Prenatal and developmental toxicity study of meclizine and caffeine combination in female albino wistar rats.

Meclizine and caffeine combination is used for the treatment of morning sickness. Both compounds are teratogenic and caffeine is known to possess anti-fertility activity also. The present study was undertaken to evaluate the reproductive toxic effect of meclizine and caffeine combination. Three doses were taken for the study; low dose (LD; meclizine 3.7 mg/kg and caffeine 3 mg/kg) was selected from commercially available formulation, middle dose (MD; meclizine 37 mg/kg and caffeine 30 mg/kg) and high dose (HD; meclizine 370 mg/kg and caffeine 300 mg/kg). The mixture was administered 1-7 days and 8-14 days for fertility and embryotoxic studies respectively. Laparotomy was done on 10th day of gestation period. Number of implants and corpora lutea were counted, pre and post-implantation losses were determined. In embryo toxicity study fetuses were evaluated for external, skeletal and visceral examination. High dose was removed from both fertility and embryotoxicity studies due to its severe toxicity to the dam. Significant anti-fertility activity was observed at middle dose. Embryotoxicity study showed significant reduction in fetal body weight, body length and body mass index, dam body weight gain on gestation day 14. Absolute kidney weight in MD and absolute and relative spleen weight in both LD and MD were significantly reduced. There was no increase in external or internal congenital anomalies at both LD and MD. The, results suggest that prescription of meclizine and caffeine for morning sickness in early pregnancy should be reviewed carefully.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report / Malformações fetais associadas ao uso de antagonista dos receptores de angiotensina II: Relato de Caso

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. .

Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão ...

Use of psychotropic medications during pregnancy: perception of teratogenic risk among physicians in two Latin American countries

Objective: Pregnant women and their health care professionals commonly believe that use of medications during pregnancy may be harmful to the unborn fetus. The objective of this study was to evaluate the risk perception of psychotropic drug use in pregnancy among physicians in different medical specialties. Method: This was a convenience survey conducted at outpatient clinics in the cities of Recife, Brazil, and La Plata, Bahía Blanca, and Buenos Aires, Argentina. Physicians who agreed to participate were asked to rate their perception of teratogenic risk among different classes of drugs, which included antidepressants, antipsychotics, anticonvulsants, and benzodiazepines. Results: Two hundred and thirty-eight physicians completed the survey (response rate, 98%). These included psychiatrists, obstetricians, neurologists, cardiologists, gastroenterologists, and general practitioners. Among different specialties, a minority of psychiatrists perceived psychotropic drugs to be highly teratogenic (antidepressants, 12.5%; antipsychotics, 15%; benzodiazepines, 25%) as compared with other specialties (p < 0.003 for each drug class). There was no difference in perceived risk of antiepileptic drugs among specialties, including psychiatrists. Conclusion: The risk associated with use of psychotropic drugs in pregnancy was overestimated by physicians of all medical specialties, except psychiatry. All physicians should be aware of the safety/risk of psychotropic agents in pregnancy, as they may be required to give advice and/or prescribe these drugs to pregnant women. .

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Consumo de medicamentos, álcool e fumo na gestação e avaliação dos riscos teratogênicos / Consumption of medications, alcohol and smoking in pregnancy and assessment of teratogenic risks / Consumo de fármacos alcohol y tabaco el embarazo y la evaluación del riesgos teratogénicos

Medicações, álcool e fumo podem gerar danos fetais. Este estudo transversal foi realizado entre 2006 e 2007, com 326 puérperas do Hospital Geral de Fortaleza, para avaliar o uso de medicamentos, álcool e fumo na gestação e potencial teratogênico relacionado a diferentes características populacionais. Incluíram-se as puérperas com partos no local da pesquisa e excluíram-se as que não tinham seus filhos internados. Na análise, utilizaram-se os testes Qui-quadrado e t de Student, adotando p < 0,05. O consumo de medicamentos ocorreu em 96,6% (2,8 medicamentos/gestante), e 11,3% automedicaram-se. Solteiras utilizaram mais medicações com alto risco teratogênico (p = 0,037). Foram observados 11 casos de malformação fetal, sendo cinco expostos a elevado risco teratogênico, na gestação. O tabagismo ocorreu em 11,3%, e o etilismo em 16%. Observou-se como fator de risco para exposição a maior risco teratogênico o estado civil solteira. Outras variáveis sociodemográficas e a qualidade do pré-natal não se mostraram relacionadas ao risco teratogênico das exposições.

