Incidence And Prevalence of Congenital Hypothyroidism in Paraguay: Analysis of Data from The National Neonatal Screening Program (2014-2023)Abstract
Congenital hypothyroidism (CH) is a preventable cause of intellectual disability, and its early diagnosis through neonatal screening enables timely and effective treatment. This study analyzed the incidence and cumulative prevalence of CH in Paraguay between 2014 and 2023, using data from the National Neonatal Screening Program (PNDN). A total of 851,560 samples from newborns up to 28 days old were processed, collected from 1,132 sites across the country’s 18 health regions. Annual incidence ranged from 1:4,250 to 1:1,621, with a cumulative prevalence of 40.2 cases per 100,000 samples. Of the confirmed cases, 74% were female, with a female-to-male ratio of 2.8. The regions with the highest number of cases were Central, Asunción, and Alto Paraná, while Alto Paraguay and Ñeembucú had the highest cumulative prevalence rates. Despite annual fluctuations, incidence remained stable over time, suggesting a consolidation of the screening system. These findings reinforce the importance of neonatal screening as a key public health policy to prevent disabilities associated with late diagnosis and highlight the need to strengthen territorial equity in program coverage.
Keywords:
Congenital hypothyroidism; Neonatal screening; Incidence; Prevalence
Introduction
Congenital hypothyroidism (CH) is a critical condition affecting approximately 1 in every 800 to 10,000 newborns, with higher prevalence among Asians, Hispanics, and Native Americans. It shows a female predominance with a 2:1 ratio [1].
Its incidence varies globally, particularly in Latin America, not only due to ethnic diversity but also because of significant socioeconomic and healthcare system disparities across countries [2]. Reported data in the region range from 1:1,500 to 1:3,200, including Colombia (1:1,886) [3], Peru (1:1,638) [2], Chile (1:3,163) [4], Brazil (1:2,500) [5], Bolivia (1:2,985) [6], and Argentina (1:2,367) [7].
In Paraguay, an initial analysis from 1999 to 2007 reported an incidence of 1:1,501 newborns, one of the highest in Latin America at the time [8]. A later 20-year program consolidation reported an incidence of 1:2,060 [9].
Recognized as one of the most common preventable causes of physical and mental disability, early diagnosis through neonatal screening and timely initiation of thyroid hormone replacement therapy has significantly reduced disability in affected children [10,11]. Delayed diagnosis and treatment can lead to irreversible neurological deficits, emphasizing the importance of early diagnosis and intervention [12]. Early detection is crucial to prevent neurodevelopmental complications and long-term intellectual disability in affected individuals [13-16]. Hence the importance of methodological changes in newborn screening programs, such as adjustments in the detection limits of thyroid-stimulating hormone (TSH), which allow the detection of even the mildest cases of CH [17].
Despite the implementation of Law No. 836 of the Health Code in 1980 mandating iodization of salt for human consumption, and its regulation under Decree 3597 of 1999 by the National Institute of Food and Nutrition (INAN), the impact of these health policies on CH incidence in Paraguay remains unclear [8].
This study aimed to investigate the annual incidence and cumulative prevalence of CH in Paraguay using data from the PNDN over a 10-year period (2014-2023), analyzing temporal trends to understand the epidemiological behavior of this condition.
Methods
This was a descriptive, retrospective, cross-sectional study that analyzed the results of coded newborn samples received by the National Neonatal Screening Program (PNDN) from January 2014 to December 2023. These samples were collected from 1,132 sampling sites distributed across the 18 Health Regions (HR) of Paraguay.
Included in the study were results from newborn samples taken within the first 28 days of life, obtained via heel prick on filter paper (Whatman 903), dried at room temperature for 2 to 4 hours, and refrigerated until sent to the PNDN.
Thyroid-stimulating hormone (TSH) levels were measured using time-resolved fluoroimmunoassay for quantification in dried blood spots on filter paper. A cut-off value >10 µIU/mL was used to trigger recall. Positive cases were confirmed in serum by measuring both TSH and thyroxine (T4) levels (Figure 1) [18].
All confirmed cases received treatment with L-thyroxine (levothyroxine), with an initial dose of 9 to 13.5 µg/kg, subsequently adjusted based on clinical and laboratory findings.
