Assessment of exposure to drugs of abuse during pregnancy by hair analysis in a Mediterranean island.

AIMS: This study aims to estimate the prevalence of drug use by pregnant women living in Ibiza, using structured interviews and biomarkers in maternal hair. In addition, the potentially detrimental effects of maternal drug abuse on their newborns were investigated. Ibiza has a large international night-life resort associated with clubs, music and use of recreational drugs. DESIGN, SETTING AND PARTICIPANTS: Hair samples were collected prospectively from January to March 2010 from a cohort of consecutive mothers after giving birth in the Hospital Can Misses in Ibiza. MEASUREMENTS: Opiates, cocaine, cannabis, methadone, amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and their metabolites were detected in a 3-cm-long proximal segment of maternal hair corresponding to the last trimester of pregnancy by gas chromatography coupled to mass spectrometry (n = 107). Data on socio-demographic characteristics and on tobacco, alcohol, drugs of prescription and drugs of abuse consumption during pregnancy were collected using a structured questionnaire. FINDINGS: Hair analysis showed an overall 16% positivity for drugs of abuse in the third trimester of pregnancy, with a specific prevalence of cannabis, cocaine, MDMA and opiates use of 10.3, 6.4, 0.9 and 0%, respectively. In the questionnaires, only 1.9% of mothers declared using drugs of abuse during pregnancy. Gestational drug of abuse consumption was associated with active tobacco smoking, a higher number of smoked cigarettes and the mother being Spanish. CONCLUSIONS: Illicit drug use is substantially under-reported among pregnant women living in Ibiza, particularly among Spanish nationals. Voluntary, routine objective biological toxicology screening should be considered as part of routine examinations in antenatal clinics on this Mediterranean island.

Cocaine use during pregnancy assessed by hair analysis in a Canary Islands cohort.

BACKGROUND: Drug use during pregnancy is difficult to ascertain, and maternal reports are likely to be inaccurate. The aim of this study was to estimate the prevalence of illicit drug use among pregnant women by using maternal hair analysis. METHODS: A toxicological analysis of hair was used to detect chronic recreational drug use during pregnancy. In 2007, 347 mother-infant dyads were included from the Hospital La Candelaria, Santa Cruz de Tenerife, Canary Islands (Spain). Data on socioeconomic characteristics and on substance misuse during pregnancy were collected using a structured questionnaire. Drugs of abuse: opiates, cocaine, cannabinoids and amphetamines were detected in maternal hair by immunoassay followed by gas chromatography-mass spectrometry for confirmation and quantitation. RESULTS: Hair analysis revealed 2.6% positivity for cocaine and its metabolites. Use of cocaine during pregnancy was associated with unusual behaviour with potentially harmful effects on the baby. CONCLUSIONS: The results of the study demonstrate significant cocaine use by pregnant women in Canary Islands. The data should be used for the purpose of preventive health and policy strategies aimed to detect and possibly to avoid in the future prenatal exposure to drugs of abuse.

Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a case report.

INTRODUCTION: Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs. CASE PRESENTATION: We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents. CONCLUSIONS: In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions.

Simultaneous analysis of frequently used licit and illicit psychoactive drugs in breast milk by liquid chromatography tandem mass spectrometry.

A liquid chromatography tandem mass spectrometry (LC-MS-MS) method for the quantification of frequently used licit (caffeine, nicotine and cotinine) and illicit drugs (opiates, cocaine, cannabinoids and amphetamines) in breast milk was developed and fully validated. Chromatography was performed on a reverse-phase column using a gradient of 2mM ammonium acetate, pH 6.6, and methyl alcohol as mobile phase at a flow rate of 0.35 mL/min. Separated analytes were quantified by electrospray ionization tandem mass spectrometry in positive ion mode using multiple reaction monitoring. Milk samples were kept at -20 °C until analysis and the compounds under investigation were extracted from the matrix by Bond Elut Certify cartridges. The concentration range covered was LOQ to 1000 ng/mL for all the investigated drugs. Intra- and inter-assay imprecision was less than 20%, analytical recovery ranged between 51.6% and 86.5%, matrix effect between 71.1% and 116.6% and process efficiency between 46.8% and 84.0%. Analytes were stable after three freeze-thaw cycles, after 6 months at -20 °C and after the pasteurization process (differences to the initial concentration always lower than 10%). matrix effect ranged from 77.6% to 116.6%, recovery from 51.6% to 86.5%, and process efficiency from 46.8% to 79.0%. This LC-MS-MS assay was applied to screen samples from the largest Spanish milk bank and samples coming from drug addicted mothers. The developed method provided adequate sensitivity and performance characteristics to prove the presence of only caffeine in a small percentage of samples from milk donating nursing mothers and the presence or absence of most commonly used illicit drugs in breast milk from addicted lactating mothers.

