analyzed 330,210,785 neonates, among whom 174,543 were diagnosed with CH. The pooled global prevalence of CH from 1969 to 2020 was 4.25 (95% confidence interval (CI) 3.96-4.57). The geographic region with highest prevalence was the Eastern Mediterranean (7.91, 95% CI 6.09-10.26), where the prevalence was 2.48-fold (95% CI 2.04-3.01) that in Europe. The national income level with the highest prevalence was upper-middle (6.76, 95% CI 5.66-8.06), which was 1.91-fold (95% CI 1.65-2.22) that in high-income countries. Global prevalence of CH was 52% (95% CI 4-122%) higher in 2011-2020 than in 1969-1980, after adjusting for geographic region, national income level, and screening strategy.  Conclusion: The global prevalence of CH increased from 1969 to 2020, which may reflect the implementation of national neonatal screening, neonatal testing for thyroid-stimulating hormone, and a lowering of the diagnostic level of this hormone. Additional factors are likely to be driving the increase, which should be identified in future research. What is Known: • Cumulated evidence had suggested that the occurrences of congenital hypothyroidism (CH) among newborns were varied in different countries.. • Up-trends of the birth prevalence of CH were observed in many European and American countries. What is New: • This is the first meta-analysis to estimate global and regional prevalence of CH among newborns. • The global prevalence of CH has increased by 127% since 1969. The Eastern Mediterranean has the highest prevalence and stands out with the most pronounced escalation in the prevalence of CH.

Non-invasive prenatal testing for the detection of trisomies 21, 18, and 13 in pregnant women with various clinical indications: A multicenter observational study of 1,854,148 women in China.

OBJECTIVE: This study aimed to evaluate the performance of noninvasive prenatal testing (NIPT) for detecting three common trisomies (T21, T18, and T13) in pregnant women with diverse clinical indications. METHODS: Frequencies of NIPT, of high chance of having one of the three trisomies, and of confirmed trisomies were determined for women with each of seven clinical indications in a national cross-sectional survey of approximately 300 prenatal diagnosis centers. Data were collected for the period from October 1, 2016 to September 30, 2018 using the Prenatal Diagnosis Technology Management On-line Information System. The performance of NIPT for detecting the three trisomies in pregnant women with different clinical indications was assessed in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value, and the corresponding 95% confidence intervals. RESULTS: A total of 5766 true positive cases for T21, T18, and T13 were detected among 1,854,148 samples, giving an overall detection rate of 0.31% (95% CI: 0.30%-0.32%). Most positive cases were associated with "NT thickening" (1.18%) and "advanced maternal age" (0.51%). The detection sensitivities of NIPT were 99.60% for T21, 99.14% for T18, and 100% for T13, while the corresponding specificities were 99.90%, 99.94%, and 99.95%. The corresponding PPVs were 69.77%, 47.24%, and 22.36%. NIPT showed high sensitivity and specificity, regardless of clinical indication. In contrast, PPV for three trisomies varied widely between 9.09% and 66.46% depending on the clinical indication. Across seven clinical indications, PPV ranged from 50.62% to 73.09% for T21, 20.00%-58.33% for T18, and 4.17%-47.37% for T13. The highest PPVs were 73.09% for T21 in pregnancies involving "advanced maternal age", 58.33% for T18 in pregnancies with "NT thickening", and 47.37% for T13 in pregnancies with "NT thickening". CONCLUSIONS: NIPT shows high sensitivity and specificity for detecting T21, T18, and T13 in pregnant women with different clinical indications. However, PPV depends strongly on clinical indication, highlighting the need to strengthen education and genetic counseling about prenatal screening.

Newborn hearing screening coverage and detection rates of hearing impairment across China from 2008-2016.

