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1.
Annu Rev Pharmacol Toxicol ; 54: 295-315, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24160701

RESUMO

Pregnant women are almost always excluded from randomized controlled clinical trials, as the risks to the fetus posed by most new chemical entities or approved drugs cannot be sufficiently ruled out. Hence, a major scientific challenge in this field is to discover and validate alternative tools that will fill the knowledge gap created by the lack of participation in gold-standard randomized trials. This review focuses on novel tools that allow estimation of fetal risks after exposure to therapeutic agents, such as placental perfusion studies, biomarkers of fetal exposure, and novel epidemiological and pharmacogenetic tools, all of which have been tested successfully in recent years.


Assuntos
Biomarcadores/sangue , Feto/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Aleitamento Materno , Projetos de Pesquisa Epidemiológica , Feminino , Feto/metabolismo , Humanos , Relações Materno-Fetais , Metanálise como Assunto , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/sangue , Farmacogenética , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Fatores de Risco
2.
Ther Drug Monit ; 36(6): 696-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24831651

RESUMO

We describe the case of a 41-year-old woman, planning a pregnancy, who had a spontaneous abortion and subsequently was found to have high blood mercury levels. The source of high mercury was in her diet that contained fish as her main source of protein. Serial measurements of mercury in hair and blood allowed the team to determine the exact time when safe levels of mercury were reached, to eliminate elevated mercury levels as a potential cause of spontaneous abortion and to use preconception counseling to minimize the risk for adverse pregnancy outcome.


Assuntos
Contaminação de Alimentos/análise , Cabelo/química , Mercúrio/análise , Cuidado Pré-Concepcional/métodos , Reprodução/fisiologia , Alimentos Marinhos , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/diagnóstico , Adulto , Animais , Feminino , Humanos , Mercúrio/efeitos adversos , Gravidez , Fatores de Risco , Alimentos Marinhos/efeitos adversos
3.
J Pediatr ; 160(6): 1050-1, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22494871

RESUMO

Secondhand smoke is associated with a myriad of adverse health outcomes. Therefore, it is essential for clinicians to ask precise questions about exposures, particularly for children. We present 4 questions that incorporate several locations of exposure and provide a more comprehensive account of children's smoke exposures than maternal smoking alone.


Assuntos
Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Inquéritos e Questionários/normas , Poluição por Fumaça de Tabaco/efeitos adversos , Pré-Escolar , Cotinina/análise , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Ontário/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Prognóstico , Radioimunoensaio , Fatores Socioeconômicos , Fatores de Tempo
4.
Anal Bioanal Chem ; 400(1): 183-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21301822

RESUMO

Previous studies have indicated that the use of high-ethanol-content (>65%) hair-care products may elevate fatty acid ethyl ester (FAEE) concentrations in hair. In this case series, nine individuals were identified by FAEE analysis to be chronic alcohol abusers in the context of child-welfare substance abuse monitoring. Based on patient claims of moderate or no alcohol consumption, the presence of ethanol in the patients' hair-care regimens was investigated. Samples were additionally tested for the presence of ethyl glucuronide (EtG). From a total of nine patients, 12 hair samples were submitted for analysis. Patient histories were obtained as well as Material Safety Data Sheets (MSDS) listing hair-care product ethanol content. Hair samples were pre-washed to remove external contamination and analyzed for FAEE and EtG by GC-MS. According to the Society of Hair Testing consensus guidelines, FAEE levels exceeding 0.50 ng/mg and/or EtG levels exceeding 30 pg/mg indicate chronic excessive alcohol consumption. Upon initial analysis, the nine samples exhibited positive FAEE findings ranging from 0.496 to 4.984 ng/mg. MSDS review revealed the presence of ethanol from 10% to 95% by volume in at least one hair-care product used by each individual. Results of the EtG analysis ranged from 1.9 to 23.5 pg/mg. These findings indicate that regular use of products with ethanol content as low as 10% can impact FAEE results. EtG analysis should be used to confirm FAEE findings and appears to be unaffected by hair-care products, likely due to alternative mechanisms of incorporation.


