Effectiveness of brief alcohol interventions for pregnant women: a systematic literature review and meta-analysis.

BACKGROUND: Prenatal alcohol exposure (PAE) can result in a range of adverse neonatal outcomes, including Fetal Alcohol Spectrum Disorder (FASD). This systematic review and meta-analysis sought to investigate the effectiveness of brief interventions (BIs) in eliminating or reducing 1) alcohol consumption during pregnancy; and 2) PAE-related adverse neonatal outcomes; and 3) cost-effectiveness of BIs. METHOD: We conducted a systematic literature search for original controlled studies (randomized control trials (RCTs); quasi-experimental) in any setting, published from 1987 to 2021. The comparison group was no/minimal intervention, where a measure of alcohol consumption was reported. Studies were critically appraised using the Centre for Evidence-based Medicine Oxford critical appraisal tool for RCTs (1). The certainty in the evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) (2). Meta-analysis of continuous and binary estimates of effect-size for similar outcome measures for BIs versus control groups were pooled and reported as mean difference (MD) Hedges' g and odds ratios (ORs), respectively. RESULTS: In total, 26 studies, all from high income countries, met inclusion criteria. Alcohol abstinence outcome available in 12 studies (n = 2620) found modest effects in favor of BIs conditions by increasing the odds of abstinence by 56% (OR = 1.56, 95% confidence interval (CI) = 1.15-2.13, I2 = 46.75%; p = 0.04). BIs effects for reduction in mean drinks/week (Cohen's d = - 0.21, 95%CI = - 0.78 to 0.36; p = 0.08) and AUDIT scores (g = 0.10, 95%CI = - 0.06 to 0.26; p = 0.17) were not statistically significant. Among seven studies (n = 740) reporting neonatal outcomes, BI receipt was associated with a modest and significant reduction in preterm birth (OR = 0.67, 95% CI = 0.46-0.98, I2 = 0.00%; p = 0.58). No statistically significant differences were observed for mean birthweight or lower likelihood of low birth weight (LBW). Certainty in the evidence was rated as 'low'. No eligible studies were found on cost-effectiveness of BIs. CONCLUSION: BIs are moderately effective in increasing abstinence during pregnancy and preventing preterm birth. More studies on the effectiveness of BIs are needed from low- and middle-income countries, as well as with younger mothers and with a broader range of ethnic groups.

Ear Abnormalities Among Children with Fetal Alcohol Spectrum Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review and conduct meta-analysis on studies that report the type and prevalence of functional and structural ear abnormalities among children with prenatal alcohol exposure and/or fetal alcohol spectrum disorder (FASD). STUDY DESIGN: MEDLINE, PubMed, Embase, Web of Science, PsycINFO, ERIC, CINAHL, and Maternity and Infant Care were searched from 1806 through March 2021. Reference lists of relevant articles were manually searched. Studies reporting on functional and/or structural ear abnormalities among children (<18 years) with prenatal alcohol exposure and/or FASD were eligible. Data extraction and quality assessment were performed by one reviewer and independently checked by another. A random effects meta-analysis was conducted. RESULTS: A total of 31 studies met the inclusion criteria and 25 were included in the meta-analyses, representing a total of 843 children with prenatal alcohol exposure and 1653 children with FASD. Functional ear abnormalities with the highest pooled prevalence were chronic serous otitis media (88.5%; 95% CI, 70.4%-99.3%), abnormal auditory filtering (80.1%; 95% CI, 76.5%-84.3%), and unspecified conductive hearing loss (68.0%; 95% CI, 51.9%-82.2%). Structural ear abnormalities with the highest pooled prevalence were microtia (42.9%; 95% CI, 26.8%-59.7%), railroad track ear (16.8%; 95% CI, 8.1%-27.7%), and misplaced ear (12.3%; 95% CI, 7.6%-17.9%). CONCLUSIONS: Our findings highlight the importance of examining the ears during assessment for FASD, and the need for public health messaging regarding the harms of prenatal alcohol exposure.

Maternal alcohol use, adverse neonatal outcomes and pregnancy complications in British Columbia, Canada: a population-based study.

