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.

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.

Effects of antenatal corticosteroids exposure on multiple systems of preterm infants: a review / 中华围产医学杂志

Administration of antenatal corticosteroids (ACS) to pregnant women at risk of preterm delivery can significantly reduce the incidence of preterm-related complications, such as respiratory distress syndrome and necrotizing enterocolitis. However, ACS may have adverse effects on multiple systems including nervous system, cardiovascular system and carbohydrate metabolism in preterm infants. Whether ACS could influence neonatal development is still controversial. On this account, this review, focusing on short- and long-term effects of ACS therapy on nervous, cardiovascular, endocrine and other systems of infants born prematurely, will help clinical management and scientific research.

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.

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.

Progress on association of obesity with common congenital heart diseases and its underlying mechanisms / 中华围产医学杂志

Maternal obesity is associated with an increased risk of a range of congenital malformations in offspring, including neurological malformations, congenital heart disease, congenital kidney and urinary system abnormalities, cleft lip and palate, anorectal atresia, etc. This may be related to existing metabolic abnormalities, including increased insulin resistance, chronic inflammation, and oxidative stress caused by excessive accumulation of fat, as well as the relative deficiency of nutrients such as folic acid in obese pregnant women. Therefore, it is recommended that obese women have a planned pregnancy, address folate and micronutrient supplementation and optimize their health status prior to conception.

Role of microRNA in complications of offspring born to mothers with gestational diabetes mellitus / 中华围产医学杂志

Gestational diabetes mellitus (GDM) can lead to adverse pregnancy outcomes and epigenetic changes in offspring due to exposure to a high-glucose intrauterine environment, resulting in related short- and long-term complications. MicroRNA (miRNA)-mediated post-transcriptional regulation, a gene expression regulation mechanism that has gained much attention in recent years, may play a role in morbidity in offspring born to mothers with GDM, such as macrosomia, heart development, neurodevelopment, and long-term metabolic diseases. This article reviews the progress of miRNA in GDM and associated complications in the offspring.

Effects of early-life exposure to angiotensinⅡ type 1 receptor autoantibody on lipid metabolism in offspring rats / 中华围产医学杂志

