Prenatal exposure to metals and concentration thereof in umbilical cord blood in a Mexico City cohort.

BACKGROUND: In Mexico, there is a paucity of evidence on the magnitude of prenatal exposure to metals. OBJECTIVE: To estimate the concentration of arsenic, cadmium, manganese and lead in umbilical cord blood (UCB) and its association with maternal blood concentrations during pregnancy and delivery. MATERIAL AND METHODS: Metal concentration in maternal blood was analyzed during pregnancy (n = 901), delivery (n = 732) and in UCB (n = 512) from participants of the PROGRESS cohort residing in Mexico City. The association between concentrations in UCB and maternal biomarkers was analyzed using generalized linear models, adjusted for relevant covariates. RESULTS: Mean concentrations (µg/L) of lead, arsenic and manganese in UCB were 27.14 (25.28-29.14), 0.77 (0.71-0.84) and 42.60 (40.45-44.83), respectively. Cadmium concentration could not be estimated because 86.2% of measurements were below the detection limit. Lead and manganese concentrations in UCB were significantly associated with maternal biomarkers during pregnancy and delivery; at delivery, association was only observed with arsenic. CONCLUSIONS: Prenatal exposure to toxic metals in sensitive periods of organogenesis shows a neglected public health problem. Biomonitoring of the population and establishment of regulations aimed at providing care to vulnerable populations is required.

ANTECEDENTES: En México es exigua la evidencia sobre la exposición prenatal a metales. OBJETIVO: Estimar la concentración de arsénico, cadmio, manganeso y plomo en sangre de cordón umbilical (SCU), y su asociación con las concentraciones en sangre materna durante el embarazo y parto. MATERIAL Y MÉTODOS: Se analizó la concentración de los metales en sangre materna durante el embarazo (n = 901), parto (n = 732) y en la SCU (n = 512) de participantes de la cohorte PROGRESS, residentes en la Ciudad de México. Se estimó la asociación entre la concentración en SCU y los biomarcadores maternos mediante modelos lineales generalizados, ajustados por covariables relevantes. RESULTADOS: La media (µg/L) de plomo, arsénico y manganeso en SCU fue 27.14 (25.28-29.14), 0.77 (0.71-0.84) y 42.60 (40.45-44.83), respectivamente. El valor del cadmio no se pudo estimar porque 86.2 % de las mediciones fueron inferiores al límite de detección. Las concentraciones de plomo y manganeso en SCU se asociaron significativamente a los biomarcadores maternos durante el embarazo y el parto; solo se observó asociación con arsénico en el parto. CONCLUSIONES: La exposición prenatal a metales tóxicos en periodos sensibles de la organogénesis evidencia un problema de salud pública desatendido. Se requiere un biomonitoreo poblacional y establecer regulación dirigida a proveer atención a población vulnerable.

Concentración de metales en sangre de cordón umbilical debido a exposición prenatal en una cohorte de la Ciudad de México / Prenatal exposure to metals and concentration thereof in umbilical cord blood in a Mexico City cohort

Resumen Antecedentes: En México es exigua la evidencia sobre la exposición prenatal a metales. Objetivo: Estimar la concentración de arsénico, cadmio, manganeso y plomo en sangre de cordón umbilical (SCU), y su asociación con las concentraciones en sangre materna durante el embarazo y parto. Material y métodos: Se analizó la concentración de los metales en sangre materna durante el embarazo (n = 901), parto (n = 732) y en la SCU (n = 512) de participantes de la cohorte PROGRESS, residentes en la Ciudad de México. Se estimó la asociación entre la concentración en SCU y los biomarcadores maternos mediante modelos lineales generalizados, ajustados por covariables relevantes. Resultados: La media (μg/L) de plomo, arsénico y manganeso en SCU fue 27.14 (25.28-29.14), 0.77 (0.71-0.84) y 42.60 (40.45-44.83), respectivamente. El valor del cadmio no se pudo estimar porque 86.2 % de las mediciones fueron inferiores al límite de detección. Las concentraciones de plomo y manganeso en SCU se asociaron significativamente a los biomarcadores maternos durante el embarazo y el parto; solo se observó asociación con arsénico en el parto. Conclusiones: La exposición prenatal a metales tóxicos en periodos sensibles de la organogénesis evidencia un problema de salud pública desatendido. Se requiere un biomonitoreo poblacional y establecer regulación dirigida a proveer atención a población vulnerable.

Abstract Background: In Mexico, there is a paucity of evidence on the magnitude of prenatal exposure to metals. Objective: To estimate the concentration of arsenic, cadmium, manganese and lead in umbilical cord blood (UCB) and its association with maternal blood concentrations during pregnancy and delivery. Material and methods: Metal concentration in maternal blood was analyzed during pregnancy (n = 901), delivery (n = 732) and in UCB (n = 512) from participants of the PROGRESS cohort residing in Mexico City. The association between concentrations in UCB and maternal biomarkers was analyzed using generalized linear models, adjusted for relevant covariates. Results: Mean concentrations (μg/L) of lead, arsenic and manganese in UCB were 27.14 (25.28-29.14), 0.77 (0.71-0.84) and 42.60 (40.45-44.83), respectively. Cadmium concentration could not be estimated because 86.2% of measurements were below the detection limit. Lead and manganese concentrations in UCB were significantly associated with maternal biomarkers during pregnancy and delivery; at delivery, association was only observed with arsenic. Conclusions: Prenatal exposure to toxic metals in sensitive periods of organogenesis shows a neglected public health problem. Biomonitoring of the population and establishment of regulations aimed at providing care to vulnerable populations is required.