BACKGROUND: The current study aimed to estimate the prevalence of alcohol use identified as a risk factor during pregnancies by the antenatal care providers, resulting in live births in British Columbia (BC) and to examine associations between alcohol use, adverse neonatal outcomes, and pregnancy complications. METHODS: This population-based cross-sectional study utilized linked obstetrical and neonatal records within the BC Perinatal Data Registry (BCPDR), for deliveries that were discharged between January 1, 2015 and March 31, 2018. The main outcome measures were alcohol use identified as a risk factor during pregnancy, associated maternal characteristics, pregnancy complications, and adverse neonatal outcomes. Estimates for the period and fiscal year prevalence were calculated. Chi-square tests were used to compare adverse neonatal outcomes and pregnancy complications by alcohol use during pregnancy identified as a risk factor. Logistic regression was used to examine the association between alcohol use identified as a risk factor during pregnancy and adverse neonatal outcomes and pregnancy complications, after adjusting for identified risk factors. RESULTS: A total of 144,779 linked records within the BCPDR were examined. The period prevalence of alcohol use during pregnancy identified as a risk factor was estimated to be 1.1% and yearly prevalence was 1.1, 1.1, 1.3 and 0.9% from the 2014/2015 to 2017/2018 fiscal years, respectively. Alcohol use identified as a risk factor was associated with younger maternal age, fewer antenatal visits, being primiparous, a history of mental illness, substance use and smoking. Neonates with alcohol use during pregnancy identified as a risk factor had greater odds of being diagnosed with: "low birth weight (1000-2499g)" (ICD-10: P07.1; aOR = 1.25; 95% CI: 1.01, 1.53), "other respiration distress of newborn" (ICD-10: P22.8; aOR = 2.57; 95% CI: 1.52, 4.07), "neonatal difficulty in breastfeeding" (ICD-10: P92.5; aOR = 1.97; 95% CI: 1.27, 2.92) and "feeding problems, unspecified" (ICD-10: P92.9; aOR = 2.06; 95% CI: 1.31, 3.09). CONCLUSIONS: The prevalence of alcohol use during pregnancy identified as a risk factor was comparable to previous estimates within the BCPDR. Identified prenatal alcohol exposure was associated with notable differences in maternal and neonatal characteristics and adverse neonatal outcomes. More consistent, thorough screening and prevention efforts targeting alcohol use in pregnancy are urgently needed in Canada.

Isobornylchalcones as Scaffold for the Synthesis of Diarylpyrazolines with Antioxidant Activity.

The pyrazoline ring is defined as a "privileged structure" in medicinal chemistry. A variety of pharmacological properties of pyrazolines is associated with the nature and position of various substituents, which is especially evident in diarylpyrazolines. Compounds with a chalcone fragment show a wide range of biological properties as well as high reactivity which is primarily due to the presence of an α, ß-unsaturated carbonyl system. At the same time, bicyclic monoterpenoids deserve special attention as a source of a key structural block or as one of the pharmacophore components of biologically active molecules. A series of new diarylpyrazoline derivatives based on isobornylchalcones with different substitutes (MeO, Hal, NO2, N(Me)2) was synthesized. Antioxidant properties of the obtained compounds were comparatively evaluated using in vitro model Fe2+/ascorbate-initiated lipid peroxidation in the substrate containing brain lipids of laboratory mice. It was demonstrated that the combination of the electron-donating group in the para-position of ring B and OH-group in the ring A in the structure of chalcone fragment provides significant antioxidant activity of synthesized diarylpyrazoline derivatives.

Fetal alcohol spectrum disorder: neurodevelopmentally and behaviorally indistinguishable from other neurodevelopmental disorders.