Medications, alcohol and smoking can cause fetal damage. A cross-sectional study was conducted with 326 mothers of the Fortaleza General Hospital to evaluate the use of drugs, alcohol and smoking during pregnancy and its relation to teratogenic potential in different population characteristics, between 2006 and 2007. Postpartum women who had their babies in the research site were included and those whose babies were not admitted as hospital inpatients were excluded. Chi-square tests and t-tests were used in the analysis, with a p value <0.05 considered significant. 96.6% of the mothers took medications (2.8 drugs/ pregnancy) and self-medication occurred in 11.3% of the cases. Single women took more drugs with high teratogenic potential (p=0.037). 11 cases of fetal malformation were observed, five of them were exposed to high teratogenic risks. Smoking occurred in 11.3% and alcohol use in 16%. Being single was found to be a risk factor for exposure to high teratogenic potential. Quality of prenatal care and other sociodemographic variables weren't related to exposure to teratogenic risks.

Medicamentos, alcohol y tabaco pueden causar daño fetal. Estudio transversal, realizado entre 2006 y 2007, con 326 madres del Hospital Geral de Fortaleza, para evaluar uso de drogas, alcohol y tabaco durante el embarazo y potencial teratogénico en relación con distintas características de la población. Madres con partos en sitio de investigación fueron incluidos y las que no tienen niños hospitalizados excluidas. En análisis, se utilizaron los test chi-cuadrado y t de Student, considerando p<0,05. Consumo de medicamentos se produjo en un 96,6% (2,8 drogas/embarazo) y automedicación en un 11,3%. Solteras utilizan más medicamentos de alto riesgo teratogénico (p=0,037). Se observaron 11 casos de malformación fetal, con cinco expuestos a riesgo teratogénico elevado. Fumar se produjo en un 11,3% y un 16% bebía alcohol. Se señaló como factor de riesgo de exposición a alto potencial teratogénico en el estado civil soltero. Otras variables sociodemográficas y calidad de la atención prenatal no se relacionaron con el riesgo teratogénico de exposición.

Embriopatía por isotretinoína con microtia-anotia y cardiopatía: Presentación de un caso / Isotretinoin embryopathy with microtia-anotia and congenital heart disease: Case report

La isotretinoína es un retinoide derivado de la vitamina A utilizado para el tratamiento del acné noduloquístico y refractario, pero ha sido catalogado como un medicamento teratogénico. Se ha comunicado un espectro de defectos congénitos que incluyen malformaciones craneofaciales, defectos cardíacos y defectos en el sistema nervioso con la exposición prenatal a este medicamento. Se presenta el caso de una recién nacida con antecedente de exposición prenatal a isotretinoína con defectos congénitos craneofaciales que incluyen parálisis facial, anotia derecha y microtia izquierda, y cardiopatía compleja.

Isotretinoin is a retinoid that derivates from vitamin A. It is indicated for recalcitrant nodular acne treatment, but it has been classifed as teratogenic. A wide spectrum of birth defects including craniofacial, heart and nervous system malformations have been described associated to prenatal exposure to this drug. We report the case of a newborn with a history of prenatal exposure to isotretinoin with craniofacial defects, including facial paralysis, right anotia, left microtia and complex heart disease.

