Table 3 - uploaded by Ida Vanessa Schwartz
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Description of causes of 148 notified cases of microcephaly in Rio Grande do Sul, Brazil, from 01 Dec 2015 to 31 Dec 2016. N (%)
Source publication
Objective:
The aim of this study was to identify the causes of congenital microcephaly in Rio Grande do Sul, a state in southern Brazil, where no ZIKV outbreak was detected, from December 2015 to December 2016, which was the period when ZIKV infection was at its peak in northeast Brazil.
Methods:
This was a cross-sectional study where all notifi...
Context in source publication
Context 1
... the 58 confirmed cases of microcephaly (prevalence = 3.8/10 000 live births), congenital infections were the lead- ing causal factor identified (n = 29; 50.0%): syphilis (n = 13; 22.4%), toxoplasmosis (n = 7; 12.1%), CMV (n = 6; 10.3%), and ZIKV (n = 3; 5.2%). Nine cases (15.5%) were classified as isolated CNS malformations (Table 3) and consisted of encephalocele (5.2%) and corpus callosum agenesis (5.2%), among others. Genetic syndromes were diagnosed in six patients (10.3%), but in 11 cases a genetic condition was suspected without confirmation of any specific syndrome. ...
Similar publications
Objective
The aim of this study was to identify the causes of congenital microcephaly in Rio Grande do Sul, a state in southern Brazil, where no ZIKV outbreak was detected, from December 2015 to December 2016, which was the period when ZIKV infection was at its peak in northeast Brazil.
Methods
This was a cross‐sectional study where all notificati...
Citations
... A microcefalia é uma malformação congênita em recém-nascidos de ambos os sexos no qual o cérebro não se desenvolve de maneira adequada, ou seja, o perímetro cefálico dos mesmos é menor que dois desvios-padrão da média para idade e sexo (Herber, 2019). ...
... Para o fechamento de diagnóstico, é necessário a realização de exames físicos e clínicos como tomografia do crânio e ressonância magnética, todos avaliam uma medida do perímetro cefálico (Herber, 2019). Segundo a Organização Mundial da Saúde (OMS), a microcefalia é assinalada pela medida do crânio do recém-nascido (RN) ao nascer, em que a demarcação cefálica apresente medida igual ou inferior de 31,9 cm, para menino, e de 31,5 cm, para menina (Félix, 2019). ...
... Rio Grande do Sul (RS) is the southernmost state of Brazil, where a cooler climate prevented an outbreak of ZIKV infection at that time. From December 2015 to December 2017, the prevalence at birth of congenital microcephaly was calculated as 9.6/10,000 live births, with confirmed cases of SCZ representing 5.2% (n=3) (Herber et al., 2019). ...
... This study aimed to compare data from records of cases of congenital microcephaly already analyzed by Herber et al. (2019) with the post-outbreak period (endemic period) from 2017 to 2022 in RS. ...
... This is a cross-sectional study analyzing all notifications of liveborn with congenital microcephaly in the state of RS, from December 1, 2015, to December 31, 2016 [Period 1 -Outbreak -data already published by Herber et al., 2019)] and from January 1, 2017, until September 30, 2022 (Period 2endemic). Microcephaly was defined as a head circumference below 2 Z-scores, corrected for gender and gestational age, according to the Intergrowth-21st charts (De Oliveira et al., 2017). ...
Northeast Brazil was the first region to detect a significant increase in babies born with microcephaly associated with prenatal zika virus infection in 2015. Rio Grande do Sul (RS) state was less impacted due to the temperate climate preventing the spread of the vector. This study investigated the prevalence and etiology of congenital microcephaly in RS in two different periods. This cross-sectional descriptive study included all live births with congenital microcephaly in RS from 2015 to 2022. Cases were divided into two groups: P1 “outbreak” (2015-16); and P2 “endemic” (2017-22). There were 58 cases of microcephaly (3.8/10,000) in P1 and 148 (1.97/10,000) in P2. Congenital Zika Virus infection was the etiology in 5.2% (n=3) in P1 and 6.7% (n=10) in P2. In conclusion, although the ZIKV outbreak in Brazil has receded, RS remains an area of concern, with a possible slight increase of live births with microcephaly secondary to ZIKV prenatal infection relative to the number of cases due to congenital infections. The broader distribution of the vector Aedes aegypti with warmer temperatures in our state might be linked to the increase in recent years. This study can be an alert to other regions of temperate or subtropical climates.
... Yockey found an overexpression of genes related to the hypoxia pathway in the placentas of animals exposed to ZIKV [25]. It is known that viral infections, such as cytomegalovirus, which is also a teratogenic virus that leads to microcephaly, can change oxygen consumption and lead to cell hypoxia [66,67]. Changes in brain development have already been associated with prenatal hypoxia [68]. ...
Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted to investigate the molecular mechanisms related to ZIKV teratogenesis. Although animal models can mimic the effects of ZIKV in human embryo development, few in vivo studies have addressed molecular changes following ZIKV infection in embryos. Moreover, few literature reviews have been conducted with these studies. The aim of this systematic review is to evaluate the molecular mechanisms of ZIKV teratogenesis determined from studies in animal models. PubMed/MEDLINE, EMBASE, Web of Science, and Scopus as well as grey literature were searched for studies that evaluated molecular alterations related to ZIKV teratogenesis which occurred during embryonic development. Nine studies were included: six with mice, one with mice and guinea pigs, one with pigs and one with chickens. In general, studies presented an unclear or high risk of bias for methodological criteria. Most of studies reported embryos exposed to ZIKV presenting microcephaly, reduced cortex thickness, and growth restriction. Different techniques were used to evaluated molecular changes in the animals following ZIKV infection: RNA sequencing, RT-qPCR, and in situ hybridization. It was found that common pathways are changed in most studies, being pathways related to immune response upregulated and those involved to neurodevelopment downregulated.
... Although numerous, almost all publications in databases were unable to answer the target question of this review. For the primary endpoint of congenital microcephaly due to an infectious cause, it was possible to extract data in only 10 articles [19][20][21][22][23][24][25][26][27][28] . All selected studies were published after the year 2015, with data obtained in the period between years 2015 and 2017, during the ZIKV epidemic in the country. ...
... A study with a similar design was conducted concomitantly in Sergipe State, and the same operational problems for the etiological confirmation were found in the evaluation of 60 cases of microcephaly reported to that Health Secretariat 22 . An article that should be highlighted is the crosssectional study by Herber et al. 28 that aimed to identify the causes of congenital microcephaly during the period of Public Health Emergency in Brazil, in Rio Grande do Sul State, where no ZIKV outbreak was detected. During the study period, 15% of microcephaly cases (n=39) with confirmed etiological infectious diagnosis and a predominance of congenital syphilis cases, with only three (1%) confirmed cases of maternal infection by ZIKV. ...
... They provided evidence on the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vacines. In addition, the casecontrol studies by Rocha et al. 27 and the cross-sectional study by Herber et al. 28 confirmed microcephaly due to ZIKV by laboratory and/or radiological methods. ...
This systematic review aimed to identify the pathogens causing or associated with congenital microcephaly in Brazil in the last 20 years due to the lack of official information by the Health Authorities and, as a consequence the uncertainty on the real infectious etiology of congenital microcephaly. A review protocol was prepared according to the PRISMA recommendation, using the PubMed, SciELO and LILACS databases to search for references presenting original data on microcephaly caused by or associated with congenital infectious in Brazil, using the descriptors “MICROCEPHALY AND INFECTION”. The search ended on 30/Jun/2020. All selected titles were read in full and analyzed independently by the three reviewers. After searching the databases, 2,389 articles were selected for title review. Of these, 109 were excluded due to duplicates and 2,236 according to the criteria defined in the review. Only 44 met the eligibility criteria and were therefore read in full. Data extraction was performed on 10 articles, all published after 2015. Seven studies were literature reviews or case series, only two were case-control, and one was a cross-sectional study. As the studies focused on the period of the ZIKV epidemic in Brazil, the cases of congenital microcephaly between 2015 and 2017 were attributed to maternal infection by this virus when it was not possible to prove the presence of other etiological agents. Among the TORCH agents, a predominance of syphilis was observed. The analyzed studies did not add consistent information about the infectious causes or association of microcephaly in Brazil outside the period of ZIKV epidemic, revealing the need for more studies on the subject.
Microcephaly; Newborn; Congenital infection
... Transmission of infectious agents from mother to fetus can be devastating for fetal brain development (Bale and Murph, 1992;Brasil et al., 2016;Marquez et al., 2011). Infections account for up to 50% of cases of congenital microcephaly (Herber et al., 2019;Mlakar et al., 2016), and those occurring in the first trimester of pregnancy are typically associated with more severe outcomes (Coyne and Lazear, 2016). Despite these overlapping phenotypes, congenital infections are caused by distinct pathogens collectively referred to as TORCH (Toxoplasma gondii, other, Rubella, human cytomegalovirus [HCMV], herpes simplex viruses 1 and 2 [HSV-1 and HSV-2, respectively], and Zika virus [ZIKV]) (Schwartz, 2017). ...
Viral infection in early pregnancy is a major cause of microcephaly. However, how distinct viruses impair human brain development remains poorly understood. Here we use human brain organoids to study the mechanisms underlying microcephaly caused by Zika virus (ZIKV) and herpes simplex virus (HSV-1). We find that both viruses efficiently replicate in brain organoids and attenuate their growth by causing cell death. However, transcriptional profiling reveals that ZIKV and HSV-1 elicit distinct cellular responses and that HSV-1 uniquely impairs neuroepithelial identity. Furthermore, we demonstrate that, although both viruses fail to potently induce the type I interferon system, the organoid defects caused by their infection can be rescued by distinct type I interferons. These phenotypes are not seen in 2D cultures, highlighting the superiority of brain organoids in modeling viral infections. These results uncover virus-specific mechanisms and complex cellular immune defenses associated with virus-induced microcephaly.