Relación entre las infecciones respiratorias de vías bajas durante el primer año de vida y el desarrollo de asma y sibilancias en niños / Relationship between Lower Respiratory Tract Infections in the First Year of Life and the Development of Asthma and Wheezing in Children

IntroducciónEn la relación entre las infecciones respiratorias de vías bajas (IRVB) y el desarrollo de asma y sibilancias durante la infancia, existen pocos datos con diseños prospectivos, de cohorte, desde el nacimiento y con población no seleccionada. El objetivo es determinar la prevalencia de asma y sibilancias recurrentes en la infancia, y establecer el efecto de las IRVB durante el primer año de vida.Pacientes y métodosCohorte poblacional de 487 recién nacidos en el Hospital del Mar, Barcelona, con seguimiento hasta los 6 años de edad. Como variables dependientes se han estudiado: presencia de asma y sibilancias; como variables independientes: IRVB ocurridas en el primer año de vida y diversas covariables como prematuridad, peso al nacer, antecedentes maternos de asma y atopia, lactancia materna y exposición prenatal al tabaco.ResultadosLa prevalencia de asma a los 6 años fue del 9,3%. Las variables asociadas al desarrollo de asma son: IRVB, ser prematuro, tener madre atópica y haber tomado lactancia artificial. Las IRVB en el primer año de vida también son un factor de riesgo relacionadas con las sibilancias recurrentes precoces y las sibilancias persistentes.ConclusionesLos resultados confirman que las IRVB durante el primer año de vida están relacionadas con el diagnóstico de asma y con los fenotipos clínicos de sibilancias precoces y de sibilancias persistentes. Estos resultados concuerdan con el concepto de que las IRVB producidas en un período crítico del desarrollo, como los primeros años de vida, tienen un papel importante en la aparición posterior de asma y de sibilancias recurrentes(AU)

IntroductionThere is limited knowledge on the relationship between lower respiratory tract infections (LRTI) and asthma and wheezing during infancy, as there are few studies with prospective design, birth cohort and in non selected population. The objectives of the present study were to determine the prevalence of asthma and recurrent wheezing in childhood and to analyse the relationship between LTRI during the first year of life and the development of asthma and/or wheezing in childhood.Patients and MethodsProspective birth cohort study conducted in the Hospital del Mar (Barcelona). We recruited 487 children, followed up from the pregnancy to the 6th year of life. As outcomes we studied: the presence of asthma and wheezing. As independent variables we studied: LTRI occurring during the first year of life, and some covariables including, among others: prematurity, birth weight, maternal history of asthma and atopy, breastfeeding, prenatal exposure to tobacco.ResultsThe asthma prevalence at 6 year of age was 9.3%. The variables associated with the development of asthma were LTRI, prematurity, atopic mother and formula breastfeeding. LTRI during the first year of life were also related with early recurrent wheezing and persistent wheezing.ConclusionsOur results confirm that LTRI during the first year of life are related to the diagnosis of asthma and with the clinical phenotypes of early wheezing and persistent wheezing. These results are in accordance with the concept that LTRI occurring during a critical period of development, as are the first years of life, have an important role on in the later development of asthma and recurrent wheezing(AU)

[Relationship between lower respiratory tract infections in the first year of life and the development of asthma and wheezing in children]. / Relación entre las infecciones respiratorias de vías bajas durante el primer año de vida y el desarrollo de asma y sibilancias en niños.

