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Article in English | WPRIM | ID: wpr-880377


BACKGROUND@#The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco.@*METHODS@#The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures.@*RESULTS@#The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies.@*CONCLUSIONS@#Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Biomarkers/blood , Child , Child Health , Child, Preschool , Cohort Studies , Environmental Exposure/adverse effects , Environmental Health , Environmental Pollutants/adverse effects , Female , Fetal Blood/chemistry , Follow-Up Studies , Growth/drug effects , Humans , Hypersensitivity/etiology , Infant , Japan/epidemiology , Male , Neurodevelopmental Disorders/etiology , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Prevalence , Smoking/adverse effects
Article in English | WPRIM | ID: wpr-880358


BACKGROUND@#The majority of studies linking exposure to metals with certain health outcomes focus on known toxic metals. Alternatively, this study assesses the extent to which exposure to a wider range of metals during gestation is associated with childhood morbidity.@*METHODS@#We analyzed the concentrations of 25 metals found in urine samples of 111 pregnant women of Arab-Bedouin origin collected prior to birth. In addition, we collected medical records on their offspring for six years following birth, including every interaction with HMOs, local hospitals, and pharmacies.@*RESULTS@#The main types of morbidities diagnosed and treated during this period were preterm births, malformations, asthma-like morbidity, cardiovascular and behavioral problems, and obesity. Multivariable analysis showed that offspring born before term were more likely to have been exposed to elevated maternal concentrations of zinc, thallium, aluminum, manganese, and uranium, all with adjusted relative risk above 1.40 for an increase by each quintile. Likewise, children with asthma had been exposed to higher levels of magnesium, strontium, and barium at gestation, while behavioral outcomes were associated with elevated biometals, i.e., sodium, magnesium, calcium, selenium, and zinc, as well as higher levels of lithium, cobalt, nickel, strontium, cadmium, vanadium, arsenic, and molybdenum. A heatmap of adjusted relative risk estimates indicates the considerable implications that exposure to metals may have for preterm birth and developmental outcomes.@*CONCLUSIONS@#The current study shows that perinatal exposure to metals is adversely associated with pediatric morbidity. Further such analyses on additional samples are warranted.

Adult , Arabs/statistics & numerical data , Child , Child, Preschool , Environmental Pollutants/urine , Female , Humans , Israel , Male , Maternal Exposure/adverse effects , Metals/urine , Morbidity , Pregnancy , Prenatal Exposure Delayed Effects/epidemiology , Young Adult
Article in English | WPRIM | ID: wpr-880352


BACKGROUND@#Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice.@*METHODS@#Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method.@*RESULTS@#The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice.@*CONCLUSIONS@#These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.

Animals , Arsenic/toxicity , Arsenites/toxicity , Behavior, Animal/drug effects , Environmental Pollutants/toxicity , Female , Gene Expression/drug effects , Genetic Markers , Male , Maternal Exposure/adverse effects , Mice , Mice, Inbred C3H , Oxidative Stress/genetics , Prefrontal Cortex/drug effects , Pregnancy , Prenatal Exposure Delayed Effects/psychology , Reverse Transcriptase Polymerase Chain Reaction , Serotonin/metabolism , Social Behavior , Sodium Compounds/toxicity
Article in English | WPRIM | ID: wpr-880327


BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

Animals , Cytoskeletal Proteins/metabolism , Female , Gene Expression Regulation , Hippocampus/metabolism , Insulin-Like Growth Factor II/metabolism , Learning , Learning Disabilities/psychology , Male , Memory Disorders/psychology , Nerve Tissue Proteins/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/psychology , Random Allocation , Rats , Rats, Wistar , Social Environment , Stress, Psychological/genetics
Braz. j. med. biol. res ; 54(11): e10192, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339447


Maternal anxiety symptoms in the perinatal period might have long-term health effects on both the mother and the developing child. Valerian is a phytotherapeutic agent that is widely used for the treatment of anxiety. This study investigated the effects of valerian treatment in postpartum rats on maternal care, toxicity, and milk composition. Postnatal development, memory, and anxiety behavior in the offspring were also assessed. Postpartum Wistar rats received the valerian (500, 1000, or 2000 mg·kg-1·day-1) by oral gavage. Clinical and biochemical toxicity was evaluated with commercial kits. Maternal behavior was observed daily. Milk composition was analyzed by colorimetric methods. Physical and neuromotor tests were used to analyze postnatal development. Anxiolytic activity was assessed by the elevated plus maze, and memory was evaluated by the step-down inhibitory avoidance task. Maternal toxicity and care behavior were not altered by the treatment, while only the highest dose promoted a significant increase of lactose, and the doses 1000 and 2000 mg·kg-1·day-1 promoted a reduction of protein contents in milk. Postnatal development was similar in all offspring. Adult offspring did not display altered anxiety behavior, while long-term memory was impaired in the female adult offspring by maternal treatment with 1000 mg·kg-1·day-1. These results suggested that high doses of valerian had significant effects on important maternal milk components and can cause long-term alterations of offspring memory; thus, treatment with high doses of valerian is not safe for breastfeeding Wistar rat mothers.