Anomalías congénitas disruptivas asociadas con misoprostol. Reporte de un caso / Disruptive congenital anomalies associated with misoprostol. Case report

Resumen ANTECEDENTES: La exposición prenatal al misoprostol puede asociarse con un espectro de defectos congénitos que varían desde anomalías del sistema nervioso central, secuencia de Moebius, defectos en la pared abdominal, defectos transversales en las extremidades hasta alteraciones fetales. Esos defectos se observan más comúnmente con esquemas de solo misoprostol para inducción del aborto. Por esos antecedentes es importante que la historia clínica de toda paciente obstétrica sea exhaustiva para permitir identificar el antecedente de la exposición prenatal luego de un aborto fallido. CASO CLINICO: Paciente de 21 años, con 32 semanas de embarazo, con diagnóstico de feto con ventriculomegalia. En la evaluación ecográfica destacó la ventriculomegalia triventricular severa, simétrica y la angulación de ambas extremidades inferiores en varo. La resonancia magnética reportó: ventriculomegalia no comunicante severa, bilateral, simétrica, por probable estenosis del acueducto de Silvio. Cariotipo 46,XY y perfil TORCH negativo. El embarazo finalizó mediante cesárea, por indicación fetal a las 35 semanas. La evaluación al nacimiento reportó: parálisis facial bilateral, macrocefalia y pie equino varo bilateral. Al volver a interrogar a la paciente refirió haber sido tratada con misoprostol en el primer trimestre del embarazo, con fines abortivos. Al descartar las alteraciones cromosómicas e infecciosas se estableció el diagnóstico de secuencia Moebius. CONCLUSIONES: La exposición prenatal al misoprostol está relacionada con la aparición de defectos vasculares en algunos fetos expuestos. Aún no se ha determinado el espectro preciso ni la estimación potencial de teratogenicidad. La historia clínica es el pilar para la asociación en estos casos.

Abstract BACKGROUND: Prenatal misoprostol exposure can be associated with a spectrum of birth defects, ranging from central nervous system abnormalities, Moebius sequence, abdominal wall defects, as well as transverse limb defects, fetal abnormalities are more commonly seen with the use of the misoprostol-only regimen for induction of abortion, such that a thorough medical history is essential to detect a history of prenatal exposure after a failed abortion. CLINICAL CASE: A 21-year-old patient, with a 32-week pregnancy, who attended the institute with a diagnosis of a fetus with ventriculomegaly, the ultrasound evaluation highlighted severe symmetric triventricular ventriculomegaly and angulation of both lower extremities in varus, magnetic resonance imaging reported severe non-communicating ventriculomegaly Symmetric bilateral, due to probable stenosis of the aqueduct of Silvio, the karyotype reported 46, XY, as well as a negative TORCH profile, however, a cesarean section was performed for fetal indication at 35 weeks, the evaluation at birth showed bilateral facial paralysis, macrocephaly and foot Bilateral equinus varus, upon re-examination the patient referred the use of misoprostol in the first trimester of pregnancy for abortive purposes, so as there were no chromosomal or infectious alterations, a Moebius sequence was suggested. CONCLUSIONS : Prenatal exposure to misoprostol is related to the appearance of vascular disruption defects in some exposed fetuses, the precise spectrum and potential estimation of teratogenicity have not yet been determined, the clinical history is the mainstay for the association in these cases.

Alteraciones neuropsiquiátricas en menores de 18 años expuestos a opioides en el periodo prenatal: Revisión Narrativa

El consumo de opioides ha venido incrementando en los últimos años, generando una crisis de salud pública que afecta a todo tipo de población. El uso de sustancias opiáceas ilegales en embarazadas también está en incremento, por lo que, en la práctica clínica se evidencian con mayor frecuencia resultados neonatales adversos como el síndrome de abstinencia neonatal (NAS). Adicionalmente, los niños expuestos prenatalmente a estas sustancias pueden sufrir alteraciones cognitivas, motoras o psiquiátricas durante el transcurso de su vida. Este artículo tiene como objetivo proporcionar una revisión de la literatura actualizada acerca del uso de opioides durante el embarazo y las consecuencias para los niños expuestos a estas sustancias.

Opioid consumption has increased greatly in recent years, creating a public health crisis that affects all types of population. The use of illegal opiates amongst pregnant women has also risen, causing a surge in the frequency in which adverse neonatal outcomes, such as Neonatal Abstinence Syndrome (NAS), are seen in clinical practice. Furthermore, children exposed prenatally to these substances have cognitive, motor and psychiatric adverse outcomes throughout their lifetime. This article's objective is to provide an updated literature review about opioid use during pregnancy and its consequences on children exposed in-utero.

Factores de riesgos heredofamiliares, prenatales y perinatales en niños cubanos con autismo primario / Family inherited, prenatal and perinatal risk factors in Cuban children with primary autism

Introducción: El autismo primario es una heterogénea alteración neuroconductual, de causa no precisa, en la que tanto los genes como el ambiente contribuyen a la patogenia del trastorno. Objetivo: Identificar factores de riesgos heredofamiliares, prenatales y perinatales en niños cubanos con autismo primario. Material y Métodos: Se realizó una investigación observacional tipo casos y controles (1:1) en niños con autismo primario, atendidos en el Hospital Pediátrico "Juan Manuel Márquez", La Habana; en el período de octubre de 2014 a septiembre de 2019. La muestra quedó conformada por 126 casos y 126 controles. Se recolectaron los datos sobre la historia de enfermedades neuropsiquiátricas de tres generaciones, antecedentes prenatales y perinatales. Se realizó una regresión logística multivariada para identificar factores de riesgos relacionados con el autismo primario. Resultados: El odds de presentar autismo primario fue aproximadamente siete y cuatro veces superior en hijos de madres y padres con edad avanzada, respectivamente. Los antecedentes de trastornos del lenguaje y epilepsia en familiares de primer grado, confirió un odds de presentar autismo 27 y 24 veces mayor, respectivamente. El odds de presentar autismo fue aproximadamente diez veces mayor en los hijos de gestantes con anemia, ocho veces en hijos de gestantes que tuvieron gestorragias y 18 veces para los nacidos de madres con antecedentes de diabetes mellitus pregestacional. Conclusiones: Los antecedentes de enfermedades heredofamiliares neuropsiquiátricas y de factores ambientales prenatales y perinatales relacionados con eventos hipoxémicos constituyen factores de riesgo para el autismo primario en la muestra de niños cubanos estudiados(AU)