BACKGROUND: The lack of universally accepted diagnostic criteria and the high rate of psychiatric comorbidity make it difficult to diagnose Fetal Alcohol Spectrum Disorder (FASD). In an effort to improve the diagnosis of FASD, the current study aimed to identify a neurodevelopmental profile that is both sensitive and specific to FASD. METHODS: A secondary analysis was conducted on data obtained from the Canadian component of the World Health Organization International Study on the Prevalence of FASD. Data on neurodevelopmental status and behavior were derived from a battery of standardized tests and the Child Behavior Checklist for 21 children with FASD, 28 children with other neurodevelopmental disorders, and 37 typically developing control children, aged 7 to 11 years. Two latent profile analyses were performed to derive discriminative profiles: i) children with FASD compared with typically developing control children, and ii) children with FASD compared with typically developing control children and children with other neurodevelopmental disorders. The classification function of the resulting profiles was evaluated using the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Confidence intervals (CIs) were approximated using 10,000 bootstrapped samples. RESULTS: The neurodevelopmental profile of FASD tested consisted of impairments in perceptual reasoning, verbal comprehension, visual-motor speed and motor coordination, processing speed (nonverbal information), attention and executive function, visuospatial processing, and language, in combination with rule-breaking behavior and attention problems. When children with FASD were compared with typically developing control children, a 2-class model fit the data best and resulted in a sensitivity of 95.2% (95% CI: 84.2-100.0%), specificity of 89.2% (95% CI: 78.4-97.5%), PPV of 83.3% (95% CI: 66.7-96.2%), and NPV of 97.1% (95% CI: 90.3-100.0%). When children with FASD were compared with typically developing control children and children with other neurodevelopmental disorders, the neurodevelopmental profile correctly identified only 56.9% (95% CI: 45.1-69.2%) of typically developing children and children with other neurodevelopmental disorders as not having FASD, and thus the profile was found not to be specific to children with FASD. CONCLUSION: The findings question the uniqueness of children with FASD with respect to their neurodevelopmental impairments and behavioral manifestations.

Population-based prevalence of fetal alcohol spectrum disorder in Canada.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is one of the most disabling potential outcomes of prenatal alcohol exposure. The population-based prevalence of FASD among the general population of Canada was unknown. The objective of this study was to determine the population-based prevalence of FASD among elementary school students, aged 7 to 9 years, in the Greater Toronto Area (GTA) in Ontario, Canada. METHODS: This screening study used a cross-sectional, observational design utilizing active case ascertainment, along with retrospective collection of prenatal alcohol exposure information. Data collection involved two phases. Phase I consisted of taking growth measurements, a dysmorphology examination, and obtaining a history of behavioral and/or learning problems. Phase II consisted of a neurodevelopmental assessment, maternal interview, and behavioral observations/ratings by parents/guardians. Final diagnostic screening conclusions were made by consensus by a team of experienced multidisciplinary experts during case conferences, using the 2005 Canadian guidelines for FASD diagnosis. The prevalence of FASD was estimated, taking into consideration the selection rate, which was used to account for students who dropped out or were lost to follow-up during each phase. Monte Carlo simulations were employed to derive the confidence interval (CI) for the point estimates. RESULTS: A total of 2555 students participated. A total of 21 cases of suspected FASD were identified. The prevalence of FASD was estimated to be 18.1 per 1000, or about 1.8%. Using a less conservative approach (sensitivity analysis), the prevalence of FASD was estimated to be 29.3 per 1000, or about 2.9%. Therefore, the population-based prevalence of FASD is likely to range between 2 and 3% among elementary school students in the GTA in Ontario, Canada. CONCLUSIONS: This study provides the first population-based estimate of the prevalence of FASD in Canada. The estimate is approximately double or possibly even triple previous crude estimates. FASD prevalence exceeds that of other common birth defects such as Down's syndrome, spina bifida, trisomy 18, as well as autism spectrum disorder in Canada. More effective prevention strategies targeting alcohol use during pregnancy, surveillance of FASD, and timely interventions and support to individuals with FASD and their families are urgently needed.