For data analysis, descriptive and inferential statistical techniques were used. Absolute and relative frequencies were calculated for categorical variables, and measures of central tendency and dispersion for continuous variables. Annual incidence of CH was estimated by dividing the number of processed samples by the number of confirmed cases per year. Cumulative prevalence was calculated based on the total number of confirmed cases during the study period (2014-2023) over the total number of processed samples.
Temporal trends in incidence were modeled using both linear and polynomial regression approaches. Linear models were initially applied to assess simple directional trends; polynomial models were considered when visual inspection of the data suggested non-linearity. Model selection was based on goodness‑of‑fit criteria, including R² and residual analysis. R² values are reported to indicate the proportion of variability in incidence explained by the model, acknowledging that lower R² values may still be informative in epidemiological time-series with inherent fluctuation.
For regional comparisons, chi‑square tests were performed to evaluate differences across HR. When multiple pairwise comparisons were required, Bonferroni correction was applied to adjust significance thresholds and reduce the risk of Type I error. A statistical significance level of 5% (p < 0.05) was established for all tests.
Data quality control included reviewing duplicate records, verifying outliers, and cross-validating with original sources. A database was created using Microsoft Excel, and statistical analyses were performed with SPSS software (version 26.0).
Results
Over the 10-year study period from 2014 to 2023, a total of 851,560 samples were analyzed. Table 1 summarizes the annual data on processed samples, confirmed cases, sex distribution, and incidence of CH confirmed by the PNDN. A significant variability in CH incidence was observed, ranging from 1:4,250 in 2014 to a peak of 1:1,621 in 2019, followed by a decrease to 1:3,147 in 2023. This difference was statistically significant (p = 0.01).
Due to the periods of increase and decrease, a polynomial distribution best fit the variability (R² = 0.627) of annual incidence throughout the study period (Figure 2). The results indicate that although there was a significant linear increase in incidence, a sharp decline was observed in the most recent years.
Temporal Trend of Congenital Hypothyroidism Incidence by Year. The number of confirmed cases of Congenital Hypothyroidism per 100,000 samples processed per year is presented with linear regression lines (blue) with a 95% Confidence Interval.
The 10-year cumulative prevalence was 40.2 CH cases per 100,000 samples analyzed (95% CI: 35.9-44.4). Of the confirmed cases, 74% were female, with an annual average of 25.2 ± 7.77 cases, while male cases accounted for only 26%, with an average of 8.9 ± 3.51 cases per year. This reflects a female predominance with a ratio of approximately 3:1 (F/M: 2.8). Gender information was missing for one patient in 2021.
Regarding distribution by HR, a statistically significant difference was found (p = 0.007) in the cumulative prevalence of confirmed cases by department. However, none of the regions showed a statistically significant variation compared to the global mean (Table 2). The HR with the highest number of CH cases were Central (11.4 ± 4.45 cases/year), Asunción (4.7 ± 2.31), and Alto Paraná (4.1 ± 2.42). However, Alto Paraguay and Ñeembucú had the highest cumulative prevalence rates and a greater likelihood of positive newborns (OR 3.39 and 1.95, respectively).
Figure 3 shows the distribution of cases by department. The regions with the highest case proportions were Central (33%), Asunción (14%), and Alto Paraná (12%). The regions with the fewest cases were Misiones, Alto Paraguay, and Caazapá, each representing 1% or less.
Discussion
The results of this study confirm that congenital hypothyroidism (CH) remains a highly relevant public health condition in Paraguay. The incidence observed during the 2014-2023 period (annual average of 1:2,666), although slightly lower than that reported in the program’s initial analysis (1:1,501 newborns) [8] and the 20-year consolidation (1:2,060 newborns) [9], aligns with global [19-21] and Latin American regional averages [2-7]. This suggests that the effectiveness of the program in detecting CH cases in Paraguay has been maintained in terms of both coverage and quality, despite structural, environmental, or genetic factors that may contribute to the disease burden.