Introduction: Primary autism is a heterogeneous neurobehavioral disorder of uncertain etiology in which both genes and the environment contribute to the pathogenesis of the disorder. Objective: To identify family inherited, prenatal and perinatal risk factors in Cuban children with primary autism. Material and Methods: An observational case-control study (1:1) was carried out in children with primary autism, treated at "Juan Manuel Márquez" Pediatric Hospital, Havana, in the period from October of 2014 to September of 2019. The sample was made up of 126 cases and 126 controls. Data on neuropsychiatric diseases, prenatal and perinatal history of three generations were collected. Multivariate logistic regression was performed to identify risk factors related to primary autism. Results: The odds of presenting primary autism were approximately seven and four times higher in children of mothers and fathers of advanced ages, respectively. A history of language disorders and epilepsy in first-degree relatives conferred 27- and 24-fold higher odds of presenting with autism, respectively. The odds of presenting autism were approximately ten times greater in children born to pregnant women with anemia, eight times in children born to pregnant women who had bleeding during pregnancy, and 18 times in those born to mothers with a history of pregestational diabetes mellitus. Conclusions: The history of inherited neuropsychiatric diseases and prenatal and perinatal environmental factors related to hypoxemic events are risk factors for primary autism in the sample of Cuban children studied(AU)

Chlorpyrifos should be banned in agriculture and livestock production in Colombia

Chlorpyrifos (CPF) is a pesticide widely used in Colombia´s agriculture, including crops, farm animals and pets, despite it has been banned for use in the European Union and the United States. Studies demonstrate that even low blood levels of CPF -which do not inhibit blood acetylcholinesterase- can lead to child developmental and neurological disorders such as smaller head circumference and brain alterations, and psychomotor and cognitive deficits related to learning ability, attention and memory. In adults, CPF is an endocrine disruptor and breast carcinogen. High direct and indirect economic costs have been associated with CPF exposure. Not only farmers and their families -who have the highest exposures- but the general population consuming crops sprayed with CPF are also at risk. For these reasons CPF was recently banned by the European Union (2020) and the USA (2021). Pesticide regulation policies vary greatly depending on which and how scientific studies are used to assess health risks. Pesticide evaluations funded by the chemical industry should be rectified to avoid conflicts of interest. Furthermore, political alignment with the interests of the industry should not take precedence over independent scientific evidence. It is discouraging, to say the least, that until stricter health laws are passed in Colombia, CPFs and related pesticides will continue to be imported from those countries that have already banned them. Colombian scientists should raise their voice to challenge blind acceptance of profits over unintended consequences, and efforts to prevent pesticide´s abuse should be encouraged.

El clorpirifos (CPF) es un pesticida ampliamente utilizado en la agricultura de Colombia, incluidos cultivos, animales de granja y mascotas, a pesar de haber sido prohibido en la Unión Europea y Estados Unidos. Los estudios han demostrado que incluso niveles bajos de CPF en sangre -que no inhiben la acetilcolinesterasa sanguínea- pueden provocar trastornos neurológicos y del desarrollo infantil, como menor circunferencia de la cabeza y alteraciones cerebrales, y déficits psicomotores y cognitivos relacionados con la capacidad de aprendizaje, la atención y la memoria. En adultos, el CPF es un disruptor endocrino y causante de cáncer de mama. Altos costos económicos directos e indirectos se han asociado con la exposición al CPF. No solo los trabajadores agrícolas y sus familias, que están más expuestos, sino también la población en general que consume cultivos rociados con CPF también están en riesgo. Por estas razones el CPF fue prohibido recientemente por la Unión Europea (2020) y los EE. UU. (2021). Las políticas de regulación de plaguicidas varían mucho según los estudios científicos escogidos para evaluar los riesgos para la salud. Las evaluaciones de plaguicidas financiadas por la industria química deben rectificarse para evitar conflictos de interés. Además, ante la evidencia científica independiente no debería prevalecer la alineación política con los intereses de dicha industria. Es desalentador, por decir lo menos, que hasta que se aprueben leyes de salud más estrictas en Colombia se seguirán importando CPF y pesticidas relacionados desde aquellos países que ya los han prohibido. Los científicos colombianos deben alzar la voz para desafiar la aceptación ciega de ganancias por encima de las consecuencias no deseadas en salud pública, y se deben alentar los esfuerzos para prevenir el abuso de pesticidas.

Clorpirifós (CPF) é um pesticida registrado amplamente utilizado na agricultura colombiana, incluindo lavouras, animais de fazenda e animais de estimação, apesar de ter sido proibido na União Europeia e nos Estados Unidos. Estudos têm demonstrado que mesmo níveis baixos de CPF no sangue -que não inibem a acetilcolinesterase sanguínea-podem levar a distúrbios neurológicos e de desenvolvimento em crianças, como menor perímetro cefálico e alterações cerebrais, além de déficits psicomotores e cognitivos relacionados à capacidade de aprendizagem, atenção e memoria. Em adultos, o CPF é um desregulador endócrino e cancerígeno da mama. Altos custos econômicos diretos (devido ao tratamento) e indiretos (devido à perda de produtividade) têm sido associados à exposição ao CPF. Não apenas os trabalhadores agrícolas e suas famílias, que têm as maiores exposições, mas a população em geral que consome culturas pulverizadas com CPF também estão em risco. Por essas razões, o CPF foi recentemente proibido pela União Europeia (2020) e pelos EUA (2021). As políticas de regulamentação de pesticidas variam muito, dependendo de quais (e como) os estudos científicos são usados para avaliar os riscos à saúde. As avaliações de pesticidas financiadas pela indústria química devem ser retificadas para evitar conflitos de interesse. Além disso, o alinhamento político com os interesses da indústria não deve ter precedência sobre as evidências científicas independentes. É desanimador - para dizer o mínimo - que até que leis de saúde mais rígidas sejam aprovadas na Colômbia, o CPF e tóxicos relacionados continuarão a ser importados dos países que já os proibiram.