Assuntos
Ácidos Graxos/análise , Preparações para Cabelo , Cabelo/química , Detecção do Abuso de Substâncias/métodos , Ésteres , Humanos
5.
Ther Drug Monit ; 32(3): 294-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20431508

RESUMO

The purpose of this study was to examine the relationship between social worker reports and the fatty acid ethyl ester (FAEE) test as a biomarker for heavy alcohol use. In 2005, a diagnostic program to detect excessive alcohol use by FAEE hair analysis in parents at high risk of having children with fetal alcohol spectrum disorders was established. All cases submitted by Child Protective Services between May and December of 2007 (n = 172) were included comparing social worker reports with FAEE test outcome by odds ratio analysis. A subanalysis of mothers (n = 119), excluding fathers, was also performed. Factors associated with testing positive for hair FAEE in parents, and mothers alone, were: knowledge of a specific instance of problem drinking within the past 6 months (odds ratio [OR] = 5.11, 2.57-10.16 and OR = 8.51, 3.59-20.18, respectively) and third party reports alleging alcohol abuse (OR = 3.31, 1.69-6.46 and OR = 3.30, 1.45-7.50, respectively). Mothers who admitted to heavy drinking were also seven times more likely to test positive for hair FAEE (OR = 6.74, 1.50-30.38) than those who did not. Factors negatively associated with testing positive for hair FAEE in parents, and mothers alone, were: social workers testing for FAEE without the suspicion of alcohol use but rather as a measure to "cover all bases" (OR = 0.09, 0.02-0.40 and (OR = 0.13, 0.03-0.58, respectively) or because of a history/suspicion of illicit drug use (OR = 0.2, 0.07-0.55 and OR = 0.26, 0.08-0.80, respectively). Eleven of 15 reports, indicating levels of consumption, were also in clinical agreement with FAEE test outcome. The FAEE hair test is being applied for the first time in the present context. Our results show the test corroborates well with social workers' suspicion of alcohol use. Reported factors directly related to alcohol use were significantly associated with testing positive for excessive alcohol use, whereas factors not directly related to alcohol use were negatively associated with testing positive.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Alcoolismo/metabolismo , Ésteres/análise , Etanol/toxicidade , Estudos de Avaliação como Assunto , Ácidos Graxos/análise , Cabelo/química , Transtornos Relacionados ao Uso de Álcool/metabolismo , Biomarcadores/análise , Criança , Ésteres/química , Ácidos Graxos/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Cabelo/efeitos dos fármacos , Humanos , Gravidez , Serviço Social/métodos , Detecção do Abuso de Substâncias
6.
Ther Drug Monit ; 32(3): 311-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20445483

RESUMO

Prenatal alcohol exposure can lead to a wide range of deficits known as fetal alcohol spectrum disorder. Epidemiologic studies regarding alcohol consumption in pregnancy have concentrated on North America, but recent reports have suggested that consumption is significant in many parts of the world. In Uruguay, alcohol consumption has changed into more risky and dangerous patterns and thus has a theoretical risk of having a high rate of prenatal alcohol exposure. This study characterizes the incidence of prenatal alcohol exposure in Montevideo, Uruguay, using a novel biomarker, fatty acid ethyl esters, in meconium as well as a survey to mothers. Nine hundred five meconium samples were collected from Hospital Pereira Rossell and Hospital de Clínicas in Montevideo, Uruguay. A maternal questionnaire was also completed. Meconium was analyzed for fatty acid ethyl esters using liquid-liquid and solid phase extraction with gas chromatography-flame ionization detection. Meconium was also analyzed for other drugs of abuse using enzyme-linked immunosorbent assay. Forty-four percent of meconium samples were above the positive cutoff for fatty acid ethyl esters and represent those newborns with risky prenatal exposure during the final two trimesters of pregnancy. Infants with prenatal alcohol exposure were more likely to have prenatal exposure to tobacco (odds ratio, 1.56; 95% confidence interval, 1.11-2.20) or any illicit drug (odds ratio, 2.29; 95% confidence interval, 0.98-5.31). Ethyl linoleate was a significant predictor of infant birth weight along with prenatal tobacco exposure, maternal body mass index, and infant sex. This study highlights a 44% incidence of prenatal alcohol exposure.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Etanol/toxicidade , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Mecônio/química , Feminino , Humanos , Incidência , Recém-Nascido , Mecônio/metabolismo , Gravidez , Uruguai/epidemiologia
7.
Ther Drug Monit ; 32(3): 305-10, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20445484

