Epilepsia y gestación. Factores asociados con la presencia de crisis en la gestación / Epilepsy and pregnancy. Factors associated with epileptic seizures during pregnancy

Introducción: El manejo de la epilepsia durante la gestación requiere un control óptimo de las crisis, evitando los potenciales efectos teratogénicos del tratamiento antiepiléptico.ObjetivosDescribir las características clínicas y los resultados perinatales de las pacientes con epilepsia gestantes. Analizar los factores que se asocian a la presencia de crisis durante la gestación. Describir los fármacos antiepilépticos más utilizados y analizar los cambios en el régimen terapéutico en dos periodos: de 2000-2010 y 2011-2018.MétodosSe realizó un estudio prospectivo observacional de pacientes con epilepsia que notificaron su gestación en el periodo de 2000-2018. Se evaluó a las pacientes en el primer y segundo trimestre de gestación, tras el parto y al año. Se recogieron variables demográficas, relacionadas con la epilepsia, perinatales y obstétricas.ResultadosSe incluyeron 101 gestaciones. La edad media fue de 32,6 años, el 55,4% tenía una epilepsia focal, el 38,6% una epilepsia generalizada y el 5,9% indeterminada. Se registraron 90 nacidos vivos, nueve abortos espontáneos y cinco malformaciones congénitas, cuatro de ellas en monoterapia con valproato. En 40 gestaciones (39,6%) se registraron crisis, siendo tónico-clónicas generalizadas en 16 (40%). Las variables asociadas con la presencia de crisis durante el embarazo fueron el mal control el año previo a la gestación (66,7% vs. 15,1%, p < 0,001), el tratamiento con dos o más fármacos antiepilépticos (30% vs. 14,8% p < 0,001) y no recibir tratamiento (25% vs. 0% p < 0,001). Los fármacos antiepilépticos más utilizados en monoterapia fueron lamotrigina (n = 19, 27,1%), valproato (n = 17, 24,2%) y levetiracetam (n = 12, 17,1%). En el periodo más reciente (2011-2018) se encontró una mayor proporción de monoterapias (81,5% vs. 55,3%), además de un descenso en el uso de carbamazepina (23,1% vs. 2,3%) y valproato (30,8% vs. 20,5%); y un aumento marcado de levetiracetam (0% vs. 27,3%). (AU)

Introduction: The management of epilepsy during pregnancy requires optimal seizure control, avoiding the potential teratogenic effects of antiepileptic drugs.ObjectivesThis study aims to describe the clinical characteristics and perinatal outcomes of pregnant patients with epilepsy; to analyse the factors associated with seizures during pregnancy; to describe the most commonly used antiepileptic drugs in these patients; and to analyse changes in treatment regimens in 2 periods, 2000-2010 and 2011-2018.MethodsWe conducted a prospective observational study of patients with epilepsy who reported their pregnancy between 2000 and 2018. Patients were evaluated in the first and second trimesters of pregnancy, after delivery, and at one year. Data were collected on demographic variables, epilepsy, and perinatal and obstetric variables.ResultsA total of 101 pregnancies were included. Patients’ mean age was 32.6 years; 55.4% had focal epilepsy, 38.6% had generalised epilepsy, and 5.9% had undetermined epilepsy. We recorded 90 live births, 9 miscarriages, and 5 cases of congenital malformations, 4 of which were born to women who received valproate monotherapy. Forty patients (39.6%) presented seizures, with 16 (40%) presenting generalised tonic-clonic seizures. The variables associated with seizures during pregnancy were poor seizure control in the year prior to pregnancy (66.7% vs. 15.1%; P < .001), treatment with 2 or more antiepileptic drugs (30% vs. 14.8%; P < .001), and untreated epilepsy (25% vs. 0%; P < .001). The antiepileptic drugs most widely used in monotherapy were lamotrigine (n = 19; 27.1%), valproate (n = 17; 24.2%), and levetiracetam (n = 12; 17.1%). In the most recent period (2011-2018), we observed a greater proportion patients receiving monotherapy (81.5%, vs. 55.3%), as well as a decrease in the use of carbamazepine (2.3%, vs. 23.1%) and valproate (20.5%, vs. 30.8%); and a marked increase in the use of levetiracetam (27.3%, vs. 0%). (AU)

Epilepsy and pregnancy. Factors associated with epileptic seizures during pregnancy.