Humans , Animals , Pregnancy , Rats , Prenatal Exposure Delayed Effects , Valerian , Rats, Wistar , Postpartum Period , Memory, Long-Term , Milk, Human
Braz. j. med. biol. res ; 54(1): 10252-0, 2021. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1142565


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.

Humans , Male , Female , Pregnancy , Infant, Newborn , Infant , Prenatal Exposure Delayed Effects/epidemiology , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Child Development , Tobacco Use , Cohort Studies
Medicina (B.Aires) ; 80(6): 685-695, dic. 2020. graf
Article in Spanish | LILACS | ID: biblio-1250292


Resumen La diabetes durante el embarazo se asocia a un mayor riesgo perinatológico para los niños. Este puede reducirse significativamente con un control glucémico adecuado en estadios tempranos de la gestación. En la última década nuevos estudios han mostrado los efectos deletéreos de la diabetes materna en la salud de los hijos a largo plazo, como las alteraciones del neurodesarrollo y los efectos sobre el pronóstico educacional y ocupacional. Las mismas pueden ser clasificadas, desde el punto de vista clínico-diagnóstico en tres grupos principales: trastornos del aprendizaje y del desarrollo intelectual, trastorno por déficit de atención e hiperactividad y trastornos del espectro autista. El presente trabajo tiene como objetivo realizar una actualización no sistemática de la evidencia más reciente en el tema y comprender los mecanismos subyacentes que provocan el daño, con el fin de desarrollar estrategias preventivas.

Abstract Diabetes during pregnancy is associated with adverse effects on offspring perinatal outcomes. These could be reduced significantly with an adequate glycemic control in early stages of gestation. In the last decade, new studies have shown the effects of maternal diabetes in the long-term health of the offspring, like impaired neurodevelopment and its impact on educational and occupational outcome. This can be classified, from the clinical and diagnostic perspective, in three main groups: learning and cognitive disorders, attention deficit hyperactivity disorder and autism spectrum disorders. This paper has the objective to give a non-systematic upgrade of the current evidence on the subject, and to understand the underlying mechanisms of adverse neurodevelopmental outcomes which in turn may lead to strategies for its prevention.

Humans , Female , Pregnancy , Prenatal Exposure Delayed Effects , Attention Deficit Disorder with Hyperactivity/etiology , Diabetes, Gestational/diagnosis , Neurodevelopmental Disorders/etiology , Neurodevelopmental Disorders/epidemiology , Autism Spectrum Disorder
Actual. osteol ; 16(1): 35-46, Ene - abr. 2020. graf, ilus
Article in Spanish | LILACS | ID: biblio-1139966


La erupción dental es un proceso estrictamente regulado y programado espacial y temporalmente. El objetivo del trabajo fue estudiar el efecto de la exposición prenatal a fluoruro de sodio (NaF) sobre los eventos morfológicos y celulares que ocurren en el hueso supracoronal del primer molar de crías de rata durante la etapa preeruptiva. Se emplearon crías (n=6-8 por grupo) provenientes de madres que bebieron crónicamente agua con diferentes concentraciones de F- en forma de NaF durante la gestación y lactancia: control y NaF (50 mg/L). En cortes histológicos de la mandíbula de crías de 3 y 10 días se analizaron parámetros de histomorfometría estática en la zona supracoronal de la canastilla ósea a la altura del primer molar inferior: volumen óseo trabecular [BV/TV (%)], número de osteoclastos por milímetro (N.Oc/mm) y las variables indirectas: número de trabéculas [Tb.N (1/mm)], espesor [Tb.Th (µm)] y separación trabecular [Tb.Sp (µm)]. En crías de 15 días se midió el grado de erupción [TED (µm)] del primer molar inferior. Los resultados se analizaron con el test "t" de Student considerando diferencias significativas a p<0,05. El análisis histomorfométrico demostró un incremento en el BV/TV (%) del hueso supracoronal (p<0,01) asociado con disminución del N.Oc/mm (p<0,01) en crías de 3 y 10 días expuestas prenatalmente al F-. El grado de erupción dental fue menor en animales expuestos prenatalmente al F- en comparación con los controles (p<0,01). En conclusión, los resultados observados en la mandíbula de crías expuestas durante la etapa prenatal y posnatal temprana al F- sugieren un efecto disruptivo sobre la actividad resortiva necesaria para formación del canal eruptivo. (AU)