RESUMO

The main objective of this study is to evaluate the clinical utility of meconium analysis for fatty acid ethyl esters as a universal screening tool intended for the detection of newborns at risk for fetal alcohol spectrum disorder. This will be accomplished by assessing the rate of voluntary participation in a nonanonymous neonatal screening program and by determining the logistics of implementing the necessary follow-up and interventions as part of routine care. Additionally, this study will determine the predictive value of fatty acid ethyl ester-positive meconium with regard to neurodevelopmental delays. This is an ongoing prospective cohort study. Written informed consent is sought from all Grey Bruce women delivering at participating birthing sites. Collected meconium samples are tested for fatty acid ethyl esters by headspace-solid-phase microextraction followed by gas chromatography-mass spectrometry. Children with positive results are followed up through an existing public health program involving regular home visits and assessments of developmental milestones by a public health nurse. These children and matched control subjects also undergo neurodevelopmental testing at 3 and 18 months of age by a clinical psychologist using Bayley Scales of Infant and Toddler Development. If delays are detected, the child is referred to diagnostic services and appropriate intervention programs. This study has been granted ethics approval and enrollment began in November 2008 at St. Joseph's Health Care in London, Ontario. The first positive case has been identified and the follow-up is currently being conducted by the public health unit. The successful completing of this study will reveal the population's willingness to participate in a neonatal screening program for prenatal alcohol exposure and determine the costs, feasibility, and utility of implementing such programs in clinical practice.


Assuntos
Alcoolismo/metabolismo , Etanol/toxicidade , Transtornos do Espectro Alcoólico Fetal/etiologia , Feto/efeitos dos fármacos , Programas de Rastreamento/métodos , Ésteres/análise , Ácidos Graxos/análise , Feminino , Transtornos do Espectro Alcoólico Fetal/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Unidades Hospitalares , Humanos , Lactente , Recém-Nascido , Londres , Mecônio/metabolismo , Ontário , Projetos Piloto , Gravidez , Cuidado Pré-Natal/legislação & jurisprudência , Desenvolvimento de Programas
8.
Paediatr Drugs ; 11(1): 26-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19127948

RESUMO

BACKGROUND: Mediators of susceptibility to alcohol-related toxicity in the prenatal environment are relatively unknown. The placenta has been proposed as a potential source of variability in the fetal environment, primarily through its significant metabolic capabilities. Meconium is a toxicological matrix unique to the developing fetus that offers an opportunity to quantify fetal exposure to alcohol through the analysis of fatty acid ethyl esters (FAEE) [nonoxidative ethanol metabolites]. OBJECTIVE: To explore the role of the placenta as a potential source of variability in mediating fetal alcohol exposure via meconium analysis of FAEE, by combining a clinical case report involving human dizygotic twins and a series of guinea pig littermates. METHODS: Meconium was collected from a pair of dizygotic twins with clinical suspicion of prenatal alcohol exposure and analyzed for FAEE to confirm prenatal alcohol exposure. Meconium was also collected from a series of guinea pig pups prenatally exposed to alcohol at a daily dose of 4 g/kg/day administered to the pregnant dam. FAEE levels were analyzed by gas chromatography with flame ionization detection following liquid-liquid extraction from meconium. RESULTS: The dizygotic twin pair yielded positive meconium FAEE results (>2.00 nmoL/g) in the female twin (2.21 nmoL/g) and no detectable FAEE in the male twin. A total of 15 meconium samples were collected from 15 pups of five pregnant guinea pig litters. With the exception of one pair of littermates, meconium FAEE concentrations differed substantially within each litter (FAEE expressed in units of nmoL/g): litter 1 (0.996, 4.43, 1.36); litter 2 (5.17, 4.15, 0.00); litter 3 (5.16, 5.27); litter 4 (18.57, 8.26, 7.46); litter 5 (0.00, 4.32, 0.00, 1.27). CONCLUSIONS: Identical maternal ethanol exposure levels produced differing levels of fetal exposure in a dizygotic human twin pair and a series of guinea pig littermates as evidenced through FAEE meconium analysis. These data indicate that the placenta may have a previously unappreciated role in mediating ethanol-induced fetal injury.