BACKGROUND: Newborn hearing screening (NHS) can reduce the economic and social burden of hearing impairment. To track the progress of the goal set by the National Program of Action for Child Development (NPACD) and to estimate the detection rates of hearing impairment, the present study examined NHS coverage in 2008-2010 and 2016 and the detection of hearing impairment across China in 2016. METHODS: Licensed medical institutions across China were surveyed in 2012 and 2018 by the National Center for Birth Defects Monitoring of China to collect data for the 2008-2010 period and for 2016 on live births, initial screening rates (total and referral), secondary screening rates (total and referral), and rates of hearing impairment diagnosis among infants who were referred in the secondary screening. To calculate universal newborn hearing screening (UNHS) coverage, the number of newborns who received NHS within 4 weeks after birth was divided by the number of live births. The detection rate of hearing impairment was calculated by combining referral rates on primary and secondary screening with the rate of diagnosis. RESULTS: National UNHS coverage increased from 29.9% in 2008 to 86.5% in 2016, with different regions showing different increases. During this period, the number of provinces with UNHS coverage over 90.0% increased from 2 to 17, with UNHS coverage in 2016 being substantially higher in eastern provinces (93.1%) than in western provinces (79.4%). In 2016, the detection rate of hearing impairment across the country was 0.23% (95% CI 0.15-0.25%), and it varied from 0.17% in western provinces to 0.22% in central provinces and 0.28% in eastern provinces. The lowest rate was 0.02% in Heilongjiang Province and the highest rate was 0.63% in Hainan Province. CONCLUSIONS: National UNHS coverage increased substantially from 2008 to 2016, although provinces and regions still showed differences. The detection rate of infant hearing impairment in China is comparable to that in other countries. A national individual-level information system is urgently needed in China to facilitate the integration of screening, diagnosis and treatment of infant hearing impairment, which may also lead to a more accurate estimate of the detection rate.

Bayesian network model structure based on binary evolutionary algorithm.

With the continuous development of new technologies, the scale of training data is also expanding. Machine learning algorithms are gradually beginning to be studied and applied in places where the scale of data is relatively large. Because the current structure of learning algorithms only focus on the identification of dependencies and ignores the direction of dependencies, it causes multiple labeled samples not to identify categories. Multiple labels need to be classified using techniques such as machine learning and then applied to solve the problem. In the environment of more training data, it is very meaningful to explore the structure extension to identify the dependencies between attributes and take into account the direction of dependencies. In this article, Bayesian network structure learning, analysis of the shortcomings of traditional algorithms, and binary evolutionary algorithm are applied to the randomized algorithm to generate the initial population. In the optimization process of the algorithm, it uses a Bayesian network to do a local search and uses a depth-first algorithm to break the loop. Finally, it finds a higher score for the network structure. In the simulation experiment, the classic data sets, ALARM and INSURANCE, are introduced to verify the effectiveness of the algorithm. Compared with NOTEARS and the Expectation-Maximization (EM) algorithm, the weight evaluation index of this article was 4.5% and 7.3% better than other schemes. The clustering effect was improved by 13.5% and 15.2%. The smallest error and the highest accuracy are also better than other schemes. The discussion of Bayesian reasoning in this article has very important theoretical and practical significance. This article further improves the Bayesian network structure and optimizes the performance of the classifier, which plays a very important role in promoting the expansion of the network structure and provides innovative thinking.

Spatial and dynamic effects of air pollution on under-five children's lower respiratory infections: an evidence from China 2006 to 2017.