Recent evaluations of PNDN provide important context for interpreting the epidemiological behavior observed in CH. According to Ascurra et al. (2025) [22], national screening coverage in Paraguay has remained consistently high in recent years, ranging between 75% and 85% from 2018 to 2023, with the program achieving full coverage of births registered in the public health system as early as 2015. These findings reflect the maturity and consolidated reach of the screening system and support the interpretation that the stability in incidence over time likely reflects true epidemiological patterns rather than fluctuations in program uptake.
Neonatal screening (NS) for CH began globally in the 1970s and has since become the gold standard for early diagnosis, significantly reducing neurological sequelae. Before NS programs, CH was diagnosed clinically at later stages, with incidence ranging from 1:7,000 to 1:10,000. After implementation, incidence increased to 1:3,000 and currently ranges from 1:1,400 to 1:2,800 [19,20].
Comparatively, Paraguay’s incidence rates fall within the global and regional ranges [2-7,19-21]. They are higher than those reported in countries like Chile (1:3,163) [4] and Bolivia (1:2,985) [6], similar to Argentina [7], and lower than those in Colombia [3] and Peru [2].
Temporal analysis showed an initial increase in incidence, particularly between 2017 and 2019, followed by a decline in subsequent years to earlier levels. Despite these fluctuations, the overall annual incidence remained stable, suggesting consolidation of the screening system and improved standardization of processes.
Several factors may have contributed to this variability, including increased sensitivity in detecting positive cases by the PNDN, greater awareness and training among healthcare personnel [23,24], measures implemented during the COVID-19 pandemic (2020-2021) [25,26], sustained implementation of policies such as salt iodization (established in 1992 under the Resolution N° 23/92) [27], declining birth rates [28], internal migration to urban areas [29], and demographic changes [20].
An additional consideration relevant to the interpretation of our findings is the influence of analytical sensitivity-particularly the TSH cut‑off used for initial screening-on diagnostic yield. Evidence shows that lowering the cut‑off increases sensitivity and facilitates detection of milder cases, but may also reduce the positive predictive value (PPV) due to higher false‑positive rates. Conversely, higher cut‑off thresholds improve PPV at the expense of missing borderline cases. Recent experiences from Latin American programs, underscore the importance of periodically re‑evaluating cut‑off values in alignment with local epidemiology and program performance capacity to ensure optimal screening outcomes [30].
The cumulative prevalence during the study period also reflects the magnitude of CH’s impact on the Paraguayan neonatal population. This data is useful for understanding the national disease burden [7,31].
Regarding variability among health regions, disparities in reported case proportions highlight the need to strengthen territorial equity in screening implementation. It is not surprising that Central, Asunción, and Alto Paraná accounted for nearly 60% of national cases, as they are the most densely populated departments. However, Alto Paraguay and Ñeembucú-regions with lower populations, higher rural and Indigenous populations, and more limited access [32]-showed higher cumulative prevalence rates and more than double the likelihood of positive cases.
From a public health perspective, the findings of this study reaffirm the importance of maintaining and strengthening the NS program as a priority policy. Early detection and timely treatment with levothyroxine have proven highly effective in preventing intellectual disability in affected newborns and improving their quality of life and that of their families. It is essential to advance and sustain the integration of clinical and endocrinological follow-up for confirmed cases [33].
This study had some limitations that should be considered when interpreting the results. As a retrospective analysis based on PNDN records, there is a possibility of underreporting or data coding errors, especially in regions with lower coverage or technical capacity. Environmental, genetic, or socioeconomic factors that could influence the observed incidence were not evaluated. Regional differences should be interpreted with caution, particularly in less populated areas such as Alto Paraguay and Ñeembucú. The small number of births and screened newborns in these regions widens confidence intervals and increases the statistical instability of prevalence estimates, potentially exaggerating apparent differences. These fluctuations may therefore reflect sample size limitations rather than true epidemiological variation.
Finally, this study highlights the need to assess the impact of policies such as mandatory salt iodization, whose effectiveness in preventing thyroid dysfunctions has not yet been clearly established in the Paraguayan context. Incorporating etiological and genetic studies, as well as improving information and surveillance systems, will be key to gaining a deeper understanding of CH’s epidemiological behavior in the country.