Tooth eruption is a tightly regulated and spatially and temporally programmed process. The aim of this study was to examine the effect of prenatal NaF exposure on the morphological and cellular events that occur in the supracoronal area of bony crypt of the first rat molar during the preeruptive stage. Offspring from two groups of rats were used (6-8 per group): Control and 50 mg/L NaF. The treatment was performed during pregnancy and lactation. Suckling pups were euthanized at 3-, 10- and 15-days-old by cervical dislocation. Mandibles were removed and histologically processed to obtain buccolingual sections stained with H&E. In sections of first mandibular molar of 3- and 10-days-old pups, the following static histomorphometric parameters were evaluated: trabecular bone volume [BV/TV (%)] and number of osteoclasts (N.Oc/mm). Also, indirect parameters were obtained: trabecular number [Tb.N (1/mm)], trabecular thickness [Tb.Th (µm)], and trabecular separation [Tb.Sp (µm)]. The degree of tooth eruption [TED (µm)] was determined. Results are expressed as mean ± SE and analyzed by Student t-test. Histomorphometric analysis showed an increase in the BV/TV (%) of the bone crypt of 3- and 10- days-old pups exposed to NaF (p <0.01); this increase was associated with a decrease in the N.Oc/mm (p <0.01). TED of mandibular first molar was lower in prenatal NaF exposed group than in control group (p<0.01). In conclusion, the increased BV/TV and the lower N.Oc observed in the bone crypt of 3- and 10- days-old pups from mothers treated with NaF suggested a disruptive effect triggered by F- on the formation events of the eruptive pathway in the offspring. (AU)

Humans , Animals , Male , Female , Infant , Child, Preschool , Rats , Sodium Fluoride/adverse effects , Tooth Eruption , Osteoclasts/cytology , Prenatal Exposure Delayed Effects , Sodium Fluoride/administration & dosage , Sodium Fluoride/metabolism , Sodium Fluoride/urine , Sodium Fluoride/chemical synthesis , Rats, Wistar , Mandible/anatomy & histology , Molar/growth & development , Fluorosis, Dental/diagnosis
Int. j. morphol ; 38(2): 400-405, abr. 2020. graf
Article in English | LILACS | ID: biblio-1056454


Accumulating evidence from preclinical and clinical studies indicates prenatal exposure to stress or excess glucocorticoids can affect offspring brain. Glucocorticoid receptor (GR) is an important target of glucocorticoid. Therefore the aim of the present study was to investigate the expression of GR in prenatally stressed adult offspring and the relationship between GR expression and behavior in offspring. Pregnant rats received restraint stress during the last week of pregnancy. Hippocampal glucocorticoid receptor expression levels in the offspring were detected on postnatal 60 (P60).Cognition function was also detected. It shows significantly lower hippocampal GR expression was observed in female prenatally stressed offspring compared with their controls at P60. Corresponding to the expression of GR, female prenatally stressed offspring exhibited poorer spatial learning and memory abilities in the Barnes maze than control, This suggests that cognitive impairment in prenatally stressed rat offspring attribute lower hippocampal GR expression.

La evidencia acumulada de estudios preclínicos y clínicos indica que la exposición prenatal al estrés, o el exceso de glucocorticoides puede afectar el desarrollo cerebral de las crías. El receptor de glucocorticoides (RG) es un objetivo importante de los glucocorticoides. Por lo tanto, el objetivo del presente estudio fue investigar la expresión de RG en crías adultas estresadas durante el período prenatal y la relación entre la expresión de RG y el comportamiento de las crías. Las ratas preñadas recibieron niveles de estrés restringido, durante la última semana de embarazo. Se determinaron niveles de expresión del receptor de glucocorticoides del hipocampo y niveles de función cognitiva en las crías. En comparación con el grupo control se observó una expresión de RG en el hipocampo, significativamente menor en las crías estresadas prenatalmente, en comparación con los controles en P60. En referencia a la expresión de RG, las crías estresadas prenatalmente exhibieron habilidades de memoria y aprendizaje espacial menores, en el laberinto de Barnes que el grupo control. Esto sugiere que el deterioro cognitivo en crías de ratas estresadas prenatalmente muestran una menor expresión de RG en el hipocampo.