Objective:To investigate the effects of early-life (intrauterine and breastfeeding period) exposure to angiotensin Ⅱ type 1 receptor autoantibody (AT 1-AA) on lipid metabolism in offspring rats. Methods:Thirty-two AT 1-AA negative healthy nonpregnant specific pathogen free female Sprague Dawley rats weighing 150-170 g were randomly divided into two groups. Those in the immune group ( n=16) were subcutaneously injected with the mixture of an equal volume of Freund's adjuvant and the second extracellular loop of human-derived angiotensin Ⅱ receptor type 1 (AT1R-ECⅡ) repeatedly to establish the AT 1-AA-positive rat model by active immunization and those in the control group ( n=16) with normal saline solution. Before each immunization, blood samples were collected from the tail of rats to detect serum AT 1-AA levels of those rats in both groups, and the AT 1-AA-positive rat model was successfully established when the serum AT 1-AA was positive and its level reached a plateau. After eight weeks of immunization, the female rats in the two groups were mated with healthy AT 1-AA-negative male rats to conceive. Serum samples were collected from the maternal and offspring rats at the gestation of 18 days (G18), postnatal 21 days (P21), and from the normally fed offspring rats from the time of weaning to 12 weeks old (W12). Active immunization was not performed on the offspring throughout the experiment. The serum AT 1-AA levels of maternal and offspring rats were determined by enzyme-linked immunosorbent assay, and serum AT1-AA was positive when the ratio of AT1-AA level of the immune group over the control group ≥2.1. The blood lipid levels of maternal and offspring rats were measured by an automatic biochemical analyzer. Serum AT 1-AA levels, total cholesterol (TC), high-density lipoprotein-cholesterol [instead of high-density lipoprotein (HDL)], low-density lipoprotein-cholesterol, and free fatty acid levels of the offspring and maternal rats were determined for correlation analysis. Two independent sample t-test, linear regression analysis, and analysis of variance were adopted for statistical analysis. Results:(1) The serum levels of AT 1-AA in maternal rats at G18 and P21 in the immune group were significantly higher than those in the control group (G18: 1.170±0.190 vs 0.114±0.016, t=14.64; P21: 0.988±0.283 vs 0.084±0.006, t=9.57; both P<0.001). (2) The serum levels of AT 1-AA in the offspring at G18 and P21 in the immune group were significantly higher than those in the control group (offspring at G18: 0.948±0.220 vs 0.105±0.010, t=10.10; male offspring at P21: 0.758±0.273 vs 0.080±0.002, t=7.46; female offspring at P21: 0.774±0.274 vs 0.084±0.005, t=7.55; all P<0.001), which showed a positive correlation with those in maternal rats at the same period (offspring at G18: R=0.78; male offspring at P21: R=0.82; female offspring at P21: R=0.82; all P<0.05). However, there was no significant difference in the serum AT 1-AA level in offspring at W12 between the immune and control group ( P>0.05). (3) The serum levels of TC at G18 and P21, and HDL at P21 in maternal rats in the immune group were all higher than those in the control group [TC at G18: (2.36±0.32) vs (1.95±0.24) mmol/L, t=2.70; P21: (2.82±0.50) vs (2.18±0.26) mmol/L, t=3.41; HDL at P21: (1.94±0.33) vs (1.57±0.23) mmol/L, t=2.80; all P<0.05]. (4) Compared with the offspring in the control group, there was no significant change in lipid metabolism at G18 and W12 in the offspring in the immune group (both P>0.05). The serum levels of TC and HDL in male and female offspring at P21 in the immune group were higher than their counterparts in the control[TC in male offspring: (2.38±0.52) vs (1.83±0.30) mmol/L, t=2.73; HDL in male offspring: (1.44±0.32) vs (1.07±0.18) mmol/L, t=2.98; TC in female offspring: (2.50±0.72) vs (1.70±0.26) mmol/L, t=3.16; HDL in female offspring: (1.41±0.33) vs (1.00±0.14) mmol/L, t=3.41; all P<0.05]. (5) The serum levels of TC and HDL in male and female offspring at P21 in the immune group showed no correlation with those in maternal rats at P21 (all R<0.5, all P>0.05). The serum levels of HDL in male and female offspring at P21 in the immune group had a positive correlation with their own serum TC levels (male offspring: R=0.98; female offspring: R=0.97; both P<0.001) and also with their own serum AT 1-AA levels (male offspring: R=0.74, P=0.023; female offspring: R=0.91, P=0.001). The serum levels of TC in male and female offspring at P21 in the immune group had a positive correlation with their serum AT 1-AA levels (male offspring: R=0.72, P=0.030; female offspring: R=0.90, P=0.001). Conclusion:The early-life exposure to AT 1-AA may cause abnormal expression of TC and HDL in offspring rats.

Impact of arsenic exposure during gestation on testosterone synthesis and sperm quality in F1 adult male rats / 环境与职业医学

