Comparison of two labor induction regimens with intravaginal misoprostol 25 µg and adverse perinatal outcomes.

OBJECTIVE: The aim of the study was to compare two labor induction regimens (4 and 6 h), to determine predictors of successful labor induction with intravaginal misoprostol 25 µg tablets, and to evaluate the association with adverse perinatal outcomes. METHODS: This was a retrospective cohort study that included singleton pregnancies undergoing induction of labor with an intravaginal misoprostol 25 µg tablet between 37 and 42 weeks of gestation. The pregnant women were divided into two groups: Group 1-intravaginal misoprostol 25 µg every 4 h and Group 2-intravaginal misoprostol 25 µg every 6 h. RESULTS: Pregnant women were divided into Group 1 (n=289) and Group 2 (n=278). Group 1 had a higher median number of intravaginal misoprostol 25 µg tablets (3.0 vs. 2.0 tablets, p<0.001), a lower prevalence of postpartum hemorrhage (7.6 vs. 32.7%, p<0.001), and a higher need for oxytocin (odds ratio [OR]: 2.1, 95%CI: 1.47-2.98, p<0.001) than Group 2. Models including intravaginal misoprostol 25 µg tablets every 4 and 6 h [x2(1)=23.7, OR: 4.35, p<0.0001], parity [x2(3)=39.4, OR: 0.59, p=0.031], and Bishop's score [x2(4)=10.8, OR: 0.77, p=0.019] were the best predictors of failure of labor induction. A statistically significant difference between groups was observed between the use of the first intravaginal misoprostol 25 µg tablet at the beginning (Breslow p<0.001) and the end of the active labor phase (Long Hank p=0.002). CONCLUSION: Pregnant women who used intravaginal misoprostol 25 µg every 4 h had a longer time from the labor induction to the beginning of the active phase of labor and higher rates of adverse perinatal outcomes than women who used intravaginal misoprostol 25 µg every 6 h.

Efficacy, Safety, and Acceptability of Misoprostol in the Treatment of Incomplete Miscarriage: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the efficacy, safety, and acceptability of misoprostol in the treatment of incomplete miscarriage. DATA SOURCES: The PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Clinical Trials databases (clinicaltrials.gov) were searched for the relevant articles, and search strategies were developed using a combination of thematic Medical Subject Headings terms and text words. The last search was conducted on July 4, 2022. No language restrictions were applied. SELECTION OF STUDIES: Randomized clinical trials with patients of gestational age up to 6/7 weeks with a diagnosis of incomplete abortion and who were managed with at least 1 of the 3 types of treatment studied were included. A total of 8,087 studies were screened. DATA COLLECTION: Data were synthesized using the statistical package Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). For dichotomous outcomes, the odds ratio (OR) and 95% confidence interval (CI) were derived for each study. Heterogeneity between the trial results was evaluated using the standard test, I2 statistic. DATA SYNTHESIS: When comparing misoprostol with medical vacuum aspiration (MVA), the rate of complete abortion was higher in the MVA group (OR = 0.16; 95%CI = 0.07-0.36). Hemorrhage or heavy bleeding was more common in the misoprostol group (OR = 3.00; 95%CI = 1.96-4.59), but pain after treatment was more common in patients treated with MVA (OR = 0.65; 95%CI = 0.52-0.80). No statistically significant differences were observed in the general acceptability of the treatments. CONCLUSION: Misoprostol has been determined as a safe option with good acceptance by patients.

OBJETIVO: Avaliar a eficácia, segurança e aceitabilidade do misoprostol no tratamento do aborto incompleto. FONTES DE DADOS: Os bancos de dados PubMed, Scopus, Embase, Web of Science, Cochrane Library e bancos de dados de Ensaios Clínicos (clinicaltrials.gov) foram pesquisados para os artigos relevantes, e estratégias de busca foram desenvolvidas usando uma combinação de termos temáticos de Medical Subject Headings e palavras de texto. A última pesquisa foi realizada em 4 de julho de 2022. Nenhuma restrição de idioma foi aplicada. SELEçãO DOS ESTUDOS: Foram incluídos ensaios clínicos randomizados com pacientes com idade gestacional até 6/7 semanas com diagnóstico de aborto incompleto e que foram manejadas com pelo menos um dos três tipos de tratamento estudados. Um total de 8.087 estudos foram selecionados. COLETA DE DADOS: Os dados foram sintetizados usando o pacote estatístico Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). Para resultados dicotômicos, o odds ratio (OR, na sigla em inglês) e o intervalo de confiança (IC) de 95% foram derivados para cada estudo. A heterogeneidade entre os resultados do ensaio foi avaliada usando o teste padrão, estatística I2. SíNTESE DOS DADOS: Ao comparar misoprostol com aspiração a vácuo médico (MVA, na sigla em inglês), a taxa de aborto completo foi maior no grupo MVA (OR = 0,16; IC95% = 0,07­0,36). Hemorragia ou sangramento intenso foi mais comum no grupo do misoprostol (OR = 3,00; 95%CI = 1,96­4,59), mas a dor após o tratamento foi mais comum em pacientes tratados com MVA (OR = 0,65; 95%CI = 0,52­0,80). Não foram observadas diferenças estatisticamente significativas na aceitabilidade geral dos tratamentos. CONCLUSãO: O misoprostol tem se mostrado uma opção segura e com boa aceitação pelos pacientes.

