Arsenic levels in immigrant children from countries at risk of consuming arsenic polluted water compared to children from Barcelona.

Arsenic is a highly toxic element that pollutes groundwater, being a major environmental problem worldwide, especially in the Bengal Basin. About 40% of patients in our outpatient clinics come from those countries, and there is no published data about their arsenic exposure. This study compares arsenic exposure between immigrant and native children. A total of 114 children (57 natives, 57 immigrants), aged 2 months to 16 years, were recruited and sociodemographic and environmental exposure data were recorded. Total arsenic in urine, hair, and nails and arsenic-speciated compounds in urine were determined. We did not find significant differences in total and inorganic arsenic levels in urine and hair, but in organic arsenic monomethylarsenic acid (MMA) and dimethylarsinous acid (DMA) in urine and in total arsenic in nails. However, these values were not in the toxic range. There were significant differences between longer than 5 years exposure and less than 5 years exposure (consumption of water from tube wells), with respect to inorganic and organic MMA arsenic in urine and total arsenic in nails. There was partial correlation between the duration of exposure and inorganic arsenic levels in urine. Immigrant children have higher arsenic levels than native children, but they are not toxic. At present, there is no need for specific arsenic screening or follow-up in immigrant children recently arrived in Spain from exposure high-risk countries.

[Eating habits in children under 2 years old according to ethnic origin in a Barcelona urban area]. / Hábitos alimentarios de niños menores de 2 años según el origen étnico de los progenitores en un área urbana de Barcelona.

INTRODUCTION: The importance of the influence of diet in the first few years of life on child growth and development and its relationship with the prevention of chronic diseases in childhood and adulthood has recently been stressed. The aim of the present study was to determine the presence or absence of inappropriate feeding practices, defined as non-compliance with dietary recommendations, in children aged less than 2 years old through a survey. SUBJECTS AND METHODS: The parents of 462 children were administered a 14-item questionnaire on compliance with dietary recommendations to define nutritional risk. Depending on the parents' country of birth, children were classified as autochthonous, gypsy, or non-autochthonous. RESULTS: In absolute results, high percentages of non-compliance with a substantial number of recommendations were found in all children and in each of the three groups, with the consequent danger of nutritional risk. CONCLUSIONS: In children in our environment, there are numerous inadequate feeding practices that constitute nutritional risk factors and require preventive and educational interventions to improve the future health of these children when they reach adulthood. In children from ethnic groups, no particularly severe inadequate feeding practices related to origin were found. The gypsy ethnic group requires additional nutritional health education interventions. Health workers should improve the information provided on nutritional recommendations and feeding practices to avoid misunderstanding, as in the case of gluten.

Prenatal exposure to arecoline (areca nut alkaloid) and birth outcomes.

The betel nut is commonly used as a drug by Asian populations. A high prevalence of adverse pregnancy outcomes has been reported in women who chewed betel quid during gestation. The hypothesis that chronic exposure of the fetus to arecoline (the principal alkaloid of the areca nut) is the cause was investigated in a clinical observational study on six newborns from Asian mothers who chewed betel nut during pregnancy.

Prenatal ethanol exposure and placental hCG and IGF2 expression.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is the main cause of preventable non-genetic mental retardation. Diagnosis of prenatal exposure to ethanol (PEE) is based on questionnaires and biomarkers in perinatal matrices. Early diagnosis of FASD is important to mitigate secondary disabilities that will arise later in life. It is important to identify biomarkers related to cellular damage caused by PEE. The main objective was to identify novel candidate biomarkers from placental tissue using an in vitro model of exposure to ethanol and to support it in placental tissue obtained from pregnancies with PEE assessed by fatty acid esters in meconium samples. METHODS: First, hormone production was examined using two different human trophoblast cell lines, JEG3 and BeWo. Viable cell count by exclusion method was analyzed and human chorionic gonadotrophin (hCG) and insulin-like growth factor 2 (IGF2) were quantified by Western blot and ELISA. Second, these techniques were used in protein lysates from human placentas from pregnancies with and without exposure to ethanol. RESULTS: Both trophoblast cell lines showed a decrease in cell viability accompanied with apoptosis activation after a chronic ethanol treatment. Moreover, we showed an increase in the secretion of hCG and IGF2 in a dose-dependent manner. Interestingly, this increase was also observed in a set of human placenta tissue from fetuses exposed prenatally to ethanol. DISCUSSION: Ethanol exposure during pregnancy causes placenta cell damage, so altering its normal function. The specific hCG and IGF2 release pattern is a candidate surrogated biomarker of the damage due to PEE.

Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy.

This study investigated the association between biomarkers of fetal exposure to cigarette smoke at the end of pregnancy, cotinine in cord serum and in maternal and newborn urine samples, and quantitative measurement of smoking intake and exposure evaluated by maternal self-reported questionnaire. Study subjects were 429 mothers and their newborns from a hospital in Barcelona, Spain. A questionnaire including smoking habits was completed in the third trimester of pregnancy and on the day of delivery. Cotinine concentration in cord serum was associated with daily exposure to nicotine in nonsmokers and with daily nicotine intake in smokers. The geometric mean of cotinine concentration in cord serum statistically discriminated between newborns from nonexposed and exposed nonsmoking mothers, and between these two classes and smokers, and furthermore was able to differentiate levels of exposure to tobacco smoke and levels of intake stratified in tertiles. Urinary cotinine levels in newborns from nonsmoking mothers exposed to more than 4 mg nicotine daily were statistically different from levels in two other categories of exposure. Cotinine concentration in urine from newborns and from mothers did not differentiate between exposure and nonexposure to environmental tobacco smoke (ETS) in nonsmoking mothers. Cord serum cotinine appeared to be the most adequate biomarker of fetal exposure to smoking at the end of pregnancy, distinguishing not only active smoking from passive smoking, but also exposure to ETS from nonexposure.

Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium.

A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of 6-monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, cocaine, benzoylecgonine and cocaethylene in meconium using nalorfine as the internal standard. The analytes are initially extracted from the matrix by methanol (6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or 0.01 M ammonium hydrogen carbonate buffer (morphine-3-glucuronide, morphine-6-glucuronide). Subsequently a solid-phase extraction with Bondelut Certify columns (6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or ethyl solid-phase extraction columns (morphine-3-glucuronide, morphine-6-glucuronide) was applied. Chromatography was performed on a C(8) reversed-phase column using a gradient of acetic acid 1%-acetonitrile as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with atmospheric pressure ionisation-electrospray (ESI) interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay and applied to analysis of meconium in newborns to assess fetal exposure to opiates and cocaine.

[Profile of the hospital case mix of the immigrant population in Barcelona, Spain]. / Perfil de la casuística hospitalaria de la población inmigrante en Barcelona.

OBJECTIVE: Although the immigrant population in cities such as Barcelona has tripled in the last five years, until now the impact of this group on the health system has not been rigorously evaluated. The aim of this study was to compare hospital resource utilization among the immigrant population with that among the native population through case mix, demographic characteristics and hospital day use. MATERIAL AMD METHODS: We analyzed 15,057 discharges from Hospital del Mar in Barcelona in 2000. This hospital attends 60% of admissions from the Ciutat Vella district. In 2000, 21% of the population of this district were immigrants. Socio-demographic patient characteristics and case mix were compared between the immigrant and the native population. Hospital resource use was compared according to age, case mix (diagnosis related groups) and seriousness (severity, complications and comorbidities) of the events requiring medical care. RESULTS: The case mix of the immigrant population differed from that of the autochthonous population due to pronounced ge differences and a higher fertility rate. Thirty-three percent of immigrant admissions were for deliveries. The mean cost of discharge of immigrants from low-income countries was 30% lower than that for the remaining discharges. After adjusting for age, case mix and severity, length of stay among the immigrant population was significantly shorter. A 5% reduction was found after adjusting for case mix and a 10% reduction was found when all the factors were considered. CONCLUSIONS: Case mix differences are due to age and socio-cultural factors. Immigrants are rejuvenating the ageing native population and the role of gynecology-obstetrics and pediatrics needs to be increased. The finding that resource use per discharge is lower among immigrants from low-income countries contradicts the expectation that lower socioeconomic status leads to higher hospital resource use intensity. Therefore, new hypotheses and analyses that explain this situation should be put forward.

Ethanol cytotoxic effect on trophoblast cells.

Prenatal ethanol exposure may cause both, altered fetal neurodevelopment and impaired placental function. These disturbances can lead to growth retardation, which is one of the most prevalent features in Fetal Alcohol Syndrome (FAS). It is not known whether there is a specific pattern of cytotoxicity caused by ethanol that can be extrapolated to other cell types. The aim of this study was to determine the cytotoxic effects caused by sustained exposure of trophoblast cells to ethanol. The cytotoxic effect of sustained exposure to standard doses of ethanol on an in vitro human trophoblast cell line, JEG3, was examined. Viable cell count by exclusion method, total protein concentration, lactate dehydrogenase (LDH) activity and activation of apoptotic markers (P-H2AX, caspase-3 and PARP-1) were determined. Sustained exposure to ethanol decreased viable cell count and total protein concentration. LDH activity did not increased in exposed cells but apoptotic markers were detected. In addition, there was a dose-dependent relationship between ethanol concentration and apoptotic pathways activation. Sustained ethanol exposure causes cellular cytotoxicity by apoptotic pathways induction as a result of DNA damage. This apoptotic induction may partially explain the altered function of placental cells and the damage previously detected in other tissues.