Background Arsenic is recognized as a kind of developmental toxicant, which can pass through the placenta barrier and induce health defects in offspring. However, the effects of environmental levels of arsenic exposure during gestation on the reproductive system of adult male offspring remain unclear. Objective To investigate the impact of environmental levels of arsenic exposure during gestation on testosterone synthesis and sperm quality in F1 adult male rats. Methods Forty sexually mature Wistar female rats were randomly divided into four groups according to body weight, namely control group, low-dose sodium arsenite (NaAsO2) group, middle-dose NaAsO2 group, and high-dose NaAsO2 group. They were mated with sexually mature Wistar male rats in a ratio of 2:1, and the day with presence of a vaginal plug or spermatozoa in the vaginal smear was designated as gestational day 0 (GD0). Pregnant rats were provided drinking water containing 0, 1, 5,, or 25 mg·L−1 NaAsO2 until delivery. At postnatal day 70, the F1 male rats were euthanized. Anogenital distance was measured, testis and epididymis were weighed, and associated organ coefficients were calculated. Epididymal sperm quality was evaluated. The histological changes of testis were observed. The levels of testosterone and estradiol in serum were determined with ELISA kit. The testicular mRNA relative expression levels of key steroidogenic enzymes were determined by quantitative real-time PCR. The protein relative expression levels of key steroidogenic enzymes were determined by Western blotting. Results Compared with the control group, the testicular coefficients and epididymis coefficients were increased in the low- and middle-dose groups (P<0.05), and the epididymis coefficient was also increased in the high-dose group (P<0.05). As for the percentage of sperm motility, compared to the control group, grade Ⅰ sperm cells were increased in the low-dose group, but significantly decreased in the middle- and high-dose groups; grade Ⅱ and Ⅲ sperm cells were decreased in the low- and high-dose groups; grade Ⅳ sperm cells were significantly increased in the middle- and high-dose groups; all the differences above were statistically significant (P<0.05). Compared with the control group, there was a significant increase in serum testosterone levels in all treated groups (P<0.05), and the serum estradiol levels were significantly decreased in the high-dose group (P<0.05). Meanwhile, compared with the control group, the relative mRNA expression levels of Hsd3β1 and Cyp19a1 were decreased (P<0.05), while those of StAR and Cyp11a1 were increased in the high-dose group (P<0.05). In addition, the relative protein expression levels of CYP11A1 were significantly increased in all treated groups compared with the control group (P<0.05). Conclusion Environmental levels of arsenic exposure during gestation can up-regulate testosterone level and reduce sperm quality, and is a potential risk for reproductive dysfunction in adult male offspring.

Research progress in influence of intrauterine hyper androgen on offspring health and mechanisms / 中华围产医学杂志

Maternal adverse endocrine environment severely affects the growth and development of offspring. This article reviews relevant cohort studies and animal experiments on the influence of intrauterine hyper androgen on offspring health and the mechanisms, aiming to provide a new perspective for further research, mechanism exploration, and early interventions in this field.

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.

Air pollution and children's health-a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter

BACKGROUND@#Particulate matter (PM), a major component of ambient air pollution, accounts for a substantial burden of diseases and fatality worldwide. Maternal exposure to PM during pregnancy is particularly harmful to children's health since this is a phase of rapid human growth and development.@*METHOD@#In this review, we synthesize the scientific evidence on adverse health outcomes in children following prenatal exposure to the smallest toxic components, fine (PM@*RESULTS@#Maternal exposure to fine and ultrafine PM directly and indirectly yields numerous adverse birth outcomes and impacts on children's respiratory systems, immune status, brain development, and cardiometabolic health. The biological mechanisms underlying adverse effects include direct placental translocation of ultrafine particles, placental and systemic maternal oxidative stress and inflammation elicited by both fine and ultrafine PM, epigenetic changes, and potential endocrine effects that influence long-term health.@*CONCLUSION@#Policies to reduce maternal exposure and health consequences in children should be a high priority. PM

Association between tobacco and/or alcohol consumption during pregnancy and infant development: BRISA Cohort