Animals , Female , Pregnancy , Rats , Prenatal Exposure Delayed Effects , Receptors, Glucocorticoid/metabolism , Cognitive Dysfunction , Hippocampus/metabolism , Stress, Physiological , Immunohistochemistry , Blotting, Western , Rats, Sprague-Dawley
Arch. endocrinol. metab. (Online) ; 64(1): 89-95, Jan.-Feb. 2020. graf
Article in English | LILACS | ID: biblio-1088770


ABSTRACT Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95

Humans , Animals , Female , Pregnancy , Rats , Pregnancy Complications/physiopathology , Brain/embryology , Cognitive Dysfunction/etiology , Hypothyroidism/complications , Maternal-Fetal Exchange/physiology , Pregnancy Complications/blood , Pregnancy Trimesters , Prenatal Exposure Delayed Effects , Brain/physiopathology , Pregnancy Outcome
Article in English | WPRIM | ID: wpr-826294


BACKGROUND@#Many studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between cobalt exposure and CHD occurrence in offspring. The aim of this study was to analyze the association between cobalt exposure in mothers and the risk of CHDs in offspring.@*MATERIALS AND METHODS@#In order to explore the association between cobalt exposure and occurrence of congenital heart defect (CHD), a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of cobalt in hair of pregnant woman and fetal placental tissue were measured and processed by a logistic regression analysis to explore the relationship between cobalt exposure and risk of CHDs.@*RESULTS@#The median concentration of hair cobalt in the control and case group was 0.023 ng/mg and 0.033 ng/mg (aOR, 1.837; 95% CI, 1.468-2.299; P < 0.001), respectively. And the median (5-95% range) fetal placental cobalt concentrations were 19.350 ng/g and 42.500 ng/g (aOR, 2.924; 95% CI, 2.211-3.868; P < 0.001) in the control and case groups, respectively. Significant differences in the middle level of cobalt in hair were found in the different CHD subtypes, including septal defects, conotruncal defects, right ventricular outflow tract obstruction, and left ventricular outflow tract obstruction (P < 0.001). Dramatically, different cobalt concentrations in fetal placental tissue were found in all subtypes of cases with CHDs (P < 0.01).@*CONCLUSIONS@#The finding suggested that the occurrence of CHDs may be associated with cobalt exposure.

Adolescent , Adult , Case-Control Studies , China , Cobalt , Female , Hair , Chemistry , Heart Defects, Congenital , Humans , Maternal Exposure , Placenta , Chemistry , Pregnancy , Prenatal Exposure Delayed Effects , Risk Factors , Young Adult
Cad. Saúde Pública (Online) ; 36(2): e00026619, 2020. tab, graf
Article in English | LILACS | ID: biblio-1055634


Abstract: This study investigated whether antenatal exposure to antidepressants (ADs) increases the risks of autism spectrum disorders (ASD), attention deficit/hyperactivity disorders (ADHD), schizophrenia and other mental illnesses, and cognitive and developmental deficits in infants or preschool children. PubMed, EMBASE, BIREME/BVS databases were searched to identify studies examining associations of ADs in pregnancy with neurodevelopmental and psychiatric disorders. Twenty studies addressed ASD and/or ADHD risks while 30 focused on developmental and cognitive deficits in infants or preschool children. Most studies detected no association of antenatal AD with ASD after adjustment of risk ratios for maternal depression or psychiatric disorders. Some studies showed that maternal depression, regardless of whether it is treated or untreated, increased ASD risks. Seven out of 8 studies found no increase in ADHD risk associated with antenatal exposure to selective serotonin reuptake inhibitors, the most commonly used AD. No consistent evidence was found linking AD in pregnancy to neurocognitive developmental deficits in infants or preschool children. A residual confounding by indication (depression severity) remained in almost all studies. This systematic review found no consistent evidence suggesting that ADs in pregnancy increase risks of ASD, ADHD, and neurocognitive development deficits. Some studies, however, found evidence that maternal depression increases ASD risks.

