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.

[Medical treatment of ectopic pregnancy]

The ectopic pregnancy [EP] is a public health problem and its frequency has doubled in most industrialized countries in 20 years. To evaluate the effectiveness of medical treatment of ectopic pregnancy with methotrexate [MTX] intramuscularly [IM]. prospective study supported between October 2006 and December 2010. The selected patients received methotrexate IM [1 mg per kg]. The monitoring was based on: the kinetics of plasma HCG, clinical examination and ultrasound. A second injection was performed if hCG on day 4 was increased by more than 25% or J7> the initial rate. Healing corresponded to obtain a zero rate of HCG in a stable manner. We used the first-line medical treatment in 122 patients. The average age of patients was 31.94 years. A haematosalpinx was found in 87.70% of cases. The initial rate of HCG plasma varied between 40 lU/ml and 4088 IU / ml, with an average of 805.88 m IU / ml. The primary success rate obtained after a single injection of intramuscular MTX was 67%. The high success rate obtained after two injections of MTX was 27%. The overall success rate after 1 or 2 injections of MTX was 82%. 17 patients underwent surgical treatment after a first injection of methotrexate. 5 patients underwent surgery after receiving two doses of methotrexate. The period of normalization of plasma levels of h CG was 24 days on average, with extremes ranging from 4 to 43 days for 67 patients cured after a single injection of MTX. This period was 33 days on average, with extremes ranging from 8 to 62 days for patients healed after two injections of MTX. Medical treatment applied to 38% of ectopic pregnancies diagnosed in our department is effective in 82% of cases if the inclusion criteria are strictly adhered to. Successful treatment is limited by patient compliance and demanding nature of monitoring

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.

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.

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 ...

Pentalogía de Cantrell en un recién nacido expuesto en útero a misoprostol / Pentalogy of Cantrell in a newborn associated with prenatal exposure to misoprostol

El misoprostol es un análogo sintético de la prostaglandina E1 y es usada por sus efectos utero-tónicos como abortivo. En los países donde se utiliza como abortivo sin éxito durante el primer trimestre de gestación, se han informado un espectro de malformaciones congenitas asociadas con la exposición prenatal, que incluyen el síndrome de Moebius, defectos de la pared abdominal, artrogriposis y anomalías por reducción de los miembros, entre otros. La pentalogía de Cantrell (PC), con una prevalencia de 1 en 65.000 nacidos vivos, es un síndrome polimalformativo que consta de 5 anomalías: un defecto de la pared abdominal, defecto esternal inferior, defecto del diafragma anterior, defecto pericárdico diafragmático y anormalidades congenitas del corazón. Se reporta un caso de pentalogía de Cantrell asociado al uso de misoprostol en el primer trimestre de la gestación, siendo este reporte el primer registro de esta asociación.

Misoprostol is a synthetic analogue of prostaglandin E1 and is used for effects such as uterotonic aborti-facient. In countries where abortion is used as unsuccessful in the first trimester of gestation, reported a spectrum of congenital malformations associated with prenatal exposure, which include Moebius syndrome, abdominal wall defects, and anomalies as artrogriposis reduction members, among others. The pentalogy of Cantrell with a prevalence of 1 in 65,000 live births, is a syndrome consisting of 5 abnormalities: a defect in the abdominal wall, lower sternal defect, defect above the diaphragm, diaphragmatic pericardial defect, and congenital abnormalities of the heart. We report a case of Pentalogy of Cantrell associated with the use of misoprostol in the first trimester of pregnancy, this report is the first record of this association.

Fibular dimelia and mirror polydactyly of the foot in a girl presenting additional features of the VACTERL association / Dimelia fibular e polidactilia em espelho do pé em uma menina apresentando achados adicionais de associação VACTERL

CONTEXT: The association between fibular dimelia and mirror polydactyly of the foot is considered to be a very rare lower-limb abnormality. On the other hand, VACTERL is an acronym for a nonrandom association of congenital anomalies for which the etiology is still poorly understood. CASE REPORT: The patient was a seven-month-old white girl whose mother had used misoprostol in the second month of pregnancy to induce abortion. On clinical evaluation, she was small for her age and presented hypotonia, anteverted nares, long philtrum and carp-like mouth. Her left hand had a reduction defect, with absence of the extremities of the second, third and fifth fingers and camptodactyly of the fourth finger. The ipsilateral lower limb presented significant shortening, especially rhizomelic shortening. Her left foot had a mirror configuration with seven toes and no identifiable hallux. The pelvis was hypoplastic. Esophageal atresia with tracheoesophageal fistula and imperforate anus were detected during the neonatal period. Abdominal ultrasound identified agenesis of the right kidney and left pyelocaliceal duplication. Radiographic evaluation on the left side showed iliac and femoral hypoplasia, absence of the tibia with a duplicated fibula and seven metatarsals and toes with no identifiable hallux on the foot. Echocardiography demonstrated an atrial septal defect. Based on the literature, we believe that the spectrum of malformations presented by our patient may be related to the vascular disruptive effect of the misoprostol. However, we cannot rule out the possibility that this association might simply be a coincidence.

