Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be ...proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult.
A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined.
Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5-26.2) had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC) of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65).
A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at-risk individuals for genetic evaluations.
The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches ...attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries.
ABSTRACT This cross-sectional study sought to evaluate motor development in infants exposed to ZIKV born with normal head circumference (HC). Thirty one children, distributed into two groups, ...participated in the study: 15 whose mothers were infected by ZIKV during pregnancy, born with HC from −1.9 to +2 Z-scores, adjusted for sex and gestational age (exposed group); and 16 randomly selected infants without known prenatal exposure to ZIKV, paired by sex and age (control group). Alberta Infant Motor Scale (AIMS) was used to evaluate gross motor development. We found no significant difference between the exposed and control groups. However, considering that AIMS is a screening test that assesses only the gross motor development and the small size of our sample, infants exposed to ZIKV during pregnancy should be continuously evaluated for different aspects of their development.
RESUMEN El presente estudio objetivó evaluar el desarrollo motor de niños expuestos al virus del Zika nacidos con la circunferencia de la cabeza (CC) normal. Estudio transversal. Participaron 31 niños en el estudio y se distribuyeron en dos grupos: 15 niños cuyas madres habían sido infectadas por el virus del Zika durante el embarazo nacieron con CC entre −1,9 y +2 puntajes Z ajustados por sexo y edad gestacional (grupo expuesto); y 16 controles seleccionados al azar pareados por sexo y edad, sin exposición prenatal conocida al virus del Zika (grupo no expuesto). La Alberta Infant Motor Scale (AIMS) se utilizó para evaluar el desarrollo motor grueso. No hubo diferencias significativas entre el grupo expuesto y el grupo no expuesto. A pesar de alentador, debemos destacar que la AIMS es una prueba de detección, que solo evalúa el desarrollo motor grueso, y que nuestra muestra fue pequeña. Por lo tanto, los niños expuestos al virus del Zika durante el embarazo se deben evaluar continuamente para que se identifiquen los diferentes aspectos de su desarrollo.
RESUMO O objetivo do estudo foi avaliar o desenvolvimento motor de crianças expostas ao ZIKV, nascidas com perímetro cefálico normal (PC). Estudo transversal. Trinta e uma crianças participaram do estudo, distribuídas em dois grupos: 15 crianças cujas mães foram infectadas pelo ZIKV durante a gravidez, nascidas com PC medido entre −1,9 e +2 escores Z ajustados para sexo e idade gestacional (grupo exposto); e 16 controles aleatoriamente selecionados pareados por sexo e idade, sem exposição pré-natal conhecida ao ZIKV (grupo não exposto). Alberta Infant Motor Scale (AIMS) foi usado para avaliar o desenvolvimento motor grosso. Não houve diferenças significativas entre os grupos expostos e não expostos. Embora reconfortante, devemos destacar que o AIMS é um teste de triagem e apenas avalia o desenvolvimento motor grosso, e nossa amostra foi pequena. Portanto, crianças expostas ao ZIKV na gravidez devem ser continuamente avaliadas quanto a diferentes aspectos de seu desenvolvimento.
Abstract
Objective
This study aims to describe clinical findings and determine the medium-term survival of congenital zika syndrome (CZS) suspected cases.
Methods
A retrospective cohort study using ...routine register-based linked data. It included all suspected cases of CZS born in Brazil from January 1, 2015, to December 31, 2018, and followed up from birth until death, 36 months, or December 31, 2018, whichever came first. Latent class analysis was used to cluster unconfirmed cases into classes with similar combinations of anthropometry at birth, imaging findings, maternally reported rash, region, and year of birth. Kaplan–Meier curves were plotted, and Cox proportional hazards models were fitted to determine mortality up to 36 months.
Results
We followed 11,850 suspected cases of CZS, of which 28.3% were confirmed, 9.3% inconclusive and 62.4% unconfirmed. Confirmed cases had almost two times higher mortality when compared with unconfirmed cases. Among unconfirmed cases, we identified three distinct clusters with different mortality trajectories. The highest mortality risk was observed in those with abnormal imaging findings compatible with congenital infections (HR = 12.6; IC95%8.8–18.0) and other abnormalities (HR = 11.6; IC95%8.6–15.6) compared with those with normal imaging findings. The risk was high in those with severe microcephaly (HR = 8.2; IC95%6.4–10.6) and macrocephaly (HR = 6.6; IC95%4.5–9.7) compared with normal head size.
Conclusion
Abnormal imaging and head circumference appear to be the main drivers of the increased mortality among suspected cases of CZS. We suggest identifying children who are more likely to die and have a greater need to optimise interventions and resource allocation regardless of the final diagnoses.
This research aimed to investigate the dentofacial characteristics of patients with Incontinentia Pigmenti (IP) (or Bloch-Sulzberger) syndrome in childhood, juvenile, and adulthood developmental ...stages.
Fifteen female patients with a clinical diagnosis of IP, genetically confirmed by molecular testing, were included in this study. The records of 25 nonsyndromic females with Class I occlusion and lateral cephalograms obtained at similar developmental stages were selected from the American Association of Orthodontists Foundation Legacy Collection as a control group. Dentofacial features of subjects with IP and those in the control group were compared statistically using t test and Mann-Whitney rank-sum test (significance was defined as P <0.05).