In conclusion, this study provides an updated and detailed overview of the incidence and cumulative prevalence of CH in Paraguay, which align with rates reported globally and regionally. The findings reinforce the importance of NS as a key tool in preventing disabilities associated with delayed diagnosis. These results should serve as a foundation for strengthening public policies aimed at early detection, timely treatment, and continuous surveillance of CH, with the goal of improving child health outcomes in the country.
References
-
1. Zapata JK, Abrigo MV, Ávila SE, Cabrera KJ. Hipotiroidismo congénito y el tamizaje neonatal. Reciamuc 2021;5(1):233-40. doi: 10.26820/reciamuc/5.(1).ene.2021.233-240.
» https://doi.org/10.26820/reciamuc/5.(1).ene.2021.233-240 - 2. Huerta-Saenz L, Del Aguila C, Espinoza O, Falen-Boggio J, Mitre N. National Screening for congenital hypothyroidism in Peru: A broken program. Rev Peru Med Exp Salud Publica 2015;32(3):579-85.
-
3. Giraldo GA, Suárez-Obando F, Sánchez P, Prieto JC. Evaluation of TSH Levels in the Program of Congenital Hypothyroidism Newborn Screening in a Pilot Study of Preterm Newborns in Bogotá, Colombia. J Inborn Errors Metab Screen 2015;3: e20190003. doi: 10.1177/2326409815597706
» https://doi.org/10.1177/2326409815597706 -
4. Nuñez A, Bedregal P, Becerra C, Grob F. Alteraciones del neurodesarrollo en pacientes con hipotiroidismo congénito: Recomendaciones para el seguimiento. Rev Med Chile 2017;145:1579-87. doi: 10.4067/s0034-98872017001201579
» https://doi.org/10.4067/s0034-98872017001201579 -
5. Brasil. Ministério da Saúde. Hipotireoidismo Congênito (HC). Published June 28, 2017. Updated November, 16 2021 Updated November, 16 2021https://www.gov.br/saude/pt-br/assuntos/pcdt/h/hipotireoidismo-congenito Accessed May, 12 2025.
» https://www.gov.br/saude/pt-br/assuntos/pcdt/h/hipotireoidismo-congenito - 6. Siacar S, Aparicio A, Soliz O. Tamiz neonatal: Detección de hipotiroidismo congénito. Hospital Materno Infantil de la Caja Nacional de Salud. Rev Soc Bol Ped 2014;53(3):121-4.
-
7. Chiesa A, Prieto L, Mendez V, Papendieck P, Calcagno Mde L, Gruñeiro-Papendieck L. Prevalence and etiology of congenital hypothyroidism detected through an argentine neonatal screening program (1997-2010). Horm Res Paediatr 2013;80(3):185-92. doi: 10.1159/000354409
» https://doi.org/10.1159/000354409 - 8. Ascurra M, Rodriguez S, Valenzuela A, Blanco F, Ortiz L, Samudio M. Incidencia de Hipotiroidismo Congénito en 14 Regiones Sanitarias del Paraguay. Pediatr (Asunción) 2009;36(2):111-6.
-
9. Ascurra M, Alvarez P, Ortiz L, Blanco F, Valenzuela A, Insaurralde A, Rodríguez S, Salinas M, Porzio G, Nuñez A. Consolidation of the neonatal screening program as a public health program in Paraguay. J Inborn Errors of Metab Screen2021. 9:e20210006. doi: 10.1590/2326-4594-JIEMS-2021-0006
» https://doi.org/10.1590/2326-4594-JIEMS-2021-0006 -
10. Kurinczuk JJ, Bower C, Lewis B, Byrne G. Congenital hypothyroidism in Western Australia 1981-1998. J Paediatr Child Health 2002 Apr;38(2):187-91. doi: 10.1046/j.1440-1754.2002.00812.x
» https://doi.org/10.1046/j.1440-1754.2002.00812.x -
11. Bekhit OE, Yousef RM. Permanent and transient congenital hypothyroidism in Fayoum, Egypt: A descriptive retrospective study. PLoS One 2013 Jun 28;8(6):e68048. doi: 10.1371/journal.pone.0068048
» https://doi.org/10.1371/journal.pone.0068048 - 12. Salim IA, Putri BR, Rosmalawati TA, Cahyono HA, Muttaqin F. Screening for congenital hypothyroidism in Malang, East Java in 2020. Ped Sci J 2021;2(2):38-43.
