Uso de misoprostol em obstetrícia / Misoprostol use in obstetrics

PONTOS-CHAVE O misoprostol é um análogo da prostaglandina E1 (PGE1) que consta na Lista de Medicamentos Essenciais da Organização Mundial da Saúde (OMS) desde 2005 O Brasil possui uma das regulações mais restritivas do mundo relacionadas ao uso do misoprostol, estabelecendo que o misoprostol tem uso hospitalar exclusivo, com controle especial, e venda, compra e propaganda proibidas por lei Atualmente, o misoprostol é a droga de referência para tratamento medicamentoso nos casos de aborto induzido, tanto no primeiro trimestre gestacional quanto em idades gestacionais mais avançadas O misoprostol é uma medicação efetiva para o preparo cervical e indução do parto O misoprostol é um medicamento essencial para o manejo da hemorragia pós-parto

Misoprostol Administration Before Hysteroscopy Procedures - A Retrospective Analysis / O uso do misoprostol prévio aos procedimentos histeroscópicos - Um estudo retrospectivo

Abstract Objective To evaluate the use of misoprostol prior to hysteroscopy procedures regarding technical ease, the presence of side effects, and the occurrence of complications. Methods This is a retrospective, observational, analytical, case-control study, with the review of medical records of 266 patients followed-up at the Gynecological Videoendoscopy Sector of the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto of the Universidade de São Paulo (HCFMRP - USP, in the Portuguese acronym) from 2014 to 2019, comparing 133 patients who used the drug before the procedure with 133 patients who did not. Results The occurrence of postmenopausal uterine bleeding was the main indication for hysteroscopy and revealed a statistical difference between groups (p < 0.001), being present in 93.23% of the patients in the study group and in 69.7% of the patients in the control group. Only 2 patients (1.5%) in the study group reported adverse effects. Although no statistical differences were observed regarding the occurrence of complications during the procedure (p = 0.0662), a higher total number of complications was noted in the group that used misoprostol (n = 7; 5.26%) compared with the group that did not use the drug (n = 1; 0.75%), a fact that is clinically relevant. When evaluating the ease of the technique (measured by the complete performance of all steps of the hysteroscopy procedure), it was verified that although there was no difference between groups (p = 0.0586), the control group had more than twice as many incompletely performed procedures (n = 17) when compared with the group that used misoprostol previously (n = 8), which is also clinically relevant. Conclusion The use of misoprostol prior to hysteroscopy in our service indicated that the drug can facilitate the performance of the procedure, but not without side effects and presenting higher complication rates.

Resumo Objetivo Avaliação do misoprostol prévio à histeroscopia quanto à facilidade técnica, efeitos colaterais e a ocorrência de complicações durante o procedimento. Métodos Estudo analítico observacional retrospectivo tipo caso controle com revisão de prontuários de 266 pacientes do Setor de Videoendoscopia Ginecológica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (HCFMRP - USP), de 2014 a 2019, sendo comparadas 133 pacientes que utilizaram o medicamento prévio ao procedimento com 133 pacientes que não o utilizaram. Resultados Sangramento uterino após a menopausa foi a principal indicação de histeroscopia, apresentando diferença estatística (p < 0,001), estando presente em 93,23% das pacientes do grupo de estudo e em 69,17% das pacientes do grupo controle. Apenas 2 pacientes (1,5%) do grupo de estudo relataram efeitos adversos. Não foram observadas diferenças quanto à presença de complicações durante o procedimento (p = 0,0662), mas observamos um número total de complicações maior no grupo de estudo (n = 7; 5,26%) do que no grupo controle (n = 1; 0,75%), o que é clinicamente relevante. Não houve diferença entre os grupos quanto à facilidade técnica (p = 0,0586), mas o grupo controle apresentou mais do que o dobro de procedimentos não completamente realizados (n = 17) quando comparado com o grupo de estudo (n = 8), o que é clinicamente relevante. Conclusão O uso de misoprostol prévio à histeroscopia no nosso serviço demonstrou que ele pode facilitar a realização do procedimento, mas não é isento de efeitos colaterais e apresenta maiores taxas de complicações.

Abordaje integral de la Interrupción Voluntaria del Embarazo: (segunda entrega) / Comprehensive approach to the voluntary interruption of pregnancy: (second issue)

La legalización de la interrupción voluntaria del embarazo ha transformado la práctica médica con respecto a la atención de las pacientes que desean interrumpir la gestación hasta la semana 14 en Argentina. En la primera entrega, el equipo PROFAM compartió su punto de vista a través de una adaptación de su material educativo destinado, sobre todo, a aclarar los aspectos legales que hacen a la práctica cotidiana. En esta entrega se desarrolla en detalle el procedimiento para realizar un aborto farmacológico con misoprostol y mifepristona, así como las generalidades del aspirado manual endouterino. (AU)

The legalization of voluntary termination of pregnancy has transformed medical practice regarding the care of patients who wish to terminate a pregnancy up to 14 weeks in Argentina. In the first issue, the PROFAM team shared its point of view through an adaptation of its educational material aimed, above all, at clarifying the legal aspects of daily practice. In this issue, the procedure to perform a pharmacological abortion with misoprostol and mifepristone is developed in detail, as well as the generalities of manual uterine aspiration technique. (AU)

Can the Induction of Labor with Misoprostol Increase Maternal Blood Loss? / Pode a indução do parto com misoprostol aumentar a perda de sangue materna?