Toxicidad del misoprostol sobre la gestación: Revisión de la literatura / Developmental toxicity of misoprostol: An update

Misoprostol, a synthetic analog of prostaglandin E1, is currently used in Chile and other countries as an antiulcer medication, mainly for the prevention of non-steroidal anti-infammatory-induced gastric ulcers. Due to its uterotonic properties, it is also indicated in obstetrics for induction of labor and termination of pregnancy. In this last case, misoprostol is either used alone or in combination with other oxytocic drugs such as methotrexate or mifepristone. The use of misoprostol as an abortifacient agent is considered to be safe since it rarely causes serious side effects. However up to 15 percent of misoprostol-induced-abortions may not be successful, even under medical supervision, leading to in utero exposure to the drug and to the induction of a series of birth defects including limb and joints defects and Moebius syndrome. Reports from the nineties failed to show a strong epidemiological association between in utero drug exposure and induction of defects, a situation that has changed now that the number of cases reported has increased. Since the practice of abortion is illegal in Chile, many women turn to off-medical procedures to interrupt their pregnancy and use misoprostol as an easy and cheap alternative, readily available in the INTERNET. The lack of medical supervision in these cases may lead to situations that favor the induction of congenital defects. Here, we present an updated review of scientifc data, to evaluate the risk of birth defects in babies exposed to the drug during pregnancy termination failed attempts.

Frecuencia de automedicación según categoría de teratogenicidad en mujeres en edad reproductiva del Municipio de Colcapirhua (Cochabamba), durante el año 2010 / Frequency of self-medication by category of teratogenicity in women of reproductive age Colcapirhua Township (Cochabamba), during 2010

La automedicación es uno de los principales problemas de salud pública. Esta práctica puede incrementar las reacciones adversas, la resistencia antimicrobiana, el riesgo de malformaciones y discapacidad en los bebés intra útero. Este estudio pretende determinar las características de uso de fármacos según categoría de teratogenicidad en mujeres en edad reproductiva del municipio de Colcapirhua (Cochabamba) durante el año 2010.Se realizó un estudio transversal descriptivo, entre agosto y septiembre de 2010, aplicándose una entrevista a 57 mujeres en edad reproductiva del municipio de Colcapirhua seleccionadas de manera aleatoria con la metodología LQAS (Lot Quality Assurance Sampling) en español “Muestreo para asegurar la calidad de los lotes”. También se aplicó la entrevista a personal que atiende las farmacias en las áreas de investigación.Se encontró automedicación en 77% de mujeres, siendo los medicamentos antigripales los más consumidos con el 39,29%, seguido por los analgésicos, AINES y antibióticos. De acuerdo a los principios activos de los medicamentos usados el 43% se encuentran en la categoría C, 31% a la categoría B, 12% a las categorías A y D, y 2% a la categoría X. No hubo diferencia significativa en relación a las variables ocupación y grado de instrucción. El motivo más frecuente mencionado por la población para automedicarse fue: el tiempo de espera para la atención en los servicios de salud (54,55%)

Defeitos congênitos e exposição a agrotóxicos no Vale do São Francisco / Congenital defects and exposure to pesticides in São Francisco Valley

OBJETIVO: avaliar a associação entre a exposição dos genitores aos agrotóxicos e nascimentos com defeitos congênitos no Vale do São Francisco, bem como o perfil sociodemográfico e os defeitos encontrados. MÉTODOS: estudo tipo caso-controle, sendo que para cada caso (recém-nascido com defeito congênito), eram dois controles (recém-nascidos saudáveis) nascidos na cidade de Petrolina, no Vale do São Francisco, em 2009. A amostra constou de 42 casos e 84 controles. Os dados formam colhidos com uso de questionário estruturado, adaptado do Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC), acrescido de questões relacionadas à exposição aos agrotóxicos, análise do prontuário e contato com a pediatra do hospital. Foi realizado o teste do χ2 com nível de significância de 5 por cento para identificar as variáveis com maiores diferenças entre os grupos caso e controle. Em seguida, foi calculado o Odds Ratio (OR) amostral, bem como o OR obtido por análise de regressão logística e, finalmente, realizou-se uma análise de regressão logística multivariada. RESULTADOS: houve maior exposição aos agrotóxicos durante a gestação em neonatos com defeitos congênitos se comparados aos saudáveis. Maior risco foi observado quando pelo menos um dos genitores foi exposto aos agrotóxicos (OR ajustado = 1,3; IC95 por cento = 0,4-3,9). As variáveis sociodemográficas associadas aos defeitos congênitos foram: baixa escolaridade, baixo peso, prematuridade, genitores jovens, doenças crônicas e fatores físicos. Foram encontrados com maior frequência os polimalformados e os defeitos dos sistemas musculoesquelético e nervoso. CONCLUSÃO: o presente estudo, a despeito de não apresentar significância, sugere associação entre a exposição aos agrotóxicos e a ocorrência de defeitos congênitos.

