Prenatal pyrethroid pesticides exposure and neurodevelopment of 2-year-old children: a birth cohort study / 中华预防医学杂志

Objective: To investigate the influence and critical windows of prenatal exposure to pyrethroid pesticides (PYRs) on neurodevelopment of 2-year-old children. Methods: The subjects of this study were derived from the Xuanwei Birth Cohort. A total of 482 pregnant women who participated in the rural district of Xuanwei birth cohort from January 2016 to December 2018 were included. Maternal urinary concentrations of PYRs metabolites during 8-12 gestational weeks, 20-23 gestational weeks and 32-35 gestational weeks were measured with ultra high performance liquid chromatography system coupled with a tandem mass spectrometry detector. Child neurodevelopment was evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. Multivariate linear regression models and binary logistic regression models were used to assess the association between PYRs exposure during pregnancy and children's neurodevelopment. Results: A total of 360 mother-child pairs had complete data on maternal urinary PYRs metabolites detection and children's neurodevelopment assessment. The detection rate of any one PYRs metabolites during the first, second and third trimester were 93.6% (337/360), 90.8% (327/360) and 94.2% (339/360), respectively. The neurodevelopmental scores of Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior of 2-year-old children were (102.3±18.9), (100.2±16.3), (102.0±20.3), (107.8±23.3) and (85.8±18.6) points, respectively. After controlling for confounding factors, 4-fluoro-3-phenoxybenzoic acid (4F3PBA, one of PYRs metabolites) exposure in the first trimester reduced Motor (β=-5.02, 95%CI: -9.08, -0.97) and Adaptive Behavior (β=-4.12, 95%CI:-7.92, -0.32) scores of 2-year-old children, and increased risk of developmental delay of adaptive behavior (OR=2.07, 95%CI:1.13-3.82). Conclusion: PYRs exposure during the first trimester of pregnancy may affect neurodevelopment of 2-year-old children, and the first trimester may be the critical window.

Inflammatory state and autism-like behavioral phenotype of offspring induced by maternal exposure to low-dose chemical mixtures during pregnancy in mice / 浙江大学学报·医学版

To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. C57BL/6 pregnant mice were given drinking water containing carbaryl dimethoate glyphosate methomyl methyl parathion triadimefon aspartame sodium benzoate calcium disodium ethylene diamine tetra-acetate ethylparaben butylparaben bisphenol A and acacia gum The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level （<0.05）. CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, and TNF-α and hippocampus IFN-γ levels in the offspring（all <0.01）. In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring. Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.

El recién nacido expuesto a cocaína antenatal: una propuesta de intervención médica y psicosocial integrada / The newborn exposed to antenatal cocaine: a proposal for integrated medical and psychosocial intervention

Introducción: El consumo de cocaína durante la gestación gatilla isquemia, muerte y licuefacción celular en el cerebro fetal, consolidando en la infancia grados variables de retraso mental. El presente estudio busca identificar mediante test de drogas en orina los recién nacidos (RN) expuestos a cocaína en el embarazo y describir el procedimiento clínico y social a seguir. Metodología: Estudio de cohorte prospectivo enero 2016 y enero 2018 en RN con exposición antenatal a cocaína, Unidad de Neonatología del Hospital Clínico San Borja Arriarán. Resultados: Se estudió a 64 RN con test en orina positivo a cocaína. El 42% fue pequeño para la edad gestacional, 33% tenía microcefalia. Se encontraron malformaciones en sistema nervioso y vías urinarias, trastornos del ritmo cardíaco e hipoacusia. Solo 32,8% de las madres controló su embarazo y 52% rechazó la rehabilitación. Servicio Social interpuso medidas de protección a los RN e instó a las madres a programas de rehabilitación. El 12,5% de los RN no tenía familia de apoyo y debió ser derivado a instituciones gubernamentales. Conclusiones: Las consecuencias de la exposición a cocaína antenatal en el RN son devastadoras. Este trabajo permite orientar la pesquisa, estudio y pasos legales a seguir con los RN afectados y sus madres.