Abstract Purpose To evaluate blood loss during misoprostol-induced vaginal births and during cesarean sections after attempted misoprostol induction. Methods We conducted a prospective observational study in 101 pregnant women indicated for labor induction; pre- and postpartum hemoglobin levels were measured to estimate blood loss during delivery. Labor was induced by administering 25 μg vaginal misoprostol every 6 hours (with a maximum of 6 doses). The control group included 30 patients who spontaneously entered labor, and 30 patients who underwent elective cesarean section. Pre- and postpartum hemoglobin levels were evaluated using the analysis of variance for repeated measurements, showing the effects of time (pre- and postpartum) and of the group (with and withoutmisoprostol administration). Results Therewere significant differences between pre- and postpartum hemoglobin levels (p < 0.0001) with regard to misoprostol-induced vaginal deliveries (1.6 ± 1.4 mg/dL), non-induced vaginal deliveries (1.4 ± 1.0 mg/dL), cesarean sections after attempted misoprostol induction (1.5 ± 1.0 mg/dL), and elective cesarean deliveries (1.8 ± 1.1 mg/dL). However, the differences were proportional between the groups with and without misoprostol administration, for both cesarean (p = 0.6845) and vaginal deliveries (p = 0.2694). Conclusions Labor induction using misoprostol did not affect blood loss during delivery.

Resumo Objetivo Avaliar a perda sanguínea em partos vaginais induzidos com misoprostol, e em cesáreas com tentativa prévia de indução do parto com misoprostol. Métodos Realizou-se estudo prospectivo observacional com 101 gestantes com indicação para indução do trabalho de parto, as quais foram avaliadas pela dosagem de hemoglobina pré e pós-parto para estimativa da perda sanguínea no parto. Procedeu-se à indução do trabalho de parto com misoprostol 25 μg, via vaginal, a cada 6 horas, em um número máximo de 6 doses. O grupo controle foi composto por 30 pacientes que entraram emtrabalho de parto espontaneamente, e por 30 pacientes que se submeteram a cesárea eletiva. O estudo da hemoglobina, antes e depois do parto, foi avaliado por ANOVA paramedidas repetidas, no qual foi verificado o efeito do tempo (pré e pós-parto) e o efeito do grupo (com e sem uso do misoprostol). Resultados Existem diferenças significativas entre os níveis de hemoglobina pré e pós-parto (p < 0,0001) nos partos vaginais induzidos pelo misoprostol (1,6 ± 1,4 mg/ dL), nos partos vaginais não induzidos (1,4 ± 1,0 mg/dL), nas cesáreas com tentativa prévia de indução (1,5 ± 1,0mg/dL), e nas cesáreas eletivas (1,8 ± 1,1mg/dL). Porém, as diferenças foram proporcionais em ambos os grupos, ou seja, ocorreu diferença tanto no grupo que fez uso do misoprostol quanto no grupo que não fez uso do medicamento, tanto na cesárea (p = 0,6845) quanto no parto vaginal (p = 0,2694). Conclusões A indução do parto com misoprostol não alterou a perda sanguínea durante o parto.

Secuencia Moebius. Análisis retrospectivo de 30 pacientes / Moebius syndrome. A retrospective analysis of 30 patients.

Introducción: La secuencia Moebius se caracteriza por el compromiso congénito de los nervios motor ocular externo y facial, y se puede asociar al compromiso de otros pares craneales y a otros defectos congénitos. Su etiología es multifactorial y no bien definida, actualmente la teoría más aceptada es la disrupción vascular durante el desarrollo del romboencéfalo. Su incidencia exacta se desconoce, pero impresiona estar en aumento y asociada a la exposición prenatal a teratógenos. Objetivos: Analizar las historias clínicas de 30 pacientes con secuencia Moebius y las características de su compromiso ocular. Materiales y métodos: Estudio retrospectivo, transversal, observacional y descriptivo. Se analizaron 30 historias clínicas de pacientes con secuencia Moebius atendidos por vez primera entre el mes de Julio de 1999 y Junio de 2012 por el servicio de Oftalmología del Hospital Garrahan. Resultados: Se estudiaron 30 pacientes 15 de sexo femenino y 15 de sexo masculino, dentro de los antecedentes maternos 7 madres refirieron ingesta de misoprostol y 4 tuvieron metrorragias durante el primer trimestre de embarazo. Todos los pacientes tuvieron compromiso del VII nervio; en 20 pacientes fue bilateral y simétrico; y en los restantes asimétrico. Todos los pacientes tuvieron compromiso del VI nervio bilateral, a algunos de los cuáles se les efectuó cirugía de estrabismo otros están en plan de cirugía y unos pocos no la requirieron por presentar fijación de ambos ojos en posición primaria de la mirada. Conclusión: la secuencia Moebius es una rara patología genética y congénita multifactorial y de compromiso multisistémico que ha visto incrementada su frecuencia desde el uso de ciertos fármacos teratógenos y que obliga a una intervención quirúrgica precoz de neuroortopedistas, oftalmólogos, cirujanos plásticos y control clínico multidisciplinario para brindarles a estos niños las mejores posibilidades de desarrollo funcional y estético reparador (AU)