PURPOSE: to evaluate associations between parental exposure to pesticides and births with congenital defects in São Francisco Valley, as well as the demographic profile and the defects found. METHODS: in this case-control study, each case (newborns with congenital defects) had two controls (healthy newborns). The subjects were born in the city of Petrolina, in São Francisco Valley, in 2009. The sample consisted of 42 cases and 84 controls. Data were gathered by a structured questionnaire adapted from Latin-American Collaborative Study of Congenital Malformations (ECLAMC), with the addition of questions related to exposure to pesticides, analysis of the medical records and contact with the hospital's pediatrician. The χ2 test was performed with a significance level of 5 percent to identify the variables with the greatest differences between case and control groups. Odds Ratio (OR) for the sample was calculated, as well as the OR obtained by logistic regression analysis, and finally, multivariate logistic regression analysis was performed. RESULTS: there was a greater exposure to pesticides during pregnancy in infants with congenital defects compared to healthy subjects. Increased risk was observed when at least one parent was exposed to pesticides (adjusted OR = 1.3; 95 percentCI = 0.4 - 3.9). The sociodemographic variables associated with congenital defects were: low school level, low weight, prematurity, young parents, chronic diseases, and physical factors. Multiple malformations and defects of the musculoskeletal and nervous systems were more frequently found. CONCLUSIONS: the present study suggests an association between exposure to pesticides and the occurrence of congenital defects, although the data were not significant.

Avaliação de riscos teratogênicos em gestações expostas ao misoprostol / Evaluation of the teratogenic risks in gestations exposed to misoprostol

OBJETIVOS: a tentativa de aborto mal sucedida com o uso do misoprostol (Cytotec®) sem indicação médica tem sido associada a malformações congênitas. Este estudo teve por objetivo identificar, em recém-nascidos malformados e controles normais, a frequência de exposição ao misoprostol e o espectro de malformações associadas. MÉTODOS: estudo de caso-controle desenvolvido em 2005 nas quatro principais maternidades públicas de Fortaleza (CE). Através de busca ativa diária, foram identificados recém-nascidos com diagnóstico de malformação fetal (caso) e controles saudáveis de mesmo sexo nascidos em seguida na mesma maternidade (pareamento 1:1). A amostra foi de 252 parturientes entrevistadas por equipe treinada utilizando questionário estruturado com base no Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC). Além de abordar questões sociodemográficas e histórico familiar de malformação, o questionário objetivou identificar exposições diversas durante a gestação, incluindo o misoprostol. A análise bivariada com teste do χ2 comparou os grupos quanto às características e fatores associados à malformação e foi calculada a Odds Ratio para verificar a razão de chances de o Grupo Caso apresentar malformação em relação ao Grupo Controle com relação à exposição ao misoprostol. RESULTADOS: não houve diferenças significativas entre os grupos caso e controle quanto à maioria dos fatores de riscos investigados para malformações. O relato de tentativa de aborto foi de 6,8 por cento, havendo uma maior exposição ao misoprostol durante a gestação em neonatos malformados comparados a saudáveis, Odds Ratio (OR)=3,65 (IC95 por cento=0,74-17,91). O espectro de malformações encontradas entre os recém-nascidos expostos ao misoprostol foi compatível com a literatura, como os decorrentes de defeitos do tubo neural e disrupção vascular. CONCLUSÕES: os achados deste estudo, apesar de não apresentarem significância estatística, sugerem que ...