Antioxidant activity of various Mauritanian date palm (Phoenix dactylifera L.) fruits at two edible ripening stages.

The increasing interest in plant phenolics and flavonoids outlined the necessity of determining their contents and biological activity in Mauritanian date palm fruits. Methanolic extracts of fruit of six date palm cultivars commonly grown in Mauritania were screened for their antioxidant activity, total phenolics, and flavonoid content at two edible ripening stages. Polyphenols and flavonoids were higher in theBlah stage, corresponding toKhalal in the standard Iraqi Arabic nomenclature, compared to the fully matureTamr stage regardless the cultivar. The average of total phenolics atBlah andTamr stages were 728.5 and 558.9 mg gallic acid equivalents (GAE) per 100 g dry matter (DM), whereas the average flavonoid content was 119.6 and 67.3 mg quercetin equivalents (QE) per 100 g DM, respectively. TheBlah stage also exhibited the highest total antioxidant activity with a Trolox equivalents antioxidant capacity (TEAC) value of 129.3 µmol/100 g DM founded in Bou seker's Blah date, followed by Tijib cultivar with TEAC value of 114.3 µmol/100 g DM and an average TEAC value of 107.5 µmol/100 g DM. Furthermore, a high positive correlation was found between total phenolics inTamr (r = 0.92) andBlah (r = 0.87) stages and TEAC of fruit methanolic extracts compared to the flavonoids, suggesting that phenolics were the major contributor to the antioxidant activity.

Feto-placental morphological effects of prenatal exposure to drugs of abuse.

The aim of the study was to find morphological changes in the feto-placental unit due to prenatal exposure to drugs of abuse. A blind histomorphometric study was performed using 225 placentas. Based on meconium testing, the fetuses were classified as exposed or unexposed to opiates, cocaine, cannabis or alcohol. To establish prenatal tobacco exposure, cotinine in cord blood was analyzed. At the microscopic level a non statistically significant reduction of placental vascularization was observed in cocaine, opiates and alcohol using mothers. In addition, alcohol-consuming mothers did not present with larger placental vessel diameter than controls. Prenatal use of cocaine and tobacco was associated with a decrease in newborn weight and length. Furthermore, tobacco use was associated with a higher rate of previous abortions. In conclusion, placentas from mothers using tobacco, cocaine, opiates or alcohol during pregnancy present vasculature changes that may explain the adverse perinatal outcomes in their newborns.

[Alternative biological materials to detect prenatal exposure to drugs of abuse in the third trimester of pregnancy]. / Matrices biológicas alternativas para detectar la exposición prenatal a drogas de abuso en el tercer trimestre de la gestación.

INTRODUCTION: Detection of prenatal drug abuse exposure is essential to ensure an appropriate monitoring of affected children. A maternal questionnaire is not an efficient screening tool. The usefulness of maternal hair and meconium as biological materials to assess this exposure has been described in last few years. The aim of this study was to compare both these alternative biological materials for prenatal drug exposure detection in the third trimester of pregnancy, in order to assess its use as a screening tool. PATIENTS AND METHODS: Between January and March 2010, samples of maternal hair and meconium from 107 mother-infant dyads were collected in Can Misses Hospital, Ibiza. The presence of opiates, cocaine, cannabis, and amphetamines, was determined in both materials, using standard chromatographic techniques. RESULTS: Maternal hair analysis showed a 15.9% positivity for drugs of abuse (17 cases): 11 cannabis, 7 cocaine, 1 cannabis and ecstasy, and 1 cannabis and cocaine. Only one mother reported cannabis consumption and another one, cocaine. Of the 7 cocaine positive cases in hair, 6 were confirmed in meconium analysis, while of 11 cannabis positive cases, only 3 were confirmed in meconium. Two different consumer profiles were defined: cocaine consumers and cannabis consumers (with only 2 cases of multiple drug use). The highest level of cocaine ever published was detected (1.582ng/g) in one case. DISCUSSION: This study reveals a high prevalence of drug abuse in this cohort during pregnancy. Improved screening methods may optimize prevention and monitoring of exposed infants. Maternal hair seems to be more sensitive than meconium to detect prenatal exposure to cannabis during the third trimester, so it might become a good screening tool.