Resumo: O estudo teve como objetivo investigar se a exposição intrauterina a antidepressivos (ADs) aumenta o risco de transtornos do espectro autista (TEA), transtorno de déficit de atenção e hiperatividade (TDAH), esquizofrenia e outros transtornos mentais e déficits cognitivos e de desenvolvimento em lactentes e pré-escolares. Foram realizadas buscas nas bases PubMed, EMBASE e BIREME/BVS para identificar estudos sobre associações entre o uso de ADs durante a gestação e transtornos de neurodesenvolvimento e psiquiátricos. Vinte estudos trataram de riscos de TEA e/ou TDAH, enquanto 30 focaram em déficits cognitivos e de desenvolvimento em lactentes ou pré-escolares. A maioria dos estudos não detectou associação entre AD na gestação e TEA, depois de ajustar as razões de risco para depressão ou outros transtornos psiquiátricos maternos. Alguns estudos mostraram que a depressão materna, quer tratada ou não, aumenta o risco de TEA. Sete entre oito estudos não detectaram aumento de risco de TDAH associado à exposição intrauterina a inibidores seletivos da recaptação da serotonina, o AD mais comumente utilizado. Não foram encontradas evidências consistentes entre o uso de AD na gestação e déficits de desenvolvimento neurocognitivo em lactentes ou pré-escolares. Em quase todos os estudos, permaneceu um confundimento residual por indicação (gravidade da depressão). A revisão sistemática não encontrou evidências consistentes de que os ADs na gestação aumentassem o risco de TEA, TDAH ou déficits de desenvolvimento neurocognitivo. Entretanto, alguns estudos evidenciaram que a depressão materna aumenta o risco de TEA.

Resumen: Este estudio investigó si la exposición prenatal a antidepresivos (ADs) incrementa los riesgos de trastornos del espectro autista (TEA), trastornos de déficit de atención/hiperactividad (TDAH), esquizofrenia, así como otras enfermedades mentales, cognitivas, y déficits en el desarrollo de niños de primaria o preescolares. Se consultaron las bases de datos PubMed, EMBASE, BIREME/BVS para identificar estudios de asociaciones de ADs durante el embarazo con trastornos de desarrollo neurológico y psiquiátricos. Veinte estudios estaban centrados en riesgos de TEA y/o TDAH, mientras que 30 se centraron en déficits de desarrollo y cognitivos en niños de primaria o preescolares. La mayor parte de los estudios no detectaron asociación de AD, durante la etapa prenatal, con TDA tras el ajuste de las ratios de riesgo para depresión materna o trastornos psiquiátricos. Algunos estudios mostraron que la depresión materna, independientemente de si es tratada o no, incrementó los riesgos de TEA. Siete de los 8 estudios no encontraron un incremento en el riesgo de TDAH, asociado con la exposición prenatal a inhibidores selectivos de la recaptación de serotonina, el antidepresivo más usado habitualmente durante el período prenatal. No se encontraron evidencias consistentes relacionando AD durante el embarazo y déficits en el desarrollo neurocognitivo de niños de primaria o preescolares. En casi todos los estudios hubo una desviación residual señalada como gravedad de la depresión. Esta revisión sistemática no halló evidencias consistentes, sugiriendo que el consumo de ADs durante el embarazo incremente el riesgo de TEA, TDAH, y déficits en el desarrollo neurocognitivo. Algunos estudios, no obstante, encontraron evidencias de que la depresión materna incrementa riesgos de TEA.

Humans , Female , Pregnancy , Infant , Child, Preschool , Prenatal Exposure Delayed Effects , Schizophrenia/epidemiology , Attention Deficit Disorder with Hyperactivity/epidemiology , Autism Spectrum Disorder/epidemiology , Antidepressive Agents/adverse effects , Schizophrenia/chemically induced , Attention Deficit Disorder with Hyperactivity/chemically induced , Brazil/epidemiology , Risk Factors , Autism Spectrum Disorder/chemically induced
Arch. argent. pediatr ; 117(6): 360-367, dic. 2019. tab, graf
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1046199


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.

Humans , Male , Female , Pregnancy , Infant, Newborn , Infant , Child, Preschool , Prenatal Exposure Delayed Effects , Cannabis/adverse effects , Indicators of Morbidity and Mortality , Follow-Up Studies , Cocaine/adverse effects , Retrospective Studies , Mothers
Rev. chil. nutr ; 46(6): 735-745, dic. 2019. tab, graf
Article in English | LILACS | ID: biblio-1058136


The aim of this study was to evaluate the nutritional and behavioral effects of a cafeteria diet in dams during the breastfeeding period and in their offspring from weaning until early adulthood (70 days old). Pregnant Wistar rats were fed a chow diet until delivery. Postnatally (D0), litters were culled to 8 pups and lactating dams received control (CTRL n= 6) or cafeteria (CAF n= 6) diets and water ad libitum. At the end of the breastfeeding period, male offspring were placed in individual boxes receiving the same treatment from their respective dams (CTRL or CAF) until adulthood (70 days). All nutritional and behavioral evaluations were performed with the dams (n= 12) during the breastfeeding phase and with the male offspring (n= 24) after weaning to adulthood. CAF dams demonstrated a lower caloric and protein intake; higher intake of fats; loss of weight; greater accumulation of adipose tissue; and an anxiolytic effect. CAF male offspring showed lower caloric intake; higher intake of fats; and accumulation of adipose tissue. In addition, these animals continued to have decreased body weight, body length and tibia-femur length in relation to CTRL. In dams, a cafeteria diet promoted alterations in body composition and anxiety, and in offspring the diet resulted in adequate development.

