Abstract The coronavirus disease 2019 (COVID-19) mortality rates varied among the states of Brazil during the course of the pandemics. The human leukocyte antigen (HLA) is a critical component of the antigen presentation pathway. Individuals with different HLA genotypes may trigger different immune responses against pathogens, which could culminate in different COVID-19 responses. HLA genotypes are variable, especially in the highly admixed Brazilian population. In this ecological study, we aimed to investigate the correlation between HLA haplotypes and the different regional distribution of COVID-19 mortality in Brazil. HLA data was obtained from 4,148,713 individuals registered in The Brazilian Voluntary Bone Marrow Donors Registry. COVID-19 data was retrieved from epidemiological bulletins issued by State Health Secretariats via Brazil’s Ministry of Health from February/2020 to July/2022. We found a positive significant correlation between the HLA-A*01~B*08~DRB1*03 haplotype and COVID-19 mortality rates when we analyzed data from 26 states and the Federal District. This result indicates that the HLA-A*01~B*08~DRB1*03 haplotype may represent an additional risk factor for dying due to COVID-19. This haplotype should be further studied in other populations for a better understanding of the variation in COVID-19 outcomes across the world. 201 COVID19 COVID 19 (COVID-19 pandemics (HLA pathway pathogens COVID-1 variable population study 4148713 4 148 713 4,148,71 Registry Brazils s February2020 February 2020 February/202 July2022 July 2022 July/2022 HLAA*01~B*08~DRB1*03 HLAA01B08DRB103 HLAABDRB A*01~B*08~DRB1*03 A 01 B 08 DRB1 03 DRB HLA-A*01~B*08~DRB1*0 2 District COVID19. 19. world 20 COVID1 1 (COVID-1 COVID- 414871 14 71 4,148,7 February202 202 February/20 July202 July/202 HLAA HLAA*01~B*08~DRB1*0 HLAA01B08DRB10 A01B08DRB103 ABDRB A*01~B*08~DRB1*0 0 HLA-A*01~B*08~DRB1* (COVID- 41487 7 4,148, February20 February/2 July20 July/20 HLAA*01~B*08~DRB1* HLAA01B08DRB1 A01B08DRB10 A*01~B*08~DRB1* HLA-A*01~B*08~DRB1 (COVID 4148 4,148 February2 February/ July2 July/2 HLAA*01~B*08~DRB1 HLAA01B08DRB A01B08DRB1 A*01~B*08~DRB1 HLA-A*01~B*08~DRB 414 4,14 July/ HLAA*01~B*08~DRB A01B08DRB A*01~B*08~DRB 41 4,1 4,

Abstract Human reproduction goes through many challenges to its success and in many cases it fails. Cases of pregnancy loss are common outcomes for pregnancies, and implantation failures (IF) are common in assisted reproduction attempts. Although several risk factors have already been linked to adverse outcomes in reproduction, many cases remain without a definitive cause. Genetics of female reproduction is a field that may bring some pieces of this puzzle; however, there are no well-defined genes that might be related to the risk for recurrent pregnancy loss (RPL) and IF. Here, we present a literature review of the studies of genetic association in RPL and IF carried out in the Brazilian population and complemented with a database search to explore genes previously related to RPL and IF, where a search for genes previously involved in these conditions was performed in OMIM, HuGE, and CTD databases. Finally, we present the next steps for reproductive genetics investigation, through genomic sequencing analyses and discuss future plans in the study of RPL genetics. The combined strategy of looking for literature and databases is useful to raise hypotheses and to identify underexplored genes related to RPL and IF. fails pregnancies (IF attempts cause puzzle however welldefined well defined (RPL Here OMIM HuGE Finally investigation