INTRODUCTION: There is limited knowledge on the relationship between lower respiratory tract infections (LRTI) and asthma and wheezing during infancy, as there are few studies with prospective design, birth cohort and in non selected population. The objectives of the present study were to determine the prevalence of asthma and recurrent wheezing in childhood and to analyse the relationship between LTRI during the first year of life and the development of asthma and/or wheezing in childhood. PATIENTS AND METHODS: Prospective birth cohort study conducted in the Hospital del Mar (Barcelona). We recruited 487 children, followed up from the pregnancy to the 6th year of life. As outcomes we studied: the presence of asthma and wheezing. As independent variables we studied: LTRI occurring during the first year of life, and some covariables including, among others: prematurity, birth weight, maternal history of asthma and atopy, breastfeeding, prenatal exposure to tobacco. RESULTS: The asthma prevalence at 6 year of age was 9.3%. The variables associated with the development of asthma were LTRI, prematurity, atopic mother and formula breastfeeding. LTRI during the first year of life were also related with early recurrent wheezing and persistent wheezing. CONCLUSIONS: Our results confirm that LTRI during the first year of life are related to the diagnosis of asthma and with the clinical phenotypes of early wheezing and persistent wheezing. These results are in accordance with the concept that LTRI occurring during a critical period of development, as are the first years of life, have an important role on in the later development of asthma and recurrent wheezing.

A comprehensive review of assay methods to determine drugs in breast milk and the safety of breastfeeding when taking drugs.

Most of the licit and illicit drugs consumed by the breastfeeding woman pass into the milk and can modify the production, volume and composition of the milk, as well as hypothetically have short- and long-term harmful effects on the infant. There is much confusion in the scientific community regarding this issue: should a woman breastfeed her baby while continuing to use prescription drugs and/or drugs of abuse? There are many case reports of clinically significant toxicity in breast-fed infants from some substances used by mothers (such as irritability, vomiting, sedation, respiratory depression, shock), but there are too few data on studies conducted in breastfeeding women and their infants to make a realistic risk assessment. The objective measurement of a drug and/or metabolites in maternal milk is the first step when investigating the amount of drug excreted in milk and subsequently calculating the daily dose administered to the breast-fed infant. The present review reports the analytical methods developed to detect different drugs in the breast milk, listing the principal characteristics and validation parameters, advantages and disadvantages. Furthermore, the mechanisms of drug transfer into breast milk are discussed, the correlation between the concentration of the drug in breast milk and potential adverse outcomes on the infant are described for each drug, and suggested harm minimization strategies and approved breastfeeding recommendations are indicated.

Exposición prenatal y posnatal al tabaco y síntomas respiratorios y alérgicos en los primeros años de vida / Perinatal Exposure to Tobacco and Respiratory and Allergy Symptoms in First Years of Life

IntroducciónEl objetivo del estudio ha sido analizar la relación de la exposición prenatal y posnatal al tabaco con la aparición de síntomas respiratorios y alérgicos en los primeros 4 años de vida.Pacientes y métodosEstudio de cohortes prospectivo y multicéntrico que incluye a sujetos del estudio AMICS (Asthma Multicentric Infant Cohort Study) en Ashford (Reino Unido), Barcelona y Menorca (España). Se incluyó a 1.611 niños que fueron seguidos desde el embarazo hasta el cuarto año de vida mediante cuestionarios anuales para obtener información sobre tabaquismo de los padres y síntomas respiratorios y alérgicos de los niños. En la cohorte de Barcelona (n=487) se procedió al análisis de un biomarcador de exposición al tabaco (cotinina) en distintas matrices.ResultadosLa exposición prenatal exclusiva al tabaco se relaciona con mayor riesgo de hospitalización por infección respiratoria, especialmente en el segundo año de vida, mientras que la exposición posnatal se asocia con la aparición de sibilancias tardías y aumenta la probabilidad del diagnóstico de asma a los 4 años. Los niños expuestos pre y posnatalmente presentan más sibilancias y roncus persistentes, tos nocturna, episodios de resfriados al año y diagnósticos de asma. El riesgo de presentar sibilancias es mayor cuanto más altos son los valores de cotinina. No existe asociación entre exposición al tabaco y síntomas atópicos.ConclusionesLa exposición pasiva al humo del tabaco durante el embarazo y la infancia tiene efectos clínicos respiratorios bien diferenciados en niños, por lo que la interrupción del hábito tabáquico en mujeres en edad fértil tiene que ser una prioridad en medicina preventiva(AU)