Association of adverse childhood experiences and neurodevelopmental disorders in people with fetal alcohol spectrum disorders (FASD) and non-FASD controls.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a highly prevalent lifelong disorder with high rates of comorbid neurodevelopmental disorders. Individuals with FASD are often exposed to abuse, neglect and foster home placements which have uncertain effects on the lifelong course of FASD. In this study we compare the prevalence of adverse childhood events (ACEs) and neurodevelopmental disorders in subjects with fetal alcohol spectrum disorders (FASD) and non-FASD controls. METHODS: A cross-sectional chart review of patients referred to a regional developmental center was used to identify people with FASD and non-FASD controls. We recorded the number of ACEs and neurodevelopmental disorders in each patient's chart. The most common diagnoses were attention deficit hyperactivity disorder, comprehension deficits, sleep disorders, and cognitive impairments. T-tests and a regression equation were utilized to determine significant differences between the groups. RESULTS: The review identified 203 subjects, 98 with FASD and 105 non-FASD controls. Group mean age was 8.6 years and 64.5% were male. People with FASD were more likely to have any ACEs (mean 5.3) with ACE scores 3.7 points higher than non-FASD controls (mean 1.69) (t = 11.29; p < .001). Increased ACEs were associated with increased rates of neurodevelopmental disorders for people with FASD (R = .179, p = .026) but not for non-FASD controls (R = .130, p = .094). CONCLUSIONS: Both FASD and subsequent exposure to ACEs are associated with increased risk for development of comorbid neurodevelopmental disorders. Prevention of ACEs during childhood may decrease risk for development of comorbid neurodevelopmental disorders.

Simultaneous atrazine degradation and E. coli inactivation by UV/S2O82-/Fe2+ process under KrCl excilamp (222 nm) irradiation.

This study is the first to reveal that the iron-catalyzed photo-activation of persulfate (UV/PS/Fe2+system) under mercury-free KrCl excilamp irradiation (222 nm) is capable of simultaneous degradation of an organic pollutant and inactivation of a microorganism in aqueous media using the herbicide atrazine (ATZ) and E. coli as model contaminants, respectively. Deionized water, natural water and wastewater effluents, contaminated with 4 mg/L ATZ and/or 105 CFU/mL E. coli, were sequentially treated by direct UV, UV/PS and UV/PS/Fe2+ processes. Lowering the pH to 3.5 accelerated both the degradation and inactivation during the UV/PS/Fe2+ treatment of natural water. Comparison of the apparent UV dose-based pseudo first-order rate constants showed the negative effect of E. coli on ATZ degradation by decreasing rates in all of the examined water matrices. This can be due to the competitive effect between ATZ and bacterial cells for reactive oxygen species (ROS). By contrast, E. coli in the presence of ATZ was inactivated faster in natural water and wastewater (but not in deionized water), as compared to the case without ATZ. A scheme of possible synergistic inactivation under ROS exposure in water, containing ATZ, natural organic matter and chloride ions as primary constituents, was proposed. Radical scavenging experiments showed a major contribution of SO4•- to ATZ degradation by UV/PS/Fe2+ treatment of deionized water and natural water. The UV doses, required for 90% removal of ATZ from natural water and wastewater, achieve 160 mJ/cm2 (pH 5.5) and concurrently provide 99.99% E. coli inactivation. These results make the UV/PS/Fe2+ system with narrow band UV light sources promising for simultaneous water treatment and disinfection.

Synthesis and Biological Evaluation of Novel Coumarins with tert-Butyl and Terpene Substituents.

Coumarins with terpene and tert-butyl substituents were synthesized via Pechmann condensation reaction. New derivatives were investigated in different model system for the exhibition of antioxidant, radical scavenging and membrane-protective activities. It has been found that 4-methylcoumarin derivatives with monoterpene moieties exhibit high antioxidant activities. The most active and promising for further investigations is 5-hydroxy-6,8-diisobornyl-4-methylcoumarin, containing two isobornyl substituents on the benzopyran ring.

Global prevalence of alcohol use and binge drinking during pregnancy, and fetal alcohol spectrum disorder.

Alcohol use during pregnancy is an established cause of fetal alcohol spectrum disorder (FASD), with heavy drinking during pregnancy being explicitly linked to fetal alcohol syndrome (FAS). This paper presents recent estimates of the prevalence of: (i) any amount of alcohol use during pregnancy; (ii) one or more binge drinking episode(s) (4 or more standard drinks on a single occasion) during pregnancy; (iii) FAS; and (iv) FASD among the general population globally and by World Health Organization region. It is apparent, based on the presented estimates, that alcohol use and binge drinking occur frequently among pregnant women in many countries and as a result, FASD is a prevalent alcohol-related developmental disability. Urgent action is required around the globe to eliminate prenatal alcohol exposure and prevent future children, adolescents, and adults from having FASD.