Assuntos
Etanol/toxicidade , Ácidos Graxos/análise , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Troca Materno-Fetal , Placenta/metabolismo , Animais , Animais Recém-Nascidos , Biomarcadores/análise , Ésteres , Feminino , Cobaias , Humanos , Recém-Nascido , Masculino , Mecônio/química , Mecônio/metabolismo , Placenta/fisiologia , Circulação Placentária , Gravidez , Gêmeos Dizigóticos
9.
CJEM ; 21(4): 477-481, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30806339

RESUMO

OBJECTIVES: Cannabis hyperemesis syndrome is characterized by bouts of protracted vomiting in regular users of cannabis. We wondered whether this poorly understood condition is idiosyncratic, like motion sickness or hyperemesis gravidarum, or the predictable dose-response effect of prolonged heavy use. METHODS: Adults with an emergency department visit diagnosed as cannabis hyperemesis syndrome, near-daily use of cannabis for ≥6 months, and ≥2 episodes of severe vomiting in the previous year were age- and sex-matched to two control groups: RU controls (recreational users without vomiting), and ED controls (patients in the emergency department for an unrelated condition). Δ9-Tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol, and 11-nor-9-carboxy-THC concentrations in scalp hair were compared for subjects with positive urine THC. RESULTS: We obtained satisfactory hair samples from 46 subjects with positive urine THC: 16 cases (age 26.8 ± 9.2 years; 69% male), 16 RU controls and 14 ED controls. Hair cannabinoid concentrations were similar between all three groups (e.g. cases THC 220 [median; IQR 100,730] pg/mg hair, RU controls 150 [71,320] and ED controls 270 [120,560]). Only the THC:CBN ratio was different between groups, with a 2.6-fold (95%CI 1.3,5.7) lower age- and sex-adjusted ratio in cases than RU controls. Hair cannabidiol concentrations were often unquantifiably low in all subjects. CONCLUSIONS: Similar hair cannabinoid concentrations in recreational users with and without hyperemesis suggest that heavy use is necessary but not sufficient for hyperemesis cannabis. Our results underline the high prevalence of chronic heavy cannabis use in emergency department patients and our limited understanding of this plant's adverse effects.


OBJECTIF: Le syndrome d'hyperémèse cannabique se caractérise par des accès prolongés de vomissements chez les grands consommateurs de cannabis. La question était donc de savoir si ce trouble, peu compris encore, relève d'un état idiosyncrasique, comme le mal des transports ou l'hyperémèse gravidique, ou d'un effet de type dose-réponse prévisible chez les grands consommateurs de cannabis. MÉTHODE: Des adultes chez qui un diagnostic de syndrome d'hyperémèse cannabique a été posé au service des urgences (SU), qui faisaient un usage presque quotidien du cannabis depuis ≥ 6 mois et qui ont connu ≥ 2 épisodes de vomissements importants au cours de l'année précédente ont été appariés à deux groupes témoins selon l'âge et le sexe : des témoins faisant un usage récréatif du cannabis, sans vomissements (UR) et des témoins traités au SU (examinés pour des troubles non connexes). La teneur des cheveux en Δ9-tétrahydrocannabinol (THC), en cannabinol (CBN), en cannabidiol et en 11-nor-9-carboxy-THC a été comparée chez les sujets ayant obtenu des résultats positifs à l'égard du THC urinaire. RÉSULTATS: Des échantillons satisfaisants de cheveux ont été prélevés chez 46 sujets ayant obtenu des résultats positifs à l'égard du THC urinaire : 16 cas (âge : 26,8 ± 9,2 ans; sexe masculin : 69%), 16 témoins UR et 14 témoins SU. La teneur des cheveux en cannabinoïdes était comparable dans les trois groupes (cas : THC : 220 pg/mg de cheveux [médiane; écart interquartile : 100­730]; témoins UR : 150 [71­320] et témoins SU : 270 [120­560]). Seul le rapport THC/CBN différait entre les groupes : il était 2,6 fois (IC à 95% : 1,3­5,7) inférieur dans les cas (rapport rajusté selon l'âge et le sexe) que chez les témoins UR. La teneur des cheveux en cannabidiol était souvent non quantifiable, et ce, chez tous les sujets. CONCLUSION: Le fait que la teneur des cheveux en cannabinoïdes était comparable chez les utilisateurs faisant un usage récréatif du cannabis, tant chez ceux qui souffraient d'hyperémèse que chez ceux qui en étaient exempts, donne à penser qu'il y a un usage nécessairement abusif de la drogue mais non suffisant pour causer l'hyperémèse cannabique. Les résultats font ressortir la forte prévalence d'un usage excessif et prolongé du cannabis chez les patients traités au SU et le peu de connaissances que la communauté médicale a des effets indésirables de cette plante.