INTRODUCTION: The management of epilepsy during pregnancy requires optimal seizure control, avoiding the potential teratogenic effects of antiepileptic drugs. OBJECTIVES: This study aims to describe the clinical characteristics and perinatal outcomes of pregnant patients with epilepsy; to analyse the factors associated with seizures during pregnancy; to describe the most commonly used antiseizure drugs in these patients; and to analyse changes in treatment regimens in 2 periods, 2000-2010 and 2011-2018. METHODS: We conducted a prospective observational study of patients with epilepsy who reported their pregnancy between 2000 and 2018. Patients were evaluated in the first and second trimesters of pregnancy, after delivery, and at one year. Data were collected on demographic variables, epilepsy, and perinatal and obstetric variables. RESULTS: A total of 101 pregnancies were included. Patients' mean age was 32.6 years; 55.4% had focal epilepsy, 38.6% had generalised epilepsy, and 5.9% had undetermined epilepsy. We recorded 90 live births, 9 miscarriages, and 5 cases of congenital malformations, 4 of which were born to women who received valproate monotherapy. Forty patients (39.6%) presented seizures, with 16 (40%) presenting generalised tonic-clonic seizures. The variables associated with seizures during pregnancy were poor seizure control in the year prior to pregnancy (66.7% vs 15.1%; P < .001), treatment with 2 or more antiseizure drugs (30% vs 14.8%; P < .001), and untreated epilepsy (25% vs 0%; P < .001). Antiseizure medications most widely used in monotherapy were lamotrigine (n = 19; 27.1%), valproate (n = 17; 24.2%), and levetiracetam (n = 12; 17.1%). In the most recent period (2011-2018), we observed a greater proportion of patients receiving monotherapy (81.5%, vs 55.3%), as well as a decrease in the use of carbamazepine (2.3%, vs 23.1%) and valproate (20.5%, vs 30.8%); and a marked increase in the use of levetiracetam (27.3%, vs 0%). CONCLUSIONS: The factors associated with the presence of seizures during pregnancy were previous poor seizure control, treatment with 2 or more antiseizure drugs, and lack of treatment during pregnancy. The most commonly used drugs were lamotrigine, valproate, and levetiracetam, with an increase in levetiracetam use and a decrease in valproate use being observed in the later period (2011-2018).

Epilepsy and pregnancy. Factors associated with epileptic seizures during pregnancy. / Epilepsia y gestación. Factores asociados con la presencia de crisis en la gestación.

INTRODUCTION: The management of epilepsy during pregnancy requires optimal seizure control, avoiding the potential teratogenic effects of antiepileptic drugs. OBJECTIVES: This study aims to describe the clinical characteristics and perinatal outcomes of pregnant patients with epilepsy; to analyse the factors associated with seizures during pregnancy; to describe the most commonly used antiepileptic drugs in these patients; and to analyse changes in treatment regimens in 2 periods, 2000-2010 and 2011-2018. METHODS: We conducted a prospective observational study of patients with epilepsy who reported their pregnancy between 2000 and 2018. Patients were evaluated in the first and second trimesters of pregnancy, after delivery, and at one year. Data were collected on demographic variables, epilepsy, and perinatal and obstetric variables. RESULTS: A total of 101 pregnancies were included. Patients' mean age was 32.6 years; 55.4% had focal epilepsy, 38.6% had generalised epilepsy, and 5.9% had undetermined epilepsy. We recorded 90 live births, 9 miscarriages, and 5 cases of congenital malformations, 4 of which were born to women who received valproate monotherapy. Forty patients (39.6%) presented seizures, with 16 (40%) presenting generalised tonic-clonic seizures. The variables associated with seizures during pregnancy were poor seizure control in the year prior to pregnancy (66.7% vs. 15.1%; P < .001), treatment with 2 or more antiepileptic drugs (30% vs. 14.8%; P < .001), and untreated epilepsy (25% vs. 0%; P < .001). The antiepileptic drugs most widely used in monotherapy were lamotrigine (n = 19; 27.1%), valproate (n = 17; 24.2%), and levetiracetam (n = 12; 17.1%). In the most recent period (2011-2018), we observed a greater proportion patients receiving monotherapy (81.5%, vs. 55.3%), as well as a decrease in the use of carbamazepine (2.3%, vs. 23.1%) and valproate (20.5%, vs. 30.8%); and a marked increase in the use of levetiracetam (27.3%, vs. 0%). CONCLUSIONS: The factors associated with the presence of seizures during pregnancy were previous poor seizure control, treatment with 2 or more antiepileptic drugs, and lack of treatment during pregnancy. The most commonly used drugs were lamotrigine, valproate, and levetiracetam, with an increase in levetiracetam use and a decrease in valproate use being observed in the later period (2011-2018).

Evolution of the meiotic prophase and of the chromosome pairing process during human fetal ovarian development.