Prevalence of externalizing disorders and Autism Spectrum Disorders among children with Fetal Alcohol Spectrum Disorder: systematic review and meta-analysis.

Owing to their central nervous system impairments, children with Fetal Alcohol Spectrum Disorder (FASD) commonly exhibit externalizing behaviours such as hyperactivity, impulsivity, and (or) delinquency. The purpose of this study was to estimate the prevalence of neurodevelopmental disorders with prominent externalizing behaviours, namely Attention-Deficit Hyperactivity Disorder (ADHD), Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), as well as Autism Spectrum Disorders (ASD) among children with FASD. A comprehensive systematic literature search was performed, followed by disorder-specific random-effects meta-analyses. Of the disorders investigated, ADHD was found to be the most common co-morbid disorder among children with FASD (52.9%), followed by ODD (12.9%), CD (7.0%), and ASD (2.6%). When compared with the general population of the USA, these rates are notably higher: 15 times higher for ADHD, 2 times higher for ASD, 3 times higher for CD, and 5 times higher for ODD. The results call attention to the need for identifying a distinct neurodevelopmental profile to aid in the accurate identification of children with FASD and the discrimination of FASD from certain idiopathic neurodevelopmental disorders.

Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is related to many comorbidities because of the permanent effects of prenatal alcohol exposure on the fetus. We aimed to identify the comorbid conditions that co-occur in individuals with FASD and estimate the pooled prevalence of comorbid conditions occurring in individuals with fetal alcohol syndrome (FAS). METHODS: We did a systematic literature search of studies reporting on the comorbidity and cause of death in individuals with FASD using multiple electronic bibliographic databases, searching for studies published up to July, 2012. We included original research published in a peer-reviewed journal in the English language. We used the following criteria for determining study quality: use of an established FASD diagnostic guideline, study setting, method of data collection, and sample size. All comorbid disease conditions were coded according to the International Classification of Diseases, tenth revision (ICD-10). To estimate the pooled prevalence of comorbid conditions found to co-occur in individuals with FAS, we did meta-analyses assuming a random-effects model. FINDINGS: Of 5068 studies found, 127 met eligibility criteria for data extraction. From those studies, we identified 428 comorbid conditions co-occurring in individuals with FASD, spanning across 18 of 22 chapters of the ICD-10. The most prevalent disease conditions were within the sections of congenital malformations, deformities, and chromosomal abnormalities, and mental and behavioural disorders. 33 studies reported data for frequency in a total of 1728 participants with FAS. The five comorbid conditions with the highest pooled prevalence (between 50% and 91%) included abnormal results of function studies of peripheral nervous system and special senses, conduct disorder, receptive language disorder, chronic serous otitis media, and expressive language disorder. INTERPRETATION: The high prevalence of comorbid conditions in individuals with FASD highlights the importance of assessing prenatal alcohol exposure as a substantial clinical risk factor for comorbidity. The harmful effects of alcohol on a developing fetus represent many cases of preventable disability, and thus, alcohol use during pregnancy should be recognised as a public health problem globally. FUNDING: Public Health Agency of Canada.

Actual and predicted prevalence of alcohol consumption during pregnancy in Latin America and the Caribbean: systematic literature review and meta-analysis.

OBJECTIVE: To estimate the prevalence of alcohol consumption during pregnancy among the general population of Latin America and the Caribbean, by country, in 2012. METHODS: Three steps were taken: a comprehensive, systematic literature search; meta-analyses, assuming a random-effects model for countries with published studies; and regression modelling (data prediction) for countries with either no published studies or too few to obtain an estimate. RESULTS: Based on 24 existing studies, the pooled prevalence of alcohol consumption during pregnancy among the general population was estimated for Brazil (15.2%; 95% confidence interval [95%CI]: 10.4%-20.8%) and Mexico (1.2%; 95%CI: 0.0%-2.7%). The prevalence of alcohol consumption during pregnancy among the general population was predicted for 31 countries and ranged from 4.8% (95%CI: 4.2%-5.4%) in Cuba to 23.3% (95%CI: 20.1%-26.5%) in Grenada. CONCLUSIONS: Greater prevention efforts and measures are needed in the countries of Latin America and the Caribbean to prevent pregnant women from consuming alcohol during pregnancy and decrease the rates of Fetal Alcohol Spectrum Disorder. Additional high quality studies on the prevalence of alcohol consumption during pregnancy in Latin America and the Caribbean are also needed.