Air pollution has been a deeply concerned issue posing an immediate and profound threat to human's lower respiratory health in China. The health of children under 5 years old, regarded as a key index of public health progress in a country, is closely related to the long-term human capital development. Hence, it is vital to investigate the potential association between air pollution and children's lower respiratory health outcomes and to explore related policy implications regarding the public health and the pollution regulation. As air pollutants diffuse across adjacent regions rather easily, considering the spatial spillover effect is meaningful in course of acquiring the aforementioned association. Based on the proposed province-level panel dataset of China during 2006-2017, this study constructs a dynamic spatial panel Durbin model to investigate the impact of air pollution on under-five children's lower respiratory infections. As a result, (1) both air pollution and children's respiratory health have obvious spatial spillover effects, and the latter has an outstanding characteristic of path dependence in time. (2) In the short term, air pollution presents significant negative impact on children's respiratory health, while in the long run, the impact decreases dramatically. (3) Regional comparison indicates that children in the western China are the most susceptible to air pollution followed by children in the central and eastern regions. (4) Other control variables have significant and varying impacts both in the short and long term. Particularly, this paper proves the existence of "siphon effect" in children healthcare system in China. From a broader and more comprehensive perspective, this study provides effective and constructive basis for policy making, in favor of improving children's health under air pollution and promoting sustainable development in China.

Birth prevalence of tetrahydrobiopterin deficiency in China: data from the national newborn screening program, 2013-2019.

BACKGROUND: Tetrahydrobiopterin deficiency (BH4D), a less common form of hyperphenylalaninemia (HPA), can lead to severe developmental retardation if untreated. Little has been reported on the prevalence of BH4D among live births worldwide. This study examined its prevalence across China and between geographical areas within the country. METHODS: We analyzed data from the Chinese national screening program for HPA in newborns between 2013 and 2019. BH4D prevalence was examined by province, region and the entire country. Provincial-level prevalence was estimated from the number of confirmed BH4D cases and screened newborns, after adjusting for HPA-positive recall rate. Regional- and national-level prevalences were estimated by summing provincial-level prevalences after weighting them by the number of live births. A Poisson distribution was assumed in order to calculate 95% confidence intervals (CIs) for prevalence. RESULTS: Among 107,078,115 newborns screened for HPA in China, 380 with BH4D were identified, corresponding to a total prevalence of 3.8 per 1,000,000 live births. Prevalence was higher in eastern regions (5.9 per 1,000,000) and northern regions (4.1 per 1,000,000) of China than in southern regions (1.6 per 1,000,000) or northwestern regions (1.7 per 1,000,000). Across the entire country, 3.9% cases of HPA were diagnosed as BH4D, and this proportion reached as high as 15.1% in the southern part of the country. CONCLUSIONS: These first insights into BH4D prevalence across China suggest slightly higher prevalence than in other countries, and it varies substantially by region. More attention should be paid to early diagnosis and timely treatment of BH4D.

Geographic variations in the incidence of congenital hypothyroidism in China: a retrospective study based on 92 million newborns screened in 2013-2018.

BACKGROUND: Although congenital hypothyroidism (CH) has been widely studied in Western countries, CH incidence at different administrative levels in China during the past decade remains unknown. This study aimed to update the incidence and revealed the spatial pattern of CH incidence in the mainland of China, which could be helpful in the planning and implementation of preventative measures. METHODS: The data used in our study were derived from 245 newborns screening centers that cover 30 provinces of the Chinese Newborn Screening Information System. Spatial auto-correlation was analyzed by Global Moran I and Getis-Ord Gi statistics at the provincial level. Kriging interpolation methods were applied to estimate a further detailed spatial distribution of CH incidence at city level throughout the mainland of China, and Kulldorff space scanning statistical methods were used to identify the spatial clusters of CH cases at the city level. RESULTS: A total of 91,921,334 neonates were screened from 2013 to 2018 and 42,861 cases of primary CH were identified, yielding an incidence of 4.66 per 10,000 newborns screened (95% confidence interval [CI]: 4.62-4.71). Neonates in 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 lower probability of CH cases compared with the eastern region. The CH incidence indicated a moderate positive global spatial autocorrelation (Global Moran I value = 0.394, P  < 0.05), and the 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 scanned. The incidence of each province and each city in the mainland of China was estimated by kriging interpolation, revealing the most affected province and city to be Zhejiang Province and Hangzhou city, respectively. CONCLUSION: This study offers an insight into the space clustering of CH incidence at provincial and city scales. Future work on environmental factors need to focus on the effects of CH occurrence.