El objetivo de este estudio fue evaluar los efectos nutricionales y de comportamiento de la dieta de la cafetería en las madres durante el período de lactancia materna y en su descendencia desde el destete hasta la edad adulta temprana (70 días de edad). Ratas Wistar embarazadas fueron alimentadas con una dieta estándar hasta el parto. Postnatalmente (D0), las camadas se ajustaron en 8 crías y las madres lactantes recibieron las dietas control (CTRL n= 6) o cafetería (CAF n= 6) además de agua ad libitum. Al final del período de lactancia materna, las proles machos fueron colocados en cajas individuales recibiendo el mismo tratamiento de sus respectivas madres (CTRL o CAF) hasta la edad adulta (70 días). Todas las evaluaciones nutricionales y comportamentales se realizaron con las madres (n= 12) durante la fase de lactancia y con la prole masculina (n= 24) después del destete hasta la edad adulta. Las madres CAF demostraron una menor ingesta calórica y proteica; mayor ingestión de grasas; pérdida de peso; mayor acumulación de tejido adiposo; y un efecto ansiolítico. La prole masculina CAF presentó menor consumo calórico; mayor ingestión de grasas; y la acumulación de tejido adiposo. Además, estos animales presentaron menor peso corporal, longitud corporal, y longitud de la tibia-fémur, en relación a CTRL. En las madres, la dieta de cafetería promovió cambios en la composición corporal y ansiedad, y en la prole la dieta comprometió el desarrollo adecuado.

Animals , Male , Female , Pregnancy , Rats , Diet/adverse effects , Feeding Behavior , Anxiety/etiology , Prenatal Exposure Delayed Effects/etiology , Weaning , Behavior, Animal , Breast Feeding , Nutrition Assessment , Adipose Tissue , Analysis of Variance , Rats, Wistar
Rev. chil. pediatr ; 90(5): 555-558, oct. 2019. graf
Article in Spanish | LILACS | ID: biblio-1058183


Resumen: En los últimos años se ha intentado comprender la etiología del Trastorno del Espectro Autista (TEA), evidenciandose que existe una compleja interacción entre factores genéticos y ambientales. Estudios epidemiológicos y en modelos animales sugieren que la activación inmune de la madre durante el embarazo puede asociarse un mayor riesgo de desarrollar TEA en los hijos, destacando el rol de las citoquinas proinflamatorias, los auto-anticuerpos y el rol de la microglia activada en la poda sináptica durante el desarrollo embrionario. Comprender mejor los factores asociados con los Trastornos del Neurodesarrollo permitirá en el futuro desarrollar estrategias de manejo y detección precoz en población de riesgo.

Abstract: Autism Spectrum Disorder (ASD) etiology has been related whit complex interaction between ge netic and environmental factors. In the last years, numerous studies have suggested that maternal immune activation during pregnancy could be related to ASD in the offspring. This relation could be explained by the effects of pro-inflammatory cytokines, autoantibodies and microglial synap tic pruning during early embryonic development. Better understanding of Neurodevelopmental Disorders risk factors will support appropriate strategies of screening and management of risk population.

Humans , Female , Pregnancy , Pregnancy Complications/immunology , Prenatal Exposure Delayed Effects/immunology , Autism Spectrum Disorder/immunology , Autoantibodies/immunology , Risk Factors , Cytokines/immunology , Microglia/immunology , Autism Spectrum Disorder/etiology
Int. j. morphol ; 37(2): 576-583, June 2019. graf
Article in English | LILACS | ID: biblio-1002261


Antidepressants use during pregnancy was associated with an increased risk of autism spectrum disorders. Animal models based on early life alterations in serotonin availability replicate some of the anatomical and behavioral abnormalities observed in autistic individuals. In recent years there has been a growing interest in the possible role of the hippocampus in autism. The aim of study is to examine the effects of neonatal antidepressant (CTM) exposure during a sensitive period of brain development on pyramidal and granule cells density of hippocampal formation. We examined the pyramidal and granular cells density of dorsal hippocampus using Nissl stained sections obtained from neonatal citalopram (CTM) exposed rats (5 mg/kg, twice daily, s.c.), from postnatal day 8 to 21 (PN8-21), saline and non-exposed rats. The density of pyramidal cells was significantly increased by 10.2 % in CA1, 10.6 % in CA3 and 13.2 % in CA4 in CTM treated compared with non-treated or saline treated animals (p<0.0001). The density of granule cells in the dentate gyrus was significantly increased by 12.0 % in CTM treated compared with non-treated or saline treated animals (p<0.0001). These findings were obtained only from male rats, suggesting a sexual dimorphism in neural development after SSRI exposure. These data suggest that the neonatal exposure to CTM may induce long-lasting changes in the hippcampal formation in adults, and such effects appear to preferentially target males.