Background and objectivesTo analyse the relationship between prenatal and postnatal tobacco exposure and the development of respiratory and allergy symptoms during the first 4 years of life.Patients and methodsProspective and multicentred cohort study that included the subjects belonging to AMICS (Asthma Multicentred Infant Cohort Study) located in Ashford (England), Barcelona and Minorca (Spain). We recruited 1611 children, followed from the pregnancy to the 4th year of life, whose parents annually answered a questionnaire on their tobacco consumption and their children's respiratory and allergy health. In the Barcelona cohort (n=487) a tobacco exposure biomarker (cotinine) was analysed on several matrices.ResultsPrenatal tobacco exposure is associated with a greater risk of hospitalisation due to respiratory infection, particularly in the second year of life, whereas postnatal tobacco exposure is associated more strongly with the presence of late wheezing presence and increases in the chance of being diagnosed with asthma at 4 years of age. The children prenatally and postnatally exposed had more persistent wheezing, persistent rhoncus, early cough, a higher number of upper respiratory infections per year and a greater number were diagnosed with asthma. The higher the levels of cotinine measured, the higher was the risk for wheezing. No relationship was seen between tobacco exposure and atopic symptoms.ConclusionsPassive smoke exposure during pregnancy and childhood has very distinct clinical respiratory effects in children. Therefore, smoking cessation of childbearing age women must be a priority of preventive medicine(AU)

[Perinatal exposure to tobacco and respiratory and allergy symptoms in first years of life]. / Exposición prenatal y posnatal al tabaco y síntomas respiratorios y alérgicos en los primeros años de vida.

BACKGROUND AND OBJECTIVES: To analyse the relationship between prenatal and postnatal tobacco exposure and the development of respiratory and allergy symptoms during the first 4 years of life. PATIENTS AND METHODS: Prospective and multicentred cohort study that included the subjects belonging to AMICS (Asthma Multicentred Infant Cohort Study) located in Ashford (England), Barcelona and Minorca (Spain). We recruited 1611 children, followed from the pregnancy to the 4th year of life, whose parents annually answered a questionnaire on their tobacco consumption and their children's respiratory and allergy health. In the Barcelona cohort (n=487) a tobacco exposure biomarker (cotinine) was analysed on several matrices. RESULTS: Prenatal tobacco exposure is associated with a greater risk of hospitalisation due to respiratory infection, particularly in the second year of life, whereas postnatal tobacco exposure is associated more strongly with the presence of late wheezing presence and increases in the chance of being diagnosed with asthma at 4 years of age. The children prenatally and postnatally exposed had more persistent wheezing, persistent rhoncus, early cough, a higher number of upper respiratory infections per year and a greater number were diagnosed with asthma. The higher the levels of cotinine measured, the higher was the risk for wheezing. No relationship was seen between tobacco exposure and atopic symptoms. CONCLUSIONS: Passive smoke exposure during pregnancy and childhood has very distinct clinical respiratory effects in children. Therefore, smoking cessation of childbearing age women must be a priority of preventive medicine.

Pancreatitis aguda secundaria a colelitiasis en una niña con síndrome de Down / Acute pancreatitis due to cholelithiasis in a girl with Down Syndrome

La litiasis biliar en pediatría es una entidad poco frecuente y generalmente asintomática; sin embargo, puede ser potencialmente grave en los casos en que desencadena una pancreatitis como complicación. Trabajos publicados recientemente indican una mayor prevalencia de la litiasis biliar en niños con síndrome de Down (SD). Presentamos el caso de una niña con SD que presenta una pancreatitis aguda secundariamente a una colelitiasis que se resuelve satisfactoriamente (AU)

Gallstones are infrequent in children, and usuallya symptomatic. However, complications can besevere if pancreatitis ensues. Recent reports indicate above-average prevalence of cholelithiasis in Down syndrome. We report the successfully treated case of a 7-year-old girl with Down syndrome who developed pancreatitis secondary to cholelithiasis (AU)

Transforming growth factor-alpha attenuates N-methyl-D-aspartic acid toxicity in cortical cultures by preventing protein synthesis inhibition through an Erk1/2-dependent mechanism.

Transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor, reduces the infarct size after focal cerebral ischemia in rat, but the molecular basis underlying the protection is unknown. Excitotoxicity and global inhibition of translation are acknowledged to contribute significantly to the ischemic damage. Here we studied whether TGF-alpha can rescue neurons from excitotoxicity in vitro and how it affects calcium homeostasis, protein synthesis, and the associated Akt and extracellular signal-regulated kinase 1/2 (Erk1/2) intracellular signaling pathways in mixed neuron-glia cortical cultures. We found that 100 ng/ml TGF-alpha attenuated neuronal cell death induced by a 30-min exposure to 35 microM N-methyl-D-aspartic acid (NMDA) (as it reduced lactate dehydrogenase release, propidium iodide staining, and caspase-3 activation) and decreased the elevation of intracellular Ca2+ elicited by NMDA. TGF-alpha induced a prompt and sustained phosphorylation of Erk1/2 and prevented the loss of Akt-P induced by NMDA 3 h after exposure. The protective effect of TGF-alpha was completely prevented by PD 98059, an inhibitor of the Erk1/2 pathway. Studies of incorporation of [3H]leucine into proteins showed that NMDA decreased the rate of protein synthesis, and TGF-alpha attenuated this effect. TGF-alpha stimulated the phosphorylation of the eukaryotic initiation factor 4E (eIF4E) but did not affect eIF2 alpha, two proteins involved in translation regulation. PD 98059 abrogated the TGF-alpha effect on eIF4E. Our data demonstrate that TGF-alpha exerts a neuroprotective action against NMDA toxicity, in which Erk1/2 activation plays a key role, and suggest that the underlying mechanisms involve recovery of translation inhibition, mediated at least in part by eIF4E phosphorylation.

Certain forms of matrix metalloproteinase-9 accumulate in the extracellular space after microdialysis probe implantation and middle cerebral artery occlusion/reperfusion.

Matrix metalloproteinases (MMPs) are activated in focal cerebral ischemia. The activation of MMP-9 is involved in blood-brain barrier breakdown and tissue remodeling. The MMPs are released to the extracellular space, but the form and fate of secreted enzymes in brain are unknown. Using microdialysis in vivo, the authors studied whether ischemia-induced MMP-9 in brain tissue was related to free MMP-9 in the extracellular fluid. A microdialysis probe was placed into the right striatum and microdialysis was initiated 24 hours later in controls (n = 7). One hour prior to microdialysis, a group of rats (n = 7) was subjected to 1-hour occlusion of the right middle cerebral artery, followed by reperfusion. Dialysates were collected at discrete time points up to 24 hours, and subjected to zymography and Western blot analysis. The MMP-9 was released after ischemia and accumulated in the extracellular space at 24 hours (P < 0.05). Free MMP-9 forms include mainly the 95-kd proform, and, to a lesser extent, dimers and cleaved active forms (70 kd), but not the 88-kd form found in tissue. Probe implantation and microdialysis increased free MMP-9 in the dialysate. This increase was concomitant with neutrophil infiltration after the mechanical lesion, as myeloperoxidase was found by means of Western blot analysis in the brain hemisphere subjected to microdialysis (P < 0.005), and immunohistochemistry revealed the presence of myeloperoxidase stain surrounding the site of probe implantation. The results suggest that certain forms of MMP-9 are released and accumulate in the extracellular space after brain injury, and that vascular alterations and neutrophil recruitment elicit MMP-9 activation in the brain after focal ischemia and trauma.

Activation of ERK and Akt signaling in focal cerebral ischemia: modulation by TGF-alpha and involvement of NMDA receptor.

Cerebral ischemia activates ERK and Akt pathways. We studied whether these activations were affected by treatment with the protective growth factor transforming growth factor-alpha (TGF-alpha), and whether they were mediated through N-methyl D-aspartate (NMDA) receptors. The middle cerebral artery was occluded in rats and signaling was studied 1 h later. Noncompetitive NMDA receptor antagonist MK-801 was injected i.p. before the occlusion, whereas in other rats TGF-alpha was given intraventricularly before and after occlusion. Ischemia caused ERK phosphorylation in the nucleus, localized in the endothelium and neurons. Phosphorylation of ERK was prevented by TGF-alpha, but it was enhanced in the nucleus and cytoplasm by MK-801. Also, MK-801 but not TGF-alpha increased p-Akt. Results suggest that preventing ERK activation is related to the protective effect of TGF-alpha, whereas the protective effect of MK-801 is associated with activation of pro-survival Akt. While results support that NMDA receptor signaling precludes Akt activation, we did not find evidence to support that it underlies ischemia-induced ERK phosphorylation. This study illustrates that neuroprotection results from a fine balance between death and survival signaling pathways.