BACKGROUND: Studies on human oocytes in prophase I are limited due to the difficulty in obtaining the sample. However, a complete study of meiotic prophase evolution and the homologue pairing process is necessary to try to understand the implication of oogenesis in the origin of human aneuploidy. METHODS: A complete analysis of meiotic prophase progression comprising the long developmental time period during which meiotic prophase takes place, based on the analysis of a total of 8603 oocytes in prophase I from 15 different cases is presented. The pairing process of chromosomes 13 and 18 is also described. RESULTS: The findings significantly relate for the first time the evolution of meiotic prophase to fetal development. Although for both chromosomes 13 and 18 a high pairing efficiency is found, pairing failure at the pachytene stage has been observed in 0.1% of oocytes. However, errors at the diplotene stage are substantially increased, suggesting that complete, premature disjunction of the homologues commonly occurs. Moreover, pre-meiotic errors are also described. CONCLUSIONS: Our findings show that homologous chromosomes pair very efficiently, but the high frequency of complete, premature homologue separation found at diplotene suggests that mechanisms other than the pairing process could be more likely to lead to the high aneuploidy rate observed in human oocytes.

Oral and vaginal misoprostol 800 microg every 8 h for early abortion.

The objective of the study was to evaluate the efficacy and safety of 800 microg misoprostol (Cytotec) every 8 h for 24 h for pharmacological abortion; the treatment was repeated if abortion did not occur in the first 24-h interval. The first misoprostol doses were always self-administered into the vagina; the second and third doses could be administered orally or vaginally depending on the amount of bleeding. Four-hundred and fifty-two women with gestations between 36 and 63 days were recruited into the study. The main outcomes assessed were: successful abortion (complete abortion without surgery), side effects, mean drop in hemoglobin, vaginal bleeding and mean time of return of menstruation. Complete abortion occurred in 409/452 (90.5%; 95% confidence interval [CI] 87%, 93%) patients. Medication to relieve symptoms was administered to all women before the first misoprostol dose. Vaginal bleeding lasted 15.9 +/- 4.4 days. The mean drop in hemoglobin, measured 14 days after abortion, was statistically significant (p = 0.0001) but without clinical relevance. According to the results obtained, 800 microg of misoprostol administered every 8 h for 24 h could be a valid method for abortion for up to 9 weeks of gestation.

Misoprostol for abortion at 9-12 weeks' gestation in adolescents.

The objectives of the present clinical study were to evaluate the safety and efficacy of misoprostol (Cytotec), self-administered into the vagina for medical abortion, in adolescents under 18 years ofage. A group of 150 adolescents with gestations between 63 and 84 days, with previous written consent from the patient and parents or guardians, received 800 microg of vaginal misoprostol every 24 h, up to a maximum of three main doses, for abortion. Outcomes assessed included successful abortion (complete abortion without surgery), side-effects, decrease in hemoglobin, mean time of vaginal bleeding, mean expulsion time and mean time for the return of menses. Complete abortion occurred in 126/150 (84.0%, 95% confidence interval 77-89) patients. The frequencies of nausea and vomiting were statistically significantly higher when compared to those obtained for adult females. Vaginal bleeding lasted for 13.2 +/- 3.8 days (median 13 days, range 1-22 days). The mean expulsion time was 8.0 +/- 3.4 h (median 8 h, range 1-14 h) for all subjects who aborted after the first misoprostol dose. The mean drop in hemoglobin was statistically significant (p = 0.001), but without clinical relevance. From the high abortion rate obtained, we concluded that misoprostol alone is a valid method for terminating unwanted pregnancies at 10-13 weeks' gestation in adolescents under 18 years of age in the absence of mifepristone.

Vaginal misoprostol 1000 microg for early abortion.

The objective of this study was to evaluate the safety and efficacy of 1000 microg misoprostol vaginally (Cytotec) self-administered into the vagina for medical abortion. Three-hundred women with gestations between 42 and 63 days, with previous written consent, received vaginal misoprostol every 24 h up to a maximum of three doses for abortion. Outcome measures assessed included: successful abortion (complete abortion without surgery), side effects, decrease in hemoglobin, mean time of vaginal bleeding, mean expulsion time and mean time of returning of menses. Complete abortion occurred in 279/300 (93.0%, 95% CI 90, 96) patients. Medication to relieve symptoms was administered to all subjects after every misoprostol dose. Vaginal bleeding lasted 14.7 +/- 5.4 days. Mean expulsion time was 8.1 +/- 3.0 h for those who aborted after the first misoprostol dose. The mean drop in hemoglobin was statistically significant (p = 0.0001) but without clinical relevance. The frequencies of nausea and diarrhea were high. According to the observed outcomes, 1000-microg misoprostol vaginally could be a valid method to terminate pregnancies up to nine weeks gestation.

Oral versus vaginal misoprostol for cervical priming in first-trimester abortion: a randomized trial.