Assuntos
Canabinoides/análise , Cabelo/química , Abuso de Maconha/complicações , Vômito/etiologia , Adulto , Estudos de Casos e Controles , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Síndrome
10.
J Pharm Biomed Anal ; 48(3): 927-33, 2008 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-18786798

RESUMO

Fatty acid ethyl esters (FAEEs) in meconium emerged as a reliable, direct biological marker for establishing fetal exposure to ethanol. We developed an LC-MS/MS method for ethyl laurate, ethyl myristate, ethyl palmitate, ethyl palmitoleate, ethyl stearate, ethyl oleate, ethyl linoleate, ethyl linolenate, and ethyl arachidonate using ethyl heptadecanoate as the internal standard. The analytes were extracted from meconium with hexane, followed by solid-phase extraction with aminopropyl-silica columns. Chromatography was performed on a C(8) reversed-phase column using water/isopropanol/acetonitrile (20:40:40, v/v/v) as a mobile phase. A triple quadrupole mass spectrometer that monitored the transitions in multiple reaction-monitoring mode was used for the detection of the analytes. Limits of quantification (LOQs) varied between 0.12 and 0.20 nmol/g. Calibration curves were linear from LOQs to 50 nmol/g for all analytes, with a minimum r(2)>0.99. At three concentrations spanning the linear dynamic range, mean recoveries ranged between 53.6 and 86.7% for the different analytes. The validated method was applied to analysis of meconium in newborns of two European cities. The two cohorts presented with different prevalence of gestational ethanol consumption during pregnancy.


Assuntos
Cromatografia Líquida/métodos , Ácidos Graxos/análise , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Mecônio/química , Efeitos Tardios da Exposição Pré-Natal , Espectrometria de Massas em Tandem/métodos , Calibragem , Cidades , Estudos de Coortes , Ésteres , Europa (Continente)/epidemiologia , Feminino , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Hexanos/química , Humanos , Recém-Nascido , Gravidez , Prevalência , Padrões de Referência , Reprodutibilidade dos Testes , Extração em Fase Sólida , População Urbana
12.
Clin Chim Acta ; 366(1-2): 101-11, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16413011

RESUMO

Prenatal substance abuse is an ongoing concern with significant impact on neonatal health and development across socioeconomic lines. Meconium, passed by neonates during their first post-natal bowel movements, is a matrix unique to the developing fetus and contains a long history of prenatal metabolism. Over the last two decades, the use of meconium as a matrix for assessing prenatal exposure to drugs of abuse has yielded methods exhibiting higher sensitivity, easier collection, and a larger window of detection than traditional matrices. Recently, a method has been developed for the analysis of fatty acid ethyl esters in meconium as a biomarker of fetal alcohol exposure, potentially facilitating the future diagnosis of Fetal Alcohol Spectrum Disorder in situations where gestational alcohol consumption history is unknown. Screening for prenatal exposure to illicit and abused licit drugs in meconium is possible by use of a variety of immunoassay methods with conformational analysis usually occurring by GCMS or LCMS. In spite of increased sample preparation time relative to blood and urine, the long metabolic history, coupled with the ease and wide window of collection of meconium make it the ideal matrix for determining fetal drug exposure.