RESUMO: Objetivos: Analisar as prevalências ao nascimento e a distribuição espacial e temporal das anomalias congênitas (ACs) entre nascidos vivos no estado do Maranhão nos anos de 2001 a 2016; descrever variáves de interesse demográficas, gestacionais e neonatais. Métodos: Estudo ecológico, de base populacional, a partir de dados secundários do Sistema de Informações sobre Nascidos Vivos (SINASC). Foram calculadas prevalências ao nascimento anuais de ACs totais e por grupos. Análises espaciais utilizaram o cálculo de Indicadores Locais de Associação Espacial (LISA) e o Índice Global de Moran I, e mapas interativos foram gerados. Variáveis de interesse demográficos, gestacionais e neonatais disponíveis no SINASC foram descritas no grupo dos recém-nascidos com ACs. Resultados: Neste estudo, foram incluídos 1.831.830 nascidos vivos, 6.110 com ACs (33,4/10 mil). Maiores frequências ocorreram nos anos mais recentes. Aglomerados espaciais foram observados em anos específicos. As prevalências de nascidos vivos com anomalias foram diferentes entre categorias de variáveis consideradas como fatores de risco para esse desfecho. Conclusão: A prevalência ao nascimento de nascidos com ACs foi inferior ao esperado para defeitos maiores na espécie humana (3%). O pico temporal de registros em 2015/2016 está provavelmente relacionado ao aumento de microcefalia causada pela infecção gestacional por vírus Zika. Os aglomerados espaciais provavelmente se deveram a variações ao acaso pelo número pequeno de nascimentos, pois não se repetem em outros anos. Estudos como este são base para o estabelecimento de programas de vigilância de defeitos congênitos.

ABSTRACT: Objectives: To analyze the prevalence at birth and the spatial and temporal distribution of congenital anomalies (CAs) among live births in the state of Maranhão in 2001 to 2016. To describe demographic, gestational and neonatal variables of interest. Methods: Ecological, population-based study, using secondary data from the Live Birth Information System (SINASC). Annual prevalence of total and per-group CAs was calculated. Spatial analyzes were based on the Local Indicators of Spatial Association (LISA) and the Moran I Index, and interactive maps were generated. Demographic, gestational and neonatal variables of interest available from SINASC were described in the group of newborns with CAs. Results: 1,831,830 live births, 6,110 with CAs (33.4/10,000) were included. Higher frequencies occurred in more recent years. Spatial clusters have been observed in specific years. The prevalence of newborns with CAs was different between categories of variables considered as risk factors for this outcome. Conclusion: The prevalence at birth of total CAs was lower than expected for major human defects (3%). The temporal peak of records in 2015/2016 is probably related to the increase in CAs caused by gestational infection by the Zika virus. The spatial clusters were probably due to variations at random due to the small number of births as they are not repeated in other years. Studies like this are the basis for the establishment of CA surveillance programs.

RESUMO: Objetivos: Analisar as prevalências ao nascimento e a distribuição espacial e temporal das anomalias congênitas (ACs) entre nascidos vivos no estado do Maranhão nos anos de 2001 a 2016; descrever variáves de interesse demográficas, gestacionais e neonatais. Métodos: Estudo ecológico, de base populacional, a partir de dados secundários do Sistema de Informações sobre Nascidos Vivos (SINASC). Foram calculadas prevalências ao nascimento anuais de ACs totais e por grupos. Análises espaciais utilizaram o cálculo de Indicadores Locais de Associação Espacial (LISA) e o Índice Global de Moran I, e mapas interativos foram gerados. Variáveis de interesse demográficos, gestacionais e neonatais disponíveis no SINASC foram descritas no grupo dos recém-nascidos com ACs. Resultados: Neste estudo, foram incluídos 1.831.830 nascidos vivos, 6.110 com ACs (33,4/10 mil). Maiores frequências ocorreram nos anos mais recentes. Aglomerados espaciais foram observados em anos específicos. As prevalências de nascidos vivos com anomalias foram diferentes entre categorias de variáveis consideradas como fatores de risco para esse desfecho. Conclusão: A prevalência ao nascimento de nascidos com ACs foi inferior ao esperado para defeitos maiores na espécie humana (3%). O pico temporal de registros em 2015/2016 está provavelmente relacionado ao aumento de microcefalia causada pela infecção gestacional por vírus Zika. Os aglomerados espaciais provavelmente se deveram a variações ao acaso pelo número pequeno de nascimentos, pois não se repetem em outros anos. Estudos como este são base para o estabelecimento de programas de vigilância de defeitos congênitos.