Introduction: The consumption of cocaine during pregnancy triggers events such as ischemia, death and cell liquefaction in the fetal brain, consolidating varying degrees of intellectual disability. This study proposed to identify by urine drug test the newborns (NB) with antenatal exposure to and describe the clinical and social procedure to follow with them and their mothers until neonatal discharge. Methodology: Prospective cohort study, conducted in RN who met criteria for risk of antenatal exposure to cocaine, Neonatology Unit of the San Borja Arriaran Clinical Hospital between January 2016 -2018. Results: Antenatal exposure to cocaine was confirmed on 64 NB. Forty-two percent of them were small for gestational age and 33% had microcephaly. Malformations were found in the nervous system urinary tract, as well as disorders in the rhythm of the heart and loss of hearing. Only 32% of mothers controlled her pregnancy, none of them was derived to the secondary. Social Services implemented all the NB protective measures in place and urged mothers to participate in rehabilitation programs. Fifty-two percent rejected rehabilitation and 12.5% of the NB have not family support and had to be referred to government institutions. Conclusions: The consequences of exposure to antenatal cocaine in the NB are devastating. This work allows orienting the research with the NB and showing the legal steps should be taken with the RN and their mothers.

Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats

The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP) on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil) and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry), and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1β expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1β-positive cells in the NP group was increased, with higher integral optical density than the control group. Compared to the control group, the serum levels of alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein in the newborn rats of the NP group were significantly increased. There was no significant difference in the serum level of high-density lipoprotein or cholesterol between the groups. Perinatal exposure to NP can interfere with the in vivo estrogen and progesterone levels of pregnant rats, resulting in threatened abortion, dystocia and other adverse delivery outcomes. High liver and serum NP levels of the newborn rats led to alteration of liver tissue structure and function. The NP-induced hepatotoxicity is probably mediated by inflammatory cytokines TNF-α and IL-1α.

Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats / Alterações cardiovasculares da exposição perinatal ao chumbo em ratos jovens e adultos: papel da terapia combinada

Background: Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. Objective: To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Results: Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). Conclusions: All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These ...

Introdução: A terapia combinada parece desempenhar papel significativo em reduzir os efeitos cardiovasculares deletérios da exposição ao chumbo (Pb). Objetivo: Para investigar esta possibilidade, ratas Wistar receberam Pb (500 ppm na água de beber) ou água durante a prenhez e a lactação. Ratos com 22 e 70 dias, expostos perinatalmente ao Pb ou não, receberam DMSA, L- arginina, enalapril e a combinação destes por 30 dias adicionais. Métodos: Curvas concentração-efeito à noradrenalina foram obtidas em aortas intactas e desnudas, de ratos com 23, 52, 70 e 100 dias expostos ou não ao Pb, tratados ou não. Resultados: A pressão arterial sistólica caudal (mmHg) foi avaliada e mostrou-se aumentada em ratos expostos ao Pb [23, 52, 70 e 100 dias, respectivamente: controle 107,1±1,8, 118,8±2,1, 126,1±1,1, 120,5±2,2; Pb 117,8±3,9*, 135,2±1,3*, 139,6±1,6* e 131,7± 2,8*]. Observou-se aumento de reatividade à noradrenalina em aorta intacta, mas não desnudada, de ratos com 52, 70 e 100 dias expostos ao Pb [resposta máxima (g de tensão) 52 dias: Pb 3,43±0,16*, controle 2,38±0,33; 70 dias: Pb 4,32±0,18*, controle 3,37±0,13; 100 dias: Pb 4,21±0,23*, controle 3,22±0,21]. (*) p < 0,05 em relação ao respectivo controle. Conclusões: Todos os tratamentos restauraram as alterações de reatividade à noradrenalina em aortas de ratos expostos perinatalmente ao Pb. Exceto pelo enalapril em ratos jovens, a terapia combinada restaurou mais precocemente a pressão arterial de ratos expostos ao Pb em relação aos tratamentos isolados. Estes resultados representam uma nova abordagem no desenvolvimento de protocolos terapêuticos no tratamento da hipertensão induzida pela exposição ao Pb. .