Assuntos
Mecônio/química , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Feminino , Humanos , Imunoensaio/métodos , Recém-Nascido , Troca Materno-Fetal , Gravidez , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias/métodos
13.
Drug Test Anal ; 6 Suppl 1: 30-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24817046

RESUMO

Clinical studies examining performance of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in identifying excessive alcohol consumption have been primarily conducted in male populations. An impact of hair cosmetics in producing both false-negative EtG results and false-positive FAEE results has been demonstrated, suggesting a possible bias in female populations. This study evaluates FAEE-positive hair samples (>0.50 ng/mg) from n = 199 female and n = 73 male subjects for EtG. Higher FAEE/EtG concordance was observed amongst male over female subjects. Performance of multiple proposed EtG cut-off levels were assessed; amongst female samples, FAEE/EtG concordance was 36.2% (30 pg/mg), 36.7% (27 pg/mg), and 43.7% (20 pg/mg). Non-coloured hair demonstrated a two-fold increase in concordance (41.8 v. 20.8%) over coloured hair in the female cohort. FAEE levels did not differ between male and female subjects; however they were lower in coloured samples (p = 0.046). EtG was lower in female subjects (p = 0.019) and coloured samples (p = 0.026). A total of n = 111 female samples were discordant. Amongst discordant samples (EtG-negative), 26% had evidence of recent alcohol use including consultation histories (n = 20) and detectable cocaethylene (n = 9); 29% of discordant samples were coloured. False-negative risk with ethyl glucuronide analysis in females was mediated by cosmetic colouring. These findings suggest that combined analysis of FAEE and EtG is optimal when assessing a female population and an EtG cut-off of 20 pg/mg is warranted when using combined analysis. While concordant FAEE/EtG-positive findings constitute clear evidence, discordant FAEE/EtG findings should still be considered suggestive evidence of chronic excessive alcohol consumption.


Assuntos
Alcoolismo/diagnóstico , Ésteres/análise , Ácidos Graxos/análise , Glucuronatos/análise , Cabelo/química , Caracteres Sexuais , Detecção do Abuso de Substâncias/métodos , Adulto , Alcoolismo/metabolismo , Biomarcadores/análise , Cocaína/análogos & derivados , Cocaína/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino
14.
CMAJ Open ; 2(2): E121-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25077128

RESUMO

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a leading preventable cause of neurodevelopmental disability in North America. The stigma associated with alcohol use and abuse during pregnancy makes it difficult to obtain information on prenatal alcohol use through self-reporting. We assessed the incidence of prenatal alcohol exposure in Prince Edward Island to facilitate future public health initiatives addressing FASD. METHODS: Prenatal alcohol exposure was examined via population-based collection of meconium and analysis of fatty acid ethyl esters (FAEEs). Fatty acid ethyl esters are nonoxidative metabolites of ethanol that are produced in the fetus. Meconium FAEE concentrations of 2.0 nmol/g or greater are indicative of frequent prenatal alcohol exposure during the last 2 trimesters of pregnancy. Samples were collected from 1307 neonates between Nov. 8, 2010, and Nov. 8, 2011, in hospitals in PEI, or from those born to mothers who resided in PEI but gave birth in Halifax, Nova Scotia. Samples were frozen and shipped for analysis. Fatty acid ethyl esters were analyzed by gas chromatography-mass spectrometry and quantified by means of deuterated internal standards. RESULTS: Of the 1307 samples collected, 1271 samples were successfully analyzed. Positive results for FAEEs were obtained in 3.1% (n = 39) of samples collected within the first 24 hours after birth. INTERPRETATION: Not all neonates exposed to heavy prenatal alcohol in utero will exhibit FASD; based on current estimates of predictive value for disease by exposure, our findings suggest that 1.3% of neonates born in PEI during this 1-year period will have FASD. In its application to an entire provincial birth cohort, this study successfully implemented a public health-centred approach for evaluating population-based risk of FASD, with implications for practice across Canada.