PURPOSE: failed attempted abortions with the use of misoprostol (Cytotec®) without medical indication have been associated with the occurrence of congenital malformations. The objective of the present study was to identify, in newborns with malformations and in normal controls, the frequency of exposure to misoprostol and the spectrum of associated malformations. METHODS: this was a case-control study involving a daily survey at four public maternities in Fortaleza (CE) for the identification of newborns with malformations and paired controls (1:1) during the period from July to November 2005. The sample comprised 252 parturients interviewed by a trained team by means of a structured questionnaire based on the Latin American Collaborative Study of Congenital Malformations (Estudo Colaborativo Latino-Americano de Malformações Congênitas, ECLAMC). The questionnaire was used to obtain sociodemographic data and a family history of malformations, as well as to identify diverse forms of exposure during pregnancy, including misoprostol. Bivariate analysis and the chi-square test were used to compare cases and controls regarding their characteristics and factors associated with malformation, and the Odds Ratio was calculated to determine the chance of the Case Group to present malformations as compared to the Control Group after exposure to misoprostol. RESULTS: there were no significant differences between groups regarding most of the risk factors for malformations investigated. Attempted abortion was reported by 6.8 percent of the mothers, with a higher exposure to misoprostol during pregnancy resulting in a greater proportion of malformed newborns, Odds Ratio (OR)=3.65 (95 percentCI=0.74-17.91). The spectrum of congenital defects encountered with exposure to misoprostol included defects of the central nervous, musculoskeletal, urogenital and cardiovascular systems, in agreement with literature data. CONCLUSION: the findings of this study suggest ...

Repercussões fetais do consumo materno de álcool / Fetal effects of maternal alcohol consumption

O álcool é o mais comum agente teratogênico humano e seus efeitos lesivos para o feto são reconhecidos desde a Antigüidade. A mais relatada conseqüência decorrente do consumo dessa substância durante a gravidez é o aparecimento de um espectro de anormalidades estruturais e alterações neurocognitivas e comportamentais, conhecido como distúrbio do espectro alcoólico fetal. A manifestação mais extrema desse conjunto é denominada síndrome alcoólica fetal (SAF) e caracteriza-se por alterações crânio-faciais, neurais, cardíacas, renogenitais, cutâneas, musculares e de crescimento. São descritas, também, associações entre o consumo de etanol pela gestante e o aparecimento de abortos espontâneos no primeiro trimestre, leucemia aguda na criança, maior incidência de infecções neonatais, síndrome de abstinência alcoólica fetal e maior incidência de dermatite atópica na infância. Neste estudo é feita uma revisão dos potenciais efeitos lesivos para o feto, provenientes do consumo de álcool pela futura mãe, num contexto atual sobre a patogênese e as manifestações desses danos, passo primordial para incentivar o surgimento de ações em saúde pública visando à prevenção do problema.

Alcohol is the most common teratogenic substance for humans, and its harmful effects to the fetus have been long known. The most mentioned consequence, which is due to the use of this substance during pregnancy, is a spectrum of structural anomalies and neurocognitive and behavioral disabilities known as fetal alcohol spectrum disorder. The most severe manifestation of this set is called fetal alcohol syndrome, characterized by craniofacial, neural, cardiac, renogenital, skin, muscle and growth changes. Another discussed association is the relation between maternal use of ethanol and spontaneous abortion during the pregnancy first trimester, acute leukemia in childhood, higher incidence of newborn infections, fetal withdrawal syndrome, and higher incidence of atopic dermatitis during childhood. In this article we will review potential harmful effects of alcohol usage by a pregnant mother and argue up-to-date data about the pathogenesis and the manifestation of such damages, in order to stimulate public health actions to prevent this problem.