El uso de antidepresivos durante el embarazo se asoció con un mayor riesgo de trastornos del espectro autista. Los modelos animales basados en alteraciones tempranas de la vida en la disponibilidad de serotonina replican algunas de las anomalías anatómicas y de comportamiento observadas en individuos autistas. En los últimos años ha habido un interés creciente en el posible papel del hipocampo en el autismo. El objetivo del estudio fue examinar los efectos de la exposición al antidepresivo neonatal (CTM) durante un período sensible del desarrollo cerebral en la densidad de las células piramidales y granulares de la formación del hipocampo. Examinamos la densidad de las células piramidales y granulares del hipocampo dorsal utilizando secciones teñidas con Nissl obtenidas de ratas expuestas al citalopram neonatal (CTM) (5 mg / kg, dos veces al día, sc), desde el día postnatal 8 a 21 (PN8-21), solución salina y ratas no expuestas. La densidad de células piramidales se incrementó significativamente en un 10,2 % en CA1, 10,6 % en CA3 y 13,2 % en CA4 en CTM tratados en comparación con animales no tratados o tratados con solución salina (p <0,0001). La densidad de células granulares en el giro dentado aumentó significativamente en un 12,0 % en los animales tratados con CTM en comparación con los animales no tratados o tratados con solución salina (p <0,0001). Estos hallazgos se obtuvieron solo en ratas macho, lo que sugiere un dimorfismo sexual en el desarrollo neural después de la exposición a ISRS. Estos datos sugieren que la exposición neonatal a la CTM puede inducir cambios de larga duración en la formación del hipocampo en adultos, y estos efectos parecen dirigirse preferentemente a los machos.

Animals , Male , Female , Pregnancy , Rats , Prenatal Exposure Delayed Effects , Citalopram/pharmacology , Hippocampus/drug effects , Antidepressive Agents/pharmacology , Autistic Disorder/chemically induced , Behavior, Animal/drug effects , Citalopram/adverse effects , Cell Count , Sex Factors , Rats, Sprague-Dawley , Pyramidal Cells/drug effects , Hippocampus/cytology , Hippocampus/growth & development , Animals, Newborn , Antidepressive Agents/adverse effects
An. bras. dermatol ; 94(3): 327-330, May-June 2019. tab
Article in English | LILACS | ID: biblio-1011107


Abstract: Background: Seborrheic dermatitis is a common disease characterized by the erythematous plaques with oily-yellow desquamation. Increased sebaceous gland activity by androgenic hormones has played a role in the etiology of the disease. The second-to-fourth digit (2D:4D) ratio is thought to be a marker of prenatal androgen exposure. Objectives: To investigate the association between 2D:4D ratios and seborrheic dermatitis in a male population. Methods: Healthy male controls and patients with seborrheic dermatitis were included in this study. One hundred seborrheic dermatitis patients and 120 healthy controls, aged 17-59, were enrolled. A digital Vernier caliper was used to measure the finger lengths. Seborrheic dermatitis severity was assessed using the Seborrheic Dermatitis Area and Severity Index (SDASI). Results: The 2D:4D ratios of the patients (x = 0.977) were significantly lower than those of the controls (x = 1.050) for right hands (t = 6.948; p = 0.000; > 0.05). No similar relationship was found between the 2D:4D ratio for left hands (t = 0.901; p = 0.368; > 0.05). Seborrheic dermatitis severity was negatively correlated with 2D:4D ratios of right hands (r = -0.391; p = 0.000-0.05). Study limitations: One of the main limitations of this study was the small sample, which got a head of us from acquiring certain findings about the 2D:4D ratio and seborrheic dermatitis. The other limitation is that the patient selection did not reflect the general population, as a single clinic was studied. Conclusion: To the authors' knowledge, this is the first study examining the relationship between 2D:4D ratios and seborrheic dermatitis. The result of this study may indicate a line of investigation and can support the theory of prenatal androgen exposure.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Dermatitis, Seborrheic/diagnosis , Fingers/anatomy & histology , Organ Size , Prenatal Exposure Delayed Effects , Severity of Illness Index , Pregnancy , Biomarkers , Case-Control Studies , Anthropometry , Hand/anatomy & histology , Androgens/metabolism
Rev. Hosp. Niños B.Aires ; 61(272): 18-24, abr. 2019.
Article in Spanish | LILACS | ID: biblio-995538


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.