Introduction: Moebius syndrome is characterized by congenital palsy of the external and facial oculomotpr nerves, and may be associated with involvement of other cranial nerves and congenital defects. The etiology is multifactorial and not well defined. Currently, the most widely accepted theory is a rhombencephalic maldevelopment. The true incidence of Moebius syndrome is unknown, but it seems to be increasing associated with prenatal exposure to teratogenic factors. Objectives: To analyze the clinical charts of 30 patients with Moebius syndrome assessing ocular involvement. Material and methods: A retrospective, cross-sectional, observational study. Thirty clinical charts of patients with Moebius syndrome that were first seen at the Department of Ophthalmology of Hospital Garrahan between July 1999 and June 2012 were assessed. Results: Of the 30 patients 15 were female and 15 male. Maternal history showed seven mothers that received misoprostol and four that had metrorrhagia in the first trimester of pregnancy. All patients had VII cranial nerve involvement; the involvement was bilateral and symmetric in 20 and asymmetric in the remaining patients. All patients had bilateral VI nerve involvement, some of whom underwent surgery for strabismus, others are on the list for surgery, and a few do not require surgery because of fixation of both eyes in primary gaze position. Conclusion: Moebius syndrome is a rare multifactorial genetic and congenital pathology with multisystemic involvement and increased incidence because of the use of teratogenic drugs requiring early surgical intervention by neuroorthopedic and plastic surgeons, and ophthalmologists, and a multidisciplinary follow-up to provide these children with the best possibilities for functional development and aesthetic repair (AU)

Analysis of agreement between Visual Analogue Scales (VAS) and numerical questions to assess perception of teratogenic risks in treatment with drugs and radiotherapy in women / Análise de concordância entre as escalas visual analógica (VAS) e questões numéricas para avaliar a percepção de riscos teratogênicos em tratamento com medicamentos e radioterapia em mulheres

To evaluate the agreement between Visual Analogue Scales (VAS) and numerical questions as a way of assessing the perception of teratogenic risk of treatment with drugs and radiotherapy. Methods: the sample comprised 144 pregnant and 143 non-pregnant women consecutively recruited at public health centers in Porto Alegre, in the State of Rio Grande do Sul, from February to August 2011. The perception of risk for congenital malformations in the general population and the perceptions of teratogenic risk for exposure to acetaminophen, meto-clopramide, misoprostol and radiotherapy were measured using VAS and numerical questions. The agreement between the results of the two techniques was tested using a Bland-Altman plot. Results: the medians for the perceptions measured using VAS were higher than those obtained using numerical questions for all variables. The perception of risk for acetaminophen showed the lower bias of the two techniques (bias=13.17; p<0.001) and exposure to radiotherapy, the higher (bias=25.02; p<0.001). Conclusion: there was no agreement between the measurements obtained using the two techniques for any of the risk perceptions under study. Risk perceptions were higher using VAS, for all kinds of exposure. Studies should be conducted to assess whether there is overestimation in other situations and social contexts owing to the use of VAS...

Avaliar a concordância entre Escalas Visuais Analógicas (EVA) e perguntas numéricas para aferir a percepção de risco teratogênico de medicamentos e radioterapia. Métodos: a amostra foi constituída por 144 gestantes e 143 não gestantes recrutadas consecutivamente em centros públicos de saúde de Porto Alegre, RS, entre fevereiro e agosto de 2011. A percepção de risco de malformações congênitas na população geral e as percepções de risco teratogênico das exposições a paracetamol, metoclo-pramida, misoprostol e radioterapia na gestação foram aferidas por EVA e perguntas numéricas. A concordância entre as duas técnicas foi avaliada pela análise gráfica de Bland-Altman Resultados: as medianas das percepções de risco teratogênico medidas por EVA foram superiores às obtidas através da pergunta numérica, para todas as variáveis. A percepção de risco ao paracetamol apresentou o menor viés entre as duas técnicas de aferição (viés=13,17; p<0,001) e a exposição à radioterapia, o maior (viés=25,02;p<0,001). Conclusões: não houve concordância entre as duas técnicas, para nenhuma das percepções de risco estudadas. As percepções de risco foram maiores para EVA, para todas as exposições. Sugerimos a realização de estudos que avaliem se também ocorre superestimação em outras situações e contextos sociais, em função do uso de EVA...

Teratogen exposure and congenital ocular abnormalities in Brazilian patients with Möbius sequence / Exposição à teratógenos e anormalidades oculares congênitas em pacientes brasileiros portadores da sequência de Möbius

Purpose: To assess the sociodemographic profiles, teratogen exposures, and ocular congenital abnormalities in Brazilian patients with Möbius sequence. Method: Forty-four patients were recruited from the Brazilian Möbius Sequence Society. This cross-section comprised 41 patients (age, mean ± standard deviation, 9.0 ± 5.5 years) who fulfilled the inclusion criteria. The parent or caregiver answered a questionnaire regarding sociodemographic data and pregnancy history. Patients underwent ophthalmological assessments. They were subdivided into groups according to misoprostol exposure during pregnancy, and the two groups were compared. Results: Mothers/caregivers reported unplanned pregnancies in 36 (88%) cases. Of these, 19 (53%) used misoprostol during their first trimesters. A stable marital status tended to be more frequent in the unexposed group (P=0.051). Incomplete elementary school education was reported by two (11%) mothers in the exposed group and by three (14%) mothers in the unexposed group (P=0.538). The mothers' gestational exposures to cocaine, marijuana, alcohol, and cigarettes were similar in both groups (P=0.297, P=0.297, P=0.428, and P=0.444, respectively). One (5%) case of Rubella infection during pregnancy was found in the unexposed group. The main malformations in the exposed and unexposed groups were the following: strabismus (72% and 77%, respectively), lack of emotional tearing (47% and 36%, respectively), and lagophthalmos (32% and 41%, respectively). Conclusion: Stable marital statuses tended to be more frequent among mothers that did not take misoprostol during pregnancy. Exposures to other teratogens and the main ocular abnormalities were similar in both groups. .