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.

Efeitos do álcool na gestação / Effects of alcohol during pregnancy

O consumo de álcool durante a gestação é importante problema de saúde pública, devido aos comprovados efeitos de toxicidade e teratogenicidade fetal a ele relacionado. Em decorrência da alta tolerância e disponibilidade para o consumo de álcool na sociedade, a freqüencia e a intensidade do uso pode tornar-se um fator de risco de grandes dimensões. O abuso do álcool está associado, de forma dose-dependente, a alterações na fertilidade, restrição do crescimento e desenvolvimento fetal, deficiências cognitivas, aumento da mortalidade, malformações congênitas, complicações no parto e problemas durante a infância. A síndrome alcoólica fetal (SAF) é uma condição irreversível caracterizada por anomalias crânio-faciais típicas, deficiência de crescimento, disfunções do sistema nervoso central e várias malformações associadas. O termo "efeitos fetais do álcool" foi proposto para um grupo de crianças expostas ao álcool intra-útero, mas que não possuíam o quadro clínico completo de SAF. O presente estudo tem o objetivo de realizar uma revisão bibliográfica dos principais aspectos do álcool relacionado à gestação, devido à grande prevalência e à gravidade dos problemas causados por essa associação

The alcohol consumption during pregnancy is an important public health problem, because of the proven toxic effects and fetal teratogenic related. In virtue the high tolerance and availability for the consumption of alcohol in the society, can make the frequency and the intensity of its use can become a factor of risk of great extents. The abuse of is associated, with a form dose-dependent, with changes in the fertiligy, restriction of the growth and fetal development, cognitive disabilities, increase of mortality, congenital malformations, labour complications and problems during the childhood. Fetal Alcohol Syndrome (FAS) is a nonreversible condition characterized by typical cranialface anomalies, disability of growth, abnormalities of the central nervous system and several malformations associate. The present study has the objective to make a bibliographic revision of the main aspects alcohol related with pregnancy, taking into consideration the great prevalence and gravity of the problems caused for this association

A Preliminary Statistical Study of Whether Pesticide use Could be Related to birth defects in a rural area of Venezuela

Objectives: This study was carried out in response to health authorities' concerns regarding what they considered to be a "high proportion" of birth defects (BD) in a rural Venezuelan state as the preliminary step towards subsequent health assessment regarding exposure to pesticides and possible association with registered BD. Methods: This was a cross-sectional descriptive study. Generalised linear modelling (GLM) was used for relating BD with county of origin and the date of the events. Pesticide-use reports were used for assessing exposure to pesticides. Infants' medical records for 1999-2002 were obtained from the state hospital. The study group consisted of 108 BD cases from 8 municipalities. Results: The cardiovascular system had the highest frequency (20,4 percent) of BD, followed by the gastro-intestinal (18,5 percent) and urogenital systems (10,2 percent). Anilides were the most frequently used group of liquid pesticides (39,8 percent), followed by phosphono-methyl-glycine (19,6 percent). The most commonly used solid pesticides were organophosphates (54,4 percent). GLM revealed some significant results; the number of BD increased exponentially throughout the years being studied. Conclusions: A causal association between BD and potential pesticide exposure could not be demonstrated due to data limitations. A more in-depth exposure assessment and epidemiological studies are still needed for characterising the risk of exposure to pesticides in terms of birth outcomes in the area being studied.