... ber of newborns, microcephaly was detected in 9.6 per 10,000 live births (from the initial sample, 60.8% were ''nonconfirmed'' microcephaly). [19] In Brazil, those differences in the prevalence of microcephaly may also have occurred because of the different cutoff points established by the Brazilian MoH from November 2015 to August 2016. During this period, four different cutoff points were considered (for term babies: 33 cm in November 2015, 32 cm in December 2015, WHO curve in March 2016, and IG curve in August 2016; for preterm babies: Fenton curve from November 2015 to March 2016, and then the IG curve). ...
Objective
We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health (MoH) at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly.
Method
This retrospective study utilized newborn participants in the Zika Cohort Study Jundiaí (ZCJ). Newborns from the ZCJ with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve (IG). At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic (ROC) curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis.
Results
Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction (IUGR); one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%).
Conclusions
Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby.
Zika virus (ZIKV) infection became a global public health concern, causing an epidemic in Latin America from 2015 to 2016, when a sudden increase in cases of microcephaly and other congenital anomalies was observed. In 2016, the Centers for Disease Control and Prevention and the World Health Organization defined congenital Zika-associated syndrome (CZS) as a set of congenital anomalies seen in children born to mothers with a history of gestational Zika fever, who have microcephaly as the most prevalent clinical sign. In order to describe the magnitude of CZS in Brazil, this study estimated the burden of disease due to CZS in Brazil using the disability-adjusted life years (DALY) indicator and other frequency measures, such as incidence and mortality rate, during the years 2015–2020. The association of these indicators with socioeconomic variables was also evaluated using Spearman's correlation coefficient. Choropleth maps were used to evaluate the spatial distribution of the indicators evaluated and the spatial autocorrelation was verified by the Bivariate Moran Local Index. From 2015 to 2020, 3,591 cases of CZS were confirmed in Brazil, with an incidence of 44.03 cases per 1000 live births, and a specific mortality of 12.35 deaths per 1000 live births. A global loss of 30,027.44 DALYs was estimated from 2015 to 2020. The Northeast region had the highest values for all health indicators assessed. Spatial correlation and autocorrelation analyses showed significant associations between health and socioeconomic indicators, such as per capita income, Gini index, illiteracy rate and basic sanitation. The study allowed us to have access to all reported cases of CZS, showing us the possible situation of the disease in Brazil; therefore, we believe that our results can help in the understanding of future studies.
Introduction:
Primary microcephaly (MCPH) is not an uncommon disorder with multiple etiologies. There is a growing number of MCPH-related genes discovered due to the extensive application of whole-exome sequencing (WES) in clinical and research settings. Biallelic mutations in the SASS6 gene cause an extremely rare MCPH, type 14. To date, only two families with SASS6 gene-related microcephaly have been reported.
Case description:
We report a case of recurrent congenital microcephaly in a Chinese family. The two affected fetuses presented with microcephaly early in the second trimester with agenesis of the corpus callosum. In the first affected fetus, trio WES detected two compound heterozygous candidate variants c.1139T>C(p.L380P) and c.1223C>G (p.T408S) in the SASS6 gene. Another affected fetus also inherited both variants, while the normal child carried neither variant through Sanger sequencing analysis. Both variants were classified as a variant of uncertain significance according to the current American College of Medical Genetics and Genomics guidelines.
Conclusion:
We reported novel biallelic variants in the SASS6 gene, encoding the SAS6 centriolar assembly protein, associated with prenatal onset of autosomal recessive microcephaly. We postulate that the pathomechanism of the compound heterozygous variants in close proximity could potentiate the overall coiled instability leading to the phenotypic features of our case.
Background and objective:
During embryonic development, the dysregulation of the proliferation and differentiation of neuronal progenitors triggers congenital brain malformations. These malformations are common causes of morbidity and mortality in patients younger than 2 years old. Animal models have provided considerable insights into the etiology of diseases that cause congenital brain malformations. However, the interspecies differences in brain structure limit the ability to transfer these insights directly to studies of humans. In recent years, brain organoids generated from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) using a 3-dimensional (3D) culture system have been used to resemble the structure and function of a developing human brain. Therefore, we aimed to summarize the different congenital brain malformations that have been modeled by organoids and discuss the ability of this model to reveal the cellular and molecular mechanisms of congenital brain malformations.
Methods:
A comprehensive search was performed using PubMed and Web of Science's Core Collection for literature published from July 1, 2000 to July 1, 2022. Keywords included terms related to brain organoids and congenital brain malformations, as well as names of individual malformations.
Key content and findings:
The self-assembled 3D aggregates have been used to recapitulate structural malformations of human brains, such as microcephaly, macrocephaly, lissencephaly (LIS), and periventricular nodular heterotopia (PH). The use of disease-specific brain organoids has revealed unprecedented details of mechanisms that cause congenital brain malformations.
Conclusions:
This review summarizes the establishment and development of brain organoid technologies and provides an overview of their applications in modeling congenital brain malformations. Although several hurdles still need to be overcome, using brain organoids has greatly expanded our ability to reveal the pathogenesis of congenital brain malformations. Compared with existing methods, the combination with cutting-edge technologies enables a more accurate diagnosis and development of increasingly personalized targeted therapy for patients with congenital brain diseases.