Objetivo: Descrever o perfil sóciodemográfico, exposição à teratógenos e anormalidades oculares congênitas em pacientes brasileiros portadores da sequência de Möbius Método: Quarenta e quatro pacientes recrutados da Sociedade Brasileira de Sequência de Möbius foram examinados. Este estudo transversal incluiu 41 pacientes que preencheram os critérios de inclusão do estudo (média das idades: 9,0 ± 5,5 anos). Mãe/responsável dos pacientes responderam a um questionário sobre perfil sóciodemográfico e história gestacional. Foi realizado exame oftalmológico de todos os pacientes. Eles foram agrupados em dois grupos de acordo com a exposição ao misoprostol durante a gestação e seus dados foram comparados. Resultados: Mães/responsáveis referiram gravidez indesejada em 36 (88%) dos casos. Destas, 19 (53%) fizeram uso de misoprostol no primeiro trimestre de gestação. Houve uma tendência do grupo de mães não expostas ao misoprostol de terem um estado civil estável (P=0,051). Duas (11%) mães do grupo de expostas ao misoprostol relataram primeiro grau incompleto e três (14%) do grupo de não expostas (P=0,538). A exposição das mães à cocaína, maconha, álcool e cigarro foi similar em ambos os grupos (P=0,297, P=0,297, P=0,428, P=0,444, respectivamente). Houve um caso (5%) de Rubéola no grupo de mães não expostas. As principais malformações associadas nos pacientes expostos e não expostos foram, respectivamente: estrabismo (72% e 77%), e diminuição da lágrima emocional (47% e 36%) e lagoftalmia (32% and 41%). Conclusão: Estado civil estável foi mais frequente em mães que não fizeram uso de misoprostol durante a gestação. Exposição à outros ...

Síndrome de Moebius, comunicación interventricular asociado a exposición prenatal a misoprostol / Moebius Syndrome, ventricular septal defect due to prenatal exposure to misoprostol

Introducción: El síndrome o secuencia de Moebius se caracteriza por la afectación del nervio facial y nervio abducens y puede estar asociado a defectos congênitos orofaciales y de las extremidades. Adicionalmente en las dos últimas décadas se han reortada una posible asociación con exposición prenatal a misoprostol. Objetivo: Presentar un caso de síndrome de Moebius con cardiopatía compleja (comunicación interventricular y pseudocoartación de aorta) asociado a exposición prenatal a misoprostol. Caso clínico: Paciente de 5 años quien consulta por antecedente de retardo en el desarrollo psicomotor, anomalías craneofaciales, cardiacas y de las extremidades, con antecedente de exposición prenatal a misoprostol, a quien se le diagnóstica síndrome de Moebius. Conclusiones: Aunque la etiología de este síndrome no es clara, un mecanismo fisiopatológico involucrado es el de la hipoxia que puede ser secundario a la exposición prenatal a misoprostol.

Introduction: Moebius syndrome/sequence is characterized by facial and abducens nerve damage and may be associated with congenital orofacial and limb defects. Additionally, in the last two decades, a possible association with prenatal exposure to misoprostol has been reported. Objective: To present a case of Moebius Syndrome with complex heart disease (ventricular septal defect and pseudocoarctation of the aorta) associated with prenatal exposure to misoprostol. Case report: A 5 year old patient diagnosed with Moebius Syndrome who consulted specialists due to psychomotor retardation, craniofacial, heart and limb defects, and with a history of prenatal exposure to misoprostol is presented. Conclusions: Although the etiology of this syndrome is not clear, hypoxia is a pathophysiological mechanism involved, which can be secondary to prenatal exposure to misoprostol.

Efficacy of rectal misoprostol for prevention of postpartum hemorrhage

Postpartum hemorrhage is an important cause of maternal morbidity and mortality after delivery. Active management of postpartum hemorrhage by an uterotonic drug decreases the rate of postpartum hemorrhage. The aim of this study is to evaluate the efficacy of rectal misoprostol for prevention of postpartum hemorrhage. This double blind randomized clinical trial was performed on full term pregnant women candidate for vaginal delivery, referred to Zahedan Imam Ali Hospital during 2008-2009. They were randomly divided into two groups of rectal misoprostol and oxytocin. The women in misoprostol group received 400 micro g rectal misoprostol after delivery and the women in oxytocin group received 3 IU oxytocin in 1 L ringer serum, intravenously. Rate of bleeding, need to any surgery interventions, rate of transfusion and changes in hemoglobin and hematocrite were compared between two groups. A total of 400 patients [200 cases in misoprostol group and 200 in oxytocin group] entered to the study. Rate of bleeding > 500 cc was significantly higher in oxytocin group than misoprostol group [33% vs. 19%] [p = 0.005]. Also, need to excessive oxytocin for management of postpartum hemorrhage was significantly lower in misoprostol group than oxytocin group [18% vs. 30%] [p = 0.003]. Decrease in hematocrite was significantly more observed in oxytocin group than misoprostol group [mean decrease of hematocrite was 1.3 +/- 1.6 in misoprostol group and 1.6 +/- 2.2 in oxytocin group]. Two groups were similar in terms of side-effects. Rectal misoprostol as an uterotonic drug can decrease postpartum hemorrhage and also can prevent from decrease of hemoglobin as compared to oxytocin

Síndrome de Moebius: descripción de una serie de 6 casos / Moebius syndrome: description of a 6 cases series

La parálisis facial y del nervio abducens congénita fue descrita como entidad clínica en 1888. Esta definición se amplió a parálisis facial unilateral o bilateral completa o incompleta, limitación de abducción ocular, disfunción de otros pares craneales, defectos oro-faciales, músculoesqueléticos y del desarrollo. Los criterios de diagnóstico varían y la entidad sigue siendo subdiagnosticada. El objetivo de este trabajo es caracterizar el cuadro clínico de pacientes con diagnóstico de Síndrome de Moebius, a través de la revisión de seis casos en control en dos Policlínicos de Neurología Infantil. En este grupo, fueron motivo de consulta: falta de esfuerzo respiratorio, hipomimiafacial, trastorno de alimentación. En dos casos hubo uso de misoprostrol durante el embarazo. Los hallazgos del examen incluyeron parálisis facial bilateral (5), unilateral (1), alteración bilateral de abducción ocular (6). Otras malformaciones asociadas fueron: paladar alto, microretrognatia, fisurapalatina, criptorquidia, polidactilia bilateral y pie bot. El conocimiento extendido de las características mínimas para el diagnóstico y de la variedad de manifestaciones de el Síndrome de Moebius, facilitan su reconocimiento y tratamiento oportuno.