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.

Misoprostol Administration Before Hysteroscopy Procedures - A Retrospective Analysis.

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.

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.

Uterine Inflammatory Response After Prostaglandin E1 (Misoprostol) Infusion Prebreeding or Immediately After Embryo Flushing in Commercial Donor Mares.

Misoprostol, a synthetic PGE1, is becoming a common therapy for mares with suspected uterine tube obstruction. Recently, there have been concerns that uterine administration of misoprostol induces exacerbated uterine inflammation; however, this has not been critically evaluated. This study aimed to assess the inflammatory response and potential systemic reactions after uterine administration of misoprostol, either during prebreeding or immediately after postembryo flushing. Privately owned embryo donor mares (n = 11) were randomly assigned in a crossover design to receive misoprostol (3 mL +200 µg) or sham (3 mL of lactate Ringer's solution) infusions, bilaterally deposited via deep-horn, at least 72 hours prebreeding (experiment 1) or immediately after embryo flushing (experiment 2). Each mare had one cycle for misoprostol and sham in both experiments and a breeding cycle (no sham or misoprostol) between experiments. Uterine edema, fluid accumulation, and the number of uterine PMN were assessed before each infusion and then daily for 72 hours. Uterine lavage was performed the day after each infusion across groups and experiments. Ovulation was hastened with a GnRH agonist and confirmed at 24 hour-intervals. Mares were bred with semen from one of six stallions per owner's choice. Embryo flushing was performed 8 to 9 days postovulation. In either experiment, misoprostol did not affect uterine edema or fluid accumulation (P > .05). However, both the sham and misoprostol infusions increased the number of PMN up to 48 hours postinfusion in both experiments. Embryo recoveries were similar between sham (45%, 5/11) and misoprostol cycles in experiments 1 (45%, 5/11; P > .05) and 2 (sham, 68%, 7/11; misoprostol, 45%, 5/11; P > .05). In conclusion, misoprostol did not induce exacerbated uterine inflammation in mares or systemic adverse reactions when infused prebreeding or immediately after embryo flushing.

Comparison between 200 µg and 800 µg of vaginal misoprostol for cervical ripening before operative hysteroscopy: A randomized controlled trial.

OBJECTIVE: To compare between 200 and 800 µg of vaginal misoprostol for cervical ripening before operative hysteroscopy. METHODS: Quadruple-blind randomized clinical trial conducted between November 2019 and September 2020 involving 76 patients undergoing cervical dilatation before surgical hysteroscopy at teaching hospitals in Pernambuco, Brazil. Women received the vaginal misoprostol dosage of 200 or 800 µg,10-12 h before operative hysteroscopy. The cervical width was the primary outcome, and secondary outcomes were patient satisfaction, adverse effects, surgical complications, and duration of cervical dilatation. Chi-square tests of association, Fisher's exact and Mann-Whitney U tests were used with an α error of <5%. RESULTS: There was no statistical difference between the groups in the mean of the cervical width (800 µg: 6.5 ± 1.6 mm vs 200 µg: 5.8 ± 1.8 mm, P = 0.055), patient satisfaction, and surgical findings, but the duration of cervical dilatation was lower in the 800-µg group (28.16 ± 28.5 s vs 41.97 ± 31.0 s, P = 0.035). Among the adverse effects, diarrhea was more frequent in the 800-µg group with statistical difference (100% vs 0%; P = 0.01). CONCLUSION: For cervical ripening, 200 µg misoprostol is equally effective with fewer adverse effects than 800 µg before operative hysteroscopy. CLINICALTRIALS: gov: NCT04152317. https://clinicaltrials.gov/ct2/show/NCT04152317.