Objetivos: En respuesta a la preocupación de autoridades de salud en lo que consideraban un "alto índice de BD" en un Estado rural en Venezuela, se condujo un estudio preliminar para una evaluación posterior relacionada con los BD registrados y su posible asociación con exposición a plaguicidas. Métodos: Estudio descriptivo de corte transversal. Se usó un modelo linear generalizado (GLM) para asociar BD con municipio de origen y fecha del evento. Para evaluar la exposición a plaguicidas, se usaron los registros de ventas. Se obtuvieron los registros médicos del Hospital estadal (1999-2002). El Grupo estudiado estuvo conformado por 108 casos de 8 municipios. Resultados: El sistema cardio-vascular resultó con la frecuencia mßs alta de BD (20,4 por ciento), seguido por el gastro-intestinal (18,5 por ciento) y el urogenital (10,2 por ciento). El grupo mßs utilizado de plaguicidas líquidos fue el de las anilidas (39,8 por ciento) seguido por fosfono-metil-glicina (19,6 por ciento). Los sólidos mas empleados fueron los organofosforados (54,4 por ciento). El GLM mostró algunos resultados significantes observándose que el número de BD aumentó exponencialmente a través de los años en estudio. Conclusiones: Debido a las limitaciones de los datos, no se pudo demostrar una asociación entre BD y exposición potencial a plaguicidas. Se requiere un estudio de exposición y epidemiológico mßs profundo para caracterizar riesgo de exposición a plaguicidas en términos de producción de malformaciones congénitas en el área.

Compuestos disruptores endocrinos y su participación en la programación del eje reproductivo / Endocrine disruptor compounds and their role on the developmental programming of the reproductive axis

Different perturbations during fetal and post natal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming"'. Endocrine disruptor compounds (EDC) are widely spread on the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lypophilyc and stored for long periods on the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women at the BO and 60 to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated to the fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.

Diversas perturbaciones durante el desarrollo fetal y posnatal desencadenan adaptaciones endocrinas que modifican permanentemente el metabolismo, incrementando la susceptibilidad para el desarrollo de enfermedades, proceso conocido como "programación durante el desarrollo". Los compuestos disruptores endocrinos (CDE) se encuentran en el medio ambiente y presentan actividad estrogénica, antiestrogénica o antiandrogénica; son altamente lipofílicos y se almacenan por periodos prolongados en el tejido adiposo. La exposición materna a CDE durante el embarazo y la lactancia permite su paso al producto a través de la placenta y la leche materna. Estudios epidemiológicos y experimentales han demostrado alteraciones en el eje reproductivo como consecuencia de la exposición intrauterina y/o neonatal a CDE. El compuesto mejor documentado es el dietilestilbestrol (DES), este estrógeno sintético fue administrado a mujeres embarazadas durante los 50s y 60s y retirado del mercado por su implicación en anormalidades urogenitales de los bebés expuestos in útero. Las denominadas "hijas del DES" son mujeres con alta incidencia de hipoplasia vaginal, malformaciones uterinas, irregularidades menstruales, baja fertilidad y alta prevalencia de aborto espontáneo y parto prematuro. Por su parte, "los hijos del DES" presentan una entidad clínica conocida como síndrome de disgenesia testicular caracterizado por hipospadias, criptorquidia y baja calidad del semen. Este síndrome también se asocia a la exposición fetal a compuestos antiandrogénicos como la ñutamida. Los efectos en el eje reproductivo dependen del estadio de desarrollo y del tiempo de exposición, así como de la dosis y el compuesto del que se trate. La extensa presencia de CDE en el ambiente afecta la salud humana e impacta al ecosistema en general por lo cual es de suma importancia el estudio de los mecanismos involucrados en su acción.

An overview of over the counter drugs in pregnancy and lactation.

Over the counter (OTC) drugs are commonly used by pregnant women. Most OTC drugs are safe in pregnancy but some have unproven safety and may adversely affect the growing foetus. The safety profile of some of the medication may change according to the gestational age of the foetus. Because an estimated 10% or more of the birth defects results from maternal drug exposure, the US Food and Drug Administration (FDA) has assigned a risk category to each drugs. Among the commonly used OTC drugs Acetaminophen, Chlorpheniramine, Kaolin and Pectin preparations and most antacids have a good safety record. The drugs like H2 blockers; Pseudoephedrine and Atropine/Diphenoxylate should be used with caution. The risk and benefit while using OTC drugs in pregnancy has to be assessed.