Congenital facial and abducens nerves palsy were first described as a clinical entity in 1888. Later the definition was expanded to unilateral or bilateral facial palsy, limitation of ocular abduction, other cranial nerves involvement, orofacial, musculoskeletal or developmental defects. Diagnostic criteria vary among authors and the condition remains probably underdiagnosed. The aim of this study is to characterize the clinical features of Moebius Syndrome in a group of six patients diagnosed and controlled at two Child Neurology Outpatients Clinics. In this group, the main complaint at first consultation was: lack of respiratory effort, facial hypomimia, eating disorder. The use of misoprostol during pregnancy was identified in two cases. Findings on physical examination included bilateral (5) and unilateral (1) facial palsy, bilaterally impaired conjugate gaze (6).Other associated findings were: high palate, microretrognathia, cleft palate, polydactyly, bilateral cryptorchidism and clubfoot. The extended knowledge of minimal criteria required for Moebius Syndrome diagnosis, as well as other associated features, will facilitate recognition and timely treatment.

Aborto e misoprostol: usos médicos, práticas de saúde e controvérsia científica / Abortion and misoprostol: health practices and scientific controversy

Este artigo coloca em perspectiva a controvérsia entre a associação do uso de misoprostol para aborto e teratogenicidade, encontrada em estudos do tipo relato de caso, e a consagração do uso de medicamentos à base do fármaco na área médico-obstétrica e em documentos normativos nacionais e internacionais que regulam o registro e a circulação de produtos farmacêuticos. Através do método monográfico, foram revisados, sistematizados e analisados documentos oficiais da Anvisa, Ministério da Saúde e Organização Mundial da Saúde sobre o uso do misoprostol, bem como 68 artigos do tipo relato de casos clínicos, publicados em periódicos científicos nacionais, que associam aborto, misoprostol e teratogenicidade. A interdição legal do aborto impede a prescrição e o uso adequados de uma droga que produz efeitos eficazes e seguros como o misoprostol. Assim, o grande malefício à saúde de mulheres está ligado não a características intrínsecas ao fármaco, mas a argumentos morais que representam descaso e desrespeito aos direitos fundamentais de mulheres.

This article puts into perspective the controversy between the association of the use of misoprostol for abortion and teratogenicity studies of the type found in a case report. The use of herbal medicinal drugs and the medical-obstetric and national and international norms governing the registration and circulation of pharmaceutical products were examined. Official documents of ANVISA, the Ministry of Health and the World Health Organization on the use of misoprostol, as well as 68 articles such as case reports published in national journals, linking abortion, misoprostol and teratogenicity were reviewed, systematically filed and analyzed using the monographic method. The legal prohibition of abortion prevents the proper prescription and use of a drug such as misoprostol that is both safe and effective. Thus, the danger for the health of women is linked not to the intrinsic characteristics of the drug, but to the moral arguments that constitute negligence and disregard for the fundamental rights of women.

Profile of ocular and systemic characteristics in Möbius sequence patients from Brazil and Italy / Perfil de características oculares e sistêmicas de pacientes com a sequência de Möbius do Brasil e da Itália

PURPOSE: To compare the profiles and clinical findings of a series of patients with Möbius sequence from Brazil with a series from Italy. METHODS: This is a multicenter study, which includes 46 Möbius sequence patients from Brazil and 20 from Italy. Socio-demographic, gestational, and neonatal profile characteristics were collected from interviews with the guardians of the Möbius sequence patients and compared. The Möbius sequence patients were submitted to an ophthalmologic examination and systemic malformations were also evaluated. RESULTS: Misoprostol was used in the first trimester of pregnancy by 26 (56.5%) of the mothers of the Möbius sequence patients in the Brazilian series and was not used by any of the Italian mothers. The mean age of the Brazilian Möbius sequence patients was 89.95 ± 7.79 months and the mean age of the Italian patients was 102.6 ± 22.94 months (P=0.6105; Mann-Whitney test). Brazilian mothers had a significantly lower education level (P=0.0002; Fisher's exact test) and Italian mothers had significantly more stable relationships (p=0.0002; Fisher's exact test). The frequency of ocular and systemic abnormalities was similar in both series. CONCLUSION: Adverse events during pregnancy varied between both groups. A history of misoprostol use during early pregnancy was present only in Brazilian mothers, who had lower levels of education and less frequent stable marital statuses. Clinical findings were similar between both groups of patients.