Infant , Risk Factors , Infant Health , Prenatal Exposure Delayed Effects , Tobacco Smoke Pollution , Respiratory Sounds
Arq. bras. cardiol ; 112(1): 67-75, Jan. 2019. tab, graf
Article in English | LILACS | ID: biblio-973833


Abstract Background: Prenatal stress may increase risk of developing cardiovascular disorders in adulthood. The cardiotoxic effects of catecholamines are mediated via prolonged adrenergic receptor stimulation and increased oxidative stress upon their degradation by monoamine oxidase A (MAO-A). Objectives: We investigated long-term effects of prenatal stress on β (1, 2, 3) adrenergic receptors and MAO-A gene expression in the hearts of adult rat offspring. Methods: Pregnant rats were exposed to unpredictable mild stress during the third week of gestation. RNA was isolated from left ventricular apex and base of adult offspring. Quantitative PCR was used to measure gene expression in collected ventricular tissue samples. The level of significance was set to p < 0.05. Results: β3 adrenergic receptor mRNA was undetectable in rat left ventricle. β1 adrenergic receptor was the predominantly expressed subtype at the apical and basal left ventricular myocardium in the control females. Male offspring from unstressed mothers displayed higher apical cardiac β1 than β2 adrenergic receptor mRNA levels. However, β1 and β2 adrenergic receptor mRNAs were similarly expressed at the ventricular basal myocardium in males. Unlike males, prenatally stressed females exhibited decreased β1 adrenergic receptor mRNA expression at the apical myocardium. Prenatal stress did not affect cardiac MAO-A gene expression. Conclusions: Collectively, our results show that prenatal stress may have exerted region- and sex-specific β1 and β2 adrenergic receptor expression patterns within the left ventricle.

Resumo Fundamento: Estresse pré-natal pode aumentar os riscos de desenvolver doenças cardiovasculares na idade adulta. Os efeitos cardiotóxicos de catecolaminas são mediados pela estimulação prolongada dos receptores adrenérgicos e pelo aumento do estresse oxidativo após sua degradação pela monoamina oxidase A (MAO-A). Objetivos: Investigamos os efeitos a longo prazo de estresse pré-natal nos receptores β (1, 2, 3) adrenérgicos e na expressão do gene MAO-A nos corações da prole adulta de ratos. Método: Ratas prenhes foram expostas a estresse crônico moderado imprevisível durante a terceira semana de gestação. O RNA foi isolado do ápice e da base do ventrículo esquerdo da prole adulta. Utilizou-se PCR quantitativa em tempo real para medir a expressão gênica nas amostras de tecido ventricular coletadas. O nível de significância foi estabelecido em p < 0,05. Resultados: Foi indetectável o mRNA do receptor adrenérgico β3 no ventrículo esquerdo dos ratos. O receptor adrenérgico β1 foi o subtipo mais expresso no miocárdio ventricular esquerdo apical e basal nas fêmeas controle. A prole masculina das mães não estressadas apresentou níveis cardíacos apicais de mRNA do receptor adrenérgico β1 mais altos do que os de β2. Porém, mRNAs dos receptores adrenérgicos β1 e β2 foram expressos de forma semelhante no miocárdio basal ventricular na prole masculina em geral. Ao contrário da prole masculina, a prole feminina exposta ao estresse pré-natal exibiu uma expressão diminuída do mRNA do receptor adrenérgico β1 no miocárdio apical. O estresse pré-natal não afetou a expressão gênica de MAO-A cardíaca. Conclusões: Coletivamente, nossos resultados mostram que estresse pré-natal pode ter exercido padrões de expressão região- e sexo-específica dos receptores adrenérgicos β1 e β2 no ventrículo esquerdo.

Animals , Female , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Stress, Psychological/metabolism , Pregnancy, Animal/psychology , Receptors, Adrenergic, beta/analysis , Monoamine Oxidase/analysis , Myocardium/metabolism , Prenatal Exposure Delayed Effects/psychology , Reference Values , Stress, Psychological/genetics , Time Factors , RNA, Messenger/analysis , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/psychology , Gene Expression , Sex Factors , Receptors, Adrenergic, beta/genetics , Rats, Wistar , Adrenocorticotropic Hormone/blood , Real-Time Polymerase Chain Reaction , Heart Ventricles/metabolism , Monoamine Oxidase/genetics , Mothers/psychology