Factors associated with prenatal stress and anxiety in pregnant women during COVID-19 in Spain.

AIM OF THE STUDY: To describe prenatal stress and state anxiety levels in pregnant women living in Spain during the lockdown of the first wave of COVID-19 and its relation with obstetric factors, perception of health care, and concerns about the socio-sanitary situation. METHODS: The present study is an observational, correlational, and cross-sectional quantitative study. The participants in the study were pregnant women recruited through non-probabilistic convenience and snowball sampling during the lockdown. A web link was provided to an online questionnaire designed for this research, which collected socio-demographic and obstetric variables, perceptions of health care received during the pandemic and preoccupations associated with COVID-19. It also included the Prenatal Stress Questionnaire (PDQ) and the State Anxiety Inventory (STAI-S). RESULTS: Based on the responses of 695 pregnant women, the results showed a mean of 16.98 (SD = 25.20) of prenatal stress and elevated levels of anxiety (M = 25.20/SD = 11.07) in the first wave of the pandemic. Risk factors for prenatal stress and anxiety were the level of preoccupation associated with COVID-19 and previous mental health issues. A specific risk factor for anxiety was having more than one child and a protective factor were perceiving accessibility and availability of health care, with clear and consistent pregnancy care and follow-up protocols. CONCLUSIONS: The lockdown period for COVID-19 was a stressful experience for pregnant women, highlighting the need to address their psychological well-being through clear and coherent protocols in terms of maternal-foetal health control and follow-up.

Exposición prenatal al monóxido de carbono y material particulado y su asociación con preeclampsia, en Colombia / Prenatal exposure to carbon monoxide and particulate matter and its association with preeclampsia in Colombia

Resumen OBJETIVO: Determinar la asociación entre la exposición a emisiones vehiculares de PM10 y monóxido de carbono y la preeclampsia en Manizales, Colombia. MATERIALES Y MÉTODOS: Estudio relacional, retrospectivo, de casos y controles efectuado entre julio de 2014 y julio de 2015 en pacientes con preeclampsia, residentes en la zona urbana de Manizales, Colombia. Se usó el sitio de residencia para la estimación de la exposición y la concentración de contaminantes a través de un instrumento de determinación de exposición a emisiones de PM10 y monóxido de carbono (toneladas por año por cada 250 metros cuadrados). Se utilizaron dos definiciones de exposición: cuartil superior (Q4) en comparación con los cuartiles restantes (Q1-Q3) y otra: comparación de los cuatro cuartiles tomando como referencia el primero (Q1). Se ajustaron modelos de regresión logística con el fin de explorar el efecto de la exposición. RESULTADOS: Se incluyeron 222 pacientes: 74 casos y 148 controles. No se observó relación entre la concentración de PM10 en el área de residencia de la madre y la probabilidad de preeclampsia con la primera definición de exposición (RM de 1.013 [IC95%: 0.35 a 2.97; p = 0.981] y la segunda [Q2; p = 0.562], [Q3; p = 0.347], [Q4; p=0.887]). Para el caso del monóxido de carbono tampoco se encontró relación estadística en las dos definiciones (RM: 0.829 [IC95%: 0.29 a 2.39] p = 0.729.). CONCLUSIONES: No se observó asociación entre las concentraciones de exposición a PM10 y monóxido de carbono y la aparición de preeclampsia durante los tiempos descritos.

Abstract OBJECTIVE: To determine the association between exposure to PM10 and carbon monoxide vehicle emissions and preeclampsia in Manizales, Colombia. MATERIALS AND METHODS: This was a relational, retrospective, case-control study in patients with pregnancy complicated by preeclampsia, residents of Manizales-Colombia between July 2014 and July 2015. The place of residence was used to estimate exposure and the concentration of pollutants through an instrument for determining exposure to PM10 and CO emissions (tons per year for every 250 square meters). Two definitions of exposure were used: upper quartile (Q4) vs the remaining quartiles (Q1-Q3) and another: comparison of the four quartiles taking the first quartile (Q1) as a reference. Logistic regression models were fitted in order to explore the effect of exposure. RESULTS: 222 patients were included, 74 cases and 148 controls. No relationship was observed between the concentration of PM10 in the mother's area of residence and the probability of presenting preeclampsia with both the first definition of exposure (OR of 1.013 (95%CI: 0.35 to 2.97) p = 0.981) as with the second (Q2 (p=0.562), Q3 (p = 0.347), Q4 (p = 0.887)). In the case of OC, no statistical relationship was found in the two definitions (OR: 0.829 (95%CI: 0.29 to 2.39) p = 0.729). CONCLUSIONS: No association was observed between the levels of exposure to PM10 and CO and the appearance of preeclampsia in pregnant women during the times described.