Determination of maternal-fetal biomarkers of prenatal exposure to ethanol: a review.

The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioural and/or learning disabilities that are included in the term fetal alcohol spectrum disorder (FASD). Objective assessment of exposure to ethanol at both prenatal and postnatal stages is essential for early prevention and intervention. Since pregnant women tend to underreport alcohol drinking by questionnaires, a number of biological markers have been proposed and evaluated for their capability to highlight gestational drinking behaviour. These biomarkers include classical biomarkers (albeit indirect) of alcohol-induced pathology (mean corpuscular volume (MCV), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) acetaldehyde-derived conjugates, and finally derivatives of non-oxidative ethanol metabolism (fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphaditylethanol (PEth)). Since ethanol itself and acetaldehyde are only measured few hours after ethanol intake in conventional matrices such as blood, urine and sweat, they are only useful to detect recent ethanol exposure. In the past few years, the non-oxidative ethanol metabolites have received increasing attention because of their specificity and in some case wide time-window of detection in non-conventional matrices from the pregnant mother (oral fluid and hair) and fetus-newborn (neonatal hair, meconium, placenta and umbilical cord). This article reviews bioanalytical procedures for the determination of these markers of ethanol consumption during pregnancy and related prenatal exposure. In addition, clinical toxicological applications of these procedures are presented and discussed.

[Validity of a maternal alcohol consumption questionnaire in detecting prenatal exposure]. / Validez del cuestionario de consumo materno de alcohol para detectar la exposición prenatal.

INTRODUCTION: Ethanol consumption by pregnant women can produce severe effects in the foetus and the newborn, mainly in neurological and weight-height development, and are included in the term FASD (Fetal Alcohol Spectrum Disorder). Questionnaires are the most used screening method to detect prenatal exposure, but a previous population study questioned its reliability. The objective of this study was to compare alcohol prenatal exposure detection by questionnaire compared with biomarkers in meconium. METHODOLOGY: Sixty two meconium samples from mothers who denied alcohol consumption during pregnancy by questionnaire were analysed. The objective analysis was made by determination of FAEEs (fatty acid ethyl esters) as exposure biomarkers in meconium as biological matrix. RESULTS: In the meconium from 10 of 62 newborns from non-alcohol consuming mothers by questionnaire (16.12%) FAEE values were positive (≥ 2 nmol/g). DISCUSSION: Questionnaires as a screening method during pregnancy are not a reliable tool. It is necessary to identify prenatal exposure to alcohol as soon as possible by biomarkers analysis in biological matrices from the newborn or the mother. The early detection will allow these patients to benefit from follow up and treatment to reach the best possible neurological development.

Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: Comparison with testing in placental and fetal remains.

UNLABELLED: Drug use by pregnant women in the first trimester of pregnancy and subsequent fetal exposure during early gestation can be assessed only by repetitive/systematic maternal blood/urine analysis or segmental hair analysis. No evidence of any relationship between maternal/fetal exposure during this specific period of gestation has been demonstrated to date in a human model. METHODS: To clarify drugs toxicokinetics and transplacental passage during early pregnancy, the presence of the most widely used recreational drugs of abuse and metabolites was investigated in the proximal 4cm hair segments of women undergoing voluntary termination of pregnancy (n=280) during the 12th week of gestation and the results were compared to those from placenta and fetal tissue samples in order to verify whether maternal hair testing can reflect fetal exposure and, if so, to what extent. Hair, placenta and fetal remains were analyzed by validated gas chromatography mass spectrometry assays. RESULTS: Eighty one positive hair samples were identified: 60 were positive for cannabis (74.1%), 28 for cocaine (34.6%), 7 for opiates (8.6%), 3 for MDMA (3.7%) and 18.5% were positive for more than one drug. The positive hair test results were confirmed in placenta/fetal tissues in 10 cases out of 60 for cannabis (16. 7%); in 7 out of 28 for cocaine (25%); and none for the 6 opiates positive cases and 3 MDMA cases, respectively. CONCLUSION: Drugs/metabolites in hair of pregnant women can be used as biomarkers of past drug use (repetitive or sporadic), although the use is not always reflected in fetal/placental tissues. There are several possible hypotheses to explain the results: (1) the use occurred before the start of pregnancy, (2) past sporadic consumption which could be measured in hair but not in fetal and placental remains because of the narrow window of drug detection in placental/fetal tissues; (3) the sensitivity of the analytical methods was not high enough for the detection of the minute amount of drugs of abuse and metabolites which reached these tissues (4) there is a large variability in the transplacental passage of drugs of abuse and in the placenta's metabolizing capacity.