Fetuses exposed to alcohol and/or tobacco are at risk for perinatal adversities. However, little is currently known about the association of the separate or concomitant use of alcohol and tobacco with infant motor and cognitive development. Thus, the objective of the present study was to investigate the association between maternal consumption of alcohol and/or tobacco during pregnancy and the motor and cognitive development of children starting from the second year of life. The study included 1006 children of a cohort started during the prenatal period (22-25 weeks of pregnancy), evaluated at birth and reevaluated during the second year of life in 2011/2013. The children were divided into four groups according to the alcohol and/or tobacco consumption reported by their mothers at childbirth: no consumption (NC), separate alcohol consumption (AC), separate tobacco consumption (TC), and concomitant use of both (ACTC). The Bayley Scale of Infant and Toddler Development Third Edition screening tool was used for the assessment of motor and cognitive development. Adjusted Poisson regression models were used to determine the association between groups and delayed development. The results indicated that only the ACTC group showed a higher risk of motor delay, specifically regarding fine motor skills, compared to the NC group (RR=2.81; 95%CI: 1.65; 4.77). Separate alcohol or tobacco consumption was not associated with delayed gross motor or cognitive development. However, the concomitant use of the two substances increased the risk of delayed acquisition of fine motor skills.

Long-term effects of intrauterine exposure to metformin on offspring / 中华围产医学杂志

As an oral antidiabetic drugs,metformin has been widely used to treat various diseases such as gestational diabetes mellitus,polycystic ovary syndrome and obesity in pregnant women.Current literature suggests that intrauterine metformin exposure has no significant impact on perinatal outcomes of the offspring,such as neonatal hypoglycemia,neonatal respiratory distress syndrome,premature delivery and others.However,considering the possible transfer of metformin across the placental barrier,intrauterine metformin exposure may potentially influence the development of placenta and the fetus,cell metabolism,and hormone levels.According to the "Developmental Origins of Health and Diseases" theory,the long-term effect of intrauterine metformin exposure on the growth,metabolism,reproductive function and neuropsychological development of offspring reviewed here still need continuous attention.

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.

Research progress in influence of prenatal xenobiotics exposure on function of hypothalamic-pituitary-adrenal axis in offspring / 中国药理学与毒理学杂志

As the most important neuroendocrine axis, the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the body's response to stress. Intrauterine exposure to foreign substances can affect the development of the fetus in varied of ways, such as by damaging the mother or the placenta, also can have direct toxic effects on the fetus, thus altering the developmental programming of the fetal HPA axis. As a result, the sensitivity to stress of HPA axis is increased after birth, and the susceptibility to disease is increased in adulthood, including mental diseases such as depression and anxiety, as well as metabolic diseases such as diabetes. The possible mechanism is related to the indirect damage through the placenta and the direct damage through epigenetic modification of fetal genes. In this paper, we reviewed the latest research progress in the abnormal function of the HPA axis and the susceptibility to adult diseases caused by adverse intrauterine environment.

Timing of pubertal development in boys born with cryptorchidism and hypospadias: A nationwide cohort study / 亚洲男科学杂志(英文版)

Pubertal development may be altered in boys with cryptorchidism and hypospadias, but existing knowledge is inconsistent. Therefore, we investigated the association between cryptorchidism and hypospadias and pubertal development in a large cohort study. Boys in the Puberty Cohort, a cohort nested within the Danish National Birth Cohort, were included in this study. Information on cryptorchidism and hypospadias was retrieved from the Danish National Patient Register. From 11 years until 18 years or full pubertal development, information on physical markers of pubertal development was provided biannually, including Tanner stages, axillary hair, acne, voice break, and first ejaculation. In multivariate regression models for interval censored data, the mean (95% confidence intervals [CIs]) differences in months in obtaining the pubertal markers between boys with and without the anomalies were estimated. Among 7698 boys, 196 (2.5%) had cryptorchidism and 60 (0.8%) had hypospadias. Boys with hypospadias experienced first ejaculation and voice break 7.7 (95% CI: 2.5-13.0) months and 4.5 (95% CI: 0.3-8.7) months later than boys without hypospadias. The age at attaining the Tanner stages for gonadal and pubic hair growth was also higher, though not statistically significant. Pubertal development seemed unaffected in boys with mild as well as severe cryptorchidism. In conclusion, hypospadias may be associated with delayed pubertal development, but pubertal development seems unaffected by cryptorchidism. The relation between hypospadias and later pubertal development may be due to the underlying shared in utero risk or genetic factors.

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.