-
13. Salerno M, Militerni R, Di Maio S, Bravaccio C, Gasparini N, Tenore A. Intellectual outcome at 12 years of age in congenital hypothyroidism. Eur J Endocrinol 1999 Aug;141(2):105-10. doi: 10.1530/eje.0.1410105
» https://doi.org/10.1530/eje.0.1410105 -
14. Calle GD, Muñoz TV, Delgado CR, Vera RS. Tamizaje neonatal de hipotiroidismo congénito. Reciamuc 2020;4(3):268-74. doi: 10.26820/reciamuc/4.(3).julio.2020.268-274.
» https://doi.org/10.26820/reciamuc/4.(3).julio.2020.268-274 -
15. Herrera-Chinchay L, Silva-Ocas I, Castro-Silva N, Villar C. Desarrollo social, cognitivo y psicomotor en niños peruanos con hipotiroidismo congénito. Andes Pediátrica 2021;92(2):235. doi: 10.32641/andespediatr.v92i2.1955.
» https://doi.org/10.32641/andespediatr.v92i2.1955 -
16. Valera Antequera D, Montealegre Páez AL, Bermúdez A, García Robles R. Importancia de una propuesta para la implementación de un programa de tamizaje neonatal expandido en Colombia. Revista Med 2019;27(2):23-35. doi: 10.18359/rmed.4195.
» https://doi.org/10.18359/rmed.4195 -
17. Wassner AJ, Brown RS. Congenital hypothyroidism: recent advances. Curr Opin Endocrinol Diabetes Obes 2015 Oct;22(5):407-12. doi: 10.1097/MED.0000000000000181.
» https://doi.org/10.1097/MED.0000000000000181 -
18. Paraguay. Ministerio de Salud Pública y Bienestar Social. Guía Nacional de Toma de Muestra [online]. Asunción, PY: MSPyBS; 2015. https://www.mspbs.gov.py/pndc/guianacional.html Accessed May, 12 2025.
» https://www.mspbs.gov.py/pndc/guianacional.html - 19. Galera RML, Ramos DC, Rocha H. Cribado neonatal del hipotiroidismo congénito. Rev Esp Salud Pública 2021;95:e1-14.
-
20. Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis 2010;5:17. doi: 10.1186/1750-1172-5-17.
» https://doi.org/10.1186/1750-1172-5-17 -
21. Olivieri A, Fazzini C, Medda E; Italian Study Group for Congenital Hypothyroidism. Multiple factors influencing the incidence of congenital hypothyroidism detected by neonatal screening. Horm Res Paediatr 2015;83(2):86-93. doi: 10.1159/000369394.
» https://doi.org/10.1159/000369394 -
22. Ascurra M, Valenzuela A, Galeano M, Rodríguez M, Porzio G, Salinas M et al Recent Trends in the Incidence of Cystic Fibrosis in Paraguay: Analysis of the Period 2018-2023. J Inborn Errors Metab Screen 2025;13:e20250001. doi: 10.1590/2326-4594-jiems-2025-0001
» https://doi.org/10.1590/2326-4594-jiems-2025-0001 -
23. Centro de Análisis y Difusión de la Economía Paraguaya (CADEP). La protección social en Paraguay: avances y desafíos. Asunción, PY: CADEP; 2015. https://www.desarrollo.org.py/admin/app/webroot/pdf/publications/17-12-2015-15-15-08-1288255036.pdf Accessed May, 12 2025.
» https://www.desarrollo.org.py/admin/app/webroot/pdf/publications/17-12-2015-15-15-08-1288255036.pdf -
24. OPS - Organización Panamericana de la Salud. Programa Nacional de Prevención de la Fibrosis Quística y del Retardo Mental [Internet]. Asunción, PY: Campus Virtual de Salud Pública. https://campus.paho.org/paraguay/programa-nacional-de-prevencion-de-la-fibrosis-quistica-y-del-retardo-mental 2025. Accessed May, 12 2025.
