Duration of Induction of Labor for Second-Trimester Medication Abortion and Adverse Outcomes.

OBJECTIVE: To evaluate the relationship between duration of labor during second-trimester medication abortion and adverse outcomes. METHODS: We conducted a retrospective cohort study including all individuals with a singleton gestation undergoing second-trimester medication abortion without evidence of advanced cervical dilation, rupture of membranes, or preterm labor at four centers. The primary exposure was duration of labor (ie, hours spent from receiving misoprostol to fetal expulsion). The primary outcome was composite morbidity , defined as uterine rupture, need for blood transfusion, clinical chorioamnionitis, intensive care unit admission, or need for readmission. We performed bivariate and multivariate negative binomial analyses. A post hoc subgroup analysis was performed to assess for the risk of the primary outcome by gestational age. We performed tests of homogeneity based on history of uterine scarring and parity. RESULTS: Six hundred eighty-one individuals were included. The median duration of labor was 11 hours (interquartile range 8-17 hours). One hundred thirty-one (19.2%) experienced the primary outcome. When duration of labor was evaluated continuously, a longer duration of labor was associated with an increased frequency of morbidity (adjusted ß=0.68, 95% CI, 0.32-1.04). When duration of labor was evaluated categorically, those experiencing the highest quartile of duration (ie, 17 hours or more) had a statistically higher risk for experiencing morbidity compared with individuals in all other quartiles (adjusted relative risk 1.99, 95% CI, 1.34-2.96). When we focused on components of the composite outcome, clinical chorioamnionitis was significantly different between those experiencing a longer duration and those experiencing a shorter duration of labor (26.2% vs 10.6%, P <.001). On subgroup analysis, gestational age was not associated with the risk of composite morbidity. Tests of homogeneity demonstrated no significant difference in the risk for morbidity among individuals with a history of uterine scarring or based on parity. CONCLUSION: Duration of labor was independently associated with risks for adverse maternal outcomes during second-trimester medication abortion, specifically clinical chorioamnionitis.

Efficacy and safety of isosorbide mononitrate plus misoprostol compared to misoprostol alone in the management of the first and second trimester abortion: a systematic review and meta-analysis.

BACKGROUND: However, misoprostol is often used to terminate a pregnancy, but it can also cause side effects. Isosorbide mononitrate (ISMN) can help the cervix mature by increasing the production of prostaglandin E2 and vasodilation. Considering that the results of studies in this field are contradictory, it is the purpose of this study to evaluate the efficacy and safety of vaginal ISMN plus misoprostol compared to misoprostol alone in the management of first- and second-trimester abortions. METHOD: The search process was conducted for MEDLINE through the PubMed interface, Scopus, Web-of-Science, Science Direct, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform until November 10, 2023. Our assessment of bias was based on version 2 of the risk-of-bias tool (RoB2) for randomized trials and our level of evidence quality was determined by GRADE. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1. RESULT: Seven randomized clinical trials were included in the systematic review and three in the meta-analysis, with mixed quality. The results of the meta-analysis revealed that in the second-trimester abortion, the inclusion of ISMN in conjunction with vaginal misoprostol results in a noteworthy reduction in the induction abortion interval, specifically by 4.21 h (95% CI: -7.45 to -0.97, P = 0.01). The addition of vaginal ISMN to misoprostol, compared to vaginal misoprostol alone, increased the odds of a completed abortion by 3.76 times. (95% CI: 1.08 to 13.15, P = 0.04). CONCLUSION: The findings of this study can offer valuable insights aimed at enhancing counseling and support for non-surgical methods of medication abortion within professional settings. Moreover, it improves the effectiveness of clinical treatment and reduces the occurrence of unnecessary surgical interventions in the abortion management protocol.

Readmission following methotrexate treatment for tubal pregnancy.