Características clínicas y factores de riesgo asociados a la exposición prenatal a drogas de abuso / Clinical features and risk factors associated with prenatal exposure to drugs of abuse

Introducción: La identificación temprana de los neonatos expuestos a drogas de abuso permite realizar un manejo clínico más preciso.Objetivos: Describir las características clínicas e identificar factores de riesgo asociados a la detección precoz de neonatos expuestos a drogas de abuso en una Unidad de Cuidados Intensivos e Intermedios Neonatales.Métodos: Estudio observacional prospectivo de neonatos con y sin sospecha clínica de exposición prenatal a drogas de abuso. Se analizó meconio empleando técnicas cromatográficas estandarizadas. Se realizaron análisis estadísticos univariante y multivariante.Resultados: Se incluyeron 372 neonatos. En 49 (13,2%) casos se detectó exposición a alguna droga de abuso; en 41 (83,7%) a una, y en ocho (16,3%) a más de una. La somatometría al nacimiento objetivó: a) menor percentil de longitud en expuestos a alguna droga, a más de una y a cannabis; b) menor percentil de peso en expuestos a cannabis, y de éstos en comparación con los expuestos a alcohol. En mayores de 34 semanas de gestación (SG): a) menor percentil de longitud en expuestos a alguna droga; b) menor percentil de longitud y peso en expuestos a más de una. Los factores de riesgo independientes clínicamente útiles para detectar casos de exposición prenatal a drogas de abuso fueron (odds ratio [IC 95%]): motivo de ingreso distinto a prematuridad (5,52 [2,55-1,93]), percentil de longitud menor a 33 (1,95 [1,05-3,60]) y (2,14 [1,04-3,40]) en mayores de 34 SG y distocia social/embarazo no controlado en mayores a 34SG (4,47 [1,03-19,29]).Conclusiones: Existen alteraciones somatométricas y factores de riesgo que pueden ayudar a detectar precozmente a los neonatos expuestos a drogas de abuso. Las alteraciones somatométricas identificadas pueden servir para ampliar su diagnóstico diferencial y el estudio de sus causas. (AU)

Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management.Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit.Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed.Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)).Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

Clinical features and risk factors associated with prenatal exposure to drugs of abuse.

INTRODUCTION: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. OBJECTIVES: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. METHODS: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. RESULTS: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). CONCLUSIONS: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

Perfil neurocognitivo y conductual del trastorno del espectro alcohólico fetal / Neurocognitive and behavioral profile of fetal alcohol spectrum disorder

La exposición prenatal al alcohol es la principal causa prevenible del déficit cognitivo en los países desarrollados y puede dar lugar al trastorno del espectro alcohólico fetal (TEAF). Este término engloba una gran variedad de efectos físicos, mentales, conductuales y cognitivos que derivan del daño causado por la exposición al alcohol durante la vida intrauterina. El consumo de esta sustancia entre la población general es frecuente en los países de la Europa del Este y, especialmente, entre las mujeres en riesgo de exclusión social, que son las mayores afectadas en procesos de pérdida o renuncia de custodia de sus hijos. Un elevado número de estos niños son adoptados en España y muchos de ellos presentan alteraciones neurocognitivas y conductuales, convirtiendo el TEAF en un problema de salud pública en nuestro país. En muchas ocasiones, este cuadro clínico está infradiagnosticado debido a la superposición de los síntomas neuropsicológicos causados por el abandono y la falta de apego. Hasta el momento, no se ha descrito un perfil neurocognitivo y conductual específico del TEAF y muchos de los síntomas son comunes a otras etiologías. El objetivo de este trabajo es revisar el perfil neuropsicológico en el diagnóstico de TEAF. (AU)

Prenatal alcohol exposure is the leading preventable cause of cognitive deficit in developed countries and can lead to fetal alcohol spectrum disorder (FASD). This term encompasses a wide range of physical, mental, behavioral, and cognitive effects that result from damage caused by exposure to alcohol during intrauterine life. Alcohol consumption among the general population is common in Eastern European countries and especially among women at risk of social exclusion, who are the ones who lose or give up custody of their children. A high number of these children are adopted in Spain and many of them present neurocognitive and behavioral disorders, causing FASD to be a public health problem in our country. In many occasions this clinical spectrum is delayed or under-diagnosed due to the overlapping of neuropsychological symptoms caused by the abandonment. A neurocognitive and behavioral profile specific for FASD has not been defined and all the symptoms are common to other etiologies. The aim of this work is to review the neuropsychological profile in the diagnosis of TEAF. (AU)

Neurocognitive and behavioral profile of fetal alcohol spectrum disorder.

Prenatal alcohol exposure is the leading preventable cause of cognitive deficit in developed countries and can lead to fetal alcohol spectrum disorder (FASD). This term encompasses a wide range of physical, mental, behavioral, and cognitive effects that result from damage caused by exposure to alcohol during intrauterine life. Alcohol consumption among the general population is common in Eastern European countries and especially among women at risk of social exclusion, who are the ones who lose or give up custody of their children. A high number of these children are adopted in Spain and many of them present neurocognitive and behavioral disorders, causing FASD to be a public health problem in our country. In many occasions this clinical spectrum is delayed or under-diagnosed due to the overlapping of neuropsychological symptoms caused by the abandonment. A neurocognitive and behavioral profile specific for FASD has not been defined and all the symptoms are common to other etiologies. The aim of this work is to review the neuropsychological profile in the diagnosis of FASD.

Asociación entre el cociente del segundo y cuarto dedo y el riesgo de cáncer de próstata: Un estudio de casos y controles en población mediterránea / Second to Fourth Digit Ratio and Prostate Cancer Risk: A Case-control Study in Mediterranean Population

Objetivo Evaluar la asociación entre el cociente de los dedos segundo y cuarto (2D:4D), como un biomarcador de la exposición prenatal a andrógenos, y la presencia de cáncer de próstata (CaP). Métodos Estudio de casos y controles con 260 hombres que consultaron en el Servicio de Urología del Hospital General Universitario Reina Sofía (Murcia, España). Los casos (n = 125) fueron pacientes diagnosticados de CaP por anatomía patológica a los que se les realizó una prostatectomía radical. Los controles (n = 135) fueron pacientes que consultaron en Urología por otro motivo y que no mostraron signos ni síntomas de patología prostática. La longitud del 2D y 4D de la mano derecha fue medida mediante un pie de rey digital y se calculó el cociente entre ambos (2D:4D). Para los análisis estadísticos se utilizaron modelos de regresión logística obteniendo Odds ratios (OR) crudas y ajustadas e intervalos de confianza al 95%. Resultados Los casos presentaron un cociente 2D:4D significativamente menor que los controles. El cociente 2D:4D se relacionó significativamente con la presencia de CaP. Tras el ajuste multivariante, se observó que los varones que se encontraban en el primer tercil de distribución del cociente 2D:4D, presentaban casi el doble de riesgo de padecer CaP (OR 1,9: IC 95% 1,1­4,0; P-valor = 0,040) en comparación con los varones que se encontraban en el segundo y tercer tercil. Conclusiones Una mayor exposición prenatal a andrógenos, reflejada por un cociente 2D:4D menor, podría estar asociado con riesgo aumentado de padecer CaP, pero más estudios son necesarios para corroborar esos hallazgos.