OBJETIVO: Comparar o perfil de características oculares e sistêmicas de uma série de pacientes com sequência de Möbius do Brasil com uma da Itália. MÉTODOS: Esse estudo multicêntrico incluiu 46 pacientes com sequencia de Möbius do Brasil e 20 da Itália. As características dos perfis sociodemográfico, gestacional e neonatal foram coletadas a partir de entrevistas com os responsáveis dos pacientes e comparadas. Os pacientes foram submetidos a um exame oftalmológico e malformações sistêmicas foram avaliadas. RESULTADOS: O misoprostol foi usado no primeiro trimestre da gestação por 26 (56,5%) mães brasileiras e por nenhuma italiana. A média de idade dos pacientes brasileiros com sequência de Möbius foi de 89,95 ± 7,79 meses e dos italianos 102,6 ± 22,94 meses (P=0,6105; teste de Mann-Whitney). Mães brasileiras tinham significantemente menor escolaridade (P=0,0002; teste exato de Fisher) e mães italianas tinha relacionamentos estáveis mais frequentemente (P=0,0002; teste exato de Fisher). A frequência de anormalidades oculares e sistêmicas foi semelhante entre as séries. CONCLUSÃO: Eventos adversos durante a gestação variaram entre os grupos. O uso de misoprostol pelas mães precocemente na gestação foi relatado apenas por mães brasileiras, que tinham menor escolaridade e status conjugal estável menos frequentemente. Achados clínicos foram semelhantes entre os grupos.

Comparación del efecto del misoprostol sublingual y la oxitocina endovenosa en la pérdida sanguínea durante la cesárea / Comparison of the effect of sublingual misoprostol and intravenous oxytocin on blood loss at caesarean section

Se realizó un estudio prospectivo, descriptivo, al azar, doble ciego para comparar la efectividad de la oxitocina endovenosa y el misoprostol sublingual en la reducción de la pérdida sanguínea durante la realización de cesárea electiva. Se estudió una muestra de 58 pacientes con embarazo simple a término e indicación de cesárea electiva ajo anestesia regional, atendidas en el servicio de Obstetricia del Hospital Universitario de Caracas entre agosto de 2007 y febrero de 2009. Se distribuyeron en 2 grupos de 29 pacientes cada uno. El grupo A recibió 400 µg de misoprostol sublingual y 100 mL de solución fisiológica en infusión endovenosa. El grupo B recibió una cantidad equivalente de placebo sublingual y 20 UI de oxitocina diluídas en 1200 mL de solución fisiológica en infusión endovenosa. La variación de la hemoglobina y el hematocrito fue de 1,5 ± 0,9 g/dL y 4,2 ± 2,6 % en el grupo A y de 1,2 ± 0,7 g/dL y 3,7 ± 3,2 % en el grupo B. Estas diferencias no fueron estadísticamente significativas. El misoprostol sublingual y la oxitocina endovenosa son igualmente efectivas en la reducción de la pérdida sanguínea durante la cesárea electiva

It was made a prospective, descriptive and randomized, double blind study to compare the effectivity between endovenous oxytocin and sublingual misoprostol in the blood loss reduction during elective cesarean section. It was studied a sample of 58 patients with term simple pregnancy and indication of elective cesarean under regional anesthesia, who were attended in the Obstetrician Service from the Hospital Universitario de Caracas between August, 2007 and February, 2009. They were distributed in two groups of 29 patients each one. Group A received 400 µg of sublingual misoprostol and 100 mL of saline solution in endovenous infusion. Group B received equal dosis of sublingual placebo and 20 UI of endovenous infusion of oxytocin diluted in 100 mL of saline solution. Hemoglobin and hematocrit variation was 1,5 ± 0,9 g/dL and 4,2 ± 2,6 % in group A and 1,2 ± 0,7 g/dL y 3,7 ± 3,2 % in group B. These differences were not statistically significative. Sublingual misoprostol and endovenous oxytocin are equally efective in the reduction of blood loss during elective cesarean

Efecto teratogénico del misoprostol: un estudio prospectivo en Argentina / Misoprostol teratogenicity: a prospective study in Argentina

Introducción. El misoprostol se emplea popularmente en la Argentina para intentar la interrupción del embarazo, pero cierta proporción de los embarazos continúa. Asimismo, diferentes informes mostraron asociación entre el misoprostol y defectos congénitos. Objetivos. Estimar el riesgo de anomalías congénitas en niños expuestos prenatalmente al misoprostol y conocer su forma de consumo durante la gestación. Método. Estudio de cohortes que comparó la frecuencia de aborto y de anomalías congénitas mayores en la descendencia de embarazadas expuestas al misoprostol (94) y de un grupo de embarazadas no expuestas (401), ambos grupos consultantes a un servicio de información sobre agentes teratogénicos. Resultados. Entre las mujeres expuestas al misoprostol solo el 8,2 por ciento lo compró con receta; el 81,5 por ciento se enteró de su efecto abortivo por una amiga, vecina o pariente; la dosis promedio fue 1439 mg; el 77,2 por ciento lo usó tanto por vía oral como vaginal; la edad gestacional promedio de consumo fue a los 48,5 días y el 35,2 por ciento empleó un agente abortivo adicional. Las mujeres expuestas al misoprostol presentaron una frecuencia significativamente mayor de abortos (expuestas: 17/94= 18,1 por ciento; no expuestas; 29/401= 7,2 por ciento; RR= 2,27; IC 95 por ciento:1,30-3,98), y de descendencia con anomalías congénitas mayores (expuestas:5/77= 6,49 por ciento; no expuestas: 8/372= 2,15 por ciento; RR= 3,02; IC 95 por ciento:1,02-8,98). Los cinco niños malformados prenatalmente expuestos al misoprostol presentaron:1) encefalocele y defectos transversales de miembros; 2) porencefalia; 3) malformación pulmonar adenomatosa quística; 4) encefalocele occipital y 5) mal rotación intestinal. Conclusiones. El estudio detectó una asociación significativa entre la exposición prenatal a misoprostol y la ocurrencia de anomalías congénitas mayores.