The objective of this study was to compare the oral and vaginal administration of misoprostol for cervical priming before surgical abortion up to 63 days' gestation. A total of 900 pregnant women, with ages ranging from 18 to 42 years, who asked for pregnancy termination, were included in this study. Women were randomly allocated to one of the following groups: oral administration of 400 microg misoprostol, 8 h before aspiration; and vaginal self-administration of 400 microg misoprostol, 4 h before aspiration. During admission, all subjects were checked on a 15-min basis. The preoperative cervical dilatation achieved was the main outcome assessed. The cervix was dilated (Hegar > or = 8) in 348 (78%) subjects from the oral treatment group and in 391 (87%) women from the vaginal treatment group; this difference was statistically significant (p = 0.0004). The mean dilatation achieved in the oral treatment group was 8.1 mm (SD 1.6 mm) and it was 8.5 mm (SD 1.5 mm) in the vaginal treatment group; this difference was statistically significant (p = 0.0001). The frequencies of side-effects such as nausea, vomiting, diarrhea and chills reported by women from the vaginal misoprostol group were 10, 8, 18 and 4 times lower, respectively, than those reported by subjects from the oral misoprostol group. In conclusion, vaginal self-administration of misoprostol was the best administration route, as it obtained the same or greater priming effectiveness of the cervix in half the time with a much lower frequency of side-effects.

Vaginal misoprostol 600 microg for early abortion.

The objective of this study was to evaluate the efficacy and safety of the vaginal self-administration of 600 microg misoprostol up to a maximum administration of three doses in a 24-h period, one every 8 h, for abortion up to 9 weeks' gestation. A group of 90 voluntary women with gestations from 35 to 63 days participated in the study. All women who aborted received a single additional dose of 600 microg misoprostol. Outcome measures included successful abortion (complete abortion without requiring surgical procedure) and side-effects. Complete abortion occurred in 57/89 (64%, 95% confidence interval 53-74%) subjects. The mean expulsion time was 7.4 +/- 3.8 h (median 7.2 h, range 3-20 h) for all women who aborted within the first 24 h of the administration of misoprostol. Thirty-two cases failed to abort, 28 cases due to failure of the method, of which 24 had a negative cardiac rhythm after the third dose, and four cases due to the doctor's decision. The results obtained in this study led us to the conclusion that the 600-microg misoprostol dose regimen was not adequate to produce a high or an acceptable abortive efficacy.

Dosis residuales post-aborto con misoprostol. Ensayo clínico aleatorizado / Residual misoprostol dose after pregnancy termination: randomized clinical study

Objetivo: Evaluar la eficacia y seguridad de dos regímenes de dosis residuales después del aborto con 800 miligramos de misoprostol aplicado en la vagina, el primero con 600 miligramos 24 horas después del aborto médico y el segundo con tres dosis de 600 miligramos cada una cada 12 horas después del aborto.Sujetos y métodos: 330 mujeres con gestaciones de hasta 63 días solicitando interrumpir su embarazo, recibieron 800 miligramos misoprostol vaginal cada 24 horas hasta un máximo de tres dosis para abortar. Fueron asignadas aleatoriamente a uno de los dos grupos de dosis residuales. Todas las participantes finalizaron el estudio.Resultados: El aborto completo ocurrió en 304//330 (92,1 por 100, 95 por 100 IC 89,95) sujetos.Conclusiones: La administración de dos dosis extras residuales de 600 miligramos de misoprostol 24 horas post aborto no mejoró dicha tasa (AU)

Misoprostol for abortion up to 9 weeks' gestation in adolescents.

The objectives of the present clinical study were to evaluate the safety and efficacy of misoprostol (Cytotec) self-administered into the vagina for medical abortion in adolescents under the age of 18 years. After obtaining written consent from the patients and parents or guardians, a group of 150 adolescents with gestations between 35 and 63 days received 800 microg of vaginal misoprostol every 24 h, up to a maximum of three main doses, for abortion. Outcomes assessed included successful abortion (complete abortion without surgery), side-effects, decrease in hemoglobin, mean time of vaginal bleeding, mean expulsion time and mean time for the return of menses. Complete abortion occurred in 133/150 (88.7%, 95% confidence interval 82-93) patients. The frequencies of nausea, vomiting and diarrhea were statistically significantly higher when compared to those obtained for adult females. Vaginal bleeding lasted for 12.7 +/- 5.7 days (median 12 days, range 1-23 days). The mean expulsion time was 6.8 +/- 2.4 h (median 6 h, range 3-14 h) for those who aborted after the first misoprostol dose. The mean time for the return of menses, for those who aborted with misoprostol, was 34.7 +/- 3.4 days. The mean decrease in hemoglobin was statistically significant (p = 0.001), but had no clinical relevance. Taking into account the high abortion rate obtained, we could conclude that misoprostol alone is a valid method for terminating unwanted pregnancies in adolescents under the age of 18 years.