ABSTRACT: Objectives: To analyze the prevalence at birth and the spatial and temporal distribution of congenital anomalies (CAs) among live births in the state of Maranhão in 2001 to 2016. To describe demographic, gestational and neonatal variables of interest. Methods: Ecological, population-based study, using secondary data from the Live Birth Information System (SINASC). Annual prevalence of total and per-group CAs was calculated. Spatial analyzes were based on the Local Indicators of Spatial Association (LISA) and the Moran I Index, and interactive maps were generated. Demographic, gestational and neonatal variables of interest available from SINASC were described in the group of newborns with CAs. Results: 1,831,830 live births, 6,110 with CAs (33.4/10,000) were included. Higher frequencies occurred in more recent years. Spatial clusters have been observed in specific years. The prevalence of newborns with CAs was different between categories of variables considered as risk factors for this outcome. Conclusion: The prevalence at birth of total CAs was lower than expected for major human defects (3%). The temporal peak of records in 2015/2016 is probably related to the increase in CAs caused by gestational infection by the Zika virus. The spatial clusters were probably due to variations at random due to the small number of births as they are not repeated in other years. Studies like this are the basis for the establishment of CA surveillance programs.

Objectives: To analyze the prevalence at birth and the spatial and temporal distribution of congenital anomalies (CAs) among live births in the state of Maranhão in the years 2001 to 2016. To describe demographic, gestational and neonatal variables of interest. Methods: Ecological, population-based study, using secondary data from the Information System on Live Births (SINASC). Annual prevalence of total and per group CAs was calculated. Spatial analyzes used the calculation of Local Indicators of Spatial Association and the Moran I Index and interactive maps were generated. Demographic, gestational and neonatal variables of interest available at SINASC were described in the group of newborns with CAs. Results: 1,831,830 live births, 6,110 with CAs (33.4/10,000) were included. Higher frequencies have occurred in more recent years. Spatial clusters have been observed in specific years. The prevalence of births of babies with CAs was different between categories of variables considered as risk factors for this outcome. Conclusion: The prevalence at birth of total CAs was lower than expected for the human species for major defects (3%). The temporal peak of records in 2015/2016 is probably related to the increase in CAs caused by gestational infection by Zika virus. The spatial clusters were probably due to variations at random due to the small number of births as they are not repeated in other years. Studies like this are the basis for the establishment of CA surveillance programs.

Objetivos: Analisar as prevalências ao nascimento e a distribuição espacial e temporal das anomalias congênitas entre nascidos vivos no estado do Maranhão nos anos de 2001 a 2016. Descrever variáves de interesse demográficas, gestacionais e neonatais. Métodos: Estudo ecológico, de base populacional, a partir de dados secundários do Sistema de Informações sobre Nascidos Vivos. Foram calculadas prevalências ao nascimento anuais de ACs totais e por grupos. Análises espaciais utilizaram o cálculo de Indicadores de Associação Espacial Locais e o Índice de Moran I e mapas interativos foram gerados. Variáveis de interesse demográficos, gestacionais e neonatais disponíveis no SINASC foram descritas no grupo dos recém-nascidos com ACs. Resultados: Foram incluídos 1.831.830 nascidos vivos, 6.110 com anomalias congênitas (33,4/10.000). Maiores frequências ocorreram nos anos mais recentes. Aglomerados espaciais foram observados em anos específicos. As prevalências de nascidos vivos com anomalias foi diferente entre categorias de variáveis consideradas como fatores de risco para este desfecho. Conclusão: A prevalência ao nascimento de nascidos com anomalias congênitas  foi  inferior ao esperado para defeitos maiores na espécie humana (3%).  O pico temporal de registros em 2015/2016 está provavelmente relacionado ao aumento de microcefalia causada pela infecção gestacional por vírus Zika. Os aglomerados espaciais provavelmente se deveram a variações ao acaso pelo número pequeno de nascimentos pois não se repetem em outros anos. Estudos como este são base para o estabelecimento de programas de vigilância de defeitos congênitos.