Hepatic damage in newborns from female rats exposed to the pesticide derivative ethylenethiourea / Lesões hepáticas em recém-nascidos de ratas expostas ao derivado de agrotóxico etilenotioureia

PURPOSE: To evaluate hepatic morphological-histological abnormalities in newborns from female rats exposed to ethylenethiourea. METHODS: A randomized study was conducted on fifty-five newborn Wistar rats were studied: 34 in the experimental group, whose mothers had been exposed to 1% ethylenethiourea; and 21 in the control group, whose mothers had received 0.9% physiological solution. The solution was administered via gavage on the 11th day of gestation. Cesarean section was performed on the 20th day of gestation. The newborns' livers were examined and any morphological-histological abnormalities were registered. The presence of megakaryocytes was quantified in 50 microscope fields, as the total number of these cells per mm². RESULTS: The entire experimental group presented abnormalities of embryonic formation, with musculoskeletal anomalies, digestive system anomalies, hepatic congestion and friability, hydrops and delayed intrauterine growth. The histopathological analysis showed that morphological-histological hepatic destructuring had occurred in all entire experimental with removal of the hepatic trabeculae and severe hepatic megakaryocytosis. The mean megakaryocyte density ranged from 107.9 to 114.2 per mm², and it was eight times greater than in the control group, thus characterizing a situation of extramedullary hematopoiesis. CONCLUSION: The fetal exposure to ethylenethiourea caused hepatic damage characterized by severe extramedullary hematopoiesis.

OBJETIVO: Avaliar alterações hepáticas morfohistológicas em recém-nascidos de ratas prenhes expostas à etilenotioureia. MÉTODOS: Realizado ensaio randomizado em animais de experimentação, onde foram estudados 55 recém-nascidos de ratas Wistar, 34 do Grupo Experimento, expostas a etilenotioureia 1% e 21 do Grupo Controle, em que a rata prenhe recebeu solução fisiológica 0,9%, ambos por gavagem no 11º dia de gestação. Realizada no 20º dia de gestação cesariana, analisados os fígados dos recém-nascidos e registradas as alterações morfohistológicas. Realizou-se a quantificação dos megacariócitos em 50 campos microscópicos, avaliando a quantidade total destas células por mm². RESULTADOS: Todos os recém-nascidos do Grupo Experimento apresentaram alterações na formação embrionária, com anomalias musculoesqueléticas, anormalidades do sistema digestório, congestão e friabilidade hepática, hidropisia e crescimento intrauterino retardado. A análise histopatológica mostrou desestruturação hepática morfohistológica em todos os recém-nascidos expostos à etilenotioureia, com destrabeculação dos hepatócitos e intensa megacariocitose hepática, apresentando média da densidade de megacariócitos de 107,9 até 114,2 por mm² sendo cerca de oito vezes maior que no Grupo Controle, caracterizando hematopoese extramedular. CONCLUSÃO: A exposição fetal a etilenotioureia provocou danos hepáticos caracterizados pela intensa hematopoese extramedular.

Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea / Anomalias da inervação do trato digestório de fetos de ratas expostas à etilenotioureia

PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9 percent physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100 percent, anorectal anomalies in 86 percent, absent tail in 71 percent, short tail in 29 percent, duodenal atresia in 5 percent, esophageal atresia in 5 percent and persistent omphalomesenteric duct in 5 percent. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