OBJECTIVE: To identify risk factors for readmission following methotrexate treatment for tubal pregnancy. METHODS: A retrospective study undertaken in two tertiary medical centers, including all individuals with medically treated tubal pregnancy (N = 511), between December 2009 and June 2021. Individuals with and without readmission following methotrexate treatment were compared. The primary outcome was the readmission rate. Secondary outcomes included the rate of post-discharge gynecological emergency department visits, tubal rupture rate, and the eventual need for surgical treatment. RESULTS: Readmission following methotrexate treatment occurred in 224/511 patients (43.8%). Most readmissions were due to abdominal pain or suspicion of treatment failure. Readmitted individuals were more likely to have a history of pelvic inflammatory disease and pretreatment serum human chorionic gonadotropin (hCG) >2000 mIU/mL. Both factors remained significantly associated with higher readmission rates in a logistic regression analysis (adjusted odds ratio [OR] 6.28, 95% confidence interval [CI] 1.30-30.45, and adjusted OR 2.73, 95% CI 1.83-4.07, respectively) after adjustment for age, endometriosis, tubal pathology, abdominal pain, and presence of yolk sac or embryo at diagnosis. A dose-dependent association was observed between pretreatment serum hCG levels and readmission rate (P < 0.001). Pretreatment hCG levels were also associated with tubal rupture and the eventual need for surgical treatment (P < 0.001 for both). A prediction model using hCG was not sufficiently accurate to predict readmission risk. CONCLUSION: Readmission following methotrexate treatment for tubal pregnancy was independently associated with previous pelvic inflammatory disease and pretreatment serum hCG levels. The latter was also associated with surgical intervention rate.

Combination of Mifepristone and Misoprostol for First-Trimester Medical Abortion: A Comprehensive Review of the Literature.

Importance: Several medications have been used to achieve medical abortion in the first trimester of pregnancy. The most commonly used is the combination of mifepristone and misoprostol; however, different doses and routes of administration have been proposed. Objective: The aim of this study was to summarize published data on the effectiveness, adverse effects, and acceptability of the various combinations of mifepristone and misoprostol in medical abortion protocols in the first trimester of pregnancy. Evidence Acquisition: This was a comprehensive review, synthesizing the findings of the literature on the current use of mifepristone and misoprostol for first-trimester abortion. Results: The combination of mifepristone and misoprostol seems to be more effective than misoprostol alone. Regarding the dosages and routes, mifepristone is administered orally, and the optimal dose is 200 mg. The route of administration of misoprostol varies; the sublingual and buccal routes are more effective; however, the vaginal route (800 µg) is associated with fewer adverse effects. Finally, the acceptability rates did not differ significantly. Conclusions: Different schemes for first-trimester medical abortion have been described so far. Future research needs to focus on identifying the method that offers the best trade-off between efficacy and safety in first-trimester medical abortion.

Retrospective cohort study comparing success of medical management of early pregnancy loss in pregnancies conceived with and without medical assistance.

OBJECTIVE: To compare the success rates of medical management using a combined mifepristone and misoprostol protocol in cases of early pregnancy loss (EPL) between women who conceived without medical assistance and those who conceived through in vitro fertilization (IVF), after fresh or frozen embryo transfer, and evaluate for the predictive factors of success, time to first passage of tissue, and time to complete resolution of pregnancy. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Women who presented with EPL below 13 weeks of gestation between June 2013 and July 2021 who were managed medically with mifepristone 200 mg orally and misoprostol 800 mcg vaginally were included in the study. INTERVENTION(S): Medical management with mifepristone and misoprostol; conception without medical assistance vs. post-IVF, after fresh or frozen embryo transfer. MAIN OUTCOME MEASURE(S): We evaluated overall success and performed subgroup analysis according to the mode of conception and compared fresh vs. frozen-thawed embryo transfers for IVF pregnancies. In all groups, we also calculated success according to gestational age and compared the time to first passage of tissue. The potential predictive factors of treatment success were analyzed. The side effects and complications of treatment were recorded. RESULT(S): A total of 930 women were included in the study, 99 (11%) of whom achieved pregnancy after IVF. The overall success of medical treatment was 89% with no statistically significant difference according to the mode of conception (89% vs. 89%) or type of transfer (fresh 89% vs. frozen 89%). Only lower gestational age by sonography was independently predictive of treatment success, showing a negative regression coefficient of ß = -0.333 and an odds ratio of 0.717. The mean time to first passage of tissue was 5.0 ± 2.1 hours. Altogether, 666 women (72%) showed pregnancy resolution on the day of medication administration, an additional 110 women at 1-week follow-up, and a further 74 women after ≥4 weeks on ultrasound. CONCLUSION(S): Medical management of EPL with mifepristone and misoprostol is a highly successful treatment option that results in completed abortion in a timely fashion in both pregnancies conceived without medical assistance and those conceived after IVF.

Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

OBJECTIVES: To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). METHODS: This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. RESULTS: A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). CONCLUSIONS: Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Adjuvant misoprostol or mifepristone for cervical preparation with osmotic dilators before dilation and evacuation.

OBJECTIVES: This study aimed to compare effectiveness and safety of cervical preparation with osmotic dilators plus same-day misoprostol or overnight mifepristone prior to dilation and evacuation (D&E). STUDY DESIGN: We conducted a retrospective cohort analysis of 664 patients initiating abortion between 18 and 22 weeks at an ambulatory health center. We abstracted medical record data from two consecutive 12-month periods in 2017 to 2019. All patients received overnight dilators plus: 600 mcg buccal misoprostol 90 minutes before D&E (period 1); 200 mg oral mifepristone at time of dilators (period 2). Our primary outcome was procedure time. We report frequency of patients experiencing any acute complication, defined as unplanned procedure (i.e., reaspiration, cervical laceration repair, uterine balloon tamponade) or hospital transfer and bleeding complications. RESULTS: We observed higher mean procedure time in the mifepristone group (9.7 ± 5.3 minutes vs 7.9 ± 4.4, p = 0.004). After adjusting for race, ethnicity, insurance, body mass index, parity, prior cesarean, prior uterine surgery, gestational age, provider, trainee participation, and long-acting reversible contraception initiation, the difference remained statistically significant (relative change 1.09, 95% CI 1.01, 1.17) but failed to reach our threshold for clinical significance. The use of additional misoprostol was more common in the mifepristone group, but the use of an additional set of dilators was not different between groups. Acute complications occurred at a frequency of 4.1% in misoprostol group and 4.3% in mifepristone group (p = 0.90). CONCLUSIONS: We found procedure time to be longer with adjunctive mifepristone compared to misoprostol; however, this difference is unlikely to be clinically meaningful. Furthermore, the frequency of acute complications was similar between groups. IMPLICATIONS: Overnight mifepristone at the time of cervical dilator placement is a safe and effective alternative to adjuvant same-day misoprostol for cervical preparation prior to D&E and may offer benefits for clinic flow and patient experience.

When Do Women with Second Trimester Pregnancy Loss Need Repeated Doses of Misoprostol? Insights from a Teaching Hospital.

BACKGROUND: Cases of second trimester pregnancy loss can be treated either pharmacologically or by surgical evacuation. Misoprostol, an E1-prostaglandin analog, is used to facilitate the evacuation of the uterus. OBJECTIVES: To determine the risk factors associated with patients who were treated with five or more repeated doses of misoprostol. METHODS: We conducted a retrospective study of patients treated with vaginal misoprostol at our institution between December 2016 and October 2021 for second trimester pregnancy loss. RESULTS: In total, 114 patients were eligible for analysis; 83 were treated with < 5 doses and 31 with ≥ 5. We recorded each case in which repeated doses were administered, irrespective of predetermined conditions such as gravidity, parity, maternal age, or gestational age. Moreover, cases of five or more misoprostol dosing were not associated with an increased complications rate, except for the increased duration of hospitalization (3.1 vs. 2.2 days, P-value < 0.01). CONCLUSIONS: Repeated dosing could not be predicted before treatment among those treated with vaginally administered misoprostol for second trimester pregnancy loss. However, low complication rates of repeated dosing may reassure both physicians and patients regarding safety, efficacy, and future fertility.

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.

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.

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.