Objective To evaluate the association between second to fourth digit (2D:4D) ratio, as a biomarker of prenatal androgen exposure, and the presence of prostate cancer (PCa). Methods This was a case-control study of 260 men attending a Department of Urology in a Murcia Region hospital (Spain). Cases (n = 125) were patients who underwent radical prostatectomy due to PCa and were diagnosed by specimen's histopathology. Controls (n = 135) were patients who showed no signs or symptoms of prostate disease. The length of 2D and 4D of the right hand was measured two times using a digital caliper, and the ratio calculated (2D:4D). Unconditional multiple logistic regressions [crude and adjusted Odds ratios (OR) and 95% confidence intervals (CI)] were performed to evaluate associations between the 2D:4D ratio and presence of PCa. Results Cases showed significantly lower 2D:4D ratios than controls. 2D:4D ratios were significantly associated with the presence of PCa. After controlling for important covariates, men in the first tertile of the 2D:4D ratio distribution, compared with the second and third tertile, were almost two-times [OR 1.9 (95% CI 1.1­4.0; P-value = 0.040] more likely to have PCa. Conclusions A higher prenatal androgen exposure, indicated by lower 2D:4D ratios, might be associated with higher PCa risk, but further research is needed to confirm these findings in other male populations.

[Clinical features and risk factors associated with prenatal exposure to drugs of abuse]. / Características clínicas y factores de riesgo asociados a la exposición prenatal a drogas de abuso.

INTRODUCTION: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. OBJECTIVES: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. METHODS: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. RESULTS: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). CONCLUSIONS: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

Trayectorias sanitarias durante 4 años de niños expuestos prenatalmente a cocaína y/o cannabis. Estudio de cohorte retrospectivo en La Pampa, Argentina / Four-year health trajectories of children prenatally exposed to cocaine and/or cannabis. A retrospective, cohort study in La Pampa, Argentina

El consumo de cocaína y/o cannabis durante el embarazo constituye un problema en ascenso, de importancia para la salud pública mundial. Los niños expuestos pueden presentar un amplio rango de complicaciones en el período perinatal, pero los conocimientos sobre la evolución posterior son escasos.Objetivo: Describir y comparar las trayectorias sanitarias de niños expuestos y no expuestos prenatalmente a cocaína y/o cannabis durante 4 años. Métodos: Estudio de cohorte retrospectivo con grupo de comparación doble. Los niños expuestos fueron detectados en el Servicio de Neonatología de un hospital público mediante una prueba de orina, entre 2009 y 2013. Resultados: Se evaluaron 29 niños expuestos y 58 no expuestos. Las principales drogas detectadas en el grupo expuesto fueron cocaína y cannabis. La mayoría de las madres fueron policonsumidoras. En los niños del grupo expuesto, se encontraron diferencias significativas en menor frecuencia de controles de salud (p < 0,0001) y mayor frecuencia de consultas en Emergencias (p = 0,0295) e Internaciones (p = 0,007), principalmente, por cuadros respiratorios. Presentaron, además, mayor frecuencia de enfermedad pulmonar obstructiva crónica, cambios de hogar y judicialización. En ese grupo, hubo 1 niño y 2 progenitores muertos por causa violenta. No hubo ninguna muerte en el grupo no expuesto.Conclusiones: Los niños expuestos a cocaína y/o cannabis prenatalmente tuvieron menor número de controles de salud y mayor frecuencia de consultas en Emergencias e Internaciones. Presentaron, además, mayor frecuencia de enfermedad pulmonar obstructiva crónica, cambios de hogar, judicialización y muertes violentas en el grupo familiar directo.

Cocaine and/or cannabis use during pregnancy is a growing problem of relevance for global public health. Exposed children may have a wide range of perinatal complications, but there is little knowledge on their course.Objective: To describe and compare the health trajectories of children prenatally exposed and unexposed to cocaine and/or cannabis over 4 years.Methods: Retrospective, cohort study with a double control group. Exposed children were detected through a urine test by the Department of Neonatology of a public hospital between 2009 and 2013. Results: A total of 29 exposed children and 58 unexposed children were assessed. The most common drugs detected in the exposed group were cocaine and cannabis. Most mothers were poly-drug users. The exposed group showed significant differences in relation to a lower frequency of health checkups (p < 0.0001) and a higher number of visits to the emergency department (p = 0.0295) and hospitalizations (p = 0.007), mainly due to respiratory conditions. In addition, they had a greater rate of chronic obstructive pulmonary disease, changes of home, and legal interventions. In this group, 1 child and 2 parents had a violent death. No deaths were reported in the unexposed group. Conclusions: Children prenatally exposed to cocaine and/or cannabis had a lower number of health checkups and a higher number of visits to the emergency department and hospitalizations. Besides, they showed a greater rate of chronic obstructive pulmonary disease, changes of home, legal interventions, and violent deaths in the direct family group.