CONTEXTO: A associação entre dimelia fibular e polidactilia em espelho do pé é considerada uma anormalidade de membro inferior bastante rara. Por outro lado, VACTERL é um acrônimo para uma associação não aleatória de anomalias congênitas cuja etiologia ainda é pouco compreendida. RELATO DO CASO: A paciente era uma menina branca de sete meses de idade, cuja mãe utilizou misoprostol no segundo mês de gravidez para indução de aborto. Na avaliação clínica, ela era pequena para a idade e apresentava hipotonia, narinas antevertidas, filtro longo e boca em carpa. A mão esquerda apresentava um defeito de redução com ausência das extremidades do segundo, terceiro e quinto dedos e camptodactilia do quarto. O membro inferior ipsilateral apresentava um importante encurtamento, especialmente rizomélico. O pé possuía uma configuração em espelho com sete dedos e nenhum hálux identificável. A pelve era hipoplásica. Atresia de esôfago com fístula traqueoesofágica e imperfuração anal foram detectadas durante o período neonatal. O ultrassom abdominal identificou agenesia do rim direito e duplicidade pielocalicial à esquerda. A avaliação radiográfica mostrou, no lado esquerdo, hipoplasia do osso ilíaco e do fêmur, ausência da tíbia com duplicação da fíbula, e presença de sete metatarsos e dedos, sem um hálux identificável, no pé. A ecocardiografia identificou um defeito do septo atrial. Acreditamos, com base na literatura, que o espectro de anormalidades apresentado por nossa paciente possa estar relacionado com o efeito disruptivo vascular do misoprostol. Entretanto, não podemos excluir a possibilidade de que essa associação possa ter sido simplesmente uma coincidência.

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.

Embriopatías asociadas al uso de misoprostol / Moebius syndrome and arthrogriposis associated to the use of misoprostol

Se presenta un caso clínico de síndrome de Moebius y artrogriposis asociado al uso de misoprostol durante el primer trimestre de gestación.

We present a case of Moebius syndrome and arthrogriposis associated to the use of misoprostol during the first trimester of gestation.

Prevention and treatment of vaginal bleeding after drug-induced abortion by Yaoliuan capsule and its effects on menses recovery / 华中科技大学学报（医学）（英德文版）

In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period < or = 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8%) of complete abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.

Misoprostal use for therapeutic abortion in Siriraj Hospital: the year 2000.

OBJECTIVE: To evaluate the efficacy and the adverse effects of misoprostal usage for therapeutic abortion in Siriraj Hospital. STUDY DESIGN: Cross-sectional, descriptive study. MATERIAL AND METHOD: A consecutive series of 101 therapeutic abortions was performed in the Department of Obstetrics & Gynecology, Siriraj Hospital in the year 2000. The patients were interviewed for general information and registered, as well as in-patient data. Any adverse events were recorded and collected from the inpatient record file. All data were analyzed statistically. RESULTS: 42 therapeutic abortions were conducted in association with misoprostal usage. Misoprostal was used for cervical ripening in 8 patients with a good outcome. 31 therapeutic abortions were induced by misoprostal alone regimen. A higher success rate (74.1%) was correlated with higher gestational age. 27 out of 31 cases were second trimester abortion. The induction to abortion interval was 18.0+/-10.5 hours (range 5-48). No factor, including age, weight, total dose of misoprostal use, nulliparity and viability of the fetus, could be demonstrated to affect the misoprostal activity defined by induction to abortion interval. There was no serious adverse event, except for severe abdominal cramping (26.2%) and fever (14.3%). CONCLUSION: Misoprostal alone can be used with caution for abortion induction especially in second trimester abortion.

Association of misoprostol, moebius syndrome and congenital central alveolar hypoventilation: case report

We report a case showing the association of Moebius syndrome, the use of misoprostol during pregnancy and the development of central congenital alveolar hypoventilation. Pathophysiological aspects of these three diseases are discussed and also the unfavorable prognosis of this association.