15.
Addict Sci Clin Pract ; 9: 8, 2014 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-24886786

RESUMO

BACKGROUND: Although screening, brief intervention, and referral to treatment (SBIRT) has shown promise for alcohol use, relatively little is known about its effectiveness for adult illicit drug use. This randomized controlled trial assessed the effectiveness of the SBIRT approach for outcomes related to drug use among patients visiting trauma and emergency departments (EDs) at two large, urban hospitals. METHODS: A total of 700 ED patients who admitted using illegal drugs in the past 30 days were recruited, consented, provided baseline measures of substance use and related problems measured with the Addiction Severity Index-Lite (ASI-Lite), and then randomized to the Life Shift SBIRT intervention or to an attention-placebo control group focusing on driving and traffic safety (Shift Gears). Both groups received a level of motivational intervention matched to their condition and risk level by trained paraprofessional health educators. Separate measurement technicians conducted face-to-face follow-ups at 6 months post-intervention and collected hair samples to confirm reports of abstinence from drug use. The primary outcome measure of the study was past 30-day drug abstinence at 6 months post-intervention, as self-reported on the ASI-Lite. RESULTS: Of 700 participants, 292 (42%) completed follow-up. There were no significant differences in self-reported abstinence (12.5% vs. 12.0% , p = 0.88) for Life Shift and Shift Gears groups, respectively. When results of hair analyses were applied, the abstinence rate was 7 percent for Life Shift and 2 percent for Shift Gears (p = .074). In an analysis in which results were imputed (n = 694), there was no significant difference in the ASI-Lite drug use composite scores (Life Shift +0.005 vs. Shift Gears +0.017, p = 0.12). CONCLUSIONS: In this randomized controlled trial, there was no evidence of effectiveness of SBIRT on the primary drug use outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT01683227.


Assuntos
Drogas Ilícitas , Programas de Rastreamento , Entrevista Motivacional , Encaminhamento e Consulta , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Adolescente , Adulto , Alcoolismo/epidemiologia , Alcoolismo/reabilitação , California , Comorbidade , Estudos Transversais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Seguimentos , Hospitais Urbanos , Humanos , Masculino , Pessoa de Meia-Idade , Detecção do Abuso de Substâncias/estatística & dados numéricos , Adulto Jovem
16.
PLoS One ; 8(12): e82647, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24312668

RESUMO

UNLABELLED: Methadone maintenance treatment (MMT) is the standard of care during pregnancy for opioid-dependency, showing efficacy in improving prenatal care and reducing risk of relapse. By design, however, MMT is only intended to prevent withdrawal thus facilitating cognitive behavioural interventions. In order to maximize the benefits of MMT, it is essential that methadone is both properly prescribed and that additional addiction treatment is concurrently administered. This study aims to determine the effectiveness of MMT engagement in high-risk pregnant women in reducing polydrug use by objective laboratory examination of neonatal meconium. PATIENTS AND METHODS: Over a 29-month period, the Motherisk Laboratory at the Hospital for Sick Children in Toronto analyzed meconium samples as per request by social services and hospitals for drugs of abuse. RESULTS: Of the 904 meconium samples received, 273 were tested for methadone with 164 positive and 109 negative for methadone. Almost half of the methadone positive samples (46.34%) were also positive for at least one other opioid compound, which did not differ statistically from the methadone-negative control samples (46.79%; Chi square test, p=0.94). No differences were found between the methadone positive and negative groups in rates of concurrent amphetamines, cocaine, cannabis, and alcohol use indicating a similar risk of polydrug use between pregnant women taking or not taking methadone in this population. DISCUSSION: The high rates of additional opioid and other drug use in the MMT group, suggest that MMT is failing this population of patients. It is possible that methadone doses during pregnancy are not appropriately adjusted for changes in pharmacokinetic parameters (e.g. blood volume, renal function) during the second and third trimesters. This may result in sub-therapeutic dosing creating withdrawal symptoms leading to additional substance use. Alternatively, these results may be demonstrating a substantial lack in delivery of addiction support services in this vulnerable population.