OBJETIVO: As anomalias associadas a lesões dos plexos mioentéricos permanecem sem plena compreensão da sua fisiopatologia. Alterações nos plexos nervosos têm sido correlacionadas com quadros suboclusivos intestinais em crianças portadoras de doença de Hirschsprung, em constipação crônica e no pós-operatório de anomalias anorretais. Este estudo avaliou as anomalias do plexo mioentérico em fetos de ratos fêmea que ingeriram etilenotioureia (ETU). MÉTODOS: Ratos fêmea foram expostos no 11º dia de gestação a ETU 1 por cento no Grupo Experimento e a solução fisiológica 0,9 por cento no Grupo Controle. Foram observadas anomalias apenas no Grupo experimento, sendo realizada morfometria da camada muscular e avaliadas alterações da frequência celular nos gânglios do plexo mioentérico e nas células intersticiais de Cajal (CIC) utilizando hematoxilina-eosina, P S-100, Enolase Neurônio Específica e C-KIT. RESULTADOS: Foram observadas anomalias musculoesqueléticas (100 por cento), anorretais (86 por cento), ausência de cauda (71 por cento), cauda curta (29 por cento), atresia duodenal (5 por cento), atresia esofágica (5 por cento) e conduto onfalomesentérico persistente (5 por cento). A análise histopatológica mostrou adelgaçamento da camada muscular associada às alterações da frequência das células ganglionares e das CIC em todos os segmentos do trato gastrointestinal. CONCLUSÃO: Foram observadas alterações graves nos plexos nervosos associadas ao adelgaçamento da camada muscular de todo o trato gastrointestinal nos fetos expostos a ETU.

Limiares auditivos em crianças expostas a mercúrio no período pré-natal / Hearing thresholds in children exposed to mercury in the prenatal period

OBJETIVO: Avaliar os limiares auditivos de crianças com histórico de exposição ao mercúrio durante o período pré-natal. MÉTODOS: Foram avaliadas 90 crianças com idades entre 8 e 10 anos, de ambos os gêneros, categorizadas em dois grupos de acordo com os níveis de exposição pré-natal ao mercúrio. O grupo de estudo foi composto por 57 crianças que apresentaram níveis de mercúrio no cordão umbilical iguais ou superiores a 8 µg/L, e o grupo de comparação por 33 crianças que apresentaram níveis de mercúrio no cordão umbilical inferiores a 8µg/L. Os procedimentos incluíram um questionário, audiometria tonal liminar, pesquisa do limiar de recepção de fala e análise das doses de mercúrio no cordão umbilical coletadas ao nascimento. RESULTADOS: O grupo de estudo apresentou mediana de mercúrio no cordão umbilical de 14,63 µg/L, e mediana dos limiares tonais das frequências de 500 Hz, 1 kHz e 2 kHz de 10 dB em ambas orelhas. O grupo de comparação apresentou mediana de mercúrio no cordão umbilical de 4,88 µg/L, e mediana dos limiares tonais das frequências de 500 Hz, 1 kHz e 2 kHz de 10 dB em ambas orelhas. Quando comparados os limiares auditivos, tanto pela média tritonal quanto para cada frequência isoladamente, não foram observadas diferenças significativas entre os grupos. CONCLUSÃO: As crianças apresentaram limiares auditivos dentro dos padrões de normalidade e não foi observada diferença significativa entre os limiares auditivos das crianças expostas e não-expostas ao mercúrio no período pré-natal.

PURPOSE: To evaluate hearing thresholds in children with a history of exposure to mercury during the prenatal period. METHODS: Participants were 90 children of both genders with ages from 8 to 10 years, divided into two groups according to prenatal mercury exposure levels. The study group was composed by 57 children who had mercury levels in the umbilical cord equal or above 8 µg/L, and the comparison group comprised 33 children who had mercury levels in the umbilical cord below 8 µg/L. Investigation procedures included the application of a questionnaire, pure-tone audiometry, speech reception threshold, and mercury level analysis in cord blood collected at birth. RESULTS: The study group showed a median mercury level in the umbilical cord of 14.63 µg/L, and the median threshold for 500 Hz, 1 kHz and 2 kHz in pure-tone audiometry was 10 dB for both ears. The comparison group had a median cord blood mercury level of 4.88 µg/L, and the median threshold for 500 Hz, 1 kHz and 2 kHz in pure-tone audiometry was 10 dB for both ears. When the hearing thresholds were compared, both by the tritonal mean and by each frequency separately, there were no significant differences between groups. CONCLUSION: The children had hearing thresholds within normal limits and there was no significant difference between the hearing thresholds of children exposed and not exposed prenatally to mercury.