Actual and predicted prevalence of alcohol consumption during pregnancy in the WHO African Region.

OBJECTIVE: To estimate the prevalence of alcohol consumption and binge drinking during pregnancy among the general population in the World Health Organization (WHO) African Region, by country. METHODS: First, a comprehensive systematic literature search was performed to identify all published and unpublished studies. Then, several meta-analyses, assuming a random-effects model, were conducted to estimate the prevalence of alcohol consumption and binge drinking during pregnancy among the general population for countries in the WHO African Region with two or more studies available. Lastly, for countries with less than two studies or no known data predictions were obtained using regression modelling. RESULTS: The estimated prevalence of alcohol consumption during pregnancy among the general population ranged from 2.2% (95% confidence interval [CI]: 1.6-2.8%; Equatorial Guinea) to 12.6% (95% CI: 9.9-15.4%; Cameroon) in Central Africa, 3.4% (95% CI: 2.6-4.3%; Seychelles) to 20.5% (95% CI: 16.4-24.7%; Uganda) in Eastern Africa, 5.7% (95% CI: 4.4-7.1%; Botswana) to 14.2% (95% CI: 11.1-17.3%; Namibia) in Southern Africa, 6.6% (95% CI: 5.0-8.3%; Mauritania) to 14.8% (95% CI: 11.6-17.9%; Sierra Leone) in Western Africa, and 4.3% (95% CI: 3.2-5.3%; Algeria) in Northern Africa. CONCLUSIONS: The high prevalence of alcohol consumption and binge drinking during pregnancy in some African countries calls for educational campaigns, screening and targeted interventions for women of childbearing age.

The Economic Burden of Fetal Alcohol Spectrum Disorder in Canada in 2013.

AIM: To estimate the economic burden and cost attributable to Fetal Alcohol Spectrum Disorder (FASD) in Canada in 2013. METHODS: This cost-of-illness study examined the impact of FASD on the material welfare of the Canadian society in 2013 by analyzing the direct costs of resources expended on health care, law enforcement, children and youth in care, special education, supportive housing, long-term care, prevention and research, as well as the indirect costs of productivity losses of individuals with FASD due to their increased morbidity and premature mortality. RESULTS: The costs totaled approximately $1.8 billion (from about $1.3 billion as the lower estimate up to $2.3 billion as the upper estimate). The highest contributor to the overall FASD-attributable cost was the cost of productivity losses due to morbidity and premature mortality, which accounted for 41% ($532 million-$1.2 billion) of the overall cost. The second highest contributor to the total cost was the cost of corrections, accounting for 29% ($378.3 million). The third highest contributor was the cost of health care at 10% ($128.5-$226.3 million). CONCLUSIONS: FASD is a significant public health and social problem that consumes resources, both economic and societal, in Canada. Many of the costs could be reduced with the implementation of effective social policies and intervention programs.

A study of embryonic stem cell-related proteins in human astrocytomas: identification of Nanog as a predictor of survival.

Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO Grade II) and 98 high-grade human gliomas (WHO Grades III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n = 42) with high levels of Nanog protein (p = 0.0067) and of Klf4 protein (p = 0.0368), in high-grade astrocytomas (n = 85) with high levels of Nanog (p = 0.0042), Klf4 (p = 0.0447), and c-Myc (p = 0.0078) and in glioblastomas only (n = 71) with high levels of Nanog (p = 0.0422) and of c-Myc (p = 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p = 0.0039), high-grade astrocytomas (p = 0.0124) and glioblastomas only (p = 0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.

Subtyping of gliomas of various WHO grades by the application of immunohistochemistry.