Trastorno del espectro alcohólico fetal: Un trastorno del neurodesarrollo infradiagnosticado y de pronóstico incierto / Fetal alcohol spectrum disorder. An underdiagnosed neuro-development disorder of uncertain prognosis

La exposición prenatal al alcohol es causa de alteraciones somáticas, cognitivas y conductuales que se agrupan bajo el término de trastorno del espectro alcohólico fetal (TEAF). La evolución a largo plazo de los sujetos afectados a menudo es desfavorable, especialmente a nivel académico y adaptativo social. En el perfil neuropsicológico es característica la disfunción ejecutiva a menudo asociada a trastornos de la conducta que evolucionan en muchos casos hacia la delincuencia a partir de la adolescencia y en la edad adulta. Se han descrito también déficits de las habilidades sociales y la empatía. La exposición prenatal al alcohol constituye la causa más frecuente de trastorno del neurodesarrollo adquirido y prevenible.

Prenatal exposure to alcohol is the cause of cognitive and behavioural disorders grouped under the term fetal alcohol spectrum disorders (FASD). The long-term evolution of subjects with FASD is often unfavourable, especially in social and academic fields. Executive dysfunction is a hallmark deficit for children with FASD with increased rates of externalizing behaviours, such as aggressiveness and frequently delinquency in adolescence and adulthood. Deficits in social skills, empathy and communication ability are frequent observed among FASD. Prenatal exposure to alcohol is the most frequent cause of acquired and preventable neurodevelopmental disorder.

Tabaquismo prenatal: impacto respiratorio en el primer año de vida / Prenatal smoking: respiratory impact in infants during the first year of life

Introducción: Los episodios de obstrucción bronquial durante el primer año de vida en los lactantes sanos, constituyen una consulta frecuente en pediatría. El objetivo es evaluar el impacto del tabaquismo prenatal como factor asociado a padecer episodios de sibilancias en el primer año de vida en lactantes sanos, sin historia familiar de asma y/o atopía. Métodos: Estudio transversal realizado entre mayo del 2012/2013 en el Hospital de Niños "Ricardo Gutiérrez", mediante una encuesta dirigida a madres de lactantes sanos de 12 a 15 meses de edad, sin antecedentes familiares de asma y /o atopía. El objetivo fue evaluar el tabaquismo prenatal como factor de riesgo asociado a padecer episodios de obstrucción bronquial en lactantes sanos, en el primer año de vida. Resultados: Se contactaron 601 madres de lactantes sanos de 12 a 15 meses de edad. Fueron elegibles 379 para completar la encuesta acerca de lo ocurrido en el primer año de vida de sus hijos. Mediante análisis multivariado, los factores de riesgo asociados a padecer al menos un episodio de sibilancia fueron: exposición prenatal (EP) al humo del tabaquismo materno (p=0.03 ODDS= 3 IC 95% 1,09 ­ 8,27), sexo masculino (p=0,002, ODDS 2,03 IC 1,29-3,20), edad del primer resfrío (p < 0,001 ODDS 0,76 IC 0,69-0,83). Conclusiones: En lactantes sanos, sin factores de riesgo para asma y/o atopía, el tabaquismo prenatal constituyó un factor de riesgo para generar sibilancias broncopulmonares e infecciones virales respiratorias a una edad más temprana.

Introduction: During the first year of life of healthy infants, bronchial obstructive episodes are a frequent reason of consultation in pediatric practice. The objective was to assess the impact of prenatal smoking as a risk factor associated to bronchospasm episodes during the first year of life in healthy infants without family history of asthma and/or atopia. Methods: Cross-sectional study performed between May, 2012 and May 2013 at Hospital de Niños "Ricardo Gutiérrez", through a survey completed by mothers of healthy infants from 12 to 15 months old without asthma and/or atopia family antecedents. Main purpose was to assess the prenatal smoking as a risk factor associated to bronchospasm episodes during the first year of life in healthy infants. Results: 601 mothers of patients 12 to 15 months old were contacted, among which 379 completed the survey in relation to what had happened during the first twelve months of their children's life. Through multivariate analysis, the risk factors associated to suffer at least one bronchial obstructive episode were: prenatal exposure to maternal smoking (p=0.03 ODDS= 3 IC 95% 1,09 ­ 8,27), male gender (p=0,002 ODDS 2,03 IC 1,29- 3,20), age at first cold (p < 0,001 ODDS 0,76 IC 0,69-0,83). Conclusions: In healthy infants, without risk factors associated to asthma y/o atopia, prenatal smoking represented a risk factor to generate bronchopulmonary wheezing and viral respiratory infections at a younger age.

Exposición a Bisfenol A (BPA) en mujeres embarazadas y su relación con la obesidad en sus hijos: Revisión Sistemática / Pregnant Women's Exposure to Bisphenol A (BPA) and its Relation to their Children's Obesity: A systematic Review / Exposição ao bisfenol a (BPA) em mulheres engravidadas e a sua relação com a obesidade em seus filhos: uma revisão sistemática

Resumen Introducción: El bisfenol A (BPA) es un contaminante químico no persistente que altera el funcionamiento normal del sistema endocrino. Se sugiere que la exposición prenatal a BPA se asocia con la obesidad en la descendencia. Objetivo: Revisar la literatura sobre la exposición al BPA en mujeres embarazadas y su relación con la obesidad en sus hijos. Metodología: Revisión sistemática de acuerdo a la guía PRISMA, donde se realizaron búsquedas en las bases de datos Pubmed, ScienceDirect, Clinical Key, Medline, Ebsco y Scielo y el motor de búsqueda Google Scholar hasta 30 de abril de 2017 por dos investigadores independientes que utilizaron iguales términos de búsqueda. Se incluyeron estudios prospectivos de cohorte realizados que midieron el BPA en la orina materna. Resultados: Se incluyeron 5 estudios con tamaños de muestra que varían entre 297 y 757 binomios madre e hijo, se encontró asociación positiva entre la exposición prenatal a BPA con la circunferencia de cintura en niños de cuatro años β: 0.28 (IC95%:0.01 a 0.57) y el índice de masa grasa β: 0.31 (IC95%: 0.01 a 0.60) en dos de los estudios. Además, se observaron asociaciones positivas y/o negativas no significativas con índice de masa corporal y su puntaje Z, porcentaje de grasa, sobrepeso/obesidad, peso y talla al nacer, porcentaje de masa grasa. Conclusión: Los resultados del cuerpo existente de estudios epidemiológicos de cohorte, limita las afirmaciones sobre un vínculo causal entre la exposición prenatal BPA y la obesidad postnatal.