Are environmental pollutants risk factors for low birth weight? / Os poluentes ambientais são fatores de risco para o baixo peso ao nascer?

The aim of this study was to assess the association between prenatal exposure to air pollutants and low birth weight in a medium-sized city. An ecological study was performed, using live birth data from São José dos Campos, São Paulo State, Brazil. The environmental data were obtained from the São Paul State Environmental Agency. The study included full-term newborns whose mothers were 20 to 34 years of age and had at least a complete high school education, seven or more prenatal visits, singleton pregnancy, and vaginal delivery, in order to minimize potential confounding from these variables. Logistic regression was used to estimate the effect of each pollutant. Low birth weight was defined as less than 2,500g. The sample included a total of 2,529 data from 2001 that met the inclusion criteria (25.6 percent of the total). We identified 99 newborns (3.95 percent of the sample) with low birth weight, and the pollutants sulfur dioxide and ozone were associated with low birth weight. The final model was À(x) = -1.79 + 1.30 (SO2) + 1.26 (O3). Thus, sulfur dioxide and ozone were identified as risk factors for low birth weight in a medium-sized city in Southeast Brazil.

O objetivo foi estimar o papel de poluentes no baixo peso ao nascer numa cidade de porte médio. Foi um estudo ecológico com dados obtidos da Declaração de Nascido Vivo relativos a São José dos Campos, São Paulo, Brasil. Os dados ambientais foram fornecidos pela Companhia de Tecnologia de Saneamento Ambiental (CETESB). Foram incluídos no estudo recém-nascidos a termo, com mães entre 20 e 34 anos de idade, segundo grau completo, sete ou mais consultas realizadas no pré-natal, gravidez única e parto normal, para minimizar o efeito de confusão destas variáveis. Utilizou-se regressão logística para estimar o efeito de cada poluente. Baixo peso ao nascer foi considerado aquele inferior a 2.500g. Foram incluídos 2.529 dados de 2001 que atenderam aos critérios de inclusão (25,6 por cento do total). Identificamos 99 recém-nascidos (3,95 por cento dessa amostra) com baixo peso e os poluentes dióxido de enxofre e ozônio como associados ao baixo peso ao nascer. O modelo final foi À(x) = -1,79 + 1,30 (SO2) + 1,26 (O3). Assim, identificou-se o dióxido de enxofre e ozônio como responsáveis pelo baixo peso ao nascer numa cidade de porte médio do Sudeste brasileiro.

Uso do trastuzumabe na gravidez / Use of trastuzumab during pregnancy

O uso do trastuzumabe, anticorpo antimonoclonal contra o receptor do fator de crescimento epidérmico HER-2, tem sido utilizado no tratamento do carcinoma mamário de pacientes que superexpressam esta proteína. Relatos de casos divergem quanto à presença ou ausência de efeitos adversos na gravidez. Quando presentes, os mais encontrados no feto foram: oligo ou anidrâmnio, insuficiência renal, síndrome de angústia respiratória e óbito fetal/neonatal. Esta revisão discutiu as vias etiopatológicas possíveis deste fármaco em causar tais efeitos e sugeriu uma propedêutica de seguimento dessas pacientes.

The use of trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2, has been a useful therapy in the treatment of breast cancer patients that overexpress such protein. Published case reports with different results regarding the presence or absence of adverse effects in pregnancy are shown. If present, the most reported ones were: oligo or anydramnios, renal insufficiency, respiratory distress syndrome, and fetal/neonatal death. This review discussed the ethiopathologic pathways of this drug in causing such effects and suggested a follow-up protocol for these patients.