AIMS: In 2010, four subtypes (classical, proneural, mesenchymal, and neural) of glioblastoma multiforme (GBM) were defined by molecular genetic analyses. The objective of this study was to assess whether gliomas, independently of the type and grade, could be subdivided into protein-based subtypes. METHODS AND RESULTS: A tissue microarray (TMA) approach was applied to incorporate tissue samples of low-grade and high-grade gliomas into five TMAs. High expression levels of epidermal growth factor receptor (EGFR), CD44, c-MER proto-oncogene tyrosine kinase (MERTK), platelet-derived growth factor receptor α, p53, oligodendrocyte transcription factor 2 (OLIG2) and isocitrate dehydrogenase 1 with the R132H mutation were assessed using immunohistochemistry (IHC). Glioma could be subdivided into four subtypes by IHC. The majority of the low-grade gliomas were of the proneural subtype, i.e. high p53 expression (63% of grade II). The classical subtype, with high EGFR and low p53 expression, was most common in GBMs (39%), followed by the proneural (29%) and mesenchymal (with high CD44 and MERTK expression) (29%) subtypes, a frequency that is in line with previously published data based on molecular genetics. CONCLUSIONS: Assessment of the expression of the five proteins EGFR, CD44, MERTK, p53 and OLIG2 is sufficient for subtyping gliomas, and can be recommended for implementation in clinical practice for both low-grade and high-grade gliomas.

What research is being done on prenatal alcohol exposure and fetal alcohol spectrum disorders in the Russian research community?

AIMS: Although Russia has one of the highest rates of alcohol consumption and alcohol-attributable burden of disease, little is known about the existing research on prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders (FASDs) in this country. The objective of this study was to locate and review published and unpublished studies related to any aspect of PAE and FASD conducted in or using study populations from Russia. METHODS: A systematic literature search was conducted in multiple English and Russian electronic bibliographic databases. In addition, a manual search was conducted in several major libraries in Moscow. RESULTS: The search revealed a small pool of existing research studies related to PAE and/or FASD in Russia (126: 22 in English and 104 in Russian). Existing epidemiological data indicate a high prevalence of PAE and FASD, which underlines the strong negative impact that alcohol has on mortality, morbidity and disability in Russia. High levels of alcohol consumption by women of childbearing age, low levels of contraception use, and low levels of knowledge by health and other professionals regarding the harmful effects of PAE put this country at great risk of further alcohol-affected pregnancies. CONCLUSIONS: Alcohol preventive measures in Russia warrant immediate attention. More research focused on alcohol prevention and policy is needed in order to reduce alcohol-related harm, especially in the field of FASD.

A comparison of the prevalence of prenatal alcohol exposure obtained via maternal self-reports versus meconium testing: a systematic literature review and meta-analysis.

BACKGROUND: Maternal self-reports, used for the detection of prenatal alcohol exposure (PAE), may lack validity, necessitating the use of an objective biomarker. The detection of fatty acid ethyl esters (products of non-oxidative ethanol metabolism) in meconium has been established as a novel biomarker of PAE. The purpose of the current study was to compare the prevalence of PAE as reported via maternal self-reports with the results of meconium testing, and to quantify the disparity between these two methods. METHODS: A systematic literature search for studies reporting on the prevalence of PAE, using maternal self-reports in combination with meconium testing, was conducted using multiple electronic bibliographic databases. Pooled prevalence estimates and 95% confidence intervals (CI) were calculated based on eight studies, using the Mantel-Haenszel method, assuming a random effects model. A random effects meta-regression was performed to test for a difference. RESULTS: The pooled prevalence of PAE as measured by meconium testing was 4.26 (95% CI: 1.34-13.57) times the pooled prevalence of PAE as measured by maternal self-reports. Large variations across the studies in regard to the difference between estimates obtained from maternal self-reports and those obtained from meconium testing were observed. CONCLUSIONS: If maternal self-reports are the sole information source upon which health care professionals rely, a number of infants who were prenatally exposed to alcohol are not being recognized as such. However, further research is needed in order to validate existing biomarkers, as well as discover new biomarkers, for the detection of PAE.