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Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction and repetitive and stereotyped behaviors. Serotoninergic transmission has been suggested as an important neuronal pathway in ASD. In this study, we analyzed four polymorphisms (5HTTLPR, rs2066713, STin2, rs1042173; 5′ → 3′ end) at the serotonin transporter gene ( SLC6A4 ) in a sample of 209 ASD children and their biological parents. Both single markers and haplotypes were tested for association with ASD diagnosis and with clinical symptoms (aggression, echolalia, seizures, mood instability, psychomotor agitation, repetitive behaviors and sleep disorders) commonly present in ASD patients. The family-based analyses showed a significant result for one haplotype (H4: S-G-12R-T), which did not hold in global analyses. In male patients, a nominal association between the rs1042173 GG genotype and a diminished psychomotor agitation was observed; a trend for an association between the 5HTTLPR LaLa genotype and mood instability was also verified. Through interesting results that are mainly related to clinical manifestations and gender differences, our study adds to knowledge of ASD. Future investigations may corroborate the relevance of our data to upcoming clinical and pharmacological interventions. [ABSTRACT FROM AUTHOR]

Caffeine intake during pregnancy is common. Caffeine crosses the placenta, raising concerns about its possible deleterious effects on the developing embryo/fetus. Studies on this subject show conflicting results, and still there is no consensus on the recommended dose of caffeine during pregnancy. We performed an integrative review with studies from six databases, using broad MESH terms to allow the identification of publications that addressed the outcomes of caffeine use during pregnancy, with no date limit for publications, in English and Portuguese language. The research returned 16,192 articles. After removing duplicates, screening by title, abstract and full-text, we evaluated 257 and included 59 articles. We found association between caffeine intake and pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. The effects were often dose dependent. No association with prematurity has been demonstrated, but one study showed a small reduction in gestational age with increasing doses of caffeine intake. Defining a safe dose for caffeine intake during pregnancy is a challenging task due to the heterogeneity in study designs and results, as well as the difficulty of reliably assessing the amount of caffeine consumed. In some studies, exposures below the recommended level of caffeine intake during pregnancy (200 mg/day), as suggested by the guidelines, were associated with pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. Well-designed studies with reliable quantification of caffeine intake are needed to assess the safety of low doses during pregnancy. • Guidelines recommend a maximum daily dose of 200 mg for caffeine during pregnancy. • There are conflicting findings on caffeine during pregnancy and congenital anomalies. • Caffeine intake during pregnancy has been associated with many adverse gestational outcomes. • Restricting caffeine consumption to < 200 mg is consistent with findings from epidemiological studies. [ABSTRACT FROM AUTHOR]

Although the thalidomide tragedy occurred more than 50 years ago, the medication is still being used worldwide for different reasons, and several aspects regarding its teratogenicity remain unsolved. Despite the strict regulation implemented, new cases of thalidomide embryopathy (TE) are still being registered in Brazil. Furthermore, the molecular processes that lead to malformations when the embryo is exposed to thalidomide have not yet been fully identified. In this article, we perform a critical analysis of thalidomide's history in Brazil, highlighting aspects of the occurrence of TE over the decades. Finally, we present the main perspectives and challenges for ongoing surveillance and prevention of TE in Brazil. The effective control of dispensing thalidomide, especially in areas where leprosy is endemic, is one of the most important and challenging points. Furthermore, the emergence of thalidomide analogues is fast approaching, and their availability would pose additional concerns. The understanding of the molecular mechanisms and targets of thalidomide in both experimental and human models is essential for generating new insights into teratogenic mechanisms, so that safer thalidomide analogues can be developed. [ABSTRACT FROM AUTHOR]

Introduction Thalidomide causes congenital defects in children, such as limb reduction defects. Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported. Methods We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil. Results A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54–1.66) and TEP was 0.11 (CI95%: 0.10–0.13) per 10,000 births. Poisson regression showed an increase in cases of TEP and limb reduction defects per 100,000 tablets dispensed. Clusters and geographical isolates were identified in several regions. Conclusions There is a correlation between thalidomide and TEP showing that thalidomide embryopathy should be monitored in countries where this medication is available. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorders (ASDs) represent a group of very complex early-onset neurodevelopmental diseases. In this study, we analyzed 5 SNPs (rs2317385, rs5918, rs15908, rs12603582, rs3809865) at the β3 integrin locus ( ITGB3 ), which has been suggested as a possible susceptibility gene, both as single markers and as part of haplotypes in 209 ASD children and their biological parents. We tested for association with the following: a) DSM-IV ASD diagnosis; b) clinical symptoms common in ASD patients (repetitive behaviors, echolalia, seizures and epilepsy, mood instability, aggression, psychomotor agitation, sleep disorders); and c) dimensional scores obtained with the Autism Screening Questionnaire and the Childhood Autism Rating Scale. These hypotheses were investigated using family-based tests, logistic regression models and analysis of covariance. The family-based tests showed an association with the H5 haplotype (composed by GTCGA alleles, the order of SNPs as above), which was transmitted less often than expected by chance (P = 0.006; P corr = 0.036). The analyses of the clinical symptoms showed a trend for an association with rs12603582 (P = 0.008; P corr = 0.064) and positive results for the haplotype composed of rs15908 and rs12603582 (P glcorr = 0.048; P indcorr = 0.015), both in symptoms of echolalia. Other nominal associations with different variants were found and involved epilepsy/seizures, aggression symptoms and higher ASQ scores. Although our positive results are not definitive, they suggest small effect associations of the ITGB3 gene with both ASD diagnosis and symptoms of echolalia. Other studies are nonetheless needed to fully understand the involvement of this locus on the etiology of ASDs and its different clinical aspects. [ABSTRACT FROM AUTHOR]