Incidence of inborn errors of metabolism detected by tandem mass spectrometry in China: A census of over seven million newborns between 2016 and 2017.

BACKGROUND: The incidence of inborn errors of metabolism varies widely across countries. Very few studies have analyzed the incidence of these disorders in Mainland China. We aimed to estimate the overall and disease-specific incidences of inborn errors of metabolism in Chinese newborns and investigate the geographical distribution of these disorders. METHODS: A national cross-sectional survey was conducted to investigate newborn inborn errors of metabolism screening by tandem mass spectroscopy in Mainland China between 2016 and 2017. A total of 246 newborn screening centers were surveyed using a standardized questionnaire. We examined the cumulative and disease-specific incidences of inborn errors of metabolism in Mainland China as a whole and in different geographical locations. RESULTS: Over 7 million newborns were screened and 2747 were diagnosed with inborn errors of metabolism, yielding an overall incidence of 38.69 per 100,000 births (95% confidence interval: 37.27-40.17). The most common disorders were amino acid disorders (17.14 per 100,000 births, 95% confidence interval: 16.21-18.13), followed by organic acid disorders (12.39 per 100,000 births, 95% confidence interval: 11.60-13.24) and fatty acid oxidation disorders (9.16 per 100,000 births, 95% confidence interval: 8.48-9.89). The overall and disease-specific incidence rates differed significantly across geographical locations (P < 0.001). CONCLUSIONS: The overall incidence of inborn errors of metabolism in Chinese newborns is relatively high. It is urgent to establish the recommended uniform screening panel for inborn errors of metabolism to guide the national and regional tandem mass spectroscopy newborn screening programs.

Analysis of HIV prevalence among pregnant women in Liangshan Prefecture, China, from 2009 to 2015.

BACKGROUND: Yi people make up about 50% of the population in Liangshan Prefecture, Sichuan Province, China, but accounted for 88.07% of new HIV cases in the prefecture from 2011 to 2013. This study evaluated HIV prevalence in pregnant women of Liangshan Prefecture using HIV sentinel surveillance (HSS) data over the period of 2009 to 2015. METHODS: Xichang, Zhaojue County, and Butuo County were selected as HSS sites. We investigated the temporal trends in HIV prevalence in these areas, and the association between demographic and behavioral characteristics and risk of HIV infection. RESULTS: Data on a total of 2797 pregnant women in Xichang and 3983 pregnant women in Zhaojue and Butuo was collected for the period 2009 to 2015. There was a fluctuating HIV prevalence among pregnant women of Xichang, with a rate of 0.75% in 2015 (χ2trend = 2.27, P = 0.13). HIV prevalence among pregnant women of Zhaojue and Butuo was consistently high, varying between 3.4% (9/267, 2011) and 10.3% (82/796, 2012) over the period of 2010 to 2015 (χ2trend = 0.12, P = 0.73). In Xichang, we found that Yi ethnicity (OR = 11.37, 95% CI = 2.92-44.25) and a husband who used drugs (OR = 32.13, 95% CI = 5.33-193.67) were significantly associated with HIV risk in pregnant women. For Zhaojue and Butuo, we observed that pregnant women had a higher risk of HIV infection when they were over 30 years old (OR = 1.72, 95% CI = 1.17-2.52), when they had a higher number of previous births, when their husbands had a history of migrating for work (OR = 1.56, 95% CI = 1.16-2.08), and when they had a history of other sexually transmitted infections (OR = 2.19, 95% CI = 1.16-2.08). Compared to those with a primary school education or below, pregnant women with a secondary or high school education level had a lower risk of HIV infection (OR = 0.28, 95% CI = 0.09-0.89). CONCLUSION: Our results indicate that there is a serious HIV epidemic among pregnant Yi women, especially for those with less education, more past births, or a husband with a history of out-migrating for work or STD infection.