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)

Misoprostol administered sublingually at a dose of 12.5 µg versus vaginally at a dose of 25 µg for the induction of full-term labor: a randomized controlled trial.

BACKGROUND: Labor induction is defined as any procedure that stimulates uterine contractions before labor begins spontaneously. The vaginal and oral routes of administration of misoprostol are those most used for the induction of labor in routine practice, with the recommended dose being 25 µg. Nevertheless, the sublingual route may reduce the number of vaginal examinations required, increasing patient comfort and lowering the risk of maternal and fetal infection. Based on a previous systematic review, the objective of this study was to compare the frequency of tachysystole as the main outcome measure when misoprostol is administered sublingually at the dose of 12.5 µg versus vaginally at a dose of 25 µg to induce labor in a full-term pregnancy with a live fetus. METHODS: A randomized, placebo-controlled, triple-blind clinical trial was conducted at two maternity hospitals in northeastern Brazil. Two hundred patients with a full-term pregnancy, a live fetus, Bishop score ≤ 6 and an indication for induction of labor were included. Following randomization, one group received 12.5 µg misoprostol sublingually and a vaginal placebo, while the other group received a sublingual placebo and 25 µg misoprostol vaginally. The primary outcome was the frequency of tachysystole. Student's t-test, the chi-square test of association and Fisher's exact test were used, as appropriate. Risk ratios and their 95% confidence intervals were calculated. RESULTS: The frequency of tachysystole was lower in the group using 12.5 µg misoprostol sublingually compared to the group using 25 µg misoprostol vaginally (RR = 0.15; 95%CI: 0.02-0.97; p = 0.002). Failure to achieve vaginal delivery within 12 and 24 h was similar in both groups. Sublingual administration was preferred to vaginal administration by women in both groups; however, the difference was not statistically significant. CONCLUSION: The effectiveness of labor induction with low-dose sublingual misoprostol was similar to that achieved with vaginal administration of the recommended dose; however, the rate of tachysystole was lower in the sublingual group, and this route of administration may prove a safe alternative. TRIAL REGISTRATION: Registration number: NCT01406392, ClinicalTrials.gov. Date of registration: August 1, 2011.

High fever after sublingual administration of misoprostol for treatment of post-partum haemorrhage: a hospital-based, prospective observational study in Argentina.

OBJECTIVE: To characterise the occurrence of fever (≥38.0°C) after treatment for post-partum haemorrhage (PPH) with sublingual misoprostol 800 mcg in Latin America, where elevated rates of misoprostol's thermoregulatory effects and recipients' increased susceptibility to high fever have been documented. METHODS: A prospective observational study in hospitals in Argentina enrolled consenting women with atonic PPH after vaginal delivery, eligible to receive misoprostol. Corporal temperature was assessed at 30, 60, 90 and 120 min post-treatment; other effects were recorded. The incidence of high fever ≥ 40.0°C (primary outcome) was compared to the rate observed previously in Ecuador. Logistic regressions were performed to identify clinical and population-based predictors of misoprostol-induced fever. RESULTS: Transient shivering and fever were experienced by 75.5% (37/49) of treated participants and described as acceptable by three-quarters of women interviewed (35/47). The high fever rate was 12.2% (6/49), [95% Confidence Interval (CI) 4.6, 24.8], compared to Ecuador's rate following misoprostol treatment (35.6% (58/163) [95% CI 28.3, 43.5], P = 0.002). Significant predictors of misoprostol-induced fever (model dependent) were as follows: pre-delivery haemoglobin < 11.0g/dl, rapid placental expulsion, and higher age of the woman. No serious outcomes were reported prior to discharge. CONCLUSIONS: Misoprostol to treat PPH in Argentina resulted in a significantly lower rate of high fever than in Ecuador, although both are notably higher than rates seen elsewhere. A greater understanding of misoprostol's side effects and factors involved in their occurrence, including genetics, will help alleviate concerns. The onset of shivering may be the simplest way to know if fever can also be expected.