Reconstrução nasal neonatal na Síndrome do Warfarin Fetal / Neonatal nasal reconstruction in Fetal Warfarin Syndrome

O objetivo deste trabalho é relatar um caso de reconstrução nasal precoce em um paciente com síndrome do Warfarin fetal, onde um paciente de 23 dias com apresentava hipoplasia nasal isolada. O ganho ponderal estava estagnado e não havia possibilidade de introdução de sonda nasoentérica devido à deformidade. Foi realizada rinoplastia aberta com incisão transcolumelar. Dois enxertos de cartilagem tragal foram confeccionados e introduzidos na região da ponta, porção cranial do septo cartilaginoso e alares. O paciente apresentou melhoria da permeabilidade ventilatória, diminuição do ruído inspiratório, ganho de peso e também da forma. Após um ano de seguimento o resultado continuava satisfatório. Concluímos que a intervenção precoce é satisfatória e pode minimizar ou mesmo prevenir procedimentos futuros.

The aim of this work is to report a case of early nasal reconstruction in a 23-day-old patient with fetal Warfarin syndrome and isolated nasal hypoplasia. Weight gain was arrested and the deformity precluded the use of a nasogastric tube. An open rhinoplasty with transcolumellar incision was performed. Two grafts of tragal cartilage were made and introduced in the tip area, cranial portion of the cartilaginous septum, and alar cartilages. The patient presented improved ventilatory permeability, decrease of inspiratory noise, and weight and shape gains. At the one-year follow-up the result was still satisfactory. We concluded that early intervention is satisfactory and may minimize or even prevent future procedures.

Exposure to misoprostol and hormones during pregnancy and risk of congenital anomalies / Exposição ao misoprostol e hormônios durante a gravidez e risco de anomalia congênita

This study evaluated the association between use of misoprostol and other drugs to induce menstruation, and congenital anomalies. A sample of 4,856 pregnant women 20 years and older were enrolled consecutively in prenatal services in the Unified National Health System, in six Brazilian State capitals. Data on socio-demographics and use of medicines were obtained using an interview from the 21st to 28th week of pregnancy. Other data, including information on delivery and diagnosis of congenital anomalies by the attending neonatal physician were obtained from patient charts. Potential confounders were adjusted by logistic regression. Use of drugs to induce menstruation was reported by 707 women (14.6 percent), of whom 120 (17 percent) reported use of misoprostol. After adjusting for the study center, a positive association was observed between misoprostol and congenital anomalies (OR = 2.64; 95 percentCI: 1.03-6.75); a positive association was also observed for sex hormones (OR = 2.24; 95 percentCI: 1.06-4.74). The results suggest that the use of misoprostol or sex hormones during pregnancy increases the risk of congenital anomalies.

Este estudo avalia a associação do uso do misoprostol e de outros produtos utilizados para induzir a menstruação com anomalia congênita. Foram arroladas consecutivamente 4.856 mulheres com vinte anos de idade ou mais, procedentes de serviços de pré-natal do Sistema Único de Saúde em seis capitais brasileiras. Dados sócio-demográficos e o uso de medicamentos foram obtidos por meio de entrevista, entre a 21ª e a 28ª semanas de gestação. Outros dados, incluindo informações sobre o parto e o diagnóstico de anomalia congênita, realizado pelo médico que assistiu o recém-nascido, foram obtidos no prontuário. Potenciais confundidores foram ajustados por meio de regressão logística. O uso de produtos para induzir a menstruação foi relatado por 707 gestantes (14,6 por cento), das quais 120 (17 por cento) referiram-se ao misoprostol. Após ajustamento para o centro de realização da pesquisa, foi verificada uma associação positiva entre misoprostol e anomalias congênitas (RC = 2,64; IC95 por cento: 1,03-6,75); para hormônios sexuais também foi verificada uma associação positiva (RC = 2,24; IC95 por cento: 1,06-4,74). Os resultados sugerem que o uso de misoprostol ou hormônios sexuais durante a gravidez aumenta o risco de anomalia congênita.