Introduction. Misoprostol is commonly used in Argentina to attempt abortion, although a certain proportion of pregnancies is not interrupted. On the other hand, various reports showed anassociation between misoprostol and congenital anomalies. Objectives. To estimate the risk of major congenitalanomalies in children prenatally exposed to misoprostol, and to know their way of consumption during pregnancy. Method. A cohort study compared the frequencyof abortion and major congenital abnormalities in offspring of pregnant women exposed to misoprostol (94) and an unexposed group of pregnant women (401), both groups consulting to a teratology information service. Results. Among women exposed to misoprostolonly the 8.2% purchased it on prescription, 81.5% heard about its abortifacient effect by friends, neighbors or relatives, the average dose was 1.439 mg which was used both orallyand vaginally by the 77.2%; the mean gestational age was 48.5 days and 35.2% used an additional abortive agent. Women exposed to misoprostolhad a significantly higher frequency of abortions (exposed: 17/94= 18.1%, unexposed, 29/401= 7.2%, RR= 2.27, 95%: 1,30-3,98), and offspring with major congenital abnormalities (exposed:5/77= 6.49%, unexposed: 8/372= 2.15%, RR= 3.02, 95%:1,02-8.98). The five malformed children prenatally exposed to misoprostol showed: 1) encephalocele and transverse limb defects; 2) porencephaly, 3) pulmonary adenomatous cystic malformation, 4) occipital encephalocele and, 5)intestinal malrotation. Conclusions. The study found a significant associationbetween prenatal exposure to misoprostol and the occurrence of major congenital anomalies.

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.

O comércio de medicamentos de gênero na mídia impressa brasileira: misoprostol e mulheres / The illegal market for gender-related drugs as portrayed in the Brazilian news media: the case of misoprostol and women

Este artigo analisa como a mídia impressa brasileira noticia o comércio clandestino do misoprostol, o principal medicamento para aborto. Foram recuperadas 1.429 notícias, de 220 veículos de informação impressos e eletrônicos, entre 2004 e 2009. A análise foi realizada em 524 notícias de 62 veículos impressos regionais e nacionais. O misoprostol é pauta permanente, mas o enquadramento das notícias é policial, diverso do aborto como uma questão religiosa, política e de saúde pública que domina a mídia brasileira. O misoprostol está inserido no mercado ilegal de medicamentos de gênero, tais como os para emagrecimento, disfunção erétil ou anabolizantes. Sessenta e quatro (12 por cento) notícias impressas apresentam histórias de vida de mulheres que abortaram com o misoprostol. As mulheres têm de 13 a 46 anos e sua inserção de classe demarca diferentes experiências de aborto. Três personagens foram identificados nos itinerários de aborto: amigas, intermediários e médicos. As histórias de aborto tardio são confundidas com a tipificação penal do infanticídio e são casos-limite para a narrativa midiática.

This article analyzes how the Brazilian news media covers the illegal market for misoprostol, the main drug used to induce abortion. A total of 1,429 news stories were retrieved from 220 print and electronic media channels from 2004 to 2009. The analysis included 524 stories from 62 regional and national newspapers. Misoprostol appeared repeatedly in the news, but was usually approached from a criminal perspective, unlike abortion as a whole, which the Brazilian media routinely covers as a religious, political, and public health issue. Misoprostol is part of the illegal gender-related drug market, along with drugs for weight loss and erectile dysfunction and anabolic steroids. Sixty-four (12 percent) of the news stories told life histories of women who had aborted with misoprostol. The women's ages ranged from 13 to 46 years, and socioeconomic status was associated with different experiences with abortion. Three characters appeared in the women's abortion itineraries: girlfriends (confidantes), go-betweens, and physicians. Stories of late-stage abortion are confused with the criminal characterization of infanticide and provide the extreme cases in the media's narrative on abortion.

comparison of two protocols of intravaginal misoprostol for second trimestrer medical termination of pregnancy

To compare the efficacy and side effect profiles of two different dosage protocols of intravaginal misoprostol. Randomized control trial. Department of Gynaecology and Obstetrics, Combined Military Hospital, Rawalpindi, from May 2006 to December 2006. A total of 128 women's, aged 18-40 years, planned for 2nd trimester pregnancy termination, were randomly assigned to two groups of 64 each. Group - I women received vaginal misoprostol 400ug three hourly for a maximum of 8 doses in 24 hours. Women in group-II received vaginal misoprostol 400ug six hourly for a maximum of four doses in 24 hours. If abortion did not occur in 24 hours, the same regimens were repeated. Without successful abortion in 48 hours, misoprostol administration was abandoned in favour of surgical induction. The median induction to abortion interval in group - I [14.4 hours] was shorter than in group - II [182] [p< 0.001]. The frequency of fever was more common in group - I [p = 0.01]. The pregnancy related symptoms decreased in both groups after misoprostol and decrease in breast tenderness was most marked two to three hours after administration. Misoprostol induced fever was seen at least five hours after administration in up to 37.5% women, this peak being slightly higher and occurring earlier in group - I than in group - II. Lower abdominal pain peaked after three to four hours in group - I and after five to six hours in group - II, with no significant difference in pain intensity or analgesic requirements. Other common side effect were diarrhea followed by nausea and vomiting in both the groups. Protocol of 400ug misoprostol administered 6 hourly / 24 hours is more effective in reducing induction - abortion interval and inducing successful abortion within 48 hours without any major increase in side effects

Prevention of NSAID-Associated Gastroduodenal Injury in Healthy Volunteers-A Randomized, Double-Blind, Multicenter Study Comparing DA-9601 with Misoprostol

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 microg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.