OBJECTIF: Caractériser la survenue de fièvre (≥ 38,0°C) après traitement d'une hémorragie post-partum (HPP) avec du misoprostol sublingual à 800 mcg en Amérique latine, où des taux élevés d'effets thermorégulateurs du misoprostol et une sensibilité accrue des receveurs à une forte fièvre ont été documentés. MÉTHODES: Une étude observationnelle prospective dans des hôpitaux en Argentine a recruté des femmes consentantes atteintes d'HPP atonique après un accouchement vaginal éligibles pour recevoir du misoprostol. La température corporelle a été évaluée 30, 60, 90 et 120 minutes après le traitement; d'autres effets ont été enregistrés. L'incidence d'une fièvre élevée ≥40,0°C (critère principal) a été comparée au taux observé précédemment en Equateur. Des régressions logistiques ont été effectuées pour identifier les prédicteurs cliniques et ceux basés sur la population de la fièvre induite par le misoprostol . RÉSULTATS: Des frissons transitoires et de la fièvre ont été ressentis par 75% (37/49) des participantes traitées et décrits comme acceptables par les trois quarts des femmes interrogées (35/47). Le taux de fièvre élevé était de 12% (6/49), [intervalle de confiance (IC) à 95%: 4,6, 24,8] contre 35,6% en Equateur après traitement au misoprostol (58/163) [IC95%: 28,3, 43,5], p = 0,002). Les prédicteurs significatifs de la fièvre induite par le misoprostol (selon le modèle) étaient: hémoglobine avant l'accouchement <11,0 g/dL, expulsion placentaire rapide et âge plus élevé de la femme. Aucun résultat sévère n'a été signalé avant le sortie d'hôpital. CONCLUSIONS: Le misoprostol pour traiter l'HPP en Argentine a entraîné un taux de fièvre élevée significativement plus bas qu'en Equateur, bien que les taux dans les deux pays soient notablement plus élevés que les taux observés ailleurs. Une meilleure compréhension des effets secondaires du misoprostol et des facteurs impliqués dans leur apparition, y compris la génétique, aidera à atténuer les inquiétudes. L'apparition de frissons peut être le moyen le plus simple de savoir si l'on peut également s'attendre à de la fièvre.

The "Abortion Pill" Misoprostol in Brazil: Women's Empowerment in a Conservative and Repressive Political Environment.

In the aftermath of the introduction of severe restrictions on abortion in several US states, some activists have argued that providing widespread access to an abortive drug, misoprostol, will transform an induced abortion into a fully private act and therefore will empower women. In Brazil, where abortion is criminalized, the majority of women who wish to terminate an unwanted pregnancy already use the illegal, but easily accessible, misoprostol. We examine the history of misoprostol as an abortifacient in Brazil from the late 1980s until today and the professional debates on the teratogenicity of this drug. The effects of a given pharmaceutical compound, we argue, are always articulated, elicited, and informed within dense networks of sociocultural, economic, legal, and political settings. In a conservative and repressive environment, the use of misoprostol for self-induced abortions, even when supported by formal or informal solidarity networks, is far from being a satisfactory solution to the curbing of women's reproductive rights.

A randomized controlled trial comparing isosorbide dinitrate-oxytocin versus misoprostol-oxytocin at management of foetal intrauterine death.

BACKGROUND: The metabolic activity of endogenous nitric oxide (NO) and the medical use of nitrovasodilatory drugs like isosorbide dinitrate have been shown to be potential inducers inducers of cervical ripening prior to surgical evacuation of the uterus. OBJECTIVE: To assess the therapeutic efficacy and safety of combined isosorbide dinitrate-oxytocin in the management of intrauterine foetal death (IUFD). METHODS: Sixty women with IUFD after 20 weeks of gestation requesting uterine evacuation were randomly selected to receive isosorbide dinitrate gel solution (80 mg/1.5 mL; n = 30) or misoprostol gel solution (100 mcg/1.5 mL; n = 30) every 3 h with a maximum of four doses or until a Bishop score >7 was reached. Subsequently, patients received a high dose of intravenous oxytocin until complete uterus evacuation was achieved. Therapeutic efficacy was evaluated by mean the relative risk of the foetal expulsion based on comparison of event rates, and the proportion of women induced to labor at 7, 10 and 15 h after the administration of isosorbide dinitrate or misoprostol. Safety was assessed on the basis of woman´s vital signs and evaluation of adverse effects, including headache, abdominal pain, pelvic pain, lower back pain, nausea, dizziness and vomiting. RESULTS: The foetal expulsion rate using the isosorbide dinitrate-oxytocin combination was approximately 4.4 times, and at least 2.1 times, the foetal expulsion rate with the misoprostol-oxytocin regimen at any given point in time. The proportion of women achieved vaginal delivery at 15 hours was 100% for the isosorbide dinitrate-oxytocin group and 86.7% for the misoprostol-oxytocin group. The average delivery induction interval was significantly lower when isosorbide dinitrate-oxytocin was used (8.7 ± 3.1 h) than when misoprostol-oxytocin (11.9 ± 3.1 h) was used. A total of 20% of patients in the isosorbide dinitrate-oxytocin group recorded headache, and no cases of uterine tachysystole, haemorrhage or coagulopathy were recorded. CONCLUSION: This study indicates that intravaginal isosorbide dinitrate followed by intravenous oxytocin was more effective than the conventional method used to induce labour in the medical management of foetal death in pregnancies after 20 weeks of gestation. TRIAL REGISTRATION: Clinicaltrials.gov NCT02488642.