[Drugs of abuse acute intoxication in paediatric emergencies]. / Consulta en urgencias de pediatría por intoxicación aguda por drogas de abuso.

Documented cases show that acute drugs of abuse intoxication in children usually is the Fritz clinical evidence of a chronic exposure. Published clinical reports of drugs of abuse acute poisonings in children are reviewed, above all those with an underlying chronic exposure to the same or another substance. Biological matrices and exposure biomarkers useful in toxicology analysis in Paediatrics are reviewed. In toxicology, biomarkers refer to original parental substances and its metabolites and matrices refer to body substances where biomarkers are detected. In these matrices acute and chronic (previous days, weeks or months) exposures can be detected. Hair analysis has become the gold standard of drugs of abuse chronic exposure. Recommendation includes to confirm previous chronic exposure to drugs of abuse by hair analysis of children and their parents. This protocol must be applied in all cases with suspicion of acute drugs of abuse intoxication, parental consumption and/or children living in a risk environment.

Pharmacokinetics of methylphenidate in oral fluid and sweat of a pediatric subject.

Methylphenidate (MPH) is a stimulant medication widely used for treating attention-deficit hyperactivity disorder (ADHD) in children and adolescents. Therapeutic monitoring for this drug is essentially lacking and alternative biological matrices, such as oral fluid and sweat, should be investigated for noninvasive assessment of short- and long-term history of drug use. We report the excretion profile of MHP and its metabolite ritalinic acid (RA) in oral fluid and sweat from a 12-year-old boy treated with the extended release drug formulation. Concentrations of MPH and RA in oral fluid, sweat and plasma were measured by liquid chromatography-mass spectrometry. Oral fluid-to-plasma ratio at each time interval was calculated at the start of the treatment and correlated with salivary pH. Excretion of MPH in sweat patches, collected up to 24h with PharmChek patches was also investigated. MPH and RA were both detected in oral fluid with a pharmacokinetic profile similar to that in plasma. Oral fluid peak concentrations of MPH ranged between 13.5 and 30.9 ng/mL at 3.0 h after drug intake. Oral fluid-to-plasma MPH ratio between 13.1 and 3.2 demonstrated an accumulation of the drug in oral fluid. Conversely, RA was found in oral fluid at peak concentration (23.4-62.9 ng/mL) equivalent to one-tenth of those found in plasma. Concentration profiles of MPH and RA in oral fluid were quite constant during the four weeks of drug administration. In sweat, MPH was detected for the first time at 5h after drug administration (range: 9.3-11.2 ng/patch) up to 24h (range: 29.8-38.7 ng/patch). RA was not detected in the sweat patches during the 24h time of collection. The results suggest that measurement of MPH in oral fluid can be used as a potential alternative to drug monitoring in plasma. Moreover, MPH measurement in sweat patches can be used for noninvasive monitoring of MPH consumption and misuse in situations where detection of recent abuse is of interest.

Exposure to psychoactive substances in women who request voluntary termination of pregnancy assessed by serum and hair testing.

Drug abuse is a worldwide phenomenon with significant health and socioeconomic impact and it is of particular concern in women of reproductive age and in pregnant women. We aimed to investigate the prevalence of drug use by serum and hair testing in a cohort of pregnant women at 12th week gestation who decided voluntarily to interrupt their pregnancy and to investigate the relationship between drug exposure and induced abortions (IA), repeated IA and contraception. The study was conducted in an obstetrics clinic authorised to perform IA in Murcia, Spain during an 18 months period (2007-2009). Apart from serum and/or hair testing, the 142 women enrolled in the study completed a detailed questionnaire regarding drug, alcohol and tobacco use in the previous 3 months. Serum and hair samples were analyzed by gas chromatography mass spectrometry assays. Hair and serum samples showed a 30% overall positivity to drugs of abuse. Of these samples, 20.4, 14.1, 4.2 and 1.4% were positive for cannabinoids, cocaine, opiates, and MDMA, respectively, with polydrug use in 5.6% cases. In this cohort, a positive association was found between drug use and repeated IA. The results highlight the need for promoting pregnancy planning for young women in general, especially when consuming psychoactive substances as well as promote safe and accessible contraception in women of reproductive age. In women requesting IA, specific drug abuse counselling should be implemented.