Abortamento provocado e o uso de contraceptivos em adolescentes / Provoked abortion and the use of contraceptives by adolescents

JUSTIFICATIVA E OBJETIVOS: A adolescência favorece as vivências da sexualidade. Com o uso incorreto dos métodos anticoncepcionais, resultando em gravidez não planejada e desfecho no abortamento provocado. Esse estudo objetivou descrever aspectos do comportamento sexual e reprodutivo e analisar o tipo de abortamento.MÉTODO: Aplicou-se um método descritivo por meio de questionário estruturado no atendimento a 201 adolescentes com abortamento incompleto submetidas à curetagem uterina, em hospital do Sistema Único de Saúde (SUS), em Maceió, AL, entre março de 2008 a abril de 2009.RESULTADOS: O desfecho da gravidez, quanto ao tipo de abortamento 1,99% abortamento espontâneo e 98,01% abortamento provocado, dados obtido através da classificação da Organização Mundial da Saúde (OMS). Destes, 81,59% são certamente provocados, 9,95%, provavelmente provocado; 6,47% são possivelmente provocados. Entre as adolescentes que assumiram a indução do aborto, 127 (77,44%) referiram o uso do misoprostol. O perfil com risco para provocarem o aborto, idade acima de 16 anos; com parceiro estável; mulatas; não usavam preservativos nas relações sexuais; média de idade de início de atividade sexual de 15 anos, não planejaram a gestação; desejavam a gravidez; primigestas; idade gestacional menor que 15 semanas.CONCLUSÃO: Recomenda-se maior investimento público na assistência ao uso de métodos contraceptivos entre os adolescentes respeitando seus direitos sexuais e reprodutivos, contribuindo assim, para a diminuição da incidência do abortamento, haja vista que as adolescentes estão engravidando e buscando o aborto como solução para gravidez não planejada.(AU)

BACKGROUND AND OBJECTIVES: Adolescence favours the coexistence of sexuality. The incorrect use of contraceptive methods results in unplanned pregnancy which leads towards provoked abortion. The very objective of this study is to describe sexual and reproductive behaviour aspects as well as to analyse the type of abortion in question.METHOD:A descriptive method carried out through interviews by means of a questionnaire was applied and it was duly structured for the data gathering from 201 adolescents facing incomplete abortion subjected to uterine curettage in hospitals which are part of the Stately Run Health Programme, in Maceió, Alagoas, Brazil, between the months of March 2008 and April 2009.RESULTS: The pregnancy data regarding the type of abortion reached the following numbers: 1.99% of spontaneous abortion and 98.01% of provoked abortion and the data was obtained through classified information from the World Health Organization. From the above cited data, 81.59% were certainly provoked; 9.95% were probably provoked; 6.47% were possibly provoked. Amongst the adolescents whom actually admitted the induction to abortion, 127 (77.44%) referred to and reported the use of misoprostol. The profiled adolescents running the risk of provoking abortion is aged above 15 years old; with a stable partner; they are mullatos; they did not use contraceptive methods during the sexual relationships; the average age for the beginning of their sexual activities was 15 years old; they did not plan gestation, but wished for pregnancy; they were first time pregnant females; with a gestational age below 15 weeks.CONCLUSION: It is hereby recommended a higher and major public investment in assistance programmes concerning the use of contraceptive methods amongst adolescents duly respecting their sexual and reproductive rights thus contributing towards the reduction of abortion incidence, considering the fact that the said adolescents are becoming pregnant and looking for abortion as a solution for their unplanned pregnancy.(AU)

Reacciones adversas del misoprostol por vía vaginal en el aborto farmacológico / Adverse reactions of misoprostol by vaginal route in the pharmacological abortion

Se analizaron retrospectivamente 9 estudios clínicos sobre las reacciones adversas del misoprostol por vía vaginal para abortar y su relación con características de las mujeres. Se utilizó la información de 3 ensayos clínicos en que se administró methotrexate oral o intramuscular previo al uso del misoprostol y de un estudio clínico en que la dosis que provocó el aborto de misoprostol fue de 1000 microgramos (µg). Las reacciones adversas más frecuentes fueron los escalofríos, náuseas, vómitos, diarreas y mareos, con excepción del escalofrío, se asociaron significativamente con casi todas las características de las mujeres estudiadas. Los resultados del análisis factorial simple, confirmó la asociación significativa entre la paridad y las náuseas (p=0.026), la paridad y los vómitos (p=0.006), y la asociación entre la ocurrencia de diarreas y la edad gestacional (p=0.0001), no fue así con el resto de las variables estudiadas. Se encontraron diferencias entre los tipos de reacciones adversas ocurridas después de un pre- tratamiento con methotrexate hasta 7 días antes de la administración de la prostaglandina. Casi todas las reacciones adversas al misoprostol cuando se administraron dosis vaginales de 1000 µg fueron muy significativamente mayores que las presentadas cuando se usaron dosis de 800 (µg).

Nine clinical studies were analyzed retrospectively on the adverse reactions of vaginal misoprostol for abortion and its relation with women characteristics. The information of 3 clinical trials was used, in which oral or intramuscular methotrexate was administered before using misoprostol and doing a clinical study, where the dose of misoprostol that caused abortion was 1000 micrograms (µg). The most frequent adverse reactions were chills, nauseas, vomits, diarrhoeas and dizziness; these characteristics, with the exception of chill, were significantly associated with almost all the characteristics of the studied women. The results of the simple factor analysis, confirmed the significant association between parity and nauseas (p=0.026), parity and vomits (p=0.006), and the association between the occurrence of diarrhoeas and the gestacional age (p=0.0001), It was not the same with the rest of the studied variables. Differences between the types of adverse reactions were detected after a previous treatment with methotrexate until 7 days before the administration of the prostaglandin. Almost all the adverse reactions to misoprostol were significantly higher when vaginal doses of 1000 µg were administered than those presented when doses of 800µg were used.