Can the Induction of Labor with Misoprostol Increase Maternal Blood Loss?

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 without misoprostol administration). Results There were 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.

Comparison between vaginal and sublingual misoprostol 50 µg for cervical ripening prior to induction of labor: randomized clinical trial.

OBJECTIVE: To compare the effectiveness and safety of sublingual versus vaginal misoprostol on improving the Bishop score after 6 h of administration. METHODS: Randomized clinical trial which includes pregnant women in gestational ages from 32/0 to 41/6, with indication of induction of labor with misoprostol. Bishop score was assessed at the time of induction and 6 h after administration of 50 µg misoprostol. Analysis was made over difference in mean Bishop score of 2 points, using a standard deviation of 2, with 90% power, reaching a 95% confidence interval. RESULTS: 102 patients were studied, 51 received sublingual misoprostol, and 51 received vaginal misoprostol. There was a statistically significant difference in cervical modifications in global terms regardless of the administration route at 6 h (P < 0.05). When analyzing each group, there was no significant difference for the mean and standard deviation for Bishop score for sublingual and vaginal route (P = 0.761). There was no significant difference in terms of mode of delivery, Apgar score, cord pH, nor in the presence of complications. CONCLUSION: There is no statistically significant difference in terms of administration route for cervical ripening using misoprostol 50 µg, whether it was sublingual or vaginal. TRIAL REGISTRATION NUMBER: NCT02732522. Registry website: https://clinicaltrials.gov/ .

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.

Nasoethmoidal meningocele in a child presenting bilateral congenital cystic adenomatoid malformation: Evidence for a new entity or consequence of gestational exposures?

BACKGROUND: Nasoethmoidal meningocele is considered an uncommon type of cephalocele, and congenital cystic adenomatoid malformation (CCAM) is a rare lung disorder characterized by overgrowth of the terminal bronchioles. CASE: We report the unusual association between a nasoethmoidal meningocele and CCAM type II in a fetus exposed to valproic acid and misoprostol. The mother was an 18-year-old woman on her first pregnancy. She had a history of absence seizures since she was 5 years old. She took valproic acid from the beginning of the gestation until the end of the third month. At the end of the third month, she attempted interruption of her pregnancy using misoprostol. The fetal nasoethmoidal meningocele and CCAM type II were identified through morphological ultrasound examination and magnetic resonance imaging. A genome-wide study detected one copy number variation classified as rare, entirely contained into the SPATA5 gene. However, it does not seem to be associated to the clinical findings of the patient. CONCLUSION: To our knowledge, there is only one case reported in the literature showing the same association between a nasoethmoidal meningocele and CCAM. Thus, the malformations observed in our patient may be related to the gestational exposures. Also, we cannot rule out that the patient may present the same condition characterized by a cephalocele and CCAM described by some authors, or even an undescribed entity, because some hallmark features, such as laryngeal atresia and limb defects, were not observed in our case. Further reports will be very important to better understand the associations described in our study.

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)

Defectos transversos terminales de miembros por exposición prenatal al misoprostol / Terminal Transverse Defects Members by Prenatal Exposure to Misoprostol

La exposición prenatal al misoprostol se ha asociado con la ocurrencia de defectos transversos terminales en miembros superiores e inferiores: gastroquisis, hipodactilia e hipoglosia entre otros defectos congénitos. El mecanismo de acción del misoprostol como agente teratogénico ha sido atribuido a un proceso de disrupción vascular con alteración del flujo sanguíneo al feto, lo cual deriva en perfusión inadecuada, hipoxia y hemorragia. Se presenta este caso de niño de dos años de edad con defectos transversos terminales de miembros superiores e inferiores cuya madre utilizó misoprostol en el primer trimestre del embarazo con fines abortivos. Se realiza esta investigación con el objetivo de brindar información sobre los efectos teratogénicos del Misoprostol y alertar sobre las posibles consecuencias de la continuación del embarazo después de su uso con fines abortivos para prevenir el nacimiento de niños con defectos congénitos incompatibles para la vida o con discapacidad permanente

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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 ...