Embriopatía por isotretinoína: Un daño evitable / Isotretinoin embryophaty: Report of one case

Retinoic acid is a widely used drug in the treatment of cystic acné. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months of female whose mother was exposed to retinoic acid in both pregestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms ofthe teratogenic effeets of retinoic acid.

Efeitos da exposição pré-natal e pós-natal ao etanol no córtex cerebral de ratos: um estudo do neurópilo / Effects of prenatal and postnatal ethanol exposure in the cerebral cortex of rats: a study of neuropil

INTRODUÇÃO: Exposição pré-natal ao etanol é freqüentemente associada a microcefalia e atraso na migração celular. O mecanismo pelo qual o etanol induz seus efeitos no desenvolvimento do sistema nervoso não é muito bem entendido. OBJETIVOS: Avaliar o efeito da exposição crônica ao etanol sobre o córtex visual de ratos durante seu desenvolvimento. MATERIAL E MÉTODO: Ratos Wistar provenientes do acasalamento de 30 fêmeas, divididos nos grupos etanol (n = 10) - 3 g/kg/dia - e controle (n = 10), foram utilizados nesse experimento. Os ratos foram perfundidos e o encéfalo, dividido em três partes: anterior, médio e posterior. Os cortes obtidos do fragmento posterior foram expostos à rotina histológica e submetidos a diferentes técnicas de coloração. Na análise estatística foi utilizado o teste t para comparar os pesos encefálicos e corporais. Considerou-se como nível de rejeição de hipótese nula um valor de p < 0,05. RESULTADO: Houve redução de peso cerebral em diferentes períodos analisados, além de ectopia e heterotopia neuronal. Não se observou deposição de fibras. DISCUSSÃO/CONCLUSÃO: O etanol atua de maneira negativa no desenvolvimento dos ratos, incluindo alterações na migração neuronal e microcefalia. Essas alterações podem ajudar a explicar as disfunções relatadas na síndrome do alcoolismo fetal (SAF).

BACKGROUND: Prenatal exposure to ethanol is frequently associated with microencephaly and delayed cell migration. The mechanism by which ethanol affects the development of the nervous system is still not fully understood. OBJECTIVE: To evaluate the effect of chronic exposure to ethanol on the visual cortex of rats during their development. MATERIAL AND METHOD: Wistar rats, born from the mating of 30 females, were divided into two groups: those exposed to ethanol (n = 10) - 3 g/kg/day - and a control group (n = 10). The rats were perfused and brain was divided into three parts: anterior, middle and posterior. Slices taken from the posterior fragment were subjected to histological analysis routine and different staining techniques. A statistical analysis was carried out using t test to compare brain and body weight. A value < 0,05 was considered a rejection of null hypothesis. RESULTS: There was a reduction of brain weight in different analyzed periods. There were no fiber deposits. Ectopia and neuronal heterotopia were observed. DISCUSSION/CONCLUSION: Ethanol has a negative effect on the development of rats, including alterations in neuronal migration and microencephaly. These alterations may help to explain some of the dysfunctions reported in patients with fetal alcohol syndrome (FAS).

Intracranial arteriovenous malformation with maternal carbamazepine use.

1 1/2 month old child born to primigravida mother on prolonged carbamazepine therapy presented with recurrent seizures. The child had abnormal facies and was diagnosed to be having arteriovenous malformation with intracranial hemorrhage on neuroimaging. This case suggests that development of arteriovenous malformation in a child with maternal carbamazepine therapy may occur as a part of clinical profile of 'fetal anticonvulsant syndrome'.

Fetal valproate syndrome.

Fetal Valproate Syndrome results from prenatal exposure to valproic acid. It is characterized by distinctive facial appearance, a cluster of minor and major anomalies and central nervous system dysfunction. Here we report a 4-year-old boy with typical facial features of Fetal Valproate Syndrome.