In general, patients with IP had shorter maxillary and mandibular length, straight skeletal profile, hypodivergent growth pattern with a tendency to mandibular protrusion, shorter anterior facial height, Class III compensatory positioning of incisors, more retruded lips, and smaller maxillary incisor exposure. The degree of hypodontia severity had a significant impact on skeletal, dental, and soft-tissue features in patients with IP.
The results of this study showed that, since childhood, the dentofacial characteristics of patients with IP were progressively distancing from those of nonsyndromic patients with Class I occlusion, presenting their own orthodontic needs.
•Patients with IP syndrome showed medium to large deviations in dentofacial features.•From childhood, IP dentofacial features were gradually moving away from normality.•IP syndorme had a straight skeletal profile, chin protrusion and short facial height.•Skeletal features were associated with dental compensation and more retruded lips.•Hypodontia influenced skeletal, dental, and soft-tissue features of patients with IP.
Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, ...which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis.
Congenital anomalies (CA) contribute to disabilities and health conditions throughout life. Furthermore, they can cause emotional distress to the mothers and children, who may also experience ...limitations in individual and social development. This study investigated the prevalence of CA and the relationship with maternal education and age according to local development in the extreme south of Brazil. This is a retrospective observational study with birth data from the Live Birth Information System from 2000 to 2017. The association between age and maternal education with the presence of CA was verified using multiple Poisson regression for robust variances in models adjusted for those variables with a preliminary significant association. A total of 5131 (1.5%) had some CA identified at birth between 2000 and 2017. Only advanced age (≥36 years) was associated with CA regardless of macro-region development (p ≤ 0.001). The highest risk was observed in regions with medium development (RR = 1.60; 95% CI 1.30−1.97). Maternal education (<8 years of study) was associated with CA only in mothers from macro-regions with very high development (RR = 1.27; 95% CI 1.03−1.54). These analyses confirmed that women of advanced age are at greater risk of having children with a CA regardless of maternal education and local development, but social characteristics can also have an influence, as regions with higher development had lower prevalence of CA.
Fetal Alcohol Spectrum Disorders: Health Needs Assessment in Brazil Rocha, Anastácia Guimarães; Souza, Paulo Ricardo Assis; Wachholz, Gabriela Elis ...
Alcoholism, clinical and experimental research,
March 2020, 2020-Mar, 2020-03-00, 20200301, Volume:
44, Issue:
3
Journal Article
Peer reviewed
Background
Fetal alcohol syndrome (FAS) is a disorder caused by alterations in embryo‐fetal development due to prenatal alcohol exposure. It is estimated that between 0.5 and 2 per 1,000 individuals ...are born with FAS every year. In Brazil, there are few studies addressing the extent of the problem of FAS/fetal alcohol spectrum disorders (FASD); these studies are confined to limited geographic areas. Therefore, we decided to perform a health needs assessment for FAS/FASD in Brazil.
Methods
To estimate the prevalence of FAS and FASD in Brazil, we used information from the literature, which estimates between 0.5 and 2/1,000 births per year for FAS and 10 to 50/1,000 for FASD.
Results
We estimated that approximately 1,500 to 6,000 children are born with FAS every year. Considering the whole population, the prevalence would be 95,377 to 380,000 affected people. However, when we consider FASD as a whole, we estimate that between 1,900,000 and 9,500,000 Brazilians might suffer the more severe consequences of alcohol exposure during pregnancy and be living with FASD.
Conclusion
The results of the current study indicate that FAS and FASD are prevalent disorders in Brazil, and more policies targeting alcohol intake during pregnancy must be developed.
Since the 1960s, drugs have been known to cause teratogenic effects in humans. Such teratogenicity has been postulated to be influenced by genetics. The aim of this review was to provide an overview ...of the current knowledge on genetic susceptibility to drug teratogenicity in humans and reflect on future directions within the field of genetic teratology. We focused on 12 drugs and drug classes with evidence of teratogenic action, as well as 29 drugs and drug classes with conflicting evidence of fetal safety in humans. An extensive literature search was performed in the PubMed and EMBASE databases using terms related to the drugs of interest, congenital anomalies and fetal development abnormalities, and genetic variation and susceptibility. A total of 29 studies were included in the final data extraction. The eligible studies were published between 1999 and 2020 in 10 different countries, and comprised 28 candidate gene and 1 whole-exome sequencing studies. The sample sizes ranged from 20 to 9,774 individuals. Several drugs were investigated, including antidepressants (nine studies), thalidomide (seven studies), antiepileptic drugs (five studies), glucocorticoids (four studies), acetaminophen (two studies), and sex hormones (estrogens, one study; 17-alpha hydroxyprogesterone caproate, one study). The main neonatal phenotypic outcomes included perinatal complications, cardiovascular congenital anomalies, and neurodevelopmental outcomes. The review demonstrated that studies on genetic teratology are generally small, heterogeneous, and exhibit inconsistent results. The most convincing findings were genetic variants in
, and
, which were associated with drug teratogenicity by antidepressants, antiepileptics, and glucocorticoids, respectively. Notably, this review demonstrated the large knowledge gap regarding genetic susceptibility to drug teratogenicity, emphasizing the need for further efforts in the field. Future studies may be improved by increasing the sample size and applying genome-wide approaches to promote the interpretation of results. Such studies could support the clinical implementation of genetic screening to provide safer drug use in pregnant women in need of drugs.
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