» https://campus.paho.org/paraguay/programa-nacional-de-prevencion-de-la-fibrosis-quistica-y-del-retardo-mental -
25. Paraguay. Ministerio de Relaciones Exteriores. Medidas implementadas por el Gobierno Nacional en el contexto de la pandemia del COVID-19. Asunción: MRE; 2020. https://www2.mre.gov.py/index.php/noticias-de-embajadas-y-consulados/el-mre-implementa-medidas-preventivas-para-la-atencion-al-publico-y-para-resguardar-la-salud-de-sus-funcionarios?ccm_paging_p=4 Accessed May, 12 2025.
» https://www2.mre.gov.py/index.php/noticias-de-embajadas-y-consulados/el-mre-implementa-medidas-preventivas-para-la-atencion-al-publico-y-para-resguardar-la-salud-de-sus-funcionarios?ccm_paging_p=4 - 26. Bordenabe ML, Maggi LG, Claudia FD. Pesquisa neonatal para hipotiroidismo congénito en el sector público de Santa Fe durante la pandemia. Rev Med Ros 2024;90:21-27.
-
27. Paraguay. Ministerio de Salud Pública y Bienestar Social. Sal yodada: mineral indispensable para el buen funcionamiento físico y mental [Internet]. Asunción: MSPBS; 2023. https://www.mspbs.gov.py/portal/28116/sal-yodada-mineral-indispensable-para-el-buen-funcionamiento-fisico-y-mental.html Accessed May, 12 2025.
» https://www.mspbs.gov.py/portal/28116/sal-yodada-mineral-indispensable-para-el-buen-funcionamiento-fisico-y-mental.html -
28. Paraguay. Instituto Nacional de Estadística. Indicador 10: Porcentaje de recién nacidos tamizados. Asunción: INE; 2016. https://www.ine.gov.py/microdatos/indicador.php?ind=10 Accessed May, 12 2025.
» https://www.ine.gov.py/microdatos/indicador.php?ind=10 -
29. Paraguay. Instituto Nacional de Estadística. Paraguay 2023: indicadores sociales y económicos [Internet]. Asunción: INE ; 2023. https://www.ine.gov.py/Publicaciones/Biblioteca/documento/211/000_Paraguay_2023.pdf Accessed May, 12 2025.
» https://www.ine.gov.py/Publicaciones/Biblioteca/documento/211/000_Paraguay_2023.pdf -
30. Teixeira PBN, Vilela AJM, Colosimo EA, Alves DVM, Januário JN, Novato Silva I. Impact of Lowering TSH Cut-Off on Neonatal Screening for Congenital Hypothyroidism in Minas Gerais, Brazil. Int J Neonatal Screen 2024;10(3):52. doi: 10.3390/ijns10030052
» https://doi.org/10.3390/ijns10030052 -
31. Dayal D, Prasad R. Congenital hypothyroidism: current perspectives. Res Rep Endocr Disord 2015;5:91-102. doi: 10.2147/RRED.S56402.
» https://doi.org/10.2147/RRED.S56402. -
32. Paraguay. Instituto Nacional de Estadística. Paraguay en cifras 2023. Asunción: INE ; 2023. https://www.ine.gov.py/publication-single.php?codec=257 Accessed May, 12 2025.
» https://www.ine.gov.py/publication-single.php?codec=257 -
33. van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, et al Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid 2021 Mar;31(3):387-419. doi: 10.1089/thy.2020.0333.
» https://doi.org/10.1089/thy.2020.0333
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Funding
This study was funded by Abbott Laboratories. The funder had no role in the study design, data collection, statistical analysis, interpretation of results, or manuscript preparation. All analytical decisions and interpretations were made independently by the authors.
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Data Availability
The data that support the findings of this study are derived from the National Neonatal Screening Program (PNDN) of the Health Ministry (MSPBS) in Paraguay. Due to the sensitive nature of health data and institutional regulations, the datasets are not publicly available. Access to anonymized data may be granted upon reasonable request to the corresponding author and subject to authorization by the responsible health authority.
The data that support the findings of this study are derived from the National Neonatal Screening Program (PNDN) of the Health Ministry (MSPBS) in Paraguay. Due to the sensitive nature of health data and institutional regulations, the datasets are not publicly available. Access to anonymized data may be granted upon reasonable request to the corresponding author and subject to authorization by the responsible health authority.