Abstract Introduction: Bisphenol A (BPA) is a non-persistent chemical pollutant which alters the normal functioning of the endocrine system. It is suggested that prenatal exposure is related to descendant obesity. Objective: Review literature on pregnant women's exposure to BPA and the relation to their children's obesity. Methodology: Systematic review in accordance with PRISMA guidelines. Searches were conducted on databases including Pubmed, ScienceDirect, Clinical Key, Medline, Ebsco and Scielo and Google Scholar search engine until April 30, 2017 by two independent researchers that used the same search terms. Prospective cohort conducted studies were included because they measured BPA in maternal urine. Results: Five studies were included with sample sizes ranging from 297 to 757 mother-child binomials. The review found a positive association between prenatal BPA exposure with 4-year-old children's waist circumference β: 0.28 (95% CI :0.01 to 0.57) and the fat mass index β: 0.31 (95%CI: 0.01 to 0.60) in two of the studies. non-significant positive and/or negative associations where observed with body mass index z-scores, overweight/ obesity, weight and size at birth, body mass percentage. Conclusion: The results of cohort epidemiological studies constrain statements regarding a causal link between prenatal BPA exposure and postnatal obesity.

Resumo Introdução: O bisfenol A (BPA) é um contaminante químico não persistente que altera o funcionamento normal do sistema endócrino. Se sugere que a exposição pré-natal se associa com a obesidade na descendência. Objetivo: Revisar a literatura sobre a exposição ao BPA em mulheres engravidadas e a sua relação com a obesidade em seus filhos. Metodologia: Revisão sistemática de acordo com a guia PRISMA. Se realizaram pesquisas nas bases de dados Pubmed, ScienceDirect, Clinical Key, Medline, Ebsco e Scielo e o motor de pesquisa Google Scholar até o 30 de Abril de 2017 por dois investigadores independentes que utilizaram os mesmos termos de busca. Se incluíram estudos prospectivos de coorte realizados que calcularam o BPA na urina materna. Resultados: Se incluíram 5 estudos com tamanhos de amostra entre 297 e 757 binômios mãe e filho, se encontrou associação positiva entre a exposição pré-natal a BPA com a circunferência de cintura em meninos de quatro anos β: 0.28 (IC95%:0.01 a 0.57) e o índice de massa de gordura β: 0.31 (IC95%: 0.01 a 0.60) em dois dos estudos. Se enxergaram associações positivas e/ou negativas não significativas com índice de massa corporal e a sua pontuação Z, porcentagem de gordura, sobrepeso/obesidade, peso e dimensão ao nascer, porcentagem de massa de gordura. Conclusão: Os resultados de estudos epidemiológicos de coorte, limita as afirmações sobre um vínculo causal entre a exposição pré-natal BPA e a obesidade pós-natal.

Prenatal Cocaine and Cocaine Consumption in Young Adult Mice / Cocaína prenatal y consumo de cocaína de ratones adultos jovenes

Resumen Con el propósito de evaluar los efectos de la Exposición Prenatal de Cocaína -EPC- (25 y 50 mg/kg/día) desde el 8 hasta el 21 día de gestación, en el consumo de cocaína oral en ratones hembras y machos en la adultez temprana (7ª semana de edad), se realizó un estudio experimental factorial mediante el modelo de "elección libre de dos botellas" que mide el consumo en mililitros. Se evaluó el consumo durante 14 días consecutivos a partir de la 7ª semana de edad. Para el análisis del consumo se utilizó el MANOVA de medidas repetidas y se encontró que la EPC 50mg/kg/día incrementó el consumo de cocaína oral en ratones hembras y machos adultos-jóvenes tanto en la fase de adquisición como la de mantenimiento. Y la EPC 25mg/kg/día aumentó el consumo únicamente en los machos en la fase de mantenimiento, mostrando la mayor susceptibilidad de estos a la EPC, en cambio el alto consumo de cocaína observado en las hembras no fue dosis-relacionado, por lo que se puede atribuir a factores situacionales. De esta forma se ve como la EPC en las dos dosis evaluadas incrementa el consumo de cocaína oral en la adultez temprana en los ratones; la dosis alta (50mg/kg) el consumo de hembras y machos y la dosis baja (25mg/kg) incrementa el consumo únicamente en los machos. Se observa que los efectos están relacionados a la dosis y que los machos son más vulnerables a los efectos de la EPC.

Abstract To evaluate the effects of Prenatal Exposure of Cocaine-EPC- (25 or 50 mg / kg / day) from 8-21 day of gestation, on oral cocaine use in female and male mice in early adulthood, was used the test of "free choice of two bottles" that measures the oral cocaine consumption in milliliters. This was evaluated for 14 consecutive days from the 7th week of age. Repeated measures MANOVA was used for the analysis of consumption. It was found that EPC 50mg/kg/day increased oral cocaine consumption in female and young adult male mice both in the acquisition and maintenance phases. And the EPC 25mg/kg/day increased the consumption only in the males in the maintenance phase, showing the greater susceptibility of these to the EPC, whereas the high cocaine consumption observed in the females was not dose-related, which can be attributed to situational factors. In this way, it is seen how the EPC in the two doses evaluated increases oral cocaine consumption in early adulthood in mice; the high dose (50mg / kg) the consumption of females and males and the low dose (25mg / kg) increases the consumption only in males. It is observed that the effects are related to the dose, and that males are more vulnerable to the EPC effects.