Assuntos
Mecônio/química , Mecônio/metabolismo , Metadona/análise , Tratamento de Substituição de Opiáceos/efeitos adversos , Adulto , Cocaína/análise , Feminino , Humanos , Recém-Nascido , Metadona/efeitos adversos , Gravidez
18.
Forensic Sci Int ; 218(1-3): 31-6, 2012 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-22047752

RESUMO

INTRODUCTION: The analysis of pediatric and adult hair is a useful non-invasive biomarker to effectively detect long term exposure to various xenobiotics, specifically drugs of abuse such as cocaine, opiates and amphetamines. Very often individuals are using, or are exposed to multiple drugs simultaneously and therefore it is important to be able to detect them in the same analysis. We have developed a sensitive and specific solid phase micro extraction (SPME) coupled with gas chromatography mass spectrometry (GC/MS) to detect 17 different analytes in hair using a single extraction method. METHOD: Five milligrams of hair is extracted overnight, subjected to solid phase extraction (SPE) and then to SPME-GC/MS. The aimed analytes include amphetamine, methamphetamine, MDA, MDMA, cocaine, benzoylecognine, norcocaine, cocaethylene, methadone, codeine, morphine, 6-AM, oxycodone, oxymorphone, hydrocodone, hydromorphone and meperidone. RESULTS: The following are the LOD of the various drugs: 0.2ng/mg hair for amphetamine, methamphetamine, MDA, MDMA, morphine, codeine, 6-AM, oxycodone, oxymorphone, hydromorphone, hydrocodone, meperidine and 0.13ng/mg hair for cocaine, benzoylecognine, cocaethylene, norcocaine and methadone. CONCLUSION: This GC/MS method is sensitive and specific to detect the presence of these 17 analytes in as little as 5mg of hair and is especially useful for newborn and child hair analysis where the amount of hair is often very limited.


Assuntos
Anfetaminas/análise , Cocaína/análise , Cromatografia Gasosa-Espectrometria de Massas , Cabelo/química , Entorpecentes/análise , Microextração em Fase Sólida , Toxicologia Forense/métodos , Humanos , Limite de Detecção , Detecção do Abuso de Substâncias/métodos
19.
Forensic Sci Int ; 196(1-3): 27-31, 2010 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-20074880

RESUMO

Neonatal hair is a clinically important toxicological matrix, as it allows determination of in utero drug exposure. This paper serves to review the physiological development of the hair follicle and hair production during fetal life. An understanding of the mechanisms and timing of hair development in the prenatal period is critical to effectively assessing the time window of exposure determination associated with toxicological analysis of neonatal hair.


Assuntos
Cabelo/embriologia , Diferenciação Celular , Fator de Crescimento Epidérmico/metabolismo , Epiderme/embriologia , Feminino , Cabelo/metabolismo , Cor de Cabelo/fisiologia , Proteínas Hedgehog/metabolismo , Humanos , Queratinócitos/metabolismo , Queratinas Específicas do Cabelo/metabolismo , Exposição Materna , Melanócitos/metabolismo , Gravidez , Transdução de Sinais/fisiologia
20.
Can J Clin Pharmacol ; 17(1): e177-93, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20436210

RESUMO

UNLABELLED: As drug abuse in our society escalates, child protection workers face mounting challenges in accurately assessing parental substance abuse in the interest of effective child protection. The impartial evaluation of substance use and abuse is fundamental, requiring objective and sensitive methods. A variety of biological specimens, some applicable to short-term and some to long-term monitoring, have been successful when applied to a child protection and drug abuse monitoring of caregivers. This article explores the complementary features of drug testing in urine, hair, and meconium, among other alternative matrices and discusses the practicality, basic science, and applicability of each to substance abuse monitoring in the context of child protection. KEYWORDS: Drug testing, hair, meconium, prenatal, toxicology, urine screen, infant, child, drug.


Assuntos
Filho de Pais com Deficiência/psicologia , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Cuidadores , Criança , Proteção da Criança , Cabelo/química , Humanos , Mecônio/